text:
Abdominal aspergillosis: CT findings
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Yeom, Suk Keu, E-mail: firstname.lastname@example.com [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Kim, Hye Jin, E-mail: email@example.com [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Byun, Jae Ho, E-mail: email@example.com [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Kim, Ah Young, E-mail: firstname.lastname@example.com [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Lee, Moon-Gyu, E-mail: firstname.lastname@example.com [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Ha, Hyun Kwon, E-mail: email@example.com [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of)
Objective: In order to retrospectively evaluate the CT findings of abdominal aspergillosis in immunocompromised patients. Materials and methods: CT scans were reviewed with regard to the sites, number, morphologic appearance, attenuation, and the contrast enhancement patterns of the lesions in six patients (5 women, 1 man; mean age, 43.4 years; range, 23-59 years) with pathologically proved abdominal aspergillosis by two gastrointestinal radiologists in consensus. Medical records were also reviewed to determine each patient's clinical status and outcome. Results: All patients were immunocompromised state: 4 patients received immunosuppressive therapy for solid organ transplantation and 2 patients received chemotherapy for acute myeloid leukemia. Aspergillosis involved blood vessels (n = 3), liver (n = 2), spleen (n = 2), gastrointestinal tract (n = 2), native kidney (n = 1), transplanted kidney (n = 1), peritoneum (n = 1), and retroperitoneum (n = 1). CT demonstrated solid organ or bowel infarction or perforation secondary to vascular thrombosis or pseudoaneurysm, multiple low-attenuating lesions of solid organs presenting as abscesses, concentric bowel wall thickening mimicking typhlitis, or diffuse or nodular infiltration of the peritoneum and retroperitoneum. Conclusion: Familiarity with findings commonly presenting as angioinvasive features or abscesses on CT, may facilitate the diagnosis of rare and fatal abdominal aspergillosis.
[Pseudotumoral allergic bronchopulmonary aspergillosis].
Otero González, I; Montero Martínez, C; Blanco Aparicio, M; Valiño López, P; Verea Hernando, H
Allergic bronchopulmonary aspergillosis (ABPA) develops as the result of a hypersensitivity reaction to fungi of the genus Aspergillus. Clinical and radiological presentation can be atypical, requiring a high degree of suspicion on the part of the physician who treats such patients. We report the cases of two patients with APBA in whom the form of presentation--with few asthma symptoms, images showing lobar atelectasia and hilar adenopathy--led to an initial suspicion of lung cancer.
Risk and Prevention of Aspergillosis
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Aspergillosis: a disease with many faces.
Miller, W T
Aspergillus causes a variety of pulmonary diseases. For the most part, they can be divided into three groups: mycetoma, invasive aspergillosis, and allergic forms of aspergillosis. The mycetoma form of aspergillosis has no effective treatment other than surgery, which is reserved for the severely symptomatic patient, usually with massive hemoptysis. Invasive aspergillosis is a dangerous pulmonary infection seen in patients who are generally severely immunocompromised. It is treated with amphotericin B and success in treatment of this form of aspergillosis is limited. Two of the allergic forms of Aspergillus infection, allergic bronchopulmonary aspergillosis and bronchocentric granulomatosis, are treated with steroids. The third allergic type of reaction, hypersensitivity lung, is best treated by removal of the patient from exposure to the antigen. Although these are the characteristic forms of aspergillosis, there is occasional overlap of the different types of aspergillosis.
Primary Aspergillosis of the Larynx
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Richard H. Law
Full Text Available Laryngeal aspergillosis is most commonly seen as a result of secondary invasion from the lungs and tracheobronchial tree in immunocompromised hosts. Primary aspergillosis of the larynx is, however, rare with few cases documented over the past fifty years. We report a case of a 73-year-old woman who presented with persistent hoarseness. She is a nonsmoker with a history of asthma and chronic bronchiectasis treated with bronchodilators, inhaled and oral corticosteroids, and nebulized tobramycin. Direct laryngoscopy with vocal cord stripping confirmed the diagnosis of invasive aspergillosis with no manifestations elsewhere. The patient was successfully treated with oral voriconazole with no signs of recurrence. Although several major risk factors contributing to the development of primary aspergillosis of the larynx have been discussed in the literature, there has been no mention of inhaled antibiotics causing this rare presentation to the best of our knowledge. We, therefore, highlight the use of inhaled tobramycin as a unique catalyst leading to the rapid onset of this rare presentation.
Invasive aspergillosis in two patients with Pearson syndrome.
Warris, A.; Verweij, P.E.; Barton, R.C.; Crabbe, D.C.G.; Evans, E.G.V.; Meis, J.F.G.M.
Invasive aspergillosis is a serious opportunistic infection in the immunocompromised host. In the pediatric population invasive aspergillosis is seen predominantly in patients with hematologic malignancie, chronic granullamotous disease (CGD) and AIDS. Invasive aspergillosis carries a high case
Invasive aspergillosis in developing countries.
Chakrabarti, Arunaloke; Chatterjee, Shiv Sekhar; Das, Ashim; Shivaprakash, M R
To review invasive aspergillosis (IA) in developing countries, we included those countries, which are mentioned in the document of the International Monetary Fund (IMF), called the Emerging and Developing Economies List, 2009. A PubMed/Medline literature search was performed for studies concerning IA reported during 1970 through March 2010 from these countries. IA is an important cause of morbidity and mortality of hospitalized patients of developing countries, though the exact frequency of the disease is not known due to inadequate reporting and facilities to diagnose. Only a handful of centers from India, China, Thailand, Pakistan, Bangladesh, Sri Lanka, Malaysia, Iran, Iraq, Saudi Arabia, Egypt, Sudan, South Africa, Turkey, Hungary, Brazil, Chile, Colombia, and Argentina had reported case series of IA. As sub-optimum hospital care practice, hospital renovation work in the vicinity of immunocompromised patients, overuse or misuse of steroids and broad-spectrum antibiotics, use of contaminated infusion sets/fluid, and increase in intravenous drug abusers have been reported from those countries, it is expected to find a high rate of IA among patients with high risk, though hard data is missing in most situations. Besides classical risk factors for IA, liver failure, chronic obstructive pulmonary disease, diabetes, and tuberculosis are the newly recognized underlying diseases associated with IA. In Asia, Africa and Middle East sino-orbital or cerebral aspergillosis, and Aspergillus endophthalmitis are emerging diseases and Aspergillus flavus is the predominant species isolated from these infections. The high frequency of A. flavus isolation from these patients may be due to higher prevalence of the fungus in the environment. Cerebral aspergillosis cases are largely due to an extension of the lesion from invasive Aspergillus sinusitis. The majority of the centers rely on conventional techniques including direct microscopy, histopathology, and culture to diagnose IA
Treatment of cerebral aspergillosis after liver transplantation.
Polo, J M; Fábrega, E; Casafont, F; Fariñas, M C; Salesa, R; Vázquez, A; Berciano, J
We report the treatment of cerebral aspergillosis with amphotericin B, flucytosine, surgery, and liposomal amphotericin B (L-AmB) after a liver transplant. The patient died 2 months after cessation of antifungal therapy, as a consequence of multiple-system organ failure. The only relevant postmortem finding in the brain was a small, encapsulated abscess containing hyphae. This case indicates that L-AmB is an effective alternative drug for cerebral aspergillosis.
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... given by mouth or IV (into a vein). Endocarditis caused by aspergillus is treated by surgically replacing ... Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Updated Edition . 8th ed. Philadelphia, PA: Elsevier ...
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[Chronic necrotizing pulmonary aspergillosis: infrequent form of aspergillosis].
Navarro, M; Domingo, C; Gallego, M; Roig, J; Mariscal, D; Marín, A
Chronic necrotizing pulmonary aspergillosis (CNPA) is a chronic pulmonary infection caused by the genus Aspergillus, which usually involves moderately immunosuppressed patients. We describe 3 patients with a toxic syndrome that had lasted several weeks or months, with lung infiltrates in the chest X-ray and the CT scan. Mycobacterium tuberculosis could not be isolated from different respiratory smears (sputum, bronchoaspiration, Barlett catheter and pulmonary punction in the third case). Moreover, there was no response to anaerobic treatment. All 3 patients were moderately immunosuppressed (2 men were COPD and the woman was an asthmatic patient). One of the men was being treated for a nocardiosis. In all three cases, A. fumigatus was isolated from de different respiratory smears. To diagnose a CPNA, a high degree of clinical suspicion is needed. The differential diagnose should be done with pulmonary tuberculosis and anaerobic infections. The presence of a member of the genus Aspergillus in the tracheobronchial secretions of a patient should not be systematically considered a saprofit, specially when other microorganisms can not be isolated.
Pictorial essay: Allergic bronchopulmonary aspergillosis
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Ritesh Agarwal
Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is the best-known allergic manifestation of Aspergillus-related hypersensitivity pulmonary disorders. Most patients present with poorly controlled asthma, and the diagnosis can be made on the basis of a combination of clinical, immunological, and radiological findings. The chest radiographic findings are generally nonspecific, although the manifestations of mucoid impaction of the bronchi suggest a diagnosis of ABPA. High-resolution CT scan (HRCT of the chest has replaced bronchography as the initial investigation of choice in ABPA. HRCT of the chest can be normal in almost one-third of the patients, and at this stage it is referred to as serologic ABPA (ABPA-S. The importance of central bronchiectasis (CB as a specific finding in ABPA is debatable, as almost 40% of the lobes are involved by peripheral bronchiectasis. High-attenuation mucus (HAM, encountered in 20% of patients with ABPA, is pathognomonic of ABPA. ABPA should be classified based on the presence or absence of HAM as ABPA-S (mild, ABPA-CB (moderate, and ABPA-CB-HAM (severe, as this classification not only reflects immunological severity but also predicts the risk of recurrent relapses.
Invasive aspergillosis: results of multicenter study
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N. N. Klimko
Full Text Available We present the results of a multicenter study of 445 patients with "proven" and "probable" invasive aspergillosis (EORTC/MSG, 2008. Invasive aspergillosis usually occurs in patients with hematological malignancies (88 %, main underlying diseases were acute myeloid and acute lymphoblastic leukemia. The risk factors: prolonged agranulocytosis (64 %, cytostatic chemotherapy (57 %, corticosteroid treatment (45 %, and allogeneic hematopoietic stem cells transplantation (29 %. The pathogens – A. fumigatus (42 %, A. niger (33 %, and A. flavus (21 %. The main site of infection were lungs (86 %. 12 week overall survival was 83 %. Bronchoscopy use for the early diagnosis (p = 0.01, adequatetherapy with voriconazole (p = 0.002 and secondary antifungal prophylaxis (p = 0.0003 were positive prognostic factors for survival of patients with invasive aspergillosis.
Pituitary aspergillosis abscess in an immunocompetent black ...
African Journals Online (AJOL)
Clinical Presentation An immunocompetent 26-year-old female patient showed up with amenorrhea-galactorrhea syndrome with infertility for several years. The CT Findings and hormonal studies strongly suggested pituitary adenoma or pituitary aspergillosis. Treatment The pituitary lesion was excised by a transsphenoidal ...
Primary Cutaneous Aspergillosis in an Immunocompetent Patient
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Case report and review of the literature. Paediatric Dermatol 2002;19: 439-44. 7. Prasad PV, Babu A, Kaviarasan PK, Anadhi C, Viswanathan P. Primary cutaneous aspergillosis. Indian J Dermatol Verner Leprol 2005;71:133-4. 8. Edlich RF, Winters KL, Britt LD, Long WD, Gubler KD, Drake DB. Difficult wounds: An update.
Azole-Resistant Central Nervous System Aspergillosis
van der Linden, Jan W. M.; Jansen, Rogier R.; Bresters, Dorine; Visser, Caroline E.; Geerlings, Suzanne E.; Kuijper, Ed J.; Melchers, Willem J. G.; Verweij, Paul E.
Three patients with central nervous system aspergillosis due to azole-resistant Aspergillus fumigatus (associated with a leucine substitution for histidine at codon 98 [L98H] and a 34-base pair repeat in tandem in the promoter region) are described. The patients were treated with combination therapy
Manifestation of invasive pulmonary aspergillosis in the formation of mycetoma
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Roos, N.; Peters, P.E.; Schellong, S.; Eiff, M. von
Invasive pulmonary aspergillosis is characterized by radiological signs allowing a correct diagnosis, including differentiation from pulmonary candidiasis, when they are associated with appropriate clinical symptoms (neutropenia and fever persisting despite broad-spectrum antibiotics). In particular the formation of a pulmonary mycetoma in a previously normal lung is one of these signs. Unlike a simple fungus ball (the saprophytic form of aspergillosis), the rounded density of invasive pulmonary aspergillosis consists of sequestrum of devitalized lung tissue owing to blood vessel invasion by Aspergillus hyphae. This morphologic phenomenon is demonstrated in the present case report and is discussed together with the other roentgenological signs of the invasive aspergillosis.
Post endodontic Aspergillosis in an immunocompetent individual.
Urs, Aadithya B; Singh, Hanspal; Nunia, Kalpana; Mohanty, Sujata; Gupta, Shalini
Non-invasive aspergillosis in immunocompetent individuals subsequent to post endodontic treatment can involve the maxillary antrum. An early and accurate diagnosis will aid in prompt and effective treatment. A 35 year old female patient reported with a painful nasomaxillary swelling. Previous records revealed the failure of the endodontic treatment of maxillary left second premolar which was subsequently extracted. Root piece was accidently left behind which resulted in a painful nasomaxillary swelling. The extraction socket was curetted and tissue was sent for histopathological examination, which revealed abundant septate fungal hyphae with numerous spores characteristic of Aspergillus. The patient showed marked improvement in the symptoms with systemic itraconazole at 3 months follow up and complete resolution occurred within 6 months. Inclusion of aspergilloma infections in the differential diagnosis is advocated when patients present with post-endodontic nasomaxillary swelling. Aspergillosis, fungal sinusitis, post root canal treatment.
Chronic Pulmonary Aspergillosis Complicating Bronchial Atresia
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Mazen O. Al-Qadi
Full Text Available Bronchial atresia is a rare pulmonary developmental anomaly characterized by the presence of a focal obliteration of a segmental or lobar bronchial lumen. The lung distal to the atretic bronchus is typically emphysematous along with the presence of mucus filled ectatic bronchi (mucoceles. BA is usually asymptomatic but pulmonary infections can rarely develop in the emphysematous lung distal to the atretic bronchus. We present a unique case of chronic pulmonary aspergillosis (CPA in a patient with BA with no evidence of immune dysfunction. The patient was treated initially with voriconazole and subsequently underwent surgical excision of the involved area. On follow-up, she has done extremely well with no evidence for recurrence. In summary, we describe the first case of chronic pulmonary aspergillosis in an immunocompetent patient with bronchial atresia.
Post endodontic Aspergillosis in an immunocompetent individual
Urs, Aadithya-Basavaraj; Singh, Hanspal; Nunia, Kalpana; Mohanty, Sujata; Gupta, Shalini
Non-invasive aspergillosis in immunocompetent individuals subsequent to post endodontic treatment can involve the maxillary antrum. An early and accurate diagnosis will aid in prompt and effective treatment. A 35 year old female patient reported with a painful nasomaxillary swelling. Previous records revealed the failure of the endodontic treatment of maxillary left second premolar which was subsequently extracted. Root piece was accidently left behind which resulted in a painful nasomaxillar...
Allergic Bronchopulmonary Aspergillosis: A Perplexing Clinical Entity
Shah, Ashok; Panjabi, Chandramani
In susceptible individuals, inhalation of Aspergillus spores can affect the respiratory tract in many ways. These spores get trapped in the viscid sputum of asthmatic subjects which triggers a cascade of inflammatory reactions that can result in Aspergillus-induced asthma, allergic bronchopulmonary aspergillosis (ABPA), and allergic Aspergillus sinusitis (AAS). An immunologically mediated disease, ABPA, occurs predominantly in patients with asthma and cystic fibrosis (CF). A set of criteria, ...
Galactomannan detection for invasive aspergillosis in immunocompromised patients
Leeflang, Mariska M. G.; Debets-Ossenkopp, Yvette J.; Wang, Junfeng; Visser, Caroline E.; Scholten, Rob J. P. M.; Hooft, Lotty; Bijlmer, Henk A.; Reitsma, Johannes B.; Zhang, Mingming; Bossuyt, Patrick M. M.; Vandenbroucke-Grauls, Christina M.
Invasive aspergillosis is the most common life-threatening opportunistic invasive mycosis in immunocompromised patients. A test for invasive aspergillosis should neither be too invasive nor too great a burden for the already weakened patient. The serum galactomannan enzyme-linked immunosorbent assay
Disseminated Aspergillosis due to Aspergillus niger in Immunocompetent Patient: A Case Report
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Ulku Ergene
Full Text Available Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients. Many cases of pulmonary, cutaneous, cerebral, and paranasal sinus aspergillosis in immunocompetent patient were defined in literature but disseminated aspergillosis is very rare. Here we present an immunocompetent case with extrapulmonary disseminated aspergillosis due to Aspergillus niger, totally recovered after effective antifungal treatment with voriconazole.
Susceptibility of convalescent turkeys to pulmonary aspergillosis.
Kunkle, R A; Sacco, R E
Pulmonary lesions resulting from Aspergillus fumigatus inoculation were assessed in convalescent turkeys and compared with those in previously noninoculated (control) turkeys. In addition, lesions observed in small Beltsville white (SBW) turkeys were compared with those in broad-breasted white (BBW) turkeys challenged with the same inoculum. Turkeys were challenged by unilateral posterior thoracic air sac (PTAS) inoculation, rechallenged via the contralateral air sac after 5 wk, and then necropsied 1 wk later. Pulmonary lesions induced by the initial challenge had resolved in 6 of 10 SBW and 9 of 10 BBW turkeys. However, convalescence did not protect against pulmonary aspergillosis subsequent to rechallenge; 10 of 10 SBW and 9 of 10 BBW developed granulomatous pulmonary lesions on the side of reexposure. A greater proportion of control SBW turkeys developed pneumonia and airsacculitis following challenge as compared with the BBW breed. Lesions were limited to the lower respiratory tract in all turkeys and were confined to the ipsilateral lung and PTAS in the singly inoculated control turkeys. This study demonstrates that convalescence from pulmonary aspergillosis does not confer protection against rechallenge but may, instead, decrease resistance to subsequent infection.
Plasminogen alleles influence susceptibility to invasive aspergillosis.
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Aimee K Zaas
Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.
Posaconazole prophylaxis in experimental azole-resistant invasive pulmonary aspergillosis
Seyedmousavi, S.; Mouton, J.W.; Melchers, W.J.G.; Verweij, P.E.
We investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistant Aspergillus fumigatus isolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with
Allergic Broncho Pulmonary Aspergillosis Complicated by Nocardiosis
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Brijesh Sharma
Full Text Available We describe a 70-year-old male with a history of diabetes mellitus, hypertension, and asthma who presented with increasing breathlessness for 5 months. He was diagnosed to have allergic bronchopulmonary aspergillosis (ABPA by serological and radiographic criteria. He was treated with steroids and itraconazole. After initial improvement, he developed fever with cough and mucopurulent sputum. X-ray chest revealed multiple cavities with air fluid level. Patient was treated with antibiotics without any response. Sputum was negative for acid fast bacilli (AFB. Sputum culture for bacteria and fungus did not reveal any significant growth; however a delayed growth of Nocardia was noted on fungal plates. Modified Ziehl Nelsen stain was positive for AFB. Patient was treated with cotrimoxazole. We discuss the serological and radiological criteria of ABPA, presentation and treatment of nocardia pulmonary infection and other possible causes of necrotizing pneumonia in immunocompromised settings.
An Economic Evaluation of Voriconazole versus Amphotericin B for the Treatment of Invasive Aspergillosis in Canada
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Coleman Rotstein
Full Text Available BACKGROUND: Invasive aspergillosis (IA is a serious fungal infection that affects immunocompromised patients. The Global Comparative Aspergillosis study demonstrated that voriconazole, a new broad-spectrum triazole, had better responses and improved survival compared with conventional amphotericin B deoxycholate (CAB and other licensed antifungal therapy (OLAT for the treatment of definite or probable aspergillosis.
Necrotizing pulmonary aspergillosis: regarding two clinical cases
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S. Carreira
Full Text Available The authors present two case reports of necrotizing pulmonary aspergillosis. This disease is part of a spectrum of clinical conditions caused by the inhalation of Aspergillus spores. The necrotizing pulmonary aspergillosis (NPA corresponds to an indolent, destructive process of the lung due to invasion by Aspergillus species, usually A. fumigatus. The diagnosis is confirmed by a histological demonstration of tissue invasion by Aspergillus species and its growth on culture. Due to the difficulty in confirming the diagnosis, the following diagnosis criteria were established and when combined are highly indicative of NPA: characteristic clinical and radiological findings, elevation of inflammatory markers and either serological results positive for Aspergillus or the isolation of Aspergillus from respiratory samples. Active tuberculosis, non tuberculosis mycobacteriosis, cavitary histoplasmosis and coccidioidomycosis should be excluded. It is necessary to raise the level of suspicion and perform the adequate diagnostic tests in order to start therapy and avoiding disease progression. Resumo: Os autores apresentam dois casos clÃnicos de aspergilose pulmonar necrotizante. Esta patologia faz parte de um espectro de condições clÃnicas provocadas pela inalação de esporos do fungo Aspergillus. A aspergilose pulmonar necrotizante (APN corresponde a um processo indolente de destruição do pulmão pelo Aspergillus, geralmente A. fumigatus. O diagnóstico definitivo faz-se através da demonstração histológica de invasão tecidual pelo Aspergillus e do seu crescimento em cultura2. Pela dificuldade em obter um diagnóstico definitivo foram estabelecidos os seguintes critérios de diagnóstico que, quando reunidos, são fortemente indicativos de APN: aspectos clÃnicos e radiológicos consistentes com o diagnóstico, elevação dos parâmetros inflamatórios (PCR, VS e marcadores serol
Accuracy of percutaneous lung biopsy for invasive pulmonary aspergillosis
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Hoffer, F.A. [Dept. of Diagnostic Imaging, St. Jude Children' s Research Hospital, Memphis, TN (United States); Gow, K.; Davidoff, A. [Dept. of Surgery, St. Jude Children' s Research Hospital, Memphis, TN (United States); Flynn, P.M. [Dept. of Infectious Diseases, St. Jude Children' s Research Hospital, Memphis, TN (United States)
Background. Invasive pulmonary aspergillosis is fulminant and often fatal in immunosuppressed patients. Percutaneous biopsy may select patients who could benefit from surgical resection. Objective. We sought to determine the accuracy of percutaneous biopsy for pediatric invasive pulmonary aspergillosis. Materials and methods. We retrospectively reviewed 28 imaging-guided percutaneous biopsies of the lungs of 24 children with suspected pulmonary aspergillosis. Twenty-two were being treated for malignancy and two for congenital immunodeficiency; 15 had received bone-marrow transplants. The accuracy of the percutaneous lung biopsy was determined by subsequent surgical resection, autopsy, or clinical course. Results. Histopathological studies showed ten biopsy specimens with septate hyphae, indicating a mold, and seven with Aspergillus flavus colonies in culture. The remaining 18 biopsies revealed no fungi. No patient had progressive aspergillosis after negative biopsy. Invasive pulmonary mold was detected by percutaneous biopsy with 100 % (10/10) sensitivity and 100 % (18/18) specificity. Percutaneous biopsy results influenced the surgical decision in 86 % (24 of 28) of the cases. Bleeding complicated the biopsy in 46 % (13/28) and hastened one death. Conclusion. Percutaneous biopsy of the lung is an accurate technique for the diagnosis of invasive pulmonary aspergillosis and correctly determines which immunosuppressed pediatric patients would benefit from therapeutic pulmonary resection. (orig.)
Immunopathology and Immunogenetics of Allergic Bronchopulmonary Aspergillosis
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Alan P. Knutsen
Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is a Th2 hypersensitivity lung disease in response to Aspergillus fumigatus that affects asthmatic and cystic fibrosis (CF patients. Sensitization to A. fumigatus is common in both atopic asthmatic and CF patients, yet only 1%–2% of asthmatic and 7%–9% of CF patients develop ABPA. ABPA is characterized by wheezing and pulmonary infiltrates which may lead to pulmonary fibrosis and/or bronchiectasis. The inflammatory response is characterized by Th2 responses to Aspergillus allergens, increased serum IgE, and eosinophilia. A number of genetic risks have recently been identified in the development of ABPA. These include HLA-DR and HLA-DQ, IL-4 receptor alpha chain (IL-4RA polymorphisms, IL-10 −1082GA promoter polymorphisms, surfactant protein A2 (SP-A2 polymorphisms, and cystic fibrosis transmembrane conductance regulator gene (CFTR mutations. The studies indicate that ABPA patients are genetically at risk to develop skewed and heightened Th2 responses to A. fumigatus antigens. These genetic risk studies and their consequences of elevated biologic markers may aid in identifying asthmatic and CF patients who are at risk to the development of ABPA. Furthermore, these studies suggest that immune modulation with medications such as anti-IgE, anti-IL-4, and/or IL-13 monoclonal antibodies may be helpful in the treatment of ABPA.
Transcript profiling of the murine immune response to invasive aspergillosis.
Dhesi, Zaneeta; Herbst, Susanne; Armstrong-James, Darius
Invasive aspergillosis is an opportunistic infection for which complex host-pathogen interactions determine infection outcome. In particular, immunosuppressive therapies and other host factors, such as neutropenia, need to be taken into account when modelling the immune response to aspergillosis. Mammalian models have been developed in order to gain a deeper understanding of these biological interactions, which cannot be easily replicated in vitro. In vivo transcript profiling is emerging as a valuable technique to gain an overview of host responses to invasive infections. This approach can be applied to specific tissue sections, whole organs, or peripheral blood leukocyte populations. Here we describe a microarray technique for analyzing transcript profiles from whole lung homogenates in the context of invasive aspergillosis. This approach has the advantage of enabling a broad overview of the immune responses that govern disease outcome. The generic techniques described, however, have wider application to other infectious processes and tissue types.
[Cerebral aspergillosis and liver transplantation: about one case].
Delwarde, B; Schmitt, Z; Bienvenu, A L; Duperret, S; Aubrun, F
Cerebral invasive aspergillosis is a rare but serious infection. Mortality is still high despite appropriate treatment. We report the case of a patient with liver transplantation in the context of alcoholic cirrhosis and transplanted back seven years later consequently to an ischemic cholangitis. Following an acquired active viral infection by HCV and treated by antiviral combination therapy the patient presented six months after this second operation a cerebral aspergillosis of tumour-like presentation. It rapidly evolved to an unfavourable outcome with intracranial hypertension state. If the therapeutic management is well established, the diagnosis is difficult. This observation allows us to discuss the various diagnostic criteria of cerebral aspergillosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Scrotal granulomatous aspergillosis in a dromedary camel (Camelus dromedarius)
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Scaglione, Frine Eleonora; Peano, Andrea; Piga, Sara
Background This report describes a case of primary subcutaneous aspergillosis in a 7-year-old neutered male dromedary camel (Camelus dromedarius). Case presentation The animal developed a large nodular lesion in the right scrotum two years after surgical intervention for neutering. The mass had...... was not performed, but a panel of mono- and polyclonal antibodies specific for different fungal genera identified the hyphae as Aspergillus sp. Conclusions The occurrence of subcutaneous lesions is a rare manifestation of aspergillosis in animals, and this appears to be the first case reported in the dromedary...
Invasive Pulmonary Aspergillosis-mimicking Tuberculosis.
Kim, Sung-Han; Kim, Mi Young; Hong, Sun In; Jung, Jiwon; Lee, Hyun Joo; Yun, Sung-Cheol; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee
Pulmonary tuberculosis is occasionally confused with invasive pulmonary aspergillosis (IPA) in transplant recipients, since clinical suspicion and early diagnosis of pulmonary tuberculosis and IPA rely heavily on imaging modes such as computed tomography (CT). We therefore investigated IPA-mimicking tuberculosis in transplant recipients. All adult transplant recipients who developed tuberculosis or IPA at a tertiary hospital in an intermediate tuberculosis-burden country during a 6-year period were enrolled. First, we tested whether experienced radiologists could differentiate pulmonary tuberculosis from IPA. Second, we determined which radiologic findings could help us differentiate them. During the study period, 28 transplant recipients developed pulmonary tuberculosis after transplantation, and 80 patients developed IPA after transplantation. Two experienced radiologists scored blindly 28 tuberculosis and 50 randomly selected IPA cases. The sensitivities of radiologists A and B for IPA were 78% and 68%, respectively (poor agreement, kappa value = 0.25). The sensitivities of radiologists A and B for tuberculosis were 64% and 61%, respectively (excellent agreement, kappa value = 0.77). We then compared the CT findings of the 28 patients with tuberculosis and 80 patients with IPA. Infarct-shaped consolidations and smooth bronchial wall thickening were more frequent in IPA, and mass-shaped consolidations and centrilobular nodules (tuberculosis. Certain CT findings appear to be helpful in differentiating between IPA and tuberculosis. Nevertheless, the CT findings of about one-third of pulmonary tuberculosis cases in transplant recipients are very close to those of IPA. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: email@example.com.
Invasive pulmonary aspergillosis: A study of 39 cases at autopsy
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Vaideeswar P
Full Text Available Background: Aspergillus is a common cause of invasive mycosis, especially in immunocompromised or immunosuppressed individuals. Aims: To study the incidence of invasive pulmonary aspergillosis and evaluate the predisposing factors and clinico-pathological manifestations. Settings and Design: Retrospective analysis of autopsy material from a tertiary care hospital. Material and Methods: All autopsies performed over a 12-year period were reviewed and cases with invasive aspergillosis were analysed with respect to their clinical presentation, predisposing factors, gross and histological features, complications and causes of death. Results: Among a total of 20475 autopsies performed in 12 years, 39 patients (0.19 % had invasive pulmonary aspergillosis. There were 28 males and 11 females. Their ages ranged from five months to 67 years. Dyspnoea, fever, cough with mucopurulent expectoration, chest pain and haemoptysis were commonly encountered symptoms. Forty-one per cent of the patients had no respiratory symptoms. Fungal aetiology was not entertained clinically in any of the patients. The major underlying conditions were prolonged antibiotic therapy, steroid therapy, and renal transplantation, often associated with underlying lung diseases. Pneumonia, abscesses, vascular thrombosis and infarction were common findings at autopsy. Antecedent tuberculosis, mucormycosis, Pneumocystis carinii pneumonia and Cytomegalovirus infection were also present. In most cases, death was related to extensive pulmonary involvement or fungal dissemination. Conclusion: A diagnosis of invasive pulmonary aspergillosis should always be borne in mind whenever one is dealing with recalcitrant lung infections even with subtle immunosuppression. Radiological investigations and serologic markers can be utilised for confirmation and prompt therapy.
Sino-orbital aspergillosis with central nervous system complication ...
African Journals Online (AJOL)
A central nervous system (CNS) complication (cerebral abscess) was diagnosed following seizures in the patient. The patient died a few days later. Conclusion: The diagnosis of aspergillosis of the orbit was only made from fungal culture after the patient's death. It requires a high index of suspicion to make a diagnosis of ...
Allergic bronchopulmonary aspergillosis as a cause of bronchial ...
African Journals Online (AJOL)
Background: Allergic bronchopulmonary aspergillosis (ABPA) occurs in patients with asthma and cystic fibrosis. When aspergillus fumigatus spores are inhaled they grow in bronchial mucous as hyphae. It occurs in non immunocompromised patients and belongs to the hypersensitivity disorders induced by Aspergillus.
Disseminated aspergillosis causing intestinal failure following colectomy for perforated colitis
McElvanna, Kevin; Loughrey, Maurice B; Gillespie, Scott; Gardiner, Keith R
Disseminated aspergillosis is a rare, invasive, opportunistic, fungal infection associated with a high mortality. We report a non-fatal case diagnosed following extensive enterectomy for intestinal infarction in a patient recovering from emergency abdominal colectomy for perforated ulcerative colitis. This resulted in intestinal failure necessitating life-long parenteral nutrition and prolonged antifungal therapy. PMID:28839844
Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis
DEFF Research Database (Denmark)
Skov, M; Koch, C; Reimert, C M
The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity...
Galactomannan detection for invasive aspergillosis in immunocompromized patients
Leeflang, Mariska M.; Debets-Ossenkopp, Yvette J.; Visser, Caroline E.; Scholten, Rob J. P. M.; Hooft, Lotty; Bijlmer, Henk A.; Reitsma, Johannes B.; Bossuyt, Patrick M. M.; Vandenbroucke-Grauls, Christina M.
Background Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mycosis in immunocompromized patients. A test for IA needs to be not too invasive and not too big a burden for the already weakened patient. The serum galactomannan ELISA seems to have potential for
Performance of Aspergillus PCR in cerebrospinal fluid for the diagnosis of cerebral aspergillosis.
Imbert, S; Brossas, J-Y; Palous, M; Joly, I; Meyer, I; Fekkar, A
Cerebral aspergillosis is a rare but often fatal form of invasive aspergillosis that remains difficult to diagnose. The literature has shown the value of Aspergillus PCR in blood-derived samples for the diagnosis of invasive aspergillosis but provides far less information for cerebrospinal fluid (CSF) in cerebral aspergillosis. Here, we evaluated the usefulness of an Aspergillus PCR assay performed on CSF for the diagnosis of cerebral aspergillosis. This retrospective study involved 72 patients with suspected cerebral aspergillosis for a total of 88 CSF samples in whom CSF Aspergillus PCR was performed. Seventeen patients had proven/probable invasive aspergillosis according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, including 12 cases of proven/probable cerebral aspergillosis. Aspergillus PCR in CSF was positive in nine of the twelve patients with cerebral aspergillosis, i.e. 75% sensitivity. In contrast, CSF culture was positive for Aspergillus in only two patients. In the non-cerebral aspergillosis group (60 patients), PCR was positive in one patient, i.e. 98.3% specificity. In this particular population of high-risk patients with suspicion of cerebral aspergillosis, the disease incidence was 16.7%. Therefore, the positive and negative predictive values of PCR were 90% and 95.2%, respectively. The results of this study indicate that Aspergillus PCR in CSF is an interesting tool that may eliminate the need for cerebral biopsy in patients with suspected cerebral aspergillosis. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Imaging features of gastric invasive aspergillosis: A report of two cases
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Yang, Dong Jin; Cho, Seung Hyun; Kim, Seong Hoon; Shin, Ji Yeol; Lee, Yil Gi [Daegu Fatima Hospital, Daegu (Korea, Republic of)
Invasive aspergillosis is an opportunistic infection that usually occurs in immunocompromised patients. Although there are a few rare reports of isolated invasive aspergillosis affecting the small intestine, isolated or disseminated gastric invasive aspergillosis is extremely rare. Herein, we report 2 cases of gastric invasive aspergillosis in a 72 year old woman and a 43 year old man; the woman had been recovering from ruptured left posterior communicating artery aneurysm, which presented as emphysematous gastritis and the man from acute subdural haemorrhage in the intensive care unit, which presented as a pseudoaneurysm on CT imaging.
Invasive pulmonary aspergillosis – case report and review of literature
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Ashutossh Naaraayan
Full Text Available Invasive pulmonary aspergillosis (IPA is a severe fungal infection with a high mortality rate. The incidence of IPA is on the rise due to an increase in the number of patients undergoing transplants and receiving chemotherapy and immunosuppressive therapy. Diagnosis is challenging due to the non-specific nature of symptoms. Voriconazole is the mainstay of therapy. We present a case of an elderly woman presenting with acute bronchitis and asthma exacerbation, who succumbed to overwhelming IPA. It is uncommon for IPA to develop in patients on short-term steroid therapy for asthma exacerbation. The possibility of aspergillosis in immunocompetent patients should be considered in those on systemic steroids and deteriorating pulmonary functions.
Nasal Aspergillosis in a Dog: A Case Report
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Camilo Padilla Peñuela
Full Text Available Nasal aspergillosis is a major chronic disease affecting the nostrils in dogs. Clinical sinology is typical in every chronic nasal disease. Epistaxis and occasional pain occurs. Rhinoscopic assessment of the area evidences findings associated with the pathology and allows collecting samples for cytology and culture. Systemic therapy with oral antifungals has had variable utility, but now it has been replaced by direct topical medication to the affected area. This article describes the case of a 4-years-old male dog, submitted to consultation by unilateral muco-bloody nasal discharge with a week of evolution. The patient was treated by another vet center with cyclonamine and vitamin K for a possible clotting disorder. After a series of tests that included rhinoscopy and fungal culture, nasal aspergillosis was diagnosed. Intranasal clotrimazole was applied twice and it allowed the resolution of the clinical signs.
Chronic fibrosing pulmonary aspergillosis: a cause of 'destroyed lung' syndrome.
Kosmidis, Chris; Newton, Pippa; Muldoon, Eavan G; Denning, David W
Chronic pulmonary aspergillosis (CPA) has substantial impact on quality of life. A subset of patients develops significant pulmonary fibrosis, identified either on biopsy or radiologically. The term chronic fibrosing pulmonary aspergillosis (CFPA) has been suggested. We describe 11 patients with CFPA referred to our centre. Mean age was 58.5 years and five were male. In nine, fibrosis was already evident on presentation, while in two it developed 3 and 6 years later. The predominant radiological feature was extensive or complete involvement of the entire lung, with minimal contralateral involvement. All patients received prolonged antifungal treatment. Two patients had surgical treatment; both developed post-operative complications. The contralateral lung remained free of significant disease in all but three patients. CFPA is a rare complication of CPA that is usually evident on presentation, but may develop after years in patients not on antifungals. Fibrosis resembles the 'destroyed lung' syndrome described after treated tuberculosis.
Chronic aspergillosis of the lungs: Unravelling the terminology and radiology
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Desai, S.R.; Hedayati, V.; Patel, K. [King' s College Hospital NHS Foundation Trust, The Department of Radiology, King' s Health Partners, King' s College London, London (United Kingdom); Hansell, D.M. [The Royal Brompton and Harefield NHS Foundation Trust, Department of Radiology, London (United Kingdom)
The propensity for Aspergillus spp. to cause lung disease has long been recognised but the satisfactory classification of these disorders is challenging. The problems caused by invasive disease in severely neutropenic patients, saprophytic infection of pre-existing fibrotic cavities and allergic reactions to Aspergillus are well documented. In contrast, a more chronic form of Aspergillus-related lung disease that has the potential to cause significant morbidity and mortality is under-reported. The symptoms of this form of Aspergillus infection may be non-specific and the radiologist may be the first to suspect a diagnosis of chronic pulmonary aspergillosis. The current review considers the classification conundrums in diseases caused by Aspergillus spp. and discusses the typical clinical and radiological profile of patients with chronic pulmonary aspergillosis. (orig.)
[Chronic Progressive Pulmonary Aspergillosis after Surgery for Lung Cancer].
Yamada, Tatsuya; Mori, Takeshi; Nishi, Wataru; Motooka, Yamato; Ikeda, Koei; Shiraishi, Kenji; Suzuki, Makoto
Case 1:A 62-year-old man underwent right S9+10 segmentectomy for non-small cell lung cancer. Three years later, pleural thickening appeared in the apex, and gradually developed cystic change. Case 2:A 64-year-old man underwent left upper lobectomy for non-small cell lung cancer. One year after surgery, chest computed tomography (CT) showed cysts in the apex of the lower lobe. The cysts expanded slowly with consolidation. Both cases were diagnosed as chronic progressive pulmonary aspergillosis. Although anti-fungal drugs were administered in both cases, case 1 died of the disease. Chronic progressive pulmonary aspergillosis is a rare late postoperative complication;when CT shows progressive cysts with consolidation in the apex area of the residual lung, frequent check-ups are needed.
Aspergillosis and proventricular impaction in an ostrich (Struthio camelus
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Shahrzad Azizi
Full Text Available Aspergillosis is the most common mycotic infection in a wide variety of bird and causes significant economic losses. The present study described concurrent occurrence of aspergillosis and proventricular impaction in a 4-year-old male ostrich. The bird had respiratory problems, coughing and anorexia. Postmortem examination revealed numerous greenish-white caseous foci, 0.5 to 1 cm in diameter distributed on the surfaces of the air sacs and throughout the lungs. In histopathological study, multifocal areas of caseous necrosis that surrounded by inflammatory cells including heterophils, lymphocytes and macrophages were present. Long branching septated hyphae were visible in the necrotic areas with hematoxylin and eosin and Periodic acid-Schiff staining. Thrombi were present in the blood vessels. The proventriculus was full of gravel.
Beware of the devastating pulmonary aspergillosis syndromes In certain environments
LENUS (Irish Health Repository)
Kooblall, M
Nowadays with more stem cell transplants and immunosuppressive therapies there has been a rise in pulmonary aspergillosis syndromes. The following illustrates such a case. A 49 year old man had a past history of ankylosing spondylitis with a bilateral hip replacement. He was also on surveillance for a superficial bladder tumour since 2007. His chest x-ray in 2008 was normal. In 2010 his CXR showed patchy opacification in the right apex. CT thorax confirm fibrotic changes.
Childhood allergic bronchopulmonary aspergillosis presenting as a middle lobe syndrome
Shah, Ashok; Gera, Kamal; Panjabi, Chandramani
Allergic bronchopulmonary aspergillosis (ABPA) is infrequently documented in children with asthma. Although collapse is not uncommon, middle lobe syndrome (MLS) as a presentation of ABPA is rather a rarity. A 9-year-old female child with asthma presented with increase in intensity of symptoms along with a right midzone patchy consolidation on a chest radiograph. In addition, an ill-defined opacity abutting the right cardiac border with loss of cardiac silhouette was noted. A right lateral vie...
Detection of Gliotoxin in Patients with Pulmonary Aspergillosis
Baheeja A.Hmood
Objective: This study was designed to detection of gliotoxin in patients with pulmonary Aspergillosis . Method: A total of 100 samples (sputum and blood) were selected from 100 outpatients who attended to Al-Qadissiyia Centre of Tuberculosis and Chest Diseases, , during the period from 2014 to May 2015. All patients had clinical manifestation in addition to 100 sample (sputum and blood) as control group. Results: All patients infected with fungi and three different genus isolated ...
Micafungin in the treatment of invasive candidiasis and invasive aspergillosis
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Nathan P Wiederhold
Full Text Available Nathan P Wiederhold1, Jason M Cota2, Christopher R Frei11University of Texas at Austin College of Pharmacy, Austin, Texas, USA; 2University of the Incarnate Word Feik School of Pharmacy, San Antonio, Texas, USAAbstract: Micafungin is an echinocandin antifungal agent available for clinical use in Japan, Europe, and the United States. Through inhibition of β-1,3-glucan production, an essential component of the fungal cell wall, micafungin exhibits potent antifungal activity against key pathogenic fungi, including Candida and Aspergillus species, while contributing minimal toxicity to mammalian cells. This activity is maintained against polyene and azole-resistant isolates. Pharmacokinetic and pharmacodynamic studies have demonstrated linear kinetics both in adults and children with concentration-dependent activity observed both in vitro and in vivo. Dosage escalation studies have also demonstrated that doses much higher than those currently recommended may be administered without serious adverse effects. Clinically, micafungin has been shown to be efficacious for the treatment of invasive candidiasis and invasive aspergillosis. Furthermore, the clinical effectiveness of micafungin against these infections occurs without the drug interactions that occur with the azoles and the nephrotoxicity observed with amphotericin B formulations. This review will focus on the pharmacology, clinical microbiology, mechanisms of resistance, safety, and clinical efficacy of micafungin in the treatment of invasive candidiasis and invasive aspergillosis.Keywords: micafungin, echinocandin, Candida, Aspergillus, invasive candidiasis, invasive aspergillosis
Screening of the central nervous system in children with invasive pulmonary aspergillosis
Broenen, E.; Mavinkurve, A.M.C.; Kamphuis-van Ulzen, K.; Brüggemann, R.J.M.; Verweij, P.E.; Warris, A.
The existing guidelines regarding the management of invasive pulmonary aspergillosis do not recommend screening of the extra-pulmonary sites. Due to the fact that the presence of central nervous system (CNS) aspergillosis will influence treatment decisions regarding which antifungal to use and the
Therapy of invasive aspergillosis with itraconazole: improvement of therapeutic efficacy by early diagnosis.
Kreisel, W; Köchling, G; von Schilling, C; Azemar, M; Kurzweil, B; Dölken, G; Lindemann, A; Blum, U; Windfuhr, M; Müller, J
We report on the treatment of invasive aspergillosis with the new triazole antimycotic agent itraconazole. All 11 patients suffered from pulmonary invasive aspergillosis. Two patients also had cerebral aspergillosis; in one of these patients the paranasal sinuses were also invaded. Underlying diseases were acute lymphoblastic leukaemia (n = 3), acute myeloid leukaemia (n = 4); one patient underwent allogeneic bone marrow transplantation before he developed aspergillosis; another was transplanted after successful aspergillosis treatment, liver cirrhosis (n = 1), lung infarction after pulmonary embolism (n = 1), chronic bronchitis after pulmonary tuberculosis (n = 1) and AIDS (n = 1). In five cases initial diagnosis was established by means of mycological methods and clinical signs. In six patients invasive pulmonary aspergillosis was initially diagnosed due to the clinical criteria presented in this paper. Secondary mycological confirmation after onset of therapy was achieved in five out of these six patients. All of the patients initially responded to therapy. One female patient experienced a relapse of aspergillosis and died of cerebral involvement and relapsing leukaemia. Two further patients died due to underlying diseases (pulmonary embolism, relapsing leukaemia). Nine patients (82%) were cured of the mycosis, including the patient with cerebral involvement; two underwent surgical resection of residual pulmonary lesions. Itraconazole is a very effective drug for treatment of invasive aspergillosis. Therapeutic efficacy can be optimized by early diagnosis using clinical criteria and prompt start of treatment.
[Fatal sino-orbital aspergillosis in an immunocompetent case].
Kaya, Selçuk; Yavuz, Ilknur; Cobanoğlu, Umit; Ural, Ahmet; Yılmaz, Gürdal; Köksal, Iftihar
The paranasal sinus infections caused by Aspergillus spp. are usually presented clinically with mild symptoms, however they may lead to invasive disease and mortality especially in immunocompromised individuals. In this report a fatal case of sino-orbital aspergillosis developed in an immunocompetent patient has been presented. Seventy-four years old female patient was admitted to the hospital with the complaints of fever and progressively increasing headache that continued for 15 days. Due to the development of nausea, vomiting, loss of consciousness and stiff neck in the following days, cerebrospinal fluid (CSF) sample was obtained. Direct microscopic examination of the Gram and acidfast staining of the CSF sample revealed no microorganisms, no growth was detected in CSF culture and PCR amplification was negative for Herpes simplex virus and Mycobacterium tuberculosis. Since no response was achieved by empirical ceftriaxone, ampicillin and conventional anti-tuberculosis treatment and tachypnea, proptosis and progressive respiratory failure developed in the patient, she was transferred to the intensive care unit. The radiological examination revealed soft tissue lesion filling the sphenoid sinus, extending to the nasal cavity and suprasellar cistern, destruction of bones, dilated orbital vein, cavernous sinus thrombosis and infarction on left cerebral peduncule. Patient was operated and pus and fungus ball were aspirated from the openings of both sphenoid sinuses. Gomori methenamine silver, periodic acid-Schiff and haematoxylin-eosine staining of the operational material exhibited dichotomously branching hyphae. The patient was diagnosed as invasive sino-orbital aspergillosis based on the clinical, radiological and histopathological findings. Despite antifungal therapy and surgical debridement, the patient died. It should always be kept in mind that aspergillosis can develop in immuncompetent individuals. Delay in diagnosis and treatment may lead to fatality. Thus
Clinical Features and Magnetic Resonance Imaging Findings in 7 Dogs with Central Nervous System Aspergillosis.
Taylor, A R; Young, B D; Levine, G J; Eden, K; Corapi, W; Rossmeisl, J H; Levine, J M
Systemic aspergillosis is a manifestation of Aspergillus sp. infection that can result in central nervous system (CNS) involvement with marked alterations in CNS function. Information regarding the clinical presentation and magnetic resonance imaging (MRI) findings in cases of aspergillosis with CNS involvement is lacking, resulting in a need for better understanding of this disease. The primary objectives were to describe the clinical features and MRI findings in dogs with CNS aspergillosis. The secondary objectives were to describe clinicopathologic findings and case outcome. Seven dogs with CNS aspergillosis. Archived records from 6 institutions were reviewed to identify cases with MRI of CNS aspergillosis confirmed with serum galactomannan enzyme immunoassay (EIA) testing, culture, or supported by histopathology. Signalment, clinical, MRI, clinicopathologic, histopathologic, and microbiologic findings were recorded and evaluated. Aspergillosis of the CNS was identified in 7 dogs from 3 institutions. The median age was 3 years and six were German Shepherd dogs. Five dogs had signs of vestibular dysfunction as a component of multifocal neurological abnormalities. The MRI findings ranged from normal to abnormal, including hemorrhagic infarction and mass lesions. Until now, all reported MRI findings in dogs with CNS aspergillosis have been abnormal. We document that CNS aspergillosis in dogs, particularly German Shepherd dogs, can be suspected based on neurologic signs, whether MRI findings are normal or abnormal. Confirmatory testing with galactomannan EIA, urine, cerebrospinal fluid (CSF) or tissue culture should be performed in cases where aspergillosis is a differential diagnosis. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Aspergillosis in hihi (Notiomystis cincta) on Mokoia Island.
Alley, M R; Castro, I; Hunter, J E
An intensive 2-year field study of 65 hihi (or stitchbirds) on Mokoia Island provided an opportunity to investigate the causes of mortality of this endangered species in a free-living environment. The birds were observed daily during the breeding season (October to March) and every 4 weeks during the remainder of the year. Any abnormalities in behaviour, voice and body weight were recorded and all sick or dead birds which could be recovered were taken to the laboratory for necropsy. Thirty-one birds died during the period of this study. Aspergillosis was found to be the cause of death in six of nine adult birds examined post mortem. Some of the affected birds experienced subtle voice changes before becoming ill and all birds had granulomatous lesions in airsacs or lungs at necropsy. A further eight birds for which carcasses could not be found or which were autolysed showed similar clinical signs before death or disappearance. Because Aspergillus is an opportunist pathogen it seems likely that affected birds were immunosuppressed. This may have occurred during the breeding season which in this species is highly stressful. The presence of fungal material in bronchial exudate and the occurrence of the disease in mates, raises the possibility that aspergillosis in hihi may be contagious.
Orphan drugs for the treatment of aspergillosis: focus on isavuconazole
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Jacobs SE
Full Text Available Samantha E Jacobs,1 Vidmantas Petraitis,1 Catherine B Small,1 Thomas J Walsh1–3 1Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, 2Department of Pediatrics, 3Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA Abstract: Invasive aspergillosis (IA is a particularly devastating manifestation of Aspergillus infection affecting profoundly immunocompromised patients. Voriconazole has been approved as first-line therapy for IA since 2003; however, nonlinear pharmacokinetics, adverse effects, and drug–drug interactions at time hinder its use. Isavuconazole is a new broad-spectrum triazole with potent activity against Aspergillus species. In animal models and clinical trials in humans, isavuconazole has shown comparable efficacy to that of voriconazole in the treatment of IA. Advantages of isavuconazole include a more favorable pharmacokinetic profile and fewer adverse events. This review summarizes the pharmacologic characteristics, in vitro activity, and clinical data supporting the use of isavuconazole as an emerging alternative therapy for IA. Keywords: isavuconazole, invasive aspergillosis, antifungal therapy, fungal infection
Development of serological technique for examination of aspergillosis in chicken
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Djaenudin Gholib
Full Text Available Aspergillosis detection by using serological method has not been reported in Indonesia. In this case, a study was conducted, by using mycelium extract of A. fumigatus as the antigen. Rabbits and chickens were injected with the antigen to produce positive serum (antiserum. The antigen and antiserum were tested serologicaly by Immunodiffusion/Agar Gel Precipitation (AGP, ELISA and Immunoblot. Chicken serum of broiler and layer collected from field were also included in the test. All positive serum of the experimentally animals gave positive results with all methods of serological tests. No bands of precipitation reaction in AGP test with chicken serum from the field. Both chicken and rabbit positive serum with ELISA test showed high Optical Density (OD, while field chicken serum from broiler commonly gave lower OD compared to layer. Immunoblot test of chicken positive serum showed bands of reaction with the antigen in nitrocellulose membrane, approximately on 33, 38, 44, 52, 70, 77, 97, and 110 kDa, meanwhile field chicken serum with high OD in ELISA test, showed bands approximately on 16, 18, 33, 38, 44, 47, 52, 70, 77, 84, 97, and 110 kDa. It means that the field chicken serum contain immunoglobulin molecules has spesific antibody of aspergillus antigen. It is concluded that the ELISA test can be used for screening on chicken aspergillosis in serological methode.
Allergic bronchopulmonary aspergillosis: a rare cause of pleural effusion.
LENUS (Irish Health Repository)
O'Connor, T M
Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome seen in patients with asthma and cystic fibrosis, and is characterized by hypersensitivity to chronic colonization of the airways with A. fumigatus. We report the case of a patient with ABPA presenting with pleural effusion. A 27-year-old male was referred with recurrent right pleural effusion. Past medical history was remarkable for asthma, allergic sinusitis, and recurrent pleurisy. Investigations revealed peripheral eosinophilia with elevated serum immunoglobulin E and bilateral pleural effusions with bilateral upper lobe proximal bronchiectasis. Precipitating serum antibodies to A. fumigatus were positive and the A. fumigatus immediate skin test yielded a positive reaction. A diagnosis of ABPA associated with bilateral pleural effusions was made and the patient was commenced on prednisolone. At review, the patient\\'s symptoms had considerably improved and his pleural effusions had resolved. ABPA may present with diverse atypical syndromes, including paratracheal and hilar adenopathy, obstructive lung collapse, pneumothorax and bronchopleural fistula, and allergic sinusitis. Allergic bronchopulmonary aspergillosis is a rare cause of pleural effusion and must be considered in the differential diagnosis of patients presenting with a pleural effusion, in particular those with a history of asthma.
Mycological and serological study of pulmonary aspergillosis in central India
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Kurhade A
Full Text Available PURPOSE: To study the prevalence and predisposing factors of Aspergillus infection and correlate microscopic, culture and serological findings along with drug sensitivity. METHODS: Sputum samples from 123 patients of pulmonary disease with clinical suspicion of having fungal, especially Aspergillus infections, were examined microscopically and for culture. Minimum inhibitory concentration (MIC of itraconazole was tested against the isolates. Serum samples from these patients were tested for precipitin against Aspergillus antigen using immunodiffusion (ID technique. RESULTS: Aspergillus species were isolated in 20 (16.26% cases and Aspergillus fumigatus was the predominant species isolated in 16 (80% cases. Precipitins were detected in 29 (23.58% cases. Serum samples collected from 50 healthy individuals to serve as controls showed no precipitin against Aspergillus antigen galactomannan. This fungus was found to be sensitive to itraconazole with MIC range 0.125-1µg/mL. CONCLUSIONS: Serological tests have an edge over routine smear and culture methods for the diagnosis of pulmonary aspergillosis. Itraconazole is more effective than amphotericin B and fluconazole in the treatment of aspergillosis.
Aspergillosis of Maxillary Sinus in an Uncontrolled Diabetic Patient: A Case Report
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Bhavna Barthunia
Full Text Available Fungal infections affecting the paranasal sinuses are common. They can affect normal as well as immunocompromised individuals. Aspergillosis and mucormycoses are the most common fungal infections involving maxillary sinus. They can manifest in two forms – noninvasive or invasive infection. These infections when properly diagnosed can be treated at the earliest without causing much tissue damage. Here, a noninvasive form of aspergillosis in an uncontrolled diabetic, elderly female patient is presented. This article also explains the etiopathogenesis, clinical and radiological features, as well as the management of aspergillosis.
A suspected case of autoinduction of voriconazole metabolism in a patient with cerebral aspergillosis
Ferguson MJ; Randles ML; de Freitas DG
Martin J Ferguson,1 Maria L Randles,2 Declan G de Freitas3 1Pharmacy Department, Beaumont Hospital, Beaumont, Dublin, 2Pharmacy Department, Wexford General Hospital, Wexford, 3Department of Transplantation, Urology and Nephrology, Beaumont Hospital Kidney Centre, Dublin, Ireland Objective: This study aims to report a case of accelerated metabolism of voriconazole in a patient with cerebral aspergillosis.Case summary: A 36-year-old woman developed cerebral aspergillosis after immunosuppressive...
The evolving landscape of new diagnostic tests for invasive aspergillosis in hematology patients: strengths and weaknesses.
Buchheidt, Dieter; Reinwald, Mark; Hoenigl, Martin; Hofmann, Wolf-Karsten; Spiess, Birgit; Boch, Tobias
The diagnosis of invasive aspergillosis in hematologic patients is a complex composite of clinical preconditions and features, imaging findings, biomarker combinations from appropriate clinical samples and microbiological and/or histological findings. Recent developments in the evolving landscape of diagnostic tests for invasive aspergillosis in adult hematology patients are highlighted. Novel approaches and tools are currently under development. Focusing optimized diagnostic performance, in particular the combination of biomarkers from appropriate clinical samples, improved diagnostic performance distinctly.
Long-term treatment of invasive sinus, tracheobroncheal, pulmonary and intracerebral aspergillosis in acute lymphoblastic leukaemia.
Björkholm, M; Kalin, M; Grane, P; Celsing, F
A 59-year-old male with acute lymphoblastic leukemia developed sinus, tracheobroncheal, pulmonary, and intracerebral aspergillosis. All lesions except the intracerebral aspergillosis healed after combination antifungal treatment. Long-term voriconazole--but not posaconazole--therapy induced partial regression of the cerebral manifestations. At the time of writing, 3.5 years after the initial diagnosis, the patient is working half-time and suffers from a possible voriconazole-induced polyneuropathy.
Allergic bronchopulmonary and sinus aspergillosis: the roentgenologic spectrum.
Shah, Ashok
Allergic bronchopulmonary aspergillosis (ABPA) and allergic Aspergillus sinusitis (AAS) are the best recognized manifestations of Aspergillus-associated hypersensitivity respiratory disorders. These conditions occur predominantly in atopic individuals. Roentgenologic techniques play a pivotal role in the diagnosis of these two conditions. ABPA, on imaging, is characterized by fleeting pulmonary infiltrates often confused with pulmonary tuberculosis. However, central bronchiectasis on computed tomography (CT) is considered to be the hallmark of the disease. Though the diagnosis of AAS is primarily based on histopathology, roentgenology is essential for the diagnosis. Haziness of one or more paranasal sinuses is almost always seen on plain roentgenograms. However, CT proffers more reliable information with characteristic features that include heterogeneous densities and serpiginous areas of increased attenuation on non-contrast scans. Early diagnosis, with the help of roentgenologic techniques, and appropriate therapy could alter the natural history of these diseases.
Disseminated invasive aspergillosis in a patient with acute leukaemia.
Gottfredsson, Magnús; Steingrímsdóttir, Hlíf
A 46-year-old previously healthy woman was diagnosed with acute lymphoblastic leukaemia. The induction phase was complicated by alpha-haemolytic streptococcal bacteremia which responded to antibacterial therapy. Subsequently, the patient developed pneumonie due to Chlamydiapneumoniae which responded to macrolides. Following this infection the patient developed recurrent fever and new pulmonary infiltrates were noted. Bronchoscopy was performed and treatment was administered with liposomal amphotericin B (L-AmB, AmBisome) for two days, but was complicated by acute renal failure. Aspergillus fumigatus was cultured from bronchoalveolar lavage fluid [corrected] L-AmB was discontinued and voriconazole and caspofungin were administered. Despite aggressive antifungal therapy the patient developed progressive invasive infection, with central nervous system involvement as well as lesions appearing in the kidneys and liver. The patient died one week following the diagnosis of aspergillosis.
[An unusual cause of acute respiratory distress: obstructive bronchial aspergillosis].
Margery, J; Perez, J-P; Vaylet, F; Bordier, E; Dot, J-M; Saint-Blancard, P; Bonnichon, A; Guigay, J; Pats, B; L'Her, P
We report the case of a 77-Year-old immunocompetent woman who required intensive care for acute dyspnea revealing complete atelectasia of the left lung related to an aspergillus mycelium plug blocking the principal bronchus. The clinical course was favorable after deobstruction by thermocoagulation and oral itraconazole given for six Months. The patient was free of parenchymatous or endobronchial sequelae. Adjuvant oral corticoid therapy was given temporarily during the second Month of treatment when signs of transition towards allergic aspergillosis developed. Four Months after discontinuing the antifungal treatment, the patient developed a new episode of acute dyspnea caused by atelectasia limited to the right lower lobe. Treatment by itraconazole was resumed and continued as long-term therapy. No recurrence has been observed for eighteen Months. The diagnostic and therapeutic problems raised by Aspergillus fumigatus are well known in the immunocompromised subject, but can also be encountered in the immunocompetent subject.
Radiological diagnosis of maxillary sinus aspergillosis. Radiologische Diagnostik der Kieferhoehlenaspergillose
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Schulte, B.; Beyer, D. (Akademisches Lehrkrankenhaus, Porz (Germany). Radiologische Abt.)
Aspergillosis of the maxillary sinuses shows an increasing incidence in even otherwise healthy patients. Next to inhalation as the mode of infection, a dental root canal filling with an orosinusal fistula can be the cause. As most infections remain initially undetected or underestimated as common sinusitis, early diagnosis must be achieved. Standard X-ray of the paranasal sinuses, conventional tomography as well as CT scans are of major importance. Centrally located hyperdense opacifications are a good criterion and can be best seen in CT. Even when the case has not progressed too much, radical surgery combined with Amphotericin B therapy is still the treatment of choice since the infection may progress rapidly. (orig.).
Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
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Frederic eLamoth
Full Text Available Invasive aspergillosis (IA is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B or cell wall (echinocandins are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation. HDACs also control the acetylation and activation status of multiple non-histone proteins, including the heat shock protein 90 (Hsp90, an essential molecular chaperone for fungal virulence and antifungal resistance. This review provides an overview of the different HDACs in Aspergillus spp. as well as their respective contribution to total HDAC activity, fungal growth, stress responses, and virulence. The potential of HDAC inhibitors, currently under development for cancer therapy, as novel alternative antifungal agents against IA is discussed.
Hyperostosis of the maxillary sinus wall in aspergillosis: is it a characteristic finding
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Kim, Ji Young; Cho, Woo Ho; Kim, Joung Sook; Kim, Myung Gyu; Kim, Young Hoon; Woo, Hoon Young [College of Medicine, Inje Univ., Kimhae (Korea, Republic of)
To determine whether the wall thickening of the maxillary sinus is a characteristic finding in aspergillosis. In 103 patients, including 26 with aspergillosis, 21 with inverted papilloma (IP), and 56 with unilateral chronic sinusitis, the thickness of the maxillary sinus wall was determined by CT scanning. All cases were proven pathologically, and patients with a history of previous surgery of bone destruction were excluded. Two neuroradiologists retrospectively reviewed the CT scans using bone window settings for sinus wall hyperostosis and the presence of intrasinus calcification. Thickening of the maxillary sinus wall was assessed visually in a semiquantitative manner, and graded as 'none' (absence of thickening), 'mild' (thickening of up to 1.5 times), or moderate ot severe(over 1.5 times thicker than normal contralateral sinus wall at its thickest point). Moderate to severe wall thickening was found only in patients with aspergillosis (21/26, 80.8%). Mild wall thickening was seen in two patients with aspergillosis (2/26, 7.7%), in 12 of 21 with IP (57.1%), and in 5 of 56 with chronic maxillary sinusitis (8.9%). Most cases of chronic maxillary sinusits( 51/56,91.1%), 9/21 IP cases (42.9%), and 3/26 cases of aspergillosis (11.5%) showed no thickening of the maxillary sinus wall. Calcifications were found in 18 patients with aspergillosis (69.2%), in no patient with IP (0%), and in one with chronic maxillary sinusitis (1.8%). We suggest that 'moderate to severe' wall thickening of the maxillary sinus is the characteristic finding of aspergillosis. Although various sinonasal diseases can cause bone change, CT findings of hyperostosis of the maxillary sinus and intrasinus calcification are very helpful in differentiating fungal sinusitis from other types of chronic inflammatory lesions.
Economic considerations in the treatment of invasive aspergillosis: a review of voriconazole pharmacoeconomic studies
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Kem P Krueger
Full Text Available Kem P Krueger, A Christie NelsonSchool of Pharmacy, University of Wyoming, Laramie, WY, USAAbstract: Invasive aspergillosis is a life-threatening fungal infection predominately affecting immunocompromised individuals. The incidence of inpatient-treated aspergillosis cases in the US is estimated to be between 3.02 and 3.80 per 10,000 hospitalized patients. The estimated difference in hospital costs of patients with an aspergillosis infection is US$36,867 to US$59,356 higher than those of patients without the infection. Voriconazole is a synthetic, broad spectrum triazole antifungal agent, with FDA-approved indications for the treatment of invasive aspergillosis, esophageal candidiasis, candidemia in nonneutropenic patients, invasive candidiasis, and infections due to Scedosporium apiospermum and Fusarium species in patients refractory to or intolerant of other therapy. Eight cost-effectiveness analyses, one cost-minimization analysis, and one cost analysis were identified from a Medline search. The 10 pharmacoeconomic analyses were conducted in six different countries comparing voriconazole to conventional amphotericin B, liposomal amphotericin B, itraconazole, and caspofungin. All the cost-effectiveness and cost-minimization analyses identified voriconazole as the most cost-effective therapy. The cost analysis demonstrated voriconazole cost-savings. While the acquisition costs of voriconazole are higher than those of conventional amphotericin B, the toxicity profile and rate of treatment success associated with voriconazole result in lower total treatment costs per successfully treated patient.Keywords: voriconazole, antifungal agents, invasive aspergillosis, pharmacoeconomics
Chronic necrotizing pulmonary aspergillosis presenting as bilateral pleural effusion: a case report
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Rajalingham Sakthiswary
Full Text Available Abstract Introduction Chronic necrotizing pulmonary aspergillosis is an uncommon subacute form of Aspergillus infection. It typically occurs in immunocompromised individuals and in those with underlying lung disease. This interesting case highlights the occurrence of this entity of aspergillosis in an immunocompetent middle-aged woman with atypical radiological findings. To the best of our knowledge this is the first case report of chronic necrotizing pulmonary aspergillosis presenting with pleural effusion. Case presentation Our patient was a 64-year-old Malay woman with a background history of epilepsy but no other comorbidities. She was a lifelong non-smoker. She presented to our facility with a six-month history of productive cough and three episodes of hemoptysis. An initial chest radiograph showed bilateral pleural effusion with bibasal consolidation. Bronchoscopy revealed a white-coated endobronchial tree and bronchoalveolar lavage culture grew Aspergillus niger. A diagnosis of chronic necrotizing pulmonary aspergillosis was made based on the clinical presentation and microbiological results. She responded well to treatment with oral itraconazole. Conclusions The radiological findings in chronic necrotizing pulmonary aspergillosis can be very diverse. This case illustrates that this condition can be a rare cause of bilateral pleural effusion.
Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole
P.E. Bunskoek (Paulien); S. Seyedmousavi (Seyedmojtaba); S. Gans (Steven); van Vierzen, P.B.J. (Peter B.J.); W.J. Melchers (Willem); C.E. van Elk; J.W. Mouton (Johan); P.E. Verweij (Paul)
textabstractInvasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded,
Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole
Bunskoek, P.E.; Seyedmousavi, S.; Gans, S.J.; Vierzen, P.B. van; Melchers, W.J.G.; Elk, C.E. van; Mouton, J.W.; Verweij, P.E.
Invasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded, high dose
Silva Filho, Rodolfo Pinho da; Xavier, Melissa Orzechowski; Martins, Aryse Moreira; Ruoppolo, Valéria; Mendoza-Sassi, Raúl Andrés; Adornes, Andréa Corrado; Cabana, Ângela Leitzke; Meireles, Mário Carlos Araújo
Aspergillosis, an opportunistic mycosis caused by the Aspergillus genus, affects mainly the respiratory system and is considered one of the most significant causes of mortality in captive penguins. This study aimed to examine a 6-yr period of cases of aspergillosis in penguins at the Centro de Recuperação de Animais Marinhos (CRAM-FURG), Rio Grande, Brazil. A retrospective cohort study was conducted using the institution's records of penguins received from January 2004 to December 2009. Animals were categorized according to the outcome "aspergillosis," and analyzed by age group, sex, oil fouling, origin, prophylactic administration of itraconazole, period in captivity, body mass, hematocrit, and total plasma proteins. A total of 327 Magellanic penguins (Spheniscus magellanicus) was studied, 66 of which died of aspergillosis. Proportionate mortality by aspergillosis was 48.5%, and incidence density was 7.3 lethal aspergillosis cases per 100 penguins/mo. Approximately 75% of the aspergillosis cases occurred in penguins that had been transferred from other rehabilitation centers, and this was considered a significant risk factor for the disease. Significant differences were also observed between the groups in regard to the period of time spent in captivity until death, hematocrit and total plasma proteins upon admission to the center, and body mass gain during the period in captivity. The findings demonstrate the negative impacts of aspergillosis on the rehabilitation of Magellanic penguins, with a high incidence density and substantial mortality.
Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis
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Ibrahim Ahmed Janahi
Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is a pulmonary disorder that often occurs in patients with asthma or cystic fibrosis (CF and is characterized by a hypersensitivity response to the allergens of the fungus Aspergillus fumigatus. In patients with CF, growth of A. fumigatus hyphae within the bronchial lumen triggers an immunoglobulin E (IgE-mediated hypersensitivity response that results in airway inflammation, bronchospasm, and bronchiectasis. In most published studies, the prevalence of ABPA is about 8.9% in patients with CF. Since the clinical features of this condition overlap significantly with that of CF, ABPA is challenging to diagnose and remains underdiagnosed in many patients. Diagnosis of ABPA in CF patients should be sought in those with evidence of clinical and radiologic deterioration that is not attributable to another etiology, a markedly elevated total serum IgE level (while off steroid therapy and evidence of A. fumigatus sensitization. Management of ABPA involves the use of systemic steroids to reduce inflammation and modulate the immune response. In patients who do not respond to steroids or cannot tolerate them, antifungal agents should be used to reduce the burden of A. fumigatus allergens. Recent studies suggest that omalizumab may be an effective option to reduce the frequency of ABPA exacerbations in patients with CF. Further randomized controlled trials are needed to better establish the efficacy of omalizumab in managing patients with CF and ABPA.
Sinonasal aspergillosis in a British Shorthair cat in the UK
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Alice Tamborini
Full Text Available Case summary A 13-year-old, castrated male, British Shorthair cat presented for investigation of chronic, intermittent, bilateral epistaxis and stertor. CT revealed severe asymmetric bilateral intranasal involvement with extensive turbinate lysis, increased soft tissue attenuation and lysis of the sphenopalatine bone and cribriform plate. On retroflexed pharyngoscopy, a plaque-like mass occluded the choanae. Rostral rhinoscopic examination revealed extensive loss of nasal turbinates, necrotic tissue and mucosal fungal plaques in the left nasal cavity. The right nasal cavity was less severely affected. The nasal cavities were debrided extensively of plaques and necrotic tissue. Aspergillus fumigatus was isolated on fungal culture, and species identity was confirmed using comparative sequence analysis of the partial β-tubulin gene. On histopathology of nasal biopsies, there was ulcerative lymphoplasmacytic and neutrophilic rhinitis, and fungal hyphae were identified on nasal mucosa, consistent with a non-invasive mycosis. The cat was treated with oral itraconazole after endoscopic debridement, but signs relapsed 4.5 months from diagnosis. Residual left nasal fungal plaques were again debrided endoscopically and oral posaconazole was administered for 6 months. Fourteen months from diagnosis, the cat remains clinically well with mild intermittent left nasal discharge secondary to atrophic rhinitis. Relevance and novel information This is the first case of rhinoscopically confirmed sinonasal aspergillosis to be diagnosed in a cat in the UK. Endoscopic confirmation of resolution of infection is useful in cases where mild nasal discharge persists after treatment.
Concomitant orbital aspergillosis and mucormycosis in a 17 months old immunocompetent child
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Fatima A. Habroosh
Full Text Available Isolated multiple orbital fungal infection (aspergillosis & mucormycosis is extremely rare disease in immunocompetent individuals and especially in children. Placement of prosthetic device during the surgery could be one of the risk factors. The presentation is usually masquerading other entities which make early diagnosis a challengeable. This case presenting a 17 months old immunocompetent child who is diagnosed with isolated multiple orbital fungal infection: aspergillosis & mucormycosis. The presentation was mimicking orbital cellulitis and chronic dacryocystitis. The definitive diagnosis was made by tissue biopsy. The child was managed by surgical debridement and IV amphotericin B liposomal. High index of suspicion to fungal infection should be considered after surgical intervention with insertion prosthetic materials. To the best of our knowledge, orbital aspergillosis in immunocompetent young children is exceptionally rare.
Etiologic Agents and Diseases Found Associated with Clinical Aspergillosis in Falcons
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Walter Tarello
Full Text Available The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (=36 or multiple coinfections (=28. Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS (=29, Caryospora sp. (=16, Serratospiculum seurati infestation (=14, cestodiasis (=6, bumblefoot (=5, trematodosis due to Strigea falconispalumbi (=5, trichomoniasis (=4, Babesia shortti (=4, Mannheimia (Pastorella haemolytica (=4, interstitial hepatitis (=4, Escherichia coli (=3, and Clostridium perfringens enterotoxemia (=2. Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis.
CLINICAL AND PATHOLOGICAL FINDINGS OF ASPERGILLOSIS IN MAGELLANIC PENGUINS (Spheniscus magellanicus
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Full Text Available We studied a series of fifteen fatal cases of aspergillosis in penguins (Spheniscus magellanicus, seen over a 4-year period at a rehabilitation center in Southern Brazil. The clinical and pathological findings based on the lesions found at necropsy are described herein. The majority of animals (11/15 had sudden death without clinical signs. In 33.3% (5/15 of the cases, aspergillosis was restricted to the respiratory system and 66.6% showed disseminateddisease, with liver, kidney, adrenal gland and gastrointestinal tract involvement. Typical lesions were characterized as white-yellowish granulomatous nodules. To the best of our knowledge, this is the largest series of aspergillosis cases described in penguins in SouthAmerica.
Direct molecular diagnosis of aspergillosis and CYP51A profiling from respiratory samples of French patients
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Yanan Zhao
Full Text Available Background: Microbiological diagnosis of aspergillosis and triazole resistance is limited by poor culture yield. To better estimate this shortcoming, we compared culture and molecular detection of A. fumigatus in respiratory samples from French patients at risk for aspergillosis. Methods: A total of 97 respiratory samples including bronchoalveolar lavages (BAL, bronchial aspirates (BA, tracheal aspirates, sputa, pleural fluids, and lung biopsy were collected from 33 patients having invasive aspergillosis (n=12, chronic pulmonary aspergillosis (n=3, allergic bronchopulmonary aspergillosis (n=7 or colonization (n=11 and 28 controls. Each specimen was evaluated by culture, pan-Aspergillus qPCR, and CYP51A PCR and sequencing. Results: One A. flavus and 19 A. fumigatus with one multiazole resistant strain (5.3% were cultured from 20 samples. Culture positivity was 62.5%, 75%, 42.9%, and 15.8% in ABPA, CPA, IA and colonized patients, respectively. Aspergillus detection rate was significantly higher by pan-Aspergillus qPCR than by culture in IA (90.5% vs 42.9%; P<0.05 and colonization group (73.7% vs 15.8%; P<0.05. The CYP51A PCR found one TR34/L98H along with 5 novel cyp51A mutations (4 non-synonymous and 1 promoter mutations, yet no association can be established currently between these novel mutations and azole resistance. The analysis of 11 matched pairs of BA and BAL samples found that 9/11 BA carried greater fungal load than BAL and CYP51A detection was more sensitive in BA than in BAL. Conclusion: Direct molecular detection of Aspergillus spp. and azole resistance markers are useful adjunct tools for comprehensive aspergillosis diagnosis. The observed superior diagnostic value of BAs to BAL fluids warrants more in-depth study.
Role of itraconazole in the management of aspergillosis in treated patients of pulmonary tuberculosis
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Gupta P
Full Text Available Sputum/ bronchial washings of 445 patients with residual tubercular cavitation were subjected to smear and culture examination to isolate fungi. Patients suffering from aspergillosis were put on oral itraconazole daily for 6 months and monitored clinicoradiologically during and after therapy. About half of the patients of aspergilloma and 85% of the patients of chronic necrotizing pulmonary aspergillosis improved by 3 months of therapy. Nausea and headache observed during therapy in 8 and 4 patients respectively were mild and self limiting. Relapses were seen in 8 out of the 37 patients who had completed 6 months therapy and available for follow-up.
Development of Aspergillosis in a cohort of non-neutropenic, non-transplant patients colonised by Aspergillus spp.
Barberán, José; García-Pérez, Francisco-Javier; Villena, Victoria; Fernández-Villar, Alberto; Malmierca, Eduardo; Salas, Cristina; Giménez, María-José; Granizo, Juan-José; Aguilar, Lorenzo
A previous study explored factors discriminating colonization and true infection among non-transplant, non-neutropenic patients with repeated Aspergillus spp. isolation from lower respiratory samples. The present study explored the evolution of patients with Aspergillus colonization in that study to determine the percentage of cases progressing to aspergillosis and time to development. Clinical records were retrospectively reviewed (for each patient from his end date in the past study) and data from all respiratory processes suffered by patients up to April 2015 were recorded. Comparisons of variables were performed between colonized patients that developed aspergillosis and those that did not. A Kaplan-Meier curve was used to describe time to development of aspergillosis in chronic obstructive pulmonary disease (COPD) patients for II-IV stages of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. Sixty seven colonized patients were followed, 12 of them (17.9%) developed aspergillosis. Diagnoses included six tracheobronchitis (4 invasive, 2 simple tracheobronchitis), four pulmonary disease (2 invasive pulmonary aspergillosis, 2 chronic pulmonary aspergillosis), one allergic bronchopulmonary aspergillosis and one pulmonary aspergilloma. Up to 47 (70.4%) of the study patients presented COPD. Among patients developing aspergillosis COPD was more frequent (100%) than among those that did not develop aspergillosis (35 out of 55; 63.6%) (p = 0.012), as well as GOLD IV patients were more frequent among COPD patients developing aspergillosis than among COPD patients that did not (50.0 vs. 26.1%, p = 0.046). Mean time to development of aspergillosis was 18.4 months (median: 8.5) with a wide range (1-58). Overtime, the percentage of patients developing aspergillosis was significantly higher among GOLD IV patients than among GOLD II-III patients (p = 0.032). The high percentage of cases progressing to aspergillosis among colonized
Allergic bronchopulmonary aspergillosis in Japan: A nationwide survey.
Oguma, Tsuyoshi; Taniguchi, Masami; Shimoda, Terufumi; Kamei, Katsuhiko; Matsuse, Hiroto; Hebisawa, Akira; Takayanagi, Noboru; Konno, Satoshi; Fukunaga, Koichi; Harada, Kazuki; Tanaka, Jun; Tomomatsu, Katsuyoshi; Asano, Koichiro
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease characterized by a hypersensitivity reaction to Aspergillus species colonizing the airways. The clinical characteristics of ABPA may differ depending on genetic and environmental background. We performed a nationwide survey to determine the clinical characteristics of ABPA in Japan. In 2013, a questionnaire on physician-diagnosed ABPA/allergic bronchopulmonary mycosis was sent to 903 medical centers specializing in respiratory or allergic diseases. Cases fulfilling the following criteria were categorized as possible ABPA-central bronchiectasis (ABPA-CB): 1) presence of specific serum immunoglobulin E (IgE) antibodies or a positive skin reaction to Aspergillus, and 2) bronchiectasis or mucoid impaction in the central bronchi. Of 499 physician-diagnosed cases reported by 132 clinical centers, 358 cases met the criteria for possible ABPA-CB. Median age of ABPA-CB onset was 57 (interquartile range, 44-68) years; later-onset disease, developing ≥50 years of age, accounted for 66% of the cases and was associated with female sex, delayed onset of asthma, and lower levels of serum IgE. A third of the patients (120 patients, 34%) exhibited low levels of serum total IgE (<1000 IU/mL). Aspergillus species were isolated from sputum in 126/213 cases (59%), and Schizophyllum commune was identified in 12 (6%) patients. During the course of the treatment, ABPA recurred in 169 (48%) cases. This nationwide survey identified several unique clinical characteristics of ABPA in Japan, such as late-onset, relatively lower serum IgE levels, and frequent recurrences/flares. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.
Pulmonary aspergillosis and aflatoxins in chronic lung diseases.
Ali, Sana; Malik, Abida; Shahid, Mohd; Bhargava, Rakesh
Fungal infections of lung have become increasingly common during the last few decades. Aspergillosis and the role of aflatoxins in various chronic lung diseases have not been extensively studied. Bronchoalveolar lavage (BAL) samples and sera from 40 patients of chronic lung diseases were analyzed for galactomannan antigen (GM) and aflatoxin by enzyme-linked immunosorbent assay. Direct microscopy and culture of BAL samples were also done to detect the Aspergillus species. Results revealed that 15 (37.5 %) of the 40 patients had growth of Aspergillus on BAL culture. Out of these culture-positive cases, 13 (86.7 %) patients were positive for galactomannan antigen also. About 62.5 % cases did not show growth of Aspergillus in BAL culture. However, galactomannan antigen could be detected in 20 % of these patients. Overall, 20 % patients were diagnosed as proven invasive fungal disease (IFD), 32.5 % were of probable IFD, 17.5 % of possible IFD. Aspergillus growth was observed in 100 % of proven and 53.8 % of probable IFD cases. Galactomannan antigen was found in 100 % cases of proven and 76.9 % of probable IFD. Ten (25 %) patients were found to be positive for aflatoxins. It was detected in 6 (40 %) of culture-positive cases. About 62.5 % of the cases with proven IFD and 46.1 % of probable IFD had aflatoxin in their samples. Aflatoxin positivity was found to be more in patients with proven IFD than in probable IFD, and higher level of aflatoxins was detected in cases with proven IFD. Significant difference was observed in aflatoxin positivity among food grain workers when compared to other occupations.
Clinical and Pathological Correlation in Pediatric Invasive Pulmonary Aspergillosis
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Nattachai Anantasit
Full Text Available IntroductionInvasive' pulmonary aspergillosis (IPA has been one of the major causes of mortality in immunocompromised patients. The gold standard method for a diagnosis of IPA is histopathological examination of the lung tissue; however, post-procedural bleeding limits the feasibility of lung biopsy. The European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and The National Institute of Allergy and Infectious Disease Mycoses Study Group (EORTC/MSG defined IPA. The objective of this study was to validate the EORTC/MSG 2008 definition of IPA, compared with histopathology in the pediatric population.MethodsHistopathological examinations of lung tissues of children aged 1 month–18 years with respiratory tract infection at the time of obtaining biopsy were retrieved. Retrospective chart reviews for clinical characteristics were performed. IPA diagnosis was classified according to the EORTC/MSG 2008 definition.ResultsDuring the 10-year period, there were 256 lung tissues, of which 58 specimens were suspected to have pulmonary infection. Fourteen patients (24% were noted to have IPA. Seven patients (50% with proven IPA were classified as probable, while the remaining 50% were classified as possible, and none were classified as no IPA, by using EORTC/MSG 2008 definition. Other 44 specimens demonstrated 14 (32%, 14 (32%, and 16 (36% were classified as probable, possible, and no IPA, respectively. When comparing probable or possible IPA with no IPA, we found that the EORTC/MSG 2008 definition had 100% sensitivity, 36% specificity, 33% positive predictive value, and 100% negative predictive value in diagnosis of IPA.ConclusionOur study illustrated that the EORTC/MSG 2008 definition provided an excellent sensitivity but low specificity for diagnosing IPA.
Detection of Gliotoxin in Patients with Pulmonary Aspergillosis
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Baheeja A.Hmood
Full Text Available Objective: This study was designed to detection of gliotoxin in patients with pulmonary Aspergillosis . Method: A total of 100 samples (sputum and blood were selected from 100 outpatients who attended to Al-Qadissiyia Centre of Tuberculosis and Chest Diseases, , during the period from 2014 to May 2015. All patients had clinical manifestation in addition to 100 sample (sputum and blood as control group. Results: All patients infected with fungi and three different genus isolated from sputum of patients ,these genus are Aspergillus sp. 60 Isolates( 60%with three species were A.fumigatus (50% A.flavus(33.3% and A.niger (16.6% Cryptococcus neoformans (20% Penicillum sp.(14% and Rhizopus sp.(6%. Seventy nine (79% from patients had gliotoxin distributed in their sputum and serum by ratio (71% and 5 (5% had GT in their serum while 3 (3% of them had GT in their sputum.. So this toxin was found in50(5% in control group distributed in sputum and serum by (40% , 6(6%in sputum and 4(4%in serum. The concentration of GT in sputum of patients was (40-63µg/kg and in sputum of control group was (16-23µg/kg and in serum of patients was (33-47µg/kg and (10-21µg/kg in serum of control group. and all A.fumigatus isolates 30 (100 %were have gliz gene. Conclusion: Several species of Aspergillus and other fungi as well as possibly yeast, produced gliotoxin both in vitro and in vivo. More attention should be paid to this mycotoxin because of its multi-faceted toxic properties.
Renal infarction secondary to invasive aspergillosis in a 5-year-old girl with acute lymphoblastic leukemia.
Lee, Ju Hyun; Im, Soo Ah; Cho, Bin
Aspergillus species have angioinvasive properties and can involve extrapulmonary organs by hematogenous spread from the lungs. However, renal involvement by Aspergillus is uncommon and is usually associated with the formation of abscesses. We report an unusual case of invasive renal aspergillosis presenting with extensive renal infarction in a 5-year-old girl with acute lymphoblastic leukemia. This case emphasizes the fact that renal aspergillosis initially presents with only renal infarction, and metastatic-embolism by invasive aspergillosis should be considered in differential diagnosis for any focal lesion of kidney in a patient with leukemia.
Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands.
Jansen, J.P.; Meis, J.F.G.M.; Blijlevens, N.M.A.; Wout, J.W. van 't
OBJECTIVE: To asses the cost-effectiveness of voriconazole in comparison to conventional amphotericin B and itraconazole for the treatment of invasive aspergillosis in the Netherlands. METHODS: The cost-effectiveness of voriconazole in comparison to conventional amphotericin B or itraconazole was
Immunoblotting, radioallergosorbent test (RAST), and enzyme-linked immunosorbent assay (ELISA) were performed to determine specific IgE and IgG responses to Aspergillus fumigatus (Af) allergens (IgE-Af; IgG-Af). Serology results were compared in patients with allergic bronchopulmonary aspergillosis
Efficacy and pharmacodynamic of voriconazole combined with anidulafungin in azole resistant invasive aspergillosis.
Seyedmousav, S.; Bruggemann, R.J.M.; Melchers, W.J.G.; Verweij, P.E.; Mouton, J.W.
OBJECTIVES: Azole resistance is an emerging problem in the treatment of Aspergillus fumigatus infections. Combination therapy may be an alternative approach to improve therapeutic outcome in azole-resistant invasive aspergillosis (IA). The in vivo efficacy of voriconazole and anidulafungin was
Endobronchial valves in the management of bronchial fistulae caused by bronchopulmonary aspergillosis.
Williams, Rhys; Krishnadas, Rakesh; Patel, Bipen; Jarad, Nabil
Following an aggressive episode of bronchopulmonary aspergillosis, a 54-year-old man developed a symptomatic air leak via a tunnel between the left upper lobe and an extra chest wall cavity. Following the failure of several surgical procedures to close the tunnel, endobronchial valves normally used in management of emphysema were used to successfully treat the air leak. 2015 BMJ Publishing Group Ltd.
IL-37 inhibits inflammasome activation and disease severity in murine aspergillosis
Moretti, S.; Bozza, S.; Oikonomou, V.; Renga, G.; Casagrande, A.; Iannitti, R.G.; Puccetti, M.; Garlanda, C.; Kim, S.; Li, S.; Veerdonk, F.L. van de; Dinarello, C.A.; Romani, L.
Since IL-37 transgenic mice possesses broad anti-inflammatory properties, we assessed whether recombinant IL-37 affects inflammation in a murine model of invasive pulmonary aspergillosis. Recombinant human IL-37 was injected intraperitoneally into mice prior to infection and the effects on lung
Rapid Diagnosis of Azole-Resistant Aspergillosis by Direct PCR Using Tissue Specimens
van der Linden, Jan W. M.; Snelders, Eveline; Arends, Jan P.; Daenen, Simon M.; Melchers, Willem J. G.; Verweij, Paul E.
We report the use of PCR techniques on a formalin-fixed and paraffin-embedded tissue specimen for direct detection of one dominant azole resistance mechanism in a case of disseminated invasive aspergillosis. Rapid detection of mutations associated with azole resistance directly in tissue
Rapid diagnosis of azole-resistant aspergillosis by direct PCR using tissue specimens.
Linden, J.W.M. van der; Snelders, E.; Arends, J.P.; Daenen, S.M.G.J.; Melchers, W.J.G.; Verweij, P.E.
We report the use of PCR techniques on a formalin-fixed and paraffin-embedded tissue specimen for direct detection of one dominant azole resistance mechanism in a case of disseminated invasive aspergillosis. Rapid detection of mutations associated with azole resistance directly in tissue
Tolerance and efficacy of amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in haematological patients
Erjavec, Z; Woolthuis, GMH; deVriesHospers, HG; Daenen, SMGJ; dePauw, B; Halie, MR
The tolerance of aerosolised amphotericin B as prophylaxis against invasive pulmonary aspergillosis was investigated in 61 granulocytopenic periods in 42 patients treated for a haematologic malignancy. Each patient was to receive amphotericin B in doses escalating to 10 mg three times daily
Invasive pulmonary aspergillosis: role of early diagnosis and surgical treatment in patients with acute leukemia
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Ursavas Ahmet
Full Text Available Abstract Background Aspergillus is a ubiquitous soil-dwelling fungus known to cause significant pulmonary infection in immunocompromised patients. The incidence of aspergillosis has increased during the past two decades and is a frequently lethal complication of acute leukemia patients that occurs following both chemotherapy and bone marrow transplantation. The diagnosis of invasive pulmonary aspergillosis (IPA according to the criteria that are established by European Organization for the Research and Treatment of Cancer and Mycoses Study Group raise difficulties in severely ill patients. Despite established improvements in field of diagnosis (galactomannan antigen, quantitative PCR, real-time PCR for Aspergillus spp., and findings of computed tomography and treatment with new antifungals, it is still a major problem in patients with acute leukemia. However, prompt and effective treatment of IPA is crucial because most patients will need subsequent chemotherapy for underlying hematologic disease as soon as possible. Case presentation We report a 33-year-old male patient with acute promyelocytic leukemia diagnosed in 1993 that developed invasive pulmonary aspergillosis due to A. flavus at relapse in 2003. The patient was successfully treated with liposomal amphotericin B and underwent surgical pulmonary resection. The operative course was uneventful. Conclusion This report emphasizes the clinical picture, applicability of recent advances in diagnostic and therapeutic approaches for IPA. For early identification of a patient infected with IPA, a high index of suspicion and careful clinical and radiological examinations with serial screening for galactomannan should be established. If aspergillosis is suspected, anti-aspergillosis drug should be administered immediately, and if a unique pulmonary lesion remains, surgical resection should be considered to prevent reactivation during consecutive chemotherapy courses and to improve the outcome.
Invasive pulmonary aspergillosis: role of early diagnosis and surgical treatment in patients with acute leukemia
Ali, Ridvan; Ozkalemkas, Fahir; Ozcelik, Tulay; Ozkocaman, Vildan; Ozkan, Atilla; Bayram, Sami; Ener, Beyza; Ursavas, Ahmet; Ozal, Guze; Tunali, Ahmet
Background Aspergillus is a ubiquitous soil-dwelling fungus known to cause significant pulmonary infection in immunocompromised patients. The incidence of aspergillosis has increased during the past two decades and is a frequently lethal complication of acute leukemia patients that occurs following both chemotherapy and bone marrow transplantation. The diagnosis of invasive pulmonary aspergillosis (IPA) according to the criteria that are established by European Organization for the Research and Treatment of Cancer and Mycoses Study Group raise difficulties in severely ill patients. Despite established improvements in field of diagnosis (galactomannan antigen, quantitative PCR, real-time PCR for Aspergillus spp., and findings of computed tomography) and treatment with new antifungals, it is still a major problem in patients with acute leukemia. However, prompt and effective treatment of IPA is crucial because most patients will need subsequent chemotherapy for underlying hematologic disease as soon as possible. Case presentation We report a 33-year-old male patient with acute promyelocytic leukemia diagnosed in 1993 that developed invasive pulmonary aspergillosis due to A. flavus at relapse in 2003. The patient was successfully treated with liposomal amphotericin B and underwent surgical pulmonary resection. The operative course was uneventful. Conclusion This report emphasizes the clinical picture, applicability of recent advances in diagnostic and therapeutic approaches for IPA. For early identification of a patient infected with IPA, a high index of suspicion and careful clinical and radiological examinations with serial screening for galactomannan should be established. If aspergillosis is suspected, anti-aspergillosis drug should be administered immediately, and if a unique pulmonary lesion remains, surgical resection should be considered to prevent reactivation during consecutive chemotherapy courses and to improve the outcome. PMID:16872530
Invasive pulmonary aspergillosis: role of early diagnosis and surgical treatment in patients with acute leukemia.
Ali, Ridvan; Ozkalemkas, Fahir; Ozcelik, Tulay; Ozkocaman, Vildan; Ozkan, Atilla; Bayram, Sami; Ener, Beyza; Ursavas, Ahmet; Ozal, Guze; Tunali, Ahmet
Aspergillus is a ubiquitous soil-dwelling fungus known to cause significant pulmonary infection in immunocompromised patients. The incidence of aspergillosis has increased during the past two decades and is a frequently lethal complication of acute leukemia patients that occurs following both chemotherapy and bone marrow transplantation. The diagnosis of invasive pulmonary aspergillosis (IPA) according to the criteria that are established by European Organization for the Research and Treatment of Cancer and Mycoses Study Group raise difficulties in severely ill patients. Despite established improvements in field of diagnosis (galactomannan antigen, quantitative PCR, real-time PCR for Aspergillus spp., and findings of computed tomography) and treatment with new antifungals, it is still a major problem in patients with acute leukemia. However, prompt and effective treatment of IPA is crucial because most patients will need subsequent chemotherapy for underlying hematologic disease as soon as possible. We report a 33-year-old male patient with acute promyelocytic leukemia diagnosed in 1993 that developed invasive pulmonary aspergillosis due to A. flavus at relapse in 2003. The patient was successfully treated with liposomal amphotericin B and underwent surgical pulmonary resection. The operative course was uneventful. This report emphasizes the clinical picture, applicability of recent advances in diagnostic and therapeutic approaches for IPA. For early identification of a patient infected with IPA, a high index of suspicion and careful clinical and radiological examinations with serial screening for galactomannan should be established. If aspergillosis is suspected, anti-aspergillosis drug should be administered immediately, and if a unique pulmonary lesion remains, surgical resection should be considered to prevent reactivation during consecutive chemotherapy courses and to improve the outcome.
An economic evaluation of voriconazole versus amphotericin B for the treatment of invasive aspergillosis in Canada.
Rotstein, Coleman; Laverdière, Michel; Marciniak, Anne; Ali, Farzad
Invasive aspergillosis (IA) is a serious fungal infection that affects immunocompromised patients. The Global Comparative Aspergillosis study demonstrated that voriconazole, a new broad-spectrum triazole, had better responses and improved survival compared with conventional amphotericin B deoxycholate (CAB) and other licensed antifungal therapy (OLAT) for the treatment of definite or probable aspergillosis. To compare costs and outcomes of voriconazole and CAB for the treatment of definite or probable aspergillosis in Canada. A cost-consequence decision tree model was designed to reflect the treatment pathways used in clinical practice when using voriconazole or CAB as primary therapy for IA. Therapy included initial treatment with either voriconazole or CAB and then switched to an OLAT in the event of an inadequate response, severe toxicity or intolerance. The principal data source used was the Global Comparative Aspergillosis study. The total cost of voriconazole when compared with CAB as initial therapy for IA was $38,319 versus $42,495 per patient, respectively, representing a 9.8% cost reduction for each patient treated with voriconazole. The higher mean cost in the CAB arm was primarily due to the high proportion of patients (73.7%) who were switched to an OLAT due to severe side effects or an inadequate response. Treating with voriconazole was a dominant strategy. The number of patients that had to be treated with voriconazole instead of CAB to save one additional life was eight. Voriconazole as primary treatment for IA increased the chances of successful treatment, improved survival and may represent a potential cost saving strategy in Canada.
The clinical presentations of pulmonary aspergillosis in children with cystic fibrosis - preliminary report.
Walicka-Serzysko, Katarzyna; Sands, Dorota
Pulmonary aspergillosis is a very serious complication in cystic fibrosis (CF) patients due to the great variety of its clinical presentations and the fact that it worsens the prognosis. We can distinguish the following: Aspergillus colonization (AC), Aspergillus infection (AI) and allergic bronchopulmonary aspergillosis (ABPA). Aspergillus colonization (AC) is defined as isolation of Aspergillus spp. from 50% ormore sputum samples over six months to one year without observing deterioration in lung function and an increase in such respiratory symptoms as cough. Aspergillus infection (AI) is diagnosed in subjects with Aspergillus colonization and a decline in lung function, respiratory exacerbation with and without cough or with an incomplete response to a 2-4 week course of appropriate broad-spectrum antibiotics. Aspergillus can also cause allergic bronchopulmonary aspergillosis (ABPA). The classic diagnostic criteria of allergic bronchopulmonary aspergillosis in cystic fibrosis have been established during the Cystic Fibrosis Foundation Conference in 2001. To establish the prevalence of pulmonary aspergillosis in children with cystic fibrosis under the care of our centre and to investigate the potential predisposing factors to Aspergillus infection (AI) and allergic bronchopulmonary aspergillosis (ABPA). An analysis was conducted of the medical documentation of 374 children aged 0-18 years monitored regularly in the Cystic Fibrosis Centre of the Institute of Mother and Child in Warsaw from 01.01.2010 to 31.08.2014. We selected 13 patients who presented an evidently worsening clinical status and course of the bronchopulmonary disease (decline in lung function parameters, respiratory exacerbations with increased cough, new or recent abnormalities in chest imaging) despite standard treatment with a high calorie diet, supplementation of pancreatic enzymes and vitamins, dornase alpha, inhaled and/or oral antibiotics, inhaled or oral corticosteroids, bronchodilators
Severe neurological disorders and refractory aspergillosis in an adolescent treated by vincristine and voriconazole.
Bennis, Y; Bodeau, S; Lutun, A; Gourmel, A; Solas, C; Quaranta, S; Guillaume, N; Chouaki, T; Lemaire-Hurtel, A-S; Masmoudi, K
Voriconazole and vincristine are major therapeutics in paediatric haematology. However, the risk-benefit ratio of the treatment of invasive aspergillosis with voriconazole in patients receiving vincristine-based chemotherapy remains unclear. We report severe peripheral and central neurological disorders in a 14-year-old girl with T-cell acute lymphoblastic leukaemia and pulmonary aspergillosis. The case describes a strong exacerbation by voriconazole of the vincristine-induced neuropathic pains. It shows the high variability of the trough serum concentration of voriconazole leading to antifungal treatment failure and suggests that its own central neurotoxicity could also be potentiated by vincristine. Given the risk of either insufficient antifungal efficacy or excessive neurological disorders, this case warns on a probable unfavourable risk-benefit profile of voriconazole during vincristine-based chemotherapy in adolescents. © 2017 John Wiley & Sons Ltd.
Invasive aspergillosis osteomyelitis in children - a case report and review of the literature
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Winterstein, Anton R.; Bohndorf, Klaus; Vollert, Kurt [Klinikum Augsburg, Department of Radiology, Augsburg (Germany); Wagner, Theodor [Klinikum Augsburg, Department of Pathology, Augsburg (Germany); Gnekow, Astrid [Klinikum Augsburg, Department of Pediatrics, Augsburg (Germany); Roemer, Frank W. [Klinikum Augsburg, Department of Radiology, Augsburg (Germany); Boston University School of Medicine, Department of Radiology, Boston, MA (United States)
Immunocompromised patients are at high risk of secondary infection associated with high morbidity. In children these complications include fungal osteomyelitis due to continuous infiltration or hematogenous spread. The case of a 4-year-old boy is presented who developed lumbalgia and thigh pain during ongoing chemotherapy for acute lymphatic leukemia. MRI revealed infarct-like lesions in the femur and L5 vertebra, which were biopsied. The histologic diagnosis was consistent with angioinvasive aspergillosis. A multifocal osseous presentation has rarely been described in children and an overview of the literature is presented. Invasive aspergillosis is a rare complication to be considered in children with MRI-detected bony lesions of infarct-like appearance. (orig.)
Pulmonary carcinosarcoma initially presenting as invasive aspergillosis: a case report of previously unreported combination
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Van Thien
Full Text Available Abstract Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for diagnosis, and mortality rate is high. We describe a case of primary carcinosarcoma of the lung concurrently occurring with invasive pulmonary aspergillosis in a 66-year old patient.
Systemic candidosis and concomitant aspergillosis and zygomycosis in two Amazon parakeets (Amazona aestiva).
Carrasco, L; Gómez-Villamandos, J C; Jensen, H E
Systemic candidosis and concomitant aspergillosis and zygomycosis were diagnosed immunohistochemically in two Amazon parakeets (Amazona aestiva). In the bird with systemic candidosis, subacute necrotic lesions were present in the lung and the gastrointestinal tract, whereas chronic giant cell-containing granulomas were located in the liver, heart, spleen and on the serosal lining of the small intestine. Although the lesions in the liver, heart and spleen most likely developed as a result of haematogenous spread, the granulomas on the serosal surface may have developed after a local transmural intestinal invasion. In the second bird, aspergillosis and zygomycosis were restricted to the lung, whereas some zygomycetes were found in the air sacs as well as in the heart and kidneys. In all organs the zygomycotic lesions were dominated by thrombosing vasculitis, supporting haematogenous dissemination.
IL-37 inhibits inflammasome activation and disease severity in murine aspergillosis.
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Silvia Moretti
Full Text Available Since IL-37 transgenic mice possesses broad anti-inflammatory properties, we assessed whether recombinant IL-37 affects inflammation in a murine model of invasive pulmonary aspergillosis. Recombinant human IL-37 was injected intraperitoneally into mice prior to infection and the effects on lung inflammation and inflammasome activation were evaluated. IL-37 markedly reduced NLRP3-dependent neutrophil recruitment and steady state mRNA levels of IL-1β production and mitigated lung inflammation and damage in a relevant clinical model, namely aspergillosis in mice with cystic fibrosis. The anti-inflammatory activity of IL-37 requires the IL-1 family decoy receptor TIR-8/SIGIRR. Thus, by preventing activation of the NLRP3 inflammasome and reducing IL-1β secretion, IL-37 functions as a broad spectrum inhibitor of the innate response to infection-mediated inflammation, and could be considered to be therapeutic in reducing the pulmonary damage due to non-resolving Aspergillus infection and disease.
Successful non-standard approaches to massive hemoptysis in invasive pulmonary aspergillosis
Mitrović Mirjana; Elezović Ivo; Suvajdžić-Vuković Nada; Antić Darko
Introduction. Invasive pulmonary aspergillosis (IA) is the most frequent invasive fungal infection in patients with hematological malignancies. Massive hemoptysis (MH) with blood loss more than 300- 600 ml in 24 hours is a rare (5-10% of IA patients) but frequently fatal complication. Standard treatment of MH, such as oxygenation, a semi-sitting position with the bleeding site down, bronchoscopical suctioning, antifungal therapy, transfusion support and surgical resection might be eithe...
The Diagnosis of Invasive and Noninvasive Pulmonary Aspergillosis by Serum and Bronchoalveolar Lavage Fluid Galactomannan Assay
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Shuzhen Zhang
Full Text Available The incidence and mortality of invasive pulmonary aspergillosis (IPA are rising, particularly in critically ill patients and patients with severe chronic obstructive pulmonary disease (COPD. Noninvasive aspergillosis occurring in these patients requires special attention because of the possibility of developing subsequent IPA, given the poor health and worsened immune state of these patients. We compared the performance of the Platelia galactomannan (GM enzyme immunoassay in the bronchoalveolar lavage fluid (BALF and serum. The sensitivity, and specificity of BALF-GM were 85.4% and 62.4%, and those of serum-GM were 67.9% and 93.5% at the cutoff index of 0.5. As the cutoff index increased, the specificity of BALF-GM detection was increased with the detriment of sensitivity. The area under the ROC curves was 0.817 (95% CI: 0.718–0.916 for BALF-GM and 0.819 (95% CI: 0.712–0.926 for serum-GM. The optimal cutoff index was 1.19 for BALF-GM, and the sensitivity and specificity were 67.9% and 89.2%. The BALF-GM assay is more sensitive in detecting pulmonary aspergillosis than serum-GM assay and fungal cultures. However, BALF-GM assay has a high false-positive rate at the cutoff index of 0.5. Hence, the diagnostic cutoff index of the BALF-GM assay should be improved to avoid the overdiagnosis of pulmonary aspergillosis in clinic.
Aspergillosis in Intensive Care Unit (ICU patients: epidemiology and economic outcomes
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Baddley John W
Full Text Available Abstract Background Few data are available regarding the epidemiology of invasive aspergillosis (IA in ICU patients. The aim of this study was to examine epidemiology and economic outcomes (length of stay, hospital costs among ICU patients with IA who lack traditional risk factors for IA, such as cancer, transplants, neutropenia or HIV infection. Methods Retrospective cohort study using Premier Inc. Perspective™ US administrative hospital database (2005–2008. Adults with ICU stays and aspergillosis (ICD-9 117.3 plus 484.6 who received initial antifungal therapy (AF in the ICU were included. Patients with traditional risk factors (cancer, transplant, neutropenia, HIV/AIDS were excluded. The relationship of antifungal therapy and co-morbidities to economic outcomes were examined using Generalized linear models. Results From 6,424 aspergillosis patients in the database, 412 (6.4% ICU patients with IA were identified. Mean age was 63.9 years and 53% were male. Frequent co-morbidities included steroid use (77%, acute respiratory failure (76% and acute renal failure (41%. In-hospital mortality was 46%. The most frequently used AF was voriconazole (71% received at least once. Mean length of stay (LOS was 26.9 days and mean total hospital cost was $76,235. Each 1 day lag before initiating AF therapy was associated with 1.28 days longer hospital stay and 3.5% increase in costs (p Conclusions Invasive aspergillosis in ICU patients is associated with high mortality and hospital costs. Antifungal timing impacts economic outcomes. These findings underscore the importance of timely diagnosis, appropriate treatment, and consideration of Aspergillus as a potential etiology in ICU patients.
Aspergillosis of the temporomandibular joint following irradiation of the parotid region: a case report.
Lo, W L; Chang, R C S; Yang, A H; Kao, S Y
We report a case of aspergillosis in the right temporomandibular joint (TMJ) with a history of parotid carcinoma and post-irradiation otitis. Previous treatment attempts with surgery and antibiotics were unsuccessful. Radical debridement of the glenoid fossae, supplemented with amphotericin B and adjunct hyperbaric oxygen (HBO) therapy, was provided to resolve the symptoms. This case report highlights the need to be aware of the possibility of invasive mycosis in immunocompromised patients.
Fatal invasive aspergillosis caused by Aspergillus niger after bilateral lung transplantation
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Enora Atchade
Full Text Available Aspergillus niger is usually considered to be a low virulence fungus, not commonly reported to cause invasive infections. Invasive pulmonary aspergillosis due to Aspergillus niger was diagnosed in a 43-year-old woman following bilateral lung transplantation. Intravenous voriconazole failed to control progression of the disease. Despite salvage therapy with a combination of voriconazole and caspofungin for 23 days, the patient developed massive hemoptysis leading to death. The authors report the clinical features and treatment of this case.
Invasive aspergillosis in the aortic arch with infectious Aspergillus lesions in pulmonary bullae
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Isao Watanabe
Full Text Available A patient with pulmonary bullae died of massive hemoptysis. At autopsy a hole was observed in the aortic wall. A microscopic examination indicated small Aspergillus lesions in pulmonary bullae and extensive necrotic lesions with Aspergillus hyphae in the media of the thoracic aorta. These findings led to a diagnosis of invasive aspergillosis in the aortic arch. This is a rare case in which Aspergillus invaded the aorta in a patient without hematologic neoplasms or neutropenia.
Severe cutaneous aspergillosis in a premature neonate linked to nonsterile disposable glove contamination?
Stock, Claire; Veyrier, Magali; Raberin, Hélène; Fascia, Pascal; Rayet, Isabelle; Lavocat, Marie Pierre; Teyssier, Georges; Berthelot, Philippe
After having eliminated a dysfunction of the hospital's ventilation system and any other possible environmental reservoir, the investigation of a fatal case of primary cutaneous aspergillosis in a neonate with extremely low birth weight led to the conclusion that nonsterile disposable gloves kept stored in their native packages were the likely source of contamination. Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.
Costo-efficacia dell'amfotericina B liposomiale nella terapia dell'aspergillosi invasiva
Mario Eandi
Invasive aspergillosis (IA) is a common and life-threatening infectious complication of immune system depression. Amphotericin B deoxycholate (AMB-d) has been considered standard therapy for IA for over 40 years, despite the fact that success rates rarely exceed 40% and adverse effects are quite common. At present two more recent pharmacological agents are available for the treatment of IA: liposomal amphotericin B (L-AMB) and voriconazole (VOR). In this article, we present a pharmaco-economi...
Pulmonary Aspergillosis in a Previously Healthy 13-Year-Old Boy
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Jonathan H. Rayment
Full Text Available Chronic granulomatous disease (CGD is a rare, polygenic primary immunodeficiency. In this case report, we describe a previously healthy 13-year-old boy who presented with multifocal pulmonary aspergillosis and was subsequently diagnosed with an autosomal recessive form of chronic granulomatous disease. CGD has a variable natural history and age of presentation and should be considered when investigating a patient with recurrent or severe infections with catalase-positive organisms.
Schwarz, Tobias; Kelley, Cristin; Pinkerton, Marie E.; Hartup, Barry K.
Respiratory diseases are a leading cause of morbidity and mortality in captivity reared, endangered whooping cranes (Grus americana). Objectives of this retrospective, case series, cross?sectional study were to describe computed tomography (CT) respiratory anatomy in a juvenile whooping crane without respiratory disease, compare CT characteristics with gross pathologic characteristics in a group of juvenile whooping cranes with respiratory aspergillosis, and test associations between the numb...
Primary aspergillosis of vocal cord: Long-term inhalational steroid use can be the miscreant
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Arpita Saha
Full Text Available Primary laryngeal aspergillosis is extremely rare, especially in an immunocompetent host. It is commonly found as a part of systemic infection in immunocompromised patients. A case of vocal cord aspergillosis with no systemic extension in an immunocompetent patient on long-term steroid metered dose inhaler (MDI is presented here, because of its rarity. The present case is a 28-year-old asthmatic female who was on inhalational steroid for 8 years, presented with sudden onset of severe dysphonia for 5 days. Fiberoptic laryngoscopy demonstrated whitish plaque involving right vocal cord, clinically suggestive of fungal laryngitis. Microlaryngeal laser surgery was performed with stripping of the plaque. Histopathology demonstrated ulcerated hyperplastic squamous epithelium with masses of fungal hyphae, which was confirmed to be Aspergillus species on fungal culture. This rare but serious adverse effect of long-term steroid MDI use must be kept in mind while treating an asthmatic patient. We also present a brief review of literature of laryngeal aspergillosis.
Invasive Aspergillosis in a Renal Transplant Recipient Successfully Treated with Interferon-Gamma
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C. Estrada
Full Text Available Invasive aspergillosis is a serious complication of solid organ transplantation. An early diagnosis is hampered by the lack of reliable serum markers and, even if appropriately diagnosed and treated with current antifungal agents, has a high mortality rate. We report a case of invasive pulmonary and cerebral aspergillosis in a renal transplant patient treated with IFN-γ in conjunction with combination anti-fungal therapy for six weeks in whom complete resolution of the fungal infection was achieved. Renal function remained intact throughout the treatment period. Surveillance CT scans of the chest and head showed resolution of prior disease but revealed a new left upper lobe mass four months after completion of treatment with IFN-γ. Biopsy of the lesion was positive for primary lung adenocarcinoma, for which she underwent left upper lobe resection. The pathology report confirmed clear surgical margins and lymph nodes and no evidence of fungal hyphae. IFN-γ should be considered early in the management of invasive aspergillosis in renal transplant patients. To date, allograft rejection has not been encountered.
Erythropoietin combined with liposomal amphotericin b improves outcome during disseminated aspergillosis in mice
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nathalie erousseau
Full Text Available Disseminated aspergillosis is responsible for a high mortality rate despite the use of antifungal drugs. Adjuvant therapies are urgently needed to improve the outcome. The aim of this study was to demonstrate that the cytoprotective effect of erythropoietin combined to amphotericin b can reduce the mortality rate in a murine model of disseminated aspergillosis. After infection with Aspergillus fumigatus, neutropenic mice were randomized to receive vehicle or 7,5 mg/Kg of Liposomal Amphotericin B (LAmB or 7,5 mg/Kg of LAmB combined with 1000 IU/Kg of EPO (16 mice per group. Aspergillus galactomannan and organ cultures were performed to evaluate fungal burden at day 5. Cumulative long-term survival was analyzed at day 12 post-infection according to the Kaplan-Meier method. At day 5, fungal burden was similar between non-treated and treated groups. At day 12, mortality rates were 75 %, 62.5 % and 31 % in control group, LAmB group and EPO/LAmB group, respectively. We observed a significant decreased in mortality using EPO/LAmB combination compared to control group (p < 0.01. LAmB single treatment did not improve the survival rate compared to control group (p = 0.155.Our results provided the first evidence that erythropoietin improved the outcome of mice presenting disseminated aspergillosis when combined with amphotericin b.
Performance of serum biomarkers for the early detection of invasive aspergillosis in febrile, neutropenic patients: a multi-state model.
Schwarzinger, Michaël; Sagaon-Teyssier, Luis; Cabaret, Odile; Bretagne, Stéphane; Cordonnier, Catherine
The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking. We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3)- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus. The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010), independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53). The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a standardized quantitative PCR assay.
Performance of serum biomarkers for the early detection of invasive aspergillosis in febrile, neutropenic patients: a multi-state model.
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Michaël Schwarzinger
Full Text Available The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking.We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus.The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010, independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53.The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a standardized quantitative PCR assay.
Invasive primary aspergillosis of the larynx presenting as hoarseness and a chronic nonhealing laryngeal ulcer in an immunocompetent host: a rare entity.
Gangopadhyay, Mimi; Majumdar, Kaushik; Bandyopadhyay, Arghya; Ghosh, Anup
Primary aspergillosis usually affects the paranasal sinuses, orbit, ear, and lower respiratory tract. Laryngeal aspergillosis usually occurs as a result of secondary invasion from the tracheobronchial tree, more commonly in immunocompromised hosts. Primary laryngeal localization of Aspergillus infection is seldom encountered. We report the case of an immunocompetent 42-year-old man who presented with hoarseness and a laryngeal ulcer of fairly long duration. A malignancy was initially suspected clinically, but a laryngoscopic biopsy led to a diagnosis of invasive primary laryngeal aspergillosis. No other focus of aspergillosis was found on x-ray and computed tomography. After identification of Aspergillus niger on culture, inquiries revealed no exposure to steroids, cytotoxic drugs, or irradiation, and workups for malignancy, human immunodeficiency virus infection, tuberculosis, and diabetes were negative. Although isolated laryngeal involvement is rare, aspergillosis may be considered in the differential diagnosis of a chronic nonhealing laryngeal ulcer that is clinically suggestive of a malignancy, even in an immunocompetent host.
Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole
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Paulien E. Bunskoek
Full Text Available Invasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded, high dose posaconazole was initiated aimed at achieving trough levels exceeding 3 mg/l. Posaconazole serum levels of 3–9.5 mg/l were achieved without significant side-effects. Follow-up bronchoscopy and computed tomography showed complete resolution of the lesions.
Evaluation of Bay R 3783 in rodent models of superficial and systemic candidiasis, meningeal cryptococcosis, and pulmonary aspergillosis.
Hector, R F; Yee, E
The triazole Bay R 3783 was compared with fluconazole, itraconazole, ketoconazole, and amphotericin B in rodent models of superficial and systemic candidiasis, meningocerebral cryptococcosis, and pulmonary aspergillosis. Overall, Bay R 3783 was comparable or slightly superior to fluconazole and markedly superior to itraconazole and ketoconazole in both survival and short-term organ load experiments in models of candidiasis and cryptococcosis but was less effective than amphotericin B. Of the antifungal agents tested, only Bay R 3783 and itraconazole showed any efficacy in the model of pulmonary aspergillosis. PMID:2159257
Chest radiographic staging in allergic bronchopulmonary aspergillosis: relationship with immunological findings.
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Kiely, J L
The question of whether a chest radiographic severity staging system could be correlated with standard blood\\/serum diagnostic indices in allergic bronchopulmonary aspergillosis (ABPA) was addressed in 41 patients. Asthma and positive Aspergillus fumigatus (AF) serology were considered essential diagnostic inclusion criteria. Eosinophil count, serum immunoglobulin (Ig)E and immediate skin hypersensitivity were also tested to grade patients as "definite" or "likely" ABPA. Definite cases had all five of these factors present, whereas likely cases had three or more. Chest radiographs were examined by experienced radiologists blinded to the clinical data. The six-stage radiographic score (0-5) was based on the severity and duration of changes seen: stage 0: normal; stage 1: transient hyperinflation; stage 2: transient minor changes; stage 3: transient major changes; stage 4: permanent minor changes; and stage 5: permanent major changes. Significant positive correlations (p<0.05) were observed between peak AF titres (expressed as an index), peak eosinophil count and radiographic severity stage. When considered as subgroups, these correlations approached, but did not reach, significance for the group with "likely" ABPA (n=28), but in the group with definite ABPA (n=13), there was a high correlation between radiographic score and peak AF index (r=0.59), as well as peak eosinophil count (r=0.62). This study suggests that the peak Aspergillus fumigatus index and eosinophil counts correlate best with the severity of radiographic stages in allergic bronchopulmonary aspergillosis. This chest radiographic staging system may be useful in the clinical assessment and management of patients with allergic bronchopulmonary aspergillosis, particularly in those patients with more severe radiographic stages.
Protective Effector Cells of the Recombinant Asp f3 Anti-Aspergillosis Vaccine.
Diaz-Arevalo, Diana; Ito, James I; Kalkum, Markus
An Aspergillus fumigatus vaccine based on recombinant Asp f3-protein has the potential to prevent aspergillosis in humans, a devastating fungal disease that is the prime obstacle to the success of hematopoietic cell transplantation. This vaccine protects cortisone acetate (CA)-immunosuppressed mice from invasive pulmonary aspergillosis via CD4(+) T cell mediators. Aside from these mediators, the nature of downstream fungicidal effectors is not well understood. Neutrophils and macrophages protect immunocompetent individuals from invasive fungal infections, and selective neutrophil depletion rendered mice susceptible to aspergillosis whereas macrophage depletion failed to increase fungal susceptibility. We investigated the effect of neutrophil depletion on rAsp f3-vaccine protection, and explored differences in pathophysiology and susceptibility between CA-immunosuppression and neutrophil depletion. In addition to being protective under CA-immunosuppression, the vaccine also had a protective effect in neutrophil-depleted mice. However, in non-immunized mice, a 10-fold higher conidial dose was required to induce similar susceptibility to infection with neutrophil depletion than with CA-immunosuppression. The lungs of non-immunized neutrophil-depleted mice became invaded by a patchy dense mycelium with highly branched hyphae, and the peribronchial inflammatory infiltrate consisted mainly of CD3(+) T cells and largely lacked macrophages. In contrast, lungs of non-immunized CA-immunosuppressed mice were more evenly scattered with short hyphal elements. With rAsp f3-vaccination, the lungs were largely clear of fungal burden under either immunosuppressive condition. We conclude that neutrophils, although important for innate antifungal protection of immunocompetent hosts, are not the relevant effectors for rAsp f3-vaccine derived protection of immunosuppressed hosts. It is therefore more likely that macrophages represent the crucial effectors of the rAsp f3-based vaccine.
Galactomannan and Real-Time PCR in the diagnosis of invasive Aspergillosis: preliminary data
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Cristina Pedrotti
Full Text Available The diagnosis of invasive aspergillosis is notoriously difficult. The standard culture-based methods have shown considerable limitations in performance. For this reason, non-culture methods have been increasingly employed for the diagnosis of invasive aspergillosis, and, among them, the methods based on Real-Time polymerase chain reaction (RT-PCR. In this study we assess the contribution in lowering diagnosis errors provided by the RT-PCR method when run alongside other methods. We analyzed 23 biological samples, 14 serum samples, and 9 bronchoalveolar lavage samples (BAL from 10 immunocompromised patients who were selected according to EORTC/MSG criteria (European Organization for Research and Treatment of Cancer/Mycoses Study Group. On the serum sample we searched the galactomannan (GM (Platelia Aspergillus® and the fungal genome (MycAssayTMAspergillus; the BAL samples were subjected also to the culture tests. In 11 serum samples the results showed concordance between GM and RT–PCR tests, while in 3 samples we report discordance: 2 results were GM positive and RT-PCR negative, and 1 results GM negative and RT-PCR indeterminate. In 5 BAL samples the results showed concordance between the two methods, while 4 were GM positive and RT-PCR negative. The data, although still preliminary, suggest an increased accuracy in the diagnosis of suspected invasive aspergillosis when employing both RT-PCR and GM tests given that the RT-PCR test eliminates the false positive results of the GM test. The PCR methods require, however, further applications of this type of diagnostic because of the severe limit given by the lack of standardization.
Spatial Patterns and Impacts of Environmental and Climatic Factors on Canine Sinonasal Aspergillosis in Northern California
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Monise Magro
Full Text Available Sinonasal aspergillosis (SNA causes chronic nasal discharge in dogs and has a worldwide distribution, although most reports of SNA in North America originate from the western USA. SNA is mainly caused by Aspergillus fumigatus, a ubiquitous saprophytic filamentous fungus. Infection is thought to follow inhalation of spores. SNA is a disease of the nasal cavity and/or sinuses with variable degrees of local invasion and destruction. While some host factors appear to predispose to SNA (such as belonging to a dolichocephalic breed, environmental risk factors have been scarcely studied. Because A. fumigatus is also the main cause of invasive aspergillosis in humans, unraveling the distribution and the environmental and climatic risk factors for this agent in dogs would be of great benefit for public health studies, advancing understanding of both distribution and risk factors in humans. In this study, we reviewed electronic medical records of 250 dogs diagnosed with SNA between 1990 and 2014 at the University of California Davis Veterinary Medical Teaching Hospital (VMTH. A 145-mile radius catchment area around the VMTH was selected. Data were aggregated by zip code and incorporated into a multivariate logistic regression model. The logistic regression model was compared to an autologistic regression model to evaluate the effect of spatial autocorrelation. Traffic density, active composting sites, and environmental and climatic factors related with wind and temperature were significantly associated with increase in disease occurrence in dogs. Results provide valuable information about the risk factors and spatial distribution of SNA in dogs in Northern California. Our ultimate goal is to utilize the results to investigate risk-based interventions, promote awareness, and serve as a model for further studies of aspergillosis in humans.
[Diagnosis of aspergillosis and other invasive filamentous fungal infections in hematology].
Gari-Toussaint, M; Piens, M A
Invasive filamentous fungal infections (FFI) are difficult to diagnose in the department of hematology; a variety of arguments are necessary to confirm the fungal origin. Our study evaluated prospectively, in a large population in South Eastern France, the diagnostic techniques used ante and post mortem (mycology, anatomopathology, serology and aspergillosis antigens) to prove an FFI. Two hundred and twenty eight neutropenic patients with obvious, probable, highly probable or presumed FFI were selected. Since completion of this study, a new classification of aspergillosis, with 3 instead of 4 levels of diagnosis, has been defined by the ICAAC in San Francisco but has not yet been published. Mycological or histological examinations were been performed on broncho-alveolar washings (BAW), puncture liquids or biopsies. Serology used precipitation, hemagglutination, immunofluorescence or ELISA techniques. Aspergillosis antigens were researched using the Pastorex method (agglutination of latex particles), launched at the beginning of the study. Invasive aspergillosis was diagnosed in 43.4% of patients, a non-aspergilla FFI in 6.5%, and no fungi was isolated in the cultures of 50% of patients. Ante mortem, 160 patients underwent BAW with a total of 175 samples. Among the latter, 41.7% mycological examinations were positive (presence of mycelium filaments and/or positive cultures) with 68.7% of Aspergillus fumigatus. Of the 48 puncture liquids, 25% of direct examinations and 29% of cultures were positive. Biopsies were taken from 59 patients and explored for mycology: 63.8% of direct examinations and 46.8% of cultures were positive; for those explored histologically, 76.7% revealed the presence of mycelium filaments. Post mortem, 17 patients out of 79 deceased underwent a total of 24 autopsy or biologic sampling. For 5 patients, FFI was diagnosed post mortem. Aspergillus serology and antigen explorations were conducted respectively in 202 and 182 patients and were positive
[Bronchopulmonary pathology with hypereosinophilia of fungal origin (excluding allergic bronchopulmonary aspergillosis)].
Lahoute, C; Tonnel, A B; Fournier, E; Ramon, P; Voisin, C
Five cases of eosinophil lung are reported in which the fungus responsible for the affection was not Aspergillus. Documented data include reports on 19 similar cases with a clinical picture suggestive of allergic bronchopulmonary aspergillosis but with negative tests for Aspergillus. The various fungal species isolated included Candida albicans, Penicillium, Geotrichum candidum, Stemphylium lanuginosum, Culvularia lunata, and Drechsleria hawaïensis. Diagnostic criteria are discussed, with particular emphasis on the importance of the inhalation provocation test, as well as possible efficacy of antifungal treatment.
Voriconazole in the treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis.
LENUS (Irish Health Repository)
Glackin, L
Allergic bronchopulmonary aspergillosis (ABPA) can cause a significant clinical deterioration in patients with cystic fibrosis. There is very little research in the current literature with regard to alternatives for treatment, apart from long courses of steroids. We conducted a retrospective review of all our patients with ABPA treated with the antifungal voriconazole and found there was a significant drop in IgE levels post treatment as well as a decrease in steroid dosing. The improvement in FEV was not statistically significant; however there was a very wide variation in pre-treatment levels.
Recurrent respiratory papillomatosis complicated by aspergillosis: A case report with review of literature
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Kuruvilla S
Full Text Available Pulmonary extension of recurrent invasive papillomatosis often poses a diagnostic challenge to the examining bronchoscopist, pathologist, radiologist and surgeon, in distinguishing it as a benign lesion that is confined to the mucosa and extending along the branches of the tracheobronchial tree from true invasion of a malignant tumor. We document here a case of recurrent invasive respiratory papillomatosis which initially presented as a laryngeal papilloma. After multiple recurrences, the patient presented with bronchopulmonary involvement, complicated by invasive aspergillosis in a non-immunocompromised setting.
A case report of Aspergillus hypersensitivity syndrome with obstructing bronchial aspergillosis.
Lee, P; Goh, S K; Yap, W M; Chan, C C
A 62-year-old Indian male with diabetes mellitus presented with atypical, overlap features of Aspergillus hypersensitivity syndrome and obstructing bronchial aspergillosis. He was febrile and tachypnoeic with diffuse crepitations and wheezing. Chest X-ray was normal but eosinophil count was 2900/mm3 and Ig E > 10,000 IU/ml. He responded initially to high dose steroid therapy but deteriorated subsequently from extensive mucus plugging of the bronchial tree which resulted in respiratory failure and death. He was HIV-negative. Culture and histologic examination of bronchoscopically identified tracheobronchial mucus plugs should be performed as early treatment may be life-saving.
Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization
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Guillaume Desoubeaux
Full Text Available Invasive aspergillosis has been studied in laboratory by the means of plethora of distinct animal models. They were developed to address pathophysiology, therapy, diagnosis, or miscellaneous other concerns associated. However, there are great discrepancies regarding all the experimental variables of animal models, and a thorough focus on them is needed. This systematic review completed a comprehensive bibliographic analysis specifically-based on the technical features of rodent models infected with Aspergillus fumigatus. Out the 800 articles reviewed, it was shown that mice remained the preferred model (85.8% of the referenced reports, above rats (10.8%, and guinea pigs (3.8%. Three quarters of the models involved immunocompromised status, mainly by steroids (44.4% and/or alkylating drugs (42.9%, but only 27.7% were reported to receive antibiotic prophylaxis to prevent from bacterial infection. Injection of spores (30.0% and inhalation/deposition into respiratory airways (66.9% were the most used routes for experimental inoculation. Overall, more than 230 distinct A. fumigatus strains were used in models. Of all the published studies, 18.4% did not mention usage of any diagnostic tool, like histopathology or mycological culture, to control correct implementation of the disease and to measure outcome. In light of these findings, a consensus discussion should be engaged to establish a minimum standardization, although this may not be consistently suitable for addressing all the specific aspects of invasive aspergillosis.
A suspected case of autoinduction of voriconazole metabolism in a patient with cerebral aspergillosis
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Ferguson MJ
Full Text Available Martin J Ferguson,1 Maria L Randles,2 Declan G de Freitas3 1Pharmacy Department, Beaumont Hospital, Beaumont, Dublin, 2Pharmacy Department, Wexford General Hospital, Wexford, 3Department of Transplantation, Urology and Nephrology, Beaumont Hospital Kidney Centre, Dublin, Ireland Objective: This study aims to report a case of accelerated metabolism of voriconazole in a patient with cerebral aspergillosis.Case summary: A 36-year-old woman developed cerebral aspergillosis after immunosuppressive treatment for suspected atypical hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. She was treated with voriconazole using therapeutic drug monitoring to guide dosing. After an initial high level, her dose was reduced, but over the following weeks, she required several dose increases in order to achieve a voriconazole level within the target range. The patient's dose requirements eventually stabilized at 700 mg twice daily. Cimetidine and omeprazole were added in an effort to inhibit the metabolism of voriconazole.Discussion: The metabolism of voriconazole is known to be highly variable among different patients depending on pharmacogenetic factors; however, an increasing rate of voriconazole metabolism in a single patient over time is not well recognized. Therapeutic drug monitoring of voriconazole in this case facilitated the use of large doses while controlling for toxicity.Conclusion: This case is further evidence of autoinduction in voriconazole metabolism. Therapeutic drug monitoring of voriconazole is useful in detecting variation in a patient's metabolism of voriconazole over time. Keywords: voriconazole, therapeutic drug monitoring, metabolism, enzyme inhibition, autoinduction
Chronic necrotizing pulmonary aspergillosis in pneumoconiosis - Clinical and radiologic findings in 10 patients
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Kato, T.; Usami, I.; Morita, H.; Goto, M.; Hosoda, M.; Nakamura, A.; Shima, S. [Nagoya City University, Nagoya (Japan). School of Medicine, Dept. of Internal Medicine
The authors studied 10 male patients with pneumoconiosis who were seen at Asahi Rosai Hospital and received a clinical diagnosis of chronic necrotizing pulmonary aspergillosis (CNPA) during a 15-year period, and detailed the long-term clinical and radiologic courses of four cases. Their occupational histories included pottery making and coal mining. Chest radiographic findings by the International Labor Organization profusion grading system were greater than category 2. All patients were symptomatic, with a productive cough, haemoptysis, and dyspnea. Serum findings were positive for the aspergillosis antibody in seven patients. The radiologic findings consisted of parenchymal infiltrates and cavities mostly containing mycetoma, which generally involved the upper lobes. The disease progressed slowly; in one patient, broad destruction of the lung was observed after > 10 years without antifungal administration. Most of the patients experienced clinical and radiologic improvement after receiving antifungal therapy, by oral, inhaled, or intracavitary administration. It was concluded that chronic persistent or progressive upper-lobe infiltrates and cavities in patients with pneumoconiosis should raise the possibility of CNPA. Early diagnosis and initiation of effective therapy are recommended to achieve a better outcome.
Invasive orbital aspergillosis in an apparently immunocompetent host without evidence of sinusitis
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Jennifer Primeggia
Full Text Available Invasive aspergillosis is uncommon in healthy individuals. We report a case of Aspergillus fumigatus orbital cellulitiswith intracranial extension in an apparently immunocompetent patient with a history of benign lymphoid hyperplasiaof the lacrimal gland. A 68 year-old man with no significant past medical history underwent orbitotomy and biopsy of alacrimal gland mass. Pathology showed benign lymphoid hyperplasia of the lacrimal gland and he completed radiationtherapy. Three months after orbitotomy and one month after completion of radiation therapy, he presented with orbitalcellulitis. Brain magnetic resonance imaging demonstrated invasion into the frontal lobe. Clinical and radiographicfindings failed to improve with prolonged antibiotic therapy; transcranial orbitotomy with right frontal craniotomy forabscess drainage and orbit washout was performed. Intraoperative cultures grew Aspergillus fumigatus. The patientcompleted a six month course of therapy with oral voriconazole and has remained free from relapse with long-termfollow-up. Efficacy of voriconazole was guided by serial imaging and voriconazole trough levels. Aspergillus may causeinvasive disease in immunocompetent hosts, even without evidence of sinusitis, and should be considered in the differentialdiagnosis when patients do not demonstrate clinical improvement with antibiotic therapy. J Microbiol Infect Dis2012; 2(3: 113-116Key words: Aspergillosis, orbital cellulitis, brain abscess
Epidemiology and antifungal resistance in invasive Aspergillosis according to primary disease: review of the literature.
Mayr, A; Lass-Flörl, Cornelia
Aspergilli, less susceptible to antifungals emerge and resistance to azoles have been found mainly in Aspergillus fumigatus; this has launched a new phase in handling aspergillosis. Resistant strains have currently been reported from Belgium, Canada, China, Denmark, France, Norway, Spain, Sweden, The Netherlands, UK and the USA. Centres in the UK (Manchester) and The Netherlands (Nijmegen) have described particularly high frequencies (15 and 10% respectively), and a significant increase in azole resistance in recent years. The reason of this high incidence may be due to long term azole therapy in patients with chronic aspergillosis in Manchester, and due to high use of agricultural azoles in Nijmegen. The primary underlying mechanism of resistance is as a result of alterations in the cyp51A target gene, with a variety of mutations found in clinical isolates and one genotype identified in the environmental (LH98). Reports on well documented in vitro and in vivo resistance to echinocandins are rare for Aspergillus species and resistance may be under-diagnosed as susceptibility testing is less frequently performed due to technical reasons.
Allergic bronchopulmonary aspergillosis in patient with cystic fibrosis - a case report.
Ionescu, Marcela Daniela; Balgradean, Mihaela; Marcu, Veronica
Asthma with allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity disease of the lungs due to an immune response to Aspergillus fumigattus (Af) antigens, is rarely seen in children, other than complicating cystic fibrosis. We present the case of a 14 - year- old female teenager with cystic fibrosis (CF), admitted in our hospital with respiratory failure and persistent cyanosis. Chest X-ray showed perihilar and upper lobes pulmonary infiltrates. Her airway cultures were positive for methicillin resistant staphilococcus aureus (MRSA) and non-mucoid Pseudomonas aeruginosa. She was prescribed intravenous antibiotherapy with ceftazidime and vancomycine (to which MRSA and Pseudomonas aeruginosa were susceptible). Pulmonary function testing (PFT) revealed severe obstructive lung disease. After ten days of intravenous antibiotics and first five days of corticosteroid, the patient's FEV1 was 68% of predicted. Total serum IgE and IgE antibodies to Aspergillus fumigatus were elevated. These results raised the possibility of allergic bronchopulmonary aspergillosis (ABPA). The possibility of ABPA should be considered in all pulmonary exacerbation and in order to determine if ABPA is developing or if an exacerbation is occurring, a serial monitoring of IgE levels should be performed.
Molecular identification of Emericella echinulata as a cause of Cerebral Aspergillosis in a patient following small bowel and liver transplantation
Molecular methods are now more commonly used for identification of the aspergilli and their teleomorphs and have led to reports of species not previously recognized as causing human disease. We report the first case of cerebral aspergillosis in a compromised patient caused by Emericella echinulata,...
Immunochemical analysis of fumigaclavine mycotoxins in respiratory tissues and in blood serum of birds with confirmed aspergillosis.
Latif, Hadri; Gross, Madeleine; Fischer, Dominik; Lierz, Michael; Usleber, Ewald
The ergoline alkaloid fumigaclavine A (FuA) is one of the major mycotoxins produced by Aspergillus fumigatus, the main causative fungal agent of avian aspergillosis. To study in situ production of FuA, post-mortem respiratory tissues of various avian species, as well as blood samples of falcons (Falco sp.), were analysed by enzyme immunoassay (EIA). At a detection limit of 1.5 ng/ml, FuA EIA positive results were obtained for tissue samples from seven (64%) out of 11 birds with confirmed aspergillosis, with a maximum concentration of 38 ng/g, while all controls (n = 7) were negative. No FuA could be detected in blood serum (detection limit 0.7 ng/ml) of 15 falcons, experimentally inoculated with A. fumigatus conidia. Fungal mycelium material from tissue of clinical aspergillosis cases, cultured on malt extract agar, was highly positive in the FuA EIA in milligrams per gram range. Chromatographic analysis of mycelium extracts revealed the co-presence of FuA and the structurally related fumigaclavine C (FuC). Alkaline hydrolysis of FuA and FuC yielded the corresponding deacetylation products, FuB and FuE. This is the first report showing that fumigaclavine alkaloids are produced by A. fumigatus in situ during the course of clinical aspergillosis in birds; however, the role of these compounds in the pathogenesis of this disease is still unknown.
Efficacy of aerosolized amphotericin B desoxycholate and liposomal amphotericin B in the treatment of invasive pulmonary aspergillosis in severely immunocompromised rats
E.J. Ruijgrok (Elisabeth); A.G. Vulto (Arnold); E.W.M. van Etten (Els)
textabstractThe effects of treatment with aerosolized amphotericin B desoxycholate and aerosolized liposomal amphotericin B were evaluated in severely immunosuppressed rats with invasive pulmonary aspergillosis. Aerosol treatment with amphotericin B desoxycholate
Aspergilosis: una patología a considerar Aspergillosis: a phatology to be considered
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Héctor Guillermo Oxilia
Full Text Available La aspergilosis pulmonar es una infección micótica causada por el Aspergillus fumigatus, saprófito del esputo humano normal. Se estudiaron cinco casos de pacientes con aspergilosis, cuatro de ellos adultos, tres del sexo femenino y uno masculino, todos de presentación no invasiva, y uno, pediátrico, sexo masculino, del tipo invasiva. Fueron estudiados con radiología convencional, tomografía computada (TC helicoidal, TC multislice y video cápsula endoscópica. Afecta 3:1 a los hombres en relación con las mujeres. Hay tres formas de presentación: a invasiva: en los pacientes neutropénicos, donde predomina la afectación pulmonar, con diseminación a cerebro, corazón, riñón, tracto gastrointestinal, hígado, tiroides y bazo; tiene mal pronóstico y la mortalidad es muy elevada; b semiinvasiva: compromete fundamentalmente a pacientes con patología pulmonar preexistente; c no invasiva: afecta cavidades preexistentes, cavernas TBC ( tuberculosis o quistes, donde coloniza el hongo, y se denomina aspergiloma o micetoma.Pulmonary aspergillosis is a mycotic infection caused by the Aspergillus fumigatus, saprophyte of the normal human sputum. Five patients with non invasive aspergillosis were studied, of whom 4 were adults (3 women, 1 man and one, pediatric, with invasive aspergillosis. All of them were studied by conventional X-ray, spiral CT, multislice CT and video capsule endoscopy. The presentation is predominant among men (3 to 1. There are three forms of presentation: a invasive: in neutropenic patients it prevails the lung affectation; the brain, heart, kidney gastrointestinal tract, liver, thyroid and spleen spreading has a bad prognosis and mortality rate is very high; b semiinvasive: it mainly compromises patients with pre-existing pulmonary pathology; c non invasive: affects pre-existing cavities, TBC caverns or cysts where the fungus establishes; it is called aspergilloma or mycetoma.
Successful Off-Label Use of Recombinant Factor VIIa and Coil Embolization in an Adolescent with Massive Hemoptysis Due to Invasive Pulmonary Aspergillosis
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Dilek Gürlek Gökçebay
Full Text Available Invasive fungal infections have turned out to be a significant cause of morbidity and mortality in pediatric patients with malignant disorders. Massive hemoptysis, a rare complication of invasive pulmonary aspergillosis, may threaten the lives of patients, usually during the resolution of neutropenia. In this report, we describe a patient with massive hemoptysis due to invasive pulmonary aspergillosis whose bleeding was controlled successfully with off-label use of recombinant factor VIIa and subsequent coil embolization of the right pulmonary artery.
Treatment of invasive pulmonary aspergillosis by combined intravenous and transthoracic injection of amphotericin B in a patient with acute leukemia: a case report
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Park, Choong Ki; Park, Dong Woo; Kim, Yong Soo; Choi, Yo Won; Jeon, Seok Chol; Seo, Heung Suk; Hahm, Chang Kok; Ahn, Myung Ju [Hanyang Univ. College of Medicine, Seoul (Korea, Republic of)
Invasive pulmonary aspergillosis may be a major cause of lethal opportunistic infection in neutropenic patients. The purpose of this report is to describe a combined treatment modality involving transthoracic injection of amphotericin B and gelatin solution for persistent mycetoma within the cavity. Mycetoma may interfere with consolidation chemotherapy after intravenous injection of ampho-tericin B for invasive pulmonary aspergillosis in a patient with acute monocytic leukemia in whom neutropenia developed during remission induction chemo-therapy.=20.
Multiple bronchoceles in a non-asthmatic patient with allergic bronchopulmonary aspergillosis.
Amin, Muhammad Umar; Mahmood, Rabia
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction due to a fungus, Aspergillus fumigatus. It is typically seen in patients with long-standing asthma. Our patient was a non-asthmatic 18 years old male who presented with chronic cough for 2 years. Peripheral blood eosinophilia and elevated scrum IgE were observed. His x-ray chest revealed v-shaped opacity in the left upper lobe close to the hilum. High resolution computed tomographic scan of the chest revealed multiple dilated bronchi filled with mucous (bronchoceles) and central bronchiectasis (CB) involving main segmental bronchi. Central bronchiectasis (CB) was typical of ABPA but bronchocele formation was a rare manifestation of the disease. The patient was managed with oral prednisolone and was relieved of his symptoms. Occurrence of ABPA in non-asthmatics is very rare and deserves reporting.
Invasive Pulmonary Aspergillosis in a Sickle Cell Patient Transplant Recipient: A Successful Treatment
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Katia Paciaroni
Full Text Available Sickle Cell Anaemia (SCA is the most common inherited blood disorder and is associated with severe morbidity and decreased survival. Allogeneic Haematopoietic Stem Cell Transplantation (HSCT is the only curative approach. Nevertheless the decision to perform a marrow transplant includes the risk of major complications and mortality transplant related. The infections represent the main cause of mortality for SCA patients undergoing transplant. Invasive Pulmonary Aspergillosis (IPA is a devastating opportunistic infection and remains a significant cause of morbidity and mortality in HSCT recipients. Data regarding IPA in the setting of SCA are lacking. In the present report, we describe a patient with SCA who developed IPA after allogeneic bone marrow transplant. The fungal infection was treated by systemic antifungal therapy in addition to the surgery, despite mild chronic GVHD and with continuing immunosuppression therapy. This case shows that IPA occurring in bone marrow recipient with SCA can be successful treated
Aspergillosis in a Patient Receiving Temozolomide for the Treatment of Glioblastoma
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Rodrigo Ramella Munhoz
Full Text Available Leukopenia and selective CD4+ lymphopenia represent major adverse events associated with the use of temozolomide (TMZ, an oral alkylating agent incorporated in the treatment of glioblastoma (GBM. The increased risk of opportunistic infections, including those caused by Pneumocystis jiroveci and cytomegalovirus, has been previously described in the literature. Here we report the case, the first to our knowledge, of a patient with pulmonary invasive aspergillosis immediately after the completion of chemoradiation with TMZ for GBM. Diagnosis was confirmed through a CT-guided lung biopsy, and the patient had excellent response to systemic voriconazole. This case illustrates that TMZ can be associated with severe opportunistic infections, presumably associated with T lymphocyte immune dysfunction, and patients exposed to this agent should be carefully monitored.
Pulseless right upper limb: an unusual manifestation of invasive pulmonary aspergillosis in acute myeloid leukemia.
Sharma, Sanjeev Kumar; Gupta, Nitin; Arav, Sudheer; Seth, Tulika; Mishra, Pravas; Mahapatra, Manoranjan; Mathur, Sandeep; Sharma, Sanjay
Aspergillus is the most common cause of fungal pneumonia in acute leukemia patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation. Despite a high index of suspicion and prompt institution of specific antifungal therapy, it causes significant morbidity and mortality in patients with hematological malignancies. It has to be differentiated from mucormycosis because the treatment differs. Histological confirmation obtained by lung biopsy is ideal, but is difficult to obtain in those patients who often have thrombocytopenia. We report a case of acute megakaryoblastic leukemia with typical manifestations of invasive pulmonary aspergillosis who developed pulseless right arm due to invasion of the right subclavian artery. When total leucocyte counts recovered, patient also developed immune reconstitution inflammatory syndrome and massive pulmonary hemorrhage, which was managed by bronchial artery embolization.
Amphotericin B releasing topical nanoemulsion for the treatment of candidiasis and aspergillosis.
Sosa, Lilian; Clares, Beatriz; Alvarado, Helen L; Bozal, Nuria; Domenech, Oscar; Calpena, Ana C
The present study was designed to develop a nanoemulsion formulation of Amphotericin B (AmB) for the treatment of skin candidiasis and aspergillosis. Several ingredients were selected on the basis of AmB solubility and compatibility with skin. The formulation that exhibited the best properties was selected from the pseudo-ternary phase diagram. After physicochemical characterization its stability was assessed. Drug release and skin permeation studies were also accomplished. The antifungal efficacy and skin tolerability of developed AmB nanoemulsion was demonstrated. Finally, our results showed that the developed AmB formulation could provide an effective local antifungal effect without theoretical systemic absorption, based on its skin retention capacity, which might avoid related side effect. These results suggested that the nanoemulsion may be an optimal therapeutic alternative for the treatment of skin fungal infections with AmB. Copyright © 2017 Elsevier Inc. All rights reserved.
Case Report Associated with Aspergillosis and Hepatitis E Virus Coinfection in Himalayan Griffons
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Heng Li
Full Text Available This study involved a death which occurred in four Himalayan griffons housed in Beijing zoo, China. Based on pathogen identification and the pathological changes observed, we did characterize the fungi and Hepatitis E virus (HEV in four dead Himalayan griffons. Pathological changes were severe. Membranous-like material was observed on the surface of the internal organs. Spleen was necrotic. Focal lymphocyte infiltration in the liver and many sunflower-like fungi nodules were evident in the tissues, especially in the kidney. PCR was used to identify the pathogen. Based on the 18SrRNA genomic sequence of known fungi, the results confirmed that all four dead Himalayan griffons were infected with Aspergillus. At the same time the detection of HEV also showed positive results. To the best of our knowledge, this work appears to be the first report of concurrent presence of Aspergillosis and Hepatitis E virus in rare avian species.
Five-years surveillance of invasive aspergillosis in a university hospital.
Graf, Karolin; Khani, Somayeh Mohammad; Ott, Ella; Mattner, Frauke; Gastmeier, Petra; Sohr, Dorith; Ziesing, Stefan; Chaberny, Iris F
As the most common invasive fungal infection, invasive aspergillosis (IA) remains a serious complication in immunocompromised patients, leading to increased mortality. Antifungal therapy is expensive and may result in severe adverse effects.The aim of this study was to determine the incidence of invasive aspergillosis (IA) cases in a tertiary care university hospital using a standardized surveillance method. All inpatients at our facility were screened for presence of the following parameters: positive microbiological culture, pathologist's diagnosis and antifungal treatment as reported by the hospital pharmacy. Patients fulfilling one or more of these indicators were further reviewed and, if appropriate, classified according to international consensus criteria (EORTC). 704 patients were positive for at least one of the indicators mentioned above. Applying the EORTC criteria, 214 IA cases were detected, of which 56 were proven, 25 probable and 133 possible. 44 of the 81 (54%) proven and probable cases were considered health-care associated. 37 of the proven/probable IA cases had received solid organ transplantation, an additional 8 had undergone stem cell transplantation, and 10 patients were suffering from some type of malignancy. All the other patients in this group were also suffering from severe organic diseases, required long treatment and experienced several clinical complications. 7 of the 56 proven cases would have been missed without autopsy. After the antimycotic prophylaxis regimen was altered, we noticed a significant decrease (p = 0.0004) of IA during the investigation period (2003-2007). Solid organ and stem cell transplantation remain important risk factors for IA, but several other types of immunosuppression should also be kept in mind. Clinical diagnosis of IA may be difficult (in this study 13% of all proven cases were diagnosed by autopsy only). Thus, we confirm the importance of IA surveillance in all high-risk patients.
Isavuconazole for the treatment of invasive aspergillosis and mucormycosis: current evidence, safety, efficacy, and clinical recommendations
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Natesan SK
Full Text Available Suganthini Krishnan Natesan,1,2 Pranatharthi H Chandrasekar1 1Division of Infectious Diseases, Department of Internal Medicine, Wayne State University, 2John D Dingell VA Medical Center, Detroit, MI, USA Abstract: The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both Aspergillus sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles. Polyenes including lipid formulations pose a problem with infusion-related side effects, electrolyte imbalance, and nephrotoxicity. Echinocandins are ineffective against mucorales and are approved as salvage therapy for refractory IA. Given that all available antifungal agents have limitations, there has been an unmet need for a broad-spectrum anti-mold agent with a favorable profile. Following phase III clinical trials that started in 2006, isavuconazole (ISZ seems to fit this profile. It is the first novel triazole agent recently approved by the United States Food and Drug Administration (FDA for the treatment of both IA and mucormycosis. This review provides a brief overview of the salient features of ISZ, its favorable profile with regard to spectrum of antifungal activity, pharmacokinetic and pharmacodynamic parameters, drug interactions and tolerability, clinical efficacy, and side effects. Keywords: isavuconazole, aspergillosis, mucormycosis, efficacy, antifungal therapy, novel azole, tolerability, drug interactions
[Allergic bronchopulmonary aspergillosis. A report of a case and literature review].
Meza Brítez, Ricardo L; del Río Navarro, Blanca E; Ochoa López, Georgina; Pietropaolo Cienfuegos, Dino; del Río Chivardi, Jaime M; Rosas Vargas, Miguel A
Allergic bronchopulmonary aspergillosis is a world rare disease with a prevalence between 1 and 2%. It presents in moderate-severe asthma and cistic fibrosis patients. The diagnosis is made in the basis of Rossenberg and Greenberg criteria that can be essential or non essential. We present the case of a 3-year-old boy with allergic bronchopulmonary aspergillosis without bronchiectasies and with a good response to corticosteroids. His mother complained of two years of nasal obstruction, purulent rinorrea, nasal pruritus, sneezing, chronic cough and recurrent wheezing, twice to thrice a month. He also occasionally had vomits and diarrhea in relation with strawberries, banana, cow's milk and chocolate. We made the diagnosis of asthma, allergic rhinitis, sinusitis, and probably food allergy. We treated him with step approach of ICS according to GINA 2006, albuterol PRN, and elimination diet, with bad response. Laboratory exams: Blood white cells with eosinophilia (6%), total serum IgE: 1684 ng/L, aspergillus skin prick test: 4mm, serum IgG-Aspergillus fumigatus: 2.3 mcg/mL, serum IgE-Aspergillus fumigatus: negative, chest roentgenographic parahiliar and apical infiltrates, and chest computed tomography without bronchiectasies. We added prednisone to the treatment for four months, and we observed a very good response; he is now in treatment as mild persistent asthma with ICS low doses. ABPA must be suspected in patients with moderate-severe persistent asthma and a skin prick test positive to Aspergillus fumigatus regardless the age. The treatment with oral corticosteroids is the mainstream of management, and most of the patients have a good response, as we observed with this patient.
Pharmacology and metabolism of voriconazole and posaconazole in the treatment of invasive aspergillosis-review of the literature
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Sandherr M
Full Text Available Abstract Invasive fungal infections, predominantly aspergillosis and candidiasis, are among the most important causes of morbidity and mortality in immunocompromised patients. Primarily, patients with acute leukemia undergoing myelosuppressive chemotherapy and allogeneic stem cell transplant recipients are affected. Up to 60% of patients with invasive aspergillosis, the most common invasive mycosis among patients with hematologic malignancies, may still die of their infection, once it has become clinically overt. The spectrum of antifungal agents for clinical use now has expanded over the past ten years and includes the novel class of the echinocandins and two newer generation triazoles with an extended spectrum of activity against a wide range of fungal pathogens. This review will address pharmacological characteristics of the two broad-spectrum antifungal azoles, voriconazole and Posaconazole, which are important for their proper use in clinical practice.
Long term outcome of medical and surgical co-management of craniospinal aspergillosis in an immunocompromised patient
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Dipu Sathyapalan
Full Text Available 35 yr old steroid dependent lady with Pulmonary TB underwent debridement of epidural abscess & posterior stabilization for paraparesis. With histopathology and cultures showing Aspergillus fumigatus, voricanozole was started. By the fourth week, she developed persistent fever, and altered mental status. Brain MRI and CSF study including multiplex PCR evaluation confirmed cerebral aspergillosis. Voricanozole was changed to intravenous lipid complex Amphotericin B to achieve sustained clinical and radiological response after six months of therapy.
CD4+ T cells mediate the protective effect of the recombinant Asp f3-based anti-aspergillosis vaccine.
Diaz-Arevalo, Diana; Bagramyan, Karine; Hong, Teresa B; Ito, James I; Kalkum, Markus
The mortality and morbidity caused by invasive aspergillosis present a major obstacle to the successful treatment of blood cancers with hematopoietic cell transplants. Patients who receive hematopoietic cell transplants are usually immunosuppressed for extended periods, and infection with the ubiquitous mold Aspergillus fumigatus is responsible for most cases of aspergillosis. Previously, we demonstrated that vaccination with recombinant forms of the A. fumigatus protein Asp f3 protected cortisone acetate-immunosuppressed mice from experimentally induced pulmonary aspergillosis. Here, we investigated the vaccine's protective mechanism and evaluated in particular the roles of antibodies and T cells. After vaccination, Asp f3-specific preinfection IgG titers did not significantly differ between surviving and nonsurviving mice, and passive transfer of anti-Asp f3 antibodies did not protect immunosuppressed recipients from aspergillosis. We experimentally confirmed Asp f3's predicted peroxisomal localization in A. fumigatus hyphae. We found that fungal Asp f3 is inaccessible to antibodies, unless both cell walls and membranes have been permeabilized. Antibody-induced depletion of CD4+ T cells reduced the survival of recombinant Asp f3 (rAsp f3)-vaccinated mice to nonimmune levels, and transplantation of purified CD4+ T cells from rAsp f3-vaccinated mice into nonimmunized recipients transferred antifungal protection. In addition, residues 60 to 79 and 75 to 94 of Asp f3 contain epitopes that induce proliferation of T cells from vaccinated survivors. Vaccine-primed CD4+ T cells are not expected to clear the fungal pathogen directly; however, they may locally activate immunosuppressed phagocytes that elicit the antifungal effect.
CD4+ T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine ▿
Diaz-Arevalo, Diana; Bagramyan, Karine; Hong, Teresa B.; Ito, James I.; Kalkum, Markus
The mortality and morbidity caused by invasive aspergillosis present a major obstacle to the successful treatment of blood cancers with hematopoietic cell transplants. Patients who receive hematopoietic cell transplants are usually immunosuppressed for extended periods, and infection with the ubiquitous mold Aspergillus fumigatus is responsible for most cases of aspergillosis. Previously, we demonstrated that vaccination with recombinant forms of the A. fumigatus protein Asp f3 protected cortisone acetate-immunosuppressed mice from experimentally induced pulmonary aspergillosis. Here, we investigated the vaccine's protective mechanism and evaluated in particular the roles of antibodies and T cells. After vaccination, Asp f3-specific preinfection IgG titers did not significantly differ between surviving and nonsurviving mice, and passive transfer of anti-Asp f3 antibodies did not protect immunosuppressed recipients from aspergillosis. We experimentally confirmed Asp f3's predicted peroxisomal localization in A. fumigatus hyphae. We found that fungal Asp f3 is inaccessible to antibodies, unless both cell walls and membranes have been permeabilized. Antibody-induced depletion of CD4+ T cells reduced the survival of recombinant Asp f3 (rAsp f3)-vaccinated mice to nonimmune levels, and transplantation of purified CD4+ T cells from rAsp f3-vaccinated mice into nonimmunized recipients transferred antifungal protection. In addition, residues 60 to 79 and 75 to 94 of Asp f3 contain epitopes that induce proliferation of T cells from vaccinated survivors. Vaccine-primed CD4+ T cells are not expected to clear the fungal pathogen directly; however, they may locally activate immunosuppressed phagocytes that elicit the antifungal effect. PMID:21422177
Evaluation of Bay R 3783 in rodent models of superficial and systemic candidiasis, meningeal cryptococcosis, and pulmonary aspergillosis.
Hector, R F; Yee, E.
The triazole Bay R 3783 was compared with fluconazole, itraconazole, ketoconazole, and amphotericin B in rodent models of superficial and systemic candidiasis, meningocerebral cryptococcosis, and pulmonary aspergillosis. Overall, Bay R 3783 was comparable or slightly superior to fluconazole and markedly superior to itraconazole and ketoconazole in both survival and short-term organ load experiments in models of candidiasis and cryptococcosis but was less effective than amphotericin B. Of the ...
Prophylaxis of invasive aspergillosis with caspofungin during construction works in patient with acute lymphoblasic leukemia treated with vincristin
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Mojca Modic
Case presentation: A 59-year old woman with common ALL relapsed after 22 years (normal cytogenetics. She was treated according to the UKALL XII regimen and achieved complete second remission. She received four cycles of vincristine 2 mg i.v. In a retrospective cohort study, prolonged neutropenia, use of steroids, nursing unit without laminar air flow during a period of construction works were associated with an increased incidence of invasive aspergillosis in patients who did not receive primary antifungal prophylaxis. Intravenous caspofungin was administered to the patient as primary aspergillosis prophylaxis on the first day of chemotherapy. Galactomannan antigen tests were negative during the period of neutropenia. There was no infection in the period of prolonged neutropenia. Conclusions: The author discusses primary prophylaxis of invasive aspergillosis with caspofungin during construction works in patients with acute lymphoblastic leukemia treated with vincristine. Because of non-conventional unit without laminar air flow during induction chemotherapy treatment, which leads to an increased risk of invasive fungal infection with Aspergillus, caspofungin prophylaxis is recommended at least until upgrade to laminar flow or cessation of construction works.
Fatal Case of Probable Invasive Aspergillosis after Five Years of Heart Transplant: A Case Report and Review of the Literature
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Toufik Mahfood Haddad
Full Text Available Invasive fungal infections are very common in solid organ transplants and occur most frequently in the first three months after transplant. A 49-year-old female with a history of two remote heart transplants with the most recent one occurring 5 years ago was admitted for increasing shortness of breath, cough, and fever. Computerized tomography (CT scan of the chest showed left lower lung ground-glass and tree-in-bud opacities. She was started on broad spectrum antibiotics along with ganciclovir and micafungin. Ganciclovir was added due to the patient's past history of CMV infection and empiric fungal coverage with micafungin. Bronchoalveolar lavage (BAL was performed as her respiratory status worsened and voriconazole was added for possible aspergillosis in combination therapy with micafungin. BAL galactomannan returned positive which was suggestive of aspergillosis. Patient worsened clinically and subsequently succumbed to cardiorespiratory arrest despite our best efforts. It is important to have a high degree of clinical suspicion for invasive aspergillosis in transplant patients even many years after transplant and initiate aggressive therapy due to poor outcomes.
Management of invasive aspergillosis in patients with COPD: rational use of voriconazole
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Florence Ader
Full Text Available Florence Ader1, Anne-Lise Bienvenu2, Blandine Rammaert3, Saad Nseir41Service des Maladies Infectieuses et Tropicales; 2Service de Parasitologie et Mycologie Médicale, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Hôpital de La Croixrousse, Lyon, France; 3Service des Maladies Infectieuses et Tropicales, Université Paris Descartes, Hôpital Necker Enfants Malades, Centre d'infectiologie Necker-Pasteur, Paris, France; 4Service de Réanimation Médicale, Hôpital A. Calmette, Centre Hospitalier Régional Universitaire, Lille, FranceAbstract: Invasive pulmonary aspergillosis (IPA is an important cause of mortality in patients with hematologic malignancies. The reported incidence of IPA in the context of chronic obstructive pulmonary disease (COPD seems to increase. Approximately 1%–2% of overall fatal cases of IPA occur in COPD patients. The combination of factors such as lung immune imbalance, long-term corticosteroid use, increasing rate of bacterial exacerbations over time, and malnutrition are responsible for the emergence of IPA in these patients. The diagnosis of IPA is difficult to establish, which explains the delay in implementing accurate antifungal therapy and the high mortality rate. Persistent pneumonia nonresponsive to appropriate antibiotic treatment raises the concern of an invasive fungal infection. Definite diagnosis is obtained from tissue biopsy evidencing Aspergillus spp. on microscopic examination or in culture. Culture and microscopy of respiratory tract samples have a sensitivity and specificity of around 50%. Other diagnostic tools can be useful in documenting IPA: computed tomography (CT scan, nonculture-based tests in serum and/or in bronchoalveolar lavage such as antibody/antigen tests for Aspergillus spp. More recent tools such as polymerase chain reaction or [1→3]-β-D-glucan have predictive values that need to be further investigated in COPD patients. Antifungal monotherapy using azole
Costo-efficacia dell'amfotericina B liposomiale nella terapia dell'aspergillosi invasiva
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Mario Eandi
Full Text Available Invasive aspergillosis (IA is a common and life-threatening infectious complication of immune system depression. Amphotericin B deoxycholate (AMB-d has been considered standard therapy for IA for over 40 years, despite the fact that success rates rarely exceed 40% and adverse effects are quite common. At present two more recent pharmacological agents are available for the treatment of IA: liposomal amphotericin B (L-AMB and voriconazole (VOR. In this article, we present a pharmaco-economical study comparing the relative costeffectiveness of 5 alternative strategies in the treatment of invasive aspergillosis, analysed from the point of view of the Italian hospital: administration of L-AMB as first line therapy, followed by no rescue treatment in case of failure (L-AMB I°; administration of L-AMB as first line therapy, followed by VOR in case of failure (LAMB I° + VOR rescue; AMB-d as first line, followed by L-AMB in case of failure (L-AMB rescue; AMB-d as first line, followed by other antifungals as needed (AMB-d I° and VOR as first line, followed by rescue treatments in case of failure (VOR I°. The cost-effectiveness analysis was conducted using decision tree modelling techniques: efficacy data were obtained from published clinical trials; costs parameters were fitted on the Italian setting. The results indicate that two strategies, L-AMB rescue and VOR I°, are dominated, i.e. induce higher costs and lower success rates than the alternatives. The three remaining strategies are neither dominated nor dominate the others, but are associated with different clinical and economical outcomes: AMB-d I° has the lowest total cost, but also the highest cost-effectiveness ratio and the lowest overall efficacy; L-AMB I° has the best cost-effectiveness, but requires the willingness to pay 2,100 euro for each additional success; L-AMB I° + VOR rescue is the most effective treatment, but this choice is associated with incremental costs of 17,200 euro
Laboratory Diagnosis of Invasive Aspergillosis: From Diagnosis to Prediction of Outcome
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Richard C. Barton
Full Text Available Invasive aspergillosis (IA, an infection caused by fungi in the genus Aspergillus, is seen in patients with immunological deficits, particularly acute leukaemia and stem cell transplantation, and has been associated with high rates of mortality in previous years. Diagnosing IA has long been problematic owing to the inability to culture the main causal agent A. fumigatus from blood. Microscopic examination and culture of respiratory tract specimens have lacked sensitivity, and biopsy tissue for histopathological examination is rarely obtainable. Thus, for many years there has been a great interest in nonculture-based techniques such as the detection of galactomannan, β-D-glucan, and DNA by PCR-based methods. Recent meta-analyses suggest that these approaches have broadly similar performance parameters in terms of sensitivity and specificity to diagnose IA. Improvements have been made in our understanding of the limitations of antigen assays and the standardisation of PCR-based DNA detection. Thus, in more recent years, the debate has focussed on how these assays can be incorporated into diagnostic strategies to maximise improvements in outcome whilst limiting unnecessary use of antifungal therapy. Furthermore, there is a current interest in applying these tests to monitor the effectiveness of therapy after diagnosis and predict clinical outcomes. The search for improved markers for the early and sensitive diagnosis of IA continues to be a challenge.
Systemic biomarkers of inflammation and haemostasis in patients with chronic necrotizing pulmonary aspergillosis
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Rødland Ernst
Full Text Available Abstract Background The purpose of this study was to investigate mediators of inflammation and haemostasis in patients with chronic necrotizing pulmonary aspergillosis (CNPA, a locally, destructive process of the lung due to invasion by Aspergillus species. Methods Measurements of selected biomarkers in 10 patients with CNPA and 19 healthy, matched controls were performed with enzyme-linked immunosorbent assay (ELISA and multiplex methodology. The gene expressions of relevant biomarkers were analyzed with real-time quantitative RT-PCR. Results Increased concentrations of circulating mediators of inflammation interleukin (IL-6, IL-8, RANTES, TNF-α, ICAM-1 and mediators involved in endothelial activation and thrombosis (vWF, TF and PAI-1 were observed in patients with CNPA. The concentration of the anti-inflammatory cytokine IL-10 was increased both in plasma and in PBMC in the patient population. The gene expression of CD40L was decreased in PBMC from the patient group, accompanied by decreased concentrations of soluble (s CD40L in the circulation. Conclusions The proinflammatory response against Aspergillus may be counteracted by reduced CD40L and sCD40L, as well as increased IL-10, which may compromise the immune response against Aspergillus in patients with CNPA.
Graft-Versus-Host Disease after Liver Transplantation Complicated by Systemic Aspergillosis with Pancarditis
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Joseph Romagnuolo
Full Text Available Acute graft-versus-host disease (GVHD is a common complication after bone marrow transplantation, with characteristic rash and diarrhea being the most common features. After liver transplantation, however, this phenomenon is very rare. Most transplant patients are on a variety of medications, including immunosuppressants; therefore, the differential diagnosis of skin rash or diarrhea is broad. A 37-year-old man who underwent liver transplantation for primary biliary cirrhosis, and developed a rash and watery diarrhea, is presented. Skin and colonic biopsies confirmed acute GVHD. A pulse of intravenous steroids was given. The skin rash improved, but he developed pancytopenia. His course was complicated by central line infection, jugular and subclavian vein thrombosis, pseudomembranous colitis, recurrent bacteremia, cholestasis on total parenteral nutrition and cytomegalovirus infection. After the onset of pleuritic chest pain and clinical sepsis, spiral computed tomography scan of his chest and abdomen revealed septic infarcts in multiple organs. Despite empirical treatment with amphotericin B, he died of multiorgan dysfunction syndrome within 72 h. Autopsy revealed systemic aspergillosis with pancarditis, endocardial vegetations, and septic pulmonary, splenic, hepatic and renal infarcts. The pathogenesis and experience with this rare, but often fatal, complication of liver transplantation are reviewed. In contrast to GVHD after bone marrow transplantation, pancytopenia is common and liver dysfunction is rare. One should have a high level of suspicion in the liver transplant recipient presenting with rash and/or diarrhea.
Successful non-standard approaches to massive hemoptysis in invasive pulmonary aspergillosis
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Mitrović Mirjana
Full Text Available Introduction. Invasive pulmonary aspergillosis (IA is the most frequent invasive fungal infection in patients with hematological malignancies. Massive hemoptysis (MH with blood loss more than 300- 600 ml in 24 hours is a rare (5-10% of IA patients but frequently fatal complication. Standard treatment of MH, such as oxygenation, a semi-sitting position with the bleeding site down, bronchoscopical suctioning, antifungal therapy, transfusion support and surgical resection might be either ineffective or not feasible in some cases. Outline of Cases. We report two patients with life threatening, non-controlled, massive hemoptysis who were successfully managed by non-standard measures. A 61-year-old male with acute myeloid leukemia developed pulmonary IA and massive hemoptysis after consolidation cure by chemotherapy. The bleeding site was localized in the VI lung segment by bronchoscopy. Local application of fibrinogen-thrombin concentrate (fibrin glue stopped the bleeding. A 22-year-old female patient with the diagnosis of severe aplastic anemia developed IA and massive hemoptysis early after application of immunosuppressive therapy (antilymphocyte globulin, cyclosporine and corticosteroids. Conventional transfusion therapy, desmopresine and antifibrinolytics were ineffective. This urgent condition was successfully treated with human activated recombinant factor VII (rFVIIa, NovoSeven®. Conclusion. Our experience together with data from the available literature suggests a potential benefit of fibrinogen-thrombin concentrate and rFVIIa in the treatment of refractory critical bleeding in hematooncological patients.
Autoinduction of voriconazole metabolism in a child with invasive pulmonary aspergillosis.
Hsu, Alice Jenh; Dabb, Alix; Arav-Boger, Ravit
Inter- and intra-patient variability in voriconazole pharmacokinetics has been described in children as the result of age-specific differences in hepatic metabolism, saturable nonlinear pharmacokinetics, CYP450 2C19 polymorphisms, decreased bioavailability compared with adults, and drug-drug interactions. We introduce dose-dependent autoinduction of metabolism as another cause for altered voriconazole pharmacokinetics in children and summarize previously published literature on this phenomenon. A 10-year-old girl with severe aplastic anemia developed invasive pulmonary aspergillosis after high-dose cyclophosphamide therapy and required high doses of voriconazole for longer than 2 months. She initially achieved a therapeutic trough of 1.4 μg/ml on voriconazole 11 mg/kg/dose orally every 12 hours but required dose escalations to 9.3 mg/kg/dose orally every 8 hours to maintain a trough above 1 μg/ml. Because there were no changes in concomitant medications, route of administration, adherence, or oral intake, we conclude that the only plausible explanation for the precipitous drop in voriconazole troughs was autoinduction of metabolism, a phenomenon previously reported in adults receiving higher than usual doses or prolonged courses (longer than 2 months). These data highlight the need for continued therapeutic drug monitoring of voriconazole after initial therapeutic troughs are achieved because autoinduction of metabolism can lead to significant declines in subsequent voriconazole troughs, potentially leading to treatment failure. © 2015 Pharmacotherapy Publications, Inc.
Breakthrough invasive fungal diseases during voriconazole treatment for aspergillosis: A 5-year retrospective cohort study.
Kim, Sun Bean; Cho, Sung-Yeon; Lee, Dong-Gun; Choi, Jae-Ki; Lee, Hyo-Jin; Kim, Si-Hyun; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong; Lee, Jong-Wook
Breakthrough invasive fungal diseases (bIFDs) during voriconazole treatment are concerning, as they are associated with high rates of mortality and pathogen distribution. To evaluate the prevalence, incidence, patient characteristics, including IFD events, and overall mortality of bIFDs during voriconazole treatment for invasive aspergillosis (IA). We retrospectively analyzed the medical records of consecutive patients who had undergone voriconazole treatment for IA and who had bIFD events between January 2011 and December 2015. Eleven bIFD events occurred in 9 patients. The prevalence and incidence of bIFDs were 2.25% (9/368) and 0.22 cases per year, respectively. Overall mortality was 44.4% (4/9). The severity of the illness and persistence of immunodeficiency, mixed infection, and low concentration of the treatment drug at the site of infection were identified as possible causes of bIFDs. Seven of 11 events (63.6%) required continued voriconazole treatment with drug level monitoring. In 4 (36.3%) cases, the treatment was changed to liposomal amphotericin B. Two cases resulted in surgical resection (18.2%). Clinicians should be aware that bIFDs during voriconazole treatment for IA can occur, and active therapeutic approaches are required in these cases. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.
Paving the way for predictive diagnostics and personalized treatment of invasive aspergillosis
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Ana eOliveira-Coelho
Full Text Available Invasive aspergillosis (IA is a life-threatening fungal disease commonly diagnosed among individuals with immunological deficits, namely hematological patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation. Vaccines are not available, and despite the improved diagnosis and antifungal therapy, the treatment of IA is associated with a poor outcome. Importantly, the risk of infection and its clinical outcome vary significantly even among patients with similar predisposing clinical factors and microbiological exposure. Recent insights into antifungal immunity have further highlighted the complexity of host-fungus interactions and the multiple pathogen-sensing systems activated to control infection. How to decode this information into clinical practice remains however a challenging issue in medical mycology. Here, we address recent advances in our understanding of the host-fungus interaction and discuss the application of this knowledge in potential strategies with the aim of moving towards personalized diagnostics and treatment (theragnostics in immunocompromised patients. Ultimately, the integration of individual traits into a clinically applicable process to predict the risk and progression of disease, and the efficacy of antifungal prophylaxis and therapy, holds the promise of a pioneering innovation benefiting patients at risk of IA.
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis.
Miller, P. W.; Hamosh, A.; Macek, M.; Greenberger, P. A.; MacLean, J.; Walden, S. M.; Slavin, R. G.; Cutting, G. R.
The etiology of allergic bronchopulmonary aspergillosis (ABPA) is not well understood. A clinical phenotype resembling the pulmonary disease seen in cystic fibrosis (CF) patients can occur in some individuals with ABPA. Reports of familial occurrence of ABPA and increased incidence in CF patients suggest a possible genetic basis for the disease. To test this possibility, the entire coding region of the cystic fibrosis transmembrane regulator (CFTR) gene was analyzed in 11 individuals who met strict criteria for the diagnosis of ABPA and had normal sweat electrolytes (< or = 40 mmol/liter). One patient carried two CF mutations (deltaF508/R347H), and five were found to carry one CF mutation (four deltaF508; one R117H). The frequency of the deltaF508 mutation in patients with ABPA was significantly higher than in 53 Caucasian patients with chronic bronchitis (P < .0003) and the general population (P < .003). These results suggest that CFTR plays an etiologic role in a subset of ABPA patients. PMID:8659542
Hospital environment fungal contamination and aspergillosis risk in acute leukaemia patients in Sousse (Tunisia).
Gheith, Soukeina; Ranque, Stéphane; Bannour, Wadiaa; Ben Youssef, Yosra; Khelif, Abderrahim; Ben Said, Moncef; Njah, Mansour; Saghrouni, Fatma
Hospital environment is considered the main source of invasive aspergillosis (IA) in leukemic patients. This study aimed to describe Aspergillus colonisation in leukemic patients and their hospital environment and to test whether Aspergillus environmental contamination was associated with IA. For a 2-year period including 14-month renovation work, 91 acute leukaemia inpatients at the hematology department of University hospital in Sousse (Tunisia) were prospectively included. The incidence of probable IA (EORTC/MSG criteria) was 9.9%. Fifty-six Aspergillus were isolated from 53 (6.5%) of 811 sputa collected from 35 (38.5%) patients. Aspergillus spp. were isolated in 59.7% of 494 air samples and in 52.8% of 1579 surface samples taken in the patients' room. Aspergillus section Nigri (72.7%) was the most frequent. Aspergillus contamination peaked in autumn and winter on surface and in summer and autumn in air samples and was higher (P = 0.03) during the renovation work period. Multivariate analysis showed that for each Aspergillus section Nigri CFU airborne contamination IA risk increased by 1.05 (P = 0.04). In Tunisia, Aspergillus section Nigri and Flavi, but not Fumigati, are chiefly involved in IA. Our findings support swift implementation of airborne fungal contamination control measures in areas where immunocompromised patient are hospitalised. © 2015 Blackwell Verlag GmbH.
Second-Hand Smoke Increases Bronchial Hyperreactivity and Eosinophilia in a Murine Model of Allergic Aspergillosis
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Brian W. P. Seymour
Full Text Available Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS on a murine model of allergic bronchopulmonary aspergillosis (ABPA. BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-γ indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia.
[Cervical aspergillosis with dissemination to the central nervous system: Case reports and review of the literature].
Vergara, Guillermo Enrique; Roura, Natalia; Del Castillo, Marcelo; Mora, Andrea; Alcorta, Santiago Condomi; Mormandi, Rubén; Cervio, Andrés; Salvat, Jorge
Invasive aspergillosis (IA) of the central nervous system (CNS) is an uncommon condition that usually occurs in immunocompromised patients. This illness can manifest as meningitis, or as a micotic aneurism, stroke or abscess. The infection affects the CNS either primarily or, more often, secondarily via blood dissemination from a distant focus, and has a poor prognosis. We present a patient with IA primarily affecting the cervical bones, with later spread into the brain. A 25-year old male was receiving chemotherapy for acute lymphocytic leukemia when he developed pneumonitis secondary to methotrexate and was started on corticosteroids. He subsequently developed cervicalgia, prompting a needle biopsy of the fourth vertebrae, after which a diagnosis of osteomyelitis was made. Even though the biopsy culture was negative, empirical antibiotics were initiated. A parietal lobe lesion was treated surgically months later after the patient presented with three episodes of transient aphasia. After A. fumigatus grew in culture, the patient's antibiotic regimen was changed to treat the specific agent with a good response. IA must be considered a possibility whenever an immunocompromised patient presents with a new brain lesion. These lesions require surgical evacuation, a procedure that allows for diagnostic confirmation and enhances prognosis. Appropriate anti-fungal therapy must be started as soon as the diagnosis is confirmed. In addition, the patient's neurological exam must be repeated and images obtained periodically to monitor treatment and detect possible recurrences.
Percutaneous treatment with amphotericin B of mycotic lung lesions from invasive aspergillosis: results in 10 immunocompromised patients
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Veltri, A.; Anselmetti, G.C.; Bartoli, G.; Martina, M.C.; Galli, J. [Sezione di Scienze Radiologiche, DiUniv. Torino (Italy); Regge, D. [Servizio di Radiodiagnostica, Istituto di Ricerca e Cura per il Cancro, Ordine Mauriziano, Candiolo (Italy); Bertini, M. [U.O.A. Ematologia, Azienda Ospedaliera San Giovanni Battista, Torino (Italy)
The aim of this study was to evaluate the efficacy of percutaneous treatment of pulmonary lesions from invasive aspergillosis in immunocompromised patients. From 1992 to 1998, ten patients (seven men and three women; mean age 56 years) affected by hematological neoplasms (8 acute myeloid leukemias, 2 non-Hodgkin's lymphomas) and post-chemotherapy prolonged neutropenia developed pulmonary lesions from invasive aspergillosis. A total of 13 lesions (diameter 2-7 cm, median 5 cm) were treated percutaneously due to insufficiency of the high-dose i. v. therapy; under CT guidance, a median of 10 cm{sup 3} per session of a 1 mg/cm{sup 3} diluted solution of amphotericin B was injected through a fine needle (21-22 G); 45 sessions overall were performed (one to five per lesion, median four), according to the volume of the nodules, tolerance, and complications. The results were retrospectively evaluated either radiologically or clinically. Complications were cough, mild hemoptysis, and small pneumothorax and/or pleural effusion. No major complications occurred. One month after the beginning of treatment, 8 lesions completely resolved, 4 greatly improved, and 1 was not significantly reduced. In all ten patients symptoms improved (eight of ten could restart chemotherapy as scheduled). After antiblastic retreatment, 1 patient had mycotic recurrence. In our experience transthoracic topical treatment with amphotericin B of single or few lung lesions from invasive aspergillosis was effective, affording a rapid improvement of the lesions and symptoms, and allowing continuation of chemotherapy as scheduled, thereby reducing the risk of recurrences. (orig.)
Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3
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Hulya Gunbatar
Full Text Available A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3. During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML.
Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3).
Gunbatar, Hulya; Demir, Cengiz; Kara, Erdal; Esen, Ramazan; Sertogullarindan, Bunyamin; Asker, Selvi
A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3). During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML.
Implementation of different histochemical methods in diagnostics of brain Aspergillosis in turkey chicks
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Kureljušić Branislav
Full Text Available Aspergillosis is a frequent fungal disease in different species of birds and mammals caused by fungi of the genus Aspergillus. It is characterized by inflammatory changes primarily in the respiratory system, even though it sometimes takes on a generalized form when several organ systems are affected. Mucotic-granulomatous meningoencephalitis with a predominant localization in the cerebellum has been described in turkeys, ducks and geese. Within this paper, examinations have been performed on a flock of broiler turkeys aged 12 days who had sustained evident neurological disorders in the form of ataxy, torticollis, paresis, and paralysis of the hind extremities and wings. In three of the ten autopsied chicks the macroscopic findings indicated granulomatous encephalitis of the cerebellum. A white-coloured granuloma, around 3mm in diameter, was situated cranioventrally and was clearly visible on the sagital section of the cerebellum. Mucological examinations of the cerebellum lesion resulted in the isolation of the fungi Aspergillus fumigatus. Haematoxylin-eosin (HE, Grocott and PAS methods were used for the evaluation of histopathological changes and proving Aspergillus fumigatusa hyphae. The microscopic examination of brain tissue sections stained with the HE method revealed the existence of a granuloma with a centrally placed necrotic area. The necrotic area was infiltrated with heterophilic granulocytes and surrounded by macrophage, giant cells and lymphocytes. A connective tissue capsule was located on the periphery of the granuloma. The fungi hyphae, as integral parts of the granuloma, were difficult to observe, and in some samples stained using the HE method they could not be seen at all. On the other hand, sections stanied using the Grocott and PAS methods showed prominent septed and branched hyphae in different parts of the granuloma. With the objective of making an etiological diagnosis of mucotic diseases, it is necessary to apply several
Clinical features of invasive pulmonary aspergillosis vs. colonization in COPD patients distributed by gold stage.
Barberan, Jose; Sanz, Francisco; Hernandez, Jose-Luis; Merlos, Silvia; Malmierca, Eduardo; Garcia-Perez, Francisco-Javier; Sanchez-Haya, Eloy; Segarra, Mar; Garcia de la Llana, Francisco; Granizo, Juan-Jose; Gimenez, Maria-Jose; Aguilar, Lorenzo
To explore clinical features of invasive pulmonary aspergillosis (IPA) vs. colonization among hospitalized COPD patients. Records of COPD patients with two respiratory cultures yielding Aspergillus were retrospectively reviewed. Cases categorized as proven/probable IPA or colonization was analyzed. 118 patients were identified: 70 (59.3%) colonized, 48 (40.7%) with IPA (42 probable, 6 proven). Higher percentage of IPA patients (vs. colonized) presented GOLD III + IV (77.1% vs. 57.1%, p = 0.025). IPA patients presented higher Charlson index (3.5 ± 2.5 vs. 2.6 ± 2.2, p = 0.027), higher rate of ICU admission (27.1% vs. 4.3%, p = 0.001) and worse prognosis (McCabe rapidly fatal category: 31.3% vs. 7.1%, p = 0.001). GOLD-I IPA patients presented risk factors other than COPD. Before hospitalization, 66.7% IPA and 28.6% colonized patients were taking steroids (p < 0.001). Antifungals were administered to 83.3% IPA and 21.4% colonized patients (p < 0.001). Mortality was higher among IPA vs. colonized patients, both in global (58.3% vs. 10.0%, p < 0.001), GOLD-I (75.0% vs. 10.0%, p = 0.041), GOLD-II (42.9% vs. 5.0%, p = 0.042) and GOLD-III patients (54.2% vs. 0.0%, p < 0.001), but not in GOLD-IV patients (69.2% vs. 31.3%, p = 0.066). IPA should be suspected not only in GOLD-III and GOLD-IV COPD patients, with higher mortality in IPA vs. colonized patients for GOLD-II and -III COPD patients. Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Population Pharmacokinetic Analysis of Voriconazole and Anidulafungin in Adult Patients with Invasive Aspergillosis
Mould, Diane R.
To assess the pharmacokinetics (PK) of voriconazole and anidulafungin in patients with invasive aspergillosis (IA) in comparison with other populations, sparse PK data were obtained for 305 adults from a prospective phase 3 study comparing voriconazole and anidulafungin in combination versus voriconazole monotherapy (voriconazole, 6 mg/kg intravenously [IV] every 12 h [q12h] for 24 h followed by 4 mg/kg IV q12h, switched to 300 mg orally q12h as appropriate; with placebo or anidulafungin IV, a 200-mg loading dose followed by 100 mg q24h). Voriconazole PK was described by a two-compartment model with first-order absorption and mixed linear and time-dependent nonlinear (Michaelis-Menten) elimination; anidulafungin PK was described by a two-compartment model with first-order elimination. For voriconazole, the normal inverse Wishart prior approach was implemented to stabilize the model. Compared to previous models, no new covariates were identified for voriconazole or anidulafungin. PK parameter estimates of voriconazole and anidulafungin are in agreement with those reported previously except for voriconazole clearance (the nonlinear clearance component became minimal). At a 4-mg/kg IV dose, voriconazole exposure tended to increase slightly as age, weight, or body mass index increased, but the difference was not considered clinically relevant. Estimated voriconazole exposures in IA patients at 4 mg/kg IV were higher than those reported for healthy adults (e.g., the average area under the curve over a 12-hour dosing interval [AUC0–12] at steady state was 46% higher); while it is not definitive, age and concomitant medications may impact this difference. Estimated anidulafungin exposures in IA patients were comparable to those reported for the general patient population. This study was approved by the appropriate institutional review boards or ethics committees and registered on ClinicalTrials.gov (NCT00531479). PMID:24913161
Population Pharmacokinetic-Pharmacodynamic Analysis of Voriconazole and Anidulafungin in Adult Patients with Invasive Aspergillosis
Mould, Diane R.
To evaluate the exposure-response relationships for efficacy and safety of voriconazole and anidulafungin in adult patients with invasive aspergillosis (IA), a population pharmacokinetic-pharmacodynamic (PK-PD) analysis was performed with data from a phase 3, prospective, double-blind, comparative study evaluating voriconazole and anidulafungin combination therapy versus voriconazole (and placebo) monotherapy. Anidulafungin/placebo treatment duration was 2 to 4 weeks, and voriconazole treatment duration was 6 weeks. Efficacy (6-week all-causality mortality and 6-week global response [n = 176]) and safety (hepatic [n = 238], visual [n = 199], and psychiatric [n = 183] adverse events [AEs]) endpoints were analyzed separately using a binary logistic regression model. In IA patients receiving voriconazole monotherapy, no positive associations between voriconazole exposure and efficacy or safety were identified. In IA patients receiving combination therapy, no positive associations between voriconazole or anidulafungin exposures and efficacy were identified. The 6-week survival rate tended to increase as anidulafungin treatment duration increased; this finding should be considered with caution. Additionally, in IA patients receiving combination therapy, a positive association between voriconazole and anidulafungin exposures (area under the curve [AUC] and trough concentration [Cmin]) and hepatic AEs was established; a weak positive association between voriconazole exposure (AUC and Cmin) and psychiatric AEs was also established, but no association between voriconazole exposure and visual AEs was identified. Besides the drug exposures, no other covariates (i.e., CYP2C19 genotype status, age, weight, body mass index, sex, race, or neutropenia status) were identified as significant predictors of the efficacy and safety endpoints in IA patients. This study was registered on ClinicalTrials.gov (NCT00531479). PMID:24914120
Causes of death in a contemporary cohort of patients with invasive aspergillosis.
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Carolina Garcia-Vidal
Full Text Available Information regarding the processes leading to death in patients with invasive aspergillosis (IA is lacking. We sought to determine the causes of death in these patients, the role that IA played in the cause, and the timing of death. The factors associated with IA-related mortality are also analyzed. We conducted a multicenter study (2008-2011 of cases of proven and probable IA. The causes of death and whether mortality was judged to be IA-related or IA-unrelated were determined by consensus using a six-member review panel. A multivariate analysis was performed to determine risk factors for IA-related death. Of 152 patients with IA, 92 (60.5% died. Mortality was judged to be IA-related in 62 cases and IA-unrelated in 30. The most common cause of IA-related death was respiratory failure (50/62 patients, caused primarily by Aspergillus infection, although also by concomitant infections or severe comorbidities. Progression of underlying disease and bacteremic shock were the most frequent causes of IA-unrelated death. IA-related mortality accounted for 98% and 87% of deaths within the first 14 and 21 days, respectively. Liver disease (HR 4.54; 95% CI, 1.69-12.23 was independently associated with IA-related mortality, whereas voriconazole treatment was associated with reduced risk of death (HR 0.43; 95% CI, 0.20-0.93. In conclusion, better management of lung injury after IA diagnosis is the main challenge for physicians to improve IA outcomes. There are significant differences in causes and timing between IA-related and IA-unrelated mortality and these should be considered in future research to assess the quality of IA care.
Cost-Effectiveness Analysis of Isavuconazole vs. Voriconazole as First-Line Treatment for Invasive Aspergillosis.
Harrington, Rachel; Lee, Edward; Yang, Hongbo; Wei, Jin; Messali, Andrew; Azie, Nkechi; Wu, Eric Q; Spalding, James
Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective. An economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. Base case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome. Isavuconazole is a cost-effective option for the treatment of IA among hospitalized patients. Astellas Pharma Global Development, Inc.
Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Case Report
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Mehmet Akif Yazar
Full Text Available SUMMARY Invasive pulmonary aspergillosis (IPA is an infection rarely seen in intensive care units (ICU. We aimed to discuss the case of IPA found in a patient followed up in our ICU due to chronic obstructive pulmonary disease (COPD. A 58-year old patient diagnosed with COPD has been admitted to our ICU due to respiratory failure. There were not any other diseases except from COPD. In his radiological imaging there were diffuse bilateral infiltrates in the chest X-ray and diffuse infiltration in the thorax tomography. Aspergillus spp was isolated in the bronchoalveolar lavage sample from patient and caspofungin was added to the treatment. On the 12th day of the treatment, it was observed that the results of the control radiological imaging became normal and there was no isolation in the control cultures. In recent years, fungal infections have been determined at an increasing rate in the patients who are not immunosuppressed and hospitalized in ICU. In the IPA cases, it has been shown that such underlying causes as diabetes, malnutrition, use of steroid, uremia, cirrhosis and COPD may create risk. Our patient did not have other disease except from COPD and there was a story of prolonged using of steroid. Steroids are quite frequently used in the ICUs. In the patients with chronic pulmonary diseases, even if it is low dose and short-term, the treatment of steroid is accepted as a risk factor in terms of IPA. Since signs and symptoms are atypical in this group of patients, it is rather difficult to diagnose IPA in the short term. The isolation of aspergillus in our patient's tracheal aspirate taken earlier enabled us to start the treatment early. Although there are not comprehensive studies, it should be kept in mind that İPA may develop in the patients who is using long-term steroid, is admitted to the ICUs due to COPD exacerbations without any other disease.
Antigenic and anticorpal diagnosis of invasive aspergillosis and candidosis in immunocompromised host
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Marco Machetti
Full Text Available Invasive aspergillosis (IA and candidemia are an increasing cause of morbidity and mortality in immunocompromised patients, but diagnostic procedures are often hampered by critical patients conditions. In recent years, non-culture methods have reached a standardization level suitable to be marketed and widely employed. A method for a panfungal antigenic diagnosis, is the detection in serum of (1→3-ß-D-Glucan (BDG, a polisaccaridic component of fungal cell wall. Best results can be obtained in Aspergillus, Candida and Fusarium infections, while the test performs poorly with Cryptococcus and in zygomycosis. The use of this method are limited by the high costs and by the need of disposable materials certified as glucan-free, in order to avoid false positive results. Galactomannan (GM antigen detection is a method for non-invasive diagnosis of IA. The assay, in latex agglutination (LA and enzymeimmunoassay (EIA format, detect GM in serum, whose presence correlates with IA. Sensitivity and specificity strongly fluctuate (50-100% and 81-98% respectively depending on the time of sampling, the positivity cut-off employed, the concomitant administration of antifungal drugs and of some antibiotics. Nevertheless the method is a very useful and widely employed tool for the diagnosis of IA. For the diagnosis of candidemia, two Candida antigens may be detected in serum: the 56°C heat-labile antigen in LA format, and the mannan antigen, in LA and EIA format. Both the methods perform quite well, but sensitivities and specificities are not so good to allow a routinely and useful use in clinical practice.
The Plasmair Decontamination System Is Protective Against Invasive Aspergillosis in Neutropenic Patients.
Fernandez-Gerlinger, Marie-Paule; Jannot, Anne-Sophie; Rigaudeau, Sophie; Lambert, Juliette; Eloy, Odile; Mignon, François; Farhat, Hassan; Castaigne, Sylvie; Merrer, Jacques; Rousselot, Philippe
OBJECTIVE Invasive aspergillosis (IA) is a rare but severe infection caused by Aspergillus spp. that often develops in immunocompromised patients. Lethality remains high in this population. Therefore, preventive strategies are of key importance. The impact of a mobile air decontamination system (Plasmair, AirInSpace, Montigny-le-Bretonneux, France) on the incidence of IA in neutropenic patients was evaluated in this study. DESIGN Retrospective cohort study METHODS Patients with chemotherapy-induced neutropenia lasting 7 days or more were included over a 2-year period. Cases of IA were confirmed using the revised European Organization for Research and Treatment of Cancer (EORTC) criteria. We took advantage of a partial installation of Plasmair systems in the hematology intensive care unit during this period to compare patients treated in Plasmair-equipped versus non-equipped rooms. Patients were assigned to Plasmair-equipped or non-equipped rooms depending only on bed availability. Differences in IA incidence in both groups were compared using Fisher's exact test, and a multivariate analysis was performed to take into account potential confounding factors. RESULTS Data from 156 evaluable patients were available. Both groups were homogenous in terms of age, gender, hematological diagnosis, duration of neutropenia, and prophylaxis. A total of 11 cases of probable IA were diagnosed: 10 in patients in non-equipped rooms and only 1 patient in a Plasmair-equipped room. The odds of developing IA were much lower for patients hospitalized in Plasmair-equipped rooms than for patients in non-equipped rooms (P=.02; odds ratio [OR] =0.11; 95% confidence interval [CI], 0.00-0.84). CONCLUSION In this study, Plasmair demonstrated a major impact in reducing the incidence of IA in neutropenic patients with hematologic malignancies. Infect Control Hosp Epidemiol 2016;37:845-851.
Allergic bronchopulmonary aspergillosis is associated with pet ownership in cystic fibrosis.
Thronicke, Anja; Heger, Nikola; Antweiler, Elisabeth; Krannich, Alexander; Roehmel, Jobst; Brandt, Claudia; Staab, Doris; Tintelnot, Kathrin; Schwarz, Carsten
Late diagnosis of allergic bronchopulmonary aspergillosis (ABPA) is associated with significant lung function decline and morbidity in cystic fibrosis (CF). The association of ABPA and domestic pet ownership in patients with CF has not been elucidated yet. Our objective was to determine the association of ABPA with pet ownership in patients with CF. Clinical and microbiological data from certified local patient registry were analyzed for 109 patients with CF aged 1-64 years: 55 pet owner and 54 non-pet owners. The primary outcome of the retrospective observational study was the occurrence of ABPA in pet owners and non-pet owners with CF. The free statistical software R was utilized to investigate logistic regression models for association factors. Of the 109 patients included in the study, 61 (56%) were female. The mean age of the total group was 25.4 ± 13.2 years. Adjusted analysis revealed that ABPA (OR 5.0227, 95% CI: 1.182-21.340, p = 0.029) was associated with pet ownership in patients with CF. Furthermore, ABPA in pet owners with CF was associated with an increased number of exacerbations (OR 6.446, 95% CI: 1.057-39.328, p = 0.043). Other outcomes did not significantly differ. Owning a pet was associated with ABPA in patients with CF. Future prospective multicenter longitudinal studies are needed to investigate chronological causality between pet ownership, ABPA development, and pulmonary exacerbations and to determine whether these estimates are generalizable for ABPA susceptible patients beyond CF (asthma, bronchiectasis). © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Serial assessment of pulmonary lesion volume by computed tomography allows survival prediction in invasive pulmonary aspergillosis
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Vehreschild, J.J.; Vehreschild, M.J.G.T. [University Hospital of Cologne, Department I of Internal Medicine, Cologne (Germany); German Centre for Infection Research, Partner Site Bonn-Cologne, Cologne (Germany); Heussel, C.P. [Chest Clinic at University Hospital Heidelberg, Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); University Hospital of Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Groll, A.H. [University Children' s Hospital, Infectious Disease Research Program, Department of Paediatric Haematology/Oncology, Muenster (Germany); Silling, G. [University of Muenster, Department of Medicine A, Haematology/Oncology, Muenster (Germany); Wuerthwein, G. [University Hospital Muenster, Centre for Clinical Trials, ZKS Muenster (Germany); Brecht, M. [Chest Clinic at University Hospital Heidelberg, Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); Cornely, O.A. [University Hospital of Cologne, Department I of Internal Medicine, Cologne (Germany); University of Cologne, Clinical Trials Center Cologne, ZKS Koeln (BMBF 01KN1106), Cologne (Germany); Center for Integrated Oncology CIO Koeln Bonn, Cologne (Germany); University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne (Germany)
Serial chest CT is the standard of care to establish treatment success in invasive pulmonary aspergillosis (IPA). Data are lacking how response should be defined. Digital CT images from a clinical trial on treatment of IPA were re-evaluated and compared with available biomarkers. Total volume of pneumonia was added up after manual measurement of each lesion, followed by statistical analysis. One-hundred and ninety CT scans and 309 follow-up datasets from 40 patients were available for analysis. Thirty-one were neutropenic. Baseline galactomannan (OR 4.06, 95%CI: 1.08-15.31) and lesion volume (OR 3.14, 95%CI: 0.73-13.52) were predictive of death. Lesion volume at d7 and trend between d7 and d14 were strong predictors of death (OR 20.01, 95%CI: 1.42-282.00 and OR 15.97, 95%CI: 1.62-157.32) and treatment being rated as unsuccessful (OR 4.75, 95%CI: 0.94-24.05 and OR 40.69, 95%CI: 2.55-649.03), which was confirmed by a Cox proportional hazards model using time-dependent covariates. Any increase in CT lesion volume between day 7 and day 14 was a sensitive marker of a lethal outcome (>50%), supporting a CT rescan each one and 2 weeks after initial detection of IPA. The predictive value exceeded all other biomarkers. Further CT follow-up after response at day 14 was of low additional value. (orig.)
Detection of invasive aspergillosis in bone marrow transplant recipients using real-time PCR
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Mojtaba Nabili
Full Text Available Objective: The invasive aspergillosis (IA is a serious opportunistic infection caused by various species of Aspergillus in immunocompromised individuals. Basically, rapid and early diagnosis prevents IA progression. In this study we performed a Real Time PCR/ Fluorescence Resonance Energy Transfer (FRET for diagnosis of IA in hematologic malignancies and bone marrow transplant recipients. Materials and Methods: Sixty two patients with hematologic malignancies and marrow transplant recipients were evaluated for IA in Sari and Tehran from 2009 to 2010. The primer and hybridization probe were designed to amplify the specific sequence of 18S rRNA genes using Light Cycler system and FRET. Galactomannan (GM assay was performed on serums which obtained from selected patients using the Platelia Aspergillus kit. Results: According to the criteria defined by the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG for IA, 18 (29% patients out of 62 patients were stratified into probable and possible groups. The female-to-male ratio was 1:2; the mean age of the patients was 36 years. The most common malignancies in these patients were acute lymphoblastic leukemia (38.9%. The minimum detection limit was 10 conidia (10 1 CFU/ml equivalents (100 fg per PCR reaction. GM assay was positive in 20.9% and real-time PCR probe set assay were positive in 17.7% patients who had clinical signs and host factor according to the mentioned criteria. Conclusion: Using the Real-Time PCR/FRET assay in whole blood specimens seems to be a promising method for diagnosis of IA, especially when used in combination with the GM detection test.
Diagnostic performance of various tests and criteria employed in allergic bronchopulmonary aspergillosis: a latent class analysis.
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Ritesh Agarwal
Full Text Available AIM: The efficiency of various investigations and diagnostic criteria used in diagnosis of allergic bronchopulmonary aspergillosis (ABPA remain unknown, primarily because of the lack of a gold standard. Latent class analysis (LCA can provide estimates of sensitivity and specificity in absence of gold standard. Herein, we report the performance of various investigations and criteria employed in diagnosis of ABPA. METHODS: Consecutive subjects with asthma underwent all the following investigations Aspergillus skin test, IgE levels (total and A.fumigatus specific, Aspergillus precipitins, eosinophil count, chest radiograph, and high-resolution computed tomography (HRCT of the chest. We used LCA to estimate the performance of various diagnostic tests and criteria in identification of ABPA. RESULTS: There were 372 asthmatics with a mean age of 35.9 years. The prevalence of Aspergillus sensitization was 53.2%. The sensitivity and specificity of various tests were Aspergillus skin test positivity (94.7%, 79.7%; IgE levels>1000 IU/mL (97.1%, 37.7%; A.fumigatus specific IgE levels>0.35 kUA/L (100%, 69.3%; Aspergillus precipitins (42.7%, 97.1%; eosinophil count>1000 cells/µL (29.5%, 93.1%; chest radiographic opacities (36.1%, 92.5%; bronchiectasis (91.9%, 80.9%; and, high-attenuation mucus (39.7%, 100%. The most accurate criteria was the Patterson criteria using six components followed by the Agarwal criteria. However, there was substantial decline in accuracy of the Patterson criteria if components of the criteria were either increased or decreased from six. CONCLUSIONS: A.fumigatus specific IgE levels and high-attenuation mucus were found to be the most sensitive and specific test respectively in diagnosis of ABPA. The Patterson criteria remain the best diagnostic criteria however they have good veridicality only if six criteria are used.
Efficacy and cost-effectiveness of voriconazole prophylaxis for prevention of invasive aspergillosis in high-risk liver transplant recipients.
Balogh, Julius; Gordon Burroughs, Sherilyn; Boktour, Maha; Patel, Samir; Saharia, Ashish; Ochoa, Robert A; McFadden, Robert; Victor, David W; Ankoma-Sey, Victor; Galati, Joseph; Monsour, Howard P; Fainstein, Victor; Li, Xian C; Grimes, Kevin A; Gaber, A Osama; Aloia, Thomas; Ghobrial, R Mark
Aspergillus infection remains a significant and deadly complication after liver transplantation (LT). We sought to determine whether the antifungal prophylactic use of voriconazole reduces the incidence of invasive aspergillosis (IA) in high-risk LT recipients without prohibitively increasing cost. During the study era (April 2008 to April 2014), 339 deceased donor LTs were performed. Of those patients, 174 high-risk recipients were administered antifungal prophylaxis with voriconazole. The median biological Model for End-Stage Liver Disease score at the time of LT was 33 (range, 18-49) with 56% requiring continuous renal replacement therapy and 50% requiring ventilatory support immediately before transplantation. Diagnosis of IA was stratified as proven, probable, or possible according to previously published definitions. No IA was documented in patients receiving voriconazole prophylaxis. At 90 days after LT, the institutional cost of prophylaxis was $5324 or 5.6% of the predicted cost associated with post-LT aspergillosis. There was no documentation of resistant strains isolated from any recipient who received voriconazole. In conclusion, these data suggest that voriconazole prophylaxis is safe, clinically effective, and cost-effective in high-risk LT recipients. © 2015 American Association for the Study of Liver Diseases.
Immunodiagnosis of systemic aspergillosis. I. Antigenemia detected by radioimmunoassay in experimental infection. [/sup 125/I tracer technique
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Weiner, M.H.; Coats-Stephen, M.
Because systemic aspergillosis is difficult to diagnose ante mortem, a study to improve immunodiagnosis was undertaken in a rabbit model of disseminated infection. We found that the predominant humoral response of infected animals was directed against four Aspergillus antigens identified by crossed immunoelectrophoresis. One of these antigens, a cell-wall carbohydrate, was purified by gel-filtration chromatography and was used to develop a radiommunoassay. The sensitivity of this assay was increased by testing for serum-bound antigen as well as for free antigen. When the sensitivity of the RIA was evaluated in the animal model, antigenemia was detected in 78% of 51 rabbits with disseminated infection and ante mortem in 86% of 42 rabbits with lethal infection. By contrast, with immunoprecipitin analysis only eight of 51 rabbits were positive for antigen, and six of 51 rabbits were positive for Aspergillus antibody. The specificity of the RIA was also tested. Negative controls for antigen included sera from 76 normal rabbits and sera from 25 rabbits with systemic candidiasis. The Candida control group is pertinent because 48% of these rabbits had specific Candida antigenemia detected by a mannan RIA. This study demonstrates that Aspergillus antigenemia occurs during the course of experimental disseminated aspergillosis and illustrates the potential of an Aspergillus antigen RIA for sensitive, specific immunodiagnosis of human infections.
Aspergillosis, a Natural Infection in Poultry: Mycological and Molecular Characterization and Determination of Gliotoxin in Aspergillus fumigatus Isolates.
de Oca, Verónica Montes; Valdés, Sara Esther; Segundo, Carolina; Gómez, Gabriela Guadalupe; Ramírez, José; Cervantes, Roberto Arnulfo
Aspergillosis affects all types of birds; it causes the loss of specimens with high ecologic value and also leads to significant economic losses within the poultry industry. The main etiologic agent is Aspergillus fumigatus , a filamentary fungus with multiple virulence factors, such as gliotoxin (GT), which is an immunosuppressive epipolythiodioxopiperazine molecule. Necropsy was performed on 73 poultry from different provenances, all of which presented with a respiratory semiology compatible with aspergillosis. A mycological culture was performed on the injured lungs of diseased birds, as was chloroform extraction of the GT, a thin-layer chromatography analysis (TLC), and a histopathology analysis with hematoxylin-eosin and Grocott stainings. The A. fumigatus identification was confirmed by PCR, where the ITS 1 5.1-5.8S-ITS 2 fragment of the rDNA complex was amplified. The in vitro GT production was studied by TLC in the recovered isolates from A. fumigatus . Seven isolates of A. fumigatus were obtained and in six of them, GT-like compounds were detected. In a lung sample, a compound with the same retention time (RF) as the reference GT was detected; whereas RF compounds different from the GT standard were observed in three lung samples.
Cavitating lung disease due to concomitant drug resistant tuberculosis and invasive pulmonary Aspergillosis in a post-partum patient: A case report.
Ray, Animesh; Suri, J C; Sen, M K; Chakrabarti, S; Gupta, Ayush; Capoor, Malini
Many disorders can present as cavitating lesions in the lung. In this case report, a case of mixed infection with drug resistant tuberculosis and invasive pulmonary aspergillosis in a post-partum patient has been presented. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.
Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary Aspergillosis infection.
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Juan Sainz
Full Text Available The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA. Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1(rs3901533 T/T and Dectin-1(rs7309123 G/G genotypes and DC-SIGN(rs4804800 G, DC-SIGN(rs11465384 T, DC-SIGN(7248637 A and DC-SIGN(7252229 C alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37-22.77; OR = 4.91 95%CI 1.52-15.89; OR = 2.75 95%CI 1.27-5.95; OR = 2.70 95%CI 1.24-5.90; OR = 2.39 95%CI 1.09-5.22 and OR = 2.05 95%CI 1.00-4.22, respectively. There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1(rs3901533_T allele and Dectin-1(rs7309123_G/G genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1(rs7309123 polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk
Resource use and cost of treatment with voriconazole or conventional amphotericin B for invasive aspergillosis.
Wingard, J R; Herbrecht, R; Mauskopf, J; Schlamm, H T; Marciniak, A; Roberts, C S
Voriconazole, a broad-spectrum triazole, has demonstrated significantly improved survival compared with conventional amphotericin B (CAB) as initial therapy for invasive aspergillosis (IA). To compare health care resource use and cost at 12 weeks following first-line treatment with voriconazole compared with CAB for IA using resource use data collected during a clinical trial. Days of hospitalization, intensive care, antifungal drug use, and outpatient care were collected during a large randomized, controlled trial of patients with IA receiving initial treatment with voriconazole or CAB. Unit costs based on published data sources were applied to healthcare use to estimate 12-week costs following initiation of therapy. Resource use and costs were compared for each treatment arm overall and by survival. The sensitivity of total costs to changes in healthcare use and unit costs was examined. Total hospital days and intensive care unit (ICU) days were similar for voriconazole and CAB (total: 27.8 vs. 27.7, P=0.97 and ICU: 5.6 vs. 8.1, P=0.11). Among survivors, voriconazole was associated with similar numbers of total hospital days (29.8 vs. 32.0 days, P=0.54) to CAB, but fewer ICU days (3.9 vs. 8.2, P=0.03). For non-survivors, those treated with voriconazole had a similar number of total hospital days (23.0 vs. 21.8, P=0.73) and ICU days (9.8 vs. 7.9, P=0.44). Patients treated with voriconazole had significantly more days alive and out of the hospital than with CAB at 12 weeks (40.3 vs. 28.4 days, P<0.001). Total costs were similar with voriconazole compared with CAB ($78,860 vs. $83,857, P=0.51). Differences in cost were not sensitive to changes in the input parameter values. Using voriconazole first-line for treatment of IA resulted in significantly fewer deaths and similar treatment costs. Hospital-free survival was significantly greater for patients initially treated with voriconazole.
Combination antifungal therapy and surgery for the treatment of invasive pulmonary aspergillosis after hematopoietic stem cell transplantation
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Tiziana Toffolutti
Full Text Available An 8-year old boy, affected by severe aplastic anemia, developed a probable pulmonary invasive aspergillosis (IA early after a second unrelated allogeneic hematopoietic stem cell transplant (HSCT. He was treated promptly with the combination of liposomal amphotericin B and caspofungin. Despite the initial stabilization, the patient deteriorated and the antifungal therapy was switched to voriconazole and caspofungin. The patient gradually improved and was discharged home on day +29 post-HSCT on oral voriconazole. On day +119, a sudden episode of hemoptysis occurred and a right superior lobectomy was decided to remove the residual aspergilloma. The patient is now alive and well more than 24 months from HSCT. This case demonstrated that antifungal combination therapy and surgery are valid options to cure pulmonary IA even in patients at high-risk and severely immunosuppressed.
Status of aspergillosis and sea fan populations in Curaçao ten years after the 1995 Caribbean epizootic
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M. M Nugues
Full Text Available In 1995, a survey of sea fan corals was conducted in Curaçao during a Caribbean-wide outbreak of the sea fan disease aspergillosis. The survey was repeated in 2005 using the same methodology and identical sites to examine changes in sea fan populations 10 years after the initial epizootic. Necrotic lesions typical of aspergillosis were present on as many sea fans in 2005 as in 1995 (mean ± SE: 52 ± 6 vs 43 ± 10%. The disease also showed no significant variation in virulence (9.6 ± 1.2 vs 8.8 ± 1.0% tissue loss per diseased colony. However, the average number of sea fan colonies per 10 m² decreased from 2.7 ± 1.1 to 0.7 ± 0.2 over the 10-year period, a decline of almost 75%. This decrease occurred for all colony sizes, but was more pronounced among small colonies, resulting in an overall trend of domination by large colonies. These results support that aspergillosis can have a significant, long-term impact on sea fan population size and structure. The continued presence of the disease in 2005 could be contributing to reduced recruitment and/or selective mortality among the smallest colonies. This study provides no indication that host resistance against aspergillosis could reverse the decline of Caribbean sea fan corals. Rev. Biol. Trop. 54 (Suppl. 3: 153-160. Epub 2007 Jan. 15.En 1995, se realizó un sondeo de los abanicos de mar durante un brote de aspergilosis, una enfermedad de abanicos de mar extendida en todo el Caribe. En el año 2005 se repitió el sondeo utilizando exactamente la misma metodología y los mismos sitios para examinar cambios en las poblaciones tras 10 años del inicio del brote. Se presentaron lesiones necróticas típicas de la aspergilosis en tantos abanicos en el 2005, como en 1995 (promedio ± ES: 52 ± 6 vs 43 ± 10%. La enfermedad tampoco mostró variaciones significativas en la virulencia (9.6 ± 1.2 vs 8.8 ± 1.0%, pérdida de tejido por colonia enferma. Sin embargo, el número promedio de colonias de
[Invasive pulmonary aspergillosis and esophageal candidiasis in a patient with decompensated liver cirrhosis due to chronic hepatitis C and alcohol].
Porubčin, Štefan; Porubčinová, I; Kristian, P; Virág, L; Štammová, E; Vyhnánková, V; Paraličová, Z
We present a rare case of combined fungal infection in a critically ill 47 year-old patient with chronic hepatitis C at the stage of liver cirrhosis. The patient was admitted for signs of decompensated cirrhosis caused by hepatitis C and increased alcohol consumption. After 2 week hospital stay, his condition was complicated by a pulmonary infiltrate and rapid deterioration followed. Despite intensive care, the patient died. Autopsy findings showed invasive pulmonary aspergillosis. The aim of this case report is to point to a broad differential diagnosis of jaundice and pulmonary infiltrates, thus stressing the value of interdisciplinary cooperation and the need to consider the possibility of invasive fungal infections when caring for liver cirrhosis patients. In addition, several risk factors contributing to the development of fungal diseases in these patients are discussed in the article.
Prophylactic inhalation of Amphotericin B in invasive pulmonary aspergillosis: distribution study. Prophylaktische Inhalation von Amphotericin B bei invasiver Aspergillose: Verteilungsstudie
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Barzen, G. (Universitaetsklinikum Rudolf Virchow, Berlin (Germany). Strahlenklinik und Poliklinik); Beyer, J. (Universitaetsklinikum Rudolf Virchow, Berlin (Germany). Medizinische Klinik und Poliklinik); Farshidfar, G. (Freie Univ. Berlin (Germany). Inst. fuer Diagnostikforschung); Kramp, W. (Freie Univ. Berlin (Germany). Inst. fuer Diagnostikforschung); Richter, W. (Universitaetsklinikum Rudolf Virchow, Berlin (Germany). Strahlenklinik und Poliklinik); Felix, R. (Universitaetsklinikum Rudolf Virchow, Berlin (Germany). Strahlenklinik und Poliklinik)
Invasive pulmonary aspergillosis (IPA) during periods of immunosuppression or prolonged neutropenia is a serious condition with high mortality. Prophylaxis is unsatisfactory bcause of the low effectiveness of systemic administration of amphotericin B (AMB) and because of its side effects. Prophylactic inhalation of AMB by means of a nebulizing system may be able to reduce the incidence of IPA. Therefore, we studied the distribution of nebulized [sup 99m]Tc-labeled AMB and estimated its particle size. AMB is homogeneously distributed in the lung and partly deposited in the terminal respiratory unit; it remains there with a half-life of at least 14 h. Therefore, prophylaxis of IPA with AMB nebulized as described can be recommended. (orig.)
Percutaneous treatment with amphotericin B in a case of invasive pulmonary aspergillosis; Tratamiento percutaneo con anfotericina B en un caso de aspergilosis pulmonar invasiva
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Ruiz, A.; Lonjedo, E.; Agramunt, M.; Martinez-Rodrigo, J. J.; Palomero, J. [Hospital Universitario Dr. Peset. Valencia (Spain)
Invasive pulmonary aspergillosis (IPA) is a serious complications that occurs in immunocompromised patients. We need a rapid and effective treatment both to treat the aspergillosis as well as to be able to continue, as soon as possible, treatment of the baseline disease. We present a case of a percutaneous treatment of the pulmonary lesions in a 55 year old male with IPA in the context of acute myeloid leukemia (AML). With Computerized Tomography (CT) control and using a fine needle, we injected intralesionally a solution of Amphotericin B (AB) (5 mg/cc of 5% glucose solution). We evaluated the complications and efficacy in relationship to the clinical improvement and reduction in lesion size. (Author) 18 refs.
The case of diagnostics of invasive pulmonary aspergillosis by in vivo probe-based confocal laser endomicroscopy of central and distal airways
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Olesya Danilevskaya
Full Text Available We present a case of 41-year-old patient with invasive pulmonary aspergillosis (IPA in which probe-based confocal laser endomicroscopy (pCLE imaging of central and distal airways was first performed in vivo. pCLE imaging showed the signs of complete or partial destruction of elastin network of alveolar wall with fibrillar branching fluorescent structures in the zone with typical IPA changes on HRCT.
Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis.
Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-Aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto
E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action-inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated.
Efficacy of Oral E1210, a New Broad-Spectrum Antifungal with a Novel Mechanism of Action, in Murine Models of Candidiasis, Aspergillosis, and Fusariosis▿
Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto
E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action—inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated. PMID:21788462
Aspergilose orbitária: relato de caso Ocular aspergillosis: case report
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Patrícia Ioschpe Gus
inicia-se o manejo, segundo o quadro de sintomas.Presence of fungus in the conjunctiva is a constant threat to the eyes, because these microorganisms, defined as opportunistic, may provoke severe ocular infections, in situations as low organic resistance, use of immunosuppressants, antibiotics and epithelial alteration. Our goal here is to report a case of ocular aspergillosis in an immunosupressed patient where paroxysmal nocturnal hemoglobinuria was diagnosed. A 51-year-old immunosupressed, thrombocytopenic patient was hospitalized with a diagnosis of paroxysmal nocturnal hemoglobinuria. On examination, she had a visual acuity of 20/40 in the right eye (RE and light perception in the left (LE. She presented hyposphagma, bilateral conjunctival edema on biomicroscopy and had some multiple and circumscribed conjunctival abscesses in both eyes; clear cornea in both eyes. Fundoscopy of the RE did show any particularity, in the LE there was a smear hemorrhage. Computed tomograph showed a fat periocular infiltration. Magnetic resonance lead to the same finding, compatible with orbital cellulitis. Hemoculture showed Aspergillus growth and direct smears of conjunctival material was negative. There was great improvement while treating her with amphotericin B, but there was complete remission after using 5% natamicyn eye drops. Orbital infections caused by Aspergillus are uncommon, usually appearing in immunosuppressed patients. Frequently they progress insidiously, and can be confounded with other orbital processes. Immunological impairment can inhibit the expression of local and systemic symptoms, resulting in diagnostic confusion. The diagnosis is established by laboratory tests, but culture can be negative in spite of the classical presentation, making the beginning of treatment difficult. In these cases management starts according to the symptoms.
Phototoxicity, Pseudoporphyria, and Photo-onycholysis Due to Voriconazole in a Pediatric Patient With Leukemia and Invasive Aspergillosis.
Willis, Zachary I; Boyd, Alan S; Di Pentima, M Cecilia
Voriconazole is a triazole antifungal agent superior to amphotericin B in the treatment of invasive aspergillosis. It is generally well tolerated and has excellent oral bioavailability, providing significant benefit in the treatment of invasive fungal infections. There have been numerous reports of dermatologic reactions to this agent, including erythroderma, cheilitis, Stevens-Johnson syndrome, discoid lupus erythematosus, pseudoporphyria, squamous cell carcinoma, and photosensitivity reactions. Pseudoporphyria, a dermatologic condition mimicking porphyria cutanea tarda, has been described as an adverse effect of voriconazole use. Clinical findings include photosensitivity, vesicles, bullae, milia, and scarring in sun-exposed areas. Photo-onycholysis is a phenomenon of nail discoloration and onycholysis that has been described in the setting of a phototoxic drug reaction and pseudoporphyria. Implicated drugs have most commonly been tetracyclines, fluoroquinolones, and psoralens; others have been reported as well. We report a case of a pediatric patient with leukemia who developed symptoms consistent with pseudoporphyria and later photo-onycholysis while being treated with voriconazole. To our knowledge, this is the first reported case of pseudoporphyria due to voriconazole in a pediatric patient and the first reported case of photo-onycholysis as a consequence of voriconazole use. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: email@example.com.
Avian morbidity and mortality from botulism, aspergillosis, and salmonellosis at Jamaica Bay Wildlife Refuge, New York, USA
Brand, C.J.; Windingstad, R.M.; Siegfried, L.M.; Duncan, R.M.; Cook, R.M.
During the summers of 1981 and 1982, studies were conducted at Jamaica Bay Wildlife Refuge, Long Island, New York, to determine whether annual water-level drawdowns used to create shorebird habitat also led to the occurrence of avian botulism (Clostridium botulinum type C). Low levels of morbidity and mortality from avian botulism occurred on the two ponds throughout both summers, but there was no apparent relationship between the occurrence or rates of botulism losses and drawdowns of the ponds. Botulism also occurred throughout both summers on other areas of the refuge. Botulinal toxin was found in fly larvae associated with avian carcasses, including birds that did not die from botulism. Toxin was not found in other samples of aquatic biota in the ponds, although it was demonstrated in a single sample of decomposing sea lettuce (Ulva lactuca) in Jamaica Bay. Aspergillosis (Aspergillus fumigatus) and salmonellosis (Salmonella spp.) were also frequently-diagnosed causes of morbidity and mortality. We believe that botulinal toxin present in carcasses of birds dying from botulism, or produced postmortem in birds dying from other causes, on the two ponds and other areas in Jamaica Bay were a major source of botulinal toxin. Toxin could be ingested by birds through direct scavenging on carcasses, or by consumption of toxic fly larvae associated with carcasses. Diligent carcass pickup at the two ponds is recommended to reduce mortality from avian botulism.
Cost-effectiveness analysis of interventions for prevention of invasive aspergillosis among leukemia patients during hospital construction activities.
Combariza, Juan F; Toro, Luis F; Orozco, John J; Arango, Marcos
Invasive Aspergillosis (IA) is a serious problem among hematological patients and it is associated with high mortality. This situation can worsen at times of hospital construction, however there are several preventive measures available. This work aims to define the cost-effectiveness of some of these interventions. A decision tree model was used, it was divided into four arms according to each 1 of the interventions performed. A cost-effectiveness incremental analysis comparing environmental control measures, high efficiency particulate absorption (HEPA) filter installation and prophylaxis with posaconazole was done. Probabilistic and deterministic sensitivity analyses were also carried out. Among 86 patients with 175 hospitalization episodes, the incidence of IA with environmental protection measures, antifungal prophylaxis and hospitalization in rooms with HEPA filters was 14.4%, 6.3% and 0%, respectively. An Incremental Cost Effectiveness Ratio analysis was performed and it was found that HEPA filtered rooms and environmental protection measures are cost saving interventions when compared with posaconazole prophylaxis (-$2665 vs -$4073 vs $42 531 US dollars, respectively) for IA episode prevented. The isolation of inpatients with acute leukemia during hospital construction periods in HEPA filtered rooms could reduce the incidence of IA and might be a cost-effective prevention strategy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Evidence Supporting a Role for Mammalian Chitinases in Efficacy of Caspofungin against Experimental Aspergillosis in Immunocompromised Rats
Verwer, Patricia E. B.; ten Kate, Marian T.; Falcone, Franco H.; Morroll, Shaun; Verbrugh, Henri A.; Bakker-Woudenberg, Irma A. J. M.; van de Sande, Wendy W. J.
Objectives Caspofungin, currently used as salvage therapy for invasive pulmonary aspergillosis (IPA), strangely only causes morphological changes in fungal growth in vitro but does not inhibit the growth. In vivo it has good efficacy. Therefore the question arises how this in vivo activity is reached. Caspofungin is known to increase the amount of chitin in the fungal cell wall. Mammals produce two chitinases, chitotriosidase and AMCase, which can hydrolyse chitin. We hypothesized that the mammalian chitinases play a role in the in vivo efficacy of caspofungin. Methods In order to determine the role of chitotriosidase and AMCase in IPA, both chitinases were measured in rats which did or did not receive caspofungin treatment. In order to understand the role of each chitinase in the breakdown of the caspofungin-exposed cells, we also exposed caspofungin treated fungi to recombinant enzymes in vitro. Results IPA in immunocompromised rats caused a dramatic increase in chitinase activity. This increase in chitinase activity was still noted when rats were treated with caspofungin. In vitro, it was demonstrated that the action of both chitinases were needed to lyse the fungal cell wall upon caspofungin exposure. Conclusion Caspofungin seemed to alter the cell wall in such a way that the two chitinases, when combined, could lyse the fungal cell wall and assisted in clearing the fungal pathogen. We also found that both chitinases combined had a direct effect on the fungus in vitro. PMID:24155872
Economic evaluation of voriconazole compared with conventional amphotericin B for the primary treatment of aspergillosis in immunocompromised patients.
Wenzel, R; Del Favero, A; Kibbler, C; Rogers, T; Rotstein, C; Mauskopf, J; Morris, S; Schlamm, H; Troke, P; Marciniak, A
The objective of this study was to conduct an economic evaluation of voriconazole compared with conventional amphotericin B deoxycholate (CAB) using data from a recently reported randomized comparative trial in patients with various underlying immunosuppressive conditions. This trial demonstrated the superiority of voriconazole in terms of clinical response, survival and safety when used as primary therapy for invasive aspergillosis. A decision analytic model was designed using an expert panel and populated primarily with efficacy and resource utilization data collected prospectively during the clinical trial. The analysis was carried out from the perspective of the health care system and all costs are reported in 2002 US dollars. Average total treatment costs per patient were 10% lower in the voriconazole arm ($30 664) than in the CAB arm ($34 144), resulting from reduced consumption of hospital resources and fewer changes in antifungal therapy. In the base case analysis, voriconazole provided an average saving of $3481 per treated patient, resulted in a lower cost per survivor ($43 310 versus $58 971) and a lower cost per successfully treated patient ($58 100 versus $108 124) compared with CAB. Sensitivity analyses demonstrated that the cost savings observed were maintained over a wide range of alternative values for both unit costs and resource utilization, including length of hospital stay, time spent in intensive care units, bed day costs and the cost of lipid formulations of amphotericin B. Incremental cost-effectiveness analysis indicated the dominance of voriconazole because of both lower costs and greater efficacy.
Computer tomography in pulmonary invasive aspergillosis in hematological patients with neutropenia: An useful tool for diagnosis and assessment of outcome in clinical trials
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Caillot, Denis, E-mail: email@example.com [Dijon University Hospital Center, Dijon (France); Latrabe, Valerie [Bordeaux University Hospital Center, Bordeaux (France); Thiebaut, Anne [Lyon University Hospital Center, Lyon (France); Herbrecht, Raoul [Strasbourg Regional University Hospital Center, Strasbourg (France); De Botton, Stephane [Lille Regional University Hospital Center, Lille (France); Pigneux, Arnaud [Bordeaux University Hospital Center, Bordeaux (France); Monchecourt, Francoise; Mahi, Lamine [Gilead Sciences, Paris (France); Alfandari, Serge [Lille Regional University Hospital Center, Lille (France); Couaillier, Jean-Francois [Dijon University Hospital Center, Dijon (France)
Background and objective: The exact timing of the evolution of lesion volumes of invasive pulmonary aspergillosis (IPA) on CT scan images could be helpful in the management of hematological patients but has never been evaluated in a prospective study. We analyzed the CT scan data from the prospective Combistrat trial. Design and methods: Volumes of aspergillosis lesions from 30 patients (including 24 acute myeloid leukaemia) with probable (n = 26) or proven (n = 4) IPA according to the EORTC-MSG modified criteria, were measured prospectively on the thoracic CT scans at the enrolment in the study on day 0 (D0), D7, D14 and end of treatment (EOT). Results: For the overall population, the volume of pulmonary aspergillosis lesions increased significantly from D0 to D7 (1.6 fold; p = 0.003). Then this volume decreased significantly from D7 to D14 (1.36 fold at D14 with p = 0.003 for D14 vs. D7, but with p = 0.56 for D14 vs. D0). At EOT (= D17, median value), the volume of lesions was significantly lower than D14 (0.76 fold the initial volume; p < 0.001) but it was not significantly different when compared to D0 (p = 0.11). Conclusions: The results of this prospective study suggest that the sequential analysis of CT scan in neutropenic patients with IPA depicts more precisely the evolution of lesion volumes than comparison to baseline images. Moreover, the systematic use of chest CT appears to be a useful tool for diagnosis and outcome evaluation of IPA in clinical trials.
Evaluation of clinical characteristics and prognosis of chronic pulmonary aspergillosis depending on the underlying lung diseases: Emphysema vs prior tuberculosis.
Koyama, Kazuya; Ohshima, Nobuharu; Suzuki, Junko; Kawashima, Masahiro; Okuda, Kenichi; Sato, Ryota; Suzukawa, Maho; Nagai, Hideaki; Matsui, Hirotoshi; Ohta, Ken
There have been scarce data evaluating the differences of clinical characteristics and prognosis of chronic pulmonary aspergillosis (CPA) depending on underlying pulmonary diseases. We tried to clarify them in CPA patients who had pulmonary emphysema or previous pulmonary tuberculosis. We reviewed and evaluated CPA patients diagnosed between 2007 and 2013 with pulmonary emphysema (PE group; n = 29), with previous pulmonary tuberculosis (PT group; n = 47) and with combination of these 2 underlying conditions (CTE group; n = 24). In CT findings, fungus balls were rare in PE group (7% in PE group and 36% in PT group; p = 0.006). Compared with PT group, PE group patients exhibited more frequent preceding antibiotics administration (45% vs 11%; p = 0.002) and fever (52% vs 17%; p = 0.002), less frequent hemosputum (24% vs 57%; p = 0.008), and more frequent consolidations in imaging (79% vs 38%; p = 0.001) and respiratory failure (34% vs 13%; p = 0.020), possibly suggesting more acute clinical manifestations of CPA in emphysematous patients. Trend of the differences between PT and PE group was not changed when patients with fungal balls were excluded. Multivariate Cox regression analysis of risks for all-cause mortality revealed age (HR, 1.079; p = 0.002) and emphysema (HR, 2.45; p = 0.040) as risk factors. Assessment of underlying lung diseases is needed when we estimate prognosis and consider treatment of CPA patients. Particularly, emphysematous patients can be presented as refractory pneumonia and show poor prognosis. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Evaluation of PCR on bronchoalveolar lavage fluid for diagnosis of invasive aspergillosis: a bivariate metaanalysis and systematic review.
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Wenkui Sun
Full Text Available BACKGROUND: Nucleic acid detection by polymerase chain reaction (PCR is emerging as a sensitive and rapid diagnostic tool. PCR assays on serum have the potential to be a practical diagnostic tool. However, PCR on bronchoalveolar lavage fluid (BALF has not been well established. We performed a systematic review of published studies to evaluate the diagnostic accuracy of PCR assays on BALF for invasive aspergillosis (IA. METHODS: Relevant published studies were shortlisted to evaluate the quality of their methodologies. A bivariate regression approach was used to calculate pooled values of the method sensitivity, specificity, and positive and negative likelihood ratios. Hierarchical summary receiver operating characteristic curves were used to summarize overall performance. We calculated the post-test probability to evaluate clinical usefulness. Potential heterogeneity among studies was explored by subgroup analyses. RESULTS: Seventeen studies comprising 1191 at-risk patients were selected. The summary estimates of the BALF-PCR assay for proven and probable IA were as follows: sensitivity, 0.91 (95% confidence interval (CI, 0.79-0.96; specificity, 0.92 (95% CI, 0.87-0.96; positive likelihood ratio, 11.90 (95% CI, 6.80-20.80; and negative likelihood ratio, 0.10 (95% CI, 0.04-0.24. Subgroup analyses showed that the performance of the PCR assay was influenced by PCR assay methodology, primer design and the methods of cell wall disruption and DNA extraction. CONCLUSIONS: PCR assay on BALF is highly accurate for diagnosing IA in immunocompromised patients and is likely to be a useful diagnostic tool. However, further efforts towards devising a standard protocol are needed to enable formal validation of BALF-PCR.
Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.
Mansh, M; Binstock, M; Williams, K; Hafeez, F; Kim, J; Glidden, D; Boettger, R; Hays, S; Kukreja, J; Golden, J; Asgari, M M; Chin-Hong, P; Singer, J P; Arron, S T
Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
Safety, Efficacy, and Exposure–Response of Voriconazole in Pediatric Patients With Invasive Aspergillosis, Invasive Candidiasis or Esophageal Candidiasis
Macias-Parra, Mercedes; Mudry, Peter; Conte, Umberto; Yan, Jean L.; Liu, Ping; Capparella, M. Rita; Aram, Jalal A.
Background: Data on safety and efficacy of voriconazole for invasive aspergillosis (IA) and invasive candidiasis/esophageal candidiasis (IC/EC) in pediatric patients are limited. Methods: Patients aged 2–voriconazole. Patients followed dosing regimens based on age, weight and indication, with adjustments permitted. Treatment duration was 6–12 weeks for IA patients, ≥14 days after last positive Candida culture for IC patients and ≥7 days after signs/symptoms resolution for EC patients. Primary analysis for both the studies was safety and tolerability of voriconazole. Secondary end points included global response success at week 6 and end of treatment (EOT), all-causality mortality and time to death. Voriconazole exposure–response relationship was explored. Results: Of 53 voriconazole-treated pediatric patients (31 IA; 22 IC/EC), 14 had proven/probable IA, 7 had confirmed IC and 10 had confirmed EC. Treatment-related hepatic and visual adverse events, respectively, were reported in 22.6% and 16.1% of IA patients, and 22.7% and 27.3% of IC/EC patients. All-causality mortality in IA patients was 14.3% at week 6; no deaths were attributed to voriconazole. No deaths were reported for IC/EC patients. Global response success rate was 64.3% (week 6 and EOT) in IA patients and 76.5% (EOT) in IC/EC patients. There was no association between voriconazole exposure and efficacy; however, a slight positive association between voriconazole exposure and hepatic adverse events was established. Conclusions: Safety and efficacy outcomes in pediatric patients with IA and IC/EC were consistent with previous findings in adult patients. PMID:27636722
Application of a low molecular weight antifungal protein from Penicillium chrysogenum (PAF) to treat pulmonary aspergillosis in mice.
Palicz, Zoltán; Gáll, Tamás; Leiter, Éva; Kollár, Sándor; Kovács, Ilona; Miszti-Blasius, Kornél; Pócsi, István; Csernoch, László; Szentesi, Péter
PAF, a small antifungal protein from Penicillium chrysogenum, inhibits the growth of several pathogenic filamentous fungi, including members of the Aspergillus genus. PAF has been proven to have no toxic effects in vivo in mice by intranasal application. To test its efficacy against invasive pulmonary aspergillosis (IPA), experiments were carried out in mice suffering from IPA. Adult mice were immunosuppressed and then infected with Aspergillus fumigatus. After stable infection, the animals were inoculated with PAF intranasally at a concentration of 2.7 mg/kg twice per day. At this concentration-which is highly toxic in vitro to A. fumigatus-the mortality of the animals was slightly delayed but finally all animals died. Histological examinations revealed massive fungal infections in the lungs of both PAF-treated and untreated animal groups. Because intranasally administered PAF was unable to overcome IPA, modified and combined therapies were introduced. The intraperitoneal application of PAF in animals with IPA prolonged the survival of the animals only 1 day. Similar results were obtained with amphotericin B (AMB), with PAF and AMB being equally effective. Combined therapy with AMB and PAF-which are synergistic in vitro-was found to be more effective than either AMB or PAF treatment alone. As no toxic effects of PAF in mammals have been described thus far, and, moreover, there are so far no A. fumigatus strains with reported inherent or acquired PAF resistance, it is worth carrying out further studies to introduce PAF as a potential antifungal drug in human therapy.
Safety, Efficacy, and Exposure-Response of Voriconazole in Pediatric Patients With Invasive Aspergillosis, Invasive Candidiasis or Esophageal Candidiasis.
Martin, Judith M; Macias-Parra, Mercedes; Mudry, Peter; Conte, Umberto; Yan, Jean L; Liu, Ping; Capparella, M Rita; Aram, Jalal A
Data on safety and efficacy of voriconazole for invasive aspergillosis (IA) and invasive candidiasis/esophageal candidiasis (IC/EC) in pediatric patients are limited. Patients aged 2-<18 years with IA and IC/EC were enrolled in 2 prospective open-label, non-comparative studies of voriconazole. Patients followed dosing regimens based on age, weight and indication, with adjustments permitted. Treatment duration was 6-12 weeks for IA patients, ≥14 days after last positive Candida culture for IC patients and ≥7 days after signs/symptoms resolution for EC patients. Primary analysis for both the studies was safety and tolerability of voriconazole. Secondary end points included global response success at week 6 and end of treatment (EOT), all-causality mortality and time to death. Voriconazole exposure-response relationship was explored. Of 53 voriconazole-treated pediatric patients (31 IA; 22 IC/EC), 14 had proven/probable IA, 7 had confirmed IC and 10 had confirmed EC. Treatment-related hepatic and visual adverse events, respectively, were reported in 22.6% and 16.1% of IA patients, and 22.7% and 27.3% of IC/EC patients. All-causality mortality in IA patients was 14.3% at week 6; no deaths were attributed to voriconazole. No deaths were reported for IC/EC patients. Global response success rate was 64.3% (week 6 and EOT) in IA patients and 76.5% (EOT) in IC/EC patients. There was no association between voriconazole exposure and efficacy; however, a slight positive association between voriconazole exposure and hepatic adverse events was established. Safety and efficacy outcomes in pediatric patients with IA and IC/EC were consistent with previous findings in adult patients.
Caspofungin for treatment of invasive aspergillosis in Germany: results of a pre-planned subanalysis of an international registry
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Egerer Gerlinde
Full Text Available Abstract Background This study is a pre-planned country-specific subanalysis of results in Germany from a multinational multicenter registry to prospectively assess real-world experience with caspofungin administered for treatment of proven or probable invasive aspergillosis (IA. Methods Data from patients treated with caspofungin for a single episode of IA were collected. Effectiveness was determined by the local investigator as favorable (complete or partial response or unfavorable (stable disease, failure or death at the end of caspofungin therapy. Descriptive statistics with binomial exact confidence intervals were employed. Results Forty-two consecutive patients were identified in three German centers. Three patients (7% had proven IA and 39/42 (93% had probable IA (modified European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG criteria. Forty-one patients had pulmonary IA and one had tracheal IA. Caspofungin monotherapy was received by 36/42 patients (86%; of these, 26/36 (72% received salvage therapy. A favorable response was observed in 29/42 patients (69%; 95% CI 53 to 82%; of these, 21/29 (72% had a complete and 8/29 (28% a partial response. Favorable response rate was 69% in patients with monotherapy (95% CI 52% to 84%; 25/36 patients, and 67% in patients receiving combination therapy (95% CI 22% to 96%; 4/6 patients. Favorable response rate in patients with first line therapy was 64% (95% CI 31% to 89%; 7/11 patients, and 73% in patients with second line therapy (95% CI 54% to 88%; 20/30 patients. No adverse events were reported. In total, 35/42 patients (83%; 95% CI 69 to 93% survived seven days after completion of caspofungin therapy. Conclusions These real-life findings in Germany are consistent with the international findings from this registry and with findings from randomized studies.
Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens.
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Allan R Brasier
Full Text Available Invasive pulmonary aspergillosis (IPA is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides, fungal polysaccharides (galactomannan, and cell wall components (β-D glucan were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS produced a greater case classification accuracy than galactomannan (GM or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients
Effectiveness of environmental control measures to decrease the risk of invasive aspergillosis in acute leukaemia patients during hospital building work.
Combariza, J F; Toro, L F; Orozco, J J
Invasive aspergillosis (IA) is a significant problem in acute leukaemia patients. Construction work near hospital wards caring for immunocompromised patients is one of the main risk factors for developing invasive pulmonary aspergillosis (IPA). To assess the impact of environmental control measures used during hospital construction for the prevention of IA in acute leukaemia patients. A retrospective cohort study was developed to evaluate the IA incidence in acute leukaemia patients with different environmental control measures employed during hospital construction. We used European Organisation for the Research and Treatment of Cancer (EORTC) criterial diagnosis parameters for definition of IA. A total of 175 episodes of inpatient care were evaluated, 62 of which did not have any environmental control measures (when an outbreak occurred), and 113 that were subject to environmental control measures directed to preventing IA. The study showed an IA incidence of 25.8% for the group without environmental control measures vs 12.4% for those who did receive environmental control measures (P=0.024). The relative risk for IA was 0.595 (95% confidence interval: 0.394-0.897) for the group with environmental control measures. The current study suggests that the implementation of environmental control measures during a hospital construction has a positive impact for prevention of IA in patients hospitalized with acute leukaemia. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Evaluation of a genus-specific ELISA and a commercial Aspergillus Western blot IgG® immunoblot kit for the diagnosis of aspergillosis in common bottlenose dolphins (Tursiops truncatus).
Desoubeaux, Guillaume; Le-Bert, Carolina; Fravel, Vanessa; Clauss, Tonya; Delaune, Alexa J; Soto, Jeny; Jensen, Eric D; Flower, Jennifer E; Wells, Randall; Bossart, Gregory D; Cray, Carolyn
Aspergillosis is a fungal infection with high mortality and morbidity rates. As in humans, its definitive diagnosis is difficult in animals, and thus new laboratory tools are required to overcome the diagnostic limitations due to low specificity and lack of standardization. In this study of common bottlenose dolphins (Tursiops truncatus), we evaluated the diagnostic performance of a new commercial immunoblot kit that had been initially developed for the serologic diagnosis of chronic aspergillosis in humans. Using this in a quantitative approach, we first established its positive cutoff within an observation cohort of 32 serum samples from dolphins with "proven" or "probable" diagnosis of aspergillosis and 55 negative controls. A novel enzyme-linked immunosorbent assay (ELISA) test was also developed for detecting anti-Aspergillus antibodies, and results were compared between the two assays. Overall, the diagnostic performance of immunoblot and ELISA were strongly correlated (P < .0001). The former showed lower sensitivity (65.6% versus 90.6%), but higher specificity (92.7% vs. 69.1%), with no cross-reaction with other fungal infections caused by miscellaneous non-Aspergillus genera. When assessing their use in a validation cohort, the immunoblot kit and the ELISA enabled positive diagnosis before mycological cultures in 42.9% and 33.3% subjects addressed for suspicion of aspergillosis, respectively. There was also significant impact of antifungal treatment on the results of the two tests (P < .05). In all, these new serological methods show promise in aiding in the diagnosis of aspergillosis in dolphins, and illustrate the opportunity to adapt commercial reagents directed for human diagnostics to detect similar changes in other animals. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: firstname.lastname@example.com.
Detection of galactomannan in bronchoalveolar lavage of the intensive care unit patients at risk for invasive aspergillosis
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Sadegh Khodavaysi
Full Text Available Background and Purpose: Invasive aspergillosis (IA is one of the most common life-threatening fungal infections among the critically ill patients including intensive care unit (ICU patients. Delayed diagnosis and therapy may lead to poor outcomes. Diagnosis may be facilitated by a test for molecular biomarkers, i.e. detection of galactomannan (GM antigen based on enzyme immunoassay, which is of increasing interest in the clinical settings for the diagnosis of IA. In the present study, we assessed GM testing of bronchoalveolar lavage (BAL fluid as a tool for early diagnosis of IA among ICU patients who were at risk for developing IA. Material and Methods: A prospective study was performed in ICU patients with underlying predisposing conditions for IA between August 2010 and September 2011. BAL samples for direct microscopic examination, culture, and GM detection were obtained once or twice weekly. GM in BAL levels was measured using the Platellia Aspergillus EIA test kit. According to modified European Organization for the Research and Treatment of Cancer/ Mycoses Study Group (EORTC/MSG criteria, patients were classified as having probable or possible IA. Results: Out of 43 suspected patients to IA, 13 (30.2% cases showed IA. According to the criteria presented by EORTC/MSG, they were categorized as: 4 cases (30.8% of possible IA and 9 (69.2% of probable IA. Out of 21 BAL samples from patients with IA, 11 (52.4% had at least one positive BAL GM index. Using a cutoff index of 0.5, the sensitivity and specificity, positive and negative predictive values of GM detection in BAL fluid were 100%, 85.7%, 65.7% and 96%, respectively. The sensitivity and specificity was 73% and 92.7% at cutoff ≥1.0, respectively. In 6 of 13 IA cases, BAL culture or direct microscopic examination remained negative, whereas GM in BAL was positive. Conclusion: Our data have revealed that the sensitivity of GM detection in BAL was better than that of conventional tests. It
Assessment of carvacrol for control of avian aspergillosis in intratracheally challenged chickens in comparison to voriconazole with a reference on economic impact.
Tartor, Y H; Hassan, F A M
This study was designed to investigate the efficacy of essential oils as an alternative prophylaxis and treatment for avian aspergillosis. The in vitro susceptibility of Aspergillus fumigatus strains to antifungal drugs and carvacrol, thymol, eugenol, thymoquinone and cinnamon was determined using the macrodiffusion and microdilution methods. Carvacrol has antifungal activity in comparison to voriconazole (VCZ) (MIC 0·5, 0·25 μg ml(-1) respectively). While cinnamon, euganol, thymol and thymoquinone displayed moderate to weak inhibitory activity. For the efficacy study, five groups of 10-day-old chicks (n = 48) were infected intratracheally either with A. fumigatus conidia or saline (negative control). Chicks in carvacrol prophylactic and treatment (CRPT) group were fed for 10 days beginning from hatch with carvacrol (200 mg kg(-1) per diet) supplemented diets. VCZ (VCZT:20 mg kg(-1) body weight (BW)), carvacrol treatment (CRT, CRPT) was started upon appearance of the first clinical signs and continued for 10 days. Birds were monitored for an additional 15 days following treatment. Fungal burden and therapeutic efficacy were assessed by survival, BW, quantitative (q) culture (CFU), quantitative real-time PCR (qPCR) and histopathological changes at several time points. Serum biochemical changes were also assessed. VCZT, CRPT, CRT in comparison to the sham-treated (SHAM) group have prolonged survival (87·5, 83·4, 79·2, 41·7% respectively). In VCZT and CRPT, a significant reduction in clinical signs, lesions, CFU and qPCR counts to the limit of detection were observed. CRPT has the lowest BW reduction, economic losses and significant low total cholesterol levels. Carvacrol has a promising potential to be used as a prophylactic and treatment against A. fumigatus. Prognosis of avian aspergillosis is often poor due to delayed diagnosis and treatment failure. However, the widespread uses of azole prophylaxis in birds are thought to be the major driver of
Galactomannan enzyme immunoassay and quantitative Real Time PCR as tools to evaluate the exposure and response in a rat model of aspergillosis after posaconazole prophylaxis.
Cendejas-Bueno, Emilio; Forastiero, Agustina; Ruiz, Isabel; Mellado, Emilia; Buitrago, María José; Gavaldà, Joan; Gomez-Lopez, Alicia
A steroid-immunosuppressed rat model of invasive pulmonary aspergillosis was use to examine the usefulness of galactomannan enzyme immunoassay (GM) and quantitative real time PCR (RT-PCR) in evaluating the association between response and exposure after a high dose of prophylactic posaconazole. Two different strains of Aspergillus fumigatus with different in vitro posaconazole susceptibility were used. Serum concentrations demonstrated similar posaconazole exposure for all treated animals. However, response to posaconazole relied on the in vitro susceptibility of the infecting strain. After prophylaxis, galactomannan index and fungal burden only decreased in those animals infected with the most susceptible strain. This study demonstrated that both biomarkers may be useful tools for predicting efficacy of antifungal compounds in prophylaxis. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Necrotizing Liver Granuloma/Abscess and Constrictive Aspergillosis Pericarditis with Central Nervous System Involvement: Different Remarkable Phenotypes in Different Chronic Granulomatous Disease Genotypes
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Sanem Eren Akarcan
Full Text Available Chronic granulomatous disease (CGD is a primary immune deficiency causing predisposition to infections with specific microorganisms, Aspergillus species and Staphylococcus aureus being the most common ones. A 16-year-old boy with a mutation in CYBB gene coding gp91phox protein (X-linked disease developed a liver abscess due to Staphylococcus aureus. In addition to medical therapy, surgical treatment was necessary for the management of the disease. A 30-month-old girl with an autosomal recessive form of chronic granulomatous disease (CYBA gene mutation affecting p22phox protein had invasive aspergillosis causing pericarditis, pulmonary abscess, and central nervous system involvement. The devastating course of disease regardless of the mutation emphasizes the importance of early diagnosis and intervention of hematopoietic stem cell transplantation as soon as possible in children with CGD.
[Preoperative Arterial Embolization with N-butyl-2 Cyanoacrylate for Chronic Cavitary Pulmonary Aspergillosis with Trauma Induced Type Ⅰ Diabetes Mellitus].
Nakanishi, Yusuke; Kojima, Fumitsugu; Kamo, Minobu; Wakejima, Ryo; Okura, Mariko; Jinta, Torahiko; Chonabayashi, Naohiko; Bando, Toru
A 50-year-old man with hemoptysis, given a diagnosis of left upper lobe pulmonary aspergilloma with cavity and fungus ball by computed tomography. He has a history of typeⅠ diabetes mellitus due to traumatic injury of pancreas and underwent diaphragm plasty. Despite of systemic anti-fungal medication, symptom and radiological findings were not progressed and surgical intervention was planned. Before surgery we performed intercostal artery embolization, in order to minimize bleeding on dissecting adhesion between the chest wall and the lobe with aspergilloma. Left upper lobectomy with muscle-flap prombage was done safely with a blood loss of 450 ml. Postoperative course was favorable. Intercostal artery embolization with N-butyl-2cyanoacrylate is an effective way to minimize hemorrhage during surgical resection for pulmonary aspergillosis with sever adhesion.
Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo
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Davies, Genna; Rolle, Anna-Maria; Maurer, Andreas
Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture...... of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography...... infection using a [64Cu] NODAGA-hJF5 tracer. The humanised antibody tracer shows a significant increase in in vivo biodistribution in A. fumigatus infected lungs compared to its radiolabeled murine counterpart [64Cu] NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds...
Successful treatment of cerebral aspergillosis: case report of a patient with T-cell large granular lymphocytic leukemia (T-LGL).
Turki, Amin T; Rashidi-Alavijeh, Jassin; Dürig, Jan; Gerken, Guido; Rath, Peter-Michael; Witzke, Oliver
Invasive aspergillosis involving patients with neutropenia or severe immunosuppression, such as patients with hematologic malignancies is associated with high mortality. Patients with T-cell large granular lymphocytic leukemia (T-LGL) on the other hand are considered to be less vulnerable for severe opportunistic fungal infection as their course of disease is chronic and marked by less violent cytopenia then in e.g. Aplastic Anemia. Only neutropenia is regarded as independent risk factor for severe opportunistic infection in T-LGL patients. We report a case of a 53 year old patient with T-LGL, Immune-Thrombocytopenia (ITP) and combined antibody deficiency, who presented with fever and reduced general condition. The patient revealed a complicated infection involving the lungs and later the brain, with the presentation of vomiting and seizures. Broad microbiological testing of blood-, lung- and cerebrospinal fluid samples was inconclusive. In the absence of mycological proof, Aspergillus infection was confirmed by pathological examination of a brain specimen and finally successfully treated with liposomal amphotericin B and voriconazole, adopting a long-term treatment scheme. Beyond typical problems in the clinical practice involving fungal infections and hematologic malignancies, this case of invasive aspergillosis in a patient with T-LGL illustrates caveats in diagnosis, therapy and follow-up. Our data support careful ambulatory monitoring for patients with T-LGL, even in the absence of neutropenia. Especially those patients with combined hematologic malignancies and immune defects are at risk. Long-term treatment adhesion for 12 months with sufficient drug levels was necessary for sustained clearance from infection.
Allergic Bronchopulmonary Aspergillosis
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... Patients Medications that Weaken Your Immune System Outbreaks Rhizopus Investigation CDC at Work Global Fungal Diseases Cryptococcal ... October 12, 2017 Content source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic ...
Direct comparison of galactomannan performance in concurrent serum and bronchoalveolar lavage samples in immunocompromised patients at risk for invasive pulmonary aspergillosis.
Boch, Tobias; Buchheidt, Dieter; Spiess, Birgit; Miethke, Thomas; Hofmann, Wolf-Karsten; Reinwald, Mark
Invasive pulmonary aspergillosis (IPA) is a life-threatening infection mainly affecting immunocompromised patients. Early diagnosis is critical, but the diagnostic gold standard (histopathology and culture) is time consuming and cannot offer early confirmation of IPA. Fungal biomarkers like galactomannan (GM) are a promising extension to the diagnostic repertoire. However, it still remains under discussion if biomarker analysis from the site of the infection is superior to testing blood samples. We retrospectively evaluated the diagnostic performance of concurrent serum GM and bronchoalveolar lavage (BAL) GM (obtained within 24 h) of immunocompromised patients at high risk of IPA. Twenty-six proven/probable patients and eight patients with no IPA according to the EORTC/MSG 2008 criteria were included in this study. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic odds ratio were for BAL GM: 85%, 88%, 96%, 64% and 38.5, and for serum GM: 23%, 88%, 88%, 26% and 2.1 respectively. BAL GM proved to be significantly more sensitive for the detection of IPA compared to same-day serum GM in patients at high risk of IPA (P superior to serum GM implying that diagnostic efforts should focus on specimens from the site of infection. © 2015 Blackwell Verlag GmbH.
High diversity of non-sporulating moulds in respiratory specimens of immunocompromised patients: should all the species be reported when diagnosing invasive aspergillosis?
Garcia-Hermoso, Dea; Alanio, Alexandre; Cabaret, Odile; Olivi, Martine; Foulet, Françoise; Cordonnier, Catherine; Costa, Jean-Marc; Bretagne, Stéphane
Non-sporulating moulds (NSMs) isolated from respiratory specimens are usually discarded without further testing although they may have pathogenic effects in immunocompromised patients. The objective of this study was to determine the identity and frequency of NSMs in patients with haematological malignancies. We analysed the mycological results of 251 consecutive respiratory samples from 104 haematology patients. Yeast and sporulating moulds were identified at the genus/species level according to their phenotypic features. NSMs were identified by internal transcribed spacer (ITS) sequencing. We detected 179 positive samples, of which 10.1% (18/179) were mixtures of moulds and 26.3% (47/179) were mixtures of moulds and yeast. We identified 142 moulds belonging to 11 different genera/species or groups, with Aspergillus fumigatus (n = 50), Penicillium spp. (n = 31) and NSM (n = 24) being the most frequently isolated species. Twenty-two NSMs were successfully sequenced: 18 were basidiomycetes and six were ascomycetes, corresponding to 16 different genera/species. NSMs were isolated with A. fumigatus in the same sample or in a subsequent sample in five patients with probable invasive aspergillosis. The conclusion is that the respiratory specimens of immunocompromised patients frequently contain very diverse mould species that may increase the virulence of pathogenic species. Reporting all mould species isolated when diagnosing invasive fungal infection could test this hypothesis. © 2015 Blackwell Verlag GmbH.
Combination of Voriconazole and Anidulafungin for Treatment of Triazole-Resistant Aspergillus fumigatus in an In Vitro Model of Invasive Pulmonary Aspergillosis
Jeans, Adam R.; Howard, Susan J.; Al-Nakeeb, Zaid; Goodwin, Joanne; Gregson, Lea; Warn, Peter A.
Voriconazole is a first-line agent for the treatment of invasive pulmonary aspergillosis. Isolates with elevated voriconazole MICs are increasingly being seen, and the optimal treatment regimen is not defined. We investigated whether the combination of voriconazole with anidulafungin may be beneficial for the treatment of A. fumigatus strains with elevated voriconazole MICs. We used an in vitro model of the human alveolus to define the exposure-response relationships for a wild-type strain (voriconazole MIC, 0.5 mg/liter) and strains with defined molecular mechanisms of triazole resistance (MICs, 4 to 16 mg/liter). All strains had anidulafungin minimum effective concentrations (MECs) of 0.0078 mg/liter. Exposure-response relationships were estimated using galactomannan as a biomarker. Concentrations of voriconazole and anidulafungin were measured using high-performance liquid chromatography (HPLC). The interaction of voriconazole and anidulafungin was described using the Greco model. Fungal growth was progressively inhibited with higher drug exposures of voriconazole. Strains with elevated voriconazole MICs required proportionally greater voriconazole exposures to achieve a comparable antifungal effect. Galactomannan concentrations were only marginally reduced by anidulafungin monotherapy. An additive effect between voriconazole and anidulafungin was apparent. In conclusion, the addition of anidulafungin does not markedly alter the exposure-response relationship of voriconazole. A rise in serum galactomannan during combination therapy with voriconazole and anidulafungin should be interpreted as treatment failure and not attributed to a paradoxical reaction related to echinocandin treatment. PMID:22825124
Clinical experience of the use of voriconazole, caspofungin or the combination in primary and salvage therapy of invasive aspergillosis in haematological malignancies.
Raad, Issam I; Zakhem, Aline El; Helou, Gilbert El; Jiang, Ying; Kontoyiannis, Dimitrios P; Hachem, Ray
Invasive aspergillosis (IA) is a life-threatening infection in severely immunocompromised haematological malignancy patients. In this study, the efficacy and safety of caspofungin, voriconazole or the combination as primary and salvage therapy in patients with IA were compared. The study included 181 patients with haematological malignancies and IA who received primary or salvage therapy with caspofungin, voriconazole or the combination. In total, 138 patients who received treatment for ≥7 days were analysed; 86 underwent primary antifungal therapy (15 with caspofungin, 38 with voriconazole and 33 with both). Among the salvage therapy patients, 17 received caspofungin, 24 received voriconazole and 35 received both. In the primary therapy group, no difference in therapy response was found, but caspofungin was associated with higher IA mortality rates. A multivariate competing risk analysis of primary antifungal therapy revealed that voriconazole was independently associated with lower IA-associated mortality rates than caspofungin (hazard ratio=0.2, 95% confidence interval 0.06-0.96; P=0.04). In the salvage therapy group, the three treatment groups had similar responses and IA-associated mortality rates. The combination of voriconazole and caspofungin did not result in better outcomes compared with voriconazole alone, as primary or salvage therapy, in haematological malignancy patients. However, voriconazole was associated with a lower Aspergillus-associated mortality rate compared with caspofungin monotherapy. Copyright © 2014. Published by Elsevier B.V.
RsmA regulates Aspergillus fumigatus gliotoxin cluster metabolites including cyclo(L-Phe-L-Ser, a potential new diagnostic marker for invasive aspergillosis.
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Relebohile Sekonyela
Full Text Available Dimeric basic leucine zipper (bZIP proteins are conserved transcriptional enhancers found in all eukaryotes. A recently reported and novel function for bZIPs is association of these proteins with secondary metabolite production in filamentous fungi. In particular a Yap-like bZIP termed RsmA (restorer of secondary metabolism A was identified in Aspergillus nidulans that positively regulates the carcinogen sterigmatocystin. To assess for conserved function for RsmA, we examined a role of this protein in secondary metabolism in the pathogen A. fumigatus. RsmA was found to positively regulate gliotoxin where overexpression (OE of rsmA led to 2-100 fold increases of twelve gli cluster metabolites in culture medium including the newly identified gli metabolite cyclo(L-Phe-L-Ser. Lungs from both wild type and OErsmA infected mice contained gliotoxin (2.3 fold higher in OErsmA treatment as well as the gliotoxin precursor cyclo(L-Phe-L-Ser (3.2 fold higher in OErsmA treatment. The data here presents a conserved role for RsmA in secondary metabolite cluster activation and suggests cyclo(L-Phe-L-Ser may serve as an alternative marker for diagnosis of invasive aspergillosis.
Molecular Detection and Species-Specific Identification of Medically Important Aspergillus Species by Real-Time PCR in Experimental Invasive Pulmonary Aspergillosis ▿
Walsh, Thomas J.; Wissel, Mark C.; Grantham, Kevin J.; Petraitiene, Ruta; Petraitis, Vidmantas; Kasai, Miki; Francesconi, Andrea; Cotton, Margaret P.; Hughes, Johanna E.; Greene, Lora; Bacher, John D.; Manna, Pradip; Salomoni, Martin; Kleiboeker, Steven B.; Reddy, Sushruth K.
Diagnosis of invasive pulmonary aspergillosis (IPA) remains a major challenge to clinical microbiology laboratories. We developed rapid and sensitive quantitative PCR (qPCR) assays for genus- and species-specific identification of Aspergillus infections by use of TaqMan technology. In order to validate these assays and understand their potential diagnostic utility, we then performed a blinded study of bronchoalveolar lavage (BAL) fluid specimens from well-characterized models of IPA with the four medically important species. A set of real-time qPCR primers and probes was developed by utilizing unique ITS1 regions for genus- and species-specific detection of the four most common medically important Aspergillus species (Aspergillus fumigatus, A. flavus, A. niger, and A. terreus). Pan-Aspergillus and species-specific qPCRs with BAL fluid were more sensitive than culture for detection of IPA caused by A. fumigatus in untreated (P PCR amplification from BAL fluid yielded similar sensitivities for untreated and treated animals. Pan-Aspergillus PCR was more sensitive than culture for detection of A. flavus in treated animals (P = 0.002). BAL fluid pan-Aspergillus and species-specific PCRs were comparable in sensitivity to BAL fluid galactomannan (GM) assay. The copy numbers from the qPCR assays correlated with quantitative cultures to determine the pulmonary residual fungal burdens in lung tissue. Pan-Aspergillus and species-specific qPCR assays may improve the rapid and accurate identification of IPA in immunocompromised patients. PMID:21976757
Evaluation of analytical and preliminary clinical performance of Myconostica MycAssay Aspergillus when testing serum specimens for diagnosis of invasive Aspergillosis.
White, P Lewis; Perry, Michael D; Moody, Adrian; Follett, Sarah A; Morgan, Gillian; Barnes, Rosemary A
Diagnosis of invasive aspergillosis remains a significant problem. PCR testing may aid diagnosis but is not yet included in disease-defining criteria due to a lack of standardization of assays and methodologies. This study investigated the analytical performance and the clinical sensitivity and specificity of the Myconostica MycAssay Aspergillus PCR (MAP) assay compared to those of a validated in-house Aspergillus PCR (IHP) test when testing serum specimens. Serum specimens spiked with Aspergillus genomic DNA had a limit of detection equivalent to 5 genomes and a linear dynamic range of 5 to >5 × 10(4) genomes for both assays. When testing clinical specimens (n = 170), the MAP assay had a sensitivity of 60 to 70% and a specificity of 90.5 to 100%. The IHP assay had a sensitivity of 50 to 80% and a specificity of 100%. A commercially available Aspergillus PCR assay provides a methodology that is standardized and reagents that are quality controlled. This facilitates multicenter evaluation of the clinical utility of PCR diagnosis. The performance of the MAP assay is comparable to that of the IHP assay and to those in previously reported studies evaluating commercial tests (galactomannan enzyme-linked immunosorbent assay).
In vivo bioluminescence imaging and histopathopathologic analysis reveal distinct roles for resident and recruited immune effector cells in defense against invasive aspergillosis
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Schwendener Reto
Full Text Available Abstract Background Invasive aspergillosis (IA is a major cause of infectious morbidity and mortality in immune compromised patients. Studies on the pathogenesis of IA have been limited by the difficulty to monitor disease progression in real-time. For real-time monitoring of the infection, we recently engineered a bioluminescent A. fumigatus strain. Results In this study, we demonstrate that bioluminescence imaging can track the progression of IA at different anatomic locations in a murine model of disease that recapitulates the natural route of infection. To define the temporal and functional requirements of distinct innate immune cellular subsets in host defense against respiratory A. fumigatus infection, we examined the development and progression of IA using bioluminescence imaging and histopathologic analysis in mice with four different types of pharmacologic or numeric defects in innate immune function that target resident and recruited phagocyte subsets. While bioluminescence imaging can track the progression and location of invasive disease in vivo, signals can be attenuated by severe inflammation and associated tissue hypoxia. However, especially under non-inflammatory conditions, such as cyclophosphamide treatment, an increasing bioluminescence signal reflects the increasing biomass of alive fungal cells. Conclusions Imaging studies allowed an in vivo correlation between the onset, peak, and kinetics of hyphal tissue invasion from the lung under conditions of functional or numeric inactivation of phagocytes and sheds light on the germination speed of conidia under the different immunosuppression regimens. Conditions of high inflammation -either mediated by neutrophil influx under corticosteroid treatment or by monocytes recruited during antibody-mediated depletion of neutrophils- were associated with rapid conidial germination and caused an early rise in bioluminescence post-infection. In contrast, 80% alveolar macrophage depletion
Effect of allergic bronchopulmonary aspergillosis on FEV1 in children and adolescents with cystic fibrosis: a European Cystic Fibrosis Society Patient Registry analysis.
Kaditis, Athanasios G; Miligkos, Michael; Bossi, Anna; Colombo, Carla; Hatziagorou, Elpis; Kashirskaya, Nataliya; de Monestrol, Isabelle; Thomas, Muriel; Mei-Zahav, Meir; Chrousos, George; Zolin, Anna
To evaluate the effect of allergic bronchopulmonary aspergillosis (ABPA) on FEV1 percent predicted in children and adolescents with cystic fibrosis. Longitudinal data analysis (2008-2010). Patients participating in the European Cystic Fibrosis Society Patient Registry. 3350 patients aged 6-17 years. FEV1 percent predicted was the main outcome measure (one measurement per year per child). To describe the effect of ABPA (main explanatory variable) on FEV1 while controlling for other prognostic factors, a linear mixed effects regression model was applied. In 2008, the mean (±SD) FEV1 percent predicted was 78.6 (±20.6) in patients with ABPA (n=346) and 88 (±19.8) in those without ABPA (n=2806). After considering other variables, FEV1 in subjects with ABPA on entry to the study was 1.47 percentage points lower than FEV1 in patients of similar age without ABPA (p=0.003). There was no FEV1 decline associated with ABPA over the subsequent study years as the interaction of ABPA with age was not significant (p>0.05). For patients aged 11.82 years (population mean age), poor body mass index had the greatest impact on FEV1 in 2008, followed by high-risk genotype (two severe mutations), female gender, diabetes mellitus, chronic Pseudomonas aeruginosa infection and ABPA in descending order of effect size. In contrast to the common clinical belief of ABPA having a serious impact on lung function, the difference in FEV1 between young patients with and without the complication was found to be modest when the effect of other prognostic factors was considered. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Pharmacodynamics of Voriconazole against Wild-Type and Azole-Resistant Aspergillus flavus Isolates in a Nonneutropenic Murine Model of Disseminated Aspergillosis.
Rudramurthy, Shivaprakash M; Seyedmousavi, Seyedmojtaba; Dhaliwal, Manpreet; Chakrabarti, Arunaloke; Meis, Jacques F; Mouton, Johan W
Invasive aspergillosis (IA) due to Aspergillus flavus is associated with high mortality. Although voriconazole (VRC) is widely recommended as the first-line treatment for IA, emergence of azole resistance in Aspergillus spp. is translating to treatment failure. We evaluated the efficacy of voriconazole in a nonneutropenic murine model of disseminated A. flavus infection using two voriconazole-resistant isolates (one harboring the Y319H substitution in the cyp51C gene) and two wild-type isolates without mutations. All isolates exhibited a dose-response relationship, and voriconazole treatment improved mouse survival in a dose-dependent manner. At 40 mg/kg of body weight, 100% efficacy was observed for 1 susceptible isolate and 1 resistant isolate (with mutation), whereas for another susceptible isolate and resistant isolate (without mutation), survival rates were 81% and 72%, respectively. The Hill equation with a variable slope fitted the relationship between the area under the concentration-time curve (AUC)/MIC ratio and 14-day survival well for each strain. An F test showed the 50% effective doses to be significantly different from each other (P = 0.0023). However, contrary to expectation, there was a significant difference in exposure-response relationships between strains, and it appeared that the susceptible strains required a relatively higher exposure than the resistant ones to result in the same treatment effect, the 50% effective pharmacokinetic/pharmacodynamic (PK/PD) index (EI 50 ) required being negatively and log-linearly related to the MIC (P = 0.04). We conclude that the efficacy of voriconazole depended on drug exposure and the voriconazole MIC of the isolates, but lower exposures are required for strains with higher MICs. These findings may have profound significance in clinical practice with respect to dosing and drug choice. Copyright © 2016 American Society for Microbiology.
Relapsed and secondary disease drive the risk profile for invasive aspergillosis prior to stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndrome.
van de Peppel, Robert J; Dekkers, Olaf M; von dem Borne, Peter A; de Boer, Mark G J
Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) are at risk for invasive aspergillosis (IA) even prior to the introduction of stem cell transplantation (SCT). In times of increasing triazole resistance and changing use of antifungal prophylaxis, insight into the risk factors for IA is needed to improve strategies for preventing IA in this population. Consecutive patients who received remission-induction therapy for AML or MDS at the Leiden Academic Medical Centre were included. Instead of standard antifungal prophylaxis, an assertive protocol for diagnosis of suspected fungal infection was in place. IA was classified according to the revised European Organization for Research and Treatment of Cancer criteria. Potential predisposing characteristics for IA were compared by uni- and multivariate analyses. In 45 (25%) of 184 included episodes (167 patients), IA was diagnosed prior to SCT. A multivariate Cox regression model demonstrated that relapsed AML (hazard ratio [HR] 2.4; 95% confidence interval [CI], 1.1-5.1; P = 0.02), secondary AML (HR, 5.2; 95% CI, 2.3-11.8; P < 0.001), and prolonged duration of neutropenia (HR, 2.2; 95% CI, 1.2-4.0; P = 0.01) were independently associated with IA. Use of granulocyte-colony-stimulating factor showed a trend toward a protective effect (HR, 0.37; 95% CI, 0.1-31.0; P = 0.06). Relapsed AML, secondary AML, and duration of neutropenia were independent factors for determining the risk for development of IA prior to SCT. The results provide further guidance for antifungal stewardship programs when integrating individual patient tailored decision making in antifungal prophylaxis strategies. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: firstname.lastname@example.com.
A double-blind comparative study of the safety and efficacy of caspofungin versus micafungin in the treatment of candidiasis and aspergillosis.
Kohno, S; Izumikawa, K; Yoshida, M; Takesue, Y; Oka, S; Kamei, K; Miyazaki, Y; Yoshinari, T; Kartsonis, N A; Niki, Y
The safety and efficacy profile of caspofungin and micafungin in Japanese patients with fungal infections were directly compared in this prospective, randomized, double-blind study. The proportion of patients who developed significant drug-related adverse event(s) (defined as a serious drug-related adverse event or a drug-related adverse event leading to study therapy discontinuation) was compared in 120 patients [caspofungin 50 mg, or 50 mg following a 70-mg loading dose on Day 1 (hereinafter, 70/50 mg) group: 60 patients; micafungin 150 mg: 60 patients]. The overall response rate was primarily evaluated in the per-protocol set (PPS) population. The proportion of patients who developed significant drug-related adverse events was 5.0 % (3/60) in the caspofungin group and 10.0 % (6/60) in the micafungin group [95 % confidence interval (CI) for the difference: -15.9 %, 5.2 %]. The favorable overall response in the PPS population for patients with esophageal candidiasis, invasive candidiasis, and chronic pulmonary aspergillosis including aspergilloma was 100.0 % (6/6), 100.0 % (3/3), and 46.7 % (14/30) in the caspofungin group, and 83.3 % (5/6), 100.0 % (1/1), and 42.4 % (14/33) in the micafungin group, respectively. In Japanese patients with Candida or Aspergillus infections, there was no statistical difference in the safety between caspofungin and micafungin. Consistent with other data on these two agents, the efficacy of caspofungin and micafungin was similar.
Second-hand Smoke Increases Nitric Oxide and Alters the IgE Response in a Murine Model of Allergic Aspergillosis
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Brian W. P. Seymour
Full Text Available This study was performed to determine the effects of environmental tobacco smoke (ETS on nitric oxide (NO and immunoglobulin (Ig production in a murine model of allergic bronchopulmonary aspergillosis (ABPA. Adult BALB/c mice were exposed to aged and diluted sidestream cigarette smoke from day 0 through day 43 to simulate "second-hand smoke". During exposure, mice were sensitized to soluble Aspergillus fumigatus (Af antigen intranasally between day 14 and 24. All Af sensitized mice in ambient air (Af + AIR made elevated levels of IgE, IgG1, IgM, IgG2a and IgA. Af sensitized mice housed in ETS (Af + ETS made similar levels of immunoglobulins except for IgE that was significantly reduced in the serum and bronchoalveolar lavage (BAL. However, immunohistochemical evaluation of the lung revealed a marked accumulation of IgE positive cells in the lung parenchyma of these Af + ETS mice. LPS stimulation of BAL cells revealed elevated levels of NO in the Af + AIR group, which was further enhanced in the Af+ETS group. In vitro restimulation of the BAL cells on day 45 showed a TH0 response with elevated levels of IL3, 4, 5, 10 and IFN-γ. However, by day 28 the response shifted such that TH2 cytokines increased while IFN-γ decreased. The Af + ETS group showed markedly reduced levels in all cytokines tested, including the inflammatory cytokine IL6, when compared to the Af+AIR group. These results demonstrate that ETS affects ABPA by further enhancing the NO production and reduces the TH2 and the inflammatory cytokines while altering the pattern of IgE responses.
Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo
Davies, Genna; Rolle, Anna-Maria; Maurer, Andreas; Spycher, Philipp R.; Schillinger, Claudia; Solouk-Saran, Djamschid; Hasenberg, Mike; Weski, Juliane; Fonslet, Jesper; Dubois, Adrien; Boschetti, Frederic; Denat, Franck; Gunzer, Matthias; Eichner, Martin; Ryder, Lauren S; Jensen, Mikael; Schibli, Roger; Pichler, Bernd J.; Wiehr, Stefan; Thornton, Christopher R.
Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [64Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus. To enable translation of the tracer to the clinical setting, we report here the development of a humanised version of the antibody (hJF5), and pre-clinical imaging of lung infection using a [64Cu]NODAGA-hJF5 tracer. The humanised antibody tracer shows a significant increase in in vivo biodistribution in A. fumigatus infected lungs compared to its radiolabeled murine counterpart [64Cu]NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds to the antigenic determinant β1,5-galactofuranose (Galf) present in a diagnostic mannoprotein antigen released by the pathogen during invasive growth in the lung. The absence of the epitope Galf in mammalian carbohydrates, coupled with the enhanced imaging capabilities of the hJF5 antibody, means that the [64Cu]NODAGA-hJF5 tracer developed here represents an ideal candidate for the diagnosis of IPA and translation to the clinical setting. PMID:28912884
Evaluation of serum galactomannan enzyme immunoassay at two different cut-offs for the diagnosis of invasive aspergillosis in patients with febrile neutropenia
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Ritin Mohindra
Full Text Available Background: Invasive aspergillosis (IA is an increasingly common and fatal opportunistic fungal infection in patients with haematological diseases. Early diagnosis is difficult as mycological culture techniques have low sensitivity and the radiological tools have low specificity. Galactomannan enzyme immunoassay (GEI detects galactomannan in the human serum with a reported sensitivity and specificity between 30% and 100%. Aims: The aim of this study was to analyse the role of GEI in diagnosis of IA in patients with febrile neutropenia and to evaluate the role of GEI in the diagnosis of IA as per the revised (2008 European Organization for Research and Treatment of Cancer–Mycoses Study Group (EORTC–MSG criteria at two different optical density (OD cut-offs of 0.5 and 1.0. Setting: This prospective study was conducted in Safdarjung Hospital, New Delhi, India. Methods: GEI testing was performed in adult patients of febrile neutropenia with evidence of IA. Results at two different OD indices (ODIs of 0.5 and 1.0 were analysed. The evaluation of the diagnostic parameter, that is, GEI was measured in terms of sensitivity, specificity and positive and negative predictive value and was validated with the revised (2008 EORTC–MSG diagnostic criteria of IA. Results: One hundred and eleven patients had evidence of IA, of which 79 patients were GEI positive when cut-off ODI was 0.5, whereas with cut-off ODI 1.0, 55 patients were GEI positive. Conclusion: ODI of 1.0 should be considered as positive while in patients with OD between 0.5 and 1.0, repeat sampling from the patient is recommended.
Aspergillosis in immunocompromised children acute myeloid leukemia and bone marrow aplasia.: Report of two cases Aspergilose em crianças imunocomprometidas com leucemia mielóide aguda e aplasta de medula óssea: Registro de 2 casos
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Maria Zilda de Aquino
Full Text Available Two cases of Aspergillosis in immunocompromised children are reported. Both were caused by Aspergillns flavus. Early diagnosis and treatment led to the remission of the process. One patient had acute myeloid leukemia; the fungus was isolated from the blood. The other patient with bone marrow aplasia, presented an invasive aspergillosis of the paranasal sinuses with dissemination of fungal infection; the diagnosis was obtained by histology and culture of biopsied tissue from a palatal ulceration.No presente trabalho são registrados dois casos de aspergilose em crianças imunocomprometidas. O estudo micológico completo identificou Aspergillus flavus como agente dos dois processos. A presença cada vez mais frequente da aspergilose invasiva deve-se ao número crescente de pacientes imunocomprometidos, muitos com hemopatias graves submetidos à quimioterapia. O diagnóstico precoce em um dos casos possibilitou remissão do processo. Tratava-se de paciente com leucemia mielóide aguda, tendo sido isolado o fungo do sangue circulante. O segundo caso evoluiu para óbito, com infecção fúngica generalizada.
Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group
Herbrecht, R.; Patterson, T.F.; Slavin, M.A.; Marchetti, O.; Maertens, J.; Johnson, E.M.; Schlamm, H.T.; Donnelly, J.P.; Pappas, P.G.
BACKGROUND: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because
Aspergillosis: a limiting factor during recovery of captive magellanic penguins Aspergilose: um fator limitante na reabilitação de pingüins-de-Magalhães
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Melissa O. Xavier
Full Text Available The article describes the epidemiology, macroscopic and histological lesions as well as the isolation of Aspergillus flavus and A. fumigatus from Magellanic penguins (Spheniscus magellanicus during recovery in the Center for Recovery of Marine Animals (CRAM - 32ºS/52ºW, over a period of two years. From January 2004 to December 2005 the Center received 52 Magellanic penguins, and 23% (12/52 died. Necropsies were performed and tissue samples were collected for histological and microbiological examination. From 12 dead animals, aspergillosis was confirmed in five animals, corresponding to 42% of the mortality. Granulomatous nodules were observed mainly on air sacs and lungs. Histologically, septate and branching hyphae, measuring 3-5 µm and PAS positive were found. Two of these cases were caused by A. fumigatus, two other by A. flavus, and in one the diagnostic was established by macroscopic lesions observed in the necropsy without sample collection for fungal isolation and identification. The five aspergillosis cases occurred in the first year of the study, when a disinfection program was not yet established in the CRAM. This paper points out the importance of aspergillosis in the rehabilitation process of captive penguins, and emphasize the necessity of an environmental disinfection on the aspergillosis prevention, mycosis that caused a high rate of mortality of the seabirds found on the Brazilian coast and admitted in the CRAM.O trabalho descreve fatores epidemiológicos, achados de necropsia, histológicos e o isolamento de Aspergillus flavus e A. fumigatus em pingüins-de-Magalhães (Spheniscus magellanicus em reabilitação no Centro de Recuperação de Animais Marinhos (CRAM - 32ºS/52ºW, durante um período de dois anos. De janeiro de 2004 a dezembro de 2005 foram recebidos no Centro, 52 pingüins-de-Magalhães, dos quais 23% (12/52 morreram. Esses animais foram necropsiados e amostras de tecidos foram coletadas para exame histol
Azole-Resistant Invasive Aspergillosis
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Stensvold, Christen Rune; Jørgensen, Lise Nistrup; Arendrup, Maiken Cavling
and classes available is impressive compared to the armamentarium in human medicine, azoles will remain the most important group in agriculture due to superior field performance and significant resistance in fungal pathogens to other compounds. Hence, further spread of environmental resistant Aspergillus...... to the considerable use of azole fungicides in agriculture and for material preservation. Three specific resistance genotypes have been found in azole naïve patients. Two of these have also been found in the environment and are characterized by a tandem repeat in the promoter region of the target gene coupled...
Treatment and Outcomes of Aspergillosis
... Patients Medications that Weaken Your Immune System Outbreaks Rhizopus Investigation CDC at Work Global Fungal Diseases Cryptococcal ... October 12, 2017 Content source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic ...
Tomografia computadorizada na avaliação da aspergilose pulmonar angioinvasiva em pacientes com leucemia aguda Computed tomography in the assessment of angioinvasive pulmonary aspergillosis in patients with acute leukemia
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Renata Carneiro Leão
Full Text Available OBJETIVO: O objetivo deste trabalho foi avaliar os principais achados na tomografia computadorizada de pacientes portadores de leucemia aguda complicada com aspergilose pulmonar angioinvasiva. MATERIAIS E MÉTODOS: Foram estudadas, retrospectivamente, as tomografias computadorizadas de 19 pacientes, avaliando-se a presença de consolidações, nódulos e massas, com ou sem sinal do halo, escavação e sinal do crescente aéreo. RESULTADOS: Áreas de consolidação foram o achado mais comum, ocorrendo em 12 dos 19 casos. A maioria delas apresentou o sinal do halo, enquanto escavação foi encontrada em 5 dos 12 casos com consolidações, sendo um deles com sinal do crescente aéreo. Nódulos e massas ocorreram em, respectivamente, seis e quatro casos, a maioria com sinal do halo. Escavação foi encontrada em apenas um caso de massa. Outros achados observados foram pavimentação em mosaico (dois casos, áreas de vidro fosco esparsas (três casos e envolvimento pleural (sete casos, sob a forma de derrame ou espessamento. CONCLUSÃO: Áreas de consolidação, massas ou nódulo, mesmo solitário, com sinal do halo, quando vistos na tomografia computadorizada em um contexto clínico apropriado, são altamente sugestivos de aspergilose angioinvasiva.OBJECTIVE: The aim of this study was to evaluate the main findings of computed tomography in patients presenting acute leukemia complicated by angioinvasive aspergillosis. MATERIALS AND METHODS: Computed tomography images of 19 patients were retrospectively studied for the presence of consolidations, nodules and masses, with or without presentation of halo sign, cavitation and air crescent sign. RESULTS: Consolidation was the most frequent finding, occurring in 12 of the 19 cases, most of them presenting the halo sign; cavitation was found in 5 of 12 cases, one of them with air crescent sign. Nodules and masses occurred respectively in six and four cases, most of them with halo sign. Cavitation was found
Pulmonary aspergillosis as first manifestation of chronic granulomatous disease in enzygotic twins-use of FDG-PET in diagnosing spread of disease; Pulmonale Aspergillose als Erstmanifestation einer septischen Granulomatose (chronic granulomatous disease, CGD) bei eineiigen weiblichen Zwillingsfruehgeborenen und Ausbreitungsdiagnostik mittels FDG-PET
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Theobald, I.; Fischbach, R.; Heindel, W. [Muenster Univ. (Germany). Radiologische Klinik und Poliklinik; Huelskamp, G.; Frosch, M.; Roth, J. [Klinik und Poliklinik fuer Kinderheilkunde und Allgemeine Kinderheilkunde des UKM, Muenster (Germany); Franzius, C. [Klinik und Poliklinik fuer Nuklearmedizin des UKM, Muenster (Germany)
Purpose. To present the unusual case of chronic granulomatous disease (CGD) manifestating as pulmonal aspergillosis in female enzygotic twins during the neonatal period. To demonstrate and to discuss the complex diagnosis and the diagnostic value of FDG-PET in monitoring the spread and activity of the disease. Patients. Plain chest X-ray and CT of the lung showed multiple, mostly round lesions in one of the former preterm twins at the age of 8 weeks. The girl with known ASD II was then suffering from dyspnoea and recurrent pulmonary infections. Because of the imaging findings invasive pulmonary aspergillosis due to an underlying immunodeficiency was suspected. Results. Aspergillosis was confirmed histologically and microbiologically by specimens taken from an open lung biopsy. Because of coexisting granulocytic dysfunction the diagnosis of CGD was made. This diagnosis was equally confirmed by noninvasive methods in the asymptomatic sister. FDG-PET did not show any evidence of extrapulmonary spread of disease. Conclusion. CGD can present as isolated pulmonal aspergillosis even in the neonatal period when an immunodeficiency is discussed. In enzygotic twins screening of the asymptomatic twin is mandatory. FDG-PET is a useful tool in screening for spread of the disease and in evaluating disease activity. (orig.) [German] Ziel. Im Rahmen einer Fallbeschreibung wird eine aussergewoehnlich fruehe Erstmanifestation einer septischen Granulomatose (chronic granulomatous disease ''CGD'') als invasive pulmonale Aspergillose in der Neonatalzeit bei eineiigen weiblichen Zwillingen vorgestellt. Zusaetzlich wird auf die komplexe Diagnostik unter besonderem Hinweis des Stellenwerts der FDG-PET zur Ausbreitungsdiagnostik und Aktivitaetsbeurteilung eingegangen. Patienten. Bei dem 8 Wochen alten ehemaligen Fruehgeborenen zeigten Roentgenthoraxbild und CT der Lunge multiple, meist rundliche Lungeninfiltrate. Bei bekanntem ASD lagen Dyspnoe und rezidivierende
Uptake and efflux kinetics, and intracellular activity of voriconazole against Aspergillus fumigatus in human pulmonary epithelial cells: a new application for the prophylaxis and early treatment of invasive pulmonary aspergillosis.
Wang, Taotao; Yang, Qianting; Chen, Lu; Li, Ying; Meng, Ti; Wang, Yan; Zhang, Tao; Lei, Jin'e; Xing, Jianfeng; Dong, Yalin
Invasive pulmonary aspergillosis (IPA), most caused by Aspergillus fumigatus, is a serious life-threatening infection in immunocompromised patients. Voriconazole is used to prevent and treat IPA. However, little is known about the pharmacological characteristics of voriconazole in pulmonary epithelial cells, which are the target site for the prophylaxis and early treatment of IPA. The aim of the study was to evaluate the kinetics and activity of voriconazole against A. fumigatus in A549 cells. High-performance liquid chromatography/tandem mass spectrometry and time-kill method were used to study the cellular pharmacokinetic and pharmacodynamics of voriconazole. Voriconazole exerted a concentration-dependent toxic effect on A549 cells and could penetrate into cells, reaching plateau concentrations of 1.14 ± 0.64, 3.72 ± 1.38 and 6.36 ± 0.95 ng/mg protein after A549 cells were exposed to voriconazole at extracellular concentrations of 2, 8 and 16 mg/L for 2 h, respectively. The efflux of voriconazole was rapid, with a half-life of 10.2 min. Voriconazole can decrease the A. fumigatus conidia invade cells, and the number of viable A. fumigatus conidia in cells can be decreased 2.1- to 20.6-fold when A549 cells were cultured in medium containing voriconazole. After 24-h incubation, 75.6% and 80.5% of intracellular A. fumigatus were killed when extracellular voriconazole concentration was 8 and 16 mg/L, respectively. This study illustrated a new application for the prophylaxis and early treatment of IPA from the cellular pharmacokinetics and pharmacodynamics and emphasized the importance of monitoring concentrations of voriconazole in epithelial lining fluid in immunocompromised patients receiving voriconazole therapy. © 2016 Société Française de Pharmacologie et de Thérapeutique.
Cerebral aspergillosis due to Aspergillus fumigatus in AIDS patient: first culture - proven case reported in Brazil Aspergilosis cerebral causada por Aspergillus fumigatus en paciente con SIDA: primer reporte de caso demostrado por cultivo en Brasil
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José E. Vidal
Full Text Available Cerebral aspergillosis is a rare cause of brain expansive lesion in AIDS patients. We report the first culture-proven case of brain abscess due to Aspergillus fumigatus in a Brazilian AIDS patient. The patient, a 26 year-old male with human immunodeficiency virus (HIV infection and history of pulmonary tuberculosis and cerebral toxoplasmosis, had fever, cough, dyspnea, and two episodes of seizures. The brain computerized tomography (CT showed a bi-parietal and parasagittal hypodense lesion with peripheral enhancement, and significant mass effect. There was started anti-Toxoplasma treatment. Three weeks later, the patient presented mental confusion, and a new brain CT evidenced increase in the lesion. He underwent brain biopsy, draining 10 mL of purulent material. The direct mycological examination revealed septated and hyaline hyphae. There was started amphotericin B deoxycholate. The culture of the material demonstrated presence of the Aspergillus fumigatus. The following two months, the patient was submitted to three surgeries, with insertion of drainage catheter and administration of amphotericin B intralesional. Three months after hospital admission, his neurological condition suffered discrete changes. However, he died due to intrahospital pneumonia. Brain abscess caused by Aspergillus fumigatus must be considered in the differential diagnosis of the brain expansive lesions in AIDS patients in Brazil.La aspergilosis cerebral es una causa rara de lesión expansiva cerebral en pacientes con SIDA. Presentamos el primer reporte de un absceso cerebral causado por Aspergillus fumigatus en un paciente brasileño con SIDA. El paciente, de 26 años de edad, presentaba antecedentes de infección por el virus de la inmunodeficiencia humana (VIH, tuberculosis pulmonar y toxoplasmosis cerebral. Manifestó fiebre, tos, disnea y dos episódios de convulsiones. La tomografía computadorizada (TC demostró una lesión hipodensa parasagital y bi-parietal con
Primary Cutaneous Aspergillosis in an Immunocompetent Patient
African Journals Online (AJOL)
immunodeficiency include, traumatic inoculation, occlusive dressing for an indwelling catheter, burns, aerosolization of fungi during the renovation of building, ... 1Department of Medicine, Infectious Disease Unit, 2Department of Histopathology, 3Department of Surgery, Pediatric Surgery. Unit, College of Medical Sciences, ...
Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group.
Herbrecht, Raoul; Patterson, Thomas F; Slavin, Monica A; Marchetti, Oscar; Maertens, Johan; Johnson, Elizabeth M; Schlamm, Haran T; Donnelly, J Peter; Pappas, Peter G
Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged. Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: email@example.com.
Spectrum of aspergillosis: Pathogenesis, risk factors and management
African Journals Online (AJOL)
African Journal of Clinical and Experimental Microbiology. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 17, No 1 (2016) >. Log in or Register to get access to full text downloads.
Immunohistochemistry for the diagnosis of aspergillosis in turkey poults
DEFF Research Database (Denmark)
Jensen, H.E.; Christensen, J.P.; Bisgaard, M.
From each of two flocks (A and B) of poults comprising 14,100 females and 11,300 males, respectively, 15 poults were examined pathologically. Poults of flock A. had signs of neurological disturbances whereas birds from flock B showed respiratory symptoms. Gross lesions were observed only in two p...
Association of Cholesterol Granuloma and Aspergillosis in the Sphenoid Sinus
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Kang, Hyun Koo; Kim, Jae Kyun; Kim, Yoon Jung [Seoul Veterans Hospital, Seoul (Korea, Republic of)
Cholesterol granuloma (CG) is usually associated with chronic middle ear disease, and is not common in the paranasal sinuses. Additionally, it is very rare for cases of CG to be associated with a fungal infection. However, in this paper, we report a case of sphenoid sinus CG that is associated with aspergilloma in a 78- year-old male patient who presented with right hemifacial pain, headache and toothache. CT revealed the presence of an expansile cystic mass lesion in the sphenoid sinus that showed a high signal intensity on both the T1 and T2 weighted images. This mass was later determined to be CG. The suspected etiologic mechanisms of both CG and aspergilloma of the paranasal sinuses are similar, and impaired drainage and obstruction of the ventilation of the paranasal sinuses are considered to be the causative mechanism of both diseases. Overall, the results of this study indicate that the use of MRI findings could be helpful for differentiating CG from other paranasal sinus mass lesions
Improving case finding of invasive aspergillosis in children using string searches.
Nadimpalli, Sruti S; Salsgiver, Elizabeth; O'Toole, Dana; Saiman, Lisa; Babina, Alla; Graham, Philip; Foca, Marc
Surveillance for invasive Aspergillus (IA) in children is complex. We performed a retrospective study (2004-2013) using string searches of relevant terms within histopathology and radiology reports in efforts to improve detection of IA. Overall, 22 children met IA criteria, of whom 5 (23%) were only identified by string searches. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Clinical and pathological findings of concurrent poxvirus lesions and aspergillosis infection in canaries.
Reza, Kheirandish; Nasrin, Askari; Mahmoud, Salehi
To investigate clinical, pathological and mycological findings in canaries, in which pox lesions and Aspergillus fumigatus (A. fumigatus) infection were observed simultaneously. This study was performed on a breeding colony (about 100 canaries) affected by fatal wasting disease. Necropsy was undertaken on 10 severely affected canaries, and gross lesions were recorded. Samples from internal organs displaying lesions were obtained for histopathological evaluation. Tracheal swap samples of internal organs of the all infected animals with lesions at necropsy were cultured in Sabouraud Dextrose Agar for mycological examination. At necropsy, caseous foci were determined in the lungs, on the air sacs, liver, spleen, heart. Swelling of the eyelids, diffuse hemorrhages in the subcutaneous tissue with small papular lesions of the skin were other typical necropsy findings. Histopathologically, pathognomonic eosinophilic intracytoplasmic inclusion bodies, which called Bollinger bodies, in both skin cells and vacuolated air way epithelial cells confirmed canary pox infection. Moreover, histopathological examination of the white-yellowish caseous foci revealed necrotic granulomatous reaction consisting of macrophages, heterophil leukocytes and giant cells encapsulated with a fibrous tissue. After the culture of the tissue samples, the formation of bluish green colonies confirmed A. fumigatus infection. Canary pox has been known as the disease that can result in high losses in a short time, as a re-emerging disease that has not been present during recent years in canary flocks in Iran. So, the current paper provides useful information to prevent misdiagnosed of canary pox disease which can cause secondary mycotic infection.
Specific IgG(4) responses during chronic and transient antigen exposure in aspergillosis
Tomee, JFC; Dubois, AEJ; Koeter, GH; Beaumont, F; vanderWerf, TS; Kauffman, HF
The factors that lead to increased production of specific IgG subclasses are still largely unknown. Recent studies suggest that increased IgG(4) responses may be related to prolonged antigen exposure. We present data showing that increased IgG(4) responses are found under conditions of chronic
Non-invasive and invasive diagnoses of aspergillosis in a rat model by mass spectrometry
Czech Academy of Sciences Publication Activity Database
Luptáková, Dominika; Pluháček, Tomáš; Petřík, M.; Novák, Jiří; Palyzová, Andrea; Sokolová, Lucie; Škríba, Anton; Šedivá, Blanka; Lemr, Karel; Havlíček, Vladimír
Roč. 7, NOV 28 (2017), č. článku 16523. ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LO1509; GA ČR(CZ) GA16-20229S Institutional support: RVO:61388971 Keywords : FUMIGATUS * SIDEROPHORES * GA-68-SIDEROPHORES Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 4.259, year: 2016
Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report
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Kang, Si Won [Daejeon St. Mary' s Hospital, College of Medicine, Catholic University, Daejeon (Korea, Republic of)
Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)
The many faces of pulmonary aspergillosis: Imaging findings with pathologic correlation
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Prasad Panse
Conclusion: In this article we correlate the radiologic findings of the various pulmonary manifestations of Aspergillus infection with their pathologic features to better understand the disease process and better comprehend the associated imaging patterns.
Post-transplant aspergillosis and the role of combined neurosurgical and antifungal therapies under belatacept immunosuppression
DEFF Research Database (Denmark)
Ekkehard, Kasper; Bartek, Jiri; Johnson, Jesper Scott
Opportunistic CNS-infection represent a major threat to patients after organ transplantation due to the need for ongoing immunosuppression and belatacept is a novel CTL4A inhibitor, which is increasingly used for patients following cadaveric kidney transplantation. Among the CNS infections, intra...... with intraoperative image guidance was performed for a gross total resection of the lesion. Twenty-four months from resection, she remains on voriconazole with no evidence of recurrence and complete neurologic recovery and preserved renal function....
Fatal fungal endocarditis by Aspergillus udagawae: an emerging cause of invasive aspergillosis.
Seki, Atsuko; Yoshida, Atsushi; Matsuda, Yoko; Kawata, Mitsuhiro; Nishimura, Takashi; Tanaka, Jun; Misawa, Yoshiki; Nakano, Yuta; Asami, Ryoko; Chida, Koji; Kikuchi, Ken; Arai, Tomio
Aspergillus udagawae has morphological similarities to Aspergillusfumigatus; however, it shows a low susceptibility to common antifungal drugs and poor in vitro sporulation. We present the first reported case of infectious endocarditis caused by A. udagawae. An awareness of this newly described Aspergillus species is vital for further clarification. Copyright © 2017 Elsevier Inc. All rights reserved.
Magnetic resonance image detection of coincidental sphenoid sinus aspergillosis and pituitary microdenoma: A potential surgical disaster
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Gupta, A.; Gupta, R.K. [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India). Department of Radiology; Banerjee, D. [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India). Department of Neurosurgery; Bhatia, E. [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India). Department of Endocrinology
While localizing the microadenoma in a patient with Cushing`s disease on magnetic resonance imaging (MRI), fungal granuloma of the sphenoid sinus was coincidentally detected. This helped in the proper management of sphenoidal disease before undergoing trans-sphenoidal removal of the microadenoma, thus averting the possible catastrophe of direct intracranial spread of aspergillus infection. Copyright (1998) Blackwell Science Pty Ltd 10 refs., 1 fig.
Prevention and treatment of invasive aspergillosis in Slovenia: data obtained in »OSPIA« observational clinical study
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Samo Zver
Conclusions: In Slovenia, IA remains a huge problem in patients with critical neutropenia. The primary reason lays in inadequate hospital treatment conditions for hematological patients. The latter we try to mitigate with posoconasole prophylaxis.
Utility of the serum galactomannan assay for the diagnosis of invasive aspergillosis in children with acute lymphoblastic leukemia
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Gulhadiye Avcu
Conclusions: GM may be detected in the serum before the clinical signs of IA appear, but its sensitivity and specificity are variable. False-positivity is a significant disadvantage, and consecutive positive GM must be taken into account in the case of clinical and imaging findings that are relevant to IA.
Aspergillosis due to voriconazole highly resistant Aspergillus fumigatus and recovery of genetically related resistant isolates from domiciles
Linden, J.W.M. van der; Camps, S.M.T.; Kampinga, G.A.; Arends, J.P.; Debets-Ossenkopp, Y.J.; Haas, P.J.; Rijnders, B.J.; Kuijper, E.J.; Tiel, F.H. van; Varga, J.; Karawajczyk, A.; Zoll, J.; Melchers, W.J.G.; Verweij, P.E.
BACKGROUND: Azole resistance is an emerging problem in Aspergillus fumigatus and complicates the management of patients with Aspergillus-related diseases. Selection of azole resistance may occur through exposure to azole fungicides in the environment. In the Netherlands a surveillance network was
The use of abatacept in debilitating cavitating lung disease associated with rheumatoid arthritis, bronchocentric granulomatosis and aspergillosis.
LENUS (Irish Health Repository)
Neff, K
A case of debilitating cavitating lung disease associated with rheumatoid arthritis and bronchocentric granulomatosis, which failed to respond to conventional medical or surgical treatment, is described. The patient was treated over 10 years with steroids, antimicrobial agents, disease-modifying antirheumatoid drugs and surgery. Lung function continued to decline and the patient presented for admission with recurrent pneumonia. Abatacept was initiated to modify the underlying immunopathology. Following 12 months of treatment with abatacept the patient has demonstrable improvement in lung function and lung anatomy, and has not presented to hospital with pneumonia. She has tolerated the treatment without complication. The use of abatacept has stabilised the lung disease in this case in the medium term and prevented readmission to hospital. These results suggest a larger role for abatacept in those with such disease in the future and may warrant further investigation.
Image findings of a false positive radioactive iodine-131 uptake mimicking metastasis in pulmonary aspergillosis identified on single photon emission computed tomography-computed tomography
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Kamaleshwaran Koramadai Karuppusamy
Full Text Available High doses of iodine-131 are commonly used in patients with differentiated thyroid cancer after total or subtotal thyroidectomy, in order to ablate the remaining cancer or normal thyroid tissue. Multiple different false-positive scans can occur in the absence of residual thyroid tissue or metastases. The authors present a case of abnormal uptake of radioactive iodine in the aspergilloma, potentially masquerading as pulmonary metastases.
Economic evaluation of targeted treatments of invasive aspergillosis in adult haematopoietic stem cell transplant recipients in the Netherlands: a modelling approach.
Ament, A.J.; Hubben, M.W.; Verweij, P.E.; Groot, R. de; Warris, A.; Donnelly, J.P.; Wout, J. van 't; Severens, J.L.
OBJECTIVES: The aim of this study was to assess the cost-effectiveness of a targeted treatment model of antifungal treatment strategies for adult haematopoietic stem cell transplant (HSCT) recipients in the Netherlands from a hospital perspective, using a decision analytic modelling approach.
Aspergilosis pulmonar secundaria a neutropenia inducida por metimazol: reporte de un caso Pulmonary aspergillosis due to methimazole-induced neutropenia: a case report
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Miguel E. Pinto
Full Text Available Se reporta el caso de una paciente de 48 años de edad con diagnóstico reciente de enfermedad de Graves, quien acudió a emergencia por presentar fiebre, palpitaciones y dolor faríngeo. Su tratamiento regular incluía metimazol. Al ingreso, los análisis mostraron TSH suprimido, T4 libre elevado y neutropenia. La paciente fue hospitalizada, se administraron antibióticos y factor estimulante de colonia. Después de diez días de tratamiento, la paciente presentó leucocitosis, fiebre y hemoptisis. La tomografía de tórax mostró una cavidad con múltiples nódulos en el lóbulo superior derecho. Los cultivos fueron positivos a Aspergillus fumigatus y Aspergillus flavus. Se inició tratamiento con anfotericina B y luego se cambió a voriconazol, a pesar de lo cual no hubo mejoría del cuadro. La paciente falleció por falla multiorgánica.A 48-year old woman with a recent diagnosis of Graves' disease arrived at the emergency room with fever, palpitations, and a sore throat. Her regular treatment included methimazole. On admission, laboratory results showed suppressed TSH, elevated free thyroxine, and neutropenia. She was admitted and started on antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf. After ten days, the patient developed leukocytosis, fever, and hemoptysis. Chest CT scan showed a lung cavity with multiple nodules in the upper right lobe. Cultures from a lung biopsy were positive for Aspergillus Fumigatus and Aspergillus Flavus. Amphotericin B was started but then switched to voriconazole, with both treatments failing to result in clinical improvement. The patient died of multi-organ failure.
Interaction between aspergilli and streptomycetes in the soil of potted indoor plants: a preliminary report (contribution to the epidemiology of human aspergillosis).
Staib, F; Mishra, S K; Blisse, A
The soil of potted ornamental plants as a reservoir for Aspergillus species pathogenic for man is of epidemiological and ecological interest. Isolation of A. niger as the sole hyphomycete from the soil of potted African violets (Saintpaulia ionantha, Gesneriaceae), prompted us to look for A. inger on the surface of the roots of this plant. Small pieces of the roots were inoculated in the nutrient-free agar-gel with and without antibiotics. On the antibiotic-free gel, a dense growth of Streptomyces griseus was consistently observed around the root pieces. But the gel fortified with antibiotics showed pure growth of only A. niger. One of the two strains of S. ariseus isolated from the African violet, showed inhibitory effect against a number of fungi including A. niger but the other strain had no effect on this fungus. The possible influence of streptomycetes on the occurrence of aspergilli in the soil of potted ornamental plants is discussed.
Early diagnosis and treatment of invasive aspergillosis as a main determinant of outcome – review of literature according to the presented case report
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Michał Borys
According to presented literature, Galactomannan assay enables early diagnosis and remains a specific and sensitive tool to diagnose Asppergillosis, both in serum and BAL fluid. The guidelines recommend voriconazole as a first line treatment in IA. Failure to detect and implement proper antifungal treatment may lead to fatal consequences, as in the presented case.
Comparative evaluation of galactomannan test with bronchoalveolar lavage and serum for the diagnosis of invasive aspergillosis in patients with hematological malignancies
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Ankit Gupta
Conclusions: Our results support BAL GM testing as a reasonably safe test with higher sensitivity compared to serum GM testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid overdiagnosis of IPA.
Successful treatment of pulmonary candidiasis and aspergillosis in patient with refractory Hodgkin lymphoma using micafungin – case study and brief literature review
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Marta Barańska
Full Text Available The number of patients with hematological malignancies who develop invasive fungal disease (IFD has increased dramatically in recent decades. This increase is attributed to impairment of the host immune system due to intensive cytotoxic chemotherapies, use of corticosteroids and profound immunosuppression after hematopoietic stem cell transplantation (HSCT. Additionally, the increasing prevalence of fungal infections caused by emerging and rare pathogens, IFD of mixed etiology or of atypical localization is observed. There are also much more patients with IFD who do not belong to a well-described risk group, like patient with lymphoproliferative disorders. Within this heterogeneous group of patients, IFD epidemiology is not well defined and antifungal prophylaxis practices vary. The aim of this paper is to present the case of a 58-year-old patient with refractory Hodgkin disease, focusing on infectious complication after subsequent lines of chemotherapy. During deep and prolonged neutropaenia the patient developed symptoms of pneumonia. Despite antifungal prophylaxis with fluconazole, IFD of mixed etiology with the presence of Candida glabrata and Aspergillus fumigatus was diagnosed. The infection showed a poor response to monotherapy with liposomal amphotericin B, but was successfully treated with therapy involving micafungin. Analysis of the presented case demonstrated the necessity of new approaches to the prevention of IFD in patients with lymphoproliferative disorders heavily pretreated with numerous chemotherapy protocols. Prolonged neutropenia and high corticosteroid exposure put these patients in high risk of IFD like patients with acute myeloid leukemia/myelodysplastic syndrome or after allogeneic HSCT.
Image findings of a false positive radioactive iodine-131 uptake mimicking metastasis in pulmonary aspergillosis identified on single photon emission computed tomography-computed tomography.
Karuppusamy, Kamaleshwaran Koramadai; Antony, Joppy; Radhakrishnan, E R; Shinto, Ajit Sugunan
High doses of iodine-131 are commonly used in patients with differentiated thyroid cancer after total or subtotal thyroidectomy, in order to ablate the remaining cancer or normal thyroid tissue. Multiple different false-positive scans can occur in the absence of residual thyroid tissue or metastases. The authors present a case of abnormal uptake of radioactive iodine in the aspergilloma, potentially masquerading as pulmonary metastases.
Exploring azole antifungal drug resistance in Aspergillus fumigatus with special reference to resistance mechanisms
Chowdhary, A.; Sharma, C.; Hagen, F.; Meis, J.F.G.M.
Aspergillus fumigatus, a ubiquitously distributed opportunistic pathogen, is the global leading cause of aspergillosis. Azole antifungals play an important role in the management of aspergillosis. However, over a decade, azole resistance in A. fumigatus isolates has been increasingly reported with
African Journals Online (AJOL)
be on the increase. About 10million people are at risk of aspergillosis, and 50% would die even with treatment. Immunodeficiency, especially neutropenia is central to the pathogenesis of aspergillosis. Diseases caused by A. fumigatus include;1) Invasive aspergillosis seen mostly in stem cell and organ transplant recipients, ...
Aspergillus spondylodiscitis in a patient with liver cirrhosis and diabetes mellitus
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Tereza Rojko
Full Text Available Aspergillus osteomyelitis is a rare manifestation of invasive aspergillosis which accounts for 1.8% to 5.6% of all invasive aspergillosis forms. As other forms of invasive aspergillosis, it predominantly occurs in immunosupressed patients with well established risk factors, but there are increasing reports of invasive aspergillosis cases in patients without traditional risk factors such as patients with chronic obstructive pulmonary disease on inhalatory corticosteroid therapy or patients with liver cirrhosis. We present a case of Aspergillus spondylodiscitis in a patient without other risk factors for invasive aspergillosis than liver cirrhosis and diabetes mellitus successfully treated with a 4-month course of voriconasole.
Epidemiology of Opportunistic Fungal Infections in Latin America
National Research Council Canada - National Science Library
Marcio Nucci; Flavio Queiroz-Telles; Angela M. Tobón; Angela Restrepo; Arnaldo L. Colombo
This review discusses the epidemiology of the most clinically relevant opportunistic fungal infections in Latin America, including candidiasis, cryptococcosis, trichosporonosis, aspergillosis, and fusariosis...
Airway Clearance Techniques (ACTs)
Full Text Available ... Clinical Care Guidelines Infant Care Clinical Care Guidelines Management of CRMS in First 2 Years and Beyond Clinical ... Bronchopulmonary Aspergillosis Clinical Care Guidelines ...
Dose optimization of voriconazole/anidulafungin combination against Aspergillus fumigatus using an in vitro pharmacokinetic/pharmacodynamic model and response surface analysis: clinical implications for azole-resistant aspergillosis.
Siopi, Maria; Siafakas, Nikolaos; Vourli, Sophia; Mouton, Johan W; Zerva, Loukia; Meletiadis, Joseph
Combination therapy of voriconazole with an echinocandin is often employed in order to increase the efficacy of voriconazole monotherapy. Four clinical Aspergillus fumigatus isolates with different in vitro susceptibilities to voriconazole (MIC 0.125-2 mg/L) and anidulafungin (MEC 0.008-0.016 mg/L) were tested in an in vitro pharmacokinetic/pharmacodynamic model simulating human serum concentrations of standard dosages of voriconazole and anidulafungin. Fungal growth was assessed using galactomannan production and quantitative PCR. Drug concentrations were determined with bioassays. Pharmacodynamic interactions were assessed using Bliss independence analysis (BI) and Loewe additivity-based canonical mixture response-surface non-linear regression analysis (LA). Probability of target attainment (PTA) was estimated with Monte Carlo analysis for different doses of anidulafungin (25, 50 and 100 mg) and azole resistance rates (5%-25%). Synergy [BI 51% (8%-80%), LA 0.63 (0.38-0.79)] was found at low anidulafungin (fC max /MEC voriconazole (fAUC/MIC voriconazole MIC distributions with high (>10%) resistance rates. PTAs for isolates with voriconazole MICs of 1, 2 and 4 mg/L was 78%, 12% and 0% with voriconazole monotherapy and 96%-100%, 68%-82% and 9%-20% with combination therapy, respectively. Optimal activity was associated with a voriconazole tC min /MIC ratio of 1.5 for monotherapy and 0.75 for combination therapy. The present study indicated that the combination of voriconazole with low-dose anidulafungin may increase the efficacy and reduce the cost and potential toxicity of antifungal therapy, particularly against azole-resistant A. fumigatus isolates and in patients with subtherapeutic serum levels. This hypothesis warrants further in vivo verification. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: email@example.com.
Elevated levels of manna-binding lectin (MBL) and eosinophilia in patients of bronchial asthma with allergic rhinitis and allergic bronchopulmonary aspergillosis associated with a novel intronic polymorphism in MBL
DEFF Research Database (Denmark)
Kaur, S.; Gupta, G.K.; Shah, A.
being determined by genetic polymorphisms in its collagen region, we investigated the association of single nucleotide polymorphisms (SNPs) in the collagen region of human MBL with respiratory allergic diseases. The study groups comprised patients of bronchial asthma with allergic rhinitis (n = 49...... conclude that the 1011A allele of MBL may contribute to elevated plasma MBL levels and activity and to increased severity of the disease markers in patients of bronchial asthma with allergic rhinitis and ABPA....
Monoclonal Antibodies to Hyphal Exoantigens Derived from the Opportunistic Pathogen Aspergillus terreus
Aspergillus terreus has been difficult to identify in cases of aspergillosis, and clinical identification has been restricted to the broad identification of aspergillosis lesions in affected organs or the detection of fungal carbohydrates. As a result, there is a clinical need to...
African Journals Online (AJOL)
The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology 2009;14:1121-1127. 4. Chishimba L, Niven RM, Cooley J, Denning DW. Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe.
Pharmacodynamics of Voriconazole in Children : Further Steps along the Path to True Individualized Therapy
Huurneman, Luc J.; Neely, Michael; Veringa, Anette; Docobo Perez, Fernando; Ramos-Martin, Virginia; Tissing, Wim J.; Alffenaar, Jan-Willem C.; Hope, William
Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this
Clinical implications of environmental sources for Aspergillus.
Warris, A.; Verweij, P.E.
Invasive aspergillosis presents a formidable problem for both diagnosis and therapy. Therefore, prevention is a very important strategy in controlling this disease. Preventing invasive aspergillosis demands a clear understanding of the environmental sources of Aspergillus spp. and how this mould is
Successful Treatment of Fanconi Anemia and T-Cell Acute Lymphoblastic Leukemia
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Terrie Flatt
Full Text Available Fanconi anemia is associated with an increased risk of malignancy. Patients are sensitive to the toxic effects of chemotherapy. We report the case of a patient with Fanconi anemia who developed T-cell acute lymphoblastic leukemia. He experienced chemotherapy-related complications including prolonged neutropenia, grade IV vincristine neuropathy, and disseminated aspergillosis. He was successfully treated with modified dosing of cytarabine and intrathecal methotrexate followed by allogeneic bone marrow transplant. The aspergillosis was treated with systemic antifungal treatment and surgical resection. Now 30 months after bone marrow transplant the patient is without evidence of aspergillosis or leukemia.
Chronic granulomatous disease associated with chronic glomerulonephritis
DEFF Research Database (Denmark)
Frifelt, J J; Schønheyder, Henrik Carl; Valerius, Niels Henrik
A boy with chronic granulomatous disease (CGD) developed glomerulonephritis at the age of 12 years. The glomerulonephritis progressed to terminal uraemia at age 15 when maintenance haemodialysis was started. The clinical course was complicated by pulmonary aspergillosis and Pseudomonas septicaemia...
Toll-like receptor 2 induced cytotoxic T-lymphocyte-associated protein 4 regulates Aspergillus-induced regulatory T-cells with pro-inflammatory characteristics
Raijmakers, R.P.H.; Sprenkeler, E.G.; Aleva, F.E.; Jacobs, C.W.M.; Kanneganti, T.D.; Joosten, L.A.B.; Veerdonk, F.L. van de; Gresnigt, M.S.
Patients with cystic fibrosis, chronic obstructive pulmonary disease, severe asthma, pre-existing pulmonary lesions, and severely immunocompromised patients are susceptible to develop infections with the opportunistic pathogenic fungus Aspergillus fumigatus, called aspergillosis. Infections in these
The pulmonary aspergilloses: three distinct entities or a spectrum of disease.
Greene, R
The fungus Aspergillus can cause any of three clinical presentations--invasive aspergillosis, mycetoma, or allergic bronchopulmonary aspergillosis--or a disease process in which one of these entities overlaps with another process such as mucoid impaction, eosinophilic pneumonia, bronchocentric granulomatosis, "farmer's lung," or asthma. More than one form of the disease may be present at the same time; in addition, limited invasion may occur even in "noninvasive" forms of the disease, and the clinical and pathological aspects of allergic aspergillosis are often indistinguishable from those of unrelated allergic conditions. Thus it is no longer possible to compartmentalize the various types of pulmonary aspergillosis into exclusive forms of the disease; rather, the radiologist should be aware that various factors can modify the mode of growth of the fungus as well as the patient's response.
Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.
Kullberg, B.J.; Sobel, J.D.; Ruhnke, M.; Pappas, P.; Viscoli, C.; Rex, J.H.; Cleary, J.D.; Rubinstein, E.; Church, L.W.; Brown, J.M.; Schlamm, H.T.; Oborska, I.T.; Hilton, F.; Hodges, M.R.
BACKGROUND: Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients.
Targeted Disruption of Nonribosomal Peptide Synthetase pes3 Augments the Virulence of Aspergillus fumigatus
DEFF Research Database (Denmark)
O'Hanlon, Karen A.; Cairns, Timothy; Stack, Deirdre
of murine pulmonary aspergillosis. Complementation restored the wild-type phenotype in the invertebrate model. Deletion of pes3 also resulted in increased susceptibility to the antifungal, voriconazole (P
Aspergillus bronchitis without significant immunocompromise
National Research Council Canada - National Science Library
Chrdle, Ales; Mustakim, Sahlawati; Bright‐Thomas, Rowland J; Baxter, Caroline G; Felton, Timothy; Denning, David W
Aspergillus bronchitis is poorly understood and described. We extracted clinical data from more than 400 referred patients with persistent chest symptoms who did not fulfill criteria for allergic, chronic, or invasive aspergillosis...
Airway Clearance Techniques (ACTs)
Full Text Available ... Next? Lung Transplantation Getting on the List Surgery, Recovery, and Life Post-Transplant Waiting for the Transplant ... Care Guidelines Sweat Test Clinical Care Guidelines Infection Prevention and Control Care Guidelines Allergic Bronchopulmonary Aspergillosis Clinical ...
Diagnose in beeld (92). Een man met koorts tijdens chemotherapie. Invasieve pulmonale mycose
van Spronsen, D J; Daenen, S M G J; Kluin-Nelemans, J C
A 64-year-old male was treated for acute myeloid leukemia with idarubicin and cytarabin. He developed pulmonary mycosis (radiologically consistent with aspergillosis), which responded to intravenous amphotericin B.
Airway Clearance Techniques (ACTs)
Full Text Available ... center. Carrier Testing for Cystic Fibrosis CFTR-Related Metabolic Syndrome (CRMS) How Babies Are Screened in IRT- ... Sweat Test Clinical Care Guidelines Infection Prevention and Control Care Guidelines Allergic Bronchopulmonary Aspergillosis Clinical Care Guidelines ...
Breakthrough Aspergillus fumigatus and Candida albicans double infection during caspofungin treatment
DEFF Research Database (Denmark)
Arendrup, Maiken Cavling; Garcia-Effron, Guillermo; Buzina, Walter
Caspofungin is used for the treatment of acute invasive candidiasis and as salvage treatment for invasive aspergillosis. We report characteristics of isolates of Candida albicans and Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery...... without FSK1 resistance mutations in liver and lung tissues. Breakthrough disseminated aspergillosis and candidiasis developed despite an absence of characteristic FKS1 resistance mutations in the Aspergillus isolates. EUCAST and CLSI methodology did not separate the candin-resistant clinical isolate from...
Aspergilosis broncopulmonar alérgica, una complicación del paciente con fibrosis quística: reporte de dos casos y revisión de la literatura = Allergic bronchopulmonary aspergillosis, a complication of patients with cystic fibrosis: Report of two cases and review of the literature
Directory of Open Access Journals (Sweden)
Ballesteros Calderón, Alicia Lucía
Full Text Available La aspergilosis broncopulmonar alérgica (ABPA es la enfermedad pulmonar resultante de hipersensibilidad a Aspergillus, que lleva a alteración de la depuración mucociliar, impactación mucosa con obstrucción de la vía aérea e infiltración pulmonar. Se caracteriza clínicamente por disnea, sibilancias, fiebre, malestar general y expectoración de color marrón o negro, y por la mala respuesta clínica al tratamiento habitual instaurado para las exacerbaciones en pacientes con enfermedad pulmonar crónica. En los pacientes con fibrosis quística (FQ puede ser difícil establecer el diagnóstico de ABPA debido a la superposición de las características clínicas, radiológicas e inmunológicas de las dos enfermedades y a la presencia frecuente de infecciones bacterianas pulmonares. Por ello, se recomienda que en el seguimiento de dichos pacientes se haga medición anual de la inmunoglobulina E (IgE sérica total y, según su resultado y el contexto clínico, se plantee el diagnóstico de ABPA y se haga el tratamiento oportuno con esteroides con el cual mejoran los síntomas, la función pulmonar, la calidad de vida y el pronóstico. Presentamos dos pacientes pediátricos con diagnóstico de FQ de difícil control, en quienes se hizo el diagnóstico de ABPA y cuya sintomatología pulmonar mejoró con el tratamiento esteroide.
Anestesia para tratamento de aspergilose cardíaca em paciente com trombocitopenia: o uso criterioso da aprotinina Anestesia para tratamiento de aspergilosis cardiaca en paciente con trombocitopenia: el uso con criterio de la aprotinina Anesthesia for treatment of cardiac aspergillosis in a patient with thrombocytopenia and the judicious use of aprotinin
Directory of Open Access Journals (Sweden)
Raquel Reis Soares
Full Text Available JUSTIFICATIVA E OBJETIVOS: A aprotinina tem sido muito utilizada em intervenções cirúrgicas cardíacas como recurso terapêutico para redução dos efeitos da circulação extracorpórea (CEC sobre a coagulação e fibrinólise. A recuperação da hemostasia adequada ao final do procedimento é um dos objetivos do anestesiologista. Porém, o uso da aprotinina tem indicação específica. O objetivo deste trabalho foi apresentar o caso de um paciente com plaquetopenia intensa submetido à intervenção cirúrgica cardíaca no qual a interconsulta com a Hematologia e o planejamento adequado permitiram o sucesso do procedimento. RELATO DO CASO: Paciente do sexo masculino, 18 anos, 64 kg, estado físico ASA IV, portador de aplasia de medula, em investigação para ser submetido a transplante de medula. Apresentava febre persistente, de um mês de evolução, sem melhora com antibioticoterapia. Na investigação com métodos de imagem, diagnosticou-se massa intra-atrial esquerda. Ao exame laboratorial apresentava hemoglobina de 9 g.dL-1 e trombocitopenia - 6.000 plaquetas.mm-3. Foi submetido à esternotomia com CEC para retirada de trombo intracavitário. Com objetivo de controlar o sangramento intra-operatório foram administrados: plaquetaférese, hidrocortisona e aprotinina. Durante a intervenção cirúrgica não houve aumento do sangramento nem instabilidade hemodinâmica e o paciente foi encaminhado à Unidade de Terapia Intensiva (UTI sem intercorrências. O exame anatomopatológico revelou trombo repleto de Aspergillus (massa fúngica. No sétimo dia de pós-operatório o paciente evoluiu com insuficiência respiratória e parada cardiorrespiratória sem resposta às manobras de reanimação. CONCLUSÕES: Apesar do grande risco de sangramento no paciente descrito, conseguiu-se realizar intervenção cirúrgica cardíaca com CEC sem intercorrências graças ao uso de aprotinina e plaquetoaférese.JUSTIFICATIVA Y OBJETIVOS: La aprotinina ha sido muy utilizada en intervenciones quirúrgicas cardiacas como recurso terapéutico para la reducción de los efectos de la circulación extracorpórea (CEC sobre la coagulación y la fibrinólisis. La recuperación de la hemostasia adecuada al final del procedimiento es uno de los objetivos del anestesiólogo. Sin embargo, el uso de la aprotinina tiene una indicación específica. El objetivo de este trabajo fue presentar el caso de un paciente con plaquetopenia intensa sometido a la intervención quirúrgica cardiaca en el cual la interconsulta con hematología y la planificación adecuada permitieron el éxito del procedimiento. RELATO DEL CASO: Paciente del sexo masculino, 18 años, 64 kg, estado físico ASA IV, portador de aplasia de medula, en investigación para ser sometido al transplante de médula. Presentaba fiebre persistente, de un mes de evolución, sin mejoría con antibioticoterapia. En la investigación con métodos de imagen, se diagnosticó masa intra atrial izquierda. En el examen de laboratorio presentaba hemoglobina de 9 g.dL-1 y trombocitopenia - 6.000 plaquetas mm-3. Se sometió a la esternotomía con CEC para retirada de trombo intracavitario. Con el objetivo de controlar el sangramiento intraoperatorio fueron administrados: plaqueto-aferesis, hidrocortisona y aprotinina. Durante la intervención quirúrgica no hubo aumento del sangramiento ni inestabilidad hemodinámica y el paciente fue llevado a la Unidad de Terapia Intensiva (UTI sin intercurrencias. El examen anátomo patológico reveló trombo repleto de Aspergilus (masa fúngica. Al sétimo día del postoperatorio el paciente evolucionó con insuficiencia respiratoria y parada cardiorrespiratoria sin respuesta a las maniobras de reanimación. CONCLUSIONES: A pesar del gran riesgo de sangramiento en el paciente descrito, se logró realizar la intervención quirúrgica cardiaca con CEC sin intercurrencias gracias al uso de aprotinina y plaquetoaféresis.BACKGROUND AND OBJECTIVES: Aprotinin has been widely used in cardiac surgeries as a therapeutic resource for reducing the effects of cardiopulmonary bypass (CPB on coagulation and fibrinolysis. Recovery of adequate hemostasia at the end of the procedure is one of the objectives of the anesthesiologist. However, aprotinin has specific indications. The objective of this report was to present the case of a patient with severe thrombocytopenia undergoing cardiac surgery in which consultation with Hematology and adequate planning were responsible for the success of the procedure. CASE REPORT: An 18-year old male patient, weighing 64 kg, physical status ASA IV, with a diagnosis of bone marrow aplasia, was being investigated to undergo bone marrow transplantation. He had persistent fever for a month, which did not improve with antibiotics. During the investigation with imaging exams, a left atrial mass was discovered. Laboratory exams revealed hemoglobin 9 g.dL-1 and thrombocytopenia with 6,000 platelets.mm³. He underwent a sternotomy with CPB to remove the intracavitary thrombus. In order to control intraoperative bleeding, the following was administered: plateletpheresis, hydrocortisone, and aprotinin. Increased bleeding and hemodynamic instability did not develop during the surgery, and the patient was transferred to the Intensive Care Unit (ICU without intercurrences. The anatomo-pathologic exam revealed the thrombus to be filled with Aspergillus (fungal mass. On the seventh postoperative day the patient developed respiratory failure and cardiorespiratory arrest that did not respond to resuscitation maneuvers. CONCLUSIONS: Despite the increased risk of bleeding in this patient, cardiac surgery with CPB was performed without intercurrences due to the use of aprotinin and plateletpheresis.
Repeated Aspergillus isolation in respiratory samples from non-immunocompromised patients not selected based on clinical diagnoses: colonisation or infection?
Barberan, Jose; Alcazar, Bernardino; Malmierca, Eduardo; Garcia de la Llana, Francisco; Dorca, Jordi; Del Castillo, Daniel; Villena, Victoria; Hernandez-Febles, Melissa; Garcia-Perez, Francisco-Javier; Granizo, Juan-Jose; Gimenez, Maria-Jose; Aguilar, Lorenzo
Isolation of Aspergillus from lower respiratory samples is associated with colonisation in high percentage of cases, making it of unclear significance. This study explored factors associated with diagnosis (infection vs. colonisation), treatment (administration or not of antifungals) and prognosis (mortality) in non-transplant/non-neutropenic patients showing repeated isolation of Aspergillus from lower respiratory samples. Records of adult patients (29 Spanish hospitals) presenting ≥ 2 respiratory cultures yielding Aspergillus were retrospectively reviewed and categorised as proven (histopathological confirmation) or probable aspergillosis (new respiratory signs/symptoms with suggestive chest imaging) or colonisation (symptoms not attributable to Aspergillus without dyspnoea exacerbation, bronchospasm or new infiltrates). Logistic regression models (step-wise) were performed using Aspergillosis (probable + proven), antifungal treatment and mortality as dependent variables. Significant (p < 0.001) models showing the highest R2 were considered. A total of 245 patients were identified, 139 (56.7%) with Aspergillosis. Aspergillosis was associated (R2 = 0.291) with ICU admission (OR = 2.82), congestive heart failure (OR = 2.39) and steroids pre-admission (OR = 2.19) as well as with cavitations in X-ray/CT scan (OR = 10.68), radiological worsening (OR = 5.22) and COPD exacerbations/need for O2 interaction (OR = 3.52). Antifungals were administered to 79.1% patients with Aspergillosis (100% proven, 76.8% probable) and 29.2% colonised, with 69.5% patients receiving voriconazole alone or in combination. In colonised patients, administration of antifungals was associated with ICU admission at hospitalisation (OR = 12.38). In Aspergillosis patients its administration was positively associated (R(2) = 0.312) with bronchospasm (OR = 9.21) and days in ICU (OR = 1.82) and negatively with Gold III + IV (OR = 0.26), stroke (OR = 0.024) and quinolone treatment (OR = 0
Serological monitoring of antibodies for an early diagnosis ofaspergillosis in captive penguins
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Ângela L. Cabana
Full Text Available Abstract: This study aimed to evaluate the efficacy of detection of anti-Aspergillus fumigatus antibodies in captive penguins by double radial agar gel immunodiffusion (AGID for the aspergillosis diagnosis. We included 134 Magellanic penguins (Spheniscus magellanicus in rehabilitation at the Center for Recovery of Marine Animals (CRAM / FURG. All of them were monitored by AGID weekly until its final destination (death or release, totalizing 660 serum samples studied. All animals were clinically accompanied and post-mortem examinations was performed in penguins that died during the studied period. A total of 28% (37/134 of the penguins died, 89.2% (33/37 due to aspergillosis, 11% (4/37 by other causes and 97 were released. From the 33 animals with proven aspergillosis, 21 presented anti- A. fumigatus antibodies by AGID, being the average interval between death and positive AGID 16.4 days. Twelve animals with negative serology died of aspergillosis. The sensitivity and specificity rates were 63.6% and 95% respectively, and the positive and negative predictive values were 80.7% and 88.9% respectively. These data demonstrate that the serological monitoring for detection of antibodies by AGID can be an important tool for the diagnosis of aspergillosis in penguins.
Aspergillus-Related Lung Disease
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Alia Al-Alawi
Full Text Available Aspergillus is a ubiquitous dimorphic fungus that causes a variety of human diseases ranging in severity from trivial to life-threatening, depending on the host response. An intact host defence is important to prevent disease, but individuals with pre-existing structural lung disease, atopy, occupational exposure or impaired immunity are susceptible. Three distinctive patterns of aspergillus-related lung disease are recognized: saprophytic infestation of airways, cavities and necrotic tissue; allergic disease including extrinsic allergic alveolitis, asthma, allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis and chronic eosinophilic pneumonia; and airway and tissue invasive disease -- pseudomembranous tracheobronchitis, acute bronchopneumonia, angioinvasive aspergillosis, chronic necrotizing aspergillosis and invasive pleural disease. A broad knowledge of these clinical presentations and a high index of suspicion are required to ensure timely diagnosis and treatment of the potentially lethal manifestations of aspergillus-related pulmonary disease. In the present report, the clinical, radiographic and pathological aspects of the various aspergillus-related lung diseases are briefly reviewed.
Cavernous sinus thrombosis secondary to aspergillus granuloma: A case report and review of the literature.
Brenet, Esteban; Boulagnon-Rombi, Camille; N'guyen, Yohan; Litré, Claude-Fabien
Cavernous sinus thrombosis is a rare but serious complication of sphenoid aspergillosis. The rarity of this pathology makes its diagnostic very difficult on a clinical, biological and radiological sense. The authors present a case of cavernous sinus thrombosis with ipsilateral internal carotid artery thrombosis secondary to a non-invasive sphenoid aspergillosis in an immunocompetent host, responsible of a cavernous syndrome associated to a Claude Bernard Horner syndrome. One year after surgery, the patient is still asymptomatic without recurrence. Diagnostic modalities are detailed and several management of this pathology are compared. Surgery is essential in a diagnostic and therapeutic sense. There is no evidence of the interest of adjuvant therapies such as antibiotic and anticoagulation. Concerning the antifungal treatment, the attitude towards a non-invasive sphenoid aspergillosis in an immunocompetent host is unclear. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Significance of lower respiratory tract cultures yielding Aspergillus spp. growth in a hospital without transplant patients.
Lucena, Paloma; Barberán, José; Eroles, Guillermo; Granizo, Juan-José; Giménez, María-José; Mir, Nuria; Aguilar, Lorenzo; Prieto, José; Cuétara, Maria Soledad
Isolation of Aspergillus spp. in non-neutropenic, non-transplant patients with chronic obstructive pulmonary disease (COPD) usually treated with corticosteroids is not easily interpretable. A retrospective review of clinical records corresponding to cultures (respiratory samples) yielding Aspergillus spp. in non- transplant patients was carried out. Patients were assigned to four categories: colonization, possible, probable or definitive aspergillosis. A logistic regression model (step-wise procedure) was performed using as dependent variable mortality, and as independent variables those showing differences (p≤0.1) in the bivariant analysis. Sixty-nine patients were identified. Most were elderly (68.1% ≥65 years), male (73.9%), presented comorbidities (84.1% Charlson index ≥3), COPD (76.8%), were receiving high corticosteroid doses (66.7%), and had previously received antibiotics (94.2%). Forty-five cases were colonizations, 4 possible, 15 probable and 5 definitive aspergillosis. A. fumigatus was isolated in 75.4% patients: 66.7% colonized, 75% possible, 93.3% probable and 100% definitive aspergillosis. Colonized patients were older (71.9 ± 11.9 vs. 65.1 ± 9.2 years; p= 0.018) and presented higher (p=0.034) comorbidity index than patients with aspergillosis. Mortality was 31.1% in colonized vs. 62.5% in aspergillosis (p=0.012). The isolation of A. fumigatus was associated with an increased probability of aspergillosis, with statistical association in the multivariate analysis between mortality and variables related to chemotherapy (no antifungal treatment), disease (diagnostic category) and immunity (leukocytosis).
Voriconazole-associated visual disturbances and hallucinations.
Bayhan, Gulsum Iclal; Garipardic, Mesut; Karaman, Kamuran; Akbayram, Sinan
Voriconazole is a second-generation azole widely used for the prevention and treatment of fungal infection in leukemia patients. Voriconazole is considered the primary antifungal agent for invasive aspergillosis. We report a case of 16-year-old girl who developed visual disturbance and visual and auditory hallucinations after intravenous voriconazole treatment for invasive pulmonary aspergillosis. Due to the visual hallucinations and visual disturbance began acutely and shortly after the initiation of voriconazole, and no other cause could be determined, the symptoms were considered to be the side effects of voriconazole. Simultaneous development of visual side effects and hallucinations rarely have been reported before.
Aspergillus tanneri sp. nov, a new pathogenic Aspergillus that causes invasive disease refractory to antifungal therapy
This is the first report documenting fatal invasive aspergillosis caused by a new pathogenic Aspergillus species that is inherently resistant to antifungal drugs. Phenotypic characteristics of A. tanneri combined with the molecular approach enabled diagnosis of this new pathogen. This study undersco...
Peroral amphotericin B polymer nanoparticles lead to comparable or superior in vivo antifungal activity to that of intravenous Ambisome® or Fungizone™.
Italia, Jagdishbhai L; Sharp, Andrew; Carter, Katharine C; Warn, Peter; Kumar, M N V Ravi
Despite advances in the treatment, the morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70-90%) in immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation; development of an oral formulation would be beneficial as well as economical. Poly(lactide-co-glycolode) (PLGA) nanoparticles encapsulating AMB (AMB-NPs) were developed for oral administration. The AMB-NPs were 113 ± 20 nm in size with ~70% entrapment efficiency at 30% AMB w/w of polymer. The in vivo therapeutic efficacy of oral AMB-NPs was evaluated in neutropenic murine models of disseminated and invasive pulmonary aspergillosis. AMB-NPs exhibited comparable or superior efficacy to that of Ambisome® or Fungizone™ administered parenterally indicating potential of NPs as carrier for oral delivery. The present investigation describes an efficient way of producing AMB-NPs with higher AMB pay-load and entrapment efficiency employing DMSO as solvent and ethanol as non-solvent. The developed oral formulation was highly efficacious in murine models of disseminated aspergillosis as well as an invasive pulmonary aspergillosis, which is refractory to treatment with IP Fungizone™ and responds only modestly to AmBisome®.
Peroral amphotericin B polymer nanoparticles lead to comparable or superior in vivo antifungal activity to that of intravenous Ambisome® or Fungizone™.
Directory of Open Access Journals (Sweden)
Jagdishbhai L Italia
Full Text Available BACKGROUND: Despite advances in the treatment, the morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70-90% in immunocompromised patients. Amphotericin B (AMB, a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation; development of an oral formulation would be beneficial as well as economical. METHODOLOGY: Poly(lactide-co-glycolode (PLGA nanoparticles encapsulating AMB (AMB-NPs were developed for oral administration. The AMB-NPs were 113 ± 20 nm in size with ~70% entrapment efficiency at 30% AMB w/w of polymer. The in vivo therapeutic efficacy of oral AMB-NPs was evaluated in neutropenic murine models of disseminated and invasive pulmonary aspergillosis. AMB-NPs exhibited comparable or superior efficacy to that of Ambisome® or Fungizone™ administered parenterally indicating potential of NPs as carrier for oral delivery. CONCLUSIONS: The present investigation describes an efficient way of producing AMB-NPs with higher AMB pay-load and entrapment efficiency employing DMSO as solvent and ethanol as non-solvent. The developed oral formulation was highly efficacious in murine models of disseminated aspergillosis as well as an invasive pulmonary aspergillosis, which is refractory to treatment with IP Fungizone™ and responds only modestly to AmBisome®.
Aspergillus and aspergilloses in wild and domestic animals : a global health concern with parallels to human disease
Seyedmousavi, Seyedmojtaba; Guillot, Jacques; Arné, Pascal; de Hoog, G Sybren; Mouton, Johan W; Melchers, Willem J G; Verweij, Paul E
The importance of aspergillosis in humans and various animal species has increased over the last decades. Aspergillus species are found worldwide in humans and in almost all domestic animals and birds as well as in many wild species, causing a wide range of diseases from localized infections to
African Journal of Neurological Sciences - 2009 Vol. 28 No 1
African Journals Online (AJOL)
In many cases, lesions involve the frontal and the temporal lobes (13). Aspergillosis is rarely due to. Aspergillus nidulans. This condition is almost exclusively observed in cases with chronic granulomatous disease (8, 15) which is an X-linked genetic condition or autosomal recessive inherited (4). This disease is secondary ...
Geographically predominant genotypes of Aspergillus terreus species complex in Austria: s microsatellite typing study
Lackner, M.; Coassin, S.; Haun, M.; Binder, U.; Kronenberg, F.; Haas, H. de; Jank, M.; Maurer, E.; Meis, J.F.; Hagen, F.; Lass-Florl, C.
Aspergillus terreus species complex is recognized as a frequent agent of invasive aspergillosis in Tyrol. The reason for this specific epidemiological situation is unclear. Aspergillus terreus strains isolated from environmental and clinical sources were genotyped using a novel panel of short tandem
Lifescience Database Archive (English)
Full Text Available H01328 Aspergillosis Infectious disease Aspergillus fumigatus [GN:afm] Aspergillus flavus [GN:afv] Aspergill...us nidulans [GN:ani] Aspergillus niger [GN:ang] ICD-10: B44 MeSH: D001228 MedlinePlus: 001326 ...
Genetic Diversity and In Vitro Antifungal Susceptibility of 200 Clinical and Environmental Aspergillus flavus Isolates
Taghizadeh-Armaki, M.; Hedayati, M.T.; Ansari, S.; Omran, S.M.; Saber, S.; Rafati, H.; Zoll, J.; Lee, H.A.L. van der; Melchers, W.J.G.; Verweij, P.E.; Seyedmousavi, S.
Aspergillus flavus has been frequently reported as the leading cause of invasive aspergillosis in certain tropical and subtropical countries. Two hundred A. flavus strains originating from clinical and environmental sources and collected between 2008 and 2015 were phylogenetically identified at the
Aspergillus PCR: one step closer to standardization.
White, P.L.; Bretagne, S.; Klingspor, L.; Melchers, W.J.G.; McCulloch, E.; Schulz, B.; Finnstrom, N.; Mengoli, C.; Barnes, R.A.; Donnelly, J.P.; Loeffler, J.
PCR has been used as an aid in the diagnosis of invasive aspergillosis for almost 2 decades. A lack of standardization has limited both its acceptance as a diagnostic tool and multicenter clinical evaluations, preventing its inclusion in disease-defining criteria. In 2006, the European Aspergillus
Global Population Genetic Analysis of Aspergillus fumigatus
Ashu, E.E.; Hagen, F.; Chowdhary, A.; Meis, J.F.G.M.; Xu, J.
Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen capable of causing invasive aspergillosis, a globally distributed disease with a mortality rate of up to 90% in high-risk populations. Effective control and prevention of this disease require a thorough understanding of its
Specific detection of Aspergillus fumigatus in sputum sample of ...
African Journals Online (AJOL)
Jan 4, 2008 ... 48:474-476. Wald A, Leisenring W, Van Burik JA, Bowden RA (1997). Successful. Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant in an Acute Leukemia Patient With Chemotherapy-Induced Marrow. Aplasia and Progressive Pulmonary Aspergillosis. Blood,. Epidemiology 94: 3273-3276.
Antifungal and Antihepatotoxic Effects of Sepia Ink Extract against ...
African Journals Online (AJOL)
Background: There is a great need for novel strategies to overcome the high mortality associated with invasive pulmonary aspergillosis (IPA) in immunocompromised patients. To evaluate the antifungal and antihepatotoxic potentials of Sepia ink extract, its effect on liver oxidative stress levels was analyzed against IPA in ...
Azole Resistance in Aspergillus fumigatus: Can We Retain the Clinical Use of Mold-Active Antifungal Azoles?
Verweij, P.E.; Chowdhary, A.; Melchers, W.J.; Meis, J.F.
Azole resistance in Aspergillus fumigatus has emerged as a global health problem. Although the number of cases of azole-resistant aspergillosis is still limited, resistance mechanisms continue to emerge, thereby threatening the role of the azole class in the management of diseases caused by
PCR-Internal Transcribed Spacer (ITS) genes sequencing and ...
African Journals Online (AJOL)
Department of Animal Breeding and Genetics, Federal University of Agriculture, Abeokuta, Nigeria. Abstract. Background: Aspergillosis has been identified as one of the hospital .... gen, Valencia, CA) with catalogue number 51304 follow- ing manufacturer's instruction. The Extracted Nucleic. African Health Sciences Vol 16 ...
Aspergillus of the lung with haemoptysis: A surgical emergency ...
African Journals Online (AJOL)
Background: Aspegillus is an important pathogen in patients with impaired host defences. These mycelial fungi can cause local as well disseminated disease. Two forms of pulmonary aspergillosis are frequently seen : 1. pulmonary or brochial aspergilloma (fungus ball) due to secondary invasion of a a tuberculous cavity ...
Aspergillus Salpingitis: A Rare Case Report | Gowardhan | Journal ...
African Journals Online (AJOL)
We describe the pathology of a unique case of fallopian tube aspergillosis in a 45 year old woman. She complained of lower abdominal pain and lump in lower abdomen since 2-3 months. Clinically she was diagnosed as benign ovarian tumor, right ovary. Pathological examination showed dilated fallopian tube containing ...
Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India
Masih, A.; Singh, P.K.; Kathuria, S.; Agarwal, K.; Meis, J.F.G.M.; Chowdhary, A.
Aspergillus species cause a wide spectrum of clinical infections. Although Aspergillus fumigatus and Aspergillus flavus remain the most commonly isolated species in aspergillosis, in the last decade, rare and cryptic Aspergillus species have emerged in diverse clinical settings. The present study
The rise and fall of a six-year coral-fungal epizootic.
Kim, Kiho; Harvell, C Drew
Drivers of disease cycles are poorly understood in marine ecosystems in spite of increasing outbreaks. We monitored a newly emerged fungal epizootic (aspergillosis) affecting sea fan corals (Gorgonia ventalina L.) in the Florida Keys to evaluate causes of its rise and fall over 6 years. Since August 1997, aspergillosis has nearly eradicated large sea fans at some sites. However, sea fan densities have remained relatively constant due to episodic recruitment replacing large fans with small. Recruitment itself was affected by infection and occurred only when prevalence of disease was low. This impact on recruitment occurred because the largest, potentially most fecund colonies had the highest prevalence of disease, and the pathogen significantly suppressed reproduction of infected fans. Moreover, high mortality among adults resulted in a demographic shift to smaller colonies. The most dramatic impact of aspergillosis was the Keys-wide loss of >50% of sea fan tissue from complete and partial mortality. Aspergillosis prevalence has declined steadily over the last 6 years, and we consider the following hypotheses for decline of the epizootic: change in environment, change in pathogen input, and increase in host resistance. We conclude that increasing host resistance is the most likely driver of the decline. However, a change in any of a number of factors, for example, recruitment of naive hosts, rate of pathogen input, or environmental conditions (water quality and temperature), is likely to promote reemergence of the epizootic.
Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry
Gerritsen, M. G.; Brinkman, P.; Escobar, N.; Bos, L. D.; de Heer, K.; Meijer, M.; Janssen, H.-G.; de Cock, H.; Wösten, H. A. B.; Visser, C. E.; van Oers, M. H. J.; Sterk, P. J.
Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a
Potentially fatal tricuspid valve aspergilloma detected after ...
African Journals Online (AJOL)
Nov 14, 2010 ... combination of voriconazole with caspofungin has led to promising results in invasive pulmonary aspergillosis, but there is limited experience in patients with endocarditis.2. Systemic antifungal agents do not achieve good penetration into the necrosed and friable vegetations. These large vegetations can ...
Aspergillus Tracheobronchitis Causing Subtotal Tracheal Stenosis in a Liver Transplant Recipient
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Sonia Radunz
Full Text Available Invasive aspergillosis is recognized as one of the most significant opportunistic infections after liver transplantation. Diagnosis of invasive aspergillosis in transplant recipients has been proven to be challenging, and optimal approach to the treatment of invasive aspergillosis is still controversial. We here present an unusual case of Aspergillus tracheobronchitis in the setting of liver transplantation. A 47-year-old female patient with persistent dry cough after liver transplantation developed respiratory insufficiency and was readmitted to the intensive care unit 55 days after liver transplantation. A CT scan revealed subtotal tracheal stenosis; bronchoscopy was performed, and extended white mucus coverings causative of the tracheal stenosis were removed. Microbiological assessment isolated Aspergillus fumigatus. The diagnosis was obstructive Aspergillus tracheobronchitis. The patient was started on a treatment of voriconazole 200 mg orally twice daily, adjusted to a trough level of 1–4 mg/L. For further airway management, a tracheal stent had to be implanted. The patient is alive and well 28 months after liver transplantation. Invasive aspergillosis should be considered a possible etiology in liver transplant patients presenting with unspecific symptoms such as persistent dry cough. Optimal strategies for improved and early diagnosis as well as prophylaxis need to be defined.
The emerging epidemiology of mould infections in developing countries.
Chakrabarti, Arunaloke; Singh, Rachna
The present review describes the emerging trends of mould infections in developing countries, and highlights the major epidemiological differences from the developed countries. The limited data available from developing countries suggest an alarming increase in invasive mould infections, especially aspergillosis and mucormycosis, and also a difference in risk factors and causative agents between the developed and developing world. Sino-orbital, cerebral and ophthalmic infections due to Aspergillus flavus are the major clinical types in aspergillosis, after pulmonary aspergillosis. Aspergillus and Fusarium spp. are frequent causes of trauma-associated keratitis in agricultural workers. Rhino-orbito-cerebral presentation associated with uncontrolled diabetes is the predominant mucormycosis. Isolated renal mucormycosis has emerged as a new clinical entity. Apophysomyces elegans and Mucor irregularis are emerging species in these regions and uncommon agents such as Rhizopus homothallicus have also been reported. Many pathogens are geographically restricted, with Pythium insidionum, Rhinocladiella mackenziei and M. irregularis being described almost exclusively from Thailand, Middle East and China, respectively. Despite limited studies, certain peculiarities have been observed in invasive mould infections in developing countries, including a high incidence of ophthalmic lesions, mucormycosis and aspergillosis; few different clinical presentations; and a varied spectrum of pathogens involved in such lesions.
African Journals Online (AJOL)
Philippe GUERRE
GARCIA MARIN, 1998. "Mammary and systemic aspergillosis in dairy sheep". Veterinary Pathology, 35:235-240. [15] - G. JM. ALLER, G. JM. FREGENEDA, MF. DIEZ, 2000. "Mammite a Aspergillus fumigatus chez les ovins". Rev. Iberoam. Micol; 17:13-17. [16] - F. LONGO, J.C. BEGUIN, P.J. CONSALVI, J.C. DELTOR 1994.
African Journals Online (AJOL)
Tijani, MO. Vol 30, No 2 (2012) - Articles Fibrosarcoma in Pond-Cultured African Catfish (Clarias gariepinus) Abstract · Vol 30, No 3 (2012) - Articles CD 33 Positive Lymphoma in a Male Alsatian Dog: A Case Report Abstract · Vol 30, No 3 (2012) - Articles Pulmonary Aspergillosis in an Adult Male Ostrich (Struthio camelus): ...
Fatal coinfection with Legionella pneumophila serogroup 8 and Aspergillus fumigatus.
Guillouzouic, Aurélie; Bemer, Pascale; Gay-Andrieu, Françoise; Bretonnière, Cédric; Lepelletier, Didier; Mahé, Pierre-Joachim; Villers, Daniel; Jarraud, Sophie; Reynaud, Alain; Corvec, Stéphane
Legionella pneumophila is an important cause of community-acquired and nosocomial pneumonia. We report on a patient who simultaneously developed L. pneumophila serogroup 8 pneumonia and Aspergillus fumigatus lung abscesses. Despite appropriate treatments, Aspergillus disease progressed with metastasis. Coinfections caused by L. pneumophila and A. fumigatus remain exceptional. In apparently immunocompetent patients, corticosteroid therapy is a key risk factor for aspergillosis.
African Journals Online (AJOL)
Nasopharyngeal cancer: a review of cases at the Korle-Bu Teaching Hospital Abstract PDF · Vol 40, No 2 (2006) - Articles Laryngeal cancer at the Korle Bu Teaching Hospital, Accra, Ghana Abstract · Vol 40, No 2 (2006) - Articles Disseminated invasive aspergillosis. Abstract · Vol 42, No 2 (2008) - Articles Cervical human ...
... fungal infections such as invasive aspergillosis (a fungal infection that begins in the lungs and spreads through the bloodstream to other organs) and invasive mucormycosis (a fungal infection that usually begins in the sinuses, brain, or lungs). Isavuconazonium injection is in a class of medications ...
African Journals Online (AJOL)
role in causing various ailments such as asthma, cystic fibrosis and invasive aspergillosis cannot be overemphasized [1-3]. These organisms has since been indicted in ..... exchange of DNA in the rice blast fungus; challenges its exclusive clonality. Phytopathology.1997; 87(3):284–294. 27.Souza-Paccola EA, Fa´varo LCL, ...
Susceptibility breakpoints and target values for therapeutic drug monitoring of voriconazole and Aspergillus fumigatus in an in vitro pharmacokinetic/pharmacodynamic model
Siopi, M.; Mavridou, E.; Mouton, J.W.; Verweij, P.E.; Zerva, L.; Meletiadis, J.
BACKGROUND: Although voriconazole reached the bedside 10 years ago and became the standard care in the treatment of invasive aspergillosis, reliable clinical breakpoints are still in high demand. Moreover, this has increased due to the recent emergence of azole resistance. METHODS: Four clinical
A case of pseudomembranous colitis after voriconazole therapy.
Kwon, Jae-Cheol; Kang, Min-Kyu; Kim, Si-Hyun; Choi, Su-Mi; Kim, Hee-Je; Min, Woo-Sung; Lee, Dong-Gun
This is a case report on a 35-year-old man with acute myelogenous leukemia who presented fever and intermittent mucoid loose stool to the emergency center. He had been taking voriconazole for invasive pulmonary aspergillosis. The flexible sigmoidoscopy was consistent with the diagnosis of pseudomembranous colitis.
Possible Environmental Origin of Resistance of Aspergillus fumigatus to Medical Triazoles
Snelders, E.; Veld, R.; Rijs, A.; Kema, G.H.J.; Melchers, W.J.G.; Verweij, P.E.
We reported the emergence of resistance to medical triazoles of Aspergillus fumigatus isolates from patients with invasive aspergillosis. A dominant resistance mechanism was found, and we hypothesized that azole resistance might develop through azole exposure in the environment rather than in
Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles.
Snelders, E.; Huis In 't Veld, R.A.; Rijs, A.J.M.M.; Kema, G.H.; Melchers, W.J.G.; Verweij, P.E.
We reported the emergence of resistance to medical triazoles of Aspergillus fumigatus isolates from patients with invasive aspergillosis. A dominant resistance mechanism was found, and we hypothesized that azole resistance might develop through azole exposure in the environment rather than in
Cytokine responses and regulation of interferon-gamma release by human mononuclear cells to Aspergillus fumigatus and other filamentous fungi.
Warris, A.; Netea, M.G.; Verweij, P.E.; Gaustad, P.; Kullberg, B.J.; Weemaes, C.M.R.; Abrahamsen, T.G.
There is substantial evidence that the production of proinflammatory cytokines is important in host resistance to invasive aspergillosis. Knowledge of the host response towards other filamentous fungi is scarce, as most studies have focused on Aspergillus fumigatus. In addition, interferon-gamma
Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide
DEFF Research Database (Denmark)
Skov, M; Main, K M; Sillesen, Ida Blok
A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic...
In vitro interactions between amphotericin B, itraconazole, and flucytosine against 21 clinical Aspergillus isolates determined by two drug interaction models.
Dorsthorst, D.T.A. te; Verweij, P.E.; Meis, J.F.G.M.; Punt, N.C.; Mouton, J.W.
Combination therapy of flucytosine (5FC) with other antifungal agents could be of use for the treatment of invasive aspergillosis. However, interpretation of the results of in vitro interactions is problematic. The fractional inhibitory concentration (FIC) index is the most commonly used method, but
Microbial and physico-chemical quality of powdered soymilk ...
African Journals Online (AJOL)
Jul 6, 2009 ... Chard soy products in New York (Gavin and Wettstein,. 1990). pathogen to the teaming consumers (Nester ... 1997). It is also non-allergic; can be easily produced with low level technology and serve as good ... 2000). Aspergillus flavus is involved in allergic asper- gillosis (pulmonary aspergillosis) and also ...
A prospective international Aspergillus terreus survey
DEFF Research Database (Denmark)
Risslegger, B; Zoran, T; Lackner, M
of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). CONCLUSIONS: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority...
Identification and antifungal activity of Streptomyces sp. S72 isolated ...
African Journals Online (AJOL)
The test of antifungal activity for several pathogens fungi causing invasive aspergillosis and systemic candidiasis revealed that the Streptomyces sp. S72 was a good moderate antifungal compound producer against Aspergillus fumigatus and Candida albicans, and had no activity against Aspergillus flavus, Aspergillus ...
Intravenous voriconazole after toxic oral administration
Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.
In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate
Multi-azole-resistant Aspergillus fumigatus in the environment in Tanzania
Chowdhary, A.; Sharma, C.; Boom, M. van den; Yntema, J.B.; Hagen, F.; Verweij, P.E.; Meis, J.F.G.M.
OBJECTIVES: Azole resistance in Aspergillus fumigatus isolates has been increasingly reported with variable prevalence worldwide and is challenging the effective management of aspergillosis. Here we report the coexistence of both TR(3)(4)/L98H and TR(4)(6)/Y121F/T289A resistance mechanisms in
A polysaccharide virulence factor from Aspergillus fumigatus elicits anti-inflammatory effects through induction of Interleukin-1 receptor antagonist.
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Mark S Gresnigt
Full Text Available The galactosaminogalactan (GAG is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice. However, the mechanisms responsible for the anti-inflammatory property of GAG remain to be elucidated. In the present study we used in vitro PBMC stimulation assays to demonstrate, that GAG inhibits proinflammatory T-helper (Th1 and Th17 cytokine production in human PBMCs by inducing Interleukin-1 receptor antagonist (IL-1Ra, a potent anti-inflammatory cytokine that blocks IL-1 signalling. GAG cannot suppress human T-helper cytokine production in the presence of neutralizing antibodies against IL-1Ra. In a mouse model of invasive aspergillosis, GAG induces IL-1Ra in vivo, and the increased susceptibility to invasive aspergillosis in the presence of GAG in wild type mice is not observed in mice deficient for IL-1Ra. Additionally, we demonstrate that the capacity of GAG to induce IL-1Ra could also be used for treatment of inflammatory diseases, as GAG was able to reduce severity of an experimental model of allergic aspergillosis, and in a murine DSS-induced colitis model. In the setting of invasive aspergillosis, GAG has a significant immunomodulatory function by inducing IL-1Ra and notably IL-1Ra knockout mice are completely protected to invasive pulmonary aspergillosis. This opens new treatment strategies that target IL-1Ra in the setting of acute invasive fungal infection. However, the observation that GAG can also protect mice from allergy and colitis makes GAG or a derivative structure of GAG a potential treatment compound for IL-1 driven inflammatory diseases.
Fungi in healthy and diseased sea fans ( Gorgonia ventalina): is Aspergillus sydowii always the pathogen?
Toledo-Hernández, C.; Zuluaga-Montero, A.; Bones-González, A.; Rodríguez, J. A.; Sabat, A. M.; Bayman, P.
Caribbean corals, including sea fans ( Gorgonia spp.), are being affected by severe and apparently new diseases. In the case of sea fans, the pathogen is reported to be the fungus Aspergillus sydowii, and the disease is named aspergillosis. In order to understand coral diseases and pathogens, knowledge of the microbes associated with healthy corals is also necessary. In this study the fungal community of healthy Gorgonia ventalina colonies was contrasted with that of diseased colonies. In addition, the fungal community of healthy and diseased tissue within colonies with aspergillosis was contrasted. Fungi were isolated from healthy and diseased fans from 15 reefs around Puerto Rico, and identified by sequencing the nuclear ribosomal ITS region and by morphology. Thirty fungal species belonging to 15 genera were isolated from 203 G. ventalina colonies. Penicillum and Aspergillus were the most common genera isolated from both healthy and diseased fans. However, the fungal community of healthy fans was distinct and more diverse than that of diseased ones. Within diseased fans, fungal communities from diseased tissues were distinct and more diverse than from healthy tissue. The reduction of fungi in diseased colonies may occur prior to infection due to environmental changes affecting the host, or after infection due to increase in dominance of the pathogen, or because of host responses to infection. Data also indicate that the fungal community of an entire sea fan colony is affected even when only a small portion of the colony suffers from aspergillosis. An unexpected result was that A. sydowii was found in healthy sea fans but never in diseased ones. This result suggests that A. sydowii is not the pathogen causing aspergillosis in the studied colonies, and suggests several fungi common to healthy and diseased colonies as opportunistic pathogens. Given that it is not clear that Aspergillus is the sole pathogen, calling this disease aspergillosis is an
Repeated Aspergillus isolation in respiratory samples from non-immunocompromised patients not selected based on clinical diagnoses: colonisation or infection?
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Barberan Jose
Full Text Available Abstract Background Isolation of Aspergillus from lower respiratory samples is associated with colonisation in high percentage of cases, making it of unclear significance. This study explored factors associated with diagnosis (infection vs. colonisation, treatment (administration or not of antifungals and prognosis (mortality in non-transplant/non-neutropenic patients showing repeated isolation of Aspergillus from lower respiratory samples. Methods Records of adult patients (29 Spanish hospitals presenting ≥2 respiratory cultures yielding Aspergillus were retrospectively reviewed and categorised as proven (histopathological confirmation or probable aspergillosis (new respiratory signs/symptoms with suggestive chest imaging or colonisation (symptoms not attributable to Aspergillus without dyspnoea exacerbation, bronchospasm or new infiltrates. Logistic regression models (step–wise were performed using Aspergillosis (probable + proven, antifungal treatment and mortality as dependent variables. Significant (p 2 were considered. Results A total of 245 patients were identified, 139 (56.7% with Aspergillosis. Aspergillosis was associated (R2 = 0.291 with ICU admission (OR = 2.82, congestive heart failure (OR = 2.39 and steroids pre-admission (OR = 2.19 as well as with cavitations in X-ray/CT scan (OR = 10.68, radiological worsening (OR = 5.22 and COPD exacerbations/need for O2 interaction (OR = 3.52. Antifungals were administered to 79.1% patients with Aspergillosis (100% proven, 76.8% probable and 29.2% colonised, with 69.5% patients receiving voriconazole alone or in combination. In colonised patients, administration of antifungals was associated with ICU admission at hospitalisation (OR = 12.38. In Aspergillosis patients its administration was positively associated (R2 = 0.312 with bronchospasm (OR = 9.21 and days in ICU (OR = 1.82 and negatively with Gold III + IV (OR = 0.26, stroke
The burden of serious fungal diseases in Russia.
Klimko, N; Kozlova, Y; Khostelidi, S; Shadrivova, O; Borzova, Y; Burygina, E; Vasilieva, N; Denning, D W
The incidence and prevalence of fungal infections in Russia is unknown. We estimated the burden of fungal infections in Russia according to the methodology of the LIFE program (www.LIFE-worldwide.org). The total number of patients with serious and chronic mycoses in Russia in 2011 was three million. Most of these patients (2,607,494) had superficial fungal infections (recurrent vulvovaginal candidiasis, oral and oesophageal candidiasis with HIV infection and tinea capitis). Invasive and chronic fungal infections (invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis and Pneumocystis pneumonia) affected 69,331 patients. The total number of adults with allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation was 406,082. © 2015 Blackwell Verlag GmbH.
Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient
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Erdoğan Çetinkaya
Full Text Available Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp. are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved.
Aspergillus galactosaminogalactan mediates adherence to host constituents and conceals hyphal β-glucan from the immune system.
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Fabrice N Gravelat
Full Text Available Aspergillus fumigatus is the most common cause of invasive mold disease in humans. The mechanisms underlying the adherence of this mold to host cells and macromolecules have remained elusive. Using mutants with different adhesive properties and comparative transcriptomics, we discovered that the gene uge3, encoding a fungal epimerase, is required for adherence through mediating the synthesis of galactosaminogalactan. Galactosaminogalactan functions as the dominant adhesin of A. fumigatus and mediates adherence to plastic, fibronectin, and epithelial cells. In addition, galactosaminogalactan suppresses host inflammatory responses in vitro and in vivo, in part through masking cell wall β-glucans from recognition by dectin-1. Finally, galactosaminogalactan is essential for full virulence in two murine models of invasive aspergillosis. Collectively these data establish a role for galactosaminogalactan as a pivotal bifunctional virulence factor in the pathogenesis of invasive aspergillosis.
Maxillary necrosis by mucormycosis : a case report and literature review
Auluck, Ajit
The maxilla rarely undergoes necrosis due to its rich vascularity. Maxillary necrosis can occur due to bacterial infections such as osteomyelitis, viral infections such as herpes zoster or fungal infections such as mucormycosis, aspergillosis etc. Mucormycosis is an opportunistic fulminant fungal infection, which mainly infects immunocompromised patients. The infection begins in the nose and paranasal sinuses due to inhalation of fungal spores. The infection can spread to orbital and intr...
African Journals Online (AJOL)
MICROBIOL. 17 (1): 35-45 http://dx.doi.org/10.4314/ajcem.v17i1.5. SPECTRUM OF ASPERGILLOSIS: PATHOGENESIS, RISK FACTORS AND MANAGEMENT. Iyalla, C. ... Le symptôme clinique d'aspergillose dépend du type et les systèmesaffectés ; les symptômes respiratoires sont plus ..... Mannose-binding lectin gene.
Fungi and molds following lung transplantation.
Hosseini-Moghaddam, S M; Husain, Shahid
The landscape of fungal infections in lung transplant recipients has significantly changed over the course of time. The initial predominance of CANDIDA species has given way to the prominence of ASPERGILLUS species in the current era followed by other mold infections, namely, SCEDOSPORIUM and Zygomycetes, which are emerging as newer pathogens. CRYPTOCOCCUS NEOFORMANS is another important pathogen responsible for the morbidity in lung transplant recipients. The use of widespread antifungal prophylaxis directed against the mold infections has resulted in delayed onset of invasive aspergillosis in lung transplant recipients. In recent studies cumulative incidence rate of invasive aspergillosis was noted to be 2.4% at 12 months. Invasive mold infections in lung transplant may present as tracheobronchitis, invasive pulmonary infections, or disseminated disease. Invasive pulmonary infections are now the most common manifestations of mold infections, followed by tracheobronchitis. Pre- or posttransplant ASPERGILLUS colonization, along with preceding cytomegalovirus infections, hypogammaglobulinemia, and single-lung transplants are considered significant risk factors for invasive aspergillosis. Recently posttransplant colonization has been implicated in the development of bronchiolitis obliterans syndrome. The appropriate antimold prophylaxis strategy, by the use of either voriconazole or inhaled amphotericin, remains to be fully determined. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in significant decreases in mortality. The risk factors for other mold infections such as SCEDOSPORIUM or Zygomycetes are being elucidated. Infections with these organisms, however, carry mortality up to 80%. The current article reviews the changes in the epidemiology of invasive molds and CRYPTOCOCCUS infections and other emerging fungal pathogens and highlights the controversies surrounding antifungal prophylaxis in lung transplant recipients.
Therapeutic drug monitoring in voriconazole-associated hyponatremia
Xu, Ren-ai; Zheng, Shuang-li; Xiao, Li-li; Cai, Xue-ding; Lai, Xi-xi; Lin, Guan-yang; Hu, Lu-feng; Zhang, Chun-hong; Xu, Zhi-sheng; Zhang, Xiu-hua
Voriconazole is a second generation triazole antifungal agent and the first choice therapy for invasive aspergillosis (IA). Although voriconazole may be associated with many adverse events, hyponatremia has been rarely reported which potentially could result in death. Therapeutic drug monitoring (TDM) and individualization of therapy by measuring voriconazole plasma concentrations improved the efficacy and safety in patients. We report the effect of TDM to adjust voriconazole dosage in a vori...
Aspergilloma of the brain: an overview
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Nadkarni T
Full Text Available Fungal infections of the central nervous system (CNS are almost always a clinical surprise. Their presentation is subtle, often without any diagnostic characteristics, and they are frequently mistaken for tuberculous meningitis, pyogenic abscess, or brain tumor. Granulocytopenia, cellular and humoral mediated immune dysfunction are predisposing factors to the development of CNS infections in immunosuppressed patients. Aspergillus fumigatus is the most common human pathogen in the genus Aspergillus .Maxillary sinusitis of dental origin or the lungs are the most common sites of primary Aspergillus infection. Infection reaches the brain directly from the nasal sinuses via vascular channels or is blood borne from the lungs and gastrointestinal tract. Single or multiple abscess formation with blood vessel invasion leading to thrombosis is a characteristic feature of Aspergillosis on neuropathologic examination. Aspergillosis should be considered in cases manifesting with acute onset of focal neurologic deficits resulting from a suspected vascular or space-occupying lesion especially in immunocompromised hosts. Aspergillosis is diagnosed on direct examinations and culture, however the diagnosis of aspergillosis of the CNS is difficult. Diagnosis of an intracranial mass lesion is best confirmed with a computed tomography or magnetic resonance imaging of the head with or without intravenous contrast. Aggressive neurosurgical intervention for surgical removal of Aspergillus abscesses, granulomas, and focally infracted brain; correction of underlying risk factors; Amphotericin B combined with flucytosine and treatment of the source of infection should form the mainstay of the management. Off late Liposomal Amphotericin B was found to be more effective and safe than conventional Amphotericin B in the management of Apergillus infections Only with a high index of suspicion, an aggressive approach to diagnosis, and rapid vigorous therapy may we hope to alter
Monitoramento sorológico com detecção de anticorpos para diagnóstico precoce da aspergilose em pinguins em cativeiro
Ângela L. Cabana; Xavier, Melissa O.; Vanice Poester; Gabriel B. Klafke; Pedro L. B.Filho; Aryse Martins; Rodolfo P. S.Filho; Meireles, Mário C. A.
Abstract: This study aimed to evaluate the efficacy of detection of anti-Aspergillus fumigatus antibodies in captive penguins by double radial agar gel immunodiffusion (AGID) for the aspergillosis diagnosis. We included 134 Magellanic penguins (Spheniscus magellanicus) in rehabilitation at the Center for Recovery of Marine Animals (CRAM / FURG). All of them were monitored by AGID weekly until its final destination (death or release), totalizing 660 serum samples studied. All animals were clin...
[Successful treatment of neuroaspergillosis in a patient with acute lymphoblastic leukemia: role of surgery, systemic antifungal therapy and intracavitary therapy].
Ozçelik, Tülay; Ozkalemkaş, Fahir; Kocaeli, Hasan; Altundal, Yildiz; Ener, Beyza; Ali, Ridvan; Ozkocaman, Vildan; Hakyemez, Bahattin; Tunali, Ahmet
Cerebral aspergillosis is a rare condition that generally exhibits a poor response to conventional antifungal drugs. We report here a case of cerebral aspergillosis in a 34-years-old man with acute lymphoblastic leukaemia who was successfully treated with a combination of aggressive neurosurgery, intracavitary instillation of amphotericin B and voriconazole. We aimed to emphazise the roles of surgery, intracavitary therapy and antifungal therapy in the management of neuroaspergillosis. Under amphotericin-B therapy, the patient developed dysarthria and paralysis of the right side of his body. Brain magnetic resonance imaging demonstrated a lesion in the left parieto-occipital region, measuring 7 cm in the greatest dimension. Diagnostic surgery was interrupted due to abundant bleeding. The culture of the aspirate from the lesion yielded Aspergillus flavus. The therapy was switched to voriconazole and caspofungin combination. Due to disease progression during combination therapy, the patient had a second surgical resection resulting in a 75% reduction in lesion size. Following surgical intervention, intracavitary instillation of amphotericin B (0.3 mg/day for 15 days) was performed alongside with combination therapy (voriconazole and caspofungin). Caspofungin was stopped after 42 days, whereas the patient was continued on voriconazole for a total of 100 days. At this point, his brain lesion resolved almost completely. However, leukemia relapsed. The patient died during his treatment course because of neutropenic typhilitis occurring in the aplastic phase. It is stated that in patients with neuroaspergillosis radical neurosurgery leads to better outcomes if performed at an earlier stage. Antifungal treatment of cerebral aspergillosis requires that the drug must cross the blood brain barrier. Voriconazole has the ability to cross the blood brain barrier. The therapy should be prolonged beyond the resolution of all lesions and until reversal of the underlying
Nosocomial Fungal Infections: Epidemiology, Infection Control, and Prevention.
Suleyman, Geehan; Alangaden, George J
Invasive fungal infections are an important cause of morbidity and mortality in hospitalized patients and in the immunocompromised population. This article reviews the current epidemiology of nosocomial fungal infections in adult patients, with an emphasis on invasive candidiasis and aspergillosis. Recently published recommendations and guidelines for the control and prevention of these nosocomial fungal infections are summarized in this article. Copyright © 2016 Elsevier Inc. All rights reserved.
Prevalence and mechanism of triazole resistance in Aspergillus fumigatus in a referral chest hospital in Delhi, India and an update of the situation in Asia
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Anuradha eChowdhary
Full Text Available Aspergillus fumigatus causes varied clinical syndromes ranging from colonization to deep infections. The mainstay of therapy of Aspergillus diseases is triazoles but several studies globally highlighted variable prevalence of triazole resistance, which hampers the management of aspergillosis. We studied the prevalence of resistance in clinical A. fumigatus isolates during 4 years in a referral Chest Hospital in Delhi, India and reviewed the scenario in Asia and the Middle East. Aspergillus species (n=2117 were screened with selective plates for azole resistance. The isolates included 45.4% A. flavus, followed by 32.4% A. fumigatus, 15.6% Aspergillus species and 6.6% A. terreus. Azole resistance was found in only 12 (1.7% A. fumigatus isolates.These triazole resistant A. fumigatus (TRAF isolates were subjected to (a calmodulin and β tubulin gene sequencing (b in vitro antifungal susceptibility testing against triazoles using CLSI M38-A2 (c sequencing of cyp51A gene and real-time PCR assay for detection of mutations and (d microsatellite typing of the resistant isolates. TRAF harbored TR34/L98H mutation in 10 (83.3% isolates with a pan-azole resistant phenotype. Among the remaining 2 TRAF isolates, one had G54E and the other had three non-synonymous point mutations. The majority of patients were diagnosed as invasive aspergillosis followed by allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. The Indian TR34/L98H isolates had a unique genotype and were distinct from the Chinese, Middle East and European TR34/L98H strains. This resistance mechanism has been linked to the use of fungicide azoles in agricultural practices in Europe as it has been mainly reported from azole naïve patients. Reports published from Asia demonstrate the same environmental resistance mechanism in A. fumigatus isolates from two highly populated countries in Asia i.e., China and India and also from the neighboring Middle East.
The impact of weakly bound 89Zr on preclinical studies: Non-specific accumulation in solid tumors and aspergillus infection
DEFF Research Database (Denmark)
Severin, Gregory; Jørgensen, Jesper T.; Wiehr, Stefan
-mediated accumulation of certain species. In the aspergillosis model, the concentration of 89Zr in lung tissue of the naïve animals was 6.0 ± 1.1 %ID/g. This was significantly different from that of the animals with advanced disease, showing 11.6% ± 1.8 %ID/g. Conclusions Given the high levels of 89Zr accumulation...
Etude de la diversité génétique d'Aspergillus fumigatus et de Chlamydophila psittaci chez les oiseaux et mise au point de modèles expérimentaux aviaires
Thierry, Simon
The filamentous fungus Aspergillus fumigatus and the bacteria Chlamydophila psittaci are two major pathogens in poultry. Although phylogenetically distant, these two microorganisms share the same aerial transmission. Mortality and morbidity associated to aspergillosis and chlamydiosis are responsible for economic losses, in particular in turkey farms. In France, investigations on human cases of chlamydiosis frequently reveal a link with duck farms. The bacteria C. psittaci is carried in the g...
Density and Molecular Epidemiology of Aspergillus in Air and Relationship to Outbreaks of Aspergillus Infection
Leenders, Alexander C. A. P.; van Belkum, Alex; Behrendt, Myra; Luijendijk, Ad; Verbrugh, Henri A.
After five patients were diagnosed with nosocomial invasive aspergillosis caused by Aspergillus fumigatus and A. flavus, a 14-month surveillance program for pathogenic and nonpathogenic fungal conidia in the air within and outside the University Hospital in Rotterdam (The Netherlands) was begun. A. fumigatus isolates obtained from the Department of Hematology were studied for genetic relatedness by randomly amplified polymorphic DNA (RAPD) analysis. This was repeated with A. fumigatus isolates contaminating culture media in the microbiology laboratory. The density of the conidia of nonpathogenic fungi in the outside air showed a seasonal variation: higher densities were measured during the summer, while lower densities were determined during the fall and winter. Hardly any variation was found in the numbers of Aspergillus conidia. We found decreasing numbers of conidia when comparing air from outside the hospital to that inside the hospital and when comparing open areas within the hospital to the closed department of hematology. The increase in the number of patients with invasive aspergillosis could not be explained by an increase in the number of Aspergillus conidia in the outside air. The short-term presence of A. flavus can only be explained by the presence of a point source, which was probably patient related. Genotyping A. fumigatus isolates from the department of hematology showed that clonally related isolates were persistently present for more than 1 year. Clinical isolates of A. fumigatus obtained during the outbreak period were different from these persistent clones. A. fumigatus isolates contaminating culture media were all genotypically identical, indicating a causative point source. Knowledge of the epidemiology of Aspergillus species is necessary for the development of strategies to prevent invasive aspergillosis. RAPD fingerprinting of Aspergillus isolates can help to determine the cause of an outbreak of invasive aspergillosis. PMID:10325319
Aspergillus vaccines: Hardly worth studying or worthy of hard study?
Levitz, Stuart M
Vaccines rank among the greatest advances in the history of public health. Yet, despite the need, there are no licensed vaccines to protect humans against fungal diseases, including aspergillosis. In this focused review, some of the major scientific and logistical challenges to developing vaccines to protect at-risk individuals against aspergillosis are discussed. Approaches that have shown promise in animal models include vaccines that protect against multiple fungal genera and those that are specifically directed to Aspergillus Advances in proteomics and glycomics have facilitated identification of candidate antigens for use in subunit vaccines. Novel adjuvants and delivery systems are becoming available that can skew vaccine responses toward those associated with protection. Immunotherapy consisting of adoptive transfer of Aspergillus-specific T cells to allogeneic hematopoietic transplant recipients has advanced to human testing but is technically difficult and of unproven benefit. While progress has been impressive, much work still needs to be done if vaccines against aspergillosis are to become a reality. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: email@example.com.
British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases.
Schelenz, Silke; Barnes, Rosemary A; Barton, Richard C; Cleverley, Joanne R; Lucas, Sebastian B; Kibbler, Christopher C; Denning, David W
Invasive fungal diseases are an important cause of morbidity and mortality in a wide range of patients, and early diagnosis and management are a challenge. We therefore did a review of the scientific literature to generate a series of key recommendations for the appropriate use of microbiological, histological, and radiological diagnostic methods for diagnosis of invasive fungal diseases. The recommendations emphasise the role of microscopy in rapid diagnosis and identification of clinically significant isolates to species level, and the need for susceptibility testing of all Aspergillus spp, if treatment is to be given. In this Review, we provide information to improve understanding of the importance of antigen detection for cryptococcal disease and invasive aspergillosis, the use of molecular (PCR) diagnostics for aspergillosis, and the crucial role of antibody detection for chronic and allergic aspergillosis. Furthermore, we consider the importance of histopathology reporting with a panel of special stains, and emphasise the need for urgent (<48 hours) and optimised imaging for patients with suspected invasive fungal infection. All 43 recommendations are auditable and should be used to ensure best diagnostic practice and improved outcomes for patients. Copyright © 2015 Elsevier Ltd. All rights reserved.
Plasma Concentrations of Itraconazole, Voriconazole, and Terbinafine When Delivered by an Impregnated, Subcutaneous Implant in Japanese Quail ( Coturnix japonica ).
Souza, Marcy J; Redig, Patrick; Cox, Sherry K
Aspergillosis is a common fungal infection in both wild and pet birds. Although effective antifungal medications are available, treatment of aspergillosis can require months of medication administration, which entails stressful handling one or more times per day. This study examined the delivery of the antifungal drugs itraconazole, voriconazole, and terbinafine to Japanese quail ( Coturnix japonica ) via an impregnated implant. Implants contained 0.5, 3, 8, or 24 mg of itraconazole, voriconazole, or terbinafine. The implants were administered subcutaneously over the dorsum and between the scapulae. Blood was collected from birds before and 2, 7, 21, 42, and 56 days after implant placement. Plasma was analyzed by high-performance liquid chromatography for concentrations of itraconazole, voriconazole, or terbinafine, as appropriate. During the course of the study, targeted terbinafine concentrations were achieved in some birds at various time points, but concentrations were inconsistent. Itraconazole and voriconazole concentrations were also inconsistent and did not reach targeted concentrations. Currently, the implant examined in this study cannot be recommended for treatment of aspergillosis in avian species.
Molecular Tools for the Detection and Deduction of Azole Antifungal Drug Resistance Phenotypes in Aspergillus Species.
Dudakova, Anna; Spiess, Birgit; Tangwattanachuleeporn, Marut; Sasse, Christoph; Buchheidt, Dieter; Weig, Michael; Groß, Uwe; Bader, Oliver
The incidence of azole resistance in Aspergillus species has increased over the past years, most importantly for Aspergillus fumigatus. This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients. Management options for invasive aspergillosis caused by azole-resistant A. fumigatus strains were recently reevaluated by an international expert panel, which concluded that drug resistance testing of cultured isolates is highly indicated when antifungal therapy is intended. In geographical regions with a high environmental prevalence of azole-resistant strains, initial therapy should be guided by such analyses. More environmental and clinical screening studies are therefore needed to generate the local epidemiologic data if such measures are to be implemented on a sound basis. Here we propose a first workflow for evaluating isolates from screening studies, and we compile the MIC values correlating with individual amino acid substitutions in the products of cyp51 genes for interpretation of DNA sequencing data, especially in the absence of cultured isolates. Copyright © 2017 American Society for Microbiology.
Molecular sub-typing suggests that the environment of rehabilitation centers may be a potential source of Aspergillus fumigatus infecting rehabilitating seabirds.
Burco, Julia D; Etienne, Kizee A; Massey, J Gregory; Ziccardi, Michael H; Balajee, S Arunmozhi
Aspergillosis remains a major cause of infection-related avian mortality in birds that are debilitated and undergoing rehabilitation for release into the wild. This study was designed to understand the source of avian aspergillosis in seabirds undergoing rehabilitation at selected northern California aquatic bird rehabilitation centers. Air, surface and water sampling was performed between August 2007 and July 2008 in three such centers and selected natural seabird loafing sites. Average air Aspergillus fumigatus counts were at least nine times higher in samples obtained from the rehabilitation sites (M = 7.34, SD = 9.78 CFU/m(3)), when compared to those found at natural sites (M = 0.76, SD = 2.24 CFU/m(3)), t (205) = -5.99, P birds with confirmed aspergillosis and 42 isolates from environmental samples were identified using both morphological and molecular methods, and subsequently sub-typed using an eight-locus microsatellite panel with the neighbor joining algorithm. Results of the study demonstrated the presence of five clonal groups, 13 genotypically related clusters, and 59 distinct genotypes. Six of the 13 genotypically related clusters contained matching genotypes between clinical isolates and local environmental isolates from the rehabilitation center in which these birds were housed. We present evidence that the environment of rehabilitation centers may be a source for A. fumigatus infection in rehabilitated seabirds.
The burden of fungal disease in Denmark.
Mortensen, Klaus L; Denning, David W; Arendrup, Maiken C
The aim of this study is to calculate the burden of fungal disease in Denmark. We identified all published epidemiology papers reporting fungal infection rates in Denmark. Where no data existed, we used numbers of specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence. Approximately, one in six Danes will suffer from a fungal infection each year, most of which are skin or mucosal diseases causing disability but no deaths. Good data exist on candidaemia where a national voluntary reporting system is in place and have shown a high rate (9.6 per 100,000 inhabitants) compared other European countries. We present estimates of invasive aspergillosis and chronic pulmonary aspergillosis with rates of 4.4 per 100,000 and 3.1 per 100,000 inhabitants, respectively. Further studies are needed in order to better ascertain high-burden fungal infections such as recurrent vulvovaginal candidiasis (~1350 cases in 100,000 women) as well as allergic bronchopulmonary aspergillosis (~131 cases in 100,000 inhabitants) and severe asthma with fungal sensitisation (cases in 100,000 inhabitants). In conclusion, more than 93,000 Danes or about 2% of Denmark's population will have a non-trivial fungal infection during 1 year, which underscores the magnitude of the fungal burden. © 2015 Blackwell Verlag GmbH.
Burden of serious fungal infections in Belgium.
Lagrou, Katrien; Maertens, Johan; Van Even, Ellen; Denning, David W
We aimed to estimate the total number of serious fungal infections occurring yearly in Belgium. The number of cryptococcal infections was retrieved from the National Reference Center for Mycosis. Populations at risk and fungal infections frequencies in these populations were used to estimate incidence or prevalence of other fungal infections. The Belgian population consists of 11.10 million people. Cryptococcal meningitis is rare. In all, 15 of the 1227 newly diagnosed HIV/AIDS cases presented with Pneumocystis jirovecii pneumonia. This accounts for ±14% of total PCP cases (n = 120). The incidence of candidaemia is estimated as 5/100,000 resulting in 555 cases and 213 deaths. A total number of 675 invasive aspergillosis cases and ≥169 deaths attributed to this infection were calculated. Chronic pulmonary aspergillosis is estimated to be prevalent in 662 cases. Allergic bronchopulmonary aspergillosis cases were estimated to be 23,119 applying a 2.5% and 15% rate in adult asthma and cystic fibrosis patients respectively. Severe asthma with fungal sensitisation cases was estimated to be 30,402. There were 174,760 women with recurrent Candida vaginitis assuming a 6% rate in women aged between 15 and 50. Approximately 233,000 people of the Belgian population (2.1%) are estimated to suffer from a fungal infection on a yearly basis. © 2015 Blackwell Verlag GmbH.
Burden of serious fungal infections in Bangladesh.
Gugnani, H C; Denning, D W; Rahim, R; Sadat, A; Belal, M; Mahbub, M S
In Bangladesh there are several published papers on superficial mycoses. Deep mycoses are also recognized as an important emerging problem. Here, we estimate the annual incidence and prevalence of serious fungal infections in Bangladesh. Demographic data were obtained from world population reports and the data on TB and HIV extracted from the online publications on tuberculosis in Bangladesh and Asia Pacific research statistical data information resources AIDS Data HUB. All the published papers on fungal infections in Bangladesh were identified through extensive search of literature. We estimated the number of affected people from populations at risk and local epidemiological data. Bangladesh has a population of ∼162.6 million, 31% children and only 6% over the age of 60 years. The pulmonary TB caseload reported in 2014 was 119,520, and we estimate a prevalence of 30,178 people with chronic pulmonary aspergillosis, 80% attributable to TB. An anticipated 90,262 and 119,146 patients have allergic bronchopulmonary aspergillosis or severe asthma with fungal sensitization. Only 8,000 people are estimated to be HIV-infected, of whom 2900 are not on ART with a CD4 count Bangladesh. Candida bloodstream infection was estimated based on a 5 per 100,000 rate (8100 cases) and invasive aspergillosis based primarily on leukemia and COPD rates, at 5166 cases. Histoplasmosis was documented in 16 cases mostly with disseminated disease and presumed in 21 with HIV infection. This study constitutes the first attempt to estimate the burden of several types of serious fungal infections in Bangladesh.
A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions
Shimizu, Kiminori; Paul, Sanjoy; Ohba, Ayumi; Gonoi, Tohru; Watanabe, Akira; Gomi, Katsuya
Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E), deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A) and putative drug efflux pump (Cdr1B). PMID:28052140
Serious fungal infections in Chile.
Alvarez Duarte, E; Denning, D W
The incidence and prevalence of fungal infections in Chile are unknown. Here, we have estimated the burden of serious fungal diseases from data obtained from clinical reports, WHO reports, Chilean census, OECD reports and comprehensive literature search available on PubMed and SciELO, among other scientific resources. Due the lack of official data about fungal diseases, frequencies were calculated based on the specific populations at risk. Recurrent vulvovaginal candidiasis (>4 episodes/year) is estimated to occur in 3108/100,000. Using a low international average rate of 5/100,000, we estimate 878 candidaemia cases and 132 patients with intra-abdominal candidiasis. Due to the low incidence of pulmonary tuberculosis (TB) in Chile, limited numbers of patients with chronic pulmonary aspergillosis are likely: a total of 1212, 25% following TB. Invasive aspergillosis is estimated to affect 296 patients following leukaemia therapy, transplantation and chronic obstructive pulmonary disease (COPD), 1.7/100,000. In addition, allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) were estimated to be around 97.9/100,000 and 127/100,000 respectively, in 675,772 adult asthmatics and 1700 CF patients. Given a 38,000 human immunodeficiency virus (HIV) population, with around 2189 new cases of acquired immune deficiency syndrome (AIDS) annually, cryptococcal meningitis and Pneumocystis pneumonia are estimated at 0.12/100,000 and 4.3/100,000, respectively. In total, 325,000 (1.9%) people in Chile develop serious fungal infections annually. Respiratory fungal disease predominates in Chile; a national action plan for fungal disease is urgently needed, including epidemiological studies to validate the estimates.
Burden of serious fungal infections in Ukraine.
Osmanov, Ali; Denning, David W
Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually. © 2015 Blackwell Verlag GmbH.
Mesenchymal stem cells transplantation in hematological patients with acute graft-versus-host disease: characteristics and risk factors for infectious complications.
Stoma, Igor; Karpov, Igor; Krivenko, Svetlana; Iskrov, Igor; Milanovich, Natalia; Koritko, Alla; Uss, Anatoly
The role of MSCs in infection prevention and treatment is still discussed in transplant and hematological patients. The spectrum and risk factors for infections after MSCs transplantation in patients with acute GVHD have not been studied before. To determine the risk factors and spectrum of infectious complications in patients received mesenchymal stem cell transplantation as a treatment for acute GVHD. A prospective observational study was performed to evaluate the risk factors and characteristics of infectious complications after MSCs transplantation in adult patients having acute GVHD. Thirty-four episodes of MSCs transplantation in patients with acute GVHD after allogeneic HSCT were enrolled in the study. MSCs were given at a median dose of 1.32 (interquartile range 0.87-2.16) mln cells/kg per infusion at 91 days (interquartile range 31-131 days) after HSCT. Data relating to age, gender, date, and type of transplantation, characteristics of MSCs, infectious agents, and antimicrobial therapy and prevention regimens were prospectively collected in all of the enrolled patients. The episode of proven infectious complication was set as a primary outcome. There were totally 68 patients with acute GVHD in the study; among them there were 34 cases of MSCs transplantation performed. Among the registered infectious episodes were viral infections (CMV-associated disease, EBV-associated disease), invasive pulmonary aspergillosis, bacterial bloodstream infections, and pneumonia. MSCs transplantation has shown no statistically significant association with risk of infectious complications in patients with acute GVHD in a performed multivariate analysis. Among the most frequent infections in acute GVHD, we have described CMV, invasive aspergillosis, and bacterial infections (bloodstream infections or pneumonia). Among risk factors for infectious complications in patients with acute GVHD with/without MSCs transplantation are progression of main disease and neutropenia below
A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions.
Directory of Open Access Journals (Sweden)
Daisuke Hagiwara
Full Text Available Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E, deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A and putative drug efflux pump (Cdr1B.
Serious fungal infections in Ecuador.
Zurita, J; Denning, D W; Paz-Y-Miño, A; Solís, M B; Arias, L M
There is a dearth of data from Ecuador on the burden of life-threatening fungal disease entities; therefore, we estimated the burden of serious fungal infections in Ecuador based on the populations at risk and available epidemiological databases and publications. A full literature search was done to identify all epidemiology papers reporting fungal infection rates. WHO, ONU-AIDS, Index Mundi, Global Asthma Report, Globocan, and national data [Instituto Nacional de Estadística y Censos (INEC), Ministerio de Salud Pública (MSP), Sociedad de Lucha Contra el Cáncer (SOLCA), Instituto Nacional de Donación y Trasplante de Órganos, Tejidos y Células (INDOT)] were reviewed. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Ecuador has a variety of climates from the cold of the Andes through temperate to humid hot weather at the coast and in the Amazon basin. Ecuador has a population of 15,223,680 people and an average life expectancy of 76 years. The median estimate of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) population at risk for fungal disease (<200 CD4 cell counts) is ∼10,000, with a rate of 11.1% (1100) of histoplasma, 7% (700) of cryptococcal meningitis, and 11% (1070) of Pneumocystis pneumonia. The burden of candidemia is 1037. Recurrent Candida vaginitis (≥4 episodes per year) affects 307,593 women aged 15-50 years. Chronic pulmonary aspergillosis probably affects ∼476 patients following tuberculosis (TB). Invasive aspergillosis is estimated to affect 748 patients (∼5.5/100,000). In addition, allergic bronchopulmonary aspergillosis (ABPA) in asthma and severe asthma with fungal sensitization (SAFS) were estimated to affect 26,642 and 45,013 people, respectively. Our estimates indicate that 433,856 (3%) of the population in Ecuador is affected by serious fungal infection.
Multifocal periostitis as a complication of chronic use of voriconazole in a lung transplant recipient.
Tedja, R; El-Sherief, A; Olbrych, T; Gordon, S
Fungal infections are common in solid organ transplantation. An increasing number of transplant recipients receive antifungal therapy for prolonged duration owing to invasive fungal infections. Herein, we describe a diagnosis of periostitis as a complication of chronic use of voriconazole in a lung transplant recipient. The patient was diagnosed with probable pulmonary aspergillosis and was treated with oral voriconazole for a total of 9 months. Evidence of multifocal periostitis was observed in the axial and appendicular skeleton. Early recognition of this phenomenon is important to prevent unnecessary tests and procedures. Prompt discontinuation of voriconazole should result in improvement of symptoms. © 2013 John Wiley & Sons A/S.
An unusual cause of hoarseness of voice in an immunocompetent individual
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Soumen Chatterjee
Full Text Available A 43-year-old female patient presented with the complaints of progressive hoarseness of voice for 6 months. There was no apparent evidence of immunodeficiency, abuse of voice, systemic infection, or trauma. Fiberoptic laryngoscopy revealed whitish plaques mimicking leukoplakia that involved both the vocal cords. Investigations ruled out malignancy and confirmed primary vocal cord aspergillosis. The lesions responded dramatically to oral antifungal drugs. High index of suspicion and micropathological awareness regarding such an entity are of utmost importance since the management depends on accurate diagnosis and timely introduction of proper antifungal therapy.
Aspergilloma of Infra Orbital Nerve in an Immunocompetent Female: A Case Report
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Pradeep A. V
Full Text Available Aspergilloma of the paranasal sinus is a non-invasive form of aspergillosis. We report a 50 year old female with chief complaints of swelling in left infra orbital area without involving maxillary sinus. Computed tomography revealed enlarged infraorbital nerve foramen with clear left maxillary sinus. Microscopy of the excised mass showed, numerous fungal hyphae, which branch at acute angle consistent with features of aspergilloma. Early diagnosis and treatment is important in aspergilloma. Since the symptom is usually nonspecific, radiographic study is nonspecific; excision biopsy should be performed for all cases.
PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant.
Wójtowicz, Agnieszka; Lecompte, T Doco; Bibert, Stephanie; Manuel, Oriol; Rüeger, Sina; Berger, Christoph; Boggian, Katia; Cusini, Alexia; Garzoni, Christian; Hirsch, Hans; Khanna, Nina; Mueller, Nicolas J; Meylan, Pascal R; Pascual, Manuel; van Delden, Christian; Bochud, Pierre-Yves
Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: email@example.com.
Aspergillus infection in pulmonary cavitating lesions with right atrial myxoma.
Sharma, Divyesh; Dorgan, Eileen; Douglas, Hannah; Trouton, Tom; McMullan, Ronan; Parissis, Haralabos
Cardiac myxomas are rare primary tumors with varied clinical presentations that may pose a diagnostic challenge. Here, we describe the case of a 21-year-old man with multiple cavitating lung lesions with aspergillosis and underlying right atrial myxoma, who presented with hemoptysis and weight loss. He was successfully treated with right atrial myxoma resection and antifungal agents, with no recurrence or complications after one year of follow-up. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Differential diagnosis of infections in a patient with Chronic Obstructive Pulmonary Disease
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Paolo Ghiringhelli
Full Text Available We describe a case of a 65-years-old patient with Chronic Obstructive Pulmonary Disease (COPD, receiving oxygen therapy and resistant to antibiotic therapy. He was admitted with high fever, productive cough, marked leukocytosis, and chest X-ray findings of infiltration and fluid levels within lung cysts. A differential diagnosis was essential to start an adequate treatment and avoid the rapid worsening of patients respiratory status. In patients with chronic pulmonary diseases under immunotherapy, micotic infections should be considered. Aspergillus fumigatus was cultured from bronchial washing fluid and we diagnosed chronic necrotizing pulmonary aspergillosis (CNPA. Oral itraconazole was started and his symptoms and laboratory data markedly improved.
Cerebralt aspergillom hos patient med immundefekt og follikulært lymfom
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Lorentzen, Kristian; Talibi, Monica Nicole; Hansen, Per Boye
We present a case of central nervous system aspergillosis in an immunocompromised 69-year-old male with a history of chemotherapeutic treatment for follicular lymphoma. The patient presented with aphasia, apraxia and confusion. An MRI of the central nervous system and Aspergillus antigen in the s...... in the spinal fluid was suggestive for this invasive fungal infection. Despite treatment with voriconazole the patient succumbed to the infection. A rise in rare, severe infectious complications as presented is expected due to increasing dose-intensity of chemotherapy....
Rhino-oculo-cerebral aspergillus and mucor co-infections in an immunocompromised patient with type 2 diabetes mellitus
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Kalidas Rit
Full Text Available Mucormycosis are pathogenic moulds of the mucorales species usually occurring in immunocompromised patients or in patients with uncontrolled diabetes mellitus. Aspergillosis is the clinical condition caused by Aspergillus species and may cause an invasive disease with high case fatality rate, especially in immunosuppressed patients. A 46-year-old male patient with Type 2 diabetes mellitus with underlying malignancy presented with proptosis of left eye. Combined infections of Mucor and Aspergillus were diagnosed by means of computed tomography (CT scan and biopsy. Treatment with Amphotericin B and Voriconazole was started, the patient died within 3 months, from multi-organ failure.
Somatostatin analogue scintigraphy in granulomatous diseases
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Vanhagen, P.M. (Dept. of Internal Medicine 3, Dijkzigt Univ. Hospital, Rotterdam (Netherlands) Dept. of Immunology, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Krenning, E.P. (Dept. of Internal Medicine 3, Dijkzigt Univ. Hospital, Rotterdam (Netherlands) Dept. of Nuclear Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Reubi, J.C. (Inst. of Pathology, Bern Univ. (Switzerland)); Kwekkeboom, D.J. (Dept. of Nuclear Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Bakker, W.H. (Dept. of Nuclear Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Mulder, A.H. (Dept. of Pathology, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Laissue, I. (Inst. of Pathology, Bern Univ. (Switzerland)); Hoogstede, H.C. (Dept. of Chest Medicine, Dijkzigt Univ. Hospital, Rotterdam (Netherlands)); Lamberts, S.W.J. (Dept. of Internal Medicine 3, Dijkzigt Univ. Hospital, Rotterdam (Netherlands))
In the present study 20 consecutive patients were investigated, 12 with sarcoidosis, one with both sarcoidosis and aspergillosis, four with tuberculosis and three with Wegener's granulomatosis. For in vivo SS-R imaging, total-body scintigraphy was performed 24 and 48 h after the administration of [sup 111]In-octreotide. Granuloma localizations could be visualized in all patients studied; additional sites were found in nine patients with sarcoidosis and in two patients with tuberculosis. In vitro autoradiography of fresh tissue biopsies, using the SS analogue [[sup 125]I-Tyr[sup 3
Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic arteritis
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Weigel, S.; Kloska, S.; Freund, M. [Dept. of Clinical Radiology, Univ. Hospital of Muenster, Muenster (Germany); Kehl, H.G. [Dept. of Pediatric Cardiology, Univ. Hospital of Muenster, Muenster (Germany)
A subarachnoid haemorrhage (SAH) occurred 67 days after cardiac transplantation in 10-year-old girl with consecutive immunocompromising therapy. Neither digital subtraction angiography (DSA) nor computed tomographic angiography showed signs of intracranial vascular malformations. One month before the lethal SAH occurred, she had developed arterial hypertension and attacks of severe headache with cerebrospinal fluid (CSF) pleocytosis while CT scans showed an infarct of the left thalamus. Pathologic findings established the rare diagnosis of SAH due to aspergillosis-related mycotic arteritis. Imaging characteristics are presented. (orig.)
Chronic Invasive Aspergillus Sinusitis and Otitis with Meningeal Extension Successfully Treated with Voriconazole.
Morgand, Marjolaine; Rammaert, Blandine; Poirée, Sylvain; Bougnoux, Marie-Elisabeth; Tran, Hugo; Kania, Romain; Chrétien, Fabrice; Jouvion, Gregory; Lortholary, Olivier
Invasive aspergillosis (IA) is a severe disseminated fungal disease that occurs mostly in immunocompromised patients. However, central nervous system IA, combining meningitis and skull base involvement, does not occur only in groups with classic risk factors for IA; patients with chronic renal failure and diabetes mellitus are also at risk for more chronic forms. In both of our proven IA cases, voriconazole monotherapy was effective without surgery, and cerebrospinal fluid and serum 1,3-β-d-glucan test results were initially positive, in contrast to galactomannan antigen results. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Single Nodula opacity of granulomatous Pneumocystis jirovecii pneumoniain an asymptomatic lymphoma patient
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Kim, Hyun Soo; Shin, Kyung Eun; Lee, Ju Hie [Kyung Hee University Hospital, Seoul (Korea, Republic of)
The radiologic findings of a single nodule from Pneumocystis jirovecii pneumonia (PJP) have been rarely reported. We described a case of granulomatous PJP manifesting as a solitary pulmonary nodule with a halo sign in a 69-year-old woman with diffuse large B cell lymphoma during chemotherapy. The radiologic appearance of the patient suggested an infectious lesion such as angioinvasive pulmonary aspergillosis or lymphoma involvement of the lung; however, clinical manifestations were not compatible with the diseases. The nodule was confirmed as granulomatous PJP by video-assisted thoracoscopic surgery biopsy.
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Bhattacharya M
Full Text Available Posaconazole is a novel second-generation Triazole oral antifungal agent. It is highly effective in the prophylaxis of invasive fungal infections in immunocompromised patients. It is used as a first-line agent as well as for salvage therapy in invasive fungal infections including aspergillosis, oropharyngeal and esophageal candidiasis. It has a good adverse effect profile. With the rising incidence of invasive fungal infections due to the HIV pandemic and medical advancements in transplantation and cancer therapy, these features make posaconazole a valuable addition in the family of antifungal agents.
An intracranial aspergilloma with low signal on T2-weighted images corresponding to iron accumulation
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Yamada, K. [Dept. of Radiology, Kyoto Prefectural Univ. of Medicine (Japan); Dept. of Radiology, Univ. of Maryland Medical Center, Baltimore MD (United States); Zoarski, G.H.; Rothman, M.I.; Zagardo, M.T. [Dept. of Radiology, Univ. of Maryland Medical Center, Baltimore MD (United States); Nishimura, T. [Dept. of Radiology, Kyoto Prefectural Univ. of Medicine (Japan); Sun, C.C.J. [Dept. of Pathology, Univ. of Maryland Medical Center, Baltimore MD (United States)
We present a case of cerebral aspergillosis in an immunocompetent patient. The MRI signal characteristics were compared with the histologic findings. Irregular low-signal zones were demonstrated between the wall of the abscess and the central necrosis on T2-weighted images; the pathology specimen revealed concentrated iron in these transitional zones but no hemosiderin. Iron is an essential element for the growth of fungal hyphae. The low-signal zones may represent the areas where there was active proliferation of aspergillus, and the unique location of the low signal may be a helpful imaging characteristic for the diagnosis of an aspergillus abscess. (orig.)
[Cutaneous manifestations of systemic mycoses].
Matsumoto, Tadahiko; Nishimoto, Katsutaro
The systemic mycoses are increasing in importance as opportunistic infections. Cutaneous lesions resulting from systemic mycoses may first alert clinicians to the presence of a life-threatening disorder, or even the presence of an unsuspected immunodeficiency state. Skin involvement is generally uncommon in disseminated aspergillosis, zygomycosis but is more common in systemic candidiasis (candidemia) and cryptococcosis. The blanket terms, hyalohyphomycosis and phaeohyphomycosis, cover the infections caused by diverse fungal opportunists. A variety of manifestations of skin lesions of the systemic mycoses are reviewed. These specific and/or non-specific lesions require early recognition, diagnosis, and aggressive antifungal treatment.
Giant Rhinolith: A Case Report
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Ji-Chang Hsiao
Full Text Available A rhinolith is a stone that forms in the nose. It occurs as a result of the solidification of mucus and nasal debris by mineral salts, calcium, magnesium phosphate and carbonate. It can be seen on radiographs as a radiopaque object in the nasal fossa and may be confused with several pathologic entities that will call for more invasive surgical procedures. We present the first case of a giant rhinolith, possibly arising from aspergillosis, and discuss its clinical and radiologic features.
Zygomycosis Associated with HIV Infection and Liver Transplantation
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Larry Nichols
Full Text Available Zygomycosis is an increasing threat to patients with human immunodeficiency virus (HIV infection. Zygomycosis (formerly called mucormycosis is the fungal infection with Mucor, Rhizopus, or other species that share a common morphology of large empty pauciseptate hyphae with rare random-angle branching and a collapsed "twisted ribbon" appearance. Morphology allows a specific diagnosis on frozen section or smear prior to growth and identification of the fungi in culture which makes it improtant because treatment is different than that for more common mycoses such as candidiasis and aspergillosis. We present an informative and illustrative case of zygomycosis in a patient with HIV infection and liver transplantation.
Proposed national strategies for the prevention of leading work-related diseases and injuries. Part 1
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Preliminary strategies developed at the National Symposium on the Prevention of Leading Work Related Diseases and Injuries, held in Atlanta, Georgia on May 1 to 3, 1985 were revised, elaborated, and further developed. Strategies were developed for the prevention of occupational lung diseases, musculoskeletal injuries, occupational cancers, severe occupational traumatic injuries, and occupational cardiovascular diseases. Lung diseases considered included silicosis, asbestosis, lung cancer mesothelioma, coal workers' pneumoconiosis, byssinosis, occupational asthma, hypersensitivity pneumonitis, asphyxiation, irritation, pulmonary edema, brucellosis, psitticosis, anthrax, mycobacterioses, histoplasmosis, aspergillosis, and coccidioidomycosis. Occupational cancers were discussed as they occur in the lung, pleura, peritoneum, bladder, kidneys, blood, nasal cavity, skin, nasal sinuses, and liver.
Mold and human health: separating the wheat from the chaff.
Pettigrew, H David; Selmi, Carlo F; Teuber, Suzanne S; Gershwin, M Eric
The term "mold" is utilized to define the ubiquitous fungal species commonly found in household dust and observed as visible multicellular filaments. Several well-defined human diseases are known to be caused or exacerbated by mold or by exposure to their byproducts. Among these, a solid connection has been established with infections, allergic bronchopulmonary aspergillosis, allergic fungal rhinosinusitis, hypersensitivity pneumonitis, and asthma. In the past decades, other less-defined and generally false conditions have also been ascribed to mold. We will herein review and critically discuss the available evidence on the influence of mold on human health.
[Iron and invasive fungal infection].
Álvarez, Florencio; Fernández-Ruiz, Mario; Aguado, José María
Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine -the first approved iron chelator- paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.
Stroke due to septic embolism resulting from Aspergillus aortitis in an immunocompetent patient.
Abenza-Abildua, M J; Fuentes-Gimeno, B; Morales-Bastos, C; Aguilar-Amat, M J; Martinez-Sanchez, P; Diez-Tejedor, E
Cerebral infarction secondary to Aspergillus arteritis or septic embolism is an exceptional finding. We present a case of multiple systemic embolism and cerebral infarction resulting from Aspergillus aortitis in an immunocompetent patient. A 65-year-old male with hypertension, hyperglycaemia and myocardial infarction with aorto-coronary by-pass surgery three years before admission, that suffered cerebral infarction in middle right cerebral artery territory and right cubital artery embolism. One month later he presented abrupt increase of his left hemiparesia and left central facial palsy associated with fever of unknown origin. Laboratory test, cranial CT and echocardiogram were performed. He died ten days later. Hemogram: leucocytes 34.700/microL (85% N, 4.8%L). Cranial CT: cerebral infarction in middle right cerebral artery territory. Transthoracic and transesophageal echocardiogram: moderate left ventricular hypertrophy and slight inferior hypokinesis. Arteriography: complete thrombosis of the left internal carotid. Necropsy: parietal aortic aspergillosis with generalized septic embolisms (brain, kidney, liver, fingers), cerebral infarction in middle right cerebral artery territory and thrombosis of the left carotid siphon with Aspergillus arteritis. Aspergillosis is an exceptional cause of cerebral infarction, especially in immunocompetent patients, and their diagnosis is complicated, being usually found at necropsy.
Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species
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Kim-Chung Lee
Full Text Available Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu–Glu–Leu–Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxybenzoic acid and (sulfooxybenzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxybenzoic acid possesses a structure similar to those of aspirin [2-(acetoxybenzoic acid] and salicylic acid (2-hydroxybenzoic acid. Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu–Glu–Leu–Glu, hydroxy-(sulfooxybenzoic acid and (sulfooxybenzoic acid are virulent factors of the pathogenic Aspergillus species.
Aspergillus fumigatus from normal and condemned carcasses with airsacculitis in commercial poultry
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Andréia Spanamberg
Full Text Available Carcass inspection is important for the detection of certain diseases and for monitoring their prevalence in slaughterhouses. The objective of this study was to assess the occurrence of aspergillosis caused by Aspergillus fumigatus in commercial poultry, through mycological and histopathological diagnosis, and to verify the causal association between the aspergillosis diagnosis criteria and condemnation due to airsacculitis in broilers through a case-control study. The study was carried out with 380 samples. Lungs were collected from broilers that were condemned (95 or not condemned (285 due to airsacculitis directly from the slaughter line. Forty-six (12% lung samples were positive for A. fumigatus in mycological culture. Among all samples, 177 (46.6% presented histopathological alterations, with necrotic, fibrinous, heterophilic pneumonia; heterophilic pneumonia and lymphoid hyperplasia being the most frequent. Out of the 380 lungs analyzed, 65.2% (30 showed histopathological alterations and isolation of fungi. The statistical analysis (McNemar's chi-square test indicated a significant association between the presence of histopathological lesions and the isolation of A. fumigatus. Mycological cultivation and histopathological diagnosis increase the probability of detecting pulmonary alterations in birds condemned by the Final Inspection System, which suggests that such diagnostic criteria can improve the assessment and condemnation of birds affected by airsacculitis.
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AnnaMaria Nosari
Full Text Available Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.
A controlled study to determine the efficacy of Loxostylis alata (Anacardiaceae in the treatment of aspergillus in a chicken (Gallus domesticus model in comparison to ketoconazole
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Suleiman Mohammed M
Full Text Available Abstract Background The poultry industry due to intensive methods of farming is burdened with losses from numerous infectious agents, of which one is the fungus Aspergillus fumigatus. In a preliminary study, the extracts of Loxostylis alata A. Spreng, ex Rchb. showed good activity in vitro against A. fumigatus with a minimum inhibitory concentration of 0.07 mg/ml. For this study crude, a crude acetone extract of L. alata leaves was evaluated for its acute toxicity in a healthy chicken model and for efficacy in an infectious model of aspergillosis (A. fumigatus. Results At a dose of 300 mg/kg, the extract induced some toxicity characterised by decreased feed intake and weight loss. Consequently, 100 and 200 mg/kg were used to ascertain efficacy in the infectious model. The plant extract significantly reduced clinical disease in comparison to the control in a dose dependant manner. The extract was as effective as the positive control ketoconazole dosed at 60 mg/kg. Conclusions The results indicate that a crude extract of L. alata leaves has potential as an antifungal agent to protect poultry against avian aspergillosis.
Overview of amphotericin B colloidal dispersion (amphocil).
Stevens, D A
Amphotericin B colloidal dispersion (ABCD) is an equimolar mixture of amphotericin B and cholesteryl sulphate with desirable preparation and stability characteristics. It allows the intravenous delivery of amphotericin B in doses up to 7 mg/kg daily. Peak serum concentrations of amphotericin B, given as ABCD, are lower, AUC0-infinity similar and half-life longer than deoxycholate amphotericin B. In vitro activity may be altered with respect to the deoxycholate preparation, some isolates being more resistant and others more susceptible. Preclinical toxicology with ABCD revealed a safety factor of five to 19-fold compared with deoxycholate amphotericin B. Animal models of coccidioidomycosis, disseminated cryptococcosis, candidiasis and invasive aspergillosis indicated a better therapeutic ratio, especially in cryptococcosis. Phase I/II studies in humans demonstrate efficacy against coccidioidomycosis, candidiasis and aspergillosis at doses from 1-7 mg/kg/day in at least 100 patients. Renal toxicity was acceptable but infusion-related side effects and anaemia were common. Side effects appear to decrease on therapy. Comparative studies with deoxycholate amphotericin B are needed.
The Crystal Structure of Peroxiredoxin Asp f3 Provides Mechanistic Insight into Oxidative Stress Resistance and Virulence of Aspergillus fumigatus.
Hillmann, Falk; Bagramyan, Karine; Straßburger, Maria; Heinekamp, Thorsten; Hong, Teresa B; Bzymek, Krzysztof P; Williams, John C; Brakhage, Axel A; Kalkum, Markus
Invasive aspergillosis and other fungal infections occur in immunocompromised individuals, including patients who received blood-building stem cell transplants, patients with chronic granulomatous disease (CGD), and others. Production of reactive oxygen species (ROS) by immune cells, which incidentally is defective in CGD patients, is considered to be a fundamental process in inflammation and antifungal immune response. Here we show that the peroxiredoxin Asp f3 of Aspergillus fumigatus inactivates ROS. We report the crystal structure and the catalytic mechanism of Asp f3, a two-cysteine type peroxiredoxin. The latter exhibits a thioredoxin fold and a homodimeric structure with two intermolecular disulfide bonds in its oxidized state. Replacement of the Asp f3 cysteines with serine residues retained its dimeric structure, but diminished Asp f3's peroxidase activity, and extended the alpha-helix with the former peroxidatic cysteine residue C61 by six residues. The asp f3 deletion mutant was sensitive to ROS, and this phenotype was rescued by ectopic expression of Asp f3. Furthermore, we showed that deletion of asp f3 rendered A. fumigatus avirulent in a mouse model of pulmonary aspergillosis. The conserved expression of Asp f3 homologs in medically relevant molds and yeasts prompts future evaluation of Asp f3 as a potential therapeutic target.
Neurologic Adverse Events Associated with Voriconazole Therapy: Report of Two Pediatric Cases
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Sevliya Öcal Demir
Full Text Available Although voriconazole, a triazole antifungal, is a safe drug, treatment with this agent is associated with certain adverse events such as hepatic, neurologic, and visual disturbances. The current report presents two cases, one a 9-year-old boy and the other a 17-year-old girl, who experienced neurologic side effects associated with voriconazole therapy. Our aim is to remind readers of the side effects of voriconazole therapy in order to prevent unnecessary investigations especially for psychological and ophthalmologic problems. The first case was a 9-year-old boy with cystic fibrosis and invasive aspergillosis that developed photophobia, altered color sensation, and fearful visual hallucination. The second case was a 17-year-old girl with cystic fibrosis and allergic bronchopulmonary aspergillosis, and she experienced photophobia, fatigue, impaired concentration, and insomnia, when the dose of voriconazole therapy was increased from 12 mg/kg/day to 16 mg/kg/day. The complaints of the two patients disappeared after discontinuation of voriconazole therapy. Our experience in these patients reminded us of the importance of being aware of the neurologic adverse events associated with voriconazole therapy in establishing early diagnosis and initiating prompt treatment. In addition, although serum voriconazole concentration was not measured in the present cases, therapeutic drug monitoring for voriconazole seems to be critically important in preventing neurologic side effects in pediatric patients.
Therapeutic drug monitoring of voriconazole helps to decrease the percentage of patients with off-target trough serum levels.
Guinea, Jesús; Escribano, Pilar; Marcos-Zambrano, Laura Judith; Peláez, Teresa; Kestler, Marta; Muñoz, Patricia; Vena, Antonio; López-Fabal, Fátima; Bouza, Emilio
We monitored trough voriconazole serum concentrations from 107 patients (n = 258 samples) at 6 hospitals in Madrid. Most of the patients were male (67%) and had the following underlying conditions: hematological cancer (42%), solid organ transplantation (15%), chronic obstructive pulmonary disease (14%), human immunodeficiency virus infection (8.4%), solid cancer (5.6%), and other (29%). The indication for voriconazole administration was aspergillosis treatment (74.6%) and prophylaxis (14%). The main reasons for voriconazole trough drug monitoring were initiation of treatment/prophylaxis (33%), patient monitoring (47%), and suspected toxicity (3.5%). Levels (μg/ml) were subtherapeutic (5.5; 10.5%). The samples percentage with on-target levels was significantly lower for the first sample than for subsequent samples (62.6% vs. 77.5%). "Subsequent samples," "admission in nonpediatric wards," "voriconazole used for treatment of invasive aspergillosis," and "use of proton pump inhibitors" were predictors of voriconazole therapeutic levels (≥1 μg/ml). © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: email@example.com.
In vitro and in vivo antifungal activities of FX0685, a novel triazole antifungal agent with potent activity against fluconazole-resistant Candida albicans.
Takahata, Sho; Okutomi, Takafumi; Ohtsuka, Keiko; Hoshiko, Shigeru; Uchida, Katsuhisa; Yamaguchi, Hideyo
To evaluate the therapeutic potential of FX0685, a new triazole antifungal agent, for the treatment of opportunistic fungal infections, particularly systemic candidiasis and aspergillosis, in vitro and in vivo studies were performed using fluconazole (FLC), itraconazole (ITC) and/or amphotericin B (AMB) as reference drugs. A preliminary in vitro study showed that the antifungal activity of FX0685 against FLC-susceptible Candida albicans, several non-C. albicans Candida species and Cryptococcus neoformans was superior to that of FLC and comparable or superior to those of ITC and AMB, while the anti-Aspergillus fumigatus activity of FX0685 was to varying degrees lower than that of ITC. FX0685 appeared to be comparable to FLC and ITC in the treatment of murine systemic C. albicans and pulmonary A. fumigatus infection, respectively. The biological property of FX0685 was characterized by its potent in vitro and in vivo activity against FLC-resistant C. albicans. Part of this unique property was explained by the finding that it retained potent inhibitory activity against those CYP51 molecules in which amino acid substitutions confer a phenotype of resistance to FLC and some other azole derivatives. All of these results lead to the possibility that FX0685 may be a potential antifungal drug candidate for the treatment of various clinical forms of systemic candidiasis, including those caused by FLC-resistant C. albicans, as well as for the treatment of pulmonary aspergillosis.
Fungal Orbital Cellulitis: Presenting Features, Management and Outcomes at a Referral Center.
Farooq, Asim V; Patel, Rakesh M; Lin, Amy Y; Setabutr, Pete; Sartori, Juliana; Aakalu, Vinay K
To report a series of patients with fungal orbital cellulitis who underwent exenteration surgery and describe presenting features, management and outcomes at a referral center. Retrospective case series. From November 2011 to March 2014, four patients underwent orbital exenteration for fungal orbital cellulitis at the University of Illinois. Three patients had mucormycosis and one had aspergillosis. All patients were treated with intravenous antifungals and underwent orbital exenteration. Two patients were successfully treated with supplemental intra-orbital catheter delivery of amphotericin B. Presenting visual acuity in the affected eye ranged from 20/25 to no light perception. Some level of ophthalmoplegia was present in three patients. Significantly elevated intraocular pressure was found in two patients. All patients with mucormycosis were found to have uncontrolled diabetes mellitus. One patient had a history of myelodysplastic syndrome, chronic hepatitis C infection, polysubstance abuse and Crohn's disease. Another patient had a history of alcoholic liver cirrhosis, Crohn's disease treated with systemic immunosuppression and renal cell carcinoma. The patient with aspergillosis had myelodysplastic syndrome and portal hypertension, and the initial presentation resembled giant cell arteritis. Two of four patients died during their hospitalization. Fungal orbital cellulitis has a high mortality rate despite aggressive antifungal treatment and orbital exenteration performed soon after the diagnosis is confirmed. Patients often have a history of immunosuppression and the onset may be insidious. There must be a high rate of suspicion for fungal orbital cellulitis given the appropriate signs and medical history in order to avoid treatment delay.
Aspergilose cerebral em paciente imunocompetente Cerebral Aspergillus abscess in immunocompetent patient
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Geraldo Pianetti Filho
Full Text Available Descrevemos um caso raro de aspergilose cerebral, como complicação de cirurgia para aneurisma cerebral, em paciente imunocompetente, e com sucesso no tratamento. A paciente, de 40 anos, havia sido submetida a craniotomia para clipagem de aneurisma da artéria pericalosa. Após cinco meses, no sitio cirúrgico, surgiram múltiplos abscessos por Aspergillus sp. Foram necessárias duas craniotomias para a retirada da massa fúngica e uso de anfotericina B. Após 14 anos de acompanhamento, a evolução mostra resolução da aspergilose, sem seqüela. O tratamento do abscesso cerebral por Aspergilus exige acompanhamento clínico contínuo, repetidas drenagens cirúrgicas intracranianas e o uso de anfotericina B no tratamento medicamentoso.We report an unusual case of brain aspergillosis with multiple recurrent abscess in a 40 years-old immunocompetent woman, with good therapeutical outcome. The patient presented a subaracnoid hemorhage caused by a ruptured pericalosal artery aneurysm and was submitted to a craniotomy for aneurysm surgery. Five months later, she developed multiple Aspergillus cerebral abscess. Two craniotomies and amphotericin B became necessary during treatment. Fourteen years later, she is asymptomatic. Treatment of brain aspergillosis abscess implied the combination of both surgical and drug therapy with amphotericin B.
Serious fungal infections in Pakistan.
Jabeen, K; Farooqi, J; Mirza, S; Denning, D; Zafar, A
The true burden of fungal infection in Pakistan is unknown. High-risk populations for fungal infections [tuberculosis (TB), diabetes, chronic respiratory diseases, asthma, cancer, transplant and human immunodeficiency virus (HIV) infection] are numerous. Here, we estimate the burden of fungal infections to highlight their public health significance. Whole and at-risk population estimates were obtained from the WHO (TB), BREATHE study (COPD), UNAIDS (HIV), GLOBOCAN (cancer) and Heartfile (diabetes). Published data from Pakistan reporting fungal infections rates in general and specific populations were reviewed and used when applicable. Estimates were made for the whole population or specific populations at risk, as previously described in the LIFE methodology. Of the 184,500,000 people in Pakistan, an estimated 3,280,549 (1.78%) are affected by a serious fungal infection, omitting all cutaneous infection, oral candidiasis and allergic fungal sinusitis, which we could not estimate. Compared with other countries, the rates of candidaemia (21/100,000) and mucormycosis (14/100,000) are estimated to be very high, and are based on data from India. Chronic pulmonary aspergillosis rates are estimated to be high (39/100,000) because of the high TB burden. Invasive aspergillosis was estimated to be around 5.9/100,000. Fungal keratitis is also problematic in Pakistan, with an estimated rate of 44/100,000. Pakistan probably has a high rate of certain life- or sight-threatening fungal infections.
Primary immunodeficiencies underlying fungal infections.
Lanternier, Fanny; Cypowyj, Sophie; Picard, Capucine; Bustamante, Jacinta; Lortholary, Olivier; Casanova, Jean-Laurent; Puel, Anne
We review the primary immunodeficiencies (PIDs) underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors. An increasing number of PIDs are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia (SCN) and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of interferon-γ immunity underlie endemic mycoses. Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis. CMC, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by PIDs. Each type of infection is highly suggestive of a specific type of PID. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases.
CT findings in severe thoracic sarcoidosis
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Hennebicque, Anne-Sophie; Brillet, Pierre-Yves; Moulahi, Hassen; Brauner, Michel W. [UFR Bobigny, Department of Radiology, Federation MARTHA and EA 2363, Bobigny Cedex (France); Nunes, Hilario; Valeyre, Dominique [UFR Bobigny, Department of Pneumology, Federation MARTHA and EA 2363, Bobigny Cedex (France)
Severe thoracic sarcoidosis includes manifestations with significant clinical and functional impairment and a risk of mortality. Severe thoracic sarcoidosis can take on various clinical presentations and is associated with increased morbidity. The purpose of this article was to describe the CT findings in severe thoracic sarcoidosis and to explain some of their mechanisms. Subacute respiratory insufficiency is a rare and early complication due to a high profusion of pulmonary lesions. Chronic respiratory insufficiency due to pulmonary fibrosis is a frequent and late complication. Three main CT patterns are identified: bronchial distortion, honeycombing and linear opacities. CT can be helpful in diagnosing some mechanisms of central airway obstruction such as bronchial distortion due to pulmonary fibrosis or an extrinsic bronchial compression by enlarged lymph nodes. An intrinsic narrowing of the bronchial wall by endobronchial granulomatous lesions may be suggested by CT when it shows evidence of bronchial mural thickening. Pulmonary hypertension usually occurs in patients with end-stage pulmonary disease and is related to fibrotic destruction of the distal capillary bed and to the resultant chronic hypoxemia. Several other mechanisms may contribute to the development of pulmonary hypertension including extrinsic compression of major pulmonary arteries by enlarged lymph nodes and secondary pulmonary veno-occlusive disease. Aspergilloma colonization of a cavity is the main cause of hemoptysis in sarcoidosis. Other rare causes are bronchiesctasis, necrotizing bronchial aspergillosis, semi-invasive pulmonary aspergillosis, erosion of a pulmonary artery due to a necrotic sarcoidosis lesion, necrosis of parenchymal sarcoidosis lesions and specific endobronchial macroscopic lesions. (orig.)
Fungal diseases of birds of prey.
Deem, Sharon L
Aspergillosis and candidiasis are ranked among the most common infectious diseases in birds of prey. The prevention of these fungal diseases is often easier than treatment. Thus the clinician should strive to prevent infection by minimizing stress, maintaining a healthy environment, limiting long-term use of antibiotics and corticosteroids, and reducing exposure to fungal organisms. Although less commonly diagnosed among wild, free-ranging birds of prey, a high incidence in a free-ranging population should make the clinician think of an immunocompromising factor (i.e., toxins, human encroachment or low prey base) that may be contributing to infection. The diagnosis of aspergillosis and candidiasis often requires more than just the identification of the agent, as these ubiquitous organisms often are cultured from healthy birds of prey. In those birds of prey in which a fungal infection is highly suspected or proven, antifungal drugs remain the mainstay of treatment, although available drugs and modes of delivery have improved in recent years.
Mucormycosis of the hard palate masquerading as carcinoma
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Bhari Sharanesha Manjunatha
Full Text Available A growing number of medically compromised patients are encountered by dentists in their practices. Opportunistic fungal infections such as mucormycosis usually occur in immunocompromised patients but can infect healthy individuals as well. Mucormycosis is an acute opportunistic, uncommon, frequently fatal fungal infection, caused by a saprophytic fungus that belongs to the class of phycomycetes. Among the clinical differential diagnosis we can consider squamous cell carcinoma. Such cases present as chronic ulcers with raised margins causing exposure of underlying bone. There is a close histopathological resemblance between mucormycosis and aspergillosis. Microscopically, aspergillosis has septate branching hyphae, which can be distinguished from mucormycotic hyphae by a smaller width and prominent acute angulations of branching hyphae. A definitive diagnosis of mucormycosis can be made by tissue biopsy that identifies the characteristic hyphae, by positive culture or both. The culture of diseased tissue may be negative and histopathologic examination is essential for early diagnosis. Mucormycosis was long regarded as a fatal infection with poor prognosis. However with early medical and surgical management survival rates are now thought to exceed 80%. In the present case, the fungus was identified by hematoxylin and eosin stain and confirmed by Grocott's silver methenamine special staining technique. Removal of the necrotic bone, which acted as a nidus of infection, was done. Post-operatively patient was advised an obturator to prevent oronasal regurgitation. Since mucormycosis occurs infrequently, it may pose a diagnostic and therapeutic dilemma for those who are not familiar with its clinical presentation.
Aspergillus-associated hypersensitivity respiratory disorders.
Shah, Ashok
The mould Aspergillus is responsible for a gamut of respiratory diseases ranging from saprobic colonisation to rapidly invasive disseminated disease. The clinical spectrum of Aspergillus-associated hypersensitivity respiratory disorders includes Aspergillus induced asthma, allergic bronchopulmonary aspergillosis (ABPA), allergic Aspergillus sinusitis (AAS) and hypersensitivity pneumonitis. Inhalant allergens, in patients with allergic asthma, play a key role in bringing about the inflammation present in the airways, and fungi are increasingly being recognised as important inhalant allergens. Aspergillus is linked to asthma in more ways than one. In the asthmatic subjects, the fungal spores are trapped in the thick and viscid secretions that are usually present in the airways. This generally develops in atopic subjects and is sustained by continuous inhalation of Aspergillus antigens, triggering asthma that may be more severe in form. Aspergillus induced asthma is yet to receive the recognition that it deserves. Allergic bronchopulmonary aspergillosis is the best known form of allergic aspergillosis and is an emerging disease in India. An immunologically mediated lung disease, ABPA occurs predominantly in patients with asthma. A set of diagnostic criteria is required as there is no single test that establishes the diagnosis apart from demonstration of central bronchiectasis with normal tapering bronchi, a feature considered to be pathognomonic of ABPA. Radiologically, ABPA is characterised by 'transient pulmonary infiltrates' or 'fleeting shadows', often confused with pulmonary tuberculosis. A comparatively more recently recognised clinical entity, AAS is characterised by mucoid impaction in the paranasal sinuses which is akin to that in ABPA. Although it appears that the patient with ABPA provides a favourable milieu for the occurrence of AAS, it is perhaps surprising that in spite of similar histopathological features the co-existence of both these diseases has
Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism.
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Eveline Snelders
Full Text Available BACKGROUND: Resistance to triazoles was recently reported in Aspergillus fumigatus isolates cultured from patients with invasive aspergillosis. The prevalence of azole resistance in A. fumigatus is unknown. We investigated the prevalence and spread of azole resistance using our culture collection that contained A. fumigatus isolates collected between 1994 and 2007. METHODS AND FINDINGS: We investigated the prevalence of itraconazole (ITZ resistance in 1,912 clinical A. fumigatus isolates collected from 1,219 patients in our University Medical Centre over a 14-y period. The spread of resistance was investigated by analyzing 147 A. fumigatus isolates from 101 patients, from 28 other medical centres in The Netherlands and 317 isolates from six other countries. The isolates were characterized using phenotypic and molecular methods. The electronic patient files were used to determine the underlying conditions of the patients and the presence of invasive aspergillosis. ITZ-resistant isolates were found in 32 of 1,219 patients. All cases were observed after 1999 with an annual prevalence of 1.7% to 6%. The ITZ-resistant isolates also showed elevated minimum inhibitory concentrations of voriconazole, ravuconazole, and posaconazole. A substitution of leucine 98 for histidine in the cyp51A gene, together with two copies of a 34-bp sequence in tandem in the gene promoter (TR/L98H, was found to be the dominant resistance mechanism. Microsatellite analysis indicated that the ITZ-resistant isolates were genetically distinct but clustered. The ITZ-sensitive isolates were not more likely to be responsible for invasive aspergillosis than the ITZ-resistant isolates. ITZ resistance was found in isolates from 13 patients (12.8% from nine other medical centres in The Netherlands, of which 69% harboured the TR/L98H substitution, and in six isolates originating from four other countries. CONCLUSIONS: Azole resistance has emerged in A. fumigatus and might be more
Isolation and identification of Aspergillus spp. from brown kiwi (Apteryx mantelli) nocturnal houses in New Zealand.
Glare, Travis R; Gartrell, Brett D; Brookes, Jenny J; Perrott, John K
Aspergillosis, a disease caused by infection with Aspergillus spp., is a common cause of death in birds globally and is an irregular cause of mortality of captive kiwi (Apteryx spp.). Aspergillus spp. are often present in rotting plant material, including the litter and nesting material used for kiwi in captivity. The aim of this study was to survey nocturnal kiwi houses in New Zealand to assess the levels of Aspergillus currently present in leaf litter. Samples were received from 11 nocturnal kiwi houses from throughout New Zealand, with one site supplying multiple samples over time. Aspergillus was isolated and quantified by colony counts from litter samples using selective media and incubation temperatures. Isolates were identified to the species level by amplification and sequencing of ITS regions of the ribosomal. Aspergillus spp. were recovered from almost every sample; however, the levels in most kiwi houses were below 1000 colony-forming units (CFU)/g of wet material. The predominant species was Aspergillus fumigatus, with rare occurrences of Aspergillus niger, Aspergillus nidulans, and Aspergillus parasiticus. Only one site had no detectable Aspergillus. The limit of detection was around 50 CFU/g wet material. One site was repeatedly sampled as it had a high loading of A. fumigatus at the start of the survey and had two recent clinical cases of aspergillosis diagnosed in resident kiwi. Environmental loading at this site with Aspergillus spp. reduced but was not eliminated despite changes of the litter. The key finding of our study is that the background levels of Aspergillus spores in kiwi nocturnal houses in New Zealand are low, but occasional exceptions occur and are associated with the onset of aspergillosis in otherwise healthy birds. The predominant Aspergillus species present in the leaf litter was A. fumigatus, but other species were also present. Further research is needed to confirm the optimal management of leaf litter to minimize Aspergillus
Burden of Serious Fungal Infections in Jordan
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Jamal Wadi
Full Text Available Objective: To estimate the burden of fungal infections in Jordan for the first time. Material and Methods: Population data was from UN 2011 statistics and TB cases from WHO in 2012. Fewer than 100 patients with HIV were recorded in Jordan in 2013. Approximately 100 renal transplants and eight liver transplants are performed annually. There were 12,233 major surgical procedures in Jordan in 2013, of which 5.3% were major abdominal surgeries; candidemia was estimated in 5% of the population based on other countries, with 33% occurring in the ICU. Candida peritonitis/intra-abdominal candidiasis was estimated to affect 50% of the number of ICU candidemia cases. No adult asthma rates have been recorded for Jordan, so the rate from the Holy Land (8.54% clinical asthma from To et al. has been used. There are an estimated 49,607 chronic obstructive pulmonary disease (COPD patients in Jordan, with 64% symptomatic, 25% Gold stage 3% or 4%, and 7% (3472 are assumed to be admitted to hospital each year. No cystic fibrosis cases have been recorded. Literature searches on fungal infections revealed few data and no prevalence data on fungal keratitis or tinea capitis, even though tinea capitis comprised 34% of patients with dermatophytoses in Jordan. Results: Jordan has 6.3 million inhabitants (65% adults, 6% are >60 years old. The current burden of serious fungal infections in Jordan was estimated to affect ~119,000 patients (1.9%, not including any cutaneous fungal infections. Candidemia was estimated at 316 cases and invasive aspergillosis in leukemia, transplant, and COPD patients at 84 cases. Chronic pulmonary aspergillosis prevalence was estimated to affect 36 post-TB patients, and 175 in total. Allergic bronchopulmonary aspergillosis (ABPA and severe asthma with fungal sensitization (SAFS prevalence in adults with asthma were estimated at 8900 and 11,748 patients. Recurrent vulvovaginal candidiasis was estimated to affect 97,804 patients, using a 6
Risk factors, clinical characteristics, and outcomes of invasive fungal infections in solid organ transplant recipients.
Bodro, M; Sabé, N; Gomila, A; Ayats, J; Baliellas, C; Roca, J; Melilli, E; Carratalà, J
Invasive fungal infection (IFI) is an important cause of morbidity and mortality among solid organ transplant (SOT) recipients. We sought to assess risk factors, clinical characteristics, and current outcomes of IFI in SOT recipients. We reviewed all episodes of IFI occurring among SOT recipients in a university hospital from 2008 to 2011. To determine risk factors for IFI we carried out a matched case-control study (1:2 ratio). Control subjects were matched for transplant type and timing. We documented 20 episodes of IFI among 744 SOT recipients (2.7%). Sixty-five percent of cases were proven IFI and 35% were probable IFI. The types of IFI documented were aspergillosis in 8 cases, candidiasis in 7, pneumocystosis in 3, Emmonsia species in infection 1, and disseminated cryptococcosis in 1. Ninety-nine percent of the patients had received a prior antibiotic therapy (3 months), 40% presented allograft rejection (3 months), and 40% had prior kidney injury. Complications of IFI included septic shock (50%), respiratory failure (55%), multiple-organ dysfunction (55%), and intensive care unit (ICU) admission (50%). Median days from transplantation to diagnosis was 103 for candidiasis (range, 27-4644) and 1195 for aspergillosis (range, 0-4319). In a comparison of case patients with 40 matched control subjects, case patients more frequently presented prior ICU stay (3 months; P = .05), hemodialysis requirement (P = .02), receipt of high-dose prednisone (6 months; P = .006), and prior antibiotic therapy (P < .001). Prior use of antibiotic treatment was the only risk factor for IFI (odds ratio [OR] 93; 95% confidence interval [CI], 8.3-1042). Case-fatality rate was 60%. In our recent experience, 2.7% of SOT recipients developed IFI, mainly aspergillosis followed by candidiasis. Prior ICU admission, hemodialysis, receipt of high-dose prednisone, and prior antibiotic use were more frequent in cases when compared with control subjects, with the latter factor being the only
A young immunocompetent patient with spontaneous Aspergillus empyema who developed severe eosinophilia
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Fumiaki Kudo
Full Text Available Aspergillus empyema is usually reported as a complication of surgical procedures, and spontaneous cases are quite rare. Here, we describe the case of a 16-year-old man who suddenly developed dyspnea despite previously being healthy. Chest computed tomography showed multiple mass-containing cavity lesions, pneumothorax, and pleural effusion in the left thorax. Within 2 weeks, Aspergillus fumigatus grew from his pleural effusion, thus he was diagnosed with Aspergillus empyema. He also developed severe eosinophilia after admission, and was treated with anti-fungal drugs. Although there are many factors that can cause eosinophilia, we suspect that infection with Aspergillus fumigatus was the major cause of the eosinophilia in this patient. The lack of bronchial symptoms and lesions were not consistent with a diagnosis of allergic bronchopulmonary aspergillosis. As far as we know, this is the first case of spontaneous Aspergillus empyema resulting in severe eosinophilia.
Aspergilloma of the maxillary sinus: report of a case
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Kang, Ju Han; Kim, Gyu Tae; Choi, Yong Suk; Hwang, Eui Hwan [School of Dentistry, Kung Hee University, Seoul (Korea, Republic of); Yu, Jae Jung [Kangdong Scared Heart Hospital, Hallym Medical Center, Seoul (Korea, Republic of)
Aspergilloma of the paranasal sinus is a non-invasive form of aspergillosis, most often in the maxillary sinus. This case presents an 86-year-old female with aspergilloma of the left maxillary sinus. The patient's chief complaint was intermittent pain on the left maxillary first premolar area. A radiopacification of the left maxillary sinus was observed on the panoramic radiograph. Cone-beam computed tomography revealed complete radiopacification of the left maxillary sinus and scattered multiple radiopaque mass inside the lesion. Biopsy was performed under local anesthesia. On microscopic examination, numerous fungal hyphae, which branch at acute angle, were observed. The diagnosis was made as an aspergilloma based on the histopathologic examination.
Maxillary necrosis by mucormycosis. a case report and literature review.
Auluck, Ajit
The maxilla rarely undergoes necrosis due to its rich vascularity. Maxillary necrosis can occur due to bacterial infections such as osteomyelitis, viral infections such as herpes zoster or fungal infections such as mucormycosis, aspergillosis etc. Mucormycosis is an opportunistic fulminant fungal infection, which mainly infects immunocompromised patients. The infection begins in the nose and paranasal sinuses due to inhalation of fungal spores. The infection can spread to orbital and intracranial structures either by direct invasion or through the blood vessels. The fungus invades the arteries leading to thrombosis that subsequently causes necrosis of hard and soft tissues. We report a case of maxillary necrosis by mucormycosis in an uncontrolled diabetic patient to emphasize early diagnosis of this potentially fatal fungal infection. We briefly discuss different diseases which can lead to maxillary necrosis and review the current concepts in management of mucormycosis. Early diagnosis and prompt treatment can reduce the mortality and morbidity of this lethal fungal infection.
Immunohistochemical diagnosis of fusariosis with monoclonal antibodies
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Jensen, H.E.; Aalbæk, B.; Jungersen, Gregers
for fusariosis. A panel of newly developed Mabs for immunohistochemical diagnosis of fusariosis was screened for specificity on experimentally infected laboratory animal tissue and on skin tissue biopsies from two neutropenic patients with Fusarium sepsis. Methods: Somatic antigens were made from F. solani (CBS...... for establishing an accurate diagnosis. Although molecular techniques (e.g. in situ hybridization and PCR) have been explored for diagnostic use, the development of specific monoclonal antibodies (Mabs) for immunohistochemical identification of Fusarium spp. will extend the availability of diagnostic options...... containing homologous (fusariosis) and heterologous (aspergillosis, candidosis, and scedosporidiosis) fungal elements. Tissue reactive Mabs were then tested on skin biopsies from two patients with fusariosis sepsis with dissemination to the skin In the patients, a diagnosis of fusariosis-sepsis had been...
The medical effects of mold exposure.
Bush, Robert K; Portnoy, Jay M; Saxon, Andrew; Terr, Abba I; Wood, Robert A
Exposure to molds can cause human disease through several well-defined mechanisms. In addition, many new mold-related illnesses have been hypothesized in recent years that remain largely or completely unproved. Concerns about mold exposure and its effects are so common that all health care providers, particularly allergists and immunologists, are frequently faced with issues regarding these real and asserted mold-related illnesses. The purpose of this position paper is to provide a state-of-the-art review of the role that molds are known to play in human disease, including asthma, allergic rhinitis, allergic bronchopulmonary aspergillosis, sinusitis, and hypersensitivity pneumonitis. In addition, other purported mold-related illnesses and the data that currently exist to support them are carefully reviewed, as are the currently available approaches for the evaluation of both patients and the environment.
[Opportunistic infections and sarcoidosis].
Jamilloux, Y; Bernard, C; Lortholary, O; Kerever, S; Lelièvre, L; Gerfaud-Valentin, M; Broussolle, C; Valeyre, D; Sève, P
Opportunistic infections (OI) are uncommon in sarcoidosis (1 to 10%) and mostly occur in patients with previously diagnosed disease or can rarely be the presenting manifestation. The most common OIs are, in descending order: aspergillosis, cryptococcosis, and mycobacterial infections. Treatment with corticosteroids is the most frequent risk factor for OI occurrence during sarcoidosis but immunosuppressive drugs and therapy with anti-TNFα are also risk factors. Overall, clinical presentation, treatment, and outcome are identical to that occur in other conditions complicated with the occurrence of OIs. However, some atypical presentations of OIs can mimic sarcoidosis exacerbation and misdiagnosis may lead clinicians to increase immunosuppression, causing worsening of the OI. The meticulous collection of patient's history along with factors differentiating OI from sarcoidosis exacerbation is key factor to optimally manage these patients. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Dental technician pneumoconiosis mimicking pulmonary tuberculosis: a case report.
Tan, Han Loong; Faisal, Mohamed; Soo, Chun Ian; Ban, Andrea Y L; Manap, Roslina Abdul; Hassan, Tidi M
Dental laboratory technicians are at risk of developing occupational respiratory diseases due to exposure to various potentially toxic substances in their working environment. Since 1939, few cases of silicosis among dental technician have been reported. We illustrate a 38 year-old female, who worked in a dental laboratory for 20 years, initially treated as pulmonary tuberculosis and chronic necrotising aspergillosis without much improvement. Computed tomography guided lung biopsy and bronchoscopic transbronchial lung biopsy were performed. Lung tissue biopsies showed presence of refractile dental materials within the areas of histiocyte proliferation. The diagnosis of dental technician pneumoconiosis was obtained and our patient underwent pulmonary rehabilitation. This case highlights the importance of obtaining a detailed occupational history in tuberculosis endemic area, as pulmonary tuberculosis is a great mimicker of other respiratory diseases.
Voriconazole-induced periostitis in a patient with overlap syndromes.
Hirota, Keisho; Yasoda, Akihiro; Fujii, Toshihito; Inagaki, Nobuya
A 52-year-old woman with overlap syndrome and interstitial pneumonia underwent immunosuppressive therapy and she was suspected to suffer from pulmonary aspergillosis. Oral voriconazole was initiated, and a rapid elevation of alkaline phosphatase (ALP) occurred after 4 weeks. After 2 months, the patient presented diffuse pain in bilateral skeletal regions, and bone scintigraphy revealed bilateral multiple areas of increased radiotracer uptake. We suspected the skeletal involvement as voriconazole-induced periostitis. Actually, the plasma fluoride level was increased. Voriconazole was replaced with itraconazole, and after 3 weeks, the patient stopped complaining of bone pain concomitant with the decrease in ALP. Voriconazole-induced periostitis is a rare condition but had previously been reported in solid organ or patients with bone marrow transplant who received a long-term voriconazole therapy. Our present case is distinctive of previous ones, because it occurred in a patient with connective tissue disease which had its rapid progression.
Bilateral pulmonary aspergilloma caused by an atypical isolate of Aspergillus terreus.
Khan, Z U; Kortom, M; Marouf, R; Chandy, R; Rinaldi, M G; Sutton, D A
A case of bilateral pulmonary aspergilloma caused by an atypical isolate of Aspergillus terreus is described. The diagnosis was established by the presence of septate, dichotomously branched fungal elements in freshly collected bronchoalveolar lavage and sputum specimens and by repeated isolation of the fungus in culture. Specific precipitating antibodies against the A. terreus isolate were demonstrated in the patient's serum. The isolate was atypical as it failed to produce fruiting structures on routine mycological media, but it did so on extended incubation on potato flake agar and produced globose, relatively heavy-walled, hyaline accessory conidia (formerly termed aleurioconidia) on both vegetative and aerial mycelia. Also, it produced an intense yellow diffusing pigment in the medium. The report underscores the increasing importance of A. terreus in the etiology of pulmonary aspergillosis. It is suggested that A. terreus antigen be included in the battery of serodiagnostic reagents to facilitate the early diagnosis of infections caused by this species.
Lung resection and application of latissimus dorsi muscle flap for pulmonary aspergilloma: Case report
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Ozan Usluer
Full Text Available Aspergilloma, is the most common form of aspergillus infectionthat presents as parenchymal cavitary lesion withsaprophytic colonization. This disease is associated withvariety of lung diseases such as tuberculosis, sarcoidosisand bronchiectasis. The patient in this study with tuberculosiswas diagnosed 12 years ago and treated for sixmonths. Most frequently referred symptom is hemoptysis.Aspergilloma get a diagnosis with chest x-ray and thoraxcomputerized tomoghraphy. In treatment usually anatomicresection is performed, bronchial stump is supportedand the remaining space is filled with a flap. The pateintwas admitted to our hospital with hemoptysis and left upperlobectomy was performed due to cavitary lesion andbronchial stump was supported with latissimus dorsi muscleflap. The postoperative period was uneventful with noreccurrence so far.Key words: Bronchopulmonary aspergillosis, thoracicsurgery, tuberculosis
Krause, Kristian J; Reavill, Drury; Weldy, Scott H; Bradway, Daniel S
A 19-yr-old female African penguin (Spheniscus demersus) presented with labored breathing and anorexia. Radiographs revealed soft-tissue density lesions in the left lung fields and fluid in the right. The penguin died during the night. Postmortem examination demonstrated multiple granulomas in the lungs and air sacs. The right coelom was filled with opaque fluid. Histopathology of the lung, liver, kidney, and spleen identified Mycobacterium as a primary disease etiology. Large numbers of acid fast-positive, rod-shaped bacteria were recognized on tissue staining. Mycobacterium genavense was detected by polymerase chain reaction (PCR) using primers specific for the species. Further confirmation of M. genavense was accomplished using PCR with universal Mycobacterium spp. primers followed by sequencing of the amplicon obtained. To our knowledge, this is the first reported case of mycobacteriosis-and specifically M. genavense -in an African penguin. This case also demonstrates the similarities of presentation between the more commonly suspected and encountered aspergillosis and mycobacteriosis.
Treatment principles for the management of mold infections.
Kontoyiannis, Dimitrios P; Lewis, Russell E
Survival rates among immunocompromised patients with invasive mold infections have markedly improved over the last decade with earlier diagnosis and new antifungal treatment options. Yet, increasing antifungal resistance, breakthrough infections with intrinsically resistant fungi, and potentially life-threatening adverse effects and drug interactions are becoming more problematic, especially with prolonged therapy. Evidence-based recommendations for treating invasive aspergillosis and mucormycosis provide excellent guidance on the initial workup and treatment of these molds, but they cannot address all of the key management issues. Herein, we discuss 10 general treatment principles in the management of invasive mold disease in immunocompromised patients and discuss how these principles can be integrated to develop an effective, individualized treatment plan. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
[An autopsy case of Aspergillus pneumonia after inhalation of a great deal of dust in a mushroom factory].
Shimaoka, Yuichi; Ishida, Takashi; Kawasaki, Satoshi; Kobayashi, Osamu
A man in his forties with alcoholic liver injury was referred to our hospital because of progressive dyspnea and diffuse infiltrative shadows in both lung fields. Two weeks before admission he had carried a lot of rotten Enoki mushrooms in his factory, and then inhaled a great deal of airborne dust. Serological examination showed extremely elevated beta-D-glucan and positive Aspergillus antigen. Culture of dust collected from the floor of the factory proved to be positive for Aspergillus fumigatus. Aspergillus pneumonia was diagnosed and treatment with anti-fungal drugs was started. In spite of intensive treatment he died of respiratory failure. The autopsy disclosed multiple abscess formation containing hyphae of Aspergillus fumigatus and granulomatous reaction with multinuclear giant cells. However, there was no Aspergillus invasion in other organs. This was a rare case of invasive pulmonary aspergillosis that developed after inhalation of organic dust in a non-immunocompromised host.
CT and MR findings of mycotic infection of the paranasal sinus: Differentiation from sinonasal neoplasm
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Lee, Kil Woo; Lim, Hyo Keun; Seo, Gwy Suk; Bae, Sang Hoon [College of Medicine, Hallyum University, Seoul (Korea, Republic of); Lee, Shin Hyung [National Medical Center, Seoul (Korea, Republic of)
When a soft tissue mass in the bony wall of the paranasal sinus is present. It is difficult to make a distinction between tumor and inflammatory mass on CT. Fungal sinusitis may have soft tissue attenuation on the bony wall of the sinus, bony sclerosis, focal bony destruction, and calcific areas on CT. This is a report of four proven cases of fungal sinusitis, aspergillosis in 3 cases and mucormycosis in 1 case. All 4 patients had CT and one patient had MRI. On CT, bony sclerosis and destruction were well visualized in all cases. On MRI, mycetoma in the maxillary sinus was hypointense on T1 weighted images and more hypointense on T2 weighted images. Although CT appears to be the best modality for initial examination of the patient with sinusitis, the differentiation of fungal sinusitis from tumor mass or other entity may be better accomplished with MRI.
Current status and future perspectives on molecular and serological methods in diagnostic mycology.
Lau, Anna; Chen, Sharon; Sleiman, Sue; Sorrell, Tania
Invasive fungal infections are an important cause of infectious morbidity. Nonculture-based methods are increasingly used for rapid, accurate diagnosis to improve patient outcomes. New and existing DNA amplification platforms have high sensitivity and specificity for direct detection and identification of fungi in clinical specimens. Since laboratories are increasingly reliant on DNA sequencing for fungal identification, measures to improve sequence interpretation should support validation of reference isolates and quality control in public gene repositories. Novel technologies (e.g., isothermal and PNA FISH methods), platforms enabling high-throughput analyses (e.g., DNA microarrays and Luminex xMAP) and/or commercial PCR assays warrant further evaluation for routine diagnostic use. Notwithstanding the advantages of molecular tests, serological assays remain clinically useful for patient management. The serum Aspergillus galactomannan test has been incorporated into diagnostic algorithms of invasive aspergillosis. Both the galactomannan and the serum beta-D-glucan test have value for diagnosing infection and monitoring therapeutic response.
[Quantitative assessment of fungal risk in the case of construction works in healthcare establishments: Proposed indicators for the determination of the impact of management precautions on the risk of fungal infection].
Gangneux, J-P; Adjidé, C-C; Bernard, L; Botterel, F; Carel, A; Castel, O; Derouin, F; Hoarau, G; Labussière, H; Lafaurie, M; Millon, L; Pottecher, B; Thiebaut, A; Turco, M; Baron, R
Construction works in healthcare establishments produce airborne fungal spores and considerably increase the risk of exposure of immunosuppressed patients. It is necessary to reinforce protective measures, or even to implement specific precautions, during this critical phase. The aim of these precautions is to protect both those areas, which are susceptible to dust, and patients at risk of a fungal infection particularly invasive aspergillosis. When construction works are planned in healthcare establishments, the first step consists in the characterisation of the environmental fungal risk and the second one in proposing risk management methods. It is then essential to establish impact indicators in order to evaluate the risk management precautions applied. The working group promoted by the French societies of medical mycology and hospital hygiene (SFMM & SF2H) details here both environmental and epidemiological impact indicators that can be used. Copyright © 2012. Published by Elsevier SAS.
CT and MRI of sphenoid tumors and pseudo tumors; Scanographie et IRM des tumeurs et pseudo-tumeurs du sphenoide
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Beaujeux, R.; Dietemann, J.L.; Brun, F.; Bourjat, P. [Centre Hospitalier Universitaire, 67 - Strasbourg (France)
The radiological features of the main tumors and pseudotumors of the sphenoid bone with CT and MRI are described in detail. The lesions are classified as tumors and pseudotumors of the sphenoid bone and sphenoid sinus and as neighboring tumors and pseudotumors with secondary sphenoid invasion. Metastases, chondromas, fibrous dysplasia, myelomas, plasmocytomas and chordomas are the most frequent sphenoid lesions. Tumors and pseudotumors of the sphenoid sinus mainly include mucoceles and cholesterin granulomas. Neighboring tumors are of intracranial origin (pituitary adenoma, meningioma, aneurysm) or originate in the nasopharynx (nasopharyngeal fibroma, malignant tumors) or the nasosinusal cavities (inverted papillomas, invasive aspergillosis, malignant tumors). The radiological features do no always allow diagnosing the tumoral type. However, the merits of CT and, even more, of MRI for an accurate assessment of extension is indisputable. (authors). 41 refs., 12 figs.
Oral administration and younger age decrease plasma concentrations of voriconazole in pediatric patients.
Kato, Karin; Nagao, Miki; Yamamoto, Masaki; Matsumura, Yasufumi; Takakura, Shunji; Fukuda, Kazuhiko; Ichiyama, Satoshi
Voriconazole is used for treating or preventing invasive aspergillosis and other invasive fungal infections. To minimize adverse reactions and to maximize treatment effects, therapeutic drug monitoring should be performed. However, it is challenging to optimize daily voriconazole dosing because limited data have been published so far on pediatric patients. We retrospectively analyzed voriconazole concentrations in patients aged 0-18 years. In addition, a literature review was conducted. In our study cohort, younger age and oral administration were significantly associated with lower plasma voriconazole concentrations (P voriconazole (P = 0.01). Reports of voriconazole administration in pediatric patients show that higher doses are required in younger children and in patients receiving oral administration. Hence, the current data suggest that we should escalate both initial and maintenance doses of voriconazole in pediatric patients, particularly in patients of younger age receiving an oral administration of voriconazole. Copyright © 2015. Published by Elsevier Ltd.
Highly Variable Plasma Concentrations of Voriconazole in Pediatric Hematopoietic Stem Cell Transplantation Patients
Wolfs, Tom; Jonker, Martine; de Waal, Marjolein; Egberts, Toine C. G.; Ververs, Tessa T.; Boelens, Jaap J.; Bierings, Marc
Invasive fungal infections are of great concern in pediatric hematopoietic stem cell transplantation (HSCT) recipients. Voriconazole is usually the drug of first choice for treating or preventing invasive aspergillosis. Optimum trough levels (Ctroughs) are between 1 and 5 mg/liter. It is unclear whether these levels are reached with currently advised pediatric dosing schedules. Between 2007 and 2011, 11 patients voriconazole in the HSCT unit of UMC Utrecht. For children 12 years) (P = 0.034). The intrapatient variability in Ctrough ranged between 1 and 238%. Voriconazole was discontinued in six patients due to toxicity. These patients had a median Ctrough of 0.5 mg/liter at the initial dose (ranging from 0.5 to 2.6 mg/liter), and a medium maximal concentration of 4 mg/liter was reached. Inter- and intrapatient variability is a major concern in voriconazole treatment and necessitates therapeutic drug monitoring of dosing, especially in young children. PMID:23114771
What is the clinical significance of filamentous fungi positive sputum cultures in patients with cystic fibrosis?
Liu, Jane C; Modha, Deborah E; Gaillard, Erol A
In patients with cystic fibrosis (CF), the isolation of filamentous fungi, in particular Aspergillus spp. in the respiratory secretions is a common occurrence. Most of these patients do not fulfil the clinical criteria for a diagnosis of allergic bronchopulmonary aspergillosis (ABPA). The clinical relevance of filamentous fungi and whether antifungal therapy should be started in patients with persistent respiratory exacerbations who do not respond to two or more courses of appropriate oral or intravenous antibiotics and in whom no other organisms are isolated from respiratory secretions is a dilemma for the CF clinician. In this article, we review the epidemiology and clinical significance of filamentous fungi in the non-ABPA CF lung, with an emphasis on Aspergillus spp. colonisation (AC), the clinical relevance of Aspergillus spp. positive respiratory cultures and the outcome following antifungal therapy in these patients. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Silicosis: controversy in detection
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Diemen Darwin Delgado García
Full Text Available In many countries, the work of mining, quarrying, construction of tunnels and galleries, abrasive jet cleaning and smelting continue to present significant risks of silica exposure and silicosis epidemics still occur, even in developed countries. Patients with silicosis are particularly susceptible to opportunistic lung infections such as aspergillosis and tuberculosis. Occasionally silicosis is associated with scleroderma, systemic lupus erythematosus, nephritis and cancer. Early detection of silicosis is made by chest X-ray method, being the presence of rounded opacities the main sign of illness. However, no systematic information is available that allows use as a standard method of evaluation because their interpretation remains operator dependent both conventional radiological technique, digital and interpretation of computed tomography with high resolution.
A retrospective study of postmortem findings in red-tailed hawks
Franson, J.C.; Thomas, N.J.; Smith, M.R.; Robbins, A.H.; Newman, S.; McCartin, P.C.
We studied necropsy results from carcasses of 163 red-tailed hawks (Buteo jamaicensis) submitted to the National Wildlife Health Center from 1975 through 1992. The most frequent postmortem finding was emaciation of unknown etiology, diagnosed in 33 (20%) carcasses. Proportionally more juveniles than adults were emaciated. Evidence of non-gunshot trauma, often suggestive of collision with vehicles or structures near roadways, was found in 29 (18%) birds. Of 25 (15%) toxicoses, 20 were attributed to agricultural pesticides, including famphur (4), fenthion (3), carbofuran (2), phosphamidon (2), endrin (1), and unidentified organophosphorus compounds (8). Lead and strychnine poisoning were diagnosed in two birds each, and selenium poisoning in one. Diseases, including aspergillosis, tuberculosis, pasteurellosis, and pox, were found in 21 (13%) hawks. Gunshot and electrocution were each diagnosed in six (4%) birds, one (0.6%) was trapped, miscellaneous conditions were found in 10 (6%), and no diagnosis could be determined for 32 (19%) of the carcasses.
Posterior reversible encephalopathy syndrome in an AIDS patient with acute renal failure and hypertension
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Olivia Bargiacchi
Full Text Available Introduction: The posterior reversible encephalopathy syndrome (PRES is a neurological entity characterized by magnetic resonance imaging (MRI evidence of bilateral subcortical edema in the occipital regions of the brain. Case report: We report the case of a female patient with AIDS, pulmonary aspergillosis, CMV infection, and acute renal failure due to Clostridium difficile diarrhea. Her clinical course was complicated by seizures and hypertension. MRI findings were consistent with PRES. The patient was treated with anticonvulsants and antihypertensive agents with clinical improvement. Discussion and conclusions: Few cases of PRES in HIV-infected patients have been described, and it is not clear whether HIV infection is a predisposing factor for this syndrome. The article reviews the literature on PRES in HIV and discusses the role of HIV-associated endothelial damage in the pathogenesis of this syndrome.
CD103+ Dendritic Cells Control Th17 Cell Function in the Lung
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Teresa Zelante
Full Text Available Th17 cells express diverse functional programs while retaining their Th17 identity, in some cases exhibiting a stem-cell-like phenotype. Whereas the importance of Th17 cell regulation in autoimmune and infectious diseases is firmly established, the signaling pathways controlling their plasticity are undefined. Using a mouse model of invasive pulmonary aspergillosis, we found that lung CD103+ dendritic cells (DCs would produce IL-2, dependent on NFAT signaling, leading to an optimally protective Th17 response. The absence of IL-2 in DCs caused unrestrained production of IL-23 and fatal hyperinflammation, which was characterized by strong Th17 polarization and the emergence of a Th17 stem-cell-like population. Although several cell types may be affected by deficient IL-2 production in DCs, our findings identify the balance between IL-2 and IL-23 productions by lung DCs as an important regulator of the local inflammatory response to infection.
Agents of coral mortality on reef formations of the Colombian Pacific
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Raúl Navas-Camacho
Full Text Available The National Monitoring System for Coral Reefs of Colombia (SIMAC monitors the impact of some of the most important agents of coral tissue loss (bleaching and/or disease in the Colombian Pacific coral formations since 1998. Physiological bleaching is among the main results of stress in the area. Signs of coral diseases resembling bacterial bleaching such as White Plague and White Band, were observed in Malpelo and Gorgona islands. Damage to the Pacific gorgonian Pacifigorgia spp., similar to those produced by Aspergillosis in Caribbean corals, was detected in Utría Bay. The presence of tumors in colonies of massive corals was also recorded. Even though coral diseases are globally widespread, their occurrence in American Pacific reefs has been poorly documented to date. Rev. Biol. Trop. 58 (Suppl. 1: 133-138. Epub 2010 May 01.
Idiopathic bronchocentric granulomatosis in an asthmatic adolescent
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Hiroki Umezawa
Full Text Available Bronchocentric granulomatosis in asthmatic patients has been generally considered to be associated with allergic bronchopulmonary aspergillosis and represent a histopathologic manifestation of fungal hypersensitivity. Here we report a case of an idiopathic bronchocentric granulomatosis in a 17-year-old man with a history of asthma. He was admitted to the hospital with a fever and cough, and a chest CT scan showed peribronchial consolidation in the pulmonary parenchyma, which was unresponsive to antibiotic therapy. The pathological findings obtained by video-assisted thoracoscopic lung biopsy revealed necrotizing granulomatous inflammation centered on bronchi and bronchioles and there was no evidence of fungal colonization, resulting in a diagnosis of idiopathic bronchocentric granulomatosis. Systemic corticosteroid therapy led to clinical and radiological recovery. Physicians should take into account the possibility of the idiopathic process in bronchocentric granulomatosis of asthmatic patients.
Calcineurin Orchestrates Hyphal Growth, Septation, Drug Resistance and Pathogenesis of Aspergillus fumigatus: Where Do We Go from Here?
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Praveen R Juvvadi
Full Text Available Studies on fungal pathogens belonging to the ascomycota phylum are critical given the ubiquity and frequency with which these fungi cause infections in humans. Among these species, Aspergillus fumigatus causes invasive aspergillosis, a leading cause of death in immunocompromised patients. Fundamental to A. fumigatus pathogenesis is hyphal growth. However, the precise mechanisms underlying hyphal growth and virulence are poorly understood. Over the past 10 years, our research towards the identification of molecular targets responsible for hyphal growth, drug resistance and virulence led to the elucidation of calcineurin as a key signaling molecule governing these processes. In this review, we summarize our salient findings on the significance of calcineurin for hyphal growth and septation in A. fumigatus and propose future perspectives on exploiting this pathway for designing new fungal-specific therapeutics.
Causes of owl mortality in Hawaii, 1992 to 1994
Work, Thierry M.; Hale, Jon
Eighty-one barn owls (Tyto alba) and five Hawaiian owls or pueo (Asio flammeus sandwichensis) from Kauai, Oahu, Lanai, Molokai, Maui and Hawaii (USA) were evaluated for cause of death, November 1992 through August 1994. The most common cause of death in barn owls was trauma (50%) followed by infectious disease (28%) and emaciation (22%). Most traumas apparently resulted from vehicular collisions. Trichomoniasis was the predominant infectious disease and appeared to be a significant cause of death in barn owls in Hawaii. Pasteurellosis and aspergillosis were encountered less commonly. No predisposing cause of emaciation was detected. Stomach contents from 28 barn owls contained mainly insects (64%) of the family Tetigoniidae and Gryllidae, and rodents (18%); the remainder had mixtures of rodents and insects or grass. Three pueo died from trauma and one each died from emaciation and pasteurellosis. We found no evidence of organochlorine, organophosphorus, or carbamate pesticides as causes of death in pueo or barn owls.
[Invasive fungal disease in hemato-oncological and hematopoietic stem cell transplantation patients from Hospital Clinico Universidad Católica, Santiago-Chile using revised EORTC/MSG diagnostic criteria].
Rabagliati B, Ricardo; Fuentes L, Gino; Guzmán D, Ana María; Orellana U, Eric; Oporto C, Jorge; Aedo C, Igor; Garrido S, Marcelo; Nervi N, Bruno
Invasive fungal disease (IFD) is a severe complication occurring mostly in haematooncological (H-O) patients and hematopoietic stem cell transplant (HSCT) receptors. Our aim was to describe the IFD occurring in our H-O and HSCT patients according to the EORTC/MSG revised criteria. IFD surveillance was performed in adult patients of the Hospital Clínico Universidad Catolica, Santiago, Chile, from January 2004 to January 2008. A total of 41 IFD episodes were identified in 39 patients; mean age was 46.6 +/- 9.9 years, and 87.8% and 12.2% occurred in H-O and HCTS patients respectively. 15/41(36.6%) episodes were proven, 36.6% probable and 11/41 (26.8%) possible. In 26 (63.4%) episodes aspergillosis was diagnosed (20 pulmonary, 3 sinus, 1 laryngeal and 1 case with pulmonary and cerebral involvement). In 7 patients (17.1%) candidiasis was diagnosed, 5 with a proven bloodstream infection and 2 with possible hepatosplenic candidiasis; mucormyeosis was diagnosed in 4 (9.8%) Fusarium infection was demonstrated in 2 patients (4.9%), and Mucor and Aspergillus pulmonary coinfection and Alternaria sp rhino-sinusitis in one patient each. The frequency of IFD among febrile neutropenic patients was 26.2% and 6.4% in H-O and HSCT receptors respectively. The overall mortality was 36%. Aspergillosis is the most common IFD infection among H-O patients and HSCT receptors in our center. Candidiasis followed although only in H-O patients most probably because of routine use of antifungal prophylaxis in HSCT recipients. Continuous surveillance is required to develop local guidelines and to evaluate antifungal strategies in different clinical scenarios.
High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?
Nabili, Mojtaba; Shokohi, Tahereh; Moazeni, Maryam; Khodavaisy, Sadegh; Aliyali, Masoud; Badiee, Parisa; Zarrinfar, Hossein; Hagen, Ferry; Badali, Hamid
Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l-1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the β-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR34/L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi.
Sensitive and selective quantification of total and free itraconazole and hydroxyitraconazole in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry.
Suzuki, Yosuke; Tanaka, Ryota; Oyama, Nobuhiro; Nonoshita, Ko; Hashinaga, Kazuhiko; Umeki, Kenji; Sato, Yuhki; Hiramatsu, Kazufumi; Kadota, Jun-Ichi; Itoh, Hiroki
Protein-free (unbound) drug concentrations have been reported to be better biomarker of pharmacodynamics compared with total drug concentrations. In this study, we developed and validated an assay for the quantification of total and free itraconazole and hydroxyitraconazole, a main metabolite with antifungal activity, in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Plasma sample was ultra-filtrated for the measurement of free itraconazole and hydroxyitraconazole concentrations. The samples were prepared by solid phase extraction, and then subject to UPLC-MS/MS quantification. The assay fulfilled the requirements of the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) guidelines for assay validation, with a lower limit of quantification of 10ng/mL for total itraconazole and hydroxyitraconazole, and 0.1 and 0.5ng/mL for free itraconazole and hydroxyitraconazole, respectively. Recovery rates of total itraconazole and hydroxyitraconazole from whole plasma ranged from 53.3% to 64.0%, and recovery rates of free itraconazole and hydroxyitraconazole from ultrafiltrated plasma ranged from 81.6% to 98.7%. Matrix effect varied between 79.1% and 109.4% for total itraconazole and hydroxyitraconazole, and between 81.3% and 99.7% for free itraconazole and hydroxyitraconazole. The assay was successfully applied to therapeutic drug monitoring of itraconazole in three patients with chronic progressive pulmonary aspergillosis or invasive pulmonary aspergillosis. Plasma free hydroxyitraconazole concentrations were 8.1-, 23.3-, and 51.1-fold higher than plasma free itraconazole concentrations in the three patients. A method for sensitive and selective quantification of plasma total and free itraconazole and hydroxyitraconazole concentrations was developed using UPLC-MS/MS. Free hydroxyitraconazole concentration may be most important in therapeutic drug monitoring of itraconazole. Copyright �
Spatial variability of disease incidence and mortality in the sea fan Gorgonia ventalina in Puerto Rico (Alcyonacea: Goorgoniidae
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Anabella Zuluaga-Montero
Full Text Available Populations of the common sea fan (Gorgonia ventalina were decimated by an aspergillosis outbreak throughout the Caribbean two decades ago. Since then, aspergillosis has been considered as the principal cause of mortality in sea fans. However, prevalence and presumably incidence of this disease have been declining in the Caribbean since the mid 1990s. Incidence indicates new cases of disease in previously healthy colonies, while prevalence indicates percent of diseased colonies at a given sample. Most coral disease studies use prevalence rather than incidence to assess the temporal dynamics of diseases. Nevertheless, conclusions based only on prevalence should be handled carefully to avoid misinterpretation. This study was carried out at six reefs in Eastern Puerto Rico. We monitored a total of 448 colonies to (1 obtain estimates of incidence and prevalence of disease and other types of lesions, and (2 to determine causes of sea fan mortality plus their spatial and temporal variation. Three transects (10x1m were haphazardly placed at each study site. At each transect, every colony was numbered and photographed and its height measured to the nearest cm. Transects were monitored at six months intervals and health status of the colonies was recorded. Also, the colonies were divided into height classes (small, medium and large for incidence, prevalence and mortality analyses. Incidence and prevalence of disease were low in all reefs, suggesting that disease currently plays a minor role in the regulation of sea fans populations. Detachment was the main cause of mortality, and size structure data suggest that recruitment may compensate for mortality rates in two of the reefs. Spatial differences in size structure and density may be related to environmental and physical characteristics at the reef scale that allow sea fans to reach a safe colony size. Rev. Biol. Trop. 60 (2: 517-526. Epub 2012 June 01.
High-resolution computed tomographic findings of Aspergillus infection in lung transplant patients
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Gazzoni, Fernando Ferreira, E-mail: email@example.com [Hospital de Clínicas de Porto Alegre, Av. Cristovão Colombo 4105, ap.603-C, Post Code: 90560-005, Porto Alegre, RS (Brazil); Hochhegger, Bruno, E-mail: firstname.lastname@example.com [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil); Severo, Luiz Carlos, E-mail: email@example.com [Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2400, 2° andar, Post Code: 90035-003, Porto Alegre, RS (Brazil); Marchiori, Edson, E-mail: firstname.lastname@example.com [Federal University of Rio de Janeiro, Radiology Department, Av. Pedro Calmon, n° 550 – Cidade Universitária, Post Code: 21941-901, Rio de Janeiro, RJ (Brazil); Pasqualotto, Alessandro, E-mail: email@example.com [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil); Sartori, Ana Paula Garcia, E-mail: email@example.com [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil); Schio, Sadi, E-mail: firstname.lastname@example.com [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil); Camargo, José, E-mail: email@example.com [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil)
Objective: The aim of this study was to assess high-resolution computed tomographic (HRCT) findings at presentation in lung transplant patients diagnosed with pulmonary Aspergillus infection. Materials and methods: We retrospectively reviewed HRCT findings from 23 patients diagnosed with pulmonary aspergillosis. Imaging studies were performed 2–5 days after the onset of symptoms. The patient sample comprised 12 men and 11 women aged 22–59 years (mean age, 43.6 years). All patients had dyspnea, tachypnea, and cough. Diagnoses were established with Platelia Aspergillus enzyme immunoassays for galactomannan antigen detection in bronchoalveolar lavage and recovery of symptoms, and HRCT findings after voriconazole treatment. The HRCT scans were reviewed independently by two observers who reached a consensus decision. Results: The main HRCT pattern, found in 65% (n = 15) of patients, was centrilobular tree-in-bud nodules associated with bronchial thickening. This pattern was described in association with areas of consolidation and ground-glass opacities in 13% (n = 3) of patients. Consolidation and ground-glass opacities were the main pattern in 22% (n = 5) of patients. The pattern of large nodules with and without the halo sign was observed in 13% (n = 3) of patients, and were associated with consolidation and ground-glass opacities in one case. Conclusion: The predominant HRCT findings in lung transplant patients with pulmonary aspergillosis were bilateral bronchial wall thickening and centrilobular opacities with the tree-in-bud pattern. Ground-glass opacities and/or bilateral areas of consolidation were also common findings. Pulmonary nodules with the halo sign were found in only 13% of patients.
Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy.
Huurneman, Luc J; Neely, Michael; Veringa, Anette; Docobo Pérez, Fernando; Ramos-Martin, Virginia; Tissing, Wim J; Alffenaar, Jan-Willem C; Hope, William
Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied. A previously published population PK model was used as the Bayesian prior. The PK-PD model was used to estimate the average area under the concentration-time curve (AUC) in each patient and the resultant galactomannan-time profile. The relationship between the ratio of the AUC to the concentration of voriconazole that induced half maximal killing (AUC/EC50) and the terminal galactomannan level was determined. The voriconazole concentration-time and galactomannan-time profiles were both highly variable. Despite this variability, the fit of the PK-PD model was good, enabling both the pharmacokinetics and pharmacodynamics to be described in individual children. (AUC/EC50)/15.4 predicted terminal galactomannan (P= 0.003), and a ratio of >6 suggested a lower terminal galactomannan level (P= 0.07). The construction of linked PK-PD models is the first step in developing control software that enables not only individualized voriconazole dosages but also individualized concentration targets to achieve suppression of galactomannan levels in a timely and optimally precise manner. Controlling galactomannan levels is a first critical step to maximizing clinical response and survival. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Hyatt, Michael W; Wiederhold, Nathan P; Hope, William W; Stott, Katharine E
Aspergillosis is a common respiratory fungal disease in African penguins ( Spheniscus demersus ) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian studies has resulted in adverse clinical drug effects in penguins. The objective of this study was to determine oral voriconazole pharmacokinetics (PK) in African penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg voriconazole were evaluated with a 4-mo washout period between trials. Plasma voriconazole concentrations were determined via high-performance liquid chromatography. Data was modeled using 3-compartamental population methodologies that supported first-order elimination. Observed mean peak concentration (1.89 μg/ml) after single dosing PK analysis was determined within the first hour following voriconazole administration. In the multiple-dose trial average plasma voriconazole concentrations were significantly higher on days 4 and 7 as compared with day 2. The mean estimates for volume of distribution (V/F) and clearance (Cl/F) for the multiple-dose study were 3.34 L and 0.18 L/hr, respectively. Monte Carlo simulations determined the median area under the curve (AUC 0-24 ) at 84 hr was 37.7 μg·h/ml. As this assessment was comparable with the average AUC in humans receiving the recommended human oral dosage 200 mg b.i.d., it suggests that 5 mg/kg p.o. s.i.d. could be a safe and effective regimen in African penguins for treatment of aspergillosis. However, due to potential drug accumulation and subsequent toxicity, therapeutic drug monitoring with dosage adjustments is recommended to individualize dosing.
Regulation of sulphur assimilation is essential for virulence and affects iron homeostasis of the human-pathogenic mould Aspergillus fumigatus.
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Jorge Amich
Full Text Available Sulphur is an essential element that all pathogens have to absorb from their surroundings in order to grow inside their infected host. Despite its importance, the relevance of sulphur assimilation in fungal virulence is largely unexplored. Here we report a role of the bZIP transcription factor MetR in sulphur assimilation and virulence of the human pathogen Aspergillus fumigatus. The MetR regulator is essential for growth on a variety of sulphur sources; remarkably, it is fundamental for assimilation of inorganic S-sources but dispensable for utilization of methionine. Accordingly, it strongly supports expression of genes directly related to inorganic sulphur assimilation but not of genes connected to methionine metabolism. On a broader scale, MetR orchestrates the comprehensive transcriptional adaptation to sulphur-starving conditions as demonstrated by digital gene expression analysis. Surprisingly, A. fumigatus is able to utilize volatile sulphur compounds produced by its methionine catabolism, a process that has not been described before and that is MetR-dependent. The A. fumigatus MetR transcriptional activator is important for virulence in both leukopenic mice and an alternative mini-host model of aspergillosis, as it was essential for the development of pulmonary aspergillosis and supported the systemic dissemination of the fungus. MetR action under sulphur-starving conditions is further required for proper iron regulation, which links regulation of sulphur metabolism to iron homeostasis and demonstrates an unprecedented regulatory crosstalk. Taken together, this study provides evidence that regulation of sulphur assimilation is not only crucial for A. fumigatus virulence but also affects the balance of iron in this prime opportunistic pathogen.
Burden of serious fungal infections in Guatemala.
Medina, N; Samayoa, B; Lau-Bonilla, D; Denning, D W; Herrera, R; Mercado, D; Guzmán, B; Pérez, J C; Arathoon, E
Guatemala is a developing country in Central America with a high burden of HIV and endemic fungal infections; we attempted to estimate the burden of serious fungal infections for the country. A full literature search was done to identify epidemiology papers reporting fungal infections from Guatemala. We used specific populations at risk and fungal infection frequencies in the population to estimate national rates. The population of Guatemala in 2013 was 15.4 million; 40% were younger than 15 and 6.2% older than 60. There are an estimated 53,000 adults with HIV infection, in 2015, most presenting late. The estimated cases of opportunistic fungal infections were: 705 cases of disseminated histoplasmosis, 408 cases of cryptococcal meningitis, 816 cases of Pneumocystis pneumonia, 16,695 cases of oral candidiasis, and 4,505 cases of esophageal candidiasis. In the general population, an estimated 5,568 adult asthmatics have allergic bronchopulmonary aspergillosis (ABPA) based on a 2.42% prevalence of asthma and a 2.5% ABPA proportion. Amongst 2,452 pulmonary tuberculosis patients, we estimated a prevalence of 495 for chronic pulmonary aspergillosis in this group, and 1,484 for all conditions. An estimated 232,357 cases of recurrent vulvovaginal candidiasis is likely. Overall, 1.7% of the population are affected by these conditions. The true fungal infection burden in Guatemala is unknown. Tools and training for improved diagnosis are needed. Additional research on prevalence is needed to employ public health measures towards treatment and improving the reported data of fungal diseases.
MR findings of nasal cavity lesions showing the infundibular widening on
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Youn, Eun Kyung; Lee, Young Uk; Lee, Young Rae [Kangbuk Samsung Hospital, Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)
Several kinds of nasal cavity lesions located in the region of the infundibulum on CT. At such time, the visualization of these lesions is very similar. The purpose of this study was to differentially diagnose these nasal cavity lesions through evaluation of the MR findings. In 51 cases of pathologically proven nasal cavity masses which on CT showed infundibular widening, we retrospectively evaluated the MR findings. The cases involved prolapsed antral mucosa from sinusitis(n=15), inverted papilloma(n=10), antrochoanal polyp(n=10), aspergillosis(n=9), and nasal polyp(n=7). All patients underwent both CT and MR. imaging. In all cases, CT findings were similar ; soft tissue masses filling the maxillary sinus and nasal cavity were associated with infundibular widening caused by pressure on the uncinate process, leading to erosion. Differential diagnosis by CT was very difficult ; MR T2 weighted imaging was most effective for differential diagnosis of these nasal cavity masses. Prolapsed antral mucosa showed central inhomogeneous mixed signal intensity, with a peripheral rim of hyperintensity along the sinus wall and nasal component. Antrochoanal polyps showed homogeneous bright signal intensity of the antral and nasal component. Aspergillosis showed central dark signal foci. Inverted papillomas showed mixed intermediate and high intensity mixed with high signal intensity. Nasal polyps showed striation mixed of intermediate and high signal intensity, while nasal polyp showed striation of intermediate and high intensity. On Gd-enhanced T1 weighted images, prolapsed antral mucosa and antrochoanal polyp showed peripheral rim enhancement of the antral and nasal component. In contrast, inverted papilloma and nasal polyp showed intense enhancement of the mass and can be separate from the sinus inflammatory disease. Various nasal cavity masses showing infundibular widening on CT can be differentiated on MR images, especially of these are T2 weighted or contrast enhanced T1
Monitoring of Microscopic Filamentous Fungi in Indoor Air of Transplant Unit.
Holý, Ondřej; Matoušková, Ivanka; Kubátová, Alena; Hamal, Petr; Svobodová, Lucie; Jurásková, Eva; Raida, Luděk
The aim of the study was to control the microbial contamination of indoor air monitored monthly at the Transplant Unit of the University Hospital Olomouc from August 2010 to July 2011. The unit is equipped with a three-stage air filtration system with HEPA filters. The MAS-100 air sampler (Merck, GER) was used. Twenty locations were singled out for the purposes of collecting a total of 720 samplings of the indoor air. Swabs of the HVAC diffusers at the sampling locations were always carried out after the sampling of the indoor air. In total, 480 samples of the indoor air were taken for Sabouraud chloramphenicol agar. In 11 cases (2.29%) the cultivation verified the presence of microscopic filamentous fungi. Only two cases involved the sanitary facilities of a patient isolation box; the other positive findings were from the facilities. The most frequent established genus was Aspergillus spp. (4x), followed by Trichoderma spp. (2x) and Penicillium spp. (2x), Paecilomyces spp., Eurotium spp., and Chrysonilia spp. (1x each). In 2 cases the cultivation established sterile aerial mycelium, unfortunately no further identification was possible. A total of 726 swabs of HVAC diffusers were collected (2 positive-0.28%). The study results demonstrated the efficacy of the HVAC equipment. With the continuing increase in the number of severely immunocompromised patients, hospitals are faced with the growing problem of invasive aspergillosis and other opportunistic infections. Preventive monitoring of microbial air contaminants is of major importance for the control of invasive aspergillosis. Copyright© by the National Institute of Public Health, Prague 2015.
Voriconazole: a new triazole antifungal agent.
Pearson, Margaret M; Rogers, P David; Cleary, John D; Chapman, Stanley W
To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. All published and unpublished trials and abstracts citing voriconazole were selected. Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other
SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections
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Paulo Henrique Silva Monteiro
Full Text Available Abstract Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs in systemic granulomatous infections in comparison with gallium-67 (67Ga citrate scintigraphy. Materials and Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99mTc-EDDA-HYNIC-TOC, and 21 after injection of 111In-DTPA-octreotide. All patients also underwent 67Ga citrate imaging, except for one patient who died before the 67Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67Ga uptake in 11 of the 20 patients with positive images and similar to 67Ga uptake in the other 9 patients. The only patient who did not undergo 67Ga scintigraphy underwent 99mTc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with 99mTc-EDDA-HYNIC-TOC or 111In-DTPA-octreotide seems to be a good alternative to 67Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.
SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections
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Monteiro, Paulo Henrique Silva; Souza, Thiago Ferreira de; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Lima, Mariana da Cunha Lopes de; Santos, Allan Oliveira; Ramos, Celso Darío, E-mail: email@example.com [Universidade de Campinas (UNICAMP), SP (Brazil). Escola de Medicina; Mengatti Jair [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)
Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ({sup 67}Ga) citrate scintigraphy. Materials And Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of {sup 99m}Tc-EDDA-HYNIC-TOC, and 21 after injection of {sup 111}In-DTPA-octreotide. All patients also underwent {sup 67}Ga citrate imaging, except for one patient who died before the {sup 67}Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by {sup 67}Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than {sup 67}Ga uptake in 11 of the 20 patients with positive images and similar to {sup 67}Ga uptake in the other 9 patients. The only patient who did not undergo {sup 67}Ga scintigraphy underwent {sup 99m}Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with {sup 99m}Tc-EDDA-HYNIC-TOC or {sup 111}In-DTPA-octreotide seems to be a good alternative to {sup 67}Ga citrate imaging for the evaluation of patients with systemic granulomatous disease. (author)
In silico Identification of Potential Peptides or Allergen Shot Candidates Against Aspergillus fumigatus
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Raman Thakur
Full Text Available Aspergillus fumigatus is capable of causing invasive aspergillosis or acute bronchopulmonary aspergillosis, and the current situation is alarming. There are no vaccine or allergen shots available for Aspergillus-induced allergies. Thus, a novel approach in designing of an effective vaccine or allergen shot candidate against A. fumigatus is needed. Using immunoinformatics approaches from the characterized A. fumigatus allergens, we have mapped epitopic regions to predict potential peptides that elicit both Aspergillus-specific T cells and B cell immune response. Experimentally derived immunodominant allergens were retrieved from www.allergen.org. A total of 23 allergenic proteins of A. fumigatus were retrieved. Out of 23 allergenic proteins, 13 of them showed high sequence similarity to both human and mouse counterparts and thus were eliminated from analysis due to possible cross-reactivity. Remaining allergens were subjected to T cell (major histocompatibility complex class I and II alleles and B cell epitope prediction using immune epitope database analysis resource. Only five allergens have shown a common B and T cell epitopic region between human and mouse. They are Asp f1 {147–156 region (RVIYTYPNKV; Mitogillin}, Asp f2 {5–19 region (LRLAVLLPLAAPLVA; Hypothetical protein}, Asp f5 {305–322 region (LNNYRPSSSSLSFKY; Metalloprotease}, Asp f17 {98–106 region (AANAGGTVY; Hypothetical protein}, and Asp f34 {74–82 region (YIQDGSLYL; PhiA cell wall protein}. The epitopic region from these five allergenic proteins showed potential for development of single peptide- or multipeptide-based vaccine or allergen shots for experimental prioritization.
Characterization and genetic variability of feed-borne and clinical animal/human Aspergillus fumigatus strains using molecular markers.
Pena, Gabriela A; Coelho, Irene; Reynoso, María M; Soleiro, Carla; Cavaglieri, Lilia R
Aspergillus fumigatus, the major etiological agent of human and animal aspergillosis, is a toxigenic fungus largely regarded as a single species by macroscopic and microscopic features. However, molecular studies have demonstrated that several morphologically identified A. fumigatus strains might be genetically distinct. This work was aimed to apply PCR-restriction length fragment polymorphisms (PCR-RFLP) and random amplification of polymorphic DNA (RAPD) molecular markers to characterize a set of feed-borne and clinical A. fumigatus sensu lato strains isolated from Argentina and Brazil and to determine and compare their genetic variability. All A. fumigatus strains had the same band profile and those typical of A. fumigatus sensu stricto positive controls by PCR-RFLP. Moreover, all Argentinian and Brazilian strains typified by RAPD showed similar band patterns to each other and to A. fumigatus sensu stricto reference strains regardless of their isolation source (animal feeds or human/animal clinical cases) and geographic origin. Genetic similarity coefficients ranged from 0.61 to 1.00, but almost all isolates showed 78% of genetic similarly suggesting that genetic variability was found at intraspecific level. Finally, benA sequencing confirmed its identification as A. fumigatus sensu stricto species. These results suggest that A. fumigatus sensu stricto is a predominant species into Aspergillus section Fumigati found in animal environments as well as in human/animal clinical cases, while other species may be rarely isolated. The strains involved in human and animal aspergillosis could come from the environment where this fungus is frequently found. Rural workers and animals would be constantly exposed. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: email@example.com.
SNaPAfu: a novel single nucleotide polymorphism multiplex assay for aspergillus fumigatus direct detection, identification and genotyping in clinical specimens.
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Rita Caramalho
Full Text Available OBJECTIVE: Early diagnosis of invasive aspergillosis is essential for positive patient outcome. Likewise genotyping of fungal isolates is desirable for outbreak control in clinical setting. We designed a molecular assay that combines detection, identification, and genotyping of Aspergillus fumigatus in a single reaction. METHODS: To this aim we combined 20 markers in a multiplex reaction and the results were seen following mini-sequencing readings. Pure culture extracts were firstly tested. Thereafter, Aspergillus-DNA samples obtained from clinical specimens of patients with possible, probable, or proven aspergillosis according to European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG criteria. RESULTS: A new set of designed primers allowed multilocus sequence typing (MLST gene amplification in a single multiplex reaction. The newly proposed SNaPAfu assay had a specificity of 100%, a sensitivity of 89% and detection limit of 1 ITS copy/mL (∼0.5 fg genomic Aspergillus-DNA/mL. The marker A49_F was detected in 89% of clinical samples. The SNaPAfu assay was accurately performed on clinical specimens using only 1% of DNA extract (total volume 50 µL from 1 mL of used bronchoalveolar lavage. CONCLUSIONS: The first highly sensitive and specific, time- and cost-economic multiplex assay was implemented that allows detection, identification, and genotyping of A. fumigatus strains in a single amplification followed by mini-sequencing reaction. The new test is suitable to clinical routine and will improve patient management.
Aspergilose pulmonar necrotizante: a propósito de dois casos clÃnicos
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S. Carreira
Full Text Available Resumo: Os autores apresentam dois casos clÃnicos de aspergilose pulmonar necrotizante. Esta patologia faz parte de um espectro de condições clÃnicas provocadas pela inalação de esporos do fungo Aspergillus. A aspergilose pulmonar necrotizante (APN corresponde a um processo indolente de destruição do pulmão pelo Aspergillus, geralmente A. fumigatus. O diagnóstico definitivo faz-se através da demonstração histológica de invasão tecidual pelo Aspergillus e do seu crescimento em cultura 2. Pela dificuldade em obter um diagnóstico definitivo foram estabelecidos os seguintes critérios de diagnóstico que, quando reunidos, são fortemente indicativos de APN: aspectos clÃnicos e radiológicos consistentes com o diagnóstico, elevação dos parâmetros inflamatórios (PCR, VS e marcadores serológicos positivos para Aspergillus ou isolamento de Aspergillus em amostras do aparelho respiratório. Deve ser feita a exclusão de tuberculose activa, micobacterioses não tuberculosas, histoplasmose cavitária e coccidiomicose. à necessário elevar o grau de suspeição desta patologia e realizar os exames de diagnóstico indicados de forma a iniciar terapêutica atempadamente. Abstract: The authors present two case reports of necrotizing pulmonary aspergillosis. This disease is part of a spectrum of clinical conditions caused by the inhalation of Aspergillus spores. The necrotizing pulmonary aspergillosis (NPA corresponds to an indolent, destructive process of the lung due to invasion by Aspergillus species, usually A. fumigatus. The diagnosis is confirmed by a histological demonstration of tissue invasion by Aspergillus species and its growth on culture. Due to the difficulty in confirming the diagnosis, the following diagnosis criteria were established and when combined are highly indicative of NPA: characteristic clinical and radiological findings, elevation of
Characterization of the FKBP12-Encoding Genes in Aspergillus fumigatus.
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Katie Falloon
Full Text Available Invasive aspergillosis, largely caused by Aspergillus fumigatus, is responsible for a growing number of deaths among immunosuppressed patients. Immunosuppressants such as FK506 (tacrolimus that target calcineurin have shown promise for antifungal drug development. FK506-binding proteins (FKBPs form a complex with calcineurin in the presence of FK506 (FKBP12-FK506 and inhibit calcineurin activity. Research on FKBPs in fungi is limited, and none of the FKBPs have been previously characterized in A. fumigatus. We identified four orthologous genes of FKBP12, the human FK506 binding partner, in A. fumigatus and designated them fkbp12-1, fkbp12-2, fkbp12-3, and fkbp12-4. Deletional analysis of the four genes revealed that the Δfkbp12-1 strain was resistant to FK506, indicating FKBP12-1 as the key mediator of FK506-binding to calcineurin. The endogenously expressed FKBP12-1-EGFP fusion protein localized to the cytoplasm and nuclei under normal growth conditions but also to the hyphal septa following FK506 treatment, revealing its interaction with calcineurin. The FKBP12-1-EGFP fusion protein didn't localize at the septa in the presence of FK506 in the cnaA deletion background, confirming its interaction with calcineurin. Testing of all deletion strains in the Galleria mellonella model of aspergillosis suggested that these proteins don't play an important role in virulence. While the Δfkbp12-2 and Δfkbp12-3 strains didn't show any discernable phenotype, the Δfkbp12-4 strain displayed slight growth defect under normal growth conditions and inhibition of the caspofungin-mediated "paradoxical growth effect" at higher concentrations of the antifungal caspofungin. Together, these results indicate that while only FKBP12-1 is the bona fide binding partner of FK506, leading to the inhibition of calcineurin in A. fumigatus, FKBP12-4 may play a role in basal growth and the caspofungin-mediated paradoxical growth response. Exploitation of differences between A
Infectious and non-infectious neurologic complications in heart transplant recipients.
Muñoz, Patricia; Valerio, Maricela; Palomo, Jesús; Fernández-Yáñez, Juan; Fernández-Cruz, Ana; Guinea, Jesús; Bouza, Emilio
Neurologic complications are important causes of morbidity and mortality in heart transplant (HT) recipients. New immunomodulating agents have improved survival rates, although some have been associated with a high rate of neurologic complications (infectious and non-infectious). We conducted this study to analyze the frequency of these complications, before and after the use of daclizumab induction therapy. We reviewed all neurologic complications in our HT cohort, comparing infectious with non-infectious complications over 2 periods of time in which different induction therapies were used (316 patients with OKT3 or antithymocyte globulin from 1988 to 2002, and 68 patients with daclizumab from 2003 to 2006). Neurologic complications were found in 75/384 patients (19.5%) with a total of 78 episodes. Non-infectious complications accounted for 68% of the 78 episodes of neurologic complications. A total of 51 patients and 53 episodes were detailed as follows: 25 episodes of stroke (25 of 78 total episodes, 32%; 19 ischemic, 6 hemorrhagic); 7 neuropathies; 6 seizures; 4 episodes of transient ischemic attack (TIA); 3 anoxic encephalopathy; 2 each brachial plexus palsy and metabolic encephalopathy; and 1 each myoclonia, central nervous system (CNS) lymphoma, subdural hematoma, and Cotard syndrome. Mean time to presentation of stroke, TIA, and encephalopathy was 1 day (range, 1-19 d) posttransplant. Mortality rate among non-infectious complications was 12/53 (22.6%). Infectious complications accounted for 32% of the 78 total episodes. We found 25 episodes in 24 patients: 17 herpes zoster (median, 268 d after HT), 3 CNS aspergillosis (median, 90 d after HT), 1 CNS toxoplasmosis and tuberculosis (51 d after HT), 1 pneumococcal meningitis (402 d after HT), and 2 Listeria meningitis (median, 108 d after HT). The 3 patients with CNS aspergillosis died. The mortality rate among patients with infectious neurologic complications was 12% (42.8% if the CNS was involved). When we
Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis).
Bechert, Ursula; Christensen, J Mark; Poppenga, Robert; Fahmy, Sahar A; Redig, Patrick
To determine pharmacokinetic parameters of orally administered terbinafine hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red-tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30, and 60 mg/kg doses with a 2-week washout period between trials. After administration of 15 mg/kg terbinafine, mean (+/- SD) plasma concentration peaked in approximately 5 hours at 0.3 +/- 0.24 microg/mL, whereas a 30 mg/kg dose resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in 3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/- 0.75 microg/mL in 5 hours. The volume of distribution decreased with increasing doses, averaging 76.8 +/- 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2 +/- 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated in deep tissues, limiting further distribution at higher doses. The harmonic mean (+/- SD) half-life was biphasic, with initial values of 14.7 +/- 6.67 hours, 17.5 +/- 8.7 hours, and 13.3 +/- 5.03 hours for 15, 30, and 60 mg/kg doses, respectively. A rapid first-elimination phase was followed by a slower second phase, and final elimination was estimated to be 161 +/- 78.2 and 147 +/- 65.6 hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the area under the curve but not for peak plasma concentrations for the 3 doses used. Calculations based on pharmacokinetic parameter values indicated that a dosage of 22 mg/kg terbinafine q24h would result in steady-state trough plasma concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6 microg/mL). This dosage is recommended as a potential treatment option for aspergillosis in raptors. However, additional research is required to determine both treatment efficacy and safety.
The Absence of NOD1 Enhances Killing of Aspergillus fumigatus Through Modulation of Dectin-1 Expression
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Mark S. Gresnigt
Full Text Available One of the major life-threatening infections for which severely immunocompromised patients are at risk is invasive aspergillosis (IA. Despite the current treatment options, the increasing antifungal resistance and poor outcome highlight the need for novel therapeutic strategies to improve outcome of patients with IA. In the current study, we investigated whether and how the intracellular pattern recognition receptor NOD1 is involved in host defense against Aspergillus fumigatus. When exploring the role of NOD1 in an experimental mouse model, we found that Nod1−/− mice were protected against IA and demonstrated reduced fungal outgrowth in the lungs. We found that macrophages derived from bone marrow of Nod1−/− mice were more efficiently inducing reactive oxygen species and cytokines in response to Aspergillus. Most strikingly, these cells were highly potent in killing A. fumigatus compared with wild-type cells. In line, human macrophages in which NOD1 was silenced demonstrated augmented Aspergillus killing and NOD1 stimulation decreased fungal killing. The differentially altered killing capacity of NOD1 silencing versus NOD1 activation was associated with alterations in dectin-1 expression, with activation of NOD1 reducing dectin-1 expression. Furthermore, we were able to demonstrate that Nod1−/− mice have elevated dectin-1 expression in the lung and bone marrow, and silencing of NOD1 gene expression in human macrophages increases dectin-1 expression. The enhanced dectin-1 expression may be the mechanism of enhanced fungal killing of Nod1−/− cells and human cells in which NOD1 was silenced, since blockade of dectin-1 reversed the augmented killing in these cells. Collectively, our data demonstrate that NOD1 receptor plays an inhibitory role in the host defense against Aspergillus. This provides a rationale to develop novel immunotherapeutic strategies for treatment of aspergillosis that target the NOD1 receptor, to enhance the
Selective Antifungal Action of Crude Extracts of Cassia fistula L.: A Preliminary Study on Candida and Aspergillus species
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Panda, S. K.
Full Text Available Preliminary studies on the phytochemicals and extracts of petroleum ether, chloroform, ethanol, methanol and aqueous of Cassia fistula leaves were examined for antifungal activity using agar cup and broth dilution methods. Although all five extracts showed promising antifungal activity against Candida albicans (12.6 mm, C. krusei (13.3 mm, C. parapsilosis (14.0 mm, and C. tropicalis (14.3 mm, yet maximum activity was observed in methanol extract followed by ethanol and aqueous extracts. Petroleum ether and ethanol extracts, showed zone of inhibition against all the three species of Aspergillus with highest zone of inhibition for A. fumigatus (12.0 mm. MIC values for most of the extracts ranged from 0.75 to 3.0 mg/mL; while the least MFC value was observed at 6.0 mg/mL. Result of MFC showed that at concentration 6.0 mg/mL, 75% of the test Candida species were killed while rests 25% were inhibited at same concentration. Phytochemical analysis exhibited the presence of alkaloids, flavonoids, carbohydrates, glycosides, protein and amino acids, saponins and triterpenoids in different extracts. These results reveal the antifungal activity of C. fistula leaves extracts which may be useful in treatment of candidiasis and aspergillosis. However, further studies with purified fractions or bioactive compounds responsible for antifungal activity need to be evaluated.
Tracheobronchial Manifestations of Aspergillus Infections
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Rafal Krenke
Full Text Available Human lungs are constantly exposed to a large number of Aspergillus spores which are present in ambient air. These spores are usually harmless to immunocompetent subjects but can produce a symptomatic disease in patients with impaired antifungal defense. In a small percentage of patients, the trachea and bronchi may be the main or even the sole site of Aspergillus infection. The clinical entities that may develop in tracheobronchial location include saprophytic, allergic and invasive diseases. Although this review is focused on invasive Aspergillus tracheobronchial infections, some aspects of allergic and saprophytic tracheobronchial diseases are also discussed in order to present the whole spectrum of tracheobronchial aspergillosis. To be consistent with clinical practice, an approach basing on specific conditions predisposing to invasive Aspergillus tracheobronchial infections is used to present the differences in the clinical course and prognosis of these infections. Thus, invasive or potentially invasive Aspergillus airway diseases are discussed separately in three groups of patients: (1 lung transplant recipients, (2 highly immunocompromised patients with hematologic malignancies and/or patients undergoing hematopoietic stem cell transplantation, and (3 the remaining, less severely immunocompromised patients or even immunocompetent subjects.
Identification of morphological and molecular Aspergillus species isolated from patients based on beta-tubulin gene sequencing
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Mahnaz Kheirkhah
Full Text Available Background: Aspergillus species are opportunistic pathogens among immunocompromised patients. In terms of pathogenesis and mycotoxin production, they are in great value. The aim of the this study was to evaluate of beta-tubulin gene for identification of clinical Aspergillus species by PCR-sequencing method compared to morphological features of clinical isolates (such as conidial shape in direct microscopic examination, colony shape in culture, and physiological tests. Materials and Methods: In this study, 465 patients referred to the Shefa laboratory of Isfahan were evaluated. Morphological and molecular identification of clinical samples were performed using culture on sabouraud agar, malt extract agar, czapekdox agar, direct microscopy, and PCR-sequencing of beta tubulin gene, respectively. Sequences were analyzed in comparison with gene bank data. Results: Thirty nine out of 465 suspected cases (8.4% had aspergillosis. The most prevalent species were Aspergillus flavus (56.4%, A. oryzae (20.5%, and A. fumigatus (10.2%, respectively. Fifty nine percent of patients were females and 49% were males. Conclusion: In comparison with phenotypic tests, sequencing of beta-tubulin gene for identification of Aspergillus species is at great value. Replacement of molecular techniques with conventional tests is recommended for precise identification of microorganism for better management of infection.
Estimating the burden of fungal disease in Vietnam.
Beardsley, J; Denning, D W; Chau, N V; Yen, N T B; Crump, J A; Day, J N
Data regarding the prevalence of fungal infections in Vietnam are limited yet they are likely to occur more frequently as increasingly sophisticated healthcare creates more iatrogenic risk factors. In this study, we sought to estimate baseline incidence and prevalence of selected serious fungal infections for the year 2012. We made estimates with a previously described actuarial method, using reports on the incidence and prevalence of various established risk factors for fungal infections from Vietnam, or similar environments, supplemented by personal communications. Global data were used if local data were unavailable. We estimated 2,352,748 episodes of serious fungal infection occurred in Vietnam in 2012. Frequent conditions included recurrent vaginal candidiasis (3893/100,000 women annually), tinea capitis (457/100,000 annually) and chronic pulmonary aspergillosis (61/100,000/5 year period). We estimated 140 cases of cryptococcal meningitis, 206 of penicilliosis and 608 of Pneumocystis jirovecii pneumonia. This is the first summary of Vietnamese fungal infections. The majority of severe disease is due to Aspergillus species, driven by the high prevalence of pulmonary tuberculosis. The AIDS epidemic highlights opportunistic infections, such as penicilliosis and cryptococcosis, which may complicate immunosuppressive treatments. These estimates provide a useful indication of disease prevalence to inform future research and resource allocation but should be verified by further epidemiological approaches. © 2015 The Authors Mycoses Published by Blackwell Verlag GmbH.
FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection
Sinha, Meenal; McCabe, Orla; Palmer, Jonathan M.; Choera, Tsokyi; Yun Lim, Fang; Wimmerova, Michaela; Carrington, Stephen D.; Yuan, Shaopeng; Lowell, Clifford A.; Oscarson, Stefan; Keller, Nancy P.; Fahy, John V.
The immune mechanisms that recognize inhaled Aspergillus fumigatus conidia to promote their elimination from the lungs are incompletely understood. FleA is a lectin expressed by Aspergillus fumigatus that has twelve binding sites for fucosylated structures that are abundant in the glycan coats of multiple plant and animal proteins. The role of FleA is unknown: it could bind fucose in decomposed plant matter to allow Aspergillus fumigatus to thrive in soil, or it may be a virulence factor that binds fucose in lung glycoproteins to cause Aspergillus fumigatus pneumonia. Our studies show that FleA protein and Aspergillus fumigatus conidia bind avidly to purified lung mucin glycoproteins in a fucose-dependent manner. In addition, FleA binds strongly to macrophage cell surface proteins, and macrophages bind and phagocytose fleA-deficient (∆fleA) conidia much less efficiently than wild type (WT) conidia. Furthermore, a potent fucopyranoside glycomimetic inhibitor of FleA inhibits binding and phagocytosis of WT conidia by macrophages, confirming the specific role of fucose binding in macrophage recognition of WT conidia. Finally, mice infected with ΔfleA conidia had more severe pneumonia and invasive aspergillosis than mice infected with WT conidia. These findings demonstrate that FleA is not a virulence factor for Aspergillus fumigatus. Instead, host recognition of FleA is a critical step in mechanisms of mucin binding, mucociliary clearance, and macrophage killing that prevent Aspergillus fumigatus pneumonia. PMID:27058347
Spontaneous thoracic air-leakage syndrome in patients following allogeneic hematopoietic stem cell transplantation: Causes, CT-follow up and patient outcome
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Vogel, Monika [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)]. E-mail: firstname.lastname@example.com; Brodoefel, Harald [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Bethge, Wolfgang [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Faul, Christoph [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Hartmann, Joerg [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Schimmel, Heiko [Department of Pathology, Eberhard-Karls-University, Liebermeisterstrasse 8, 72076 Tuebingen (Germany); Wehrmann, Manfred [Department of Pathology, Eberhard-Karls-University, Liebermeisterstrasse 8, 72076 Tuebingen (Germany); Claussen, Claus D. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Horger, Marius [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)
Objective: The purpose of this article is to describe and illustrate the acute and follow-up imaging features, clinical constellation and outcome of patients with thoracic air-leakage syndrome following allogeneic hematopoietic stem cell transplantation (allo-HCT). Methods: Patients with evidence of thoracic air-leakage, i.e. spontaneous pneumomediastinum, spontaneous pneumothorax or interstitial emphysema after allo-HCT were retrospectively identified by a chart review. Acute and follow-up morphology, duration and patient outcome were analyzed on CT (HRCT or MSCT with HR-reconstructions). Correlation was made with histological results of transbronchial biopsy. Results: The 6 patients included (3 male and 3 female, 14-64 years old) with thoracic air-leakage after allo-HCT all had histologically proven bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP). Thoracic air-leakage consisted of spontaneous pneumomediastinum associated with active invasive pulmonary aspergillosis (IPA) in 4/6 and spontaneous pneumothorax or interstitial emphysema each in 1/6 patients. Duration of thoracic air-leakage was 7-135 days. Of the patients with spontaneous pneumomediastinum, 3/4 died of IPA. One patient survived until complete regression of spontaneous pneumomediastinum. One patient died 7 days after spontaneous pneumothorax and one survived developing chronic interstitial emphysema. Conclusion: In all cases, thoracic air-leakage was associated to BO or BOOP. In the majority of cases with additional IPA, thoracic air-leakage is more indicative for severity of pulmonary disease than a life-threatening entity itself.
Radioiodine uptake in inactive pulmonary tuberculosis
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Bakheet, S.M.; Powe, J.; Al Suhaibani, H. [Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Hammami, M.M.; Bazarbashi, M. [Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)
Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases. (orig.) With 4 figs., 1 tab., 9 refs.
Determining the analytical specificity of PCR-based assays for the diagnosis of IA: What is Aspergillus?
Morton, C Oliver; White, P Lewis; Barnes, Rosemary A; Klingspor, Lena; Cuenca-Estrella, Manuel; Lagrou, Katrien; Bretagne, Stéphane; Melchers, Willem; Mengoli, Carlo; Caliendo, Angela M; Cogliati, Massimo; Debets-Ossenkopp, Yvette; Gorton, Rebecca; Hagen, Ferry; Halliday, Catriona; Hamal, Petr; Harvey-Wood, Kathleen; Jaton, Katia; Johnson, Gemma; Kidd, Sarah; Lengerova, Martina; Lass-Florl, Cornelia; Linton, Chris; Millon, Laurence; Morrissey, C Orla; Paholcsek, Melinda; Talento, Alida Fe; Ruhnke, Markus; Willinger, Birgit; Donnelly, J Peter; Loeffler, Juergen
A wide array of PCR tests has been developed to aid the diagnosis of invasive aspergillosis (IA), providing technical diversity but limiting standardisation and acceptance. Methodological recommendations for testing blood samples using PCR exist, based on achieving optimal assay sensitivity to help exclude IA. Conversely, when testing more invasive samples (BAL, biopsy, CSF) emphasis is placed on confirming disease, so analytical specificity is paramount. This multicenter study examined the analytical specificity of PCR methods for detecting IA by blind testing a panel of DNA extracted from a various fungal species to explore the range of Aspergillus species that could be detected, but also potential cross reactivity with other fungal species. Positivity rates were calculated and regression analysis was performed to determine any associations between technical specifications and performance. The accuracy of Aspergillus genus specific assays was 71.8%, significantly greater (P PCR assay targeting the rRNA genes (P = .0011). Conversely, there was a significant association between rRNA PCR targets and false positivity (P = .0032). To conclude current Aspergillus PCR assays are better suited for detecting A. fumigatus, with inferior detection of most other Aspergillus species. The use of an Aspergillus genus specific PCR assay targeting the rRNA genes is preferential. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: email@example.com.
The Impact of Fusarium Mycotoxins on Human and Animal Host Susceptibility to Infectious Diseases
Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska
Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well. PMID:24476707
[Mold infections in lung transplants].
Solé, Amparo; Ussetti, Piedad
Invasive infections by molds, mainly Aspergillus infections, account for more than 10% of infectious complications in lung transplant recipients. These infections have a bimodal presentation: an early one, mainly invading bronchial airways, and a late one, mostly focused on lung or disseminated. The Aspergillus colonization at any time in the post-transplant period is one of the major risk factors. Late colonization, together with chronic rejection, is one of the main causes of late invasive forms. A galactomannan value of 0.5 in bronchoalveolar lavage is currently considered a predictive factor of pulmonary invasive infection. There is no universal strategy in terms of prophylaxis. Targeted prophylaxis and preemptive treatment instead of universal prophylaxis, are gaining more followers. The therapeutic drug monitoring level of azoles is highly recommended in the treatment. Monotherapy with voriconazole is the treatment of choice in invasive aspergillosis; combined antifungal therapies are only recommended in severe, disseminated, and other infections due to non-Aspergillus molds. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.
Systemic mycosis caused by Trichophyton spp. in an olive ridley sea turtle (Lepidochelys olivacea): an immunohistochemical study.
Oros, J; Calabuig, P; Arencibia, A; Camacho, M; Jensen, He
A sub-adult female olive ridley sea turtle (Lepidochelys olivacea) was found floating off the coast of Gran Canaria, Canary Islands, Spain. The turtle was lethargic and weak, and died one day after it was found. Necropsy was performed and selected samples of lung and liver were routinely processed for histopathological and immunohistological studies. Grossly, round, ulcerative lesions were observed on the rear flippers. The liver, spleen, coelomic wall, gastric serosa, lungs and urinary bladder were covered by various amounts of fibrin and small granulomas. Histopathologically, a severe fibrinous and granulomatous polyserositis (liver, spleen, stomach, urinary bladder, coelomic wall), severe fibrinous pleuritis and severe multifocal granulomatous pneumonia were diagnosed. Numerous fungal hyphae were observed associated with the lesions. Specific monoclonal and heterologously absorbed polyclonal antibodies served as the primary reagents for identification of aspergillosis, candidiasis, fusariosis, geotricosis, dermatophytosis, scedosporiosis, and zygomycosis. All hyphae were identified as Trichophyton spp., because a strong and uniform reactivity was obtained only with an heterologously absorbed polyclonal antibody raised against somatic antigens of Trichophyton spp. Systemic mycosis caused by Trichophyton spp. There are no known previous reports of Trichophyton spp. causing skin disease or systemic mycotic infection in sea turtles. The usefulness of immunohistochemistry for identifying fungi in sea turtles is reinforced.
Iatrogenic Cushing syndrome in patients receiving inhaled budesonide and itraconazole or ritonavir: two cases and literature review.
Blondin, Marie-Christine; Beauregard, Hugues; Serri, Omar
To present two cases of iatrogenic Cushing syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with ritonavir and itraconazole. We present the clinical and biochemical data of two patients in whom diagnosis of Cushing syndrome was caused by this interaction. We also reviewed the pertinent literature and management options. A 71-year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient rapidly developed a typical Cushing syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 AM cortisol concentrations were suppressed at 0.76 and 0.83 μg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46-year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of human immunodeficiency virus (HIV). In the following months, she developed typical signs of Cushing syndrome. Her morning serum cortisol concentration was 1.92 μg/dL. A cosyntropin stimulation test showed values of serum cortisol of Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir.
Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents.
Kim, Jong H; Campbell, Bruce C; Mahoney, Noreen; Chan, Kathleen L; Molyneux, Russell J; Balajee, Arunmozhi
A number of benzoic acid analogues showed antifungal activity against strains of Aspergillus flavus, Aspergillus fumigatus and Aspergillus terreus, causative agents of human aspergillosis, in in vitro bioassays. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids were increased by addition of a methyl, methoxyl or chloro group at position 4 of the aromatic ring, or by esterification of the carboxylic acid with an alkyl group, respectively. Thymol, a natural phenolic compound, was a potent chemosensitizing agent when co-applied with the antifungal azole drugs fluconazole and ketoconazole. The thymol-azole drug combination demonstrated complete inhibition of fungal growth at dosages far lower than the drugs alone. Co-application of thymol with amphotericin B had an additive effect on all strains of aspergilli tested with the exception of two of three strains of A. terreus, where there was an antagonistic effect. Use of two mitogen-activated protein kinase (MAPK) mutants of A. fumigatus, sakAΔ and mpkCΔ, having gene deletions in the oxidative stress response pathway, indicated antifungal and/or chemosensitization activity of the benzo analogues was by disruption of the oxidative stress response system. Results showed that both these genes play overlapping roles in the MAPK system in this fungus. The potential of safe, natural compounds or analogues to serve as chemosensitizing agents to enhance efficacy of commercial antifungal agents is discussed. Published by Elsevier Ltd.
Pulmonary infection in patients with cyclosporine, azathioprine, and corticosteroids after cardiac transplantation; Clinical and radiographic assessment
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Murayama, Sadayuki; Ikezoe, Junpei; Godwin, J.D.; Marglin, S.I.; Allen, M.D. (University of Washington Medical Center, Seattle, WA (United States))
Between November 1985 and November 1989, 54 patients have undergone 55 cardiac transplants, 5 of whom died during operation or one week after transplantation. The remaining 49 patients with a minimum follow-up of 5 months were studied to examine pulmonary infection clinically and radiologically while receiving triple drug immunosuppression consisting of cyclosporine, azathioprine, and prednisolone. Pulmonary infection occurred in 14 patients (29%) with a total of 21 occasions. Causative organisms were identified in 9 occasions, with the most common organism being Cytomegalovirus (CMV). One patient died of pulmonary infection with Aspergillus. Causative organisms occurring in the remaining 12 occasions of pulmonary infection were unknown, which did not lead to death. Because pulmonary infection of unknown organisms rapidly responded to convensional antibiotics, it seemed to have been caused by bacteria. Pulmonary infection of unknown organism occurred 13.2{+-}3.2 months after transplantation, as compared with 3.3{+-}1.0 months in pulmonary infection of known organisms. Chest plain radiographic features fell into four types: (1) interstitial shadow seen in pulmonary infection of CMV, Pneumocystis carinii, or Hemophilia influenza, (2) patchy, and basilar and lobular consolidation shadows in bacterial pneumonia, (3) localized nodular shadow in aspergillosis, and (4) multiple patchy and confluent opacity patterns occurring in herpes simplex viral infection. Pulmonary infection of influenza bacteria for one patient and pulmonary infection of unknown organisms for 4 patients were difficult to identify from pulmonary infection of CMV. (N.K.).
Sick Building Syndrome: is mould the cause?
Terr, Abba I
Moulds are responsible for diseases in humans through the three pathogenetic mechanisms of infection, allergy, and toxicity. Fungal infection is especially a risk factor for immunodeficient patients, but it occurs in immunocompetent patients as well. Fungal allergy is manifested as bronchial asthma, hypersensitivity pneumonitis, allergic bronchopulmonary aspergillosis, or allergic fungal sinusitis. Mycotoxicosis is almost exclusively the result of ingestion of mould-contaminated foodstuffs. In each case there is specificity for the etiologic mould. There is controversy regarding the ability of indoor airborne mould spores to cause human disease through non-specific toxicity via the inhalation route. Pulmonary mycotoxicosis is an established, although rare, occupational disease of farmers who inhale enormous quantities of mycotoxins, endotoxins, and other toxic chemicals from contaminated silage. Other conditions attributed to indoor airborne mycotoxin are unproven. These include infantile pulmonary hemosiderosis, epistaxis, 'toxic encephalopathy', immune dysregulation and a variety of subjective complaints without objective signs of pathology such as fatigue, headache, dyspnea, gastrointestinal distress, neuromuscular and skeletal complaints, etc. Non-specific irritation from moulds via the inhalation route is also a controversial subject that remains unproven. Published studies alleging an epidemiologic causal relationship are unconvincing.
Long-term follow-up and treatment of congenital alveolar proteinosis
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Muensterer Oliver J
Full Text Available Abstract Background Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP due to mutations in the GM-CSF receptor are not well known. Case presentation A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child. Conclusions The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.
Co-morbidities in severe asthma: Clinical impact and management.
Porsbjerg, Celeste; Menzies-Gow, Andrew
Patients with severe asthma represent a minority of the total asthma population, but carry a majority of the morbidity and healthcare costs. Achieving better asthma control in this group of patients is therefore of key importance. Systematic assessment of patients with possible severe asthma to identify treatment barriers and triggers of asthma symptoms, including co-morbidities, improves asthma control and reduces healthcare costs and is recommended by international guidelines on management of severe asthma. This review provides the clinician with an overview of the prevalence and clinical impact of the most common co-morbidities in severe asthma, including chronic rhinosinusitis, nasal polyposis, allergic rhinitis, dysfunctional breathing, vocal cord dysfunction, anxiety and depression, obesity, obstructive sleep apnoea syndrome (OSAS), gastroesophageal reflux disease (GERD), bronchiectasis, allergic bronchopulmonary aspergillosis (ABPA) and eosinophilic granulomatous with polyangiitis (EGPA). Furthermore, the review offers a summary of recommended diagnostic and management approaches for each co-morbidity. Finally, the review links co-morbid conditions to specific phenotypes of severe asthma, in order to guide the clinician on which co-morbidities to look for in specific patients. © 2017 Asian Pacific Society of Respirology.
To the problem of secondary mycotic infections and their etiological agents.
Otcenásek, M; Hamácek, F
Modern therapeutic procedures that are based on advanced chemotherapy and modern medical technique have led to a prolongation of chronic patient's survival, but have also created conditions for the development of till now little known infectious complications. Among these are, no doubt, mycotic diseases caused by opportunistic microorganisms. Primarily apathogenic fungi, living as a rule in the external environment as saprophytes or colonizing as harmless epiphytes the integumental localizations of healthy humans, start to behave in the subjects with reduced resistance as invasive pathogens. The authors summarize pertinent information of most important systemic mycotic infections of this nature, which occur on the territory of Czechoslovakia: candidiasis, aspergillosis, phycomycosis, cryptococcosis and nocardiosis. Considering the mycological, ecological and pathophysiological aspects of these infections, the authors try to elucidate not only theoretical principles of the etiological agents' opportunism, but also practical impacts of the sustained increase in the number of these diseases. Apart from data on the extrahuman existence of these microorganisms, the authors provide characteristics of the most important pathogenetic mechanisms facilitating their paratrophic propagation. Since the basic conditions of the onset of complications caused by the opportunistic mycotic agents are in principle complied with in almost every hospitalized patient, emphasis is put particularly on factors leading to iatrogenic lesions. Constant close cooperation between the attending physician and microbiologist is considered as one of the basic preconditions for a successful therapeutical control of these pathological conditions.
Aspergillus fumigatus Trehalose-Regulatory Subunit Homolog Moonlights To Mediate Cell Wall Homeostasis through Modulation of Chitin Synthase Activity
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Arsa Thammahong
Full Text Available Trehalose biosynthesis is found in fungi but not humans. Proteins involved in trehalose biosynthesis are essential for fungal pathogen virulence in humans and plants through multiple mechanisms. Loss of canonical trehalose biosynthesis genes in the human pathogen Aspergillus fumigatus significantly alters cell wall structure and integrity, though the mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslA and tslB, which encode proteins that contain domains similar to those corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic residues for phosphatase activity. Loss of tslA reduces trehalose content in both conidia and mycelia, impairs cell wall integrity, and significantly alters cell wall structure. To gain mechanistic insights into the role that TslA plays in cell wall homeostasis, immunoprecipitation assays coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS were used to reveal a direct interaction between TslA and CsmA, a type V chitin synthase enzyme. TslA regulates not only chitin synthase activity but also CsmA sub-cellular localization. Loss of TslA impacts the immunopathogenesis of murine invasive pulmonary aspergillosis through altering cytokine production and immune cell recruitment. In conclusion, our data provide a novel model whereby proteins in the trehalose pathway play a direct role in fungal cell wall homeostasis and consequently impact fungus-host interactions.
Contaminação do ar por Aspergillus em ambiente de reabilitação de animais marinhos
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Melissa Orzechowski Xavier
Full Text Available Aspergillosis in captivity seabirds is often associated with elevated rates of mortality. The infection is usually acquired by inhalation of airborne fungal conidia. The aim of this study was to evaluate the presence of Aspergillus species in the indoor environment of a rehabilitation centre for marine animals in Southern Brazil. This centre continuously receives injured penguins, seagulls, albatrosses and petrels. Petri dishes plates with Agar Sabouraud dextrose and chloramphenicol were left open for 15 minutes in 3 distinct points in the rehabilitation centre and then incubated at 25ºC. During a period of two years the indoor air was sampled in 81 occasions. A total of 43 isolates belonging to 7 different Aspergillus species were recovered. Aspegillus fumigatus was the predominant species (27.9%, followed by A. niger (25.6%, and A. flavus (16.3%. Four other Aspergillus species were isolated. This study demonstrates that seabirds were exposed to pathogenic Aspergillus species in our rehabilitation centre, reinforcing the need for a strict microbiology control of the indoor air in the captivity environment.
ISOLATION AND IDENTIFICATION OF Aspergillus spp. FROM THE WATER USED FOR REHABILITATION OF MAGELLANIC PENGUINS
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Vanice Rodrigues Poester
Full Text Available Aspergillosis is the main cause of mortality in captivity penguins. The infection occurs mainly by conidia inhalation of the Aspergillus genus, however, the fungus can also be dispersed by water. Therefore, this study aimed to evaluate water quality of the pool where the rehabilitated penguins remain at Centro de Recuperação de Animais Marinhos in Rio Grande city, Brazil, searching for the presence of the fungus Aspergillus spp. Water samples were collected weekly during a ten-month period and processed within six hours, applying the technique of filtrating membrane, with incubation at 25 ºC and 37 ºC during seven days. Of the forty samples analyzed, thirty-two were positive for the presence of Aspergillus genus, from these 60% correspond to A. fumigatus. Some variables significantly interfered on the isolation of Aspergillus genus and/or Aspergillus fumigatus specie, such as incubation temperature, seasonality and population density. This study showed Aspergillus spp. is present in the water, being one of the possible sources of infections for penguins in rehabilitation.
A retrospective study of cutaneous fungal infections in patients referred to Imam Reza Hospital of Mashhad, Iran during 2000-2011
Berenji, F; Mahdavi Sivaki, M; Sadabadi, F; Andalib Aliabadi, Z; Ganjbakhsh, M; Salehi, M
Background and Purpose: Detection of agents responsible for cutaneous mycosis may be effective in the prevention of fungal infections from environmental and animal sources. With this background in mind, in this study, we aimed to identify the distribution of cutaneous mycotic infections in patients referred to Imam Reza Hospital of Mashhad, Iran during 2000- 2011. Materials and Methods: In total, 8694 patients suspected of superficial and cutaneous mycosis, referred to the Medical Mycology Laboratory of Imam Reza Hospital of Mashhad, Iran, were recruited during March 2000-2011 and were examined in terms of fungal infections. Results: Of 8694 suspected patients, 3804 (43.75%) cases suffered from superficial and cutaneous mycosis. In total, 1936 (50.9%) patients were male, and 1868 (49.1%) were female. Malassezia infections (58.1%), dermatophytosis (33.1%), cutaneous candidiasis (6.8%), aspergillosis (1.6%), and saprophytic cutaneous mycosis (0.4%) were the most common infections. Conclusion: In this study, Malassezia infections were the most common superficial and cutaneous mycoses. Therefore, it seems essential to focus on the prevention of these infections in our society. PMID:28681008
Burden of fungal infections in Algeria.
Chekiri-Talbi, M; Denning, D W
We report for the first time in Algeria and provide burden estimates. We searched for existing data and estimated the incidence and prevalence of fungal diseases based on the population at risk and available epidemiological data. Demographic data were derived from the National Office of Statistics (Office National des Statistiques: ONS), World Health Organization (WHO), The Joint Nations Programme on HIV/AIDS (UNAIDS) and national published reports. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. Algeria has 40.4 million inhabitants, and probably at least 568,900 (1.41%) of Algerians have a serious fungal infection each year. Recurrent vulvovaginal candidiasis (485,000) and fungal asthma (72,000) are probably the commonest problems, as there are over 1 million adult asthmatics. Candidaemia is estimated in 2,020 people, invasive aspergillosis in 2,865 people, and intra-abdominal candidiasis in 303 people; these are the most common life-threatening problems. AIDS is uncommon, but cancer is not (45,000 new cases of cancer including 1,500 in children), nor is COPD (an estimated 317,762 patients, of whom 20.3% are admitted to hospital each year). A focus on improving the diagnosis and epidemiological data related to fungal infection is necessary in Algeria.