infectious diseases
Toxoplasmosis
Treatment of Toxoplasmosis
Pyrimethamineandsulfadiazineplusleucovorin(to prevent bone marrow suppression); alternatively, the fixed drug combinationtrimethoprim-sulfamethoxazole in some situations Clindamycinoratovaquonepluspyrimethaminewhen the patient is allergic to sulfonamides or does not toleratesulfadiazine Treatment of toxoplasmosis is not indicated for immunocompetent patients who are asymptomatic or have mild, uncomplicated acute infection; treatment is required only when visceral disease is present or symptoms are severe or persist. However, specific treatment is indicated for acute toxoplasmosis in the following: Neonates Pregnant women with acute toxoplasmosis Immunocompromised patients No treatment is required for immunocompetent patients who are asymptomatic or have mild, uncomplicated acute toxoplasmosis. The most effective regimen in immunocompetent patients with visceral involvement or severe or persistent symptoms ispyrimethamineplussulfadiazine, for 2 to 4 weeks. Dosage is Pyrimethamine50 mg twice a day for 2 days, then 25 to 50 mg once a day in adults (in children, 2 mg/kg orally on day 1, then 1 mg/kg once a day; maximum 25 mg/day)plus Sulfadiazine1 g orally 4 times a day in adults (in children, 50 mg/kg twice a day) Folinic acid (leucovorin) is given concurrently to help protect against bone marrow suppression: adults 10 to 20 mg orally once a day (children 7.5 mg orally once a day) In patients who have or develop sulfonamide hypersensitivity,clindamycin600 to 800 mg orally 3 times a day is given withpyrimethamineandleucovorininstead of sulfonamides. Another option isatovaquonepluspyrimethamineandleucovorin. The fixed combination oftrimethoprimwith sulfamethoxazole has been used as an alternative as well aspyrimethamineandleucovorinplusclarithromycin, ordapsone, orazithromycin, but they have not been extensively studied. It is important to optimize Antiretroviral therapy: General principles . Higher doses ofpyrimethamineare used in immunocompromised patients, most of whom have AIDS with CNS toxoplasmosis or, uncommonly, involvement of other organs. A loading dose ofpyrimethamine200 mg orally is given the first day, then 50 mg once a day in patients < 60 kg and 75 mg once a day in those > 60 kg, plussulfadiazine1,000 mg orally 4 times a day in patients < 60 kg and 1,500 mg orally 4 times a day in patients > 60 kg for at least 6 weeks and 4 to 6 weeks after resolution of clinical signs and symptoms.Pyrimethaminebone marrow suppression can be minimized withleucovorin(also called folinic acid—not folate, which blocks the therapeutic effect). Dosage ofleucovorinis 10 to 25 mg orally once a day (7.5 mg once a day in children). Even whenleucovorinis given, the complete blood count should be monitored weekly. Ifpyrimethamineis not available,trimethoprim-sulfamethoxazole, 5 mg/kgtrimethoprimand 25 mg/kg sulfamethoxazole IV or orally twice a day is a potentially effective alternative, butpyrimethamineis more active thantrimethoprimagainst the parasite's dihydrofolate reductase. If patients cannot take sulfonamides,pyrimethamineandleucovorinplusclindamycin600 mg 4 times a day can be used.Atovaquone1,500 mg twice a day with or withoutpyrimethamineandleucovorinis another option. Chronic maintenance therapyis used after successful treatment of acute disease to prevent relapses in patients who remain immunocompromised. Relapses are particularly common in AIDS patients with CD4 counts < 200/mcL. Maintenance therapy is continued until the CD4 counts remain > 200/mcL for > 6 months on antiretroviral therapy. There are several options for maintenance therapy: Sulfadiazine,pyrimethamine, andleucovorin Clindamycin,pyrimethamine, andleucovorin Atovaquone,pyrimethamine, andleucovorin Atovaquoneandsulfadiazine Atovaquone 10 to 25 mg once a day, but an additional agent is needed to Prevention . If Treatment of ocular toxoplasmosis is based on results of a complete ophthalmologic evaluation (degree of inflammation; visual acuity; size, location, and persistence of lesion). Doses are Pyrimethamine100 mg day 1 as a single loading dose, then 25 to 50 mg orally once a day in adults (in children, 2 mg/kg on day 1, then 1 mg/kg once a day)plus Sulfadiazine2 to 4 g orally day 1as a loading dose, then 500 mg to 1 g four times a day in adults (in children, 50 mg/kg twice a day)plus Folinic acid (leucovorin) 5 to 25 mg orally once a day with each dose ofpyrimethamineas long aspyrimethamineis given in adults (in children, 7.5 mg once a day) The Centers for Disease Control and Prevention (CDC) recommends that therapy for ocular toxoplasmosis be continued for 4 to 6 weeks, followed by reevaluation of the patient's condition (see alsoCDC: Toxoplasmosis: Resources for Health Professionals). Patients with ocular toxoplasmosis are also frequently given corticosteroids to reduce inflammation. Treatment of pregnant women with acute toxoplasmosis can decrease the incidence of fetal infection. Spiramycin 1 g orally 3 or 4 times a day has been used safely to reduce transmission to the fetus in pregnant women with acute toxoplasmosis during the first 18 weeks of pregnancy, but spiramycin is less active thanpyrimethamineplus sulfonamide and does not cross the placenta. Spiramycin is continued until fetal infection is documented or excluded at 18 weeks gestational age when amniotic fluid is obtained and tested using a polymerase chain reaction (PCR)–based assay. If no transmission has occurred, spiramycin can be continued to term. If the fetus is infected or a mother becomes infected after 18 weeks,pyrimethamineplussulfadiazineplusleucovorinis used.Pyrimethamineis a potent teratogen and should not be used during the 1st and early 2nd trimester. NOTE: Spiramycin is not commercially available in the US, but is available through the U.S. Food and Drug Administration's Division of Anti-Infective Drug Products (phone: 301-796-1400). Consultation with an infectious diseases expert is recommended. plus a sulfonamide for 1 year ( Treatment reference ). Infants should also receive Pyrimethamine1 mg/kg orally twice a day for the first 2 days; then from day 3 to 2 months (or 6 months if symptomatic) 1 mg/kg once a day, then 1 mg/kg 3 times per week to complete 12 months of therapyplus Sulfadiazine50 mg/kg twice a dayplus Folinic acid (leucovorin) 10 mg 3 times a week 1.Maldonado YA, Read JS, Committee on Infectious Diseases: Diagnosis, treatment, and prevention of congenital toxoplasmosis in the United States.Pediatrics139(2):e20163860, 2017. doi:10.1542/peds.2016-3860 