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Clinical Profile of Pediatric Tuberculosis and MGIT sensitivity: A Prospective Study from a Tertiary care Institute

Introduction: Tuberculosis (TB) is a major global health problem. Childhood tuberculosis (TB) is common in our community but it is relatively neglected, due to greater challenges in diagnosis. Clinical manifestations of childhood TB differ from adults. The diagnosis in most cases is based on clinical evidence but chest X-ray, Mantoux test and sputum/gastric sample microscopy are important supporting investigations. Objective 1) To study the clinical profile of TB. 2) To determine incidence of extra-pulmonary TB in children. 3) To know MGIT sensitivity in diagnosis of Tuberculosis. Methods: This prospective study was conducted among admitted and OPD patients in the department of Pediatrics over a period of 1 year. Clinically suspected cases of TB in the age group 0-14 years who met the diagnostic criteria made the study group. Refusal of consent by parent and children already on TB treatment were excluded from this study. Investigations like chest X-ray, Mantoux test, sputum/gastric aspirate microscopy and MGIT were done to confirm the clinical diagnosis. Results: The incidence of tuberculosis was found 36/10000. Pulmonary tuberculosis was more common (53.9%) than extra pulmonary (35.3%) tuberculosis. BCG scar was present in 87.42%. History of contact was present in 41.2% and Mantoux test was positive in 51.98%. MGIT sensitivity was 30% in our study. The most common symptoms were fever (79.4%), anorexia (61%) and cough (59%). Conclusion: This study supports that detailed history, clinical evaluation and active investigative workup has a major role in diagnosing childhood tuberculosis.


Introduction
Tuberculosis (TB) is a major global health problem. It causes ill health among millions of people each year and ranks alongside the human immunodeficiency (HIV) as a leading cause of death worldwide. [1] Childhood tuberculosis remains an important cause of morbidity and mortality in developing countries. [2] Although data on childhood TB is scarce, tuberculin surveys conducted in children suggest a high rate of infection in the community with annual risk of TB infection is about 1.5%. [3] The high prevalence and incidence of TB in developing countries is probably due to a high prevalence of TB in adults acting as contacts, poor socioeconomic condition, malnutrition, overcrowding and HIV coinfections. [4,5,6] Since the declaration by WHO of a 'Global TB emergency' in 1993, a wealth of publications have addressed important aspects of the burden, management and control of tuberculosis. In general, however, the emphasis has been on adult disease. By contrast, the pediatric TB has been relatively neglected, mainly by the challenges in the diagnosis and the lower priority by TB control programs. While the burden of TB in India is not known, regional data from WHO indicate that the sputum smear positive TB in children < 14 years old accounts for 0.6% to 3.6% of all reported cases. However, because the majority of children are sputum smear negative, this data underestimate the true burden of childhood TB. It is estimated that childhood TB constitutes 10-20% of all TB in high burden countries and accounts for 8-10% TB related deaths. [7] Literature on tuberculosis in children is scarce in the developing countries including India. Further, no such study has been done earlier in Himachal Pradesh, so our aim was to determine the clinical profile of TB in children between 0-14 years of age.

Aims and Objectives
1. To study the clinical profile of TB in children 0-14 years age group.

2.
To determines the incidence of extra pulmonary TB in children. 3. To study MGIT sensitivity in diagnosis of tuberculosis.

Material and Methods
It is a prospective observational type of study carried out over a period of one year in both outpatient and inpatient population in department of pediatrics. All patients in 0- 14  . After the clinical diagnosis, the disease was classified as per the system involved. Investigations like tuberculin skin test, sputum/gastric aspirate for AFB and MGIT-960 were done for confirmation of clinical diagnosis. Radiological investigations like chest X-ray, USG abdomen (for abdominal TB) and CT/MRI were performed in relevant cases. Specific condition like lymphadenitis required FNAC, for pleural, pericardial and peritoneal effusions, fluid aspiration studies were done and samples were sent for bacteriological confirmation and biochemical profile. In meningitis lumbar puncture was done and CSF was sent for bacteriological confirmation and biochemical profile. CT/MRI was done in cases of suspected tuberculoma.

Observations
During one-year study period, 28200 children visited our hospital including both outdoor and indoor patients, of theses 102 were diagnosed as TB. Incidence of TB was calculated as 36 per 10000 children. Out of 102 cases, 50.9% were males and 49.1% were females. Male to female ratio was 1.04.   MGIT was done in 30 patients, 9 patients were MGIT positive while 21 being MGIT negative. Sensitivity of MGIT was found to be 30%. Maximum positive cases of MGIT were found in pulmonary TB followed by Disseminated TB.

Discussion
The incidence of tuberculosis was 36 cases per 10000 patients. Incidence of pulmonary and extra pulmonary TB was 19 and 13 per 10000 patients. The incidence of TB in India in year 2014 was 12.6/10000. As diagnosis of childhood TB is very challenging in community, so most cases of suspected TB are referred to tertiary care centre. This can be the reason to explain the higher incidence of tuberculosis in our study than the actual incidence in India. Sex wise distribution of cases showed a slight male preponderance (50.9%), which is similar to study by Franco Et al in Brazil which showed a male preponderance of 51.6%. [8] Sivanandan S [9] and Xi-Rong Wu et al [10] also observed a male preponderance of 63% and 58% respectively. Majority of cases in our study belonged to age group 11-14 years of age which is in accordance to study by Kakarani with 54% cases in age group 6-12 years. [11] Analyzing and comparing the above studies with the present study, it may be concluded than in early adolescence there is a slight female preponderance. The increased risk may be due to combination of increased biological susceptibility, immunological response following puberty or difference in socialization patterns of male compared to female adolescents. Most of cases belonged to lower (50%) and middle (44.1%) class. A study on children from south India showed similar results with 55.8% belonging to lower class, 38.9% middle class, and 5.3% to high socioeconomic group. [12] The frequency of clinical symptoms was observed as fever in 79.4%, anorexia 63%, cough 57.8% and weight loss in 40%. Similar observations were reported in a study from north India by Garg P with fever and anorexia being commonest symptoms followed by weight loss and cough. [13] In a study by Franco et al [8] fever was documented in 73.1% cases and weight loss in 53.1%. Positive family history of contact was found in 42 patients (41.2%), most number of cases 18(42.9%) were in age group 0-5 years. This was similar to various Indian studies done in children under 15 years of age showing positive history of contact in 33-52% cases. [12,13,14] Study by Franco et al [8] reported a recent contact in age group 1-5 years.
In our study pulmonary TB constituted the major group (53.9%), followed by extra pulmonary TB (35.3%). Our results are consistent with the various studies described in literature [8,9,11,13,15] In our study CNS tuberculosis accounted for 11.8% cases, this was comparable with study of Pontual et al [16] where 16.67% cases were had isolated CNS tuberculosis. Lymphadenopathy was seen in 23.5% and isolated lymphadenopathy was seen in 1.96% cases. This was comparable to study done by Garg P, which showed 16.7% cases of tubercular lymphadenopathy 13 . Franco et al [8] showed 21.5% cases of tubercular lymphadenopathy. Primary complex was most common finding on X ray accounting for 36(50.7%) cases and 15(21.1%) cases showed pleural effusion. Similar to study by Franco et al [8 ] observed primary complex in 44.3% cases. History of BCG vaccination was positive in 87.42% cases and 13.72% of those vaccinated did not have a BCG mark on examination. Higher vaccination coverage in our study in comparison to others indicates effective implementation of National Immunization Programme.  [9] reported Mantoux positivity in 66% cases which is similar as to our study. In present study, sputum/gastric aspirate microscopy was positive for AFB in 31(30.4%) cases. This was in accordance to study done by Franco et al, [8] which showed sputum positivity in 32.8% cases, and frequency of sputum positivity was higher in individual aged 11-15 years. Maximum sputum positivity i.e 25.5% was seen in age group 11-14 years followed by 4.9% in 6-10 years. This finding emphasizes that as age increases percentage of sputum positivity increases and hence bacteriological sputum examination is a useful method above 10 years. The reported sensitivity of MGIT is upto 90% and most of these studies were done in adults. The sensitivity of MGIT in our study was 30%, which was in accordance to various studies showing sensitivity of 48.5% [17] , 21.9% [18] and 15%. [19] The reason low sensitivity of MGIT in children was attributed to following factors-as children less than 8 years could not expectorate so we used gastric lavage, pleural fluid, CSF and these samples have low bacterial counts. Other factors like delay in transportation, storage and neutralization of sample would have inactivated tubercle bacilli. (as MGIT detects live bacteria)

Conclusion
Tuberculosis is a major global health problem. Most of work is done in the field of adult TB. Pediatric TB has been relatively neglected mainly due to greater challenges in diagnosis and lower priority tradionally afforded to children by TB control programmes. Detailed clinical evaluation, refinement of existing investigations and development/testing of new methods like MGIT are promptly required to improve diagnosis and treatment of TB in children.