Aparna Mukherjee

Quality of life and psychosocial functioning of HIV infected children.

ObjectiveTo assess the quality of life (QOL) and the psychosocial problems of HIV infected children.MethodsThe present study was a comparative, cross-sectional survey conducted in the clinic of a tertiary care hospital in north India from July–December 2007. Children suffering from cystic fibrosis (CF) were chosen as a comparison group. Children ³ 6 yr of age with HIV infection or Cystic Fibrosis, with no acute illness at the time of survey were included in the study. Quality of life of the enrolled children was assessed by using the Pediatric Quality of Life Inventory™ (PedsQL™). Pediatric Symptom Checklist (PSC) was used for assessing the psychosocial problems in the enrolled children.ResultsForty one HIV infected and 30 children with cystic fibrosis were enrolled. According to child self -report in the PedsQL™ 4.0, the difference of perceived physical health status between the two study groups was statistically significant (p=0.04), with HIV infected children demonstrating a better QOL in this domain. A significantly greater number of children with cystic fibrosis (8/30 or 26.67%) suffered from psychosocial problems as compared to HIV children (3/41 or 7.32%) [p=0.026].ConclusionsThe quality of life and psychosocial functioning is reasonably good in children with HIV infection. Thus, we should strive to maintain and optimize the overall quality of life of these children so that they can have a productive and meaningful future.

Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum

The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress “Towards Zero Deaths”. Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70–80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years, and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups “upstream” towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1, and TIMP2) or “downstream” towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R, and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%).

Effect of micronutrient supplementation on treatment outcomes in children with intrathoracic tuberculosis: a randomized controlled trial

BACKGROUND Micronutrients play an important role in immune function. To our knowledge, there have been no comprehensive studies on the role of micronutrient supplementation in children with tuberculosis. OBJECTIVE We assessed the effect of micronutrient supplementation in children treated with antituberculosis therapy (ATT). DESIGN A randomized, double-blind, placebo-controlled trial that used a 2 × 2 factorial design was undertaken at 2 teaching hospitals in Delhi. Children with newly diagnosed intrathoracic tuberculosis were enrolled, and they received ATT together with daily supplementation for 6 mo with either zinc alone, micronutrients without zinc, micronutrients in combination with zinc, or a placebo. Main outcomes were weight gain and an improvement in a chest X-ray (CXR) lesion assessed at 6 mo of treatment. RESULTS A total of 403 children were enrolled and randomly assigned. A microbiological diagnosis of tuberculosis was confirmed in 179 children (44.4%). The median (95% CI) increase in weight-for-age z score at 6 mo was not significantly different between subjects who received micronutrients [0.75 (0.66, 0.84)] and those who did not receive micronutrients [0.76 (0.67, 0.85)] and between subjects who received zinc [0.76 (0.68, 0.85)] and those who did not receive zinc [0.75 (0.66, 0.83)]. An improvement in CXR was observed in 285 children, but there was no difference between those receiving zinc and no zinc or between those receiving micronutrients and no micronutrients after 6 mo of ATT. However, children who received micronutrients had a faster gain in height over 6 mo than did those who did not receive micronutrients (height-for-age z score Δ = 0.08; P = 0.014). CONCLUSIONS Micronutrient supplementation did not modify the weight gain or clearance of lesions on CXR in children with intrathoracic tuberculosis. However, micronutrient supplementation during treatment may improve height gain in children with intrathoracic tuberculosis. This trial was registered at clinicaltrials.gov as NCT00801606.

Changing Trends in Childhood Tuberculosis

Several changes have been observed in the epidemiology, clinical manifestations, diagnostic modalities and treatment of tuberculosis. Emergence of HIV epidemic and drug resistance have posed significant challenges. With increase in the number of diseased adults and spread of HIV infection, the infection rates in children are likely to increase. It is estimated that in developing countries, the annual risk of tuberculosis infection in children is 2.5%. Nearly 8–20% of the deaths caused by tuberculosis occur in children. Extra pulmonary tuberculosis has increased over last two decades. HIV infected children are at an increased risk of tuberculosis, particularly disseminated disease. In last two decades, drug resistant tuberculosis has increased gradually with emergence of MDR and XDR-TB. The rate of drug resistance to any drug varied from 20% to 80% in different geographic regions. Significant changes have occurred in TB diagnostics. Various diagnostic techniques such as flourescence LED microscopy, improved culture techniques, antigen detection, nucleic acid amplification, line probe assays and IGRAs have been developed and evaluated to improve diagnosis of childhood tuberculosis. Serodiagnosis is an attractive investigation but till date none of the tests have desirable sensitivity and specificity. Tests based on nucleic acid amplification are a promising advance but relatively less experience in children, need for technical expertise and high cost are limiting factors for their use in children with tuberculosis. Short-course chemotherapy for childhood tuberculosis is well established. Directly observed treatment strategy (DOTS) have shown encouraging result. DOTS plus strategy has been introduced for MDR TB.

Role of the QuantiFERON®-TB Gold In-Tube test in the diagnosis of intrathoracic childhood tuberculosis.

SETTING Tertiary care hospitals in India. OBJECTIVE To compare the performance of the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) with that of the tuberculin skin test (TST) in the diagnosis of intrathoracic childhood tuberculosis (TB). METHODS Children with intrathoracic TB were enrolled in a randomised controlled trial studying micronutrient supplementation in intrathoracic TB. They underwent TST and QFT-GIT before starting daily anti-tuberculosis treatment. RESULTS Of 362 children (median age 115.5 months, IQR 73-144, 55% girls) enrolled in the study, microbiological confirmation of TB was obtained in 128 (35%). The TST was positive in 337 (93%, 95%CI 90-95.5) and QFT-GIT in 297 (82%, 95%CI 77.8-85.6). Sensitivity of TST and QFT-GIT in culture-confirmed TB cases was respectively 90.5% (95%CI 84.1-94.5) and 82.6% (95%CI 74.9-88.4). QFT-GIT positivity rate correlated with TST induration (P < 0.001). TST was influenced by the disease spectrum (P = 0.004) and the age of the children (P = 0.002); QFT-GIT remained unaffected by these factors. Bacille Calmette-Guérin immunisation status, weight-for-age Z-scores and microbiological confirmation of Mycobacterium tuberculosis did not influence the performance of either test. CONCLUSION In high-burden countries, QFT-GIT is comparable to TST and offers no added advantage in the diagnosis of childhood intrathoracic TB.

Does Neutralization of Gastric Aspirates from Children with Suspected Intrathoracic Tuberculosis Affect Mycobacterial Yields on MGIT Culture

ABSTRACT The microbiological confirmation of pulmonary tuberculosis in children relies on cultures of gastric aspirate (GA) specimens. Conventionally, GAs are neutralized to improve culture yields of mycobacteria. However, there are limited data to support this practice. To study the utility of neutralization of GAs with sodium bicarbonate in children with intrathoracic tuberculosis, a total of 116 children of either sex, aged 6 months to 14 years (median age, 120 months; interquartile range [IQR], 7 to 192 months), underwent gastric aspiration on 2 consecutive days. Gastric aspirates were divided into two aliquots, and only one aliquot was neutralized with 1% sodium bicarbonate. Both aliquots were processed for smear and culture examinations. Out of the 232 gastric aspirates, 12 (5.17%) were acid-fast bacilli (AFB) smear positive. There were no differences in smear positivity rates from samples with or without neutralization. The yield of Mycobacterium tuberculosis on a Bactec MGIT 960 culture system was significantly lower in the neutralized samples (16.3% [38/232]) than in the nonneutralized samples (21.5% [50/232]) (P = 0.023). There was no significant difference between the neutralized and the nonneutralized samples in time to detection using the MGIT 960 system (average, 24.6 days; IQR, 12 to 37 days) (P = 0.9). The contamination rates were significantly higher in the neutralized samples than in the nonneutralized samples (17.2% [40/232] versus 3.9% [9/232]) (P = 0.001). The agreement for positive mycobacterial culture between the two approaches was 66.5% (P = 0.001). Hence, we recommend that gastric aspirate samples not be neutralized with sodium bicarbonate prior to culture for M. tuberculosis.

Zinc Supplementation for One Year Among Children with Cystic Fibrosis Does Not Decrease Pulmonary Infection

BACKGROUND: Children with cystic fibrosis may have a deficiency of micronutrients, including zinc, which may affect their susceptibility to infections. There is a paucity of data on zinc supplementation among children with cystic fibrosis. We hypothesized that a pharmacologic dose of zinc administered daily for 12 months would reduce the need for antibiotics by 50%. METHODS: This double-blind randomized placebo-controlled trial was conducted among children with cystic fibrosis to assess the effect of zinc supplementation on the need for antibiotics and pulmonary function tests. The children, age 5–15 y, of either sex, received either 30-mg zinc tablets or similar looking placebo tablets daily in addition to standard care. They were followed up every month for a period of 12 months and whenever they had pulmonary exacerbations. Their serum zinc was estimated at baseline and at 12 months of enrollment. During each visit, the children underwent a pulmonary function test and sputum culture. RESULTS: Of a total of 43 children screened, 40 were enrolled, and of them, 37 completed the study. The median (interquartile range) number of days of the administration of antibiotics over 12 months of follow-up among the children receiving zinc was 42 (14–97) d. In the placebo group, it was 38 (15–70) d (P = .79). There were no significant differences in the percent-of-predicted FEV1 or change in FEV1 values at 12 months (P = .44). The number of children in whose respiratory specimens Pseudomonas was isolated was similar for the 2 groups at different time intervals. The adverse events reported were similar in the 2 groups. CONCLUSION: We did not find any significant difference in the need for antibiotics, pulmonary function tests, hospitalization, colonization with Pseudomonas, or the need for antibiotics for children with cystic fibrosis receiving zinc supplementation of 30 mg/d.

High prevalence of primary drug resistance in children with intrathoracic tuberculosis in India

Background: Drug susceptibility testing (DST) of Mycobacterium tuberculosis (Mtb) isolates is crucial for the effective treatment of tuberculosis. Data on DST patterns in Mtb isolates in childhood tuberculosis are scanty. Aims: To determine drug resistance patterns in Mtb isolates from a paediatric TB cohort in North India. Methods: 403 children aged 6 months to14 year with probable intrathoracic tuberculosis were enrolled prospectively. All were treatment-naïve. 802 ambulatory-induced sputa (IS) and 787 gastric aspirate (GA) samples were cultured in BACTEC-MGIT960 system, and DST of the Mtb isolates was undertaken using the automated BACTEC-MGIT960 SIRE kit. Results: Of the 403 children, 147 (36.4%) were culture-confirmed: 132 (89.8%) isolates were Mtb and 15 (10.2%) non-tuberculous mycobacteria (NTM). Five Mtb isolates were contaminated and the remaining 127 were subjected to in-vitro drug susceptibility testing against streptomycin, isoniazid, rifampicin and ethambutol. Twenty-six (20.47%) isolates were resistant to one or more drugs, seven (5.5%) were resistant to rifampicin singly or in combination, and 11 (8.7%) were resistant to isoniazid singly or in combination. Mono-resistance to isoniazid, rifampicin, streptomycin and ethambutol was detected in four (3.1%), one (0.8%), four (3.1%) and two (1.6%), respectively. Five children (3.9%) had MDR-TB; 101 (79.9%) children had Mtb isolates which were sensitive to all four drugs. Conclusions: The rifampicin and isoniazid resistance rates were much higher than those in the adult TB population in India.

Immunologic effect of zinc supplementation in HIV-infected children receiving highly active antiretroviral therapy: a randomized, double-blind, placebo-controlled trial.

Background:We conducted this study to assess the immunologic effect of daily 20 mg zinc supplementation for 24 weeks in HIV-infected children older than 6 months receiving highly active antiretroviral therapy (ART). Methods:Fifty-two HIV-infected children older than 6 months in whom ART was initiated were randomized to receive either 20 mg of zinc or placebo for a period of 24 weeks. Children underwent clinical examination, anthropometry, and laboratory evaluations: CD4% and count, viral load, and serum zinc level at baseline, 12 weeks, and 24 weeks. The primary outcome evaluated was CD4% value at the end of 12 and 24 weeks of study intervention in the enrolled children. Results:Of 52 children enrolled, 49 completed the study. The median CD4% value rose from 10% to 23% at 12 weeks and to 24.5% at 24 weeks in the zinc group, whereas in the placebo group, the value rose from 11% to 20% at 12 weeks and to 22% at 24 weeks (P = 0.188 for comparison between the zinc and the placebo group at 12 wk and P = 0.3 for comparison at 24 wk). The median (interquartile range) log reductions in the viral load at 12 weeks in the 2 arms were similar at 12 (P = 0.84) and 24 weeks (P = 0.43). Conclusions:Supplementation of 20 mg zinc daily for 24 weeks did not have any statistically significant effect on the increase in CD4%, decrease in viral load, anthropometric indices, and morbidity profile in HIV-infected children started on ART.

Effect of micronutrient deficiency on QuantiFERON-TB Gold In-Tube test and tuberculin skin test in diagnosis of childhood intrathoracic tuberculosis.

Background/Objectives:Data on performance of QuantiFERON-TB Gold In-Tube test (QFT) and tuberculin skin test (TST) in children with active tuberculosis from high burden countries in the context of micronutrient deficiency are scarce. The objective of this study was to evaluate the effect of micronutrient deficiency on the performance of TST and QFT in children with intrathoracic tuberculosis.subjects/Methods:Children with probable intrathoracic tuberculosis underwent TST, QFT, gastric lavages and induced sputum examination for AFB (Acid-Fast Bacilli) smear and culture. Zinc, copper, ferritin and vitamin D were measured on stored serum samples. The study used cross-sectional data at initiation of anti-tubercular therapy.Results:Three hundred and sixty-two children (median age 115.5 months (interquartile range: 73, 144), 200 (55.3%) girls) were enrolled in the study. Microbiological confirmation of tuberculosis could be obtained in 128 patients. TST and QFT were positive in 337 (93%) and 297 (82%) children, respectively. Performance of both the tests was unaffected by weight-for-age and height-for-age ‘z-scores’ or by serum copper levels. TST was not affected by serum zinc and ferritin levels. Children with negative QFT results had lower mean serum zinc level (P=0.01) and higher ferritin levels (P=0.007) as compared to those with positive test. Higher proportion of children with positive TST were vitamin D deficient/insufficient (P=0.003).Conclusion:Micronutrient status, especially serum levels of zinc, may influence the performance of QFT in children with intrathoracic tuberculosis. Considering the high prevalence of zinc deficiency in developing countries, QFT should be used cautiously for diagnosing tuberculosis.