World Health Organization and Canadian Institutes of Health Research.

BackgroundContact investigation is an active case finding strategy to increase detection of Tuberculosis (TB) and a key component of TB control programs. The household contacts are at a higher risk of exposure than members of the general population. The information on the value and yield of household contact screening and the approaches used in high incidence settings like India is limited.ObjectiveTo evaluate the yield of active case finding in household contacts of newly diagnosed smear positive TB patients and the factors associated with increased yield.MethodRetrospective record review of the household contacts of newly diagnosed sputum smear positive patients (index case) enrolled in a clinical trial at National Institute of Research in Tuberculosis, Chennai during the period 2007–2014. A sequential screening algorithm with chest x-ray followed by symptom screen was employed to identify presumptive TB patients.Results643 household contacts of 280 index TB patients were identified out of which 544 (85%) consented for screening. 71/544 (13%) patients had an abnormal chest radiograph and out of them 70% were symptomatic. A total of 29/544 (5.3%) contacts were found to have TB among whom 23/29 (79%) were sputum smear positive. The number needed to screen (NNS) to identify a new TB case among all household contacts was 19 and among those with an abnormal CXR was 02. Age group > 44 years, male gender and siblings of the index case was associated with abnormal chest radiograph whereas age group between 15–44 was significantly associated with developing TB disease among household contacts.ConclusionActive screening among household contacts is an effective way to improve TB case detection. The yield for new TB cases among contacts with abnormal x-ray was high in this study and the use of Chest X-rays in combination with symptom screen is recommended.

The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (C max ) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median C max and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC 0 -8 ]) of INH (C max , 2.5 versus 5.1 g/ml, respectively [P ‫؍‬ 0.016]; AUC 0 -8 , 11.1 versus 22.0 g/ml · h, respectively [P ‫؍‬ 0.047[) and PZA (C max , 34.1 versus 42.3 g/ml, respectively [P ‫؍‬ 0.055]; AUC 0 -8 , 177.9 versus 221.7 g/ml · h, respectively [P ‫؍‬ 0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median C max of RMP (1.0 versus 2.8 g/ml, respectively; P ‫؍‬ 0.002) and PZA (31.9 versus 44.4 g/ml, respectively; P ‫؍‬ 0.045) were significantly lower. Among all factors studied, the PZA C max influenced TB treatment outcome (P ‫؍‬ 0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP C max . The PZA C max significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.

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BackgroundThe Government of India declared TB as a notifiable disease in 2012. There is a paucity of information on the government's mandatory TB notification order from the perspective of private medical practitioners (PPs).ObjectiveTo understand the awareness, perception and barriers on TB notification among PPs in Chennai, India.MethodsTotal of 190 PPs were approached in their clinics by trained field staff who collected data using a semi-structured and pre-coded questionnaire after getting informed consent. The data collected included PPs' specialization, TB management practices, awareness about the TB notification order, barriers in its implementation and their suggestions to improve notification.ResultsOf 190 PPs from varied specializations, 138 (73%) had diagnosed TB cases in the prior three months, of whom 78% referred these patients to government facilities. Of 138 PPs, 73% were aware of the order on mandatory TB notification, of whom 46 (33%) had ever notified a TB case. Of 120 PPs, 63% reported reasons for not notifying TB cases. The main reasons reported for not notifying were lack of time (50%), concerns regarding patients' confidentiality (24%) and fear of offending patients (11%). Of 145 PPs, 76% provided feedback about information they felt uncomfortable reporting during notification. PPs felt most uncomfortable reporting patient's government-issued Aadhar number (77%), followed by patient's phone number (37%) and residential address (26%). The preferred means of notification was through mobile phone communication (24%), SMS (18%) and e-mail (17%).ConclusionThis study highlights that one-fourth of PPs were not aware of the TB notification order and not all those who were aware were notifying. While it is important to sensitize PPs on the importance of TB notification it is also important to understand the barriers faced by PPs and to make the process user-friendly in order to increase TB notification.

IntroductionThere is lack of information on the proportion of new smear—positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome.ObjectiveTo estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined.MethodologyAdult (aged ≥ 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared “treatment success” at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence.ResultsOf the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2–21.6] and TB recurrence rate per 100 person–years was 12.7 [95% CI: 0.4–25]. TB recurrence per 100 person–years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence.ConclusionA substantial proportion of new smear positive PTB patients successfully treated with 6 –month thrice-weekly regimen have TB recurrence under program settings.