Background Two-thirds of children with tuberculosis have non-severe disease. Method SHINE was an open-label treatment-shortening non-inferiority trial in children with non-severe, symptomatic, presumed drug-susceptible, smear-negative tuberculosis, in Uganda, Zambia, South Africa and India. Children aged <16 years were randomised to 16- versus 24-week standard first-line anti-tuberculosis treatment using WHO-recommended paediatric fixed-dose-combinations and a non-inferiority margin of 6% was used. The primary efficacy outcome was a composite of treatment failure, anti-tuberculosis treatment changes/restarts, on-treatment loss-to-follow-up, TB recurrence or death by 72 weeks, excluding children not reaching 16 weeks follow-up (modified-intent-to-treat). Primary safety outcome was on-treatment grade ≥3 adverse events. Results 1204 children (602 in each group) were enrolled between July 2016 and July 2018; median age 3.5 years (range 2 months-15 years), 52% male, 11% HIV-infected, 14% bacteriologically-confirmed tuberculosis. Retention by 72 weeks and adherence to allocated anti-tuberculosis treatment were 95% and 94%, respectively. Sixteen (3%) versus 18 (3%) children reached the primary efficacy outcome in 16- versus 24-week arms respectively: unadjusted difference -0.4%, 95% CI (-2.2, 1.5). Non-inferiority of 16-weeks was consistent across intention-to-treat, per-protocol and key secondary analyses including when restricting analysis to the 958 (80%) children independently adjudicated to have tuberculosis at baseline. 95 (8%) children experienced grade ≥3 adverse events, including 17 adverse reactions (11 hepatic, all except three occurred within first 8 weeks, when treatment arms were the same). Conclusions 4-months anti-tuberculosis treatment was non-inferior to 6 months for children treated for drug-susceptible non-severe smear-negative tuberculosis. (Supported by University College London; Trial Registration: ISRCTN 63579542)

We found a high burden of community-onset antimicrobial-resistant infection among patients with acute febrile illness in India. Multidrug-resistant infection was associated with prior antibiotic use and an increased risk of mortality.

BackgroundTuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed.Methods/designSHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations.DiscussionAlthough recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB.Recruitment to the SHINE trial begun in July 2016; results are expected in 2020.Trial registrationInternational Standard Randomised Controlled Trials Number: ISRCTN63579542, 14 October 2014.Pan African Clinical Trials Registry Number: PACTR201505001141379, 14 May 2015.Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2608-5) contains supplementary material, which is available to authorized users.

Use of kerosene cooking fuel is positively associated with TB in analysis using reported sources of exposure. Ubiquitously high levels of particulates limited detection of a difference in household PM between cases and controls.

Introduction Household air pollution (HAP) is poorly characterized in low-income urban Indian communities. Materials and Methods A questionnaire assessing sources of HAP and 24-hour household concentrations of particulate matter less than 2.5 microns in diameter (PM2.5) were collected in a sample of low-income homes in Pune, India. Results In 166 homes, the median 24-hour average concentration of PM2.5 was 167 µg/m3 (IQR: 106 – 294). Although kerosene and wood use were highly prevalent (22% and 25% of homes, respectively), primarily as secondary fuel sources, high PM2.5 concentrations were also found in 95 (57%) homes reporting LPG use alone (mean 141 µg/m3; IQR: 92 – 209). In adjusted linear regression, log PM2.5 concentration was positively associated with wood cooking fuel (GMR 1.5, 95% CI: 1.1 – 2.0), mosquito coils (GMR 1.5, 95% CI: 1.1 – 2.1), and winter season (GMR 1.7, 95% CI: 1.4 – 2.2). Households in the highest quartile of exposure were positively associated with wood cooking fuel (OR 1.3, 95% CI: 1.1 – 1.5), incense (OR 1.1, 95% CI: 1.0 – 1.3), mosquito coils (OR 1.3, 95% CI: 1.1 – 1.6), and winter season (OR 1.2, 95% CI: 1.1 – 1.4). Discussion We observed high concentrations of PM2.5 and identified associated determinants in urban Indian homes.