IntroductionTuberculosis disease (TB) remains an important global health threat. An evidence-based response, tailored to local disease epidemiology in high-burden countries, is key to controlling the global TB epidemic. Reliable surrogate biomarkers that predict key active disease and latent TB infection outcomes are vital to advancing clinical research necessary to ‘End TB’. Well executed longitudinal studies strengthening local research capacity for addressing TB research priorities and advancing biomarker discovery are urgently needed.Methods and analysisThe Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH) study conducted in Byramjee Jeejeebhoy Government Medical College (BJGMC), Pune and National Institute for Research in Tuberculosis (NIRT), Chennai, India, will establish and maintain three prospective cohorts: (1) an Active TB Cohort comprising 800 adults with pulmonary TB, 200 adults with extrapulmonary TB and 200 children with TB; (2) a Household Contact Cohort of 3200 adults and children at risk of developing active disease; and (3) a Control Cohort consisting of 300 adults and 200 children with no known exposure to TB. Relevant clinical, sociodemographic and psychosocial data will be collected and a strategic specimen repository established at multiple time points over 24 months of follow-up to measure host and microbial factors associated with (1) TB treatment outcomes; (2) progression from infection to active TB disease; and (3) Mycobacterium tuberculosis transmission among Indian adults and children. We anticipate CTRIUMPH to serve as a research platform necessary to characterise some relevant aspects of the TB epidemic in India, generate evidence to inform local and global TB control strategies and support novel TB biomarker discovery.Ethics and disseminationThis study is approved by the Institutional Review Boards of NIRT, BJGMC and Johns Hopkins University, USA. Study results will be disseminated through peer-reviewed journals and research conferences.FundingNIH/DBT Indo-US Vaccine Action Programme and the Indian Council of Medical Research.

Background Metformin, by reducing intracellular Mycobacterium tuberculosis growth, can be considered as an adjunctive therapy to anti-tuberculosis treatment (ATT). We evaluated whether metformin with standard ATT reduces time to sputum culture conversion and tissue inflammation in adults with pulmonary tuberculosis (PTB). Methods In a randomized 8-weeks clinical trial, newly diagnosed, culture positive PTB patients were randomized to standard ATT (HREZ = Control arm) or standard ATT plus daily 1000mg metformin (MET-HREZ = METRIF arm) for 8-weeks, during 2018-2020 at five sites in India. The primary endpoint was time to sputum culture conversion by liquid culture during 8 weeks of ATT. Plasma inflammatory markers were estimated in a subset. Cox proportional hazard model were used to estimate time and predictors of culture conversion. Results Of the 322 patients randomized, 239 (74%) were male, 212 (66%) had bilateral disease on chest radiograph with 54 (18%) showing cavitation. The median time to sputum culture conversion by liquid culture was 42 days in the METRIF arm and 41 days in the Control arm [HR 0.8, 95% CI (0.624 – 1.019)]. After 8-weeks of ATT, cavitary lesions on x-ray [7 (5.3%) vs 18 (12.9%), RR 0.42 (0.18, 0.96), p=0.041] and inflammatory markers were significantly lower in METRIF arm. Higher BMI and lower sputum smear grading were associated with faster sputum culture conversion. Conclusion The addition of metformin to standard ATT did not hasten sputum culture conversion, but diminished excess inflammation thus reducing lung tissue damage as seen by faster clearance on x-ray and reduced inflammatory markers.

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Dysmenorrhea is a recurrent and chronic primary health care issue. Mefenamic acid and NSAID based therapy regimens have unwanted side effects on its long-term usage. NSAIDs reduce pain, albeit they do not address the enhanced pain sensitivity and other neuronal symptoms of dysmenorrhea. Hence, there is a need for supportive therapy which can target both pelvic pain and the neuronal symptoms. Historically, European medicinal plants and their extracts such as, valeriana officinalis, humulus lupulus, and passiflora incarnata have been used in menstrual disorders for centuries. The current review is focused on the available evidence for its use as monotherapy or as supportive therapy in combination with other conventional medications.