Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial.

BACKGROUND: In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis. METHODS: In this field-based, open-label, cluster-randomised controlled trial, we enrolled household contacts of 2800 patients with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units of the National Tuberculosis Elimination Programme in four districts of Jharkhand, India. The tuberculosis units were randomly allocated 1:1 by block randomisation to the control group or the intervention group, by a statistician using computer-generated random numbers. Although microbiologically confirmed pulmonary tuberculosis patients in both groups received food rations (1200 kcal, 52 grams of protein per day with micronutrients) for 6 months, only household contacts in the intervention group received monthly food rations and micronutrients (750 kcal, 23 grams of protein per day with micronutrients). After screening all household contacts for co-prevalent tuberculosis at baseline, all participants were followed up actively until July 31, 2022, for the primary outcome of incident tuberculosis (all forms). The ascertainment of the outcome was by independent medical staff in health services. We used Cox proportional hazards model and Poisson regression via the generalised estimating equation approach to estimate unadjusted hazard ratios, adjusted hazard ratios (aHRs), and incidence rate ratios (IRRs). This study is registered with CTRI-India, CTRI/2019/08/020490. FINDINGS: Between Aug 16, 2019, and Jan 31, 2021, there were 10 345 household contacts, of whom 5328 (94·8%) of 5621 household contacts in the intervention group and 4283 (90·7%) of 4724 household contacts in the control group completed the primary outcome assessment. Almost two-thirds of the population belonged to Indigenous communities (eg, Santhals, Ho, Munda, Oraon, and Bhumij) and 34% (3543 of 10 345) had undernutrition. We detected 31 (0·3%) of 10 345 household contact patients with co-prevalent tuberculosis disease in both groups at baseline and 218 (2·1%) people were diagnosed with incident tuberculosis (all forms) over 21 869 person-years of follow-up, with 122 of 218 incident cases in the control group (2·6% [122 of 4712 contacts at risk], 95% CI 2·2-3·1; incidence rate 1·27 per 100 person-years) and 96 incident cases in the intervention group (1·7% [96 of 5602], 1·4-2·1; 0·78 per 100 person-years), of whom 152 (69·7%) of 218 were patients with microbiologically confirmed pulmonary tuberculosis. Tuberculosis incidence (all forms) in the intervention group had an adjusted IRR of 0·61 (95% CI 0·43-0·85; aHR 0·59 [0·42-0·83]), with an even greater decline in incidence of microbiologically confirmed pulmonary tuberculosis (0·52 [0·35-0·79]; 0·51 [0·34-0·78]). This translates into a relative reduction of tuberculosis incidence of 39% (all forms) to 48% (microbiologically confirmed pulmonary tuberculosis) in the intervention group. An estimated 30 households (111 household contacts) would need to be provided nutritional supplementation to prevent one incident tuberculosis. INTERPRETATION: To our knowledge, this is the first randomised trial looking at the effect of nutritional support on tuberculosis incidence in household contacts, whereby the nutritional intervention was associated with substantial (39-48%) reduction in tuberculosis incidence in the household during 2 years of follow-up. This biosocial intervention can accelerate reduction in tuberculosis incidence in countries or communities with a tuberculosis and undernutrition syndemic. FUNDING: Indian Council of Medical Research-India TB Research Consortium.

Tuberculosis-Learning the Impact of Nutrition (TB LION): protocol for an interventional study to decrease TB risk in household contacts.

BACKGROUND: Comorbidities such as undernutrition and parasitic infections are widespread in India and other tuberculosis (TB)-endemic countries. This study examines how these conditions as well as food supplementation and parasite treatment might alter immune responses to Mycobacterium tuberculosis (Mtb) infection and risk of progression to TB disease. METHODS: This is a 5-year prospective clinical trial at Jawaharlal Institute of Post Graduate Medical Education and Research in Puducherry, Tamil Nadu, India. We aim to enroll 760 household contacts (HHC) of adults with active TB in order to identify 120 who are followed prospectively for 2 years: Thirty QuantiFERON-TB Gold Plus (QFT-Plus) positive HHCs ≥ 18 years of age in four proposed groups: (1) undernourished (body mass index [BMI] < 18.5 kg/m2); (2) participants with a BMI ≥ 18.5 kg/m2 who have a parasitic infection (3) undernourished participants with a parasitic infection and (4) controls-participants with BMI ≥ 18.5 kg/m2 and without parasitic infection. We assess immune response at baseline and after food supplementation (for participants with BMI < 18.5 kg/m2) and parasite treatment (for participants with parasites). Detailed nutritional assessments, anthropometry, and parasite testing through polymerase chain reaction (PCR) and microscopy are performed. In addition, at serial time points, these samples will be further analyzed using flow cytometry and whole blood transcriptomics to elucidate the immune mechanisms involved in disease progression. CONCLUSIONS: This study will help determine whether undernutrition and parasite infection are associated with gene signatures that predict risk of TB and whether providing nutritional supplementation and/or treating parasitic infections improves immune response towards this infection. This study transcends individual level care and presents the opportunity to benefit the population at large by analyzing factors that affect disease progression potentially reducing the overall burden of people who progress to TB disease. Trial registration ClinicalTrials.gov; NCT03598842; Registered on July 26, 2018; https://clinicaltrials.gov/ct2/show/NCT03598842.

Universal health coverage and tuberculosis care in India in the times of Covid-19: Aligning Ayushman Bharat (National Health Assurance Scheme) to improve case detection, reduce deaths and catastrophic health expenditure.

India has the largest global burden of new cases of tuberculosis (TB) and deaths due to TB. These occur predominantly in the poor who suffer catastrophic costs during diagnosis and treatment. The National Tuberculosis Elimination Programme has ambitious goals of 80% reduction of incidence of TB, 90% reduction in mortality due to TB by 2025 and 0% occurrence of catastrophic costs to households affected by TB by 2020. The Covid-19 pandemic and the resulting disruption to TB services are expected to worsen the situation. There are gaps in case finding at the peripheral level and access to care at the higher level for patients with TB. An estimated 32% patients with active TB do not access diagnostic services, while catastrophic costs associated with hospitalization are a barrier to access for seriously ill patients. Deaths due to TB in India occur largely at home and not in medical facilities, and are preventable with appropriate inpatient care. The Ayushman Bharat scheme with its Health and Wellness Centres (HWCs) and coverage for inpatient care under the Pradhan Mantri Jan Arogya Yojana (PM-JAY) can facilitate, the achievement of the goals of TB elimination. The HWCs provide an opportunity to close the case-finding gap as first point of contact by enabling sputum transport services to the designated microscopy centres. This will facilitate case detection, reduce diagnostic delays, and decrease community transmission and the incidence of TB. The benefit package of PM-JAY can cover patients with pulmonary TB, inpatient evaluation for other forms of TB, enhance the allocation for treatment and cover management of comorbid conditions such as severe undernutrition, anaemia, HIV and diabetes.

Retraction Note: Development and In Vitro-In Vivo Characterization of Chronomodulated Pulsatile Delivery Formulation of Terbutaline Sulphate by Box-Behnken Statistical Design.

This article has been retracted by the journal because the editors have clear evidence that the scientific findings in this article are unreliable.

Scrub typhus in Uttarakhand & adjoining Uttar Pradesh: Seasonality, clinical presentations & predictors of mortality.

BACKGROUND & OBJECTIVES: Scrub typhus is a re-emerging mite-borne rickettsiosis, which continues to be underdiagnosed, with lethal consequences. The present study was conducted to determine the seasonality, clinical presentation and predictors of mortality in patients with scrub typhus at a tertiary care teaching hospital in northern India. METHODS: Scrub typhus was suspected in patients attending the hospital as per the standard case definition and serological evidence was obtained by performing an IgM ELISA. RESULTS: A total of 284 patients with scrub typhus from urban and rural areas were seen, predominantly from July to November. The most common clinical presentation was a bilateral community-acquired pneumonia (CAP), which resembled pneumonia due to atypical pathogens and often progressed to acute respiratory distress syndrome (ARDS). An acute undifferentiated febrile illness (AUFI) or a febrile illness associated with altered sensorium, aseptic meningitis, shock, abdominal pain, gastrointestinal bleeding or jaundice was also seen. Eschars were seen in 17 per cent of patients, and thrombocytopenia, transaminitis and azotaemia were frequent. There were 24 deaths (8.5%) caused predominantly by ARDS and multi-organ dysfunction. The mortality in patients with ARDS was high (37%). ARDS [odds ratio (OR)=38.29, 95% confidence interval (CI): 9.93, 147.71] and acute kidney injury (OR=8.30, 95% CI: 2.21, 31.21) were the major predictors of death. INTERPRETATION & CONCLUSIONS: The present findings indicate that scrub typhus may be considered a cause of CAP, ARDS, AUFI or a febrile illness with multisystem involvement, in Uttarakhand and Uttar Pradesh, especially from July to November. Empiric therapy of CAP may include doxycycline or azithromycin to ensure coverage of underlying unsuspected scrub typhus.

DHR-ICMR Guidelines for diagnosis & management of Rickettsial diseases in India.

Rickettsial diseases, caused by a variety of obligate intracellular, gram-negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and Anaplasma, belonging to the Alphaproteobacteria, are considered some of the most covert emerging and re-emerging diseases and are being increasingly recognized. Among the major groups of rickettsioses, commonly reported diseases in India are scrub typhus, murine flea-borne typhus, Indian tick typhus and Q fever. Rickettsial infections are generally incapacitating and difficult to diagnose; untreated cases have case fatality rates as high as 30-45 per cent with multiple organ dysfunction, if not promptly diagnosed and appropriately treated. The vast variability and non-specific presentation of this infection have often made it difficult to diagnose clinically. Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications and in turn reduces morbidity and mortality due to rickettsial diseases. There is a distinct need for physicians and health care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy of these infections. Therefore, a Task Force was constituted by the Indian Council of Medical Research (ICMR) to formulate guidelines for diagnosis and management of rickettsial diseases. These guidelines include presenting manifestations, case definition, laboratory criteria (specific and supportive investigations) and treatment.

Undernutrition and the incidence of tuberculosis in India: national and subnational estimates of the population-attributable fraction related to undernutrition.

BACKGROUND: India has the largest global burden of tuberculosis (TB)-related morbidity and mortality as well as undernutrition. Undernutrition impairs cell-mediated immunity, is a risk factor for the development of TB, and has the largest potential impact on the incidence of TB in countries with a high burden of TB. METHODS: We refined the national estimate of the population-attributable fraction (PAF) for undernutrition in India to report the first subnational estimates, and stratified these further for age, gender, residence, caste and socioeconomic status. We also compared the PAF related to undernutrition in India with that in 15 other countries with a high burden of TB. We used data on body mass index (BMI) from the National Family Health Survey-3 (NFHS-3), as well as risk estimates for a low BMI from a recently published population-based study which had controlled for several confounders. RESULTS: The overall prevalence of undernutrition in the age group of 15-49 years was 35.6% among women and 34.2% among men. About half (55.4%; 95% CI 27.4- 75.9) of all cases of active TB among women and 54.4% (95% CI 26.5-75.2) of all cases among men were attributable to undernutrition. In the age group of 15-19 years, the PAFs for undernutrition were 62% and 67% among women and men, respectively. The PAF of undernutrition was higher in rural areas, in scheduled castes, scheduled tribes and other backward classes, and in the lower quintiles of the wealth index. The PAF of undernutrition exceeded 50% in most states, and the largest PAFs were seen among women of scheduled tribes in central India. Among countries with a high burden of TB, India had the highest PAF related to undernutrition. CONCLUSION: Addressing the problem of endemic undernutrition among adolescents and adults in India could complement the current TB control strategy based on case management, and help reduce the incidence of TB in India in line with global targets.

Can social interventions prevent tuberculosis?: the Papworth experiment (1918-1943) revisited.

RATIONALE: There is consensus on the need to address social determinants of tuberculosis (TB) to achieve TB control, but evidence based on interventions is lacking. OBJECTIVES: We reanalyzed data from the sociomedical experiment performed at the Papworth Village Settlement in England, where the impact of stable employment and adequate housing and nutrition on the incidence of TB infection and disease in children living with parents with active TB was documented during 1918-1943. METHODS: Information on 315 children of patients, who lived at Papworth, was abstracted from a published monograph. Overall and age-specific occurrence of TB infection, disease, and deaths among children born in the settlement (village-born cohort) were compared with those of children born outside and admitted later (admitted cohort) to Papworth. MEASUREMENTS AND MAIN RESULTS: The annual risks of infection in the village-born and admitted cohorts were 20 and 24%, respectively. Of 24 children who developed TB disease, only one was village-born. Among children 5 years of age or less, there was zero incidence of TB in the village-born, compared with five cases (1,217/100,000 person-years) among children born outside Papworth. In the admitted cohort, among children 13 years of age and older, the incidence of TB before admission to Papworth was 5,263/100,000 person-years, whereas it was 341/100,000 person-years while living in Papworth. CONCLUSIONS: At Papworth social interventions including adequate nutrition did not reduce TB transmission but did reduce the incidence of TB disease in children living with parents with active TB. These results are relevant today for prevention of TB in children of patients with active TB, particularly with multidrug-resistant TB in high-burden settings.

Nutritional support for adult patients with microbiologically confirmed pulmonary tuberculosis: outcomes in a programmatic cohort nested within the RATIONS trial in Jharkhand, India.

BACKGROUND: Undernutrition is a common comorbidity of tuberculosis in countries with a high tuberculosis burden, such as India. RATIONS is a field-based, cluster-randomised controlled trial evaluating the effect of providing nutritional support to household contacts of adult patients with microbiologically confirmed pulmonary tuberculosis in Jharkhand, India, on tuberculosis incidence. The patient cohort in both groups of the trial was provided with nutritional support. In this study, we assessed the effects of nutritional support on tuberculosis mortality, treatment success, and other outcomes in the RATIONS patient cohort. METHODS: We enrolled patients (aged 18 years or older) with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units. Patients received nutritional support in the form of food rations (1200 kcal and 52 g of protein per day) and micronutrient pills. Nutritional support was for 6 months for drug-susceptible tuberculosis and 12 months for multidrug-resistant tuberculosis; patients with drug-susceptible tuberculosis could receive an extension of up to 6 months if their BMI was less than 18·5 kg/m2 at the end of treatment. We recorded BMI, diabetes status, and modified Eastern Cooperative Oncology Group (ECOG) performance status at baseline. Clinical outcomes (treatment success, tuberculosis mortality, loss to follow-up, and change in performance status) and weight gain were recorded at 6 months. We assessed the predictors of tuberculosis mortality with Poisson and Cox regression using adjusted incidence rate ratios (IRRs) and adjusted hazard ratios (HRs). The RATIONS trial is registered with the Clinical Trials Registry of India (CTRI/2019/08/020490). FINDINGS: Between Aug 16, 2019, and Jan 31, 2021, 2800 patients (mean age 41·5 years [SD 14·5]; 1979 [70·7%] men and 821 [29·3%] women) were enrolled. At enrolment, 2291 (82·4%) patients were underweight (BMI <18·5 kg/m2), and 480 (17·3%) had a BMI of less than 14 kg/m2. The mean weight and BMI were 42·6 kg (SD 7·8) and 16·4 kg/m2 (2·6) in men and 36·1 kg (7·3) and 16·2 kg/m2 (2·9) in women. During the 6-month follow-up, treatment was successful in 2623 (93·7%) patients, 108 (3·9%) tuberculosis deaths occurred, 28 (1·0%) patients were lost to follow-up, and treatment failure was experienced by five (0·2%) patients. The median weight gain was 4·6 kg (IQR 2·8-6·8), but 1441 (54·8%) of 2630 patients remained underweight. At 2 months, 1444 (54·0%) of 2676 patients gained at least 5% of baseline weight. Baseline weight (adjusted IRR 0·95, 95% CI 0·90-0·99), BMI (0·88, 0·76-1·01), poor performance status (ECOG categories 3-4; 5·33, 2·90-9·79), diabetes (3·30, 1·65-6·72), and haemoglobin (0·85, 0·71-1·00) were predictors of tuberculosis mortality. A reduced hazard of death (adjusted HR 0·39, 95% CI 0·18-0·86) was associated with a 5% weight gain at 2 months. INTERPRETATION: In this study, nutritional support was provided to a cohort with a high prevalence of severe undernutrition. Weight gain, particularly in the first 2 months, was associated with a substantially decreased hazard of tuberculosis mortality. Nutritional support needs to be an integral component of patient-centred care to improve treatment outcomes in such settings. FUNDING: India Tuberculosis Research Consortium, Indian Council of Medical Research.

Ending TB in South-East Asia: flagship priority and response transformation.

Over the decades, the global tuberculosis (TB) response has evolved from sanatoria-based treatment to DOTS (Directly Observed Therapy Shortcourse) strategy and the more recent End TB Strategy. The WHO South-East Asia Region, which accounted for 45% of new TB patients and 50% of deaths globally in 2021, is pivotal to the global fight against TB. "Accelerate Efforts to End TB" by 2030 was adopted as a South-East Asia Regional Flagship Priority (RFP) in 2017. This article illustrates intensified and transformed approaches to address the disease burden following the adoption of RFP and new challenges that emerged during the COVID-19 pandemic. TB case notifications improved by 25% and treatment success rates improved by 6% between 2016 and 2019 due to interventions ranging from galvanising political commitments to empowering and engaging communities. Cumulative TB programme budget allocations in 2022 reached US$ 1.4 billion, about two and a half times the budget in 2016. An ambitious Regional Strategic Plan towards ending TB, 2021-2025, identifies priority interventions that will need investments of up to US$ 3 billion a year to fully implement them. Moving forward, countries in the Region need to leverage RFP and take up intensified, people-centred, holistic interventions for prevention, diagnosis, treatment and care of TB with commensurate investments and cross-ministerial and multi-sectoral coordination.

Attributable is preventable: Corrected and revised estimates of population attributable fraction of TB related to undernutrition in 30 high TB burden countries.

Introduction: The Global TB Report 2020 estimated the population attributable fractions (PAF) for the major risk factors of TB. Undernourishment emerged as the leading risk factor accounting for 19% of the cases. The WHO however used the terms undernourishment and undernutrition interchangeably in its computation of PAF. Undernourishment is an indirect model derived estimate of decreased per capita energy availability, while undernutrition is defined by direct anthropometric measurements of nutritional status. An estimate of PAF for a risk factor should use the prevalence and the risk ratio of the same risk factor, which is not the case with the current methodology. Methods: We re- estimated the PAF of undernutrition (instead of undernourishment) in 30 high TB burden countries as defined by WHO for the period 2016-2020, using the prevalence of undernutrition (age standardized estimate of BMI < 18.5 kg/m2 in adults for both sexes), and the relative risk (RR) of 3.2. Further, we revised PAF estimates of undernutrition with an RR of 4.49 (95% CI: 2.28, 8.86), in light of recent evidence. Findings: In 30 high TB burden countries, 24.1% (95% CI: 17.6,30.0) of incident TB is attributable to undernutrition. The PAF of undernutrition was highest in Asian countries, unlike the PAF of undernourishment that was highest in Africa. The corrected estimate led up to 65% increase in number of cases attributable to undernutrition in Asian countries. If a revised relative risk was used, 33.0% (95% CI: 10.1, 60.1) of incident TB cases in the selected countries could be attributable to undernutrition. More than one-third to nearly half of incident TB cases in India could be attributable to undernutrition. Interpretation: Estimation of the PAF of TB related to undernutrition is methodologically valid and operationally relevant, rather than PAF related to undernourishment, and should be used for future Global TB reports by WHO. Addressing undernutrition, the leading driver of TB in high TB burden countries (especially Asia) could enable achievement of END TB milestones of TB incidence for 2025.

Lignans: a versatile source of anticancer drugs.

Background: Cancer is considered as the second deadliest disease globally. Plants have continuously offered unique secondary metabolites with remarkable biological applications. Lignans have gained great importance due to their biological activity. Previous studies revealed that the most remarkable bioactivity of lignan class of molecules is anticancer. They are derived from the oxidative dimerization of two phenylpropanoid units. This review covers the isolated anticancer lignans and their mechanistic aspects. Main body: A bibliographic investigation was performed by analyzing the information available on anticancer lignans in the internationally accepted scientific databases including Web of Science, SciFinder, PubMed, Scopus, and Google Scholar. In this review we have tried to sum up the isolated anticancerous lignan, its source, active plant part, extract and various cell lines used to establish different studies. Here we have included a total number of 113 natural lignans. Many studies that mainly performed in human cell lines have reported. Very few plants have been evaluated for their in vivo anticancer activity. Conclusion: It can be concluded that in near future the lignans may be an effective pharmacon for the treatment of cancer. Fruitful areas of future research may be in modifying natural lignans or synthesizing new lignans with structural diversity and potent pharmacological activities. Extensive studies are needed to be done highlighting the mechanism of anticancer action of explored and unexplored plants. The data will definitely attract many researchers to start further experimentation that might lead to the drugs for the cancer treatment.

Screening for Severe Illness at Diagnosis Has the Potential to Prevent Early TB Deaths: Programmatic Experience From Karnataka, India.

Due to the coronavirus disease (COVID-19) pandemic and its associated response, TB deaths increased for the first time in a decade. In any potentially fatal illness, an assessment of severity is essential. This is not systematically done for adults with TB, mostly due to a lack of policy and/or limited availability of diagnostic and clinical capacity. We developed a screening tool using simple and easily measurable indicators that can be used by paramedical TB program staff to quickly identify people with severe illness. During October-November 2020 in Karnataka, India, the paramedical program staff from 16 districts screened people with TB (aged ≥15 years) notified by public facilities for "high risk of severe illness," which was defined as the presence of any of the following indicators: (1) body mass index (BMI) ≤14.0 kg/m2; (2) BMI ≤16.0 kg/m2 with bilateral leg swelling; (3) respiratory rate >24/minute; (4) oxygen saturation <94%; (5) inability to stand without support. In this cohort study, we determined the incidence of program-recorded early deaths (within 2 months) and its association with high risk of severe illness. Of 3,010 people with TB, 1,529 (50.8%) were screened at diagnosis/notification, of whom 537 (35.1%) had a high risk of severe illness. There were 195 (6.5%, 95% CI=5.7, 7.4) early deaths: 59 (30.2%) within a week and 100 (51.3%) within 2 weeks of treatment initiation. The incidence of early deaths was significantly higher among those with high risk of severe illness (8.9%) at diagnosis compared to those without (3.8%) [adjusted relative risk: 2.36 (95% confidence interval=1.57, 3.55)]. To conclude, early deaths were especially high during the first 2 weeks and strongly associated with a high risk of severe illness at diagnosis/notification. Screening for severe illness should be explored as a potential strategy to end TB deaths.

Saved by a syncretic faith? A case from 1995.

Physicians in countries like India have to take on the care of seriously ill patients that, in a strict sense, maybe beyond their means to handle. They do so often because their patients trust them or the institutions that they may be a part of. The author reflects on his stint as a young physician in a rural medical college in Gujarat in the 1990s. He narrates the experience of dealing with a critically ill young man brought by road from a hospital in Bombay, 500 km away, to his hometown. The patient survived because the correct diagnosis was reached, and the family assisted in his intensive care with a remarkable composure which owed its origins to a faith crossing the boundaries of religion.

Social determinants of tuberculosis: context, framework, and the way forward to ending TB in India.

INTRODUCTION: Social determinants are involved in the causation of TB and its adverse outcomes. This review was conducted to evolve a framework for action on social determinants with special reference to India in the context of the new END TB strategy. AREAS COVERED: We reviewed the social context of TB in India as a neglected disease of the poor, its emergence in epidemic form in the colonial period, and the factors that resulted in its perpetuation and expansion in post-independence India. We examined the role of social determinants in two key pathways - the pathway of TB causation and its outcomes, and the care cascade for patients with TB, and its consequences. We reviewed the most important social determinants of TB including poverty, membership of certain castes and indigenous population, undernutrition and poor access to healthcare, especially in rural areas. EXPERT OPINION: We suggest that TB elimination will require an optimal mix of enhanced biomedical and social interventions. TB elimination strategy in India needs a pro-poor model of patient - centered care inclusive of nutritional, psycho-social and financial support, universal health coverage, and social protection; and convergence with multi-sectoral efforts to address poverty, undernutrition, unsafe housing, and indoor pollution.

Food for thought: addressing undernutrition to end tuberculosis.

Tuberculosis is the leading cause of deaths from an infectious disease worldwide. WHO's End TB Strategy is falling short of several 2020 targets. Undernutrition is the leading population-level risk factor for tuberculosis. Studies have consistently found that undernutrition is associated with increased tuberculosis incidence, increased severity, worse treatment outcomes, and increased mortality. Modelling studies support implementing nutritional interventions for people living with tuberculosis and those at risk of tuberculosis disease to ensure the success of the End TB Strategy. In this Personal View, we highlight nutrition-related immunocompromisation, implications of undernutrition for tuberculosis treatment and prevention, the role of nutritional supplementation, pharmacokinetics and pharmacodynamics of antimycobacterial medications in undernourished people with tuberculosis, and the role of social protection interventions in addressing undernutrition as a tuberculosis risk factor. To catalyse action on this insufficiently addressed accelerant of the global tuberculosis epidemic, research should be prioritised to understand the immunological pathways that are impaired by nutrient deficiencies, develop tools to diagnose clinical and subclinical tuberculosis in people who are undernourished, and understand how nutritional status affects the efficacy of tuberculosis vaccine and therapy. Through primary research, modelling, and implementation research, policy change should also be accelerated, particularly in countries with a high burden of tuberculosis.