Cytolytic T lymphocytes (CTLs) kill intracellular pathogens by a granule-dependent mechanism. Granulysin, a protein found in granules of CTLs, reduced the viability of a broad spectrum of pathogenic bacteria, fungi, and parasites in vitro. Granulysin directly killed extracellular Mycobacterium tuberculosis, altering the membrane integrity of the bacillus, and, in combination with perforin, decreased the viability of intracellular M. tuberculosis. The ability of CTLs to kill intracellular M. tuberculosis was dependent on the presence of granulysin in cytotoxic granules, defining a mechanism by which T cells directly contribute to immunity against intracellular pathogens.

SummaryBackground18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016.MethodsUsing all available data sources, the India State-level Disease Burden Initiative estimated burden (metrics were deaths, disability-adjusted life-years [DALYs], prevalence, incidence, and life expectancy) from 333 disease conditions and injuries and 84 risk factors for each state of India from 1990 to 2016 as part of GBD 2016. We divided the states of India into four epidemiological transition level (ETL) groups on the basis of the ratio of DALYs from communicable, maternal, neonatal, and nutritional diseases (CMNNDs) to those from non-communicable diseases (NCDs) and injuries combined in 2016. We assessed variations in the burden of diseases and risk factors between ETL state groups and between states to inform a more specific health-system response in the states and for India as a whole.FindingsDALYs due to NCDs and injuries exceeded those due to CMNNDs in 2003 for India, but this transition had a range of 24 years for the four ETL state groups. The age-standardised DALY rate dropped by 36·2% in India from 1990 to 2016. The numbers of DALYs and DALY rates dropped substantially for most CMNNDs between 1990 and 2016 across all ETL groups, but rates of reduction for CMNNDs were slowest in the low ETL state group. By contrast, numbers of DALYs increased substantially for NCDs in all ETL state groups, and increased significantly for injuries in all ETL state groups except the highest. The all-age prevalence of most leading NCDs increased substantially in India from 1990 to 2016, and a modest decrease was recorded in the age-standardised NCD DALY rates. The major risk factors for NCDs, including high systolic blood pressure, high fasting plasma glucose, high total cholesterol, and high body-mass index, increased from 1990 to 2016, with generally higher levels in higher ETL states; ambient air pollution also increased and was highest in the low ETL group. The incidence rate of the leading causes of injuries also increased from 1990 to 2016. The five leading individual causes of DALYs in India in 2016 were ischaemic heart disease, chronic obstructive pulmonary disease, diarrhoeal diseases, lower respiratory infections, and cerebrovascular disease; and the five leading risk factors for DALYs in 2016 were child and maternal malnutrition, air pollution, dietary risks, high systolic blood pressure, and high fasting plasma glucose. Behind these broad trends many variations existed between the ETL state groups and between states within the ETL groups. Of the ten le...

growing political momentum to definitively address tuberculosis, could all make ending the pandemic within a generation more feasible than ever before. Moving forward with bold, comprehensive strategies Globally, the priority must be to deliver person-centred and family-centred services to all individuals with tuberculosis who present to care. This approach means ensuring that high-quality diagnostics, treatment, and prevention modalities are available to all, wherever they seek care. Improving quality of tuberculosis care in the private sector is crucial to end tuberculosis in high incidence countries such as India, the country with the highest tuberculosis burden. Modelling shows that optimising private sector engagement in India could avert 8 million deaths from tuberculosis between 2019 and 2045 (appendix p 3). In high drug-resistant tuberculosis burden countries, access to rapid drug susceptibility testing (DST) and second-line drugs is essential to success. In Moldova, where more than 25% of all tuberculosis cases are drug-resistant, improving access to DST and second-line drugs would reduce mortality from drug-resistant tuberculosis by 44% in the coming generation (appendix p 3). Secondly, tuberculosis programme budgets must increase to enable reaching these people and populations at high risk of tuberculosis. In Kenya, for example, where the proportions of HIV and tuberculosis coinfection are high, scaling up access to both antiretroviral therapy and tuberculosis preventive therapy can help save an additional 3 million lives over the next generation (appendix p 3). However, ultimately, the fight against tuberculosis will not be won unless countries also ensure that everyone, not just high-risk groups, can access essential health Key messages The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer the question of how countries with high-burden tuberculosis and their development partners should target their future investments to ensure that ending tuberculosis is achievable. Invest first to ensure that high quality rapid diagnostics and treatment are provided to all individuals receiving care for tuberculosis, wherever they seek care This priority includes rapid drug susceptibility testing and second-line treatment for resistant forms of tuberculosis. Achieving universal, high-quality person-centred and family-centred care-including sustained improvement in the performance of private sector providers-usually should be the top policy and budget priority. Reach people and populations at high risk for tuberculosis (such as household and other close contacts of people with tuberculosis, and people with HIV) and bring them into care Active case-finding and treatment in high-risk populations demands adequate resources to reach and care for these populations. At the same time, reaching certain high-risk populations, such as people co-infec...

BackgroundWhile diabetes mellitus (DM) is a known risk factor for tuberculosis, the prevalence among TB patients in India is unknown. Routine screening of TB patients for DM may be an opportunity for its early diagnosis and improved management and might improve TB treatment outcomes. We conducted a cross-sectional survey of TB patients registered from June–July 2011 in the state of Kerala, India, to determine the prevalence of DM.Methodology/Principal FindingsA state-wide representative sample of TB patients in Kerala was interviewed and screened for DM using glycosylated hemoglobin (HbA1c); patients self-reporting a history of DM or those with HbA1c ≥6.5% were defined as diabetic. Among 552 TB patients screened, 243(44%) had DM – 128(23%) had previously known DM and 115(21%) were newly diagnosed - with higher prevalence among males and those aged >50years. The number needed to screen(NNS) to find one newly diagnosed case of DM was just four. Of 128 TB patients with previously known DM, 107(84%) had HbA1c ≥7% indicating poor glycemic control.Conclusions/SignificanceNearly half of TB patients in Kerala have DM, and approximately half of these patients were newly-diagnosed during this survey. Routine screening of TB patients for DM using HbA1c yielded a large number of DM cases and offered earlier management opportunities which may improve TB and DM outcomes. However, the most cost-effective ways of DM screening need to be established by futher operational research.