Recurrence of pulmonary tuberculosis in India: Findings from the 2019-2021 nationwide community-based TB prevalence survey.

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019-2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107-131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management.

Prevalence and factors associated with tuberculosis infection in India.

BACKGROUND: The risk of tuberculosis (TB) disease is higher in individuals with TB infection. In a TB endemic country like India, it is essential to understand the current burden of TB infection at the population level. The objective of the present analysis is to estimate the prevalence of TB infection in India and to explore the factors associated with TB infection. METHODS: Individuals aged > 15 years in the recently completed National TB prevalence survey in India who were tested for TB infection by QuantiFERON-TB Gold Plus (QFT-Plus) assay were considered for this sub-analysis. TB infection was defined as positive by QFT-Plus (value >0.35 IU/ml). The estimates for prevalence, prevalence ratio (PR) and adjusted risk ratio (aRR) estimates with 95% confidence intervals (CIs) were calculated. RESULTS: Of the 16864 individuals analysed, the prevalence of TB infection was 22.6% (95% CI:19.4 -25.8). Factors more likely to be associated with TB infection include age > 30 years (aRR:1.49;95% CI:1.29-1.73), being male (aRR:1.26; 95%CI: 1.18-1.34), residing in urban location (aRR:1.58; 95%CI: 1.03-2.43) and past history of TB (aRR:1.49; 95%CI: 1.26-1.76). CONCLUSION: About one fourth (22.6%) of the individuals were infected with TB in India. Individuals aged > 30 years, males, residing in urban location, and those with past history of TB were more likely to have TB infection. Targeted interventions for prevention of TB and close monitoring are essential to reduce the burden of TB in India.

Persistent high prevalence of pulmonary tuberculosis in a resource-limited setting: threat to India's TB Free campaign.

BACKGROUND: Tuberculosis (TB) is a major public health problem among Saharia, a particularly vulnerable tribal group residing in remote rural areas in central India. This article presents the findings from the baseline survey among Saharias and provides comprehensive prevalence data of pulmonary TB (PTB) in this marginalised community. METHODS: A community-based cross-sectional PTB prevalence survey was carried out during January-May 2019 in selected villages using multistage stratified cluster sampling. All eligible adults (≥15 years of age) were screened for the symptoms of PTB. Sputum samples were collected and processed for microscopy and culture for Mycobacterium tuberculosis. RESULTS: A total of 20 114 eligible individuals were screened for symptoms of PTB. Among these, 3001 (14.9%) individuals reported at least one PTB symptom and sputum was collected from 2890 (96.3%) individuals. Among these, 273 (9.4%) were bacteriologically positive for PTB. The overall prevalence was 1357 per 100 000 population. CONCLUSIONS: The findings indicate that TB continues to be a major health problem in this marginalised community despite large investments by the government for TB control. This emphasizes the need to look into the causes and barriers in implementation of the TB elimination programme in the community, especially in view of India's TB elimination goal by 2025.

High incidence of pulmonary tuberculosis in an indigenous Saharia tribe in Madhya Pradesh, central India-A prospective cohort study.

BACKGROUND: Lack of TB incidence data is an important evidence gap among Saharia-a high TB burden indigenous community in Madhya Pradesh, central India. The present study was undertaken to calculate the incidence of pulmonary tuberculosis in this tribe. OBJECTIVE: To calculate the incidence of pulmonary tuberculosis (PTB) among the Saharia tribal population in Madhya Pradesh, central India. METHODS: A prospective cohort study was conducted among the Saharia tribal population (aged 15 years and above) of Shivpuri district in Madhya Pradesh state in central India. A total of 9,756 individuals were screened for TB in the baseline TB prevalence survey during 2012-13. All available household members were screened for symptoms suggestive of pulmonary TB (presumptive TB). Two sputum specimens were collected from persons having symptoms suggestive of TB and examined by smear and culture tests. A cohort of all non-TB individuals in the baseline survey was followed-up for one year and re-screened for the sysmptoms of PTB in the year 2014-15. Based on the data collected, the incidence of TB over one year period was estimated per 100,000 population. RESULTS: A total of 9756 and 9044 individuals (≥ 15 years) were screened for symptoms suggestive of PTB during baseline and endline surveys respectively. The sputum specimens of presumptive TB cases were collected and examined by smear and culture tests. The overall incidence of bacteriologically positive (smear and/or culture) PTB over one year period was 1504 (95% Confidence Interval (CI): 1273-1776) per 100,000 in the study population, the incidence of smear-positive PTB was 1106 (95% CI: 910-1343), and the incidence of culture-positive PTB was 1084 (95% CI: 890-1319) per 100,000 population. The incidence for both smear and culture-positive PTB was 686 (95% CI: 535-878) per 100,000 population in the year 2014-15. The incidence of PTB was 2.8 times higher in males compared to females (2259 vs 807 per 100,000) and was positively correlated with age. CONCLUSION: The findings of the study, the first of its kind in the Saharia tribal population, indicate a high incidence of TB in this tribal community thereby highlighting the urgent need for focused and intensified efforts to achieve the goal of TB elimination in the country.

Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India, June-July 2021: A population-based cross-sectional study.

BACKGROUND: India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March-June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs). METHODS AND FINDINGS: We did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6-9 years, 5,798 (20%) were aged 10-17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey. CONCLUSIONS: Nearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June-July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.

Reasons for loss to follow-up (LTFU) of pulmonary TB (PTB) patients: A qualitative study among Saharia, a particularly vulnerable tribal group of Madhya Pradesh, India.

BACKGROUND: Loss to follow-up (LTFU) among pulmonary tuberculosis (PTB) patients is a significant challenge for TB control. However, there is a dearth of information about the factors leading to LTFU among marginalized communities. This study highlights the factors associated with LTFU in Saharia, a tribe of Madhya Pradesh having high tuberculosis (TB) prevalence. METHODS: A qualitative study was carried out during January-April 2020 among twenty-two pulmonary TB patients, recorded as LTFU in NIKSHAY, with ten treatment supporters and ten patient's family members. Semi-structured personal interview tools were used to collect the information on the history of anti-tuberculosis treatment, adverse drug events (ADE), social cognitive, behaviors, myths, and misbeliefs. The interviews were transcribed and thematically analysed to examine underlying themes. RESULTS: The study explored various social, behavioral factors leading to loss to follow-up among PTB patients. Drug side effects, alcoholism, social stigma, lack of awareness of the seriousness of the diseases and poor counseling are the main barriers to treatment adherence in this community. CONCLUSIONS: The study highlights the need to address the issues related to LTFU during TB treatment. The enhanced efforts of treatment supporters, health staff, and family & community persons must motivate and support the patients.

Comparative Yield of Pulmonary Tuberculosis by Different Symptoms among Saharia Tribe of Madhya Pradesh, India.

BACKGROUND: Symptom elicitation is a simple and inexpensive screening tool used for population screening in tuberculosis (TB) prevalence surveys. However, the information on the yield of TB cases by symptoms is sparsely available. METHODS: A cross-sectional pulmonary TB (PTB) prevalence survey was conducted. All available eligible individuals were interviewed for symptoms of PTB. Sputum samples were collected and tested for PTB by smear microscopy and culture. RESULTS: Among 2890 individuals tested for PTB, 77% had cough for 2 weeks or more and one-third reported chest pain for 1 month or more. About 31% were having a history of anti-TB treatment. Cough contributed to 82% PTB cases and the history of anti-TB treatment contributed to another 8.4% confirmed cases. Fever recorded lowest yield among the symptoms of PTB. CONCLUSION: The study suggests that fever alone may be ignored from symptomatic elicitation, and history of previous anti-TB treatment should be treated as an important indication for PTB symptomatic elicitation.

Extensively drug-resistant tuberculosis treated with bedaquiline: A case report in the particularly vulnerable tribal group of Madhya Pradesh, India.

The management of drug-resistant (DR) tuberculosis (TB) remains a challenge particularly in remote rural areas of the country. Although the treatment with wholly oral drug regimens, including bedaquiline (BDQ) and delamanid, is rolled out under the National TB Elimination Program, little is known about its coverage and the effectiveness in hard-to-reach tribal areas. The present report describes the early identification and successful management, through team effort, of a case of extensively DR TB belonging to the Saharia tribe - a Particularly Vulnerable Tribal Groups (PVTGs) of Madhya Pradesh, which has a very high prevalence of TB. The BDQ-containing regimen was well tolerated and found effective with minimal side effects and contributed to the reduced time to culture conversion and radiological improvements. The concerted efforts and strategies need to be adopted for effective implementation of Programmatic management of DR TB (PMDT) guidelines in remote tribal areas of the country.

Experiences and needs of patients with MDR/XDR-TB: a qualitative study among Saharia tribe in Madhya Pradesh, Central India.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) continues to be a major public health threat posing a critical challenge to TB treatment and control worldwide. The present study was conducted among patients with DR-TB of the Saharia tribe residing in Madhya Pradesh state of Central India to document their experiences and needs, and to identify gaps for treatment adherence as this population is known to be poor because of migration and other factors. METHODS: We conducted 16 in-depth interviews on purposively selected patients with DR-TB among the Saharia tribe using a predesigned open-ended in-depth interview guide, which included questions on domains like general physical health, diagnosis, treatment adherence, side-effects of drugs and experience related to the health facility. Out of these interviews, various subthemes were extracted. The obtained qualitative data were subjected to thematic analysis. RESULTS: The study helped to understand the experiences and needs of the patients with DR-TB in various stages from diagnosis to treatment. Also, there was the impact of factors like lack of education and awareness, poor living conditions and lack of healthcare facilities on predominance of the disease in the community. Poor access to a healthcare facility, high pill burden and related side-effects, longer duration of treatment, financial burden, misbeliefs and misconceptions were prominent issues posing a challenge to treatment adherence. The narratives pointed out their struggle at every stage be it with diagnosis, treatment initiation or treatment adherence. CONCLUSION: It is paramount to address the needs and experiences of patients with DR-TB to develop a patient-centric and context-specific approach conducive to the sociocultural set-up of tribal people. This will scale down the attrition rate of tribal patients while adhering to the complete treatment process and reducing the high burden of TB among the Saharia community. In addition, tribal patients should be counselled at regular intervals to increase their confidence in the treatment.

Long-term survival of patients treated for tuberculosis: a population-based longitudinal study in a resource-poor setting.

OBJECTIVE: We assessed the long-term survival of TB patients belonging to the Saharia tribe, a high TB burden community in Shivpuri district, Madhya Pradesh, central India. METHODS: Population-based, longitudinal study conducted among 9756 Saharia population in 2013, and a resurvey done 2 years later in 2015 using the same methods. The status of the individuals during resurvey was recorded as non-TB, relapse and death. The deaths recorded in this period were used to measure the mortality among TB-affected population and the non-TB population in this cohort. RESULTS: The standardised mortality ratio for the study cohort was 122.9 per 1000 population; males had higher mortality than females (129.9 vs. 96.8). The expected mortality among the non-TB population was 30.2, and the observed mortality among TB-affected population was 122.9 per 1000 population. CONCLUSION: In the Saharia tribe, post-treatment mortality in the TB-affected population is significantly higher than in the general population. This highlights an urgent need for implementation of effective public health strategies to prevent disproportionate deaths among TB-affected individuals in resource-poor settings, and the importance of periodic follow-up of patients after cure/completion of treatment, especially in vulnerable populations.

SARS-CoV-2 seroprevalence among the general population and healthcare workers in India, December 2020-January 2021.

BACKGROUND: Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May-June 2020 and 7.1% in August-September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India. METHODS: The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated. RESULTS: Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0-25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5-27.8%). CONCLUSIONS: Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020.

SARS-CoV-2 antibody seroprevalence in India, August-September, 2020: findings from the second nationwide household serosurvey.

BACKGROUND: The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May-June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0·73% (95% CI 0·34-1·13). We aimed to assess the more recent nationwide seroprevalence in the general population in India. METHODS: We did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. 3-5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys. FINDINGS: Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6·6% (95% CI 5·8-7·4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7·1% (6·2-8·2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74·3 million infections in the country by Aug 18, 2020, with 26-32 infections for every reported COVID-19 case. INTERPRETATION: Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country. FUNDING: Indian Council of Medical Research.

Epidemiology of rotavirus diarrhea among children less than 5 years hospitalized with acute gastroenteritis prior to rotavirus vaccine introduction in India.

BACKGROUND: Rotavirus is an important cause of severe diarrhea requiring hospitalization, accounting for approximately 78,000 deaths annually in Indian children below 5 years of age. We present epidemiological data on severe rotavirus disease collected during hospital-based surveillance in India before the introduction of the oral rotavirus vaccine into the national immunization schedule. METHODS: The National Rotavirus Surveillance Network was created involving 28 hospital sites and 11 laboratories across the four geographical regions of India. From September 2012 to August 2016 children less than 5 years of age hospitalized for diarrhea for at least 6 h, were enrolled. After recording clinical details, a stool sample was collected from each enrolled child, which was tested for rotavirus antigen using enzyme immunoassay (EIA). Nearly 2/3rd of EIA positive samples were genotyped using reverse transcription polymerase chain reaction to identify the G and P types. RESULTS: Of the 21,421 children enrolled during the 4 years surveillance, 36.3% were positive for rotavirus. The eastern region had the highest proportion of rotavirus associated diarrhea (39.8%), while the southern region had the lowest (33.8%). Rotavirus detection rates were the highest in children aged 6-23 months (41.8%), and 24.7% in children aged < 6 months. Although rotavirus associated diarrhea was seen throughout the year, the highest positivity was documented between December and February across all the regions. The most common rotavirus genotype was G1P[8] (52.9%), followed by G9P4 (8.7%) and G2P4 (8.4%). CONCLUSIONS: There is high burden of rotavirus gastroenteritis among Indian children below 5 years of age hospitalized for acute diarrhea thereby highlighting the need for introduction of rotavirus vaccine into the national immunization program and also for monitoring circulating genotypes.

Diversity of rotavirus genotypes circulating in children < 5 years of age hospitalized for acute gastroenteritis in India from 2005 to 2016: analysis of temporal and regional genotype variation.

BACKGROUND: From 2016, the Government of India introduced the oral rotavirus vaccine into the national immunization schedule. Currently, two indigenously developed vaccines (ROTAVAC, Bharat Biotech; ROTASIIL, Serum Institute of India) are included in the Indian immunization program. We report the rotavirus disease burden and the diversity of rotavirus genotypes from 2005 to 2016 in a multi-centric surveillance study before the introduction of vaccines. METHODS: A total of 29,561 stool samples collected from 2005 to 2016 (7 sites during 2005-2009, 3 sites from 2009 to 2012, and 28 sites during 2012-2016) were included in the analysis. Stools were tested for rotavirus antigen using enzyme immunoassay (EIA). Genotyping was performed on 65.8% of the EIA positive samples using reverse transcription- polymerase chain reaction (RT-PCR) to identify the G (VP7) and P (VP4) types. Multinomial logistic regression was used to quantify the odds of detecting genotypes across the surveillance period and in particular age groups. RESULTS: Of the 29,561 samples tested, 10,959 (37.1%) were positive for rotavirus. There was a peak in rotavirus positivity during December to February across all sites. Of the 7215 genotyped samples, G1P[8] (38.7%) was the most common, followed by G2P[4] (12.3%), G9P[4] (5.8%), G12P[6] (4.2%), G9P[8] (4%), and G12P[8] (2.4%). Globally, G9P[4] and G12P[6] are less common genotypes, although these genotypes have been reported from India and few other countries. There was a variation in the geographic and temporal distribution of genotypes, and the emergence or re-emergence of new genotypes such as G3P[8] was seen. Over the surveillance period, there was a decline in the proportion of G2P[4], and an increase in the proportion of G9P[4]. A higher proportion of mixed and partially typed/untyped samples was also seen more in the age group 0-11 months. CONCLUSIONS: This 11 years surveillance highlights the high burden of severe rotavirus gastroenteritis in Indian children < 5 years of age before inclusion of rotavirus vaccines in the national programme. Regional variations in rotavirus epidemiology were seen, including the emergence of G3P[8] in the latter part of the surveillance. Having pre-introduction data is important to track changing epidemiology of rotaviruses, particularly following vaccine introduction.

Prevalence of SARS-CoV-2 infection in India: Findings from the national serosurvey, May-June 2020.

BACKGROUND & OBJECTIVES: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India. METHODS: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity. RESULTS: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths. INTERPRETATION & CONCLUSIONS: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country.

Recurrence of tuberculosis among newly diagnosed sputum positive pulmonary tuberculosis patients treated under the Revised National Tuberculosis Control Programme, India: A multi-centric prospective study.

INTRODUCTION: There 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. OBJECTIVE: To 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. METHODOLOGY: Adult (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. RESULTS: Of 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. CONCLUSION: A substantial proportion of new smear positive PTB patients successfully treated with 6 -month thrice-weekly regimen have TB recurrence under program settings.

A comparative study of the socio-economic risk factors for pulmonary tuberculosis in the Saharia tribe of Madhya Pradesh, India.

Background: To determine the socio-economic risk factors for pulmonary tuberculosis (PTB) in the Saharia tribal community in Madhya Pradesh, Central India. Methods: PTB cases detected during the year 2013-14 through a community active TB prevalence survey in the Shivpuri district, Madhya Pradesh were included in the study. For each case, three controls were selected randomly among the non-cases from the same village and the data on socio-economic risk factors were collected. Using logistic regression analysis, the risk factors for PTB disease were identified. Results: A total of 220 cases and 660 controls participated in the study. Of the 13 risk factors studied, on multivariate analysis the risk of PTB was found to be significantly associated with malnutrition (adjusted odds ratio [AOR] 2.02 [95% confidence interval {CI} 1.46 to 2.79]), living in a kaccha (built of naturally occurring materials) house (AOR 2.72 [95% CI 1.44 to 5.11]) and tobacco smoking (mostly beedis; AOR 1.59 [95% CI 1.12 to 2.18]). Conclusions: The findings highlight that malnutrition, poor living conditions in a Kaccha house (built of naturally occurring materials) and tobacco smoking are the major risk factors for PTB among Saharias, which need to be studied among other tribal populations in the country. There is a need to strengthen health and nutrition programmes in this community.

Investigation of the risk factors for pulmonary tuberculosis: A case-control study among Saharia tribe in Gwalior district, Madhya Pradesh, India.

BACKGROUND & OBJECTIVES: Prevalence of pulmonary tuberculosis (PTB) is known to be high in the indigenous tribal community Saharia in Madhya Pradesh, India. The risk factors for PTB are not well known among them. This study was done to determine various risk factors associated with PTB in the indigenous community Saharia. METHODS: A prevalence survey was conducted among Saharias of Gwalior district of Madhya Pradesh. The population surveyed was 12,123 which was the source of cases and controls for the present study. All the bacillary-positive cases and controls in the ratio of 1:5 were included in the survey. Data were collected by the trained health workers from the patients and controls using a semi-structured pre-coded and pre-tested questionnaire which included data on risk factors including demographic factors, host-related factors and household factors. The individuals were also screened for diabetes mellitus and HIV. RESULTS: Malnutrition and history of asthma were associated with an increased risk of PTB. More than 56 per cent cases were attributed to malnutrition and 12 per cent attributed to asthma. Low family income, alcohol consumption and smoking were the other contributors. The risk was higher in males as compared to females. INTERPRETATION & CONCLUSIONS: The study emphasized that the main contributors were social factors. Nutrition supplementation, especially in tuberculosis (TB) patients and integrated approach to improve their living conditions are needed to control TB in this community.

Discovery of Imidazo[1,2-a]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis.

The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo[1,2-a]pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure-activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection.