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.

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.

Gender differences in COVID-19 knowledge, risk perception, and public stigma among the general community: Findings from a nationwide cross-sectional study in India.

Introduction: Individual and community characteristics predictive of knowledge, perception, and attitude on COVID-19, specifically on gender, have not been adequately explored. Objective: To examine the gender differences in COVID-19 knowledge, self-risk perception and public stigma among the general community and to understand other socio-demographic factors which were predictive of them. Method: A nationally representative cross-sectional multi-centric survey was conducted among adult individuals(≥18 yrs) from the community member (N = 1978) from six states and one union territory of India between August 2020 to February 2021. The participants were selected using systematic random sampling. The data were collected telephonically using pilot-tested structured questionnaires and were analyzed using STATA. Gender-segregated multivariable analysis was conducted to identify statistically significant predictors (p < 0.05) of COVID-19-related knowledge, risk perception, and public stigma in the community. Results: Study identified significant differences between males and females in their self-risk perception (22.0% & 18.2% respectively) and stigmatizing attitude (55.3% & 47.1% respectively). Highly educated males and females had higher odds of having COVID-19 knowledge (aOR: 16.83: p < 0.05) than illiterates. Highly educated women had higher odds of having self-risk perception (aOR: 2.6; p < 0.05) but lower public stigma [aOR: 0.57; p < 0.05]. Male rural residents had lower odds of having self-risk perception and knowledge [aOR: 0.55; p < 0.05 & aOR: 0.72; p < 0.05] and female rural residents had higher odds of having public stigma [aOR: 1.36; p < 0.05]. Conclusion: Our study findings suggest the importance of considering thegender differentials and their background, education status and residential status in designing effective interventions to improve knowledge and reduce risk perception and stigma in the community about COVID-19.

Status of Universal Drug Susceptibility Testing in Pulmonary Tuberculosis Patients Initiated on Treatment in an Urban Setting, South India.

Introduction: Early initiation of drug susceptibility testing (DST) guided anti-tuberculosis treatment benefits the patient in terms of better treatment outcomes and possibly reduces the transmission of tuberculosis (TB) disease in the community. To determine the status of universal DST (UDST) coverage in smear-positive pulmonary TB patients (PTB) initiated on treatment under the TB program in Greater Chennai Corporation. In addition, the barriers and facilitators for UDST were explored. Material and Methods: The data of PTB patients who were initiated on anti-TB treatment from July to December 2019 was abstracted from the NI-KSHAY database of TB Program. The barriers and facilitators for UDST were explored in 5 focus group discussions (FGDs) among the TB program healthcare workers (HCW). UDST coverage was based on the availability of Cartridge-based Nucleic Acid Amplification test (CBNAAT) results in the NI-KSHAY database. Results: The CBNAAT result was available for 1628 (82.6%) of the 1970 smear-positive PTB patients. Non-availability of CBNAAT results was significantly higher among the older age group (>50 years), in female PTB patients, and the Private Sector. Issues with sputum collection, transport of specimens, and receipt of results were highlighted by the HCWs for the non-availability of UDST results. Conclusion: Universal DST coverage in smear-positive PTB patients initiated on treatment in 2019 in Chennai was optimal as per National Strategic Plan for TB elimination UDST target of 80% for the year 2020 but with scope for improvement. The low UDST coverage in the private sector, among female patients and older age groups, needs to be addressed.

Revisiting the Chingleput BCG vaccination trial for the impact of BCG revaccination on the incidence of tuberculosis disease.

Background & objectives: Vaccines play a crucial role in the prevention of tuberculosis (TB). Revaccination with Bacille Calmette-Guerin (BCG) for the prevention of TB is an important strategy that is currently gaining interest. The objective of this study was to reanalyze the community-based Chingleput BCG vaccination trial for protective efficacy of BCG revaccination against incident TB disease. Methods: A retrospective analysis of the Chingleput BCG vaccination trial (conducted in 1968) data was carried out. Data on participants with evidence of prior BCG vaccination at trial intake and randomized to BCG vaccine [low dose (0.01 mg), high dose (0.1 mg)] and placebo arms were analyzed. The incidence of TB disease, which was based on sputum culture and/or chest X-ray was compared between the BCG and placebo arms over a 15 yr follow up period. Results: Of the 269,727 individuals randomized in the trial; 263,158 had no evidence of TB at baseline, of which 4436 (1.68%) had evidence of BCG vaccination at trial intake (2890 in the BCG vaccine and 1546 in the placebo arms, respectively). There were 77 (190 per 100,000) and 64 (296 per 100,000) incident TB cases in the BCG and placebo arm, respectively, at 15 yr post-vaccination. The incidence of TB disease was significantly lower in the BCG arm [Hazard ratio of BCG arm (95% confidence interval): 0.64 (0.46-0.89)]. Interpretation & conclusions: Retrospective data analysis of this community-based trial revealed that BCG revaccination in a community offered modest protection against the development of TB disease at the end of 15 years which, however, requires further evaluation.

Standardization of a stool concentration method for Mycobacterium tuberculosis detection in the pediatric population.

Background: The inability of young children to expectorate sputum and paucibacillary status of Mycobacterium tuberculosis (MTB) increases its diagnostic complexity. In this study, we aimed to standardize a stool concentration method for the detection of MTB and its drug resistance by line probe assay (LPA). Methods: The stool from 10 healthy children spiked with H37Rv in five different dilutions (1:1, 1:10, 1:100, 1:1000, and 1:10,000), and stool from 10 confirmed TB and 54 clinically diagnosed TB children were subjected to an in-house stool concentration protocol. All the processed filtrates were subjected to smear microscopy, solid culture, Xpert ultra testing, and LPA. Results: Of 10 control samples, growth was seen in four samples (neat 1:1). In smear microscopy, bacilli could be seen in eight samples (1:1 and 1:10). Xpert ultra testing could detect MTB in eight samples in all dilutions with different loads. LPA could detect MTB in all samples and dilutions. In microbiologically confirmed children, seven out of 10 stool samples tested were positive. Out of 54 children with clinically diagnosed TB, 4 (7.4%) could be confirmed by microbiological diagnosis. Conclusion: The protocol standardized in this study proves to be better working in the molecular detection of MTB.

Factors associated with COVID-19 stigma during the onset of the global pandemic in India: A cross-sectional study.

Objective: To assess factors associated with COVID-19 stigmatizing attitudes in the community and stigma experiences of COVID-19 recovered individuals during first wave of COVID-19 pandemic in India. Methods: A cross-sectional study was conducted in 18 districts located in 7 States in India during September 2020 to January 2021 among adults > 18 years of age selected through systematic random sampling. Data on socio demographic and COVID-19 knowledge were collected from 303 COVID-19 recovered and 1,976 non-COVID-19 infected individuals from community using a survey questionnaire. Stigma was assessed using COVID-19 Stigma Scale and Community COVID-19 Stigma Scale developed for the study. Informed consent was sought from the participants. Univariate and multivariate binary logistic regression analysis were conducted. Results: Half of the participants (51.3%) from the community reported prevalence of severe stigmatizing attitudes toward COVID-19 infected while 38.6% of COVID-19 recovered participants reported experiencing severe stigma. Participants from the community were more likely to report stigmatizing attitudes toward COVID-19 infected if they were residents of high prevalent COVID-19 zone (AOR: 1.5; CI: 1.2-1.9), staying in rural areas (AOR: 1.5; CI:1.1-1.9), belonged to the age group of 18-30 years (AOR: 1.6; CI 1.2-2.0), were male (AOR: 1.6; CI: 1.3-1.9), illiterate (AOR: 2.7; CI: 1.8-4.2), or living in Maharashtra (AOR: 7.4; CI: 4.8-11.3). COVID-19 recovered participants had higher odds of experiencing stigma if they had poor knowledge about COVID-19 transmission (AOR: 2.8; CI: 1.3-6.3), were staying for 6-15 years (AOR: 3.24; CI: 1.1-9.4) in the current place of residence or belonged to Delhi (AOR: 5.3; CI: 1.04-26.7). Conclusion: Findings indicated presence of stigmatizing attitudes in the community as well as experienced stigma among COVID-19 recovered across selected study sites in India during the first wave of COVID-19 pandemic. Study recommends timely dissemination of factual information to populations vulnerable to misinformation and psychosocial interventions for individuals affected by stigma.

Development & validation of scales to assess stigma related to COVID-19 in India.

Background & objectives: COVID-19 pandemic has triggered social stigma towards individuals affected and their families. This study describes the process undertaken for the development and validation of scales to assess stigmatizing attitudes and experiences among COVID-19 and non-COVID-19 participants from the community. Methods: COVID-19 Stigma Scale and Community COVID-19 Stigma Scale constituting 13 and six items, respectively, were developed based on review of literature and news reports, expert committee evaluation and participants' interviews through telephone for a multicentric study in India. For content validity, 61 (30 COVID-19-recovered and 31 non-COVID-19 participants from the community) were recruited. Test-retest reliability of the scales was assessed among 99 participants (41 COVID-19 recovered and 58 non-COVID-19). Participants were administered the scale at two-time points after a gap of 7-12 days. Cronbach's alpha, overall percentage agreement and kappa statistics were used to assess internal consistency and test-retest reliability. Results: Items in the scales were relevant and comprehensible. Both the scales had Cronbach's α above 0.6 indicating moderate-to-good internal consistency. Test-retest reliability assessed using kappa statistics indicated that for the COVID-19 Stigma Scale, seven items had a moderate agreement (0.4-0.6). For the Community COVID-19 Stigma Scale, four items had a moderate agreement. Interpretation & conclusions: Validity and reliability of the two stigma scales indicated that the scales were comprehensible and had moderate internal consistency. These scales could be used to assess COVID-19 stigma and help in the development of appropriate stigma reduction interventions for COVID-19 infected, and mitigation of stigmatizing attitudes in the community.

Measuring tuberculosis patient perceived quality of care in public and public-private mix settings in India: an instrument development and validation study.

BACKGROUND: At present, there are no validated quantitative scales available to measure patient-centred quality of care in health facilities providing services for tuberculosis (TB) patients in India and low-income and middle-income countries. METHODS: Initial themes and items reflective of TB patient's perceived quality of care were developed using qualitative interviews. Content adequacy of the items were ascertained through Content validity Index (CVI) and content validity ratio (CVR). Pilot testing of the questionnaire for assessing validity and reliability was undertaken among 714 patients with TB. Sampling adequacy and sphericity were tested by Kaiser-Meyer-Olkin and Bartlett's test, respectively. Exploratory and confirmatory factor analysis was undertaken to test validity. Cronbach's α and test-retest scores were used to test reliability. RESULTS: A 32-item tool measuring patient-perceived quality of TB distributed across five domains was developed initially based on a CVI and CVR cut-off score of 0.78 and cognitive interviews with patients with TB. Bartlett's test results showed a strong significance f (χ2=3756 and p<0.001) and Kaiser-Meyer-Olkin was measured to be 0.698 highlighting data adequacy and correlation between the variables. Exploratory factor analysis with varimax rotation extracted 4 factors related to 14 items with Eigen values >1 which accounted for 60.9% of the total variance of items. Correlation (z-value >1.96) between items and factors was highly significant and Cronbach's α was acceptable for the global scale (0.76) for the four factors. Intraclass correlation coefficient and the test retest scores for four factors were (<0.001) significant. CONCLUSION: We validated a measurement tool for patient-perceived quality of care for TB (PPQCTB) which measured the patient's satisfaction with healthcare provider and services. PPQCTB tool could enrich quality of care evaluation frameworks for TB health services in India.

An influence of dew point temperature on the occurrence of Mycobacterium tuberculosis disease in Chennai, India.

Climate factors such as dew point temperature, relative humidity and atmospheric temperature may be crucial for the spread of tuberculosis. This study was conducted for the first time to investigate the relationship of climatic factors with TB occurrence in an Indian setting. Daily tuberculosis notification data during 2008-2015 were generated from the National Treatment Elimination Program, and analogous daily climatic data were obtained from the Regional Meteorological Centre at Chennai city, Tamil Nadu, India. The decomposition method was adopted to split the series into deterministic and non-deterministic components, such as seasonal, non-seasonal, trend and cyclical, and non-deterministic climate factors. A generalized linear model was used to assess the relation independently. TB disease progression from latent stage infection to active was supported by higher dew point temperature and moderate temperature. It had a significant association with TB progression in the summer and monsoon seasons. The relative humidity may be favored in the winter and post-monsoon. The water tiny dew droplets may support the TB bacterium to recuperate in the environment.

Psychological distress and burnout among healthcare worker during COVID-19 pandemic in India-A cross-sectional study.

BACKGROUND: COVID-19 has inundated the entire world disrupting the lives of millions of people. The pandemic has stressed the healthcare system of India impacting the psychological status and functioning of health care workers. The aim of this study is to determine the burnout levels and factors associated with the risk of psychological distress among healthcare workers (HCW) engaged in the management of COVID 19 in India. METHODS: A cross-sectional study was conducted from 1 September 2020 to 30 November 2020 by telephonic interviews using a web-based Google form. Health facilities and community centres from 12 cities located in 10 states were selected for data collection. Data on socio-demographic and occupation-related variables like age, sex, type of family, income, type of occupation, hours of work and income were obtained was obtained from 967 participants, including doctors, nurses, ambulance drivers, emergency response teams, lab personnel, and others directly involved in COVID 19 patient care. Levels of psychological distress was assessed by the General health Questionnaire -GHQ-5 and levels of burnout was assessed using the ICMR-NIOH Burnout questionnaire. Multivariable logistic regression analysis was performed to identify factors associated with the risk of psychological distress. The third quartile values of the three subscales of burnout viz EE, DP and PA were used to identify burnout profiles of the healthcare workers. RESULTS: Overall, 52.9% of the participants had the risk of psychological distress that needed further evaluation. Risk of psychological distress was significantly associated with longer hours of work (≥ 8 hours a day) (AOR = 2.38, 95% CI(1.66-3.41), income≥20000(AOR = 1.74, 95% CI, (1.16-2.6); screening of COVID-19 patients (AOR = 1.63 95% CI (1.09-2.46), contact tracing (AOR = 2.05, 95% CI (1.1-3.81), High Emotional exhaustion score (EE ≥16) (AOR = 4.41 95% CI (3.14-6.28) and High Depersonalisation score (DP≥7) (AOR = 1.79, 95% CI (1.28-2.51)). About 4.7% of the HCWs were overextended (EE>18); 6.5% were disengaged (DP>8) and 9.7% HCWs were showing signs of burnout (high on all three dimensions). CONCLUSION: The study has identified key factors that could have been likely triggers for psychological distress among healthcare workers who were engaged in management of COVID cases in India. The study also demonstrates the use of GHQ-5 and ICMR-NIOH Burnout questionnaire as important tools to identify persons at risk of psychological distress and occurrence of burnout symptoms respectively. The findings provide useful guide to planning interventions to mitigate mental health problems among HCW in future epidemic/pandemic scenarios in the country.

Can Students Learn from Their Co-Students About Tuberculosis? Outcomes from Student-Friendly Quasi-Experimental Intervention Study in India.

Background: The World Health Organization's "End TB Strategy" aims to end global tuberculosis (TB) epidemic through a holistic combination of health and social interventions placing the patients and communities at the heart of the response. This study aimed to assess the effectiveness of utilizing school children as ambassadors in TB advocacy. Materials and Methods: We adopted a quasi-experimental intervention design where students' awareness level was assessed before and after the intervention. A total of 185 student ambassadors were trained to conduct interventions in schools, and 920 students were randomly selected to assess the impact of the ambassador's intervention. A structured questionnaire was used to assess the correct and incorrect knowledge on specific aspects of TB. This intervention study was implemented in a phased manner which involved a participatory formative phase. A student-friendly and culturally relevant educational materials and activities for providing TB knowledge for the study student population were developed. Data collected from the baseline and end-line evaluation surveys were analyzed using STAT Ver. 16.0.- Stata Corp., June 2016, USA. Results: A significant increase (>80%; P < 0.05) in the correct knowledge on diagnosis and prevention for TB was noted among sampled students (n = 818) before and after intervention. Reduction in incorrect knowledge, like understanding TB as hereditary disease, was found to be less (50%; P < 0.05). Conclusions: School students lead intervention could significantly improve correct knowledge on TB and could be replicated.

Long-term Survival of Treated Tuberculosis Patients in Comparison to a General Population In South India: A Matched Cohort Study.

OBJECTIVES: This study aimed to measure the mortality rate, potential years of life lost, and excess general mortality among individuals treated for pulmonary tuberculosis (TB) in a TB endemic country. METHODS: A retrospective analysis was conducted on a population-based cohort study of 4022 TB patients and 12,243 gender-matched and age-matched controls from prevalence surveys conducted between 2000 and 2004 in the Thiruvallur district of Tamil Nadu, South India. RESULTS: The mortality rate among TB patients was 59/1000 person-years. The excess standardized mortality ratio was 2.3 (95% CI: 1.7-3.1). The rate of potential years of life lost was 6.15/1000 (95% CI: 5.97-6.33) in the TB cohort compared to the general population of 1.52/1000 (95% CI: 1.46-1.60). Individuals aged >50 years, those underweight (<40 kg), with treatment failures, or lost to follow-up had higher mortality rates when compared with the rest of the TB cohort. The risk of death was significantly higher in the TB cohort until the end of the fourth year when compared with later years. CONCLUSION: Mortality in the TB cohort was 2.3 times higher than in the age-matched general population. Most deaths occurred in the first year after completing treatment. Post-treatment follow-ups and interventions for reducing comorbid conditions are necessary to prevent deaths.

The RATIONS (Reducing Activation of Tuberculosis by Improvement of Nutritional Status) study: a cluster randomised trial of nutritional support (food rations) to reduce TB incidence in household contacts of patients with microbiologically confirmed pulmonary tuberculosis in communities with a high prevalence of undernutrition, Jharkhand, India.

INTRODUCTION: India has the largest burden of cases and deaths related to tuberculosis (TB). Undernutrition is the leading risk factor accounting for TB incidence, while severe undernutrition is a common risk factor for mortality in patients with TB in India. The impact of nutritional supplementation on TB incidence is unknown, while few underpowered studies have assessed its impact on TB mortality. We designed an open-label, field-based cluster randomised trial to assess the impact of nutritional supplementation (with food rations) on TB incidence in a group at higher risk of TB infection and disease, viz household contacts (HHC) of patients with microbiologically confirmed pulmonary TB (PTB) in Jharkhand, a state with a high prevalence of undernutrition. METHODS AND ANALYSIS: We shall enrol 2800 adult patients with PTB of the national TB programme, across 28 treatment units in 4 districts, and their approximately 11 200 eligible contacts. The sample size has 80% power to detect the primary outcome of 50% reduction in incidence of active TB in HHC over 2 years of follow-up. Patients and HHC in both the arms will undergo nutritional assessment and counselling. Patients will receive monthly food rations (supplying 1200 kcal and 52 g proteins/day) and multivitamins along with antitubercular treatment. The HHC in the intervention arm will receive food rations (supplying 750 kcal and 23 g proteins/day) and multivitamins while HHC in control arm will be on usual diet. The secondary outcomes in HHC will include effects on nutritional status, non-TB infections. Secondary outcomes in patients are effects on TB mortality, adherence, adverse effects, nutritional and performance status. Substudies will examine micronutrient status and effects on dietary intake, body composition, muscle strength and immune function. ETHICS AND DISSEMINATION: The institutional ethics committee of ICMR-NIRT, Chennai, approved the study (289/NIRT-IEC/2018). The results will be disseminated in publications and presentations. TRIAL REGISTRATION NUMBER: Clinical Trial Registry of India: CTRI/2019/08/020490.

Tuberculosis screening in household contacts of pulmonary tuberculosis patients in an urban setting.

BACKGROUND: Household contacts (HHC) of tuberculosis (TB) patients are at risk of TB infection and disease. The study assessed the utility of "Household contact card and register" for screening of HHC of pulmonary TB (PTB) patients for TB and explored the reasons for HHC not being screened and followed-up. METHODS: The "Household contact card and register" was implemented by the Health Care Workers (HCW) of the TB Control Programme in Chennai District for screening HHC of index PTB patients initiated on treatment between June and August, 2018. Contacts were required to be screened within 2 months of treatment initiation of the index patient. Details collected included age, gender, smoking, alcohol use, immunosuppressive conditions and TB treatment. Symptom screening along with chest radiograph and or sputum examination was attempted. Follow-up TB screening at 6 and 12 months were performed. Screening of HHC was compared pre and post implementation phase. Proportions were computed for the data analysed. RESULTS: HHC information was documented for 93% (1268/1364) of Index PTB patients. The main reasons of non-listing of HHC in 96 PTB patients were HCW non-availability or non-co-operation of the HHC. There were 2150 (80%) contacts who were screened for TB. Inconvenient time, feeling healthy, stigma, out-station visit were the main reasons for 537 contacts not undergoing TB screening. Anti-TB treatment was initiated in 21 (1%) of contacts diagnosed with TB. Preventive therapy was initiated in 59% (81/138) of contacts aged <6 years. The screening of HHC improved from 36% to 80% during the implementation phase. Follow-up TB screening at 12 months was performed in 50% of HHC and 2 incident TB cases were identified. CONCLUSION: "Household contact card and register" is a useful tool for HCWs for TB screening in HHC of PTB patients. Reasons for non-adherence to contact screening needs to be addressed.

Impact of rapid molecular diagnostic tests on time to treatment initiation and outcomes in patients with multidrug-resistant tuberculosis, Tamil Nadu, India.

BACKGROUND: India is replacing culture and drug sensitivity testing (CDST) with rapid molecular tests for diagnosing MDR-TB. We assessed the impact of rapid tests on time to initiation of treatment and outcomes in patients with MDR-TB compared with CDST. METHODS: A retrospective cohort study involving MDR-TB patients from six districts in Tamil Nadu state, who underwent CDST (2010-2011) and rapid tests (2012-2013). RESULTS: There were 135 patients in the CDST group and 389 in the rapid diagnostic test group. Median time from sputum receipt at the laboratory to initiation of MDR-TB treatment was 130 days (IQR 75-213) in the CDST group and 22 days (IQR 14-38) in the rapid diagnostic test group (p<0.001). Overall treatment success was 30% with CDST and 41% with rapid tests (p<0.05), but there was high loss to follow-up >30% in both groups and missing data were higher in CDST (13%) compared with rapid tests (3%). There were significantly higher risks of unfavourable treatment outcomes in males (aRR 1.3, 95% CI 1.1-1.5) and those with treatment initiation delays >30 days (aRR 1.3, 95% CI 1.0-1.6). CONCLUSION: Rapid molecular diagnostic tests shortened the time to initiate treatment which was associated with reduced unfavourable outcomes in MDR-TB patients. This supports the policy to scale up these tests in India.

Household Contact Screening and Yield of Tuberculosis Cases-A Clinic Based Study in Chennai, South India.

BACKGROUND: Contact investigation is an active case finding strategy to increase detection of Tuberculosis (TB) and a key component of TB control programs. The household contacts are at a higher risk of exposure than members of the general population. The information on the value and yield of household contact screening and the approaches used in high incidence settings like India is limited. OBJECTIVE: To evaluate the yield of active case finding in household contacts of newly diagnosed smear positive TB patients and the factors associated with increased yield. METHOD: Retrospective record review of the household contacts of newly diagnosed sputum smear positive patients (index case) enrolled in a clinical trial at National Institute of Research in Tuberculosis, Chennai during the period 2007-2014. A sequential screening algorithm with chest x-ray followed by symptom screen was employed to identify presumptive TB patients. RESULTS: 643 household contacts of 280 index TB patients were identified out of which 544 (85%) consented for screening. 71/544 (13%) patients had an abnormal chest radiograph and out of them 70% were symptomatic. A total of 29/544 (5.3%) contacts were found to have TB among whom 23/29 (79%) were sputum smear positive. The number needed to screen (NNS) to identify a new TB case among all household contacts was 19 and among those with an abnormal CXR was 02. Age group > 44 years, male gender and siblings of the index case was associated with abnormal chest radiograph whereas age group between 15-44 was significantly associated with developing TB disease among household contacts. CONCLUSION: Active screening among household contacts is an effective way to improve TB case detection. The yield for new TB cases among contacts with abnormal x-ray was high in this study and the use of Chest X-rays in combination with symptom screen is recommended.

Effectiveness of TB sensitization initiatives in improving the involvement of self help group members in rural TB control in south India.

Background: The 'End TB strategy' has highlighted the importance of inter-sectoral collaboration and community mobilization for achieving zero TB deaths by 2020. Objective: The aim of the study was to develop and test a model TB sensitization programme involving self help groups (SHGs). Methodology: This experimental study was conducted in two blocks (intervention and control), in Tiruvallur district. The intervention content included short-lecture, musical story telling activity, role play, short film on TB. The impact was compared at baseline, third and sixth months in terms of SHGs' awareness, promotion of awareness, identification and referral of presumptive TB cases and provision of TB treatment. Results: A total of 764 vs 796 SHGs were enrolled in control and intervention groups, respectively. The knowledge attitude, and practice score (lower score indicated a better attitude and practice), from baseline to 6 months was significantly reduced (29 to 24) in the intervention group. Similarly, a significant difference was observed in identification and referral of chest symptomatics in the intervention group at 3 and 6 months. During the 3 month follow-up a significantly higher proportion of SHG members were involved in TB awareness activities in the intervention (623/748 [83.3%]) vs control group (471/728 [64.7%]; p<0.001). Conclusions: Findings from this study highlight the feasibility of involving SHGs through a model TB sensitization program for strengthening TB prevention and control activities.

Prevalence of chest symptoms amongst brick kiln migrant workers and care seeking behaviour: a study from South India.

BACKGROUND: Early detection and treatment of tuberculosis (TB) have been key principles of TB control. However, this can be a challenge with 'hard to reach' populations such as migrants. Brick kiln workers are one such group of migrants who are exposed to smoke, heat and dust from brick kilns which are one of the major causes of respiratory illnesses. METHODOLOGY: A cross-sectional community based study was carried out in Thiruvallur, Tamil Nadu, South India, from August 2011 to June 2012. A total of 4002 individuals from 55 brick kiln chambers were interviewed to determine the prevalence of chest symptoms and care seeking behaviour patterns. RESULTS: Three hundred and seventy-seven (9.4%) chest symptomatics were identified. The most significant variables associated with chest symptoms were illiteracy, alcohol abuse and heavy smoking. Of the chest symptomatics identified, 50.4% took action to get relief from their symptoms. The duration of over 6-month stay in the chamber was significantly associated with taking action (OR, 5.5, 95% CI: 2.3, 13.3). CONCLUSIONS: The TB control programme needs to further explore how to extend its services to such 'hard to reach' groups. Active case finding to ensure early diagnosis and treatment initiation amongst such groups needs consideration.

Profile and response to anti-tuberculosis treatment among elderly tuberculosis patients treated under the TB Control programme in South India.

INTRODUCTION: The demographic transition in India has resulted in an increase in the elderly population. There is limited data on the profile of elderly tuberculosis (TB) patients and their treatment outcomes in India. OBJECTIVE: To compare the clinical profile, presentation and response to anti-TB treatment among elderly (≥ 60 yrs) and younger (15-59 yrs) TB patients treated under the Revised National TB Control programme. METHODOLOGY: Retrospective cohort analysis of TB patients treated from May 1999 to December 2004 in one Tuberculosis Unit of Tiruvallur district, South India. RESULTS: Records of 865 elderly and 4343 younger TB patients were examined: elderly were more likely to be male (84% vs. 71%), smokers (46% vs.37%), illiterate (63% vs. 45%), identified by active case finding through survey (19% vs. 11%), have pulmonary TB (96% vs. 91%) and initial smear negative disease (46% vs. 36%) compared to younger (for all p<0.001). Among a total of 352 elderly and 1933 younger new smear positive pulmonary TB, the elderly had higher loss to follow-up (15% vs. 11%; p = 0.03) and death rates (9% vs. 4%; p<0.001). Mycobacterium tuberculosis susceptibility to first line anti-TB drugs did not differ (elderly 87% vs. younger 84%) (p = 0.20). Side effects related to anti-TB drugs were reported by a higher proportion of elderly patients (63% vs. 54%) (p = 0.005). Previously treated patients had similar treatment outcomes in both the groups. CONCLUSION: Elderly TB patients are less likely to have smear positive disease. Newly diagnosed elderly TB patients are more likely to be lost to follow-up or die and report drug side effects. Suitable interventions need to be developed for effective management and better treatment outcomes of TB in the elderly.