Constructing care cascades for active tuberculosis: A strategy for program monitoring and identifying gaps in quality of care.

The cascade of care is a model for evaluating patient retention across sequential stages of care required to achieve a successful treatment outcome. This approach was first used to evaluate HIV care and has since been applied to other diseases. The tuberculosis (TB) community has only recently started using care cascade analyses to quantify gaps in quality of care. In this article, we describe methods for estimating gaps (patient losses) and steps (patients retained) in the care cascade for active TB disease. We highlight approaches for overcoming challenges in constructing the TB care cascade, which include difficulties in estimating the population-level burden of disease and the diagnostic gap due to the limited sensitivity of TB diagnostic tests. We also describe potential uses of this model for evaluating the impact of interventions to improve case finding, diagnosis, linkage to care, retention in care, and post-treatment monitoring of TB patients.

Counting the lives saved by DOTS in India: a model-based approach.

BACKGROUND: Against the backdrop of renewed efforts to control tuberculosis (TB) worldwide, there is a need for improved methods to estimate the public health impact of TB programmes. Such methods should not only address the improved outcomes amongst those receiving care but should also account for the impact of TB services on reducing transmission. METHODS: Vital registration data in India are not sufficiently reliable for estimates of TB mortality. As an alternative approach, we developed a mathematical model of TB transmission dynamics and mortality, capturing the scale-up of DOTS in India, through the rollout of the Revised National TB Control Programme (RNTCP). We used available data from the literature to calculate TB mortality hazards amongst untreated TB; amongst cases treated under RNTCP; and amongst cases treated under non-RNTCP conditions. Using a Bayesian evidence synthesis framework, we combined these data with current estimates for the TB burden in India to calibrate the transmission model. We simulated the national TB epidemic in the presence and absence of the DOTS programme, measuring lives saved as the difference in TB deaths between these scenarios. RESULTS: From 1997 to 2016, India's RNTCP has saved 7.75 million lives (95% Bayesian credible interval 6.29-8.82 million). We estimate that 42% of this impact was due to the 'indirect' effects of the RNTCP in averting transmission as well as improving treatment outcomes. CONCLUSIONS: When expanding high-quality TB services, a substantial proportion of overall impact derives from preventive, as well as curative, benefits. Mathematical models, together with sufficient data, can be a helpful tool in estimating the true population impact of major disease control programmes.

The Tuberculosis Cascade of Care in India's Public Sector: A Systematic Review and Meta-analysis.

BACKGROUND: India has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world's "missing" patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The "cascade of care" is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions. METHODS AND FINDINGS: The care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India's TB patients. We define the TB cascade as including the following patient populations: total prevalent active TB patients in India, TB patients who reach and undergo evaluation at RNTCP diagnostic facilities, patients successfully diagnosed with TB, patients who start treatment, patients retained to treatment completion, and patients who achieve 1-y recurrence-free survival. We estimate each step of the cascade for 2013 using data from two World Health Organization (WHO) reports (2014-2015), one WHO dataset (2015), and three RNTCP reports (2014-2016). In addition, we conduct three targeted systematic reviews of the scientific literature to identify 39 unique articles published from 2000-2015 that provide additional data on five indicators that help estimate different steps of the TB cascade. We construct separate care cascades for the overall population of patients with active TB and for patients with specific forms of TB-including new smear-positive, new smear-negative, retreatment smear-positive, and multidrug-resistant (MDR) TB. The WHO estimated that there were 2,700,000 (95%CI: 1,800,000-3,800,000) prevalent TB patients in India in 2013. Of these patients, we estimate that 1,938,027 (72%) TB patients were evaluated at RNTCP facilities; 1,629,906 (60%) were successfully diagnosed; 1,417,838 (53%) got registered for treatment; 1,221,764 (45%) completed treatment; and 1,049,237 (95%CI: 1,008,775-1,083,243), or 39%, of 2,700,000 TB patients achieved the optimal outcome of 1-y recurrence-free survival. The separate cascades for different forms of TB highlight different patterns of patient attrition. Pretreatment loss to follow-up of diagnosed patients and post-treatment TB recurrence were major points of attrition in the new smear-positive TB cascade. In the new smear-negative and MDR TB cascades, a substantial proportion of patients who were evaluated at RNTCP diagnostic facilities were not successfully diagnosed. Retreatment smear-positive and MDR TB patients had poorer treatment outcomes than the general TB population. Limitations of our analysis include the lack of available data on the cascade of care in the private sector and substantial uncertainty regarding the 1-y period prevalence of TB in India. CONCLUSIONS: Increasing case detection is critical to improving outcomes in India's TB cascade of care, especially for smear-negative and MDR TB patients. For new smear-positive patients, pretreatment loss to follow-up and post-treatment TB recurrence are considerable points of attrition that may contribute to ongoing TB transmission. Future multisite studies providing more accurate information on key steps in the public sector TB cascade and extension of this analysis to private sector patients may help to better target interventions and resources for TB control in India.

Training strategies practiced for TB elimination.

Training is the backbone of any public health program and it is true for a vast program like TB. It is urgent when the program is aiming to End TB. The strategy that is followed in India for capacity building of TB workers is presented in this article. Various types of trainings that are needed are described in detail. Also enlisted are the different trainings undertaken at NTI for the last five years. Recent times the effect of Covid-19 has resulted in the acceleration of the effort of going for digital platforms and onlinetrainings and is described.

Tuberculosis preventive treatment: the next chapter of tuberculosis elimination in India.

The End TB Strategy envisions a world free of tuberculosis-zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per million people to <100 cases per million people within the next two decades. Expanding testing and treatment of tuberculosis infection is critical to achieving this goal. In high-burden countries, like India, the implementation of tuberculosis preventive treatment (TPT) remains a low priority. In this analysis article, we explore potential challenges and solutions of implementing TPT in India. The next chapter in tuberculosis elimination in India will require cost-effective and sustainable interventions aimed at tuberculosis infection. This will require constant innovation, locally driven solutions to address the diverse and dynamic tuberculosis epidemiology and persistent programme monitoring and evaluation. As new tools, regimens and approaches emerge, midcourse adjustments to policy and practice must be adopted. The development and implementation of new tools and strategies will call for close collaboration between local, national and international partners-both public and private-national health authorities, non-governmental organisations, research community and the diagnostic and pharmaceutical industry. Leading by example, India can contribute to global knowledge through operational research and programmatic implementation for combating tuberculosis infection.

Operational research within a Global Fund supported tuberculosis project in India: why, how and its contribution towards change in policy and practice.

BACKGROUND: The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices. OBJECTIVES: To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice. METHODS: From September 2010 to September 2016, three key OR-related activities were implemented. First, practical output-oriented modular training courses were conducted (n = 3) to build research capacity of personnel involved in the TB programme, co-facilitated by The Union, in collaboration with the national TB programme, WHO country office and CDC, Atlanta. Second, two large-scale Knowledge, Attitude and Practice (KAP) surveys were conducted at baseline and mid-project to assess the changes pertaining to TB knowledge, attitudes and practices among the general population, TB patients and health care providers over the project period. Third, studies were conducted to describe the project's core activities and outcomes. RESULTS: In the training courses, 44 participant teams were supported to develop research protocols on topics of national priority, resulting in 28 peer-reviewed scientific publications. The KAP surveys and description of project activities resulted in 14 peer-reviewed publications. Of the published papers at least 12 have influenced change in policy or practice. CONCLUSIONS: OR within a Global Fund supported TB project has resulted in building OR capacity, facilitating research in areas of national priority and influencing policy and practice. We believe this experience will provide guidance for undertaking OR in Global Fund projects.

Drug-Induced Hypothyroidism during Anti-Tuberculosis Treatment of Multidrug-Resistant Tuberculosis: Notes from the Field.

We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment; the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on anti-retroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted.

Relationship between Nutritional Support and Tuberculosis Treatment Outcomes in West Bengal, India.

INTRODUCTION: Poverty and poor nutrition are associated with the risk of developing tuberculosis (TB). Socioeconomic factors may interfere with anti-tuberculosis treatment compliance and its outcome. We examined whether providing nutritional support (monthly supply of rice and lentil beans) to TB patients who live below the poverty line was associated with TB treatment outcome. METHODS: This was a retrospective cohort study of sputum smear-positive pulmonary TB patients living below the poverty line (income of <$1.25 per day) registered for anti-tuberculosis treatment in two rural districts of West Bengal, India during 2012 to 2013. We compared treatment outcomes among patients who received nutritional support with those who did not. A log-binomial regression model was used to assess the relation between nutritional support and unsuccessful treatment outcome (loss-to-follow-up, treatment failure and death). RESULTS: Of 173 TB patients provided nutritional support, 15 (9%) had unsuccessful treatment outcomes, while 84 (21%) of the 400 not provided nutrition support had unsuccessful treatment outcomes (p < 0.001). After adjusting for age, sex and previous treatment, those who received nutritional support had a 50% reduced risk of unsuccessful treatment outcome than those who did not receive nutritional support (Relative Risk: 0.51; 95% Confidence Intervals: 0.30 - 0.86). CONCLUSION: Under programmatic conditions, monthly rations of rice and lentils were associated with lower risk of unsuccessful treatment outcome among impoverished TB patients. Given the relatively small financial commitment needed per patient ($10 per patient per month), the national TB programme should consider scaling up nutritional support among TB patients living below the poverty line.

Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models.

BACKGROUND: The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. METHODS: 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. FINDINGS: Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31-62%) and a 72% reduction in mortality (range 64-82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. INTERPRETATION: Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. FUNDING: Bill and Melinda Gates Foundation.

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.

BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. FINDINGS: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. INTERPRETATION: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. FUNDING: Bill & Melinda Gates Foundation.

Prevalence of pulmonary tuberculosis in Wardha district of Maharashtra, Central India.

A house based survey was conducted during 2007-2009 in a representative sample of population in Wardha district implementing Directly Observed Treatment Short Course strategy for tuberculosis (TB) control since 2001. The objective was to estimate prevalence of bacillary pulmonary TB (PTB) in individuals aged 15 years or above, and to estimate trends in prevalence when compared to a previous survey carried out in mid 1980's. Two sputum samples (one spot, one early morning) collected from individuals having symptoms suggestive of PTB, history of previous anti-TB treatment (ATT) or abnormal pulmonary shadow on Mass Miniature Radiography (MMR) consistent with possibly or probably active tuberculosis were subjected to Ziehl-Neelsen microscopy and culture on Lowenstein-Jensen medium. Of 55,096 individuals registered into the survey, 50,332 (91.4%) were screened by interview for symptoms and history of ATT and/or by MMR. Of them, 4805 were eligible for sputum collection; both specimens were collected in 4285 (89.2%) and only one specimen in 27 (0.6%). A total of 86 bacillary cases were detected during the survey. Prevalence of bacillary PTB was estimated at 188.7 (140.3-236.9) per 100,000 populations. There was a decline of 61% in the prevalence of PTB over a period of 22 years.

Prevalence of pulmonary tuberculosis among adults in a north Indian district.

BACKGROUND: Recent population prevalence estimates of pulmonary tuberculosis (PTB) are not available for several areas in India. We conducted a field-based population survey at a north Indian district to estimate point prevalence of bacteriologically positive PTB. METHODS: A stratified cluster sampling design was used to conduct the survey in both urban and rural areas within the district. All adults aged more than 15 years, in 18 rural and 12 urban clusters of 3000 subjects each, were interviewed using a symptom card. Two sputum samples were collected from all persons having symptoms suggestive of PTB, or history of antitubercular treatment, for smear microscopy for acid-fast bacilli and mycobacterial culture. Those having at least one sputum specimen positive on microscopy and/or culture were categorized as having PTB. Prevalence was estimated after adjusting for cluster sampling and incomplete data (through individual level analysis with robust standard error). RESULTS: Of 91,030 eligible adult participants (47,714 men and 43,316 women), 85,770 (94.2%) completed the symptom cards. Of them, 2,898 persons were considered eligible for sputum examination and 2,839 (98.0%) provided at least one sample. Overall, 21 persons had bacteriologically positive PTB, and cluster level prevalence was estimated at 24.5 per 100,000 population (95% CI 12.8-36.2). Individual level analysis with robust standard error yielded a prevalence estimate of 24.1 per 100,000 populations (95% CI 12.8-35.4). CONCLUSION: The observed prevalence of bacteriologically positive PTB in this district is lower than empiric national estimates, probably as a result of successful implementation of tuberculosis control measures in the area.

Trend in annual risk of tuberculous infection in north India.

SETTING: Six selected districts in Northern India. OBJECTIVES: To find out the trend in Annual risk of tuberculous infection (ARTI) in north India. STUDY DESIGN: Two rounds of community level surveys were conducted during 2000-2001 and 2009-10 respectively. Representative samples of children 1-9 years of age were tuberculin tested and maximum transverse diameter of induration was recorded in mm at about 72 hours. ARTI was computed from the estimated Prevalence of infection using mirror-image technique and anti-mode method. RESULTS: ARTI was found to decline from 1.9% (confidence interval: 1.7-2.1) at round I to 1.1% (confidence interval: 0.8-1.3) at round II at the rate of 8% per year during the intervening period. CONCLUSION: A significant reduction in the risk of tuberculous infection among children was observed between two rounds of surveys carried out at an interval of about 9 years.

Prevalence of pulmonary tuberculosis among adults in a rural sub-district of South India.

BACKGROUND: We conducted a survey to estimate point prevalence of bacteriologically positive pulmonary TB (PTB) in a rural area in South India, implementing TB program DOTS strategy since 2002. METHODS: Survey was conducted among persons ≥ 15 years of age in fifteen clusters selected by simple random sampling; each consisting of 5-12 villages. Persons having symptoms suggestive of PTB or history of anti-TB treatment (ATT) were eligible for sputum examination by smear microscopy for Acid Fast Bacilli and culture for Mycobacterium tuberculosis; two sputum samples were collected from each eligible person. Persons with one or both sputum specimen positive on microscopy and/or culture were labeled suffering from PTB. Prevalence was estimated after imputing missing values to correct for bias introduced by incompleteness of data. In six clusters, registered persons were also screened by X-ray chest. Persons with any abnormal shadow on X-ray were eligible for sputum examination in addition to those with symptoms and ATT. Multiplication factor calculated as ratio of prevalence while using both screening tools to prevalence using symptoms screening alone was applied to entire study population to estimate prevalence corrected for non-screening by X-ray. RESULTS: Of 71,874 residents ≥ 15 years of age, 63,362 (88.2%) were screened for symptoms and ATT. Of them, 5120 (8.1%) - 4681 (7.4%) with symptoms and an additional 439 (0.7%) with ATT were eligible for sputum examination. Spot specimen were collected from 4850 (94.7%) and early morning sputum specimens from 4719 (92.2%). Using symptom screening alone, prevalence of smear, culture and bacteriologically positive PTB in persons ≥ 15 years of age was 83 (CI: 57-109), 152 (CI: 108-197) and 196 (CI :145-246) per 100,000 population respectively. Prevalence corrected for non-screening by X-ray was 108 (CI: 82-134), 198 (CI: 153-243) and 254 (CI: 204-301) respectively. CONCLUSION: Observed prevalence suggests further strengthening of TB control program.

Prevalence of pulmonary tuberculosis--a baseline survey in central India.

BACKGROUND: The present study provides an estimate of the prevalence of bacteriologially positive pulmonary tuberculosis in Jabalpur, a district in central India. METHODOLOGY/PRINCIPAL FINDINGS: A community based cross-sectional survey was undertaken in Jabalpur District of the central Indian state of Madhya Pradesh. A stratified cluster sampling design was adopted to select the sample. All eligible individuals were questioned for pulmonary symptoms suggestive of TB disease. Two sputum samples were collected from all eligible individuals and were examined by Ziehl-Neelsen smear microscopy and solid media culture methods. Of the 99,918 individuals eligible for screening, 95,071 (95.1%) individuals were screened. Of these, 7,916 (8.3%) were found to have symptoms and sputum was collected from 7,533 (95.2%) individuals. Overall prevalence of bacteriologically positive PTB was found to be 255.3 per 100,000 population (95% C.I: 195.3-315.4). Prevalence was significantly higher (p<0.001) amongst males (355.8; 95% C.I: 304.4-413.4) compared with females (109.0; 95% C.I: 81.2-143.3). Prevalence was also significantly higher in rural areas (348.9; 95% C.I: 292.6-412.8) as compared to the urban (153.9; 95% C.I: 123.2-190.1). CONCLUSIONS/SIGNIFICANCE: The TB situation in Jabalpur district, central India, is observed to be comparable to the TB situation at the national level (255.3 versus 249). There is however, a need to maintain and further strengthen TB control measures on a sustained and long term basis in the area to have a significant impact on the disease prevalence in the community.

Guidelines for conducting tuberculin skin test surveys in high-prevalence countries.

This Supplement provides an update on guidelines first published in 1996 on conducting a tuberculin skin test survey and analyzing the resulting data. The updated guidelines add experiences gained from community surveys, revisit the proposed sampling strategies, and provide additional information on ethical considerations.

Relationship of nutritional status with tuberculin sensitivity.

OBJECTIVE: To estimate the prevalence of under-nutrition among school children and to find out the relationship between nutritional status and tuberculin sensitivity. METHODS: A cross sectional study was carried out among 3335 children between 5-8 years of age attending 60 schools in Bangalore city selected by stratified random sampling. The nutritional anthropometric indices were calculated using reference median as recommended by World Health Organization, classified according to standard deviation units termed as Z-scores. The nutritional status of the children was assessed by Weight for age, Height for age and Bio-mass-index (BMI). RESULTS: Depending upon the method for classifying nutritional status, the prevalence of under-nutrition (including mild and severe under-nutrition) varied between 14.9-29.8%. The prevalence of severe under-nutrition varied from 2.9-6.7%. The frequency distributions of reaction sizes were found to be similar among children classified by nutritional status. The differences in proportions of significant reactions (=10 mm) and mean tuberculin reaction sizes between children classified by nutritional status were not found to be statistically significant. CONCLUSION: Tuberculin sensitivity was not influenced by nutritional status among apparently healthy school children.