Assessing the impact of COVID-19 management on the workload of human resources working in India's National Tuberculosis Elimination Program.

BACKGROUND: In 1993, WHO declared tuberculosis (TB) as a global health emergency considering 10 million people are battling TB, of which 30% are undiagnosed annually. In 2020 the COVID-19 pandemic took an unprecedented toll on health systems in every country. Public health staff already engaged in TB control and numerous other departments were additionally tasked with managing COVID-19, stretching human resource (HR) capacity beyond its limits. As part of an assessment of HR involved in TB control in India, The World Bank Group and partners conducted an analysis of the impact of COVID-19 on TB human resources for health (HRH) workloads, with the objective of describing the extent to which TB-related activities could be fulfilled and hypothesizing on future HR requirements to meet those needs. METHODS: The study team conducted a Workload Indicators and Staffing Needs (WISN) analysis according to standard WHO methodology to classify the workloads of priority cadres directly or indirectly involved in TB control activities as over-, adequately or under-worked, in 18 districts across seven states in India. Data collection was done via telephone interviews, and questions were added regarding the proportion of time dedicated to COVID-19 related tasks. We carried out quantitative analysis to describe the time allocated to COVID-19 which otherwise would have been spent on TB activities. We also conducted key informant interviews (KII) with key TB program staff about HRH planning and task-shifting from TB to COVID-19. RESULTS: Workload data were collected from 377 respondents working in or together with India's Central TB Division (CTD). 73% of all respondents (n = 270) reported carrying out COVID-19 tasks. The average time spent on COVID-19 tasks was 4 h / day (n = 72 respondents). Multiple cadres highly instrumental in TB screening and diagnosis, in particular community outreach (ASHA) workers and CBNAAT/TrueNAAT laboratory technicians working at peripheral, block and district levels, were overworked, and spending more than 50% of their time on COVID-19 tasks, reducing time for TB case-finding. Qualitative interviews with laboratory technicians revealed that PCR machines previously used for TB testing were repurposed for COVID-19 testing. CONCLUSIONS: The devastating impact of COVID-19 on HR capacity to conduct TB case-finding in India, as in other settings, cannot be overstated. Our findings provide clear evidence that NTEP human resources did not have time or essential material resources to carry out TB tasks during the COVID pandemic without doing substantial overtime and/or compromising on TB service delivery. To minimize disruptions to routine health services such as TB amidst future emerging infectious diseases, we would do well, during periods of relative calm and stability, to strategically map out how HRH lab staff, public health resources, such as India's Health and Wellness Centers and public health cadre, and public-private sector collaboration can most optimally absorb shocks to the health system.

Strategies to detect and manage latent tuberculosis infection among household contacts of pulmonary TB patients in high TB burden countries - a systematic review and meta-analysis.

OBJECTIVE: To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high-TB burden countries. METHODS: PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol-driven (PROSPERO-CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised. RESULTS: From 3694 unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%-100%; 46 studies). Random-effects meta-analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%-49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%-97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%-74%; 108,679 TPT-initiated contacts, 28 studies). Heterogeneity was significant (I2 ≥ 95%-100%) and could not be explained in subgroup analyses. Median proportions (IQR) were: LTBI 44% (28%-59%); TPT initiation 86% (60%-100%); TPT completion 68% (44%-82%). Nine broad themes related to diagnostic testing, health system structure and functions, risk perception, documentation and adherence were considered likely to influence the LTBI care cascade. CONCLUSION: The proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient.

Building communities of practice through case-based e-learning to prevent and manage TB among people living with HIV-India.

BACKGROUND: Co-management of HIV-TB coinfection remains a challenge globally. Addressing TB among people living with HIV (PLHIV) is a key priority for the Government of India (GoI). In 2016, GoI implemented single-window services to prevent and manage TB in PLHIV. To strengthen HIV-TB service delivery, case-based e-learning was introduced to health care providers at Antiretroviral Therapy centres (ARTc). METHODS: We implemented a hub and spoke model to deliver biweekly, virtual, case-based e-learning at select ARTc (n = 115), from four states of India-Delhi, Uttar Pradesh, Andhra Pradesh and Tamil Nadu. We evaluated feasibility and acceptability of case-based e-learning and its impact on professional satisfaction, self-efficacy, knowledge retention using baseline and completion surveys, session feedback, pre-and post-session assessments. We reviewed routine programmatic data and patient outcomes to assess practices among participating ARTc. RESULTS: Between May 2018 and September 2020, 59 sessions were conducted with mean participation of 55 spokes and 152 participants. For 95% and 88% of sessions ≥ 80% of respondents agreed that topics were clear and relevant to practice, and duration of session was appropriate, respectively. Session participants significantly improved in perceived knowledge, skills and competencies (+ 8.6%; p = 0.025), and technical knowledge (+ 18.3%; p = 0.04) from baseline. Participating ARTc increased TB screening (+ 4.2%, p < 0.0001), TB diagnosis (+ 2.7%, p < 0.0001), ART initiation (+ 4.3%, p < 0.0001) and TB preventive treatment completion (+ 5.2%, p < 0.0001). CONCLUSION: Case-based e-learning is an acceptable and effective modus of capacity building and developing communities of practice to strengthen integrated care. E-learning could address demand for accessible and sustainable continuing professional education to manage complex diseases, and thereby enhance health equity. We recommend expansion of this initiative across the country for management of co-morbidities as well as other communicable and non-communicable diseases to augment the existing capacity building interventions by provide continued learning and routine mentorship through communities of practice.

Integrating HCV testing with HIV programs improves hepatitis C outcomes in people who inject drugs: A cluster-randomized trial.

BACKGROUND & AIMS: There have been calls to integrate HCV testing into existing services, including harm reduction and HIV prevention and treatment, but there are few empirical trials to date. We evaluated the impact of integrating HCV testing/education into integrated care centers (ICCs) delivering HIV services to people who inject drugs (PWID) across India, using a cluster-randomized trial. METHODS: We compared ICCs with usual care in the PWID stratum (12 sites) of a 22-site cluster-randomized trial. In 6 sites, ICCs delivering HIV testing, harm reduction, other preventive services and linkage to HIV treatment were scaled from opioid agonist therapy centers and operated for 2 years. On-site rapid HCV antibody testing was integrated after 1 year. To assess impact, we conducted baseline and evaluation surveys using respondent-driven sampling (RDS) across the 12 sites (n = 11,993 recruited at baseline; n = 11,721 recruited at evaluation). The primary outcome was population-level self-reported HCV testing history. RESULTS: At evaluation, HCV antibody prevalence ranged from 7.2-76.6%. Across 6 ICCs, 5,263 ICC clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were 4-fold more likely to report being tested for HCV than in usual care clusters, adjusting for baseline testing (adjusted prevalence ratio [aPR] 3.69; 95% CI 1.34-10.2). PWID in ICC clusters were also 7-fold more likely to be aware of their HCV status (aPR 7.11; 95% CI 1.14-44.3) and significantly more likely to initiate treatment (aPR 9.86; 95% CI 1.52-63.8). CONCLUSIONS: We provide among the first empirical data supporting the integration of HCV testing into HIV/harm reduction services. To achieve elimination targets, programs will need to scale-up such venues to deliver comprehensive HCV services. CLINICALTRIALS. GOV IDENTIFIER: NCT01686750. LAY SUMMARY: Delivering hepatitis C virus (HCV) testing to people who inject drugs (PWID) in places where they also have access to HIV prevention and treatment services is an effective way to improve uptake of HCV testing among communities of PWID. To achieve the World Health Organization's ambitious elimination targets, integrated programs will need to be scaled up to deliver comprehensive HCV services.

Tuberculosis treatment in the private healthcare sector in India: an analysis of recent trends and volumes using drug sales data.

BACKGROUND: There is a pressing need for systematic approaches for monitoring how much TB treatment is ongoing in the private sector in India: both to cast light on the true scale of the problem, and to help monitor the progress of interventions currently being planned to address this problem. METHODS: We used commercially available data on the sales of rifampicin-containing drugs in the private sector, adjusted for data coverage and indication of use. We examined temporal, statewise trends in volumes (patient-months) of TB treatment from 2013 to 2016. We additionally analysed the proportion of drugs that were sold in combination packaging (designed to simplify TB treatment), or as loose pills. RESULTS: Drug sales suggest a steady trend of TB treatment dispensed by the private sector, from 18.4 million patient-months (95% CI 17.3-20.5) in 2013 to 16.8 patient-months (95% CI 15.5-19.0) in 2016. Overall, seven of 29 states in India accounted for more than 70% of national-level TB treatment volumes, including Uttar Pradesh, Maharashtra and Bihar. The overwhelming majority of TB treatment was dispensed not as loose pills, but in combination packaging with other TB drugs, accounting for over 96% of private sector TB treatment in 2017. CONCLUSIONS: Our findings suggest consistent levels of TB treatment in the private sector over the past 4 years, while highlighting specific states that should be prioritized for intervention. Drug sales data can be helpful for monitoring a system as large, disorganised and opaque as India's private sector.

Evaluation of key survey components of bio-behavioral surveillance among HIV high-risk subpopulation in Western India.

BACKGROUND: High-quality data are of prime importance in any health survey because survey data are considered as a gold standard for nationally representative data. The quality of data collection largely depends on the design of the questionnaire, training, and skills of the interviewer. OBJECTIVES: In the present study, we tried to evaluate three key components, such as questionnaire design, human resource and training of the field staff for Integrated Biological and Behavioural Surveillance carried out among the HIV high-risk subpopulation. METHODS: A mixed-methods approach was used. Qualitative and quantitative data collection was carried out in the year 2015 with cross-sectional survey design in western states of India. The in-depth interviews of 10 stakeholders, structured interviews of the survey respondents (n = 560), and field investigators (n = 71) were conducted. Data triangulation was used to find out the concurrence of the qualitative and quantitative data. RESULTS: Comprehensive and standardized survey questionnaire, structured training agenda, and strategic preparation for recruiting human resources were the overall strengths of the survey. However, during the implementation of the survey, there were some difficulties reported in data collection process. Overall, the respondents and investigators felt that the questionnaire was long and exhaustive. Difficulties were faced while collecting data on sexual history. The field staffs were not adequately experienced to work with sensitive population. CONCLUSIONS: In order to have accurate, reliable data, especially on sexual behavior; emphasis should be given on simple questionnaire with the use of community-friendly language, skilled and experienced interviewers for data collection, and extensive field training.

Facilitators and Barriers for Private Health Sector Engagement for TB Care in India: A Systematic Review and Meta-Synthesis of Qualitative Research.

INTRODUCTION: Private sector engagement is recognized as one of the most critical interventions to achieve the End TB goals in India. We conducted a systematic review and a meta-synthesis of qualitative studies to identify the barriers and facilitators for private sector engagement in TB care in India. METHODS: A systematic search in electronic databases was done. We assessed the methodological limitations of individual studies, synthesized the evidence using thematic analysis, and assessed our confidence in each finding. RESULTS: Of the 19 eligible articles included for the qualitative synthesis, 31.5% (6/19) were conducted in northern states of India. Included studies had details from 31 focus group discussions and 303 in-depth interviews conducted among various stakeholders. The synthesis revealed that barriers to engaging the private sector were lack of coordination mechanisms, lack of the National TB Elimination Program (NTEP) staff capacity to deal with the private sector, lack of private practitioners' knowledge on various programmatic aspects, and perceived complexity of the data exchange mechanism. The private sector felt that NTEP was not sensitive to the patient's confidentiality and demanded too much patient data. The private sector considered nonfinancial incentives like recognition, feedback, involving them in planning, and giving them equal status in partnership as powerful enablers for their engagement in TB care. CONCLUSION: Factors related to the context in which the engagement occurs, the architecture of the engagement, and interaction among the actors contribute to barriers to engaging the private sector for TB care in India. Strengthening policies to protect patient confidentiality, using behavior change communication to NTEP program managers, providing managerial and soft-skill training to NTEP staff, promoting nonfinancial incentives to private providers, establishing a coordination mechanism between the sectors, and simplifying the data exchange mechanisms need to be done to further strengthen the private-sector engagement.

Patient adherence to tuberculosis treatment in the Indian subcontinent: systematic review and meta-synthesis of qualitative research.

OBJECTIVES: How well patients adhere to their tuberculosis (TB) treatment influences their recovery and development of drug resistance, but influences on adherence are multiple and often competing. We synthesised qualitative studies from our setting in the Indian subcontinent to understand the dimensions and dynamics involved to help inform service provision. DESIGN: Qualitative synthesis comprising inductive coding, thematic analysis and forming a conceptual framework. DATA SOURCES: Medline (OVID), Embase (OVID), CINAHL (EBSCOHost), PsycINFO (EBSCOHost), Web of Science Core Collection, Cochrane Library and Epistemonikos were databases searched on 26 March 2020 for studies published since 1 January 2000. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included reports in English from the Indian subcontinent that used qualitative or mixed-methodology designs and reported findings around adherence to TB treatment. Full texts meeting eligibility were sampled based on 'thickness' (the richness of the qualitative data reported). DATA EXTRACTION AND SYNTHESIS: Two reviewers used standardised methods to screen abstracts and code. Included studies were assessed for reliability and quality using a standard tool. Qualitative synthesis was performed by inductive coding, thematic analysis and developing conceptual framework. RESULTS: Of 1729 abstracts screened from initial search, 59 were shortlisted for full-text review. Twenty-four studies that qualified as 'thick' were included in the synthesis. Studies were set in India (12), Pakistan (6), Nepal (3), Bangladesh (1) or in two or more of these countries (2). Of the 24 studies, all but one included people who were taking TB treatment (1 study included only healthcare providers), and 17 included healthcare workers, community members or both.We identified three themes: (1) personal influences on the people with TB include interconnections between their social role in the family unit, their own priorities in day-to-day living and their experience to date with the disease; (2) adherence is profoundly influenced by how individual healthcare providers interact with patients on treatment and address their needs; (3) adherence is influenced across communities by structural, social, economic and cultural factors related to treatment. CONCLUSION: Staff in TB programmes require an understanding of the various competing influences on individuals undergoing treatment. Programmes need to have more flexible and people-centred approaches to service provision in order to achieve adherence, and thus improve treatment outcomes. PROSPERO REGISTRATION NUMBER: CRD42020171409.

Test and Treat Model for Tuberculosis Preventive Treatment among Household Contacts of Pulmonary Tuberculosis Patients in Selected Districts of Maharashtra: A Mixed-Methods Study on Care Cascade, Timeliness, and Early Implementation Challenges.

Tuberculosis preventive treatment (TPT) is an important intervention in preventing infection and reducing TB incidence among household contacts (HHCs). A mixed-methods study was conducted to assess the "Test and Treat" model of TPT care cascade among HHCs aged ≥5 years of pulmonary tuberculosis (PTB) patients (bacteriologically/clinically confirmed) being provided TPT care under Project Axshya Plus implemented in Maharashtra (India). A quantitative phase cohort study based on record review and qualitative interviews to understand the challenges and solutions in the TPT care cascade were used. Of the total 4181 index patients, 14,172 HHCs were screened, of whom 36 (0.3%) HHCs were diagnosed with tuberculosis. Among 14,133 eligible HHCs, 10,777 (76.3%) underwent an IGRA test. Of them, 2468 (22.9%) tested positive for IGRA and were suggested for chest X-ray. Of the eligible 2353 HHCs, 2159 (91.7%) were started on TPT, of whom 1958 (90.6%) completed the treatment. The median time between treatment initiation of index PTB patient and (a) HHC screening was 31 days; (b) TPT initiation was 64 days. The challenges in and suggested solutions for improving the TPT care cascade linked to subthemes were tuberculosis infection testing, chest X-ray, human resources, awareness and engagement, accessibility to healthcare facilities, TPT drugs, follow-up, and assessment. A systematic monitoring and time-based evaluation of TPT cascade care delivery followed by prompt corrective actions/interventions could be a crucial strategy for its effective implementation and for the prevention of tuberculosis.

Addressing poverty through disease control programmes: examples from Tuberculosis control in India.

INTRODUCTION: Tuberculosis remains a major public health problem in India with the country accounting for one-fifth or 21% of all tuberculosis cases reported globally. The purpose of the study was to obtain an understanding on pro-poor initiatives within the framework of tuberculosis control programme in India and to identify mechanisms to improve the uptake and access to TB services among the poor. METHODOLOGY: A national level workshop was held with participation from all relevant stakeholder groups. This study conducted during the stakeholder workshop adopted participatory research methods. The data was elicited through consultative and collegiate processes. The research study also factored information from primary and secondary sources that included literature review examining poverty headcount ratios and below poverty line population in the country; and quasi-profiling assessments to identify poor, backward and tribal districts as defined by the TB programme in India. RESULTS: Results revealed that current pro-poor initiatives in TB control included collaboration with private providers and engaging community to improve access among the poor to TB diagnostic and treatment services. The participants identified gaps in existing pro-poor strategies that related to implementation of advocacy, communication and social mobilisation; decentralisation of DOT; and incentives for the poor through the available schemes for public-private partnerships and provided key recommendations for action. Synergies between TB control programme and centrally sponsored social welfare schemes and state specific social welfare programmes aimed at benefitting the poor were unclear. CONCLUSION: Further in-depth analysis and systems/policy/operations research exploring pro-poor initiatives, in particular examining service delivery synergies between existing poverty alleviation schemes and TB control programme is essential. The understanding, reflection and knowledge of the key stakeholders during this participatory workshop provides recommendations for action, further planning and research on pro-poor TB centric interventions in the country.

New vision for Revised National Tuberculosis Control Programme (RNTCP): Universal access - "reaching the un-reached".

The Phase II (2006-2012) of the Revised National Tuberculosis Control Programme (RNTCP) has been successful in achieving its objectives. Tuberculosis (TB) disease burden (prevalence and mortality) in India has reduced significantly when compared to 1990 levels, and India is on track to achieve the TB related millennium development goals. Despite significant progress, TB still continues to be one of the major public health problems in the country, and intensified efforts are required to reduce TB transmission and accelerate reductions in TB incidence, particularly in urban areas and difficult terrains. Achieving 'Universal access' is possible and necessary for the country. RNTCP during the 12 th Five Year Plan (2012-2017) aims to achieve 'Universal access' to quality assured TB diagnosis and treatment and elaborate plans are being made. This requires broad and concerted efforts and support from all stakeholders with substantial enhancement of commitment and financing at all levels. This paper describes the new vision of RNTCP and an overview of how this will be achieved.

Recovering from the Impact of the Covid-19 Pandemic and Accelerating to Achieving the United Nations General Assembly Tuberculosis Targets.

In 2020, the novel COVID-19 pandemic replaced TB as the world's top cause of death from an infectious disease. The October 21, 2020 the UN Secretary-General report on progress towards implementation of the UNHLM political declaration on TB stresses that although high-level commitments and targets had galvanized global and national progress towards ending TB, urgent and more ambitious investments and actions were required, especially in lieu of the COVID-19 pandemic where associated public health measures and travel restrictions, have disrupted health services universally. The report sets out 10 priority recommendations to get the world on track to reach agreed targets by 2022. Political commitment is more critical than ever. COVID-19 diagnostic and vaccination health services need to be aligned to TB services with active early case finding in communities, engaging the private sector care providers and mitigation of fear and stigma. Healthcare staff and community workers and leaders need to be provided with COVID-19 vaccination and personal protective equipment. The UNHLM declaration committed to mobilize 15 billion USD per annum for TB, of which 13 billion USD is for TB care and 2 billion USD per annum for TB R&D. The Global Fund needs to increase funding for TB. Learning from the unprecedented speed of COVID-19 vaccine development, fastracking development and evaluation of TB vaccines is essential. World leaders need to urgently address and reverse the socio-economic consequences of the COVID-19 pandemic and these will determine to what extent they will impact on achieving TB targets.

Active Case Finding for Tuberculosis in India: A Syntheses of Activities and Outcomes Reported by the National Tuberculosis Elimination Programme.

India launched a national community-based active TB case finding (ACF) campaign in 2017 as part of the strategic plan of the National Tuberculosis Elimination Programme (NTEP). This review evaluated the outcomes for the components of the ACF campaign against the NTEP's minimum indicators and elicited the challenges faced in implementation. We supplemented data from completed pretested data proformas returned by ACF programme managers from nine states and two union territories (for 2017-2019) and five implementing partner agencies (2013-2020), with summary national data on the state-wise ACF outcomes for 2018-2020 published in annual reports by the NTEP. The data revealed variations in the strategies used to map and screen vulnerable populations and the diagnostic algorithms used across the states and union territories. National data were unavailable to assess whether the NTEP indicators for the minimum proportions identified with presumptive TB among those screened (5%), those with presumptive TB undergoing diagnostic tests (>95%), the minimum sputum smear positivity rate (2% to 3%), those with negative sputum smears tested with chest X-rays or CBNAAT (>95%) and those diagnosed through ACF initiated on anti-TB treatment (>95%) were fulfilled. Only 30% (10/33) of the states in 2018, 23% (7/31) in 2019 and 21% (7/34) in 2020 met the NTEP expectation that 5% of those tested through ACF would be diagnosed with TB (all forms). The number needed to screen to diagnose one person with TB (NNS) was not included among the NTEP's programme indicators. This rough indicator of the efficiency of ACF varied considerably across the states and union territories. The median NNS in 2018 was 2080 (interquartile range or IQR 517-4068). In 2019, the NNS was 2468 (IQR 1050-7924), and in 2020, the NNS was 906 (IQR 108-6550). The data consistently revealed that the states that tested a greater proportion of those screened during ACF and used chest X-rays or CBNAAT (or both) to diagnose TB had a higher diagnostic yield with a lower NNS. Many implementation challenges, related to health systems, healthcare provision and difficulties experienced by patients, were elicited. We suggest a series of strategic interventions addressing the implementation challenges and the six gaps identified in ACF outcomes and the expected indicators that could potentially improve the efficacy and effectiveness of community-based ACF in India.

Evolutionary journey of programmatic services and treatment outcomes among drug resistant tuberculosis (DR-TB) patients under National TB Elimination Programme in India (2005-2020).

Introduction: India, with one-fourth of global burden of tuberculosis as well as multidrug-resistant TB, made bold commitment to end TB by 2025. There is no documented comprehensive review of the evolutionary journey of India's DRTB service expansion and changes in the treatment outcome so far.Area Covered: The current document presents evolution and journey of programmatic services and the progress in treatment outcomes among DRTB patients since 2005 with efforts cum challenges in nationwide scale-up of evidence-based policies and services, opportunities and future prospects for universalizing quality care - an essential ingredient to end TB in India. In the era of standardized longer treatment regimen till 2017, only half of the patients were successfully treated. Interventions to address factors associated with access and quality of care introduced since 2018 like universal drug susceptibility testing (UDST) guided treatment with shorter regimen, newer drugs, social protection; accelerated detection and began enhancing survival and success rate in recent DR-TB patient cohorts.Expert Opinion: Patient-centric care; robust TB/DR-TB surveillance system, shorter effective safer regimens and innovations, a milestone essential to end TB in India by 2025 to accomplish the vision of the Prime Minister of India.

Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates-Chennai, India, 2013-2016.

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013-2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB.

What would it cost to scale-up private sector engagement efforts for tuberculosis care? Evidence from three pilot programs in India.

BACKGROUND: Private providers dominate health care in India and provide most tuberculosis (TB) care. Yet efforts to engage private providers were viewed as unsustainably expensive. Three private provider engagement pilots were implemented in Patna, Mumbai and Mehsana in 2014 based on the recommendations in the National Strategic Plan for TB Control, 2012-17. These pilots sought to improve diagnosis and treatment of TB and increase case notifications by offering free drugs and diagnostics for patients who sought care among private providers, and monetary incentives for providers in one of the pilots. As these pilots demonstrated much higher levels of effectiveness than previously documented, we sought to understand program implementation costs and predict costs for their national scale-up. METHODS AND FINDINGS: We developed a common cost structure across these three pilots comprising fixed and variable cost components. We conducted a retrospective, activity-based costing analysis using programmatic data and qualitative interviews with the respective program managers. We estimated the average recurring costs per TB case at different levels of program scale for the three pilots. We used these cost estimates to calculate the budget required for a national scale up of such pilots. The average cost per privately-notified TB case for Patna, Mumbai and Mehsana was estimated to be US$95, US$110 and US$50, respectively, in May 2016 when these pilots were estimated to cover 50%, 36% and 100% of the total private TB patients, respectively. For Patna and Mumbai pilots, the average cost per case at full scale, i.e. 100% coverage of private TB patients, was projected to be US$91 and US$101, respectively. In comparison, the national TB program's budget for 2015 averages out to $150 per notified TB case. The total annual additional budget for a national scale up of these pilots was estimated to be US$267 million. CONCLUSIONS: As India seeks to eliminate TB, extensive national engagement of private providers will be required. The cost per privately-notified TB case from these pilots is comparable to that already being spent by the public sector and to the projected cost per privately-notified TB case required to achieve national scale-up of these pilots. With additional funds expected to execute against national TB elimination commitments, the scale-up costs of these operationally viable and effective private provider engagement pilots are likely to be financially viable.

Insights in tuberculosis immunology: Role of NKT and T regulatory cells.

Background: Tuberculosis (TB) control is challenging due to poor drug compliance and emerging resistance. The need of the hour is to determine the prediction of disease cure and relapse. Patients' immune response is crucial to the disease outcome. This study was designed to study the immune profile of TB patients during treatment and cure. Methods: The cross-sectional study included newly diagnosed pulmonary TB patients and healthy controls. Levels of serum cytokines/chemokines (Th1/Th2/Th17) were measured by BD cytometric bead array. The cell surface markers assessed in the study were CD3, CD4, CD8, CD16, CD56, and BD human regulatory T cell cocktail (CD4/CD25/CD127). Results: Data analysis observed statistically significant differences in CD3dim/CD56 + natural killer T (NKT) among TB patients with significantly low levels in healthy controls and after treatment completion (P < 0.0001). The analysis also revealed a high percentage of CD3dim/CD56 + NKT in fast responders. The percentage of T regulatory was found to be high in patients when compared with healthy controls; the values were statistically significant (0.0002). Interleukin-6 was significantly associated with the disease (P < 0.0485). Discussion: A comprehensive understanding of role of CD3dim/CD56+ NKT in antimycobacterial immunity may enable new possibilities for NK cell-based prophylactic and/or therapeutic strategies against TB.

Assessing tuberculosis control priorities in high-burden settings: a modelling approach.

BACKGROUND: In the context of WHO's End TB strategy, there is a need to focus future control efforts on those interventions and innovations that would be most effective in accelerating declines in tuberculosis burden. Using a modelling approach to link the tuberculosis care cascade to transmission, we aimed to identify which improvements in the cascade would yield the greatest effect on incidence and mortality. METHODS: We engaged with national tuberculosis programmes in three country settings (India, Kenya, and Moldova) as illustrative examples of settings with a large private sector (India), a high HIV burden (Kenya), and a high burden of multidrug resistance (Moldova). We collated WHO country burden estimates, routine surveillance data, and tuberculosis prevalence surveys from 2011 (for India) and 2016 (for Kenya). Linking the tuberculosis care cascade to tuberculosis transmission using a mathematical model with Bayesian melding in each setting, we examined which cascade shortfalls would have the greatest effect on incidence and mortality, and how the cascade could be used to monitor future control efforts. FINDINGS: Modelling suggests that combined measures to strengthen the care cascade could reduce cumulative tuberculosis incidence by 38% (95% Bayesian credible intervals 27-43) in India, 31% (25-41) in Kenya, and 27% (17-41) in Moldova between 2018 and 2035. For both incidence and mortality, modelling suggests that the most important cascade losses are the proportion of patients visiting the private health-care sector in India, missed diagnosis in health-care settings in Kenya, and drug sensitivity testing in Moldova. In all settings, the most influential delay is the interval before a patient's first presentation for care. In future interventions, the proportion of individuals with tuberculosis who are on high-quality treatment could offer a more robust monitoring tool than routine notifications of tuberculosis. INTERPRETATION: Linked to transmission, the care cascade can be valuable, not only for improving patient outcomes but also in identifying and monitoring programmatic priorities to reduce tuberculosis incidence and mortality. FUNDING: US Agency for International Development, Stop TB Partnership, UK Medical Research Council, and Department for International Development.