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.

Heterogeneity in the endocytic capacity of individual macrophage in a population determines its subsequent phagocytosis, infectivity and subcellular trafficking.

Phagocytosis is a complex cellular uptake process involving multiple distinct steps of cargo recognition, uptake, phagosome maturation and eventual phagolysosome resolution. Emerging literature shows that heterogeneity of phagocytosis at multiple steps at a single cell level influences the population outcome. However, the determinants of phagocytic heterogeneity are not clear. Here we show that the variance in the endocytic capacity of individual cells in a macrophage population determines subsequent phagocytic uptake and trafficking. Our results document the extensive heterogeneity in the endocytic uptake of individual macrophages, and show that cells with higher endocytic capacity preferentially phagocytose diverse cargo, including pathogenic Mycobacterium tuberculosis. Interestingly, M. tuberculosis infected cells sustain the higher endocytic capacity following infection. Modulating endocytic capacity by inhibiting endocytosis reduces phagocytic uptake. Differential uptake of M. tuberculosis into cells with different endocytic capacities correlates with the efficiency of phagocytic delivery to lysosomes, thus contributing further to phagocytic as well as mycobacterial heterogeneity. Thus, variance in endocytic capacity is a determinant of generating heterogeneity in phagocytosis at multiple steps.

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.

Mycobacterium tuberculosis (Mtb) lipid mediated lysosomal rewiring in infected macrophages modulates intracellular Mtb trafficking and survival.

Intracellular pathogens commonly manipulate the host lysosomal system for their survival. However, whether this pathogen-induced alteration affects the organization and functioning of the lysosomal system itself is not known. Here, using in vitro and in vivo infections and quantitative image analysis, we show that the lysosomal content and activity are globally elevated in Mycobacterium tuberculosis (Mtb)-infected macrophages. We observed that this enhanced lysosomal state is sustained over time and defines an adaptive homeostasis in the infected macrophage. Lysosomal alterations are caused by mycobacterial surface components, notably the cell wall-associated lipid sulfolipid-1 (SL-1), which functions through the mTOR complex 1 (mTORC1)-transcription factor EB (TFEB) axis in the host cells. An Mtb mutant lacking SL-1, MtbΔpks2, shows attenuated lysosomal rewiring compared with the WT Mtb in both in vitro and in vivo infections. Exposing macrophages to purified SL-1 enhanced the trafficking of phagocytic cargo to lysosomes. Correspondingly, MtbΔpks2 exhibited a further reduction in lysosomal delivery compared with the WT. Reduced trafficking of this mutant Mtb strain to lysosomes correlated with enhanced intracellular bacterial survival. Our results reveal that global alteration of the host lysosomal system is a defining feature of Mtb-infected macrophages and suggest that this altered lysosomal state protects host cell integrity and contributes to the containment of the pathogen.

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.

Effect of delamanid on interim outcomes of bacteriological conversion amongst pediatric drug resistant tuberculosis cases in India.

AIM: To determine the bacteriological conversion rate after 6 months of Delamanid (DLM) based treatment in children with drug-resistant tuberculosis (DR-TB) and determine factors associated with bacteriological conversion. METHODS: This is a descriptive retrospective study done in children between the age of 6-17 years with DR-TB who received DLM-based therapy from October 2018 to May 2021. The drug resistance pattern of TB was detected using Xpert RIF/MTB and phenotypic drug sensitivity testing (DST) on TB-MGIT culture reports. Follow-up sputum TB MGIT culture was carried out monthly after DLM initiation for 6 months. Factors associated with sputum bacteriological conversion such as age, gender, pulmonary TB (PTB) versus disseminated TB, unilateral or bilateral lung involvement, type of DR-TB, prior treatment failure, and type of DR-TB regimen were analyzed. RESULTS: Sixty patients received DLM of which two had extrapulmonary TB (EPTB) and sputum conversion could not be assessed. The mean age at presentation was 12.69 ± 3.03 years. Five patients (8.3%) died while on DLM treatment. On follow-up, 8 (13.7%) out of 58 patients had no sputum bacteriological conversion after 6 months of DLM initiation of which three patients were on salvage therapy; 46 (79.3%) had sputum bacteriological conversion within 6 months of DLM initiation. CONCLUSION: Sputum bacteriological conversion rate was almost 80% at the end of 6 months of DLM-based treatment.

Increased neuronal expression of the early endosomal adaptor APPL1 leads to endosomal and synaptic dysfunction with cholinergic neurodegeneration.

Dysfunction of the endolysosomal system within neurons is a prominent feature of Alzheimer's disease (AD) pathology. Multiple AD-risk factors are known to cause hyper-activity of the early-endosome small GTPase rab5, resulting in neuronal endosomal pathway disruption. APPL1, an important rab5 effector protein, is an interface between endosomal and neuronal function through a rab5-activating interaction with the BACE1-generated C-terminal fragment (ßCTF or C99) of the amyloid precursor protein (APP), a pathogenic APP fragment generated within endolysosomal compartments. To better understand the role of APPL1 in the AD endosomal phenotype, we generated a transgenic mouse model over-expressing human APPL1 within neurons (Thy1-APPL1 mice). Consistent with the important endosomal regulatory role of APPL1, Thy1-APPL1 mice have enlarged neuronal early endosomes and increased synaptic endocytosis due to increased rab5 activation. We additionally demonstrate pathological consequences of APPL1 overexpression, including functional changes in hippocampal long-term potentiation (LTP) and long-term depression (LTD), as well as degeneration of the large projection cholinergic neurons of the basal forebrain and impairment of hippocampal-dependent memory. Our findings show that increased neuronal APPL1 levels lead to a cascade of pathological effects within neurons, including early endosomal alterations, synaptic dysfunction, and neurodegeneration. Multiple risk factors and molecular regulators, including APPL1 activity, are known to contribute to the endosomal dysregulation seen in the early stages of AD, and these findings further highlight the shared pathobiology and consequences to a neuron of early endosomal pathway disruption. Significance Statement: Dysfunction in the endolysosomal system within neurons is a key feature of Alzheimer's disease (AD). Multiple AD risk factors lead to hyperactivity of the early-endosome GTPase rab5, disrupting neuronal pathways including the cholinergic circuits involved early in memory decline. APPL1, a crucial rab5 effector, connects endosomal and neuronal functions through its interaction with a specific amyloid precursor protein (APP) fragment generated within endosomes. To understand APPL1's role, a transgenic mouse model over-expressing human APPL1 in neurons (Thy1-APPL1 mice) was developed. These mice show enlarged early endosomes and increased synaptic endocytosis due to rab5 activation, resulting in impaired hippocampal long-term potentiation and depression, the degeneration of basal forebrain cholinergic neurons, and memory deficits, highlighting a pathological cascade mediated through APPL1 at the early endosome.

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.

Estimation of tuberculosis incidence at subnational level using three methods to monitor progress towards ending TB in India, 2015-2020.

OBJECTIVES: We verified subnational (state/union territory (UT)/district) claims of achievements in reducing tuberculosis (TB) incidence in 2020 compared with 2015, in India. DESIGN: A community-based survey, analysis of programme data and anti-TB drug sales and utilisation data. SETTING: National TB Elimination Program and private TB treatment settings in 73 districts that had filed a claim to the Central TB Division of India for progress towards TB-free status. PARTICIPANTS: Each district was divided into survey units (SU) and one village/ward was randomly selected from each SU. All household members in the selected village were interviewed. Sputum from participants with a history of anti-TB therapy (ATT), those currently experiencing chest symptoms or on ATT were tested using Xpert/Rif/TrueNat. The survey continued until 30 Mycobacterium tuberculosis cases were identified in a district. OUTCOME MEASURES: We calculated a direct estimate of TB incidence based on incident cases identified in the survey. We calculated an under-reporting factor by matching these cases within the TB notification system. The TB notification adjusted for this factor was the estimate by the indirect method. We also calculated TB incidence from drug sale data in the private sector and drug utilisation data in the public sector. We compared the three estimates of TB incidence in 2020 with TB incidence in 2015. RESULTS: The estimated direct incidence ranged from 19 (Purba Medinipur, West Bengal) to 1457 (Jaintia Hills, Meghalaya) per 100 000 population. Indirect estimates of incidence ranged between 19 (Diu, Dadra and Nagar Haveli) and 788 (Dumka, Jharkhand) per 100 000 population. The incidence using drug sale data ranged from 19 per 100 000 population in Diu, Dadra and Nagar Haveli to 651 per 100 000 population in Centenary, Maharashtra. CONCLUSION: TB incidence in 1 state, 2 UTs and 35 districts had declined by at least 20% since 2015. Two districts in India were declared TB free in 2020.

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.

The paradigm shift in the approach to management of latent tuberculosis infection in high tuberculosis burden countries.

Introduction: Addressing the reservoir of Latent Tuberculosis Infection (LTBI) is critical to TB elimination because if left untreated LTBI can progress to active TB disease. This additional burden can prevent achieving the global targets of TB elimination. Management of LTBI has been a low priority target for National TB Elimination Programs (NTEP) due to various challenges in the field settings.Areas covered: This article reviews the most recent advances in the field of LTBI management including newer diagnostics, treatments, vaccines, programmatic challenges, and gaps and suggests a way forward that can be adopted by NTEPs for LTBI. We searched the electronic databases of PubMed, Scopus, and Web of Science for studies published between 2010 to 2020 using MeSH terms: Latent TB Diagnosis, TB preventive therapy, Vaccines, LTBI, and HIV/ COVID.Expert opinion: NTEPs of developing countries should offer a better, point-of-care diagnostic, and effective treatment for LTBI to reduce the number of new TB cases arising from people infected with M.tb. Awareness about LTBI should be increased among the health system staff and the public. More funding is needed to advance research as well as implement the newer findings in the NTEP to achieve the End TB targets by 2035.

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.