Chagas cardiomyopathy in Boston, Massachusetts: Identifying disease and improving management after community and hospital-based screening.

BACKGROUND: Limited data exist regarding cardiac manifestations of Chagas disease in migrants living in non-endemic regions. METHODS: A retrospective cohort analysis of 109 patients with Chagas disease seen at Boston Medical Center (BMC) between January 2016 and January 2023 was performed. Patients were identified by screening and testing migrants from endemic regions at a community health center and BMC. Demographic, laboratory, and cardiac evaluation data were collected. RESULTS: Mean age of the 109 patients was 43 years (range 19-76); 61% were female. 79% (86/109) were diagnosed with Chagas disease via screening and 21% (23/109) were tested given symptoms or electrocardiogram abnormalities. Common symptoms included palpitations (25%, 27/109) and chest pain (17%, 18/109); 52% (57/109) were asymptomatic. Right bundle branch block (19%, 19/102), T-wave changes (18%, 18/102), and left anterior fascicular block (11%, 11/102) were the most common electrocardiogram abnormalities; 51% (52/102) had normal electrocardiograms. Cardiomyopathy stage was ascertained in 94 of 109 patients: 51% (48/94) were indeterminate stage A and 49% (46/94) had cardiac structural disease (stages B1-D). Clinical findings that required clinical intervention or change in management were found in 23% (25/109), and included cardiomyopathy, apical hypokinesis/aneurysm, stroke, atrial or ventricular arrhythmias, and apical thrombus. CONCLUSIONS: These data show high rates of cardiac complications in a cohort of migrants living with Chagas disease in a non-endemic setting. We demonstrate that Chagas disease diagnosis prompts cardiac evaluation which often identifies actionable cardiac disease and provides opportunities for prevention and treatment.

Inclusion, Diversity, Access, and Equity in Infectious Diseases Fellowship Training: Tools for Program Directors.

The Infectious Diseases Society of America (IDSA) has set clear priorities in recent years to promote inclusion, diversity, access, and equity (IDA&E) in infectious disease (ID) clinical practice, medical education, and research. The IDSA IDA&E Task Force was launched in 2018 to ensure implementation of these principles. The IDSA Training Program Directors Committee met in 2021 and discussed IDA&E best practices as they pertain to the education of ID fellows. Committee members sought to develop specific goals and strategies related to recruitment, clinical training, didactics, and faculty development. This article represents a presentation of ideas brought forth at the meeting in those spheres and is meant to serve as a reference document for ID training program directors seeking guidance in this area.

Heterogeneity in Vaccinal Immunity to SARS-CoV-2 Can Be Addressed by a Personalized Booster Strategy.

SARS-CoV-2 vaccinations were initially shown to substantially reduce risk of severe disease and death. However, pharmacokinetic (PK) waning and rapid viral evolution degrade neutralizing antibody (nAb) binding titers, causing loss of vaccinal protection. Additionally, there is inter-individual heterogeneity in the strength and durability of the vaccinal nAb response. Here, we propose a personalized booster strategy as a potential solution to this problem. Our model-based approach incorporates inter-individual heterogeneity in nAb response to primary SARS-CoV-2 vaccination into a pharmacokinetic/pharmacodynamic (PK/PD) model to project population-level heterogeneity in vaccinal protection. We further examine the impact of evolutionary immune evasion on vaccinal protection over time based on variant fold reduction in nAb potency. Our findings suggest viral evolution will decrease the effectiveness of vaccinal protection against severe disease, especially for individuals with a less durable immune response. More frequent boosting may restore vaccinal protection for individuals with a weaker immune response. Our analysis shows that the ECLIA RBD binding assay strongly predicts neutralization of sequence-matched pseudoviruses. This may be a useful tool for rapidly assessing individual immune protection. Our work suggests vaccinal protection against severe disease is not assured and identifies a potential path forward for reducing risk to immunologically vulnerable individuals.

Vaccines Alone Cannot Slow the Evolution of SARS-CoV-2.

The rapid emergence of immune-evading viral variants of SARS-CoV-2 calls into question the practicality of a vaccine-only public-health strategy for managing the ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent the emergence of future immune-evading mutants. Here, we examined that proposition using stochastic computational models of viral transmission and mutation. Specifically, we looked at the likelihood of emergence of immune escape variants requiring multiple mutations and the impact of vaccination on this process. Our results suggest that the transmission rate of intermediate SARS-CoV-2 mutants will impact the rate at which novel immune-evading variants appear. While vaccination can lower the rate at which new variants appear, other interventions that reduce transmission can also have the same effect. Crucially, relying solely on widespread and repeated vaccination (vaccinating the entire population multiple times a year) is not sufficient to prevent the emergence of novel immune-evading strains, if transmission rates remain high within the population. Thus, vaccines alone are incapable of slowing the pace of evolution of immune evasion, and vaccinal protection against severe and fatal outcomes for COVID-19 patients is therefore not assured.

Chagas Disease.

Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi, is a leading neglected tropical disease in the United States. An estimated 240 000 to 350 000 persons in the United States are infected, primarily immigrants from Mexico, Central America, and South America, where the disease is endemic. The parasite is transmitted by the triatomine bug but can also be passed through blood transfusion, via organ transplant, or congenitally. Approximately 30% of infected persons later develop cardiac and/or gastrointestinal complications. Health care providers should consider screening at-risk patients with serologic testing. Early diagnosis and treatment with benznidazole or nifurtimox can help prevent complications.

Comparison of IGRA and TST in the diagnosis of latent tuberculosis among women of reproductive age in South India.

BACKGROUND: Latent tuberculosis infection (LTBI) is a mycobacterial infection defined on the basis of cellular immune response to mycobacterial antigens. The tuberculin skin test (TST) and the Interferon-Gamma Release Assay (IGRA) are the two tests currently used to establish the diagnosis of LTB. Literature suggests that a study regarding tuberculosis (TB) infection among women of reproductive age group is limited. METHODS: Female household contact, married, aged 18-49 years underwent written consent form and are screened for LTBI using the TST and IGRA. Participants are injected with TST [5 tuberculin unit (TU), purified protein derivative (PPD)] and IGRA [QuantiFERON®-TB Gold Plus kit (QFT-Plus)]. All the household contacts were followed-up for one year for incident TB cases. Statistical analysis was done using STATA version 14 (StataCorp., Texas, USA). Cohen's kappa test was used to determine the agreement between two tests. RESULTS: The prevalence of LTBI was found to be 69% (either TST or IGRA positive). Positivity rate of IGRA was higher when compared to that of TST. Out of 139 participants, 68 (49%) tested positive for TST, 80 (57.6%) tested positive for IGRA and 52 (37.4%) tested positive for both. Discordant results were observed in about two fifth of the study population and there was poor agreement between the two tests. CONCLUSION: Longitudinal studies are required to detect incident TB cases to evaluate the usefulness of these tests. The study was found that IGRA is more consistent to diagnosis of latent tuberculosis infection than the TST. Such studies can also be performed in varied settings among different populations which would help us to improve the diagnosis of LTBI and consequently help in TB control.

Performance of three screening tools to predict COVID-19 positivity in emergency department patients.

BACKGROUND: COVID-19 symptoms vary widely. This retrospective study assessed which of three clinical screening tools-a nursing triage screen (NTS), an ED review of systems (ROS) performed by physicians and physician assistants and a standardised ED attending (ie, consultant) physician COVID-19 probability assessment (PA)-best identified patients with COVID-19 on a subsequent reverse transcription PCR (RT-PCR) confirmation. METHODS: All patients admitted to Boston Medical Center from the ED between 27 April 2020 and 17 May 2020 were included. Sensitivity, specificity and positive predictive value (PPV) and negative predictive value (NPV) were calculated for each method. Logistic regression assessed each tool's performance. RESULTS: The attending physician PA had higher sensitivity (0.62, 95% CI 0.53 to 0.71) than the NTS (0.46, 95% CI 0.37 to 0.56) and higher specificity (0.76, 95% CI 0.72 to 0.80) than the NTS (0.71, 95% CI 0.66 to 0.75) and ED ROS (0.62, 95% CI 0.58 to 0.67). Categorisation as moderate or high probability on the ED physician PA was associated with the highest odds of having COVID-19 in regression analyses (adjusted OR=4.61, 95% CI 3.01 to 7.06). All methods had a low PPV (ranging from 0.26 for the ED ROS to 0.40 for the attending physician PA) and a similar NPV (0.84 for both the NTS and the ED ROS, and 0.89 for the attending physician PA). CONCLUSION: The ED attending PA had higher sensitivity and specificity than the other two methods, but none was accurate enough to replace a COVID-19 RT-PCR test in a clinical setting where transmission control is crucial. Therefore, we recommend universal COVID-19 testing prior to all admissions.

Comparison of gene set scoring methods for reproducible evaluation of multiple tuberculosis gene signatures.

Rationale: Many blood-based transcriptional gene signatures for tuberculosis (TB) have been developed with potential use to diagnose disease, predict risk of progression from infection to disease, and monitor TB treatment outcomes. However, an unresolved issue is whether gene set enrichment analysis (GSEA) of the signature transcripts alone is sufficient for prediction and differentiation, or whether it is necessary to use the original statistical model created when the signature was derived. Intra-method comparison is complicated by the unavailability of original training data, missing details about the original trained model, and inadequate publicly-available software tools or source code implementing models. To facilitate these signatures' replicability and appropriate utilization in TB research, comprehensive comparisons between gene set scoring methods with cross-data validation of original model implementations are needed. Objectives: We compared the performance of 19 TB gene signatures across 24 transcriptomic datasets using both re-rebuilt original models and gene set scoring methods to evaluate whether gene set scoring is a reasonable proxy to the performance of the original trained model. We have provided an open-access software implementation of the original models for all 19 signatures for future use. Methods: We considered existing gene set scoring and machine learning methods, including ssGSEA, GSVA, PLAGE, Singscore, and Zscore, as alternative approaches to profile gene signature performance. The sample-size-weighted mean area under the curve (AUC) value was computed to measure each signature's performance across datasets. Correlation analysis and Wilcoxon paired tests were used to analyze the performance of enrichment methods with the original models. Measurement and Main Results: For many signatures, the predictions from gene set scoring methods were highly correlated and statistically equivalent to the results given by the original diagnostic models. PLAGE outperformed all other gene scoring methods. In some cases, PLAGE outperformed the original models when considering signatures' weighted mean AUC values and the AUC results within individual studies. Conclusion: Gene set enrichment scoring of existing blood-based biomarker gene sets can distinguish patients with active TB disease from latent TB infection and other clinical conditions with equivalent or improved accuracy compared to the original methods and models. These data justify using gene set scoring methods of published TB gene signatures for predicting TB risk and treatment outcomes, especially when original models are difficult to apply or implement.

Impact of Undernutrition on Tuberculosis Treatment Outcomes in India: A Multicenter, Prospective, Cohort Analysis.

BACKGROUND: Undernutrition is the leading risk factor for tuberculosis (TB) globally. Its impact on treatment outcomes is poorly defined. METHODS: We conducted a prospective cohort analysis of adults with drug-sensitive pulmonary TB at 5 sites from 2015-2019. Using multivariable Poisson regression, we assessed associations between unfavorable outcomes and nutritional status based on body mass index (BMI) nutritional status at treatment initiation, BMI prior to TB disease, stunting, and stagnant or declining BMI after 2 months of TB treatment. Unfavorable outcome was defined as a composite of treatment failure, death, or relapse within 6 months of treatment completion. RESULTS: Severe undernutrition (BMI <16 kg/m2) at treatment initiation and severe undernutrition before the onset of TB disease were both associated with unfavorable outcomes (adjusted incidence rate ratio [aIRR], 2.05; 95% confidence interval [CI], 1.42-2.91 and aIRR, 2.20; 95% CI, 1.16-3.94, respectively). Additionally, lack of BMI increase after treatment initiation was associated with increased unfavorable outcomes (aIRR, 1.81; 95% CI, 1.27-2.61). Severe stunting (height-for-age z score <-3) was associated with unfavorable outcomes (aIRR, 1.52; 95% CI, 1.00-2.24). Severe undernutrition at treatment initiation and lack of BMI increase during treatment were associated with a 4- and 5-fold higher rate of death, respectively. CONCLUSIONS: Premorbid undernutrition, undernutrition at treatment initiation, lack of BMI increase after intensive therapy, and severe stunting are associated with unfavorable TB treatment outcomes. These data highlight the need to address this widely prevalent TB comorbidity. Nutritional assessment should be integrated into standard TB care.

No magic bullet: Limiting in-school transmission in the face of variable SARS-CoV-2 viral loads.

In the face of a long-running pandemic, understanding the drivers of ongoing SARS-CoV-2 transmission is crucial for the rational management of COVID-19 disease burden. Keeping schools open has emerged as a vital societal imperative during the pandemic, but in-school transmission of SARS-CoV-2 can contribute to further prolonging the pandemic. In this context, the role of schools in driving SARS-CoV-2 transmission acquires critical importance. Here we model in-school transmission from first principles to investigate the effectiveness of layered mitigation strategies on limiting in-school spread. We examined the effect of masks and air quality (ventilation, filtration and ionizers) on steady-state viral load in classrooms, as well as on the number of particles inhaled by an uninfected person. The effectiveness of these measures in limiting viral transmission was assessed for variants with different levels of mean viral load (ancestral, Delta, Omicron). Our results suggest that a layered mitigation strategy can be used effectively to limit in-school transmission, with certain limitations. First, poorly designed strategies (insufficient ventilation, no masks, staying open under high levels of community transmission) will permit in-school spread even if some level of mitigation is present. Second, for viral variants that are sufficiently contagious, it may be difficult to construct any set of interventions capable of blocking transmission once an infected individual is present, underscoring the importance of other measures. Our findings provide practical recommendations; in particular, the use of a layered mitigation strategy that is designed to limit transmission, with other measures such as frequent surveillance testing and smaller class sizes (such as by offering remote schooling options to those who prefer it) as needed.

Corrigendum: Malnutrition leads to increased inflammation and expression of tuberculosis risk signatures in recently exposed household contacts of pulmonary tuberculosis.

[This corrects the article DOI: 10.3389/fimmu.2022.1011166.].

Malnutrition leads to increased inflammation and expression of tuberculosis risk signatures in recently exposed household contacts of pulmonary tuberculosis.

Background: Most individuals exposed to Mycobacterium tuberculosis (Mtb) develop latent tuberculosis infection (LTBI) and remain at risk for progressing to active tuberculosis disease (TB). Malnutrition is an important risk factor driving progression from LTBI to TB. However, the performance of blood-based TB risk signatures in malnourished individuals with LTBI remains unexplored. The aim of this study was to determine if malnourished and control individuals had differences in gene expression, immune pathways and TB risk signatures. Methods: We utilized data from 50 tuberculin skin test positive household contacts of persons with TB - 18 malnourished participants (body mass index [BMI] < 18.5 kg/m2) and 32 controls (individuals with BMI ≥ 18.5 kg/m2). Whole blood RNA-sequencing was conducted to identify differentially expressed genes (DEGs). Ingenuity Pathway Analysis was applied to the DEGs to identify top canonical pathways and gene regulators. Gene enrichment methods were then employed to score the performance of published gene signatures associated with progression from LTBI to TB. Results: Malnourished individuals had increased activation of inflammatory pathways, including pathways involved in neutrophil activation, T-cell activation and proinflammatory IL-1 and IL-6 cytokine signaling. Consistent with known association of inflammatory pathway activation with progression to TB disease, we found significantly increased expression of the RISK4 (area under the curve [AUC] = 0.734) and PREDICT29 (AUC = 0.736) progression signatures in malnourished individuals. Conclusion: Malnourished individuals display a peripheral immune response profile reflective of increased inflammation and a concomitant increased expression of risk signatures predicting progression to TB. With validation in prospective clinical cohorts, TB risk biomarkers have the potential to identify malnourished LTBI for targeted therapy.

Case Report: Tuberculosis Autoregression after Minimal Treatment and Review of the Literature.

Mycobacterium tuberculosis (Mtb) is a complex pathogen causing multiple possible disease states in its host including latency, active disease, and elimination. While there is reasonable indirect evidence of elimination of tuberculosis (TB) in the absence of treatment, direct reports of autoregression are rare. We report a case of smear-negative, polymerase chain reaction (PCR)-positive TB disease regression in the absence of therapy due to severe adverse effects from antimycobacterial drugs. Indirect reports of TB autoregression, or self-cure, in the literature are reviewed, and an updated framework for conceptualizing Mtb infection is discussed.

Undernutrition is feeding the tuberculosis pandemic: A perspective.

Tuberculosis (TB) is a major cause of death worldwide, with 1.5 million deaths in 2020. While TB incidence and mortality had previously been on a downwards trend, in 2020, TB mortality actually rose for the first time in a decade, largely due to the COVID-19 pandemic. Undernutrition is the leading risk factor for TB, with a population attributable fraction (PAF) of 15%, compared to 7.6% for HIV. Individuals who are undernourished are more likely to develop active TB compared to those with a healthy bodyweight. They are also more likely to have greater severity of TB, and less likely to have successful TB treatment outcomes. The likelihood of TB mortality significantly increases as weight decreases. Nutritional interventions are likely to improve both nutritional status and TB treatment success, thereby decreasing TB mortality. However, many previous studies focusing on nutritional interventions have provided insufficient calories or been underpowered. Nutritional supplementation will be particularly important as factors such as the COVID-19 pandemic, climate change, and political conflict further threaten food security. The global TB elimination effort can no longer afford to ignore undernutrition.

Acute hepatitis A in international travellers: a GeoSentinel analysis, 2008-2020.

BACKGROUND: Non-immune international travellers are at risk of acquiring hepatitis A. Although hepatitis A vaccination is recommended for unvaccinated travellers to high or intermediate hepatitis A virus endemicity, compliance with this recommendation is not universal.The main objective was to describe the demographic and travel characteristics of international travellers infected with hepatitis A during travel. METHODS: Available data on travellers with confirmed (positive molecular test) or probable (symptomatic individuals with a single positive IgM test) hepatitis A diagnosed during and after travel from January 2008 to December 2020 were obtained from the GeoSentinel Surveillance Network database. We analysed demographic and travel characteristics of infected travellers. RESULTS: Among 254 travellers with hepatitis A (185 confirmed and 69 probable), the median age was 28 years (interquartile range: 19-40), 150 (59%) were male, and among 54 travellers with information available, 53 (98%) were unvaccinated. The most common reasons for travel included tourism (n = 120; 47%) and visiting friends or relatives (VFR; n = 72; 28%). About two-thirds of VFR travellers with hepatitis A (n = 50; 69%) were younger than 20 years old. Hepatitis A was acquired most frequently in South-Central Asia (n = 63; 25%) and sub-Saharan Africa (n = 61; 24%), but 16 travellers (6%) acquired hepatitis A in regions with low endemicity including Western Europe (n = 7; 3%), the Caribbean (n = 6; 2%) and North America (n = 3; 1%). Median duration from illness onset to GeoSentinel site presentation was ~7 days (interquartile range : 4-14 days). Among 88 travellers with information available, 59% were hospitalized. CONCLUSIONS: Despite availability of highly effective vaccines, travellers still acquire hepatitis A, even when traveling to low-endemicity destinations. Providing pre-departure hepatitis A vaccine to susceptible travellers is crucial to reducing travel-associated hepatitis A and should be offered to all travellers as part of the pre-travel consultation, regardless of destination.

Development and Validation of a Parsimonious Tuberculosis Gene Signature Using the digital NanoString nCounter Platform.

BACKGROUND: Blood-based biomarkers for diagnosing active tuberculosis (TB), monitoring treatment response, and predicting risk of progression to TB disease have been reported. However, validation of the biomarkers across multiple independent cohorts is scarce. A robust platform to validate TB biomarkers in different populations with clinical end points is essential to the development of a point-of-care clinical test. NanoString nCounter technology is an amplification-free digital detection platform that directly measures mRNA transcripts with high specificity. Here, we determined whether NanoString could serve as a platform for extensive validation of candidate TB biomarkers. METHODS: The NanoString platform was used for performance evaluation of existing TB gene signatures in a cohort in which signatures were previously evaluated on an RNA-seq dataset. A NanoString codeset that probes 107 genes comprising 12 TB signatures and 6 housekeeping genes (NS-TB107) was developed and applied to total RNA derived from whole blood samples of TB patients and individuals with latent TB infection (LTBI) from South India. The TBSignatureProfiler tool was used to score samples for each signature. An ensemble of machine learning algorithms was used to derive a parsimonious biomarker. RESULTS: Gene signatures present in NS-TB107 had statistically significant discriminative power for segregating TB from LTBI. Further analysis of the data yielded a NanoString 6-gene set (NANO6) that when tested on 10 published datasets was highly diagnostic for active TB. CONCLUSIONS: The NanoString nCounter system provides a robust platform for validating existing TB biomarkers and deriving a parsimonious gene signature with enhanced diagnostic performance.

Nutritional Supplementation Would Be Cost-Effective for Reducing Tuberculosis Incidence and Mortality in India: The Ration Optimization to Impede Tuberculosis (ROTI-TB) Model.

BACKGROUND: Undernutrition is the leading cause of tuberculosis (TB) in India and is associated with increased TB mortality. Undernutrition also decreases quality of life and economic productivity. METHODS: We assessed the cost-effectiveness of providing augmented rations to undernourished Indians through the government's Targeted Public Distribution System (TPDS). We used Markov state transition models to simulate disease progression and mortality among undernourished individuals in 3 groups: general population, household contacts (HHCs) of people living with TB, and persons living with human immunodeficiency virus (HIV). The models calculate costs and outcomes (TB cases, TB deaths, and disability-adjusted life years [DALYs]) associated with a 2600 kcal/day diet for adults with body mass index (BMI) of 16-18.4 kg/m2 until they attain a BMI of 20 kg/m2 compared to a status quo scenario wherein TPDS rations are unchanged. We employed deterministic and probabilistic sensitivity analyses to test result robustness. RESULTS: Over 5 years, augmented rations could avert 81% of TB cases and 88% of TB deaths among currently undernourished Indians. Correspondingly, this intervention could forestall 78% and 48% of TB cases and prevent 88% and 70% of deaths among undernourished HHCs and persons with HIV, respectively. Augmented rations resulted in 10-fold higher resolution of undernutrition and were highly cost-effective with (incremental cost-effectiveness ratio [ICER] of $470/DALY averted). ICER was lower for HHCs ($360/DALY averted) and the HIV population ($250/DALY averted). CONCLUSIONS: A robust nutritional intervention would be highly cost-effective in reducing TB incidence and mortality while reducing chronic undernutrition in India.

Recommendations for Screening and Diagnosis of Chagas Disease in the United States.

BACKGROUND: Chagas disease affects an estimated 326 000-347 000 people in the United States and is severely underdiagnosed. Lack of awareness and clarity regarding screening and diagnosis is a key barrier. This article provides straightforward recommendations, with the goal of simplifying identification and testing of people at risk for US healthcare providers. METHODS: A multidisciplinary working group of clinicians and researchers with expertise in Chagas disease agreed on 6 main questions, and developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, after reviewing the relevant literature on Chagas disease in the United States. RESULTS: Individuals who were born or resided for prolonged time periods in endemic countries of Mexico and Central and South America should be tested for Trypanosoma cruzi infection, and family members of people who test positive should be screened. Women of childbearing age with risk factors and infants born to seropositive mothers deserve special consideration due to the risk of vertical transmission. Diagnostic testing for chronic T. cruzi infection should be conducted using 2 distinct assays. CONCLUSIONS: Increasing provider-directed screening for T. cruzi infection is key to addressing this neglected public health challenge in the United States.

'People listen more to what actors say': A qualitative study of tuberculosis-related knowledge, behaviours, stigma, and potential interventions in Puducherry, India.

India has made substantial advancements in reducing the burden of tuberculosis (TB), but persons living with active TB (PLWATB) still face myriad challenges in seeking and receiving care, including TB-related stigma. To meet the END TB targets, it is critical that PLWATB engage in care and are able to adhere to treatment. This qualitative study aimed to understand TB-related stigma (perceived, enacted, and internalised) and possible interventions to reduce stigma in Puducherry and Tamil Nadu, India. We conducted 47 in-depth interviews with PLWATB and household members and eight focus group discussions: two each with PLWATB, their household members, healthcare workers, and key informants. We found varying TB-related knowledge: the vast majority of interview participants reported incorrect modes of transmission, although most were also aware that TB is curable. Participants reported high levels of perceived stigma, with nearly two-thirds of PLWATB choosing to hide their disease to avoid being stigmatised in their community. Participants supported interventions including celebrity advocacy and school-based programming to increase community knowledge and reduce enacted stigma as well as support groups and counselling to reduce internalised stigma in PLWATB. This study has the potential to inform future interventions to reduce TB-related stigma in India.