Long-term follow-up of persons diagnosed with multidrug-resistant TB in Chennai, India, 2013-2020

India has the largest number of multidrug-resistant TB (MDR-TB) cases, defined as Mycobacterium tuberculosis resistant to at least isoniazid (INH) and rifampicin (RIF).1 However, less than half of all persons with MDR-TB in India successfully complete treatment.1 Although initial end-of-treatment outcomes offer a standardised time point to assess the effect of treatment, these tend to underestimate the overall burden of unfavourable long-term outcomes among persons treated for TB.2,3 The long-term outcomes of persons diagnosed with MDR-TB in India, including the proportion with recurrent TB disease or mortality, are unknown. This analysis was conducted under programmatic conditions in a high-burden setting, with no regular check-ups after treatment. The results can be used to show the burden of recurrent illness and death following treatment, and can be used as a benchmark to measure improvement

The Predicted Potential Impact of COVID-19 Pandemic on Tuberculosis Epidemic in Tamil Nadu, South India

Objective: To estimate the prevalence and incidence of TB before and during the COVID-19 pandemic in Tamil Nadu, south India. Methods: In the present study, the effect of COVID-19 epidemiology on the TB epidemic was assessed by the SEIR (Susceptible-Exposed-Infected-Recovered), a compartmental epidemiological model. The model input parameters on compartments of TB and incidence of COVID-19 were collected from the published literature. Based on the data collected, point prevalence and incidence of TB per 100,000 population is calculated with and without COVID- 19. A prediction was conducted up to 2025, trend analysis was performed, and a trend chi-square test and chi-square test of independence were used to test the difference between the prevalence with and without COVID-19. R software 2000 (R 4.0.0) was used for analysis. Results: The TB prevalence without and with COVID-19 decreases from 289 in 2020 to 271 in 2025 and from 289 in 2020 to 269 in 2025, respectively. Similarly, the incidence of TB was decreasing from 144 in 2020 to 135 in 2025 without COVID-19 and 143 in 2020 to 134 in 2025 with COVID-19. Though the TB burden is decreasing over the years, the trend was not statistically significant (p > 0.05). With respect to the district level, the prevalence and incidence of TB with and without COVID-19 is also found to be decreasing over the years. It was also found that the difference in the prevalence and incidence of TB with and without COVID-19 was not statically significant. Conclusion: The results of our study shows that there was an annual decline of around 2% from 2020 to 2025 in the trend of the prevalence and incidence of TB with and without COVID-19. Overall, there is a reduction, but it was not significant, and there is no significant effect of COVID-19 on TB in Tamil Nadu

Operational Challenges in Conducting a Subnational TB Prevalence Survey in India: Lessons Learned for Resource-Limited, High-Burden Settings

Estimating the burden of TB at the subnational level is critical to planning and prioritizing resources for TB control activities according to the local epidemiological situation. We report the experiences and operational challenges of implementing a TB prevalence survey at the subnational level in India. Information was collected from research reports that gathered data from periodic meetings, informal discussions with study teams, letters of communication, and various site visit reports. During the implementation of the survey, several challenges were encountered, including frequent turnover in human resources, lack of survey participation and community engagement, breakdown of X-ray machines, laboratory issues that delayed sputum sample testing, delays in X-ray reading, and network and Internet connectivity issues that impeded data management. To help ensure the survey was implemented in a timely manner, we developed several solutions, including planning ahead to anticipate challenges, ensuring timely communication, having a high commitment from all stakeholders, having strong team motivation, providing repetitive hands-on training, and involving local leaders to increase community engagement. This experience may help future states and countries that plan to conduct TB prevalence surveys to address these anticipated challenges and develop alternative strategies well in advance

Association of CYP27B1 gene polymorphisms with pulmonary tuberculosis and vitamin D levels

Background and Objectives: Genetic factors are reported to be connected with tuberculosis (TB) infection. Studies have shown that genetic variations in genes involved in the vitamin D pathway influence the levels of vitamin D found in the bloodstream (serum). Cyp27b1 (1α-hydroxylase) is an enzyme that activates the synthesis of bioactive vitamin D3 by hydroxylation of 25(OH)D3. The in vitro studies reported rare gene variants of Cyp27b1 such as rs118204011 and rs118204012, associated with loss of Cyp27b1 function and lower serum vitamin D levels. Globally, a critical gap exists in understanding the link between these gene variants with TB and vitamin D levels. Hence, the study objective is to comprehend the association of Cyp27b1 rs118204009 (G/A), rs118204011 (C/T), and rs118204012 (A/G) with tuberculosis susceptibility/protection and to assess the influence of gene variants on vitamin D levels in both healthy controls (HCs) and those with pulmonary tuberculosis (PTB) in South India

A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis

Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore,the first step in solving this problem is to identify biomarkers to distinguish the different disease states of an individual and treat them accordingly. Circulating microRNA (miRNA) biomarkers are promising candidates for various diseases. In fact, we are yet to conceptualize how miRNA expression influences and predicts TB disease outcomes. Thus, this systematic review and meta-analysis aimed to assess the diagnostic efficacy of circulating miRNAs in Latent TB (LTB) and Active Pulmonary TB (PTB)

Ethambutol-induced optic neuropathy: should we mandate ophthalmic examination in TB treatment?

India’s National Tuberculosis Elimination Programme (NTEP)1 and the WHO have recommended ethambutol (EMB) for use in the continuation phase of TB treatment due to the higher prevalence of isoniazid resistance in the patient community. This leaves only a single drug in the continuation phase that might adversely affect treatment outcomes.2 While reporting adverse drug reactions (ADRs), we found that EMB often induced optic neuropathy during anti-TB therapy (ATT) for drugsusceptible TB (DS-TB). In the study presented here, we define these ADRs and recommend adopting safety precautions when treating DS-TB patients

Seropersistence of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine): 6-month follow-up of a randomized,controlled, observer-blind, phase 2/3 immuno-bridging study in Indian adults

AZD1222 (ChAdOx1 nCoV-19) is a replication-deficient adenoviral vectored coronavirus disease-19 (COVID-19) vaccine that is manufactured as SII-ChAdOx1 nCoV-19 by the Serum Institute of India Pvt Ltd following technology transfer from Oxford University/AstraZeneca. The non-inferiority of SII-ChAdOx1 nCoV-19 with AZD1222 was previously demonstrated in an observer-blind, phase 2/3 immuno-bridging study (trial registration: CTRI/2020/08/027170). In this analysis of immunogenicity and safety data 6 months post first vaccination (Day 180), 1,601 participants were randomized 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (immunogenicity/reactogenicity cohort n = 401) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort n = 1,200). Immunogenicity was measured by anti-severe acute respiratory syndrome coronavirus 2 spike (anti-S) binding immunoglobulin G and neutralizing antibody (nAb) titers. A decline in anti-S titers was observed in both vaccine groups, albeit with a greater decline in SII-ChAdOx1 nCoV-19 vaccinees (geometric mean titer [GMT] ratio [95% confidence interval (CI) of SII-ChAdOx1 nCoV-19 to AZD1222]: 0.60 [0.41-0.87]). Consistent similar decreases in nAb titers were observed between vaccine groups (GMT ratio [95% CI]: 0.88 [0.44-1.73]). No cases of severe COVID-19 were reported following vaccination, while one case was observed in the placebo group. No causally related serious adverse events were reported through 180 days. No thromboembolic or autoimmune adverse events of special interest were reported. Collectively, these data illustrate that SII-ChAdOx1 nCoV-19 maintained a high level of immunogenicity 6 months post-vaccination. SII-ChAdOx1 nCoV-19 was safe and well tolerated

Elucidating the Immune Response to SARS-CoV-2: Natural Infection versus Covaxin/Covishield Vaccination in a South Indian Population

A natural infection or a vaccination can initially prime the immune system to form immunological memory. The immunity engendered by vaccination against COVID-19 versus natural infection with SARS-CoV-2 has not been well studied in the Indian population. In this study, we compared the immunity conferred by COVID-19 vaccines to naturally acquired immunity to SARS-CoV-2 in a South Indian population. We examined binding and neutralizing antibody (NAb) levels against the ancestral and variant lineages and assessed the ex vivo cellular parameters of memory T cells,memory B cells, and monocytes and finally measured the circulating cytokine response. COVID-19vaccination stimulates heightened levels of IgG antibodies against the original strain of SARS-CoV-2,as well as increased binding to the spike protein and neutralizing antibody levels. This enhanced response extends to variant lineages such as B.1.617.2 (Delta, India), B.1.1.529 (Omicron, India),B.1.351 (Beta, South Africa), and B.1.1.7 (Alpha, UK). COVID-19 vaccination differs from SARS-CoV-2 infection by having increased frequencies of classical memory B cells, activated memory B and plasma cells, CD4/CD8 T cells of effector memory, effector cells, stem cell-like memory T cells, and classical and intermediate monocytes and diminished frequencies of CD4/CD8 T cells of central memory and non-classical monocytes in vaccinated individuals in comparison to those with natural infection.Thus, COVID-19 vaccination is characterized by enhanced humoral responses and robust activation of innate and memory T cell responses in comparison to natural infection in a South Indian populatio

Effectiveness of food supplement on treatment outcomes and quality of life in pulmonary tuberculosis: Phased implementation approach

By encouraging treatment adherence and lowering mortality, dietary supplements can serve as adjuvant therapy for the success of medical interventions. We determined the effect of locally accessible food supplements on treatment outcomes, and health-related quality of life in patients with pulmonary tuberculosis initiating anti-tuberculosis treatment (ATT) in Odisha, India

Tuberculosis preventive treatment in eight SEAR countries – Current practices, implementation challenges and operations research priorities

Countries in the South East Asian region face similar challenges in control of infectious diseases. There is limited access to experiences and learnings of neighboring countries. The Indian Council - of Medical Research (ICMR) has established a Regional Enabler for the South-East Asia Research Collaboration for Health (RESEARCH) Platform for South East Asian Region (SEAR) countries to address the above issues. This paper discusses about current practices, implementation challenges and operations research priorities of Tuberculosis Preventive therapy (TPT) in eight SEAR countries