End Tuberculosis Research Articles

Spatial-temporal patterns and influencing factors for pulmonary tuberculosis transmission in China: an analysis based on 15 years of surveillance data.

Profiting from a series of anti-tuberculosis programs in China, the number of tuberculosis (TB) cases has diminished dramatically in the past decades. However, long-term spatial-temporal variations, regional trends of prevalence, and mechanisms of determinant factors remain unclear. Age-period-cohort analysis and Bayesian space-time hierarchy statistics were conducted to identify high-risk populations and areas in mainland China, and the geographical detector model was used to evaluate the important drivers of the disease. The prevalence of pulmonary TB has declined from 73.3/100,000 in 2004 to 55.45/100,000 in 2018. A bimodal distribution was found in age groups, and the birth cohorts before 1978 had relative higher risk. The high-risk areas were mainly distributed in western China and south-central China, and several provinces in eastern China showed a potential increasing trend, including Beijing, Shanghai, Liaoning, and Guangdong province. The index of night light (Q = 0.46), the population density (Q = 0.41), PM10 (Q = 0.38), urbanization rate (Q = 0.32), and PM 2.5 (Q = 0.31) contributed substantially to the spatial distribution of pulmonary tuberculosis. The identifications of epidemic patterns, high-risk areas and influence factors would help design targeted intervention measures to achieve milestones of the end TB strategy.

Outcomes of bedaquiline-containing regimen in the treatment of adults with drug-resistant tuberculosis in a tertiary care center in Rajasthan.

The emergence of drug-resistant strains of Mycobacterium tuberculosis has become a significant public health problem and has led to a setback in the efforts to end tuberculosis (TB) worldwide. The longer duration, heavier pill load, and higher toxicity profile of drug-resistant TB regimens compared to those for drug-susceptible TB lead to reduced adherence and worse treatment results, including mortality. This study was conducted to estimate treatment outcomes and adverse effects in patients with drug-resistant TB on a bedaquiline-containing regimen. Patients after the pre-treatment evaluation were enrolled in a bedaquiline-containing regimen. These patients were followed up for 18 months, and the final outcome was assessed along with the adverse effects. It was found that 49 (84.4%) patients achieved culture conversion by 3 months, 54 (93.1%) achieved culture conversion by 6 months, 52 (83.81%) had favorable outcomes (cured, treatment completed), and 10 had unfavorable outcomes (died, lost to follow-up, failed). Coupled with gradually increasing trends in success rates since 2012, lesser failure rates and fewer concerns regarding grave adverse effects are a silver lining in the cloud of increasing burden and widening resistance patterns. More funding has to be directed towards ensuring adherence and finding high-risk individuals to expedite the achievement of sustainable development goals.

What matters most? A qualitative study exploring priorities for supportive interventions for people with tuberculosis in urban Viet Nam

IntroductionThe health and economic burden of tuberculosis (TB) in urban Viet Nam is high. Social protection and support interventions can improve treatment outcomes and reduce costs. However, evidence regarding optimal...

Evaluation of drug-resistant tuberculosis treatment outcome in Limpopo province, South Africa.

South Africa has the second-highest tuberculosis (TB) incidence globally. Drug-resistant TB (DR-TB) treatment has less successful treatment outcomes as compared with susceptible TB, and it hinders TB control and management programmes. This study aimed to evaluate drug-resistant TB treatment outcomes and factors associated with successful treatment outcomes. The study was conducted in five districts in Limpopo province. The study design was retrospective and descriptive. Patients' demographic data, data on clinical characteristics and treatment outcomes data were extracted from the electronic drug-resistant tuberculosis register (EDRWeb) database system for the period, 2010-2018, in Limpopo province. Frequency, percentages and bivariate and multivariate logistic regression were used to analyse data using Statistical Package for Social Sciences version 27.0. The significance difference was determined at a 95% confidence interval and p 0.05. A total of 385 drug-resistant records were included in this study. The treatment success rate was 223 (57.9%). A total of 197 (51.2%) patients were cured, 26 (6.8%) completed treatment, 19 (4.9%) treatment failure, 62 (16.1%) died, 78 (20.6%) were recorded as the loss to follow-up, 1 (0.3%) moved to another country and 2 (0.5%) were transferred out. The treatment success rate was 57.9%, which is still below targets set by National Strategic Plan in South Africa and World Health Organization End TB targets.Contribution: The findings of the study reveal that to achieve successful DR-TB control programme and attain End TB targets, monitoring of treatment outcomes is crucial.

Effectiveness of NTEP training program in the improvement of knowledge of medical interns

Objectives: Compulsory Residential Medical Interns (CRMI) is being a part of health-care professionals they have a role and responsibilities for counseling the patients on tuberculosis (TB). The objective of the study is to assess the awareness about National Tuberculosis Elimination Programme (NTEP) among CRMI and determine the effectiveness of the training program in the improvement of knowledge of CRMI. Material and Methods: It was a pre-test and post-test design conducted among CRMI posted in the Department of Community medicine, Sri Manakula Vinayagar Medical College and Hospital in Villupuram district of Tamil Nadu. A total of 600 CRMIs from 2014 to 2022 were trained in batches. The training program was conducted as per NTEP guidelines released by Central TB division guidelines. At the end of the session, feedback was obtained. Pre- and post-test data were entered and analyzed in Epi_Info software. The paired test was used to test the statistical significance. Results: It was found 57.8% improvement in the knowledge of the participants about TB after the training program. In the analysis of feedback, the consensus score for all the responses was above 83%. Manual content analysis of the open-ended feedback was done. Conclusion: Health education dissemination strategies (e.g. campaign to end TB) on TB needs to be continuously done at the community and health facility level by trained CRMI.

Barriers and Facilitators to Integrating Depression Treatment Within a TB Program and Primary Care in Brazil.

Tuberculosis (TB) and depression is common and is associated with poor TB outcomes. The World Health Organization End TB Strategy explicitly calls for the integration of TB and mental health services. Interpersonal Counseling (IPC) is a brief evidence-based treatment for depression that can be delivered by non-mental health specialists with expert supervision. The goal of this study was to explore potential barriers and facilitators to training non-specialist providers to deliver IPC within the TB Control Program and primary care in Itaboraí, Rio de Janeiro state. Data collection consisted of six focus groups (n = 42) with health professionals (n = 29), program coordinators (n = 7), and persons with TB (n = 6). We used open coding to analyze the data, followed by deductive coding using the Chaudoir multi-level framework for implementation outcomes. The main structural barriers identified were poverty, limited access to treatment, political instability, violence, and social stigma. Organizational barriers included an overburdened and under-resourced health system with high staff turnover. Despite high levels of stress and burnout among health professionals, several provider-level facilitators emerged including a high receptivity to, and demand for, mental health training; strong community relationships through the community health workers; and overall acceptance of IPC delivered by any type of health provider. Patients were also receptive to IPC being delivered by any type of professional. No intervention-specific barriers or facilitators were identified. Despite many challenges, integrating depression treatment into primary care in Itaboraí using IPC was perceived as acceptable, feasible, and desirable.

Comparing Additionality of Tuberculosis Cases Using GeneXpert or Smear-Based Active TB Case-Finding Strategies among Social Contacts of Index Cases in Nepal.

This study compares the yield and additionality of community-based active tuberculosis (TB) active case-finding strategies using either smear microscopy or GeneXpert as the TB diagnostic test. Active case-finding strategies screened social contacts of index cases and high-risk groups in four districts of Nepal in July 2017-2019. Two districts (Chitwan and Dhanusha) applied GeneXpert testing and two districts (Makwanpur and Mahotarri) used smear microscopy. Two control districts implemented standard national TB program activities. Districts implementing GeneXpert testing screened 23,657 people for TB, tested 17,114 and diagnosed 764 TB cases, producing a yield of 4.5%. Districts implementing smear microscopy screened 19,961 people for TB, tested 13,285 and diagnosed 437 cases, producing a yield of 3.3%. The screening numbers required were 31 for GeneXpert and 45.7 for smear districts. The test numbers required were 22.4 and 30.4 for GeneXpert and smear. Using the TB REACH additionality method, social contact tracing for TB through GeneXpert testing contributed to a 20% (3958/3322) increase in district-level TB notifications, smear microscopy 12.4% (3146/2798), and -0.5% (2553/2566) for control districts. Therefore, social contact tracing of TB index cases using GeneXpert testing should be implemented throughout Nepal within the TB FREE initiative to close the notification gap and accelerate progress toward END TB strategy targets.

A Novel Microfluidic Dielectrophoresis Technology to Enable Rapid Diagnosis of Mycobacteria tuberculosis in Clinical Samples

To achieve the global efforts to end tuberculosis, affordable diagnostics suitable for true point-of-care implementation are required to reach the missing millions. In addition, diagnostics with increased sensitivity and expanded drug susceptibility testing are needed to address drug resistance and to diagnose low-bacterial burden cases. The laboratory-on-a-chip technology described herein used dielectrophoresis to selectively isolate Mycobacterium tuberculosis from sputum samples, purifying the bacterial population ahead of molecular confirmation by multiplex real-time quantitative PCR. After optimization using a panel of 50 characterized sputum samples, the performance of the prototype was assessed against the current gold standards, screening 100 blinded sputum samples using characterized and biobanked sputum provided by Foundation for Innovative New Diagnostics. Concordance with culture diagnosis was 100% for smear-negative samples and 87% for smear-positive samples. Of the smear-positive samples, the high burden sample concordance was 100%. Samples were diagnosed on the basis of visual assessment of the dielectrophoresis array and by multiplex real-time quantitative PCR assay. The results described herein demonstrate the potential of the CAPTURE-XT technology to provide a powerful sample preparation tool that could function as a front-end platform for molecular detection. This versatile tool could equally be applied as a visual detection diagnostic, potentially associated withbacterial identification for low-cost screening or coupled with an expanded PCR assay for genotypic drug susceptibility testing.

Varied trends of tuberculosis and HIV dual epidemics among different countries during 2000–2020: lessons from an ecological time-trend study of 9 countries

Background While Human Immunodeficiency Virus (HIV) infection is a well-established risk factor for tuberculosis (TB), the effect of HIV infection on TB incidence varies across countries given differences in local epidemiological factors and disparate progress with respect to TB elimination goals. Methods In this descriptive epidemiological study, we explored the country-specific associations between HIV prevalence and TB incidence in nine countries representing four WHO regions using data between 2000 and 2020. For each of these countries, we (1) described the trends of TB incidence and HIV prevalence, and (2) examined country-level associations between TB incidence and HIV prevalence, using negative binomial regression. Results The trends of TB incidence and HIV prevalence, and the country-level associations, varied across the study countries. Angola, Thailand and Zimbabwe showed parallel TB incidence and HIV prevalence trends while the two trends diverged in Brazil, Liberia and Indonesia during the study period. Additionally, the strength of association between HIV prevalence and TB incidence varied widely between countries, with the risk ratio ranging from 0.42 (95% CI: 0.36, 0.49) in Indonesia to 2.78 (95% CI: 2.57, 3.02) in Thailand. Conclusions The association of HIV infection with TB incidence varied across high burden settings, suggesting that HIV is not a ubiquitous driver of TB incidence. Without acknowledging the local drivers of TB epidemics across countries, the END TB Strategy cannot be adapted at the country level. The findings from this analysis can inform the design of future studies to identify country-specific drivers of TB using individual-level data.

Capacity Building, Knowledge Enhancement, and Consultative Processes for Development of a Digital Tool (Ni-kshay SETU) to Support the Management of Patients with Tuberculosis: Exploratory Qualitative Study.

Achieving the target for eliminating tuberculosis (TB) in India by 2025, 5 years ahead of the global target, critically depends on strengthening the capacity of human resources as one of the key components of the health system. Due to the rapid updates of standards and protocols, the human resources for TB health care suffer from a lack of understanding of recent updates and acquiring necessary knowledge. Despite an increasing focus on the digital revolution in health care, there is no such platform available to deliver the key updates in national TB control programs with easy access. Thus, the aim of this study was to explore the development and evolution of a mobile health tool for capacity building of the Indian health system's workforce to better manage patients with TB. This study involved two phases. The first phase was based on a qualitative investigation, including personal interviews to understand the basic requirements of staff working in the management of patients with TB, followed by participatory consultative meetings with stakeholders to validate and develop the content for the mobile health app. Qualitative information was collected from the Purbi Singhbhum and Ranchi districts of Jharkhand and Gandhinagar, and from the Surat districts of Gujarat State. In the second phase, a participatory design process was undertaken as part of the content creation and validation exercises. The first phase collected information from 126 health care staff, with a mean age of 38.4 (SD 8.9) years and average work experience of 8.9 years. The assessment revealed that more than two-thirds of participants needed further training and lacked knowledge of the most current updates to TB program guidelines. The consultative process determined the need for a digital solution in easily accessible formats and ready reckoner content to deliver practical solutions to address operational issues for implementation of the program. Ultimately, the digital platform named Ni-kshay SETU (Support to End Tuberculosis) was developed to support the knowledge enhancement of health care workers. The development of staff capacity is vital to the success or failure of any program or intervention. Having up-to-date information provides confidence to health care staff when interacting with patients in the community and aids in making quick judgments when handling case scenarios. Ni-kshay SETU represents a novel digital capacity-building platform for enhancing human resource skills in achieving the goal of TB elimination.

Optimizing tuberculosis treatment efficacy: Comparing the standard regimen with Moxifloxacin-containing regimens.

Tuberculosis (TB) continues to be one of the deadliest infectious diseases in the world, causing ~1.5 million deaths every year. The World Health Organization initiated an End TB Strategy that aims to reduce TB-related deaths in 2035 by 95%. Recent research goals have focused on discovering more effective and more patient-friendly antibiotic drug regimens to increase patient compliance and decrease emergence of resistant TB. Moxifloxacin is one promising antibiotic that may improve the current standard regimen by shortening treatment time. Clinical trials and in vivo mouse studies suggest that regimens containing moxifloxacin have better bactericidal activity. However, testing every possible combination regimen with moxifloxacin either in vivo or clinically is not feasible due to experimental and clinical limitations. To identify better regimens more systematically, we simulated pharmacokinetics/pharmacodynamics of various regimens (with and without moxifloxacin) to evaluate efficacies, and then compared our predictions to both clinical trials and nonhuman primate studies performed herein. We used GranSim, our well-established hybrid agent-based model that simulates granuloma formation and antibiotic treatment, for this task. In addition, we established a multiple-objective optimization pipeline using GranSim to discover optimized regimens based on treatment objectives of interest, i.e., minimizing total drug dosage and lowering time needed to sterilize granulomas. Our approach can efficiently test many regimens and successfully identify optimal regimens to inform pre-clinical studies or clinical trials and ultimately accelerate the TB regimen discovery process.

Treatment Outcomes and Associated Factors among Tuberculosis Patients from Selected Rural Eastern Cape Hospitals: An Ambidirectional Study.

An essential metric for determining the efficacy of tuberculosis (TB) control programs is the evaluation of TB treatment outcomes; this study was conducted to investigate treatment outcomes and associated factors among tuberculosis patients in rural areas of Eastern Cape, South Africa. Assessing treatment outcomes is fundamental to facilitating the End TB Strategy's set target. Clinic records from 457 patients with DR-TB were examined for data collection while 101 patients were followed up prospectively. Data were analyzed using Stata version 17.0. The odds ratio and 95% confidence interval were calculated to check the association between variables. p ≤ 0.05 was considered statistically significant. Of the 427 participants, 65.8% had successful treatment whilst 34.2% had unsuccessful TB treatment. A total of 61.2% and 39% of the HIV-positive and HIV-negative participants had a successful TB treatment whilst 66% and 34% of both HIV-negative and positive participants had unsuccessful TB treatment. From the 101 patients that were followed up, smokers took longer to have treatment outcomes compared to non-smokers. In the study with HIV/TB co-infection, men predominated. HIV and tuberculosis co-infection made therapy difficult with unfavorable effects on TB management. The treatment success rate (65.8%) was lower than the WHO threshold standard with a high proportion of patients being lost to the follow up. The co-infection of tuberculosis and HIV resulted in undesirable treatment outcomes. Strengthening TB surveillance and control is recommended.

Risk of mortality and clinical outcomes associated with healthcare delay among patients with tuberculosis

BackgroundTo eliminate tuberculosis (TB), World Health Organization (WHO) initiated “The End TB Strategy” with the goal of a 95% reduction in deaths. While many resources are contributed to eradicating TB, a substantial number of TB patients are still unlikely to receive timely treatment. Thus, we aimed to measure healthcare delay and its association with clinical outcomes from 2013 to 2018. MethodsWe conducted a retrospective cohort study using linked data of the National Tuberculosis Surveillance Registry and the health insurance claims data of South Korea. We included incident TB patients, and healthcare delay was defined as the period between the first medical visit with TB-related symptoms and the initiation of an anti-TB regimen. We described the distribution of healthcare delay, and the study population was classified into two groups with mean as a cutoff. The association between healthcare delay and clinical outcomes (all-cause mortality, pneumonia, progression to multi/extensively drug-resistant, intensive care unit admission, and mechanical ventilation use) was evaluated using the Cox proportional hazard model. Several stratified and sensitivity analyses were also conducted. ResultsAmong 39,747 patients with pulmonary TB, mean healthcare delay was 42.3 days and delayed and non-delayed groups, classified by mean (or average), were 10,680 (26.9%) and 29,067 (73.1%), respectively. Healthcare delay was associated with an increased risk of all-cause mortality (HR 1.10, 95% CI 1.03–1.17), pneumonia (HR 1.13, 95% CI 1.09–1.18), and mechanical ventilation use (HR 1.15, 95% CI 1.01–1.32). We also observed the duration-response of healthcare delay. Stratified analyses showed patients with respiratory diseases were at higher risk, and consistent results were observed in sensitivity analyses. ConclusionsWe observed a substantial number of patients experiencing healthcare delays, and it was associated with the deterioration of clinical outcomes. Our findings suggest that attention from authorities and healthcare professionals is needed to attenuate the preventable burden caused by TB through timely treatment.

Biapenem, a Carbapenem Antibiotic, Elicits Mycobacteria Specific Immune Responses and Reduces the Recurrence of Tuberculosis.

Tuberculosis (TB) still tops the list of global health burdens even after COVID-19. However, it will sooner transcend the current pandemic due to the prevailing risk of reactivation of latent TB in immunocompromised individuals. The indiscriminate misuse and overuse of antibiotics have resulted in the emergence of deadly drug-resistant variants of Mycobacterium tuberculosis (M.tb). This study aims to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM) in generating long-lasting immunity against TB. BPM treatment significantly boosted the activation status of the innate immune arm-macrophages by augmenting p38 signaling. Macrophages further primed and activated the adaptive immune cells CD4+ and CD8+ T-cells in the lung and spleen of the infected mice model. Furthermore, BPM treatment significantly amplified the polarization of T lymphocytes toward inflammatory subsets, such as Th1 and Th17. The treatment also helped generate a long-lived central memory T-cell subset. The generation of central memory T lymphocyte subset upon BPM treatment in the murine model led to a significant curtailing in the recurrence of TB due to reactivation and reinfection. These results suggest the potentiality of BPM as a potent adjunct immunomodulator to improve host defense against M.tb by enriching long-term protective memory cells. IMPORTANCE Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) tops the list of infectious killers around the globe. The emergence of drug-resistant variants of M.tb has been a major hindrance toward realizing the "END TB" goal. Drug resistance has amplified the global burden toward the quest for novel drug molecules targeting M.tb. Host-directed therapy (HDT) offers a lucrative alternative to tackle emerging drug resistance and disease relapse by strengthening the host's immunity. Through our present study, we have tried to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM). BPM treatment significantly augmented long-lasting immunity against TB by boosting the innate and adaptive immune arms. The generation of long-lived central memory T lymphocyte subset significantly improved the disease outcome and provided sterilizing immunity in the murine model of TB. The present investigation's encouraging results have helped us depict BPM as a potent adjunct immunomodulator for treating TB.

Drivers determining TB disease screening yield in four European screening programmes: a comparative analysis.

The WHO End-TB Strategy emphasises screening for early diagnosis of tuberculosis (TB) in high-risk groups, including migrants. We analysed key drivers of TB yield differences in four large migrant TB screening programmes to inform TB control planning and feasibility of a European approach. We pooled individual TB screening episode data from Italy, the Netherlands, Sweden, and the UK and analysed predictors and interactions for TB case yield using multivariable logistic regression models. Between 2005-2018 in 2,302,260 screening episodes among 2,107,016 migrants to four countries; the programmes identified 1,658 TB cases (yield 72.0 per 100,000; 95% confidence interval, CI68.6-75.6). In logistic regression analysis, we found associations between TB screening yield and age (>55 years odds ratio, OR2.91, CI2.24-3.78), being an asylum seeker (OR3.19, CI1.03-9.83) or on a settlement visa (OR1.78, CI1.57-2.01), close TB contact (OR12.25, 11.73-12.79), and higher TB incidence in the country of origin (CoO). We demonstrated interactions between migrant typology and age, as well as CoO. For asylum seekers, the elevated TB risk remained similar above CoO incidence thresholds of 100 per 100,000. Key determinants of TB yield included close contact, increasing age, incidence in CoO and specific migrant groups including asylum seekers and refugees. For most migrants such as UK students and workers, TB yield significantly increased with levels of incidence in CoO. The high, CoO-independent TB risk in asylum seekers above a 100 per 100,000 threshold could reflect higher transmission and reactivation risk of migration routes; with implications for selecting populations for TB screening.

Pooling sputum testing to diagnose tuberculosis using xpert MTB/RIF and xpert ultra: a cost-effectiveness analysis

BackgroundThe World Health Organization (WHO) recommends the diagnosis of tuberculosis (TB) using molecular tests, such as Xpert MTB/RIF (MTB/RIF) or Xpert Ultra (Ultra). These tests are expensive and resource-consuming, and cost-effective approaches are needed for greater coverage.MethodsWe evaluated the cost-effectiveness of pooling sputum samples for TB testing by using a fixed amount of 1,000 MTB/RIF or Ultra cartridges. We used the number of people with TB detected as the indicator for cost-effectiveness. Cost-minimization analysis was conducted from the healthcare system perspective and included the costs to the healthcare system using pooled and individual testing.ResultsThere was no significant difference in the overall performance of the pooled testing using MTB/RIF or Ultra (sensitivity, 93.9% vs. 97.6%, specificity 98% vs. 97%, p-value > 0.1 for both). The mean unit cost across all studies to test one person was 34.10 international dollars for the individual testing and 21.95 international dollars for the pooled testing, resulting in a savings of 12.15 international dollars per test performed (35.6% decrease). The mean unit cost per bacteriologically confirmed TB case was 249.64 international dollars for the individual testing and 162.44 international dollars for the pooled testing (34.9% decrease). Cost-minimization analysis indicates savings are directly associated with the proportion of samples that are positive. If the TB prevalence is ≥ 30%, pooled testing is not cost-effective.ConclusionPooled sputum testing can be a cost-effective strategy for diagnosis of TB, resulting in significant resource savings. This approach could increase testing capacity and affordability in resource-limited settings and support increased testing towards achievement of WHO End TB strategy.

Cartridge Based Nucleic Acid Amplification Test, an Important Diagnostic Tool for Tuberculosis both Pulmonary and Extra-Pulmonary Tuberculosis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), one of the top 10 causes of death worldwide (ranking above HIV/AIDS). About a quarter of the world's population is infected with TB and thus at risk of developing TB disease. The Global TB Report 2019 states that in 2018 a total of 1.5 million people died from TB, an estimated 10 million (range, 9.0–11.1 million) people fell ill worldwide.(1) Eight countries accounted for two-thirds of the total, with India leading the count, followed by China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh, and South Africa.(1) Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. The WHO estimates that there were 484 000 new cases with resistance to rifampicin (RIF) – the most effective first-line drug, which accounts for 78% MDR-TB cases. The MDR-TB burden largely falls on three countries – India, China, and the Russian Federation. About 6.2% of MDR-TB cases had extensively drug-resistant TB (XDR-TB) in 2018. Worldwide, only 56% of MDR-TB patients are currently successfully treated. Globally, TB incidence is falling at about 2% per year. This needs to accelerate to a 4%–5% annual decline to reach the 2020 milestones of the End TB Strategy.

Potential Repurposed Drug Candidates for Tuberculosis Treatment: Progress and Update of Drugs Identified in Over a Decade.

The devastating impact of Tuberculosis (TB) has been a menace to mankind for decades. The World Health Organization (WHO) End TB Strategy aims to reduce TB mortality up to 95% and 90% of overall TB cases worldwide, by 2035. This incessant urge will be achieved with a breakthrough in either a new TB vaccine or novel drugs with higher efficacy. However, the development of novel drugs is a laborious process involving a timeline of almost 20-30 years with huge expenditure; on the other hand, repurposing previously approved drugs is a viable technique for overcoming current bottlenecks in the identification of new anti-TB agents. The present comprehensive review discusses the progress of almost all the repurposed drugs that have been identified to the present day (∼100) and are in the development or clinical testing phase against TB. We have also emphasized the efficacy of repurposed drugs in combination with already available frontline anti-TB medications along with the scope of future investigations. This study would provide the researchers a detailed overview of nearly all identified anti-TB repurposed drugs and may assist them in selecting the lead compounds for further in vivo/clinical research.

A Systematic Review and Meta-Analysis of Tuberculous Preventative Therapy Adverse Events.

Tuberculosis preventive therapy (TPT) is a key part of the WHO's end TB strategy. However, the occurrence of potentially serious adverse events (AE) is a limitation of TPT regimens. We conducted a systemic review and metanalysis to estimate the incidence of AE and hepatotoxicity with various TPT regimens to help inform clinical decision making. We searched MEDLINE, Cochrane, Health Star and EMBASE from 1952 to April 2021 for studies reporting AE associated with TPT. Included studies reported AE stratified by regimen and provided the number of participants receiving each regimen. We used a random-effect model to meta-analyze the cumulative incidence of AE. We included 175 publications describing TPT-related AE in 277 cohorts. Among adults, the incidence of any AE, and hepatotoxicity leading to drug discontinuation was 3.7% and 1.1% respectively, compared to 0.4% and 0.02% respectively in children. The highest incidence of any AE, and AE leading to drug discontinuation was with 3 months isoniazid and rifapentine (3HP) and the lowest was with 4 months rifampin (4R). 4R also had the lowest incidence of hepato-toxic AE and drug discontinuation due to hepato-toxic AE. 3HP also had a low incidence of hepato-toxic AE. Although our study was limited by variability in methods and quality of AE reporting in the studies reviewed, pediatric populations had a very low incidence of AE with all TPT regimens reviewed. In adults, compared to mono-H regimens all rifamycin-based regimens were safer, although 4R had the lowest incidence of TPT-related AE of all types and of hepatotoxicity.

When should we be able to divert the cost of tuberculosis to other diseases?

Dear Editor, A country’s development and progress are based on its economy and gross domestic product (GDP). A recently published article in your journal introduces the past, present, and future of the Indian economy specifically related to healthcare. The author has nicely described the high burden of communicable and noncommunicable diseases. The authors have covered tuberculosis (TB) under communicable disease. We want to add some perspective to point out the status of TB burden on the Indian health economy.[1] Southeast Asian countries share more than 40% of the global TB burden and India is one of them. India belongs to the bracket of lower-middle-income countries.[2] Each and every single expenditure thing will have an effect on our country’s economy, either the share market or the healthcare system. As per recently published data, the Indian economy cost around $32 billion every year in TB-related fatalities.[1] TB is an old and infectious disease that makes a patient immunocompromised. TB patients have more chance to get other infectious diseases which makes patient’s life more troublesome in health and wealth both ways. The World Health Organization (WHO) and Government provide free testing and treatment for TB patients but this is not enough to control and eliminate the disease.[3] Majority of the patients belong to the lower and lower-middle-class family, which does not have the facility to get proper nutritious food; due to malnourishment, the patient does not get the treatment benefits that they need. Various studies revealed that several risk factors are responsible for the development of TB specifically drug-resistant TB and malnutrition, low body mass index, and low economy are few of them.[4] The Indian government is giving some amount to the patient to comply with treatment but that is not enough. To get benefits from the government, patients need to pass various documentary processes. Many patients stop the treatment in between due to these hectic procedures.[5] WHO and the government had the goal of END TB program to eradicate TB from India by the year 2025. Government and supportive people are on the right way but coronavirus disease 2019 (COVID-19) pandemic took us back foot.[6] TB not only is a fatal disease but also puts a lot of stress on the treasury. So, if TB is eliminated, a lot of funds can then be diverted to take care of other infectious diseases. So realistically, we can eliminate TB maybe by 2030. Out of all the programs mentioned, maybe TB is one entity, we can believe can be taken care of monetarily. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.