Intricacies of Global Tuberculosis Management—EndTB-2035 on the Fence?
Abstract
:1. Introduction
2. Technical Challenges in TB Testing
2.1. Improvement in Bacteriological Confirmation and Rifampicin Status with Upfront Molecular Testing
2.2. Follow-On Testing for Additional Resistance and Newer Definitions of Drug Resistance
2.3. Alternative Samples for TB Testing and Concept of Improved Diagnostic Yield
3. Clinical Challenges in TB Treatment
3.1. Introduction of Newer Anti-TB Drugs
3.2. All-Oral Treatment Regimens for RR/MDR-TB
4. Challenges in TB Preventive Therapy
4.1. Definition of Population for LTBI Testing and Preventive Therapy
4.2. Improved Diagnosis of LTBI Cases
4.3. TB Preventive Treatment Regimen
4.4. Vaccination for TB Prevention
5. Operational Challenges in Achieving EndTB-2035
5.1. Disruptions in TB Testing Due to COVID-19 Pandemic
5.2. Role of Social Determinants in TB Testing
5.3. Need to Strengthen Universal Health Coverage (UHC)
5.4. Economic Evaluation and Improving Finance for TB Management
6. Conclusions
- (a).
- In 2020, WHO endorsed the use of rapid molecular tests as the initial diagnostic test for the confirmation of TB, replacing smear microscopy. Low- and moderate-complexity NAATs were recommended for respiratory samples from pulmonary TB along with the detection of RIF resistance or RIF and INH, thus enhancing the rate of bacteriological confirmation of TB.
- (b).
- For paucibacillary samples like smear-negative ones and samples from PL-HIV, children, and EP-TB patients, Xpert MTB/RIF Ultra was superior to Xpert MTB/RIF. Besides sputum, alternative samples like stools, nasopharyngeal aspirate, and gastric lavage could be used to test pulmonary TB. For PL-HIV patients, urine testing was performed using LAM and a blood sample in Xpert MTB/RIF. With molecular tests, the bacteriological confirmation of TB continued to improve.
- (c).
- Line probe assays (Hains and Nipro) were performed for RIF, INH, ETH, FQs, SLID, and PZA recommended on respiratory samples (Mtb culture for PZA) for additional drug resistance. However, the collection and transport of a second sample caused delays and the failure of additional testing in many cases. The introduction of Xpert MTB/XDR (which detects INH, FQs, SLID, and ETH) as a low-complexity NAAT which can be used with the same buffer system as MTB/RIF or MTB/RIF Ultra optimized rapid DR-TB diagnosis.
- (d).
- Additionally, the introduction of tNGS from respiratory samples with higher bacillary loads promises rapid DST for a fair share of pulmonary TB patients with access to the facility. tNGS can be used in different platforms across medium- and high-end/advanced labs offering flexibility for rapid DR-TB diagnosis over phenotypic DST, particularly for newer drugs.
- (e).
- Despite the advances in DR-TB diagnosis, only 48% of new cases were diagnosed using molecular tests for initial diagnosis. This emphasizes that patients lack access to health care due to intricate reasons that need to be addressed.
- (f).
- Initial TB treatment regimens were longer with SLIDs, contributing to lower adherence and patient compliance. The importance of HR-TB was recognized, and an all-oral, 6-month regimen was introduced in 2018. Also, newer drugs like BDQ, DLM, and PTM were introduced for the RR/MDR-TB regimen in the past 10–15 years, effecting a huge change in treating TB.
- (g).
- In 2020, all-oral shorter regimens were introduced for RR/MDR-TB, with an additional BPaL regimen in operational research mode and further inclusion of BPaLM in 2022. These shortened the treatment and oral medication, and promised better patient compliance. However, only 75% of treatment coverage was attained in 2023, which fails to reflect the advantages of the newer regimen, indicating the need for an improved initiation of treatment after diagnosis.
- (h).
- BCG is the only approved vaccine to prevent TB with 88% coverage globally, but there are 15 vaccine candidates in different phases of clinical trials offering promise for better vaccination.
- (i).
- LTBI testing has improved with TST, IGRA, and TBST approved for selected populations based on the operational feasibility of use. Different TPT regimens are available that can be chosen, with improved coverage of household contacts reported in 2023 compared to previous years.
- (j).
- The COVID-19 pandemic worsened TB diagnosis and access to health care between 2019 and 2021, but this improved in 2022 and 2023. NAATs were directed to COVID-19 testing in many countries, causing an interruption in TB testing. In 2023, there was an increased trend in the diagnosis and treatment of TB cases.
- (k).
- Risk factors including diabetes, malnutrition, HIV, smoking, and alcohol abuse were considered for TB. However, additional vulnerable populations like pregnant and breastfeeding women, refugees, homeless people, prisoners, migrants, and displaced people are known to contribute to poor TB management. There is a need for the implementation of comprehensive domestic medical screening for LTBI among migrants or refugees when they arrive, in particular into low-TB-burden countries, such as the USA.
- (l).
- UHC is advocated in terms of service coverage and reducing catastrophic costs. Strengthening UHC with political commitment and proportionating funds for TB management is globally planned for enhanced TB management.
- (m).
- Economic evaluation with increased financial profiling is required for improved TB management, particularly in resource-limited countries. Domestic funding contributes to the majority of national TB management costs, with additional scope for resource mobilization and disease tracking as well as planned budgeting. In addition to the vertical national TB program, private–public partnerships and the role of PHC are vital for effective TB management.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Category | Year 2020 | Year 2024 | |
---|---|---|---|
Pre-COVID-19 | Post-COVID-19 | ||
Burden | Incidence | 10 million (56% men, 32% women, and 12% children) | 10.8 million (55% men, 33% women, and 12% children) |
Mortality | 1.2 million deaths | 1.25 million deaths | |
Diagnosis | Diagnostic tests | Upfront molecular testing using low-complexity NAATs, LAMP, and Urine-LAM Follow-on molecular testing for first and second-line drug resistance | Follow-on testing includes rapid molecular testing by tNGS for all anti-TB drugs |
Bacteriological confirmation and rifampicin testing | 57% of diagnosed people were bacteriologically confirmed using molecular tests, with 61% tested for rifampicin resistance | 62% of diagnosed people were bacteriologically confirmed using molecular tests, with 79% tested for rifampicin resistance | |
RR/MDR-TB cases | 0.21 million | 0.16 million, with an additional 28,982 cases of XDR-TB | |
Treatment | Regimen for RR/MDR-TB | Shorter oral and longer oral BDQ-containing regimen for RR/MDR-TB patients BPaL regimen in operational research mode | Shorter oral, longer oral and BPaLM regimen for RR/MDR-TB patients BPaL regimen for pre-XDR or XDR-TB patients |
RR/MDR-TB treatment enrolment | 0.18 million | 0.18 million | |
Treatment success rate for RR/MDR-TB | 57% | 68% | |
Prevention | Treatment options for LTBI | 6H, 4R, and 3HR | 6H, 4R, and 3HR, with the addition of 3HP and 1HP |
Number of potential LTBI cases offered TPT | 4.1 million | 4.7 million | |
BCG vaccination coverage | 89% | 87% |
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Gopalaswamy, R.; Subbian, S. Intricacies of Global Tuberculosis Management—EndTB-2035 on the Fence? J. Respir. 2025, 5, 4. https://doi.org/10.3390/jor5010004
Gopalaswamy R, Subbian S. Intricacies of Global Tuberculosis Management—EndTB-2035 on the Fence? Journal of Respiration. 2025; 5(1):4. https://doi.org/10.3390/jor5010004
Chicago/Turabian StyleGopalaswamy, Radha, and Selvakumar Subbian. 2025. "Intricacies of Global Tuberculosis Management—EndTB-2035 on the Fence?" Journal of Respiration 5, no. 1: 4. https://doi.org/10.3390/jor5010004
APA StyleGopalaswamy, R., & Subbian, S. (2025). Intricacies of Global Tuberculosis Management—EndTB-2035 on the Fence? Journal of Respiration, 5(1), 4. https://doi.org/10.3390/jor5010004