Optimizing drug-resistant tuberculosis diagnosis: cost-effectiveness of rapid molecular and phenotypic assays in South Africa.
| Title: | Optimizing drug-resistant tuberculosis diagnosis: cost-effectiveness of rapid molecular and phenotypic assays in South Africa. |
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| Authors: | Fekadu G; School of Pharmacy, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia. take828pharm@gmail.com.; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong. take828pharm@gmail.com.; Tolossa T; Deakin Health Economics, School of Health and Social Development, Institute for Health Transformation, Deakin University, Victoria, Australia.; School of Public Health, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia.; Gao L; Deakin Health Economics, School of Health and Social Development, Institute for Health Transformation, Deakin University, Victoria, Australia.; Tola HH; Department of Public Health, College of Health Sciences, Salale University, Fitche, Ethiopia.; Department of Epidemiology and Biostatistics, School of Public Health, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.; Feyissa TR; Deakin Rural Health, School of Medicine, Faculty of Health, Deakin University, Victoria, Australia.; Yang L; School of Public Health, Sun Yat-Sen University, Guangzhou, China.; Institute for Global Health and Development, Peking University, Beijing, China.; Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.; Chen S; International Centre for Evidence in Disability, Faculty of Epidemiology and Population Health, London, School of Hygiene & Tropical Medicine , London, UK.; Chaiyakunapruk N; Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT, USA.; IDEAS Center, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT, USA.; Asfaw E; Department of Economics, School of Accounting, Economics, and Finance (SAEF), University of KwaZulu Natal, Durban, South Africa.; Health Economics and Financing Division, Africa Centres for Disease Control and Prevention (Africa CDC), Addis Ababa, Ethiopia.; Siegel M; Chair of General Economics, Health Economics and Econometrics, University of Greifswald, Greifswald, Germany.; Ming WK; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong. wkming2@cityu.edu.hk.; Institute of Global Governance and Innovation for a Shared Future, City University of Hong Kong, Kowloon, Hong Kong. wkming2@cityu.edu.hk. |
| Source: | BMC medicine [BMC Med] 2026 Feb 09; Vol. 24 (1). Date of Electronic Publication: 2026 Feb 09. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 101190723 Publication Model: Electronic Cited Medium: Internet ISSN: 1741-7015 (Electronic) Linking ISSN: 17417015 NLM ISO Abbreviation: BMC Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BioMed Central, 2003- |
| MeSH Terms: | Tuberculosis, Multidrug-Resistant*/diagnosis ; Tuberculosis, Multidrug-Resistant*/economics ; Tuberculosis, Multidrug-Resistant*/drug therapy ; Mycobacterium tuberculosis*/drug effects ; Mycobacterium tuberculosis*/genetics ; Molecular Diagnostic Techniques*/economics ; Molecular Diagnostic Techniques*/methods; Antitubercular Agents/therapeutic use ; Antitubercular Agents/pharmacology ; Microbial Sensitivity Tests/economics ; Microbial Sensitivity Tests/methods ; Humans ; South Africa ; Cost-Benefit Analysis ; Cost-Effectiveness Analysis ; Rapid Diagnostic Tests ; Phenotype |
| Abstract: | Background: Timely detection of drug-resistant tuberculosis (DR-TB) is essential for effective treatment and preventing poor outcomes. Rapid molecular diagnostics are promising alternatives to conventional phenotypic drug susceptibility testing (pDST), offering faster and more accessible detection of resistance. This study evaluated the cost-effectiveness of rapid molecular assays, alone or combined with pDST, for detecting resistance to isoniazid, rifampicin, and fluoroquinolones from a South African healthcare provider perspective.; Methods: A decision-analytic model was developed to simulate TB-related outcomes for a hypothetical cohort of microbiologically confirmed TB patients. Nine diagnostic strategies were evaluated: pDST alone; four rapid molecular tests (line probe assays [LPAs], Xpert MTB/RIF [Xpert] followed by Xpert MTB/XDR [Xpert XDR], Xpert MTB/RIF Ultra [Xpert Ultra] followed by Xpert XDR, and targeted next-generation sequencing [tNGS]); and combinations pairing each molecular test with pDST. Outcomes included early treatment rates, mortality, direct medical costs, disability-adjusted life-years (DALYs), and incremental cost-effectiveness ratios (ICERs). Base-case, sensitivity, and scenario analyses were performed.; Results: In the base-case analysis, 'Xpert followed by Xpert XDR + pDST' was the preferred cost-effective strategy, with an ICER of USD 6,554/DALY averted-below South Africa's GDP per capita threshold. While 'tNGS + pDST' yielded the greatest health benefits-lowest DALYs (1.9877), highest early treatment rate (995.54/1,000 tested), and lowest mortality (90.22/1000 tested)-its ICER (USD 25,918/DALY averted) exceeded three times the GDP per capita, rendering it not cost-effective. Sensitivity analyses highlighted the impact of diagnostic accuracy and treatment timing on cost-effectiveness outcomes. Probabilistic sensitivity analysis showed 'tNGS + pDST' had the highest probability of being cost-effective when the willingness-to-pay threshold exceeded USD 10,500/DALY averted. Diagnostic replacement scenario analysis revealed that tNGS alone could be a cost-effective alternative (ICER = USD 1712 per DALY averted) when pDST was unavailable. An extended two-year time horizon analysis confirmed base-case robustness.; Conclusions: Combining rapid molecular diagnostics with pDST offers a cost-effective and clinically beneficial approach for DR-TB detection in high-burden settings. The Xpert-based strategy provides an optimal balance of diagnostic yield, early treatment, and economic efficiency in South Africa. tNGS represents a feasible alternative in settings where pDST is inaccessible, warranting further evaluation for broader implementation.; (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: Not applicable. This study is a decision-analytic cost-effectiveness modeling study based exclusively on published, publicly available, aggregated, and de-identified data obtained from scientific literature and public health reports. It did not involve direct interaction with human participants, nor did it involve access to individual-level patient data or identifiable records. Therefore, institutional ethics approval and informed consent were not required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. |
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| Contributed Indexing: | Keywords: Cost-effectiveness; Drug resistance; High-burden settings; Phenotypic testing; Rapid molecular diagnostics; Tuberculosis |
| Substance Nomenclature: | 0 (Antitubercular Agents) |
| Entry Date(s): | Date Created: 20260210 Date Completed: 20260707 Latest Revision: 20260707 |
| Update Code: | 20260707 |
| PubMed Central ID: | PMC12983700 |
| DOI: | 10.1186/s12916-026-04693-3 |
| PMID: | 41664022 |
| Database: | MEDLINE |
Journal Article