Diagnostic accuracy of whole-genome sequencing for detecting drug resistance in Mycobacterium tuberculosis: A systematic review
DOI:
https://doi.org/10.5281/zenodo.17795762Keywords:
Drug-resistant tuberculosis, Whole genome sequencing, Diagnostic accuracy, Sensitivity and specificity, Systematic reviewAbstract
Background: Drug-resistant tuberculosis (DR-TB) is a public health crisis. The reference standard for diagnosis, phenotypic drug susceptibility testing (DST), is accurate but takes 6–8 weeks, delaying treatment. Whole-genome sequencing (WGS) emerges as a rapid alternative, but its accuracy versus the reference standard requires rigorous synthesis of primary evidence.
Objective: To evaluate available primary evidence on the diagnostic accuracy of WGS (index test) compared with phenotypic DST (reference test) for detecting drug resistance in clinical Mycobacterium tuberculosis isolates.
Methods: A systematic review was conducted following PRISMA 2020 and QUADAS-2. Systematic searches were run in PubMed/MEDLINE, Embase and LILACS without restrictions. Eligibility focused on primary diagnostic accuracy studies. Sensitivity and specificity data were extracted and critically appraised.
Results: The search identified 20 records. After screening, 19 were excluded (mostly secondary reviews). A single primary study (Enkirch et al., 2020), including 1,248 clinical isolates in Sweden, met criteria. It reported high diagnostic accuracy: for rifampicin, sensitivity 100% and specificity 99.5%; for isoniazid, sensitivity 93.5% and specificity 100%. Risk of bias in the included study was “unclear” in blinding domains.
Conclusion: The identified primary evidence, though limited to one study, corroborates high WGS accuracy for resistance detection. Genotype–phenotype discordance, such as disputed rpoB mutations, and implementation barriers (cost and bioinformatics) appear more significant challenges than the test’s technical accuracy.
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Copyright (c) 2025 Monique Suzan Monteiro de Souza, Rafaela Vieira Mota, Gabriella Esper Cury de Araujo, Patricia Jazmín Martínez Gallardo, Rafael Corrêa de Souza, Maria Luján Britez, Nathalia do Rego Barros Araújo Vasconcelos, Júlia Beatriz Nunes da Silva, Gustavo Boostel Menezes de Assis, Rogério Ribeiro, Andrea Paola Britos Gómez (Autor/a)
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