MIRU-VNTR in the genomic era: A systematic review of its role in molecular epidemiology and tuberculosis surveillance

Sánchez Guillén J.C.; Ita Balta Y.A.; Manrique Sam M.C. · Indian Journal of Tuberculosis (2026) · DOI: 10.1016/j.ijtb.2026.05.001

Resumen

Background: Molecular epidemiology is essential for understanding tuberculosis (TB) transmission, strain diversity, and the dynamics of drug-resistant Mycobacterium tuberculosis. Among genotyping methods, mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) typing has been widely implemented worldwide. However, its role and importance among new molecular-based genotyping methods remains debated. Methods: A systematic review was conducted following PRISMA 2020 guidelines and assessed using the QUADAS-2 tool. Electronic databases were searched for studies published between 2019 and 2025 that applied MIRU-VNTR for genotyping, molecular epidemiology, or comparative analysis in M. tuberculosis. Ninety-seven studies met inclusion criteria and were included in the qualitative synthesis. Data were extracted on geographic setting, genotyping approach, comparator methods, and study objectives. Results: Across all included studies, MIRU-VNTR was consistently applied as a molecular epidemiology and surveillance tool rather than as a primary diagnostic assay. It was most frequently used for transmission clustering, lineage assignment, strain diversity analysis, and differentiation between relapse and reinfection (references 14–110). Spoligotyping was commonly employed as a complementary method but showed limited discriminatory power when used alone. Comparative analyses demonstrated superior resolution of WGS for fine-scale transmission and mixed-infection detection; however, operational constraints limited its routine implementation in many high-burden settings. PCR-based assays, including GeneXpert, were primarily used for rapid diagnosis and resistance screening and did not replace genotyping approaches. Conclusions: The evidence positions MIRU-VNTR as an intermediate-resolution, operationally feasible genotyping method that bridges low-resolution lineage tools and high-resolution genomic sequencing. While WGS represents the current gold standard for transmission analysis, MIRU-VNTR remains a valuable component of tuberculosis surveillance programs, particularly in resource-limited settings. Integrated strategies combining rapid diagnostics, MIRU-VNTR genotyping, and targeted WGS are likely to provide the greatest public health impact.

Instituciones: Universidad Católica de Santa María