ArticlePloS one2026
Genetic surveillance of first- and second-line drug-resistant isolates of Mycobacterium tuberculosis in Peru.
Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Tuberculosis (TB) remains a critical public health crisis in Peru, which bears the highest multidrug-resistant TB (MDR-TB) burden in the Americas. The objective of this study was to conduct a nationwide genetic surveillance of first- and second-line drug-resistant Mycobacterium tuberculosis isolates in Peru to characterize their structural and geographic distribution using a multilocus genotype approach. We analyzed 38,339 valid results from first- and second-line line probe assays (LPA 1L, GenoType MTBDRplus v2; and LPA 2L, GenoType MTBDRsl v2) routinely collected between 2019 and 2022 by the Peruvian National Institute of Health. First-line (G1) and second-line (G2) multilocus genotypes were generated by concatenating specific hybridization banding patterns across resistance-associated loci. Additionally, targeted next-generation sequencing was performed on a stratified proportional sample of 170 isolates exhibiting "inferred" resistance genotypes, defined by a missing wild-type signal without a corresponding mutant probe, to elucidate their underlying mutational profiles. Resistance genotypes were identified in 13.5% and 11.8% of LPA 1L and LPA 2L results, respectively. The genotypic landscape was highly concentrated: 13 dominant G1 genotypes and 19 dominant G2 genotypes accounted for over 85% of their respective resistant cohorts. Structurally, these dominant genotypes mainly carried globally successful, canonical mutations (e.g., katG S315T1, rpoB S450L). Geographically, dominant genotypes were heavily consolidated within the hyper-endemic central coastal axis (Lima, Callao, and Ica) and the Amazonian department of Ucayali, maintaining highly stable temporal frequencies. Conversely, heteroresistance and complex multi-mutational patterns were exclusively restricted to low-frequency rare and orphan genotypes. Targeted sequencing of inferred patterns successfully expanded the national catalog of resistance variants, identifying non-canonical determinants (e.g., inhA g-17t, gyrB T500N) and preventing false-positive resistance calls driven by synonymous mutations. This large-scale mapping demonstrates that Peru's drug-resistant TB epidemic is characterized by the widespread consolidation of a restricted number of canonical multilocus genotypes. Integrating targeted sequencing with routine molecular screening is essential to resolve unclassified hybridization patterns and optimize epidemiological management in high-burden settings.
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