Abstract
Peru has the highest burden of multidrug-resistant tuberculosis in the Americas region. Since 1999, the annual number of extensively drug-resistant tuberculosis (XDR-TB) Peruvian cases has been increasing, becoming a public health challenge. The objective of this study was to perform genomic characterization of Mycobacterium tuberculosis strains obtained from Peruvian patients with XDR-TB diagnosed from 2011 to 2015 in Peru. Whole genome sequencing (WGS) was performed on 68 XDR-TB strains from different regions of Peru. 58 (85.3%) strains came from the most populated districts of Lima and Callao. Concerning the lineages, 62 (91.2%) strains belonged to the Euro-American Lineage, while the remaining 6 (8.8%) strains belonged to the East-Asian Lineage. Most strains (90%) had high-confidence resistance mutations according to pre-established WHO-confident grading system. Discordant results between microbiological and molecular methodologies were caused by mutations outside the hotspot regions analysed by commercial molecular assays (rpoB I491F and inhA S94A). Cluster analysis using a cut-off ≤ 10 SNPs revealed that only 23 (34%) strains evidenced recent transmission links. This study highlights the relevance and utility of WGS as a high-resolution approach to predict drug resistance, analyse transmission of strains between groups, and determine evolutionary patterns of circulating XDR-TB strains in the country.
Highlights
Tuberculosis (TB) is a preventable and curable disease and one of the top 10 causes of death in the world[1]
Drug resistance of mycobacterial strains is detected through genotypic or phenotypic laboratory tests that detect the presence of DNA mutations conferring resistance or the growth of Mycobacterium tuberculosis (MTB) in the presence of anti-TB drugs, respectively
This study highlights the relevance and utility of performing Whole Genome Sequencing as a high-resolution approach to perform genetic analysis of XDR-TB strains circulating in Peru
Summary
Tuberculosis (TB) is a preventable and curable disease and one of the top 10 causes of death in the world[1]. Analysis of the restriction fragment length polymorphisms of the IS6110 gene (IS6110-RFLP), spacer oligonucleotide typing (Spoligotyping) and mycobacterial interspersed repetitive units-variable number of DNA tandem repeats (MIRU-VNTR) have been used globally These methodologies have been applied in Peru for exploration of the genetic diversity of drug resistant TB s trains[10,11,12]. The revolution of Generation Sequencing (NGS) technology and its wider availability have allowed to perform Whole Genome Sequencing (WGS) analysis to provide information about speciation, drug resistance prediction and better determination of relatedness for epidemiologic p urposes[15,16,17] In this way it is possible to obtain a greater amount of information that allows a complete characterization and discrimination of strains with repeated or ambiguous conventional genotypic patterns[18,19]. To date no high-resolution genomic study has been performed on Peruvian XDR-TB strains
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