Abstract
BackgroundTuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown.Methods and FindingsWe analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42–4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43–5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status.ConclusionsWe found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian region.
Highlights
Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a global health threat with an estimated nine million incident cases and 440,000 multidrug-resistant TB cases worldwide [1]
This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian region
Mycobacterium tuberculosis complex (MTBC) has a global phylogeographic population structure consisting of six main phylogenetic lineages [4,5,6]: Lineage 1, Lineage 2 (East-Asian Lineage, includes the Beijing genotype), Lineage 3 (Delhi/CAS), Lineage 4
Summary
Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a global health threat with an estimated nine million incident cases and 440,000 multidrug-resistant TB cases worldwide [1]. Mycobacterium tuberculosis complex (MTBC) has a global phylogeographic population structure consisting of six main phylogenetic lineages [4,5,6]: Lineage 1 ( known as Indo-Oceanic Lineage), Lineage 2 (East-Asian Lineage, includes the Beijing genotype), Lineage 3 (Delhi/CAS), Lineage 4 Lineage 2 (includes the Beijing genotype) has been repeatedly associated with drug resistance in a wide range of settings and countries [20,21,22,23], while a few studies could not find evidence for such an association [24,25,26]. The phylogenetic diversity of M. tuberculosis in Nepal is unknown
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