First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal

• Published in: PloS one 2012-12, Vol.7 (12), p.e52297-e52297
• Main Authors: Malla, Bijaya, Stucki, David, Borrell, Sonia, Feldmann, Julia, Maharjan, Bhagwan, Shrestha, Bhawana, Fenner, Lukas, Gagneux, Sebastien
• Format: Article
• Language: English
• Subjects: Adult; Analysis; Antitubercular agents; Bacillus Calmette-Guerin vaccine; BCG; Biodiversity; Care and treatment; Chromosomes; Confidence intervals; Deoxyribonucleic acid; Disease hot spots; DNA; Drug resistance; Drug Resistance, Bacterial - genetics; Epidemiology; Female; Gender differences; Gene sequencing; Genetic aspects; Genetic diversity; Genetic Variation; Genotype; Genotype & phenotype; Health aspects; Health care; HIV; Human immunodeficiency virus; Humans; Immunization; Laboratories; Male; Medicine; Microbial drug resistance; Multiculturalism & pluralism; Multidrug resistance; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Mycobacterium tuberculosis - physiology; Nepal; Patients; Phylogenetics; Phylogeny; Polymorphism, Single Nucleotide; Public health; Sex ratio; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Spoligotyping; Tuberculosis; Tuberculosis, Pulmonary - microbiology; Vaccination
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052297

Tuberculosis (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. We 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. We 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.