Characterization of the Genetic Diversity of Extensively-Drug Resistant Mycobacterium tuberculosis Clinical Isolates from Pulmonary Tuberculosis Patients in Peru

Omar Cáceres (1) , Nalin Rastogi (2) , Carlos Bartra (3) , David Couvin (2) , Marco Galarza (1) , Luis Asencios (3) , Alberto Mendoza-Ticona (4)

1 Biotechnology and Molecular Biology Laboratory
2 Institut Pasteur de la Guadeloupe
3 Mycobacterias National Reference Laboratory
4 Ministerio de Salud (MINSA), Lima

BACKGROUND: Peru holds the fourth highest burden of tuberculosis in the Americas. Despite an apparently well-functioning DOTS control program, the prevalence of multidrug resistant tuberculosis (MDR-TB) continues to increase. To worsen this situation, cases of extensively drug resistance tuberculosis (XDR-TB) have been detected. Little information exists about the genetic diversity of drug-susceptible vs. MDR-TB and XDR-TB. METHODS: Cryopreserved samples of XDR strains from 2007 to 2009 (second semester), were identified and collected. Starting from 227 frozen samples, a total of 142 XDR-TB strains of Mycobacterium tuberculosis complex (MTBC; 1 isolate per patient) were retained for this study. Each strain DNA was analyzed by spoligotyping and the 15-loci Mycobacterial Interspersed Repetitive Unit (MIRU-15). RESULTS: Among the 142 isolates analyzed, only 2 samples (1.41%) could not be matched to any lineage. The most prevalent sublineage was Haarlem (43.66%), followed by T (27.46%), LAM (16.2%), Beijing (9.15%), and X clade (1.41%). Spoligotype analysis identified clustering for 128/142 (90.1%) isolates vs. 49/142 (34.5%) with MIRUs. Of the samples, 90.85% belonged to retreated patients. The drug resistant profile demonstrated that 62.67% showed resistance to injectable drugs capreomycin (CAP) and kanamycin (KAN) vs. 15.5% to CAP alone and 21.8% to KAN alone. The SIT219/T1 and SIT50/H3 were the most prevalent patterns in our study. The spoligoforest analysis showed that SIT53/T1 was at the origin of many of the T lineage strains as well as a big proportion of Haarlem lineage strains (SIT50/H3, followed by SIT47/H1, SIT49/H3, and SIT2375/H1), as opposed to the SIT1/Beijing strains that did not appear to evolve into minor Beijing sublineages among the XDR-TB strains. CONCLUSION: In contrast with other Latin-American countries where LAM sublineage is the most predominant, we found the Haarlem to be the most common followed by T sublineage among the XDR-TB strains.

Mots clés: Mycobacterium tuberculosis; Peru; Extensively Drug-Resistant Tuberculosis; Genetic Diversity; Tuberculosis; Spoligotyping; MIRU-VNTR; Molecular Epidemiology

Domaines: Santé publique et épidémiologie; Bactériologie

Omar Cáceres, Nalin Rastogi, Carlos Bartra, David Couvin, Marco Galarza, et al.. Characterization of the Genetic Diversity of Extensively-Drug Resistant Mycobacterium tuberculosis Clinical Isolates from Pulmonary Tuberculosis Patients in Peru. PLoS ONE, 2014, 9 (12), pp.e112789. ⟨10.1371/journal.pone.0112789⟩. ⟨pasteur-01153013⟩