%0 Journal Article %T Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance. %+ Laboratorios de Investigación y Desarrollo (LID) %+ Institut Pasteur de la Guadeloupe %+ Centre and Department of Clinical Research %+ Department of Infectious Disease Epidemiology [London] (DIDE) %+ Department of International Health %A Sheen, Patricia %A Couvin, David %A Grandjean, Louis %A Zimic, Mirko %A Dominguez, Maria %A Luna, Giannina %A Gilman, Robert H %A Rastogi, Nalin %A Moore, David a J %Z DAJM was supported by Wellcome Trust Fellowships (064672/Z/01/Z and 078067/Z/05/Z; www.wellcome.ac.uk) %< avec comité de lecture %@ 1932-6203 %J PLoS ONE %I Public Library of Science %V 8 %N 6 %P e65873 %8 2013 %D 2013 %R 10.1371/journal.pone.0065873 %M 23826083 %Z Life Sciences [q-bio]/Microbiology and Parasitology/BacteriologyJournal articles %X BACKGROUND: There is limited available data on the strain diversity of M tuberculosis in Peru, though there may be interesting lessons to learn from a setting where multidrug resistant TB has emerged as a major problem despite an apparently well-functioning DOTS control programme. METHODS: Spoligotyping was undertaken on 794 strains of M tuberculosis collected between 1999 and 2005 from 553 community-based patients and 241 hospital-based HIV co-infected patients with pulmonary tuberculosis in Lima, Peru. Phylogenetic and epidemiologic analyses permitted identification of clusters and exploration of spoligotype associations with drug resistance. RESULTS: Mean patient age was 31.9 years, 63% were male and 30.4% were known to be HIV+. Rifampicin mono-resistance, isoniazid mono-resistance and multidrug resistance (MDR) were identified in 4.7%, 8.7% and 17.3% of strains respectively. Of 794 strains from 794 patients there were 149 different spoligotypes. Of these there were 27 strains (3.4%) with novel, unique orphan spoligotypes. 498 strains (62.7%) were clustered in the nine most common spoligotypes: 16.4% SIT 50 (clade H3), 12.3% SIT 53 (clade T1), 8.3% SIT 33 (LAM3), 7.4% SIT 42 (LAM9), 5.5% SIT 1 (Beijing), 3.9% SIT 47 (H1), 3.0% SIT 222 (clade unknown), 3.0% SIT1355 (LAM), and 2.8% SIT 92 (X3). Amongst HIV-negative community-based TB patients no associations were seen between drug resistance and specific spoligotypes; in contrast HIV-associated MDRTB, but not isoniazid or rifampicin mono-resistance, was associated with SIT42 and SIT53 strains. CONCLUSION: Two spoligotypes were associated with MDR particularly amongst patients with HIV. The MDR-HIV association was significantly reduced after controlling for SIT42 and SIT53 status; residual confounding may explain the remaining apparent association. These data are suggestive of a prolonged, clonal, hospital-based outbreak of MDR disease amongst HIV patients but do not support a hypothesis of strain-specific propensity for the acquisition of resistance-conferring mutations. %G English %2 https://riip.hal.science/pasteur-00870729/document %2 https://riip.hal.science/pasteur-00870729/file/journal.pone.0065873.pdf %L pasteur-00870729 %U https://riip.hal.science/pasteur-00870729 %~ RIIP %~ RIIP_GUADELOUPE