Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.

<h4>Background</h4>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....

Full description

Saved in:
Bibliographic Details
Main Authors: Patricia Sheen, David Couvin, Louis Grandjean, Mirko Zimic, Maria Dominguez, Giannina Luna, Robert H Gilman, Nalin Rastogi, David A J Moore
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0065873&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849434050545057792
author Patricia Sheen
David Couvin
Louis Grandjean
Mirko Zimic
Maria Dominguez
Giannina Luna
Robert H Gilman
Nalin Rastogi
David A J Moore
author_facet Patricia Sheen
David Couvin
Louis Grandjean
Mirko Zimic
Maria Dominguez
Giannina Luna
Robert H Gilman
Nalin Rastogi
David A J Moore
author_sort Patricia Sheen
collection DOAJ
description <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
format Article
id doaj-art-5544b8cb3a464db5be6aa94d48a54bef
institution Kabale University
issn 1932-6203
language English
publishDate 2013-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-5544b8cb3a464db5be6aa94d48a54bef2025-08-20T03:26:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6587310.1371/journal.pone.0065873Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.Patricia SheenDavid CouvinLouis GrandjeanMirko ZimicMaria DominguezGiannina LunaRobert H GilmanNalin RastogiDavid A J Moore<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0065873&type=printable
spellingShingle Patricia Sheen
David Couvin
Louis Grandjean
Mirko Zimic
Maria Dominguez
Giannina Luna
Robert H Gilman
Nalin Rastogi
David A J Moore
Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.
PLoS ONE
title Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.
title_full Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.
title_fullStr Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.
title_full_unstemmed Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.
title_short Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.
title_sort genetic diversity of mycobacterium tuberculosis in peru and exploration of phylogenetic associations with drug resistance
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0065873&type=printable
work_keys_str_mv AT patriciasheen geneticdiversityofmycobacteriumtuberculosisinperuandexplorationofphylogeneticassociationswithdrugresistance
AT davidcouvin geneticdiversityofmycobacteriumtuberculosisinperuandexplorationofphylogeneticassociationswithdrugresistance
AT louisgrandjean geneticdiversityofmycobacteriumtuberculosisinperuandexplorationofphylogeneticassociationswithdrugresistance
AT mirkozimic geneticdiversityofmycobacteriumtuberculosisinperuandexplorationofphylogeneticassociationswithdrugresistance
AT mariadominguez geneticdiversityofmycobacteriumtuberculosisinperuandexplorationofphylogeneticassociationswithdrugresistance
AT gianninaluna geneticdiversityofmycobacteriumtuberculosisinperuandexplorationofphylogeneticassociationswithdrugresistance
AT roberthgilman geneticdiversityofmycobacteriumtuberculosisinperuandexplorationofphylogeneticassociationswithdrugresistance
AT nalinrastogi geneticdiversityofmycobacteriumtuberculosisinperuandexplorationofphylogeneticassociationswithdrugresistance
AT davidajmoore geneticdiversityofmycobacteriumtuberculosisinperuandexplorationofphylogeneticassociationswithdrugresistance