title: Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratorio de Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sheen
authors.forename: David
authors.initials: D
authors.lastname: Couvin
authors.forename: Louis
authors.initials: L
authors.lastname: Grandjean
authors.forename: Mirko
authors.initials: M
authors.lastname: Zimic
authors.forename: Maria
authors.initials: M
authors.lastname: Dominguez
authors.forename: Giannina
authors.initials: G
authors.lastname: Luna
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.forename: Nalin
authors.initials: N
authors.lastname: Rastogi
authors.forename: David A J
authors.initials: DA
authors.lastname: Moore
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D023801:Directly Observed Therapy; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics*; D010568:Peru; D010802:Phylogeny; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin