title: The Association between Mycobacterium Tuberculosis Genotype and Drug Resistance in Peru.
abstract: BACKGROUND
  The comparison of Mycobacterium tuberculosis bacterial genotypes with phenotypic, demographic, geospatial and clinical data improves our understanding of how strain lineage influences the development of drug-resistance and the spread of tuberculosis.
  
  
  METHODS
  To investigate the association of Mycobacterium tuberculosis bacterial genotype with drug-resistance. Drug susceptibility testing together with genotyping using both 15-loci MIRU-typing and spoligotyping, was performed on 2,139 culture positive isolates, each from a different patient in Lima, Peru. Demographic, geospatial and socio-economic data were collected using questionnaires, global positioning equipment and the latest national census.
  
  
  RESULTS
  The Latin American Mediterranean (LAM) clade (OR 2.4, p<0.001) was significantly associated with drug-resistance and alone accounted for more than half of all drug resistance in the region. Previously treated patients, prisoners and genetically clustered cases were also significantly associated with drug-resistance (OR's 2.5, 2.4 and 1.8, p<0.001, p<0.05, p<0.001 respectively).
  
  
  CONCLUSIONS
  Tuberculosis disease caused by the LAM clade was more likely to be drug resistant independent of important clinical, genetic and socio-economic confounding factors. Explanations for this include; the preferential co-evolution of LAM strains in a Latin American population, a LAM strain bacterial genetic background that favors drug-resistance or the "founder effect" from pre-existing LAM strains disproportionately exposed to drugs.
authors.affiliation: Wellcome Centre for Clinical Tropical Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, United Kingdom; London School of Hygiene and Tropical Medicine, TB Centre and Department of Clinical Research, Keppel St., London, United Kingdom; Laboratorio de Investigacion y Desarrollo, Universidad Peruana Cayetano Heredia, San Martin de Porres, Lima, Peru.
authors.forename: Louis
authors.initials: L
authors.lastname: Grandjean
authors.affiliation: Department of Infectious Diseases, Kobe Institute of Health, Chuo-ku, Kobe, Japan.
authors.forename: Tomotada
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: London School of Hygiene and Tropical Medicine, TB Centre and Department of Clinical Research, Keppel St., London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Lithgow
authors.affiliation: Laboratorio de Investigacion y Desarrollo, Universidad Peruana Cayetano Heredia, San Martin de Porres, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Department of Infectious Diseases, Kobe Institute of Health, Chuo-ku, Kobe, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Arikawa
authors.affiliation: Department of Infectious Diseases, Kobe Institute of Health, Chuo-ku, Kobe, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakanishi
authors.affiliation: Wellcome Centre for Clinical Tropical Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, United Kingdom; Laboratorio de Investigacion y Desarrollo, Universidad Peruana Cayetano Heredia, San Martin de Porres, Lima, Peru.
authors.forename: Laura
authors.initials: L
authors.lastname: Martin
authors.affiliation: DIRESA de Callao, Bellavista, Callao, Peru.
authors.forename: Edith
authors.initials: E
authors.lastname: Castillo
authors.affiliation: Unidad Tecnica TB-MDR, Lima, Peru.
authors.forename: Valentina
authors.initials: V
authors.lastname: Alarcon
authors.affiliation: Laboratorio de Investigacion y Desarrollo, Universidad Peruana Cayetano Heredia, San Martin de Porres, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Coronel
authors.affiliation: Laboratorio de Investigacion y Desarrollo, Universidad Peruana Cayetano Heredia, San Martin de Porres, Lima, Peru.
authors.forename: Walter
authors.initials: W
authors.lastname: Solano
authors.affiliation: TB-Insight Research Group, Rensselaer Polytechnic Institute, Troy, New York, United States of America.
authors.forename: Minoo
authors.initials: M
authors.lastname: Aminian
authors.affiliation: Naval Medical Research Unit 6-Bellavista, Callao, Peru.
authors.forename: Claudia
authors.initials: C
authors.lastname: Guezala
authors.affiliation: WHO Supranational TB Reference Laboratory, Institut Pasteur de la Guadeloupe, Abymes, Guadeloupe, France.
authors.forename: Nalin
authors.initials: N
authors.lastname: Rastogi
authors.affiliation: WHO Supranational TB Reference Laboratory, Institut Pasteur de la Guadeloupe, Abymes, Guadeloupe, France.
authors.forename: David
authors.initials: D
authors.lastname: Couvin
authors.affiliation: Laboratorio de Investigacion y Desarrollo, Universidad Peruana Cayetano Heredia, San Martin de Porres, Lima, Peru.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sheen
authors.affiliation: Laboratorio de Investigacion y Desarrollo, Universidad Peruana Cayetano Heredia, San Martin de Porres, Lima, Peru.
authors.forename: Mirko
authors.initials: M
authors.lastname: Zimic
authors.affiliation: London School of Hygiene and Tropical Medicine, TB Centre and Department of Clinical Research, Keppel St., London, United Kingdom; Laboratorio de Investigacion y Desarrollo, Universidad Peruana Cayetano Heredia, San Martin de Porres, Lima, Peru.
authors.forename: David A J
authors.initials: DA
authors.lastname: Moore
mesh_terms: D000328:Adult; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D010568:Peru; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology*