title: Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain.
abstract: The rise of drug-resistant strains is a major challenge to containing the tuberculosis (TB) pandemic. Yet, little is known about the extent of resistance in early years of chemotherapy and when transmission of resistant strains on a larger scale became a major public health issue. Here we reconstruct the timeline of the acquisition of antimicrobial resistance during a major ongoing outbreak of multidrug-resistant TB in Argentina. We estimate that the progenitor of the outbreak strain acquired resistance to isoniazid, streptomycin and rifampicin by around 1973, indicating continuous circulation of a multidrug-resistant TB strain for four decades. By around 1979 the strain had acquired additional resistance to three more drugs. Our results indicate that Mycobacterium tuberculosis (Mtb) with extensive resistance profiles circulated 15 years before the outbreak was detected, and about one decade before the earliest documented transmission of Mtb strains with such extensive resistance profiles globally.
authors.affiliation: Division of Infectious Disease Control, Norwegian Institute of Public Health, Lovisenberggata 8, Oslo 0456, Norway.
authors.forename: Vegard
authors.identifier: 0000000167213375
authors.initials: V
authors.lastname: Eldholm
authors.affiliation: Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Vélez Sarsfield 563, Buenos Aires 1281, Argentina.
authors.forename: Johana
authors.initials: J
authors.lastname: Monteserin
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
authors.forename: Adrien
authors.initials: A
authors.lastname: Rieux
authors.affiliation: Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Vélez Sarsfield 563, Buenos Aires 1281, Argentina.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lopez
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sobkowiak
authors.affiliation: Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Vélez Sarsfield 563, Buenos Aires 1281, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Ritacco
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
authors.forename: Francois
authors.initials: F
authors.lastname: Balloux
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001118:Argentina / Q000453:epidemiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004196:Disease Outbreaks; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology* / Q000635:transmission*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins