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Genomic Epidemiology of Multidrug-Resistant Mycobacterium tuberculosis During Transcontinental Spread

Coscolla, Mireia ; Barry, Pennan M. ; Oeltmann, John E. ; Koshinsky, Heather ; Shaw, Tambi ; Cilnis, Martin ; Posey, Jamie ; Rose, Jordan ; Weber, Terry ; Fofanov, Viacheslav Y. ; Gagneux, Sebastien ; Kato-Maeda, Midori ; Metcalfe, John Z.

In: The Journal of Infectious Diseases, 2015, vol. 212, no. 2, p. 302-310

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    Title
    • Genomic Epidemiology of Multidrug-Resistant Mycobacterium tuberculosis During Transcontinental Spread
    Author
    • Coscolla, Mireia. Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute
    • Barry, Pennan M.. Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond
    • Oeltmann, John E.. Centers for Disease Control and Prevention, Atlanta, Georgia
    • Koshinsky, Heather. Eureka Genomics, Hercules
    • Shaw, Tambi. Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond
    • Cilnis, Martin. Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond
    • Posey, Jamie. Centers for Disease Control and Prevention, Atlanta, Georgia
    • Rose, Jordan. Division of Pulmonary and Critical Care Medicine, Francis J. Curry International Tuberculosis Center, San Francisco General Hospital, University of California
    • Weber, Terry. Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond
    • Fofanov, Viacheslav Y.. Eureka Genomics, Hercules
    • Gagneux, Sebastien. Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute
    • Kato-Maeda, Midori. Division of Pulmonary and Critical Care Medicine, Francis J. Curry International Tuberculosis Center, San Francisco General Hospital, University of California
    • Metcalfe, John Z.. Division of Pulmonary and Critical Care Medicine, Francis J. Curry International Tuberculosis Center, San Francisco General Hospital, University of California
    Document Type
    • Postprint
    Language
    • English
    Published in
    • The Journal of Infectious Diseases, 2015, vol. 212, no. 2, p. 302-310. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:295835
    Summary
    The transcontinental spread of multidrug-resistant (MDR) tuberculosis is poorly characterized in molecular epidemiologic studies. We used genomic sequencing to understand the establishment and dispersion of MDR Mycobacterium tuberculosis within a group of immigrants to the United States. We used a genomic epidemiology approach to study a genotypically matched (by spoligotype, IS6110 restriction fragment length polymorphism, and mycobacterial interspersed repetitive units-variable number of tandem repeat signature) lineage 2/Beijing MDR strain implicated in an outbreak of tuberculosis among refugees in Thailand and consecutive cases within California. All 46 MDR M. tuberculosis genomes from both Thailand and California were highly related, with a median difference of 10 single-nucleotide polymorphisms (SNPs). The Wat Tham Krabok (WTK) strain is a new sequence type distinguished from all known Beijing strains by 55 SNPs and a genomic deletion (Rv1267c) associated with increased fitness. Sequence data revealed a highly prevalent MDR strain that included several closely related but distinct allelic variants within Thailand, rather than the occurrence of a single outbreak. In California, sequencing data supported multiple independent introductions of WTK with subsequent transmission and reactivation within the state, as well as a potential super spreader with a prolonged infectious period. Twenty-seven drug resistance-conferring mutations and 4 putative compensatory mutations were found within WTK strains. Genomic sequencing has substantial epidemiologic value in both low- and high-burden settings in understanding transmission chains of highly prevalent MDR strains