Dominant incidence of multidrug and extensively drug-resistant specific Mycobacterium tuberculosis clones in Osaka Prefecture, Japan

PLoS One. 2012;7(8):e42505. doi: 10.1371/journal.pone.0042505. Epub 2012 Aug 31.

Abstract

Infection and transmission of multidrug-resistant Mycobacterium tuberculosis (MDR-Mtb) and extensively drug-resistant M. tuberculosis (XDR-Mtb) is a serious health problem. We analyzed a total of 1,110 Mtb isolates in Osaka Prefecture and neighboring areas from April 2000 to March 2009. A total of 89 MDR-Mtb were identified, 36 (48.5%) of which were determined to be XDR-Mtb. Among the 89 MDR-Mtb isolates, 24 (27.0%) phylogenetically distributed into six clusters based on mycobacterial interspersed repetitive units-various number of tandem repeats (MIRU-VNTR) typing. Among these six clusters, the MIRU-VNTR patterns of four (OM-V02, OM-V03, OM-V04, and OM-V06) were only found for MDR-Mtb. Further analysis revealed that all isolates belonging to OM-V02 and OM-V03, and two isolates from OM-V04 were clonal. Importantly such genotypes were not observed for drug-sensitive isolates. These suggest that few but transmissible clones can transmit after acquiring multidrug resistance and colonize even in a country with a developed, well-organized healthcare system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Extensively Drug-Resistant Tuberculosis / epidemiology*
  • Extensively Drug-Resistant Tuberculosis / genetics*
  • Extensively Drug-Resistant Tuberculosis / microbiology
  • Genetic Variation
  • Genotype
  • Humans
  • Incidence
  • Japan
  • Microbial Sensitivity Tests
  • Models, Genetic
  • Mutation
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / metabolism
  • Phylogeny
  • Public Health
  • Repetitive Sequences, Nucleic Acid
  • Sequence Analysis, DNA
  • Tuberculosis, Multidrug-Resistant / epidemiology
  • Tuberculosis, Multidrug-Resistant / genetics*
  • Tuberculosis, Multidrug-Resistant / microbiology

Grants and funding

This work was supported by a grant from the Ministry of Health, Labour and Welfare (Research on Emerging and Reemerging Infectious Diseases, Health Sciences Research Grants) to AT, TW, KK and SM, and a grant from Osaka City University to SM, RM and AT, by a grant from United States-Japan Cooperative Medical Science Programs, by the Global Center of Excellence Program, “Establishment of International Collaboration Centers for Zoonosis Control”, Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, by Grants-in-Aid for the Program of Founding Research Center for Emerging and Re-emerging Infectious Diseases from MEXT to YS as well as by Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science to YS and CN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.