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Transmission of Specific Genotype Streptomycin Resistant Strains of Mycobacterium tuberculosis in the Tokyo Metropolitan Area in Japan

Akihiro Ohkado1*, Yoshiro Murase2, Masaaki Mori3, Naoki Hasegawa4, Goro Otsuka5, Michiko Nagamine6, Hideo Maeda6, Kazuhiro Uchimura1, Masako Ohmori1, Norio Yamada7, Shinji Maeda2, Seiya Kato8, Toru Mori8 and Nobukatsu Ishikawa8

Author Affiliations

1 Department of Epidemiology and Clinical Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Matsuyama 3-1-24, Kiyose, Tokyo, Japan

2 Department of Reference for Mycobacteria, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Tokyo, Japan

3 Health Centre, Keio University, Yokohama, Japan

4 Department of Respiratory Medicine, Keio University, Yokohama, Japan

5 Department of Health and Clinical Medicine, Bureau of Health and Welfare, Kawasaki, Japan

6 Bureau of Social Welfare and Public Health, Tokyo Metropolitan Government, Shinjuku, Tokyo, Japan

7 Department of International Cooperation, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Tokyo, Japan

8 Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Tokyo, Japan

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BMC Infectious Diseases 2009, 9:138  doi:10.1186/1471-2334-9-138

Published: 26 August 2009



From 2003 through to 2004, an outbreak of tuberculosis was identified at a university campus in Yokohama City, located in the southern part of the Tokyo Metropolitan Area (TMA). All Mycobacterium tuberculosis (M. tuberculosis) strains detected with regards to this outbreak turned out to be Streptomycin resistant with matched patterns of 14 IS6110 bands of Restriction Fragment Length Polymorphism (RFLP). The M. tuberculosis bacilli, which had the matched IS6110 band patterns with resistance to Streptomycin to those of bacilli isolated in the outbreak, were also concurrently detected through either the population-based or the hospital-based DNA fingerprinting surveillance of M. tuberculosis either in Shinjuku City or in Kawasaki City respectively.

The aim of the present study is to describe the spread of the specific genotype strains of M. tuberculosis in the TMA as observed in the above incident, and to identify the possible transmission routes of the strains among people living in urban settings in Japan.


We applied Variable Numbers of Tandem Repeats (VNTR) analysis to all M. tuberculosis isolates which were resistant to Streptomycin with a matched IS6110-RFLP band pattern (M-strains). They were isolated either from cases related to the tuberculosis outbreak that happened at a university, or through DNA fingerprinting surveillance of M. tuberculosis both in Shinjuku City and in Kawasaki City. For VNTR analysis, 12MIRU loci, 4ETR loci, seven loci by Supply, four loci by Murase (QUB15, Mtub24, VNTR2372, VNTR3336) were selected.


Out of a total of 664 isolates collected during the study period, 46 isolates (6.9%) were identified as M-strains. There was a tendency that there was a higher proportion of those patients whose isolates belonged to M4-substrains, with four copies of tandem repeat at the ETR-C locus, to have visited some of the internet-cafés in the TMA than those whose isolates belonged to M5-substrains, with five copies at the ETR-C locus, although statistically not significant (38.1% vs. 10.0%, Exact p = 0.150).


Although firm conclusions could not be reached through the present study, it suggested that we have to take into consideration that tuberculosis can be transmitted in congregated facilities like internet cafés where tuberculosis high-risk people and general people share common spaces.