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Use of Rapid Genomic Deletion Typing To Monitor a Tuberculosis Outbreak within an Urban Homeless Population

Robert Freeman,¹ Midori Kato-Maeda,^2, Kirsten A. Hauge,¹ Kathleen L. Horan,¹ Eyal Oren,³ Masahiro Narita,³ Carolyn K. Wallis,⁴ Don Cave,⁵ Charles M. Nolan,³ Peter M. Small,^2, and Gerard A. Cangelosi^1*

Seattle Biomedical Research Institute and the University of Washington, Seattle, Washington,¹ Public Health Seattle-King County Tuberculosis Control Program, Seattle, Washington,² Division of Infectious Diseases and Geographic Medicine, Stanford University Medical Center, Stanford, California,³ Harborview Medical Center, Seattle, Washington,⁴ University of Arkansas for Medical Sciences, Little Rock, Arkansas⁵

Received 11 May 2005/ Returned for modification 24 June 2005/ Accepted 9 August 2005

Beginning in mid-2002, a large tuberculosis outbreak occurred among homeless persons in King County, Washington. In order to further monitor the outbreak following its peak in 2003, Mycobacterium tuberculosis isolates from all new King County tuberculosis (TB) patients in 2004 and the first half of 2005 (n = 220) were genotyped by using a rapid comparative genomics-based (genomic deletion-typing) approach, with confirmation by mycobacterial interspersed repetitive units and repetitive-sequence-based PCR (rep-PCR). Results were compared to retrospective genotypic data from 1995 to 2003. The outbreak strain SBRI9, which was not seen among King County homeless persons prior to 2002, accounted for 16 out of 30 TB cases (53%) within this population in 2002. This trend continued with 27 out of 35 cases (77%) caused by the outbreak strain in 2003, 11 out of 13 cases (85%) caused by the outbreak strain in 2004, and 4 out of 10 cases (40%) caused by the outbreak strain in the first 5 months of 2005. Thus, the outbreak strain remained well established within this homeless population throughout the study period. At least four SBRI9 cases were in people who had previously been infected by other strains. The novel PCR-based strain-typing approach used in this investigation proved to be cost-effective and very rapid. In most cases, it was possible to analyze DNA extracted directly from primary isolation (Mycobacterium growth indicator tube) cultures submitted by clinical laboratories, a feature that markedly reduced the delay between diagnosis and strain typing results. This rapid turnaround facilitated public health efforts to prevent new outbreaks involving this strain.

Present address: San Francisco General Hospital and University of California, San Francisco, Calif.

Present address: Institute for Systems Biology, Seattle, Wash.

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