In 2002, public health officials detected a 100% increase in tuberculosis (TB) among homeless people in Seattle. Genotypic strain typing of Mycobacterium tuberculosis
isolates identified an outbreak cluster involving a pansusceptible strain designated SBRI9 (13
). This strain had also caused case clusters in New York, New Jersey, and Michigan (13
). The first King County cases were diagnosed in May 2002, and by the end of 2003, the outbreak exceeded 48 cases. Most transmission occurred in facilities and social centers catering to the homeless, with only a few cases occurring outside of the homeless community.
An aggressive public health response substantially curbed the outbreak by the end of 2003 (K. L. Lofy et al., submitted for publication). Nevertheless, it was deemed useful to continue to monitor the transmission of strain SBRI9 in 2004 and beyond for two reasons. First, the Centers for Disease Control and Prevention estimated that at least 1,000 persons were exposed to the outbreak strain in 2002-2003, mostly in Seattle homeless facilities. Tuberculin skin test positivity among people who spent nights at these facilities was >4-fold greater than the baseline level for this population (Lofy et al., submitted). Due to the difficulties associated with monitoring the treatment of homeless people, few of the exposed individuals with positive tuberculin skin tests received treatment for latent tuberculosis. This left within the community a reservoir of people who are infected with the outbreak strain and at risk of starting new outbreaks. This risk was addressed in part by continuing to track the transmission of the outbreak strain within the community.
A second incentive for ongoing monitoring of SBRI9 transmission arose from genotypic analysis, which placed the strain into the N subfamily of the pandemic W-Beijing family of M.tuberculosis
). The Beijing family is one of several phylogenetic clades of M. tuberculosis
that are thought to account for disproportionately large numbers of TB case clusters worldwide (2
). Beijing strains may have innate characteristics that favor clonal expansion within human populations. In nonhuman models of tuberculosis infection, Beijing strains have hypervirulent phenotypes and elicit altered cytokine responses relative to control strains (11
). Specific genetic and phenotypic properties which might account for these observations have been described previously (16
). Localized studies have shown that Beijing family strains can spread aggressively within some populations (1
). However, it remains unclear whether the Beijing family is truly expanding globally, as the global abundance of certain phylogenetic clades of M. tuberculosis
could alternatively be explained by stable association with human populations that have themselves expanded (8
). Despite these uncertainties, the introduction of a new Beijing family strain into a population is potentially significant from the epidemiological and public health standpoints.
Standard M. tuberculosis
strain fingerprinting methods, including spoligotyping, IS6110
-targeted restriction fragment length polymorphism (IS6110
-RFLP) analysis, mycobacterial interspersed repetitive unit (MIRU) analysis, and repetitive-sequence-based PCR (rep-PCR) (5
), are too time consuming or expensive for a postoutbreak investigation aimed at diagnosing new cases involving a single genotype. Therefore, a new approach was designed that took advantage of the expanding M. tuberculosis
comparative genomic databases in the literature. This information was used to generate a PCR-based test for strain SBRI9 based on genomic deletion typing (deligotyping). This approach allowed us to identify new SBRI9 cases in a very rapid and cost-effective fashion and to observe the clonal expansion of this strain within this homeless population.