MDR TB, California, USA, 2004–2007 | CDC EID

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Volume 16, Number 9–September 2010
Research
Determinants of Multidrug-Resistant Tuberculosis Clusters, California, USA, 2004–2007
John Z. Metcalfe, Elizabeth Y. Kim, S.-Y. Grace Lin, Adithya Cattamanchi, Peter Oh, Jennifer Flood, Philip C. Hopewell, and Midori Kato-Maeda
Author affiliations: University of California, San Francisco, California, USA (J.Z. Metcalfe, E.Y. Kim, A. Cattamanchi, P.C. Hopewell, M. Kato-Maeda); and California Department of Public Health, Richmond, California, USA (S.-Y.G. Lin, P. Oh, J. Flood)

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Abstract
Laboratory and epidemiologic evidence suggests that pathogen-specific factors may affect multidrug-resistant (MDR) tuberculosis (TB) transmission and pathogenesis. To identify demographic and clinical characteristics of MDR TB case clustering and to estimate the effect of specific isoniazid resistance–conferring mutations and strain lineage on genotypic clustering, we conducted a population-based cohort study of all MDR TB cases reported in California from January 1, 2004, through December 31, 2007. Of 8,899 incident culture-positive cases for which drug susceptibility information was available, 141 (2%) were MDR. Of 123 (87%) strains with genotype data, 25 (20%) were aggregated in 8 clusters; 113 (92%) of all MDR TB cases and 21 (84%) of clustered MDR TB cases occurred among foreign-born patients. In multivariate analysis, the katG S315T mutation (odds ratio 11.2, 95% confidence interval 2.2–¥; p = 0.004), but not strain lineage, was independently associated with case clustering.
In 2007, >500,000 cases of multidrug-resistant (MDR) tuberculosis (TB), defined as resistance to at least isoniazid and rifampin, occurred worldwide (1). Although demographic and clinical risk factors for transmission and pathogenesis of both drug-susceptible and drug-resistant Mycobacterium tuberculosis have been well described (2,3), little is known about the microbial factors that influence the generation of secondary MDR TB cases (4,5).

Community- and population-based molecular epidemiologic studies of isoniazid-monoresistant M. tuberculosis (6–8) have shown that specific resistance-conferring mutations are associated with variable degrees of genotypic clustering, a measure of strain pathogenicity that incorporates host factors, transmissibility of the organism, and capacity of the organism to cause active disease. For example, isoniazid-monoresistant strains with a serine-to-threonine substitution at position 315 (S315T) are more often associated with secondary cases than are strains without the S315T mutation (6,7), likely because of reduced or absent catalase–peroxidase production (9). However, the effects of specific isoniazid resistance–conferring mutations on genotypic clustering in multidrug resistance are less well characterized. The studies reported to date have been limited by inadequate genotypic discrimination (10,11) and/or nonrepresentative sampling of cases (10,12–14).

California reports the highest annual number of TB cases (15), more than one fourth of all MDR TB cases (16), and the highest immigration rates in the United States (17). We conducted a population-based cohort study of all incident MDR TB cases in California during a 4-year period (January 2004–December 2007) to 1) describe demographic and clinical characteristics of clustering and 2) estimate the effect of specific isoniazid resistance–conferring mutations and strain lineage on genotypic clustering of MDR M. tuberculosis.

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MDR TB, California, USA, 2004–2007 | CDC EID