Tuberculosis Genotyping in Six Low-Incidence States, 2000–2003

Published:January 22, 2007DOI:


      As tuberculosis incidence declines in the United States, a new tool for TB control efforts is Mycobacterium tuberculosis genotyping. Colorado, Iowa, Montana, New Hampshire, West Virginia, and Wisconsin began routine genotyping of all culture-confirmed TB cases in October 2000.


      M. tuberculosis isolates from cases reported October 2000 through December 2003 were genotyped by spoligotyping, mycobacterial interspersed repetitive units, and IS6110-based restriction fragment length polymorphism methods. Genotyping results were linked to demographic variables from national surveillance records. Patients who were in genotype clusters were interviewed and their records reviewed to determine possible transmission links among clustered patients. Final analysis was completed during April 2004 through June 2005.


      Of 971 reported TB cases, 774 (80%) were culture-confirmed, of which 728 (94%) were genotyped. Most genotyped isolates (634 [87%]) were unique. Within 36 clusters linking 94 individuals, four clusters involved both U.S.- and foreign-born individuals. For eight clusters, genotyping results led to the discovery of previously unsuspected transmission. Transmission links between individuals were established in 21 (58%) of the 36 clusters.


      In these six low-incidence states, most isolates had unique genotypes, suggesting that most cases arose from activation of latent infection. Few TB clusters involved the foreign-born. For 58% of genotype clusters, epidemiologic investigation ascertained that clustering represented recent M. tuberculosis transmission.
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        • Centers for Disease Control and Prevention
        A strategic plan for the elimination of tuberculosis in the United States.
        MMWR Morb Mortal Wkly Rep. 1989; 38: 1-25
        • Institute of Medicine
        Ending neglect: the elimination of tuberculosis in the United States. National Academies Press, Washington, D.C2000
        • Centers for Disease Control and Prevention
        Trends in tuberculosis—United States, 2005.
        MMWR Morb Mortal Wkly Rep. 2006; 55: 305-308
        • Centers for Disease Control and Prevention, Advisory Council for the Elimination of Tuberculosis
        Progressing toward tuberculosis elimination in low-incidence areas of the United States.
        MMWR Morb Mortal Wkly Rep. 2002; 51: 1-16
        • Centers for Disease Control and Prevention
        Tuberculosis Genotyping Network.
        Emerg Infect Dis. 2002; 8 (theme issue): 1187-1364
        • Trepka M.J.
        • Beyer T.O.
        • Proctor M.E.
        • Davis J.P.
        An evaluation of the completeness of tuberculosis case reporting using hospital billing and laboratory data—Wisconsin, 1995.
        Ann Epidemiol. 1999; 9: 419-423
        • Curtis A.B.
        • McCray E.
        • McKenna M.
        • Onorato I.M.
        Completeness and timeliness of tuberculosis case reporting: a multistate study.
        Am J Prev Med. 2001; 20: 108-112
      1. Montero JT, Donovan D, Proctor J. Sensitivity of TB and LTBI reporting in New Hampshire, 2000–2001. In: Proceedings of the 9th Annual Conference of the International Union Against Tuberculosis and Lung Disease, North America Region, Vancouver, British Columbia, Canada, February 23–26, 2005.

        • Molhuizen H.O.F.
        • Bunschoten A.E.
        • Schouls L.M.
        • van Embden J.D.A.
        Rapid detection and simultaneous strain differentiation of Mycobacterium tuberculosis complex bacteria by spoligotyping.
        Methods Mol Biol. 1998; 101: 381-394
        • Cowan L.S.
        • Diem L.
        • Brake M.C.
        • Crawford J.T.
        Transfer of a Mycobacterium tuberculosis genotyping method, spoligotyping, from a reverse line-blot hybridization, membrane-based assay to the Luminex multianalyte profiling system.
        J Clin Microbiol. 2004; 42: 474-477
        • Mazars E.S.
        • Lesjean A.-L.
        • Banuls M.
        • et al.
        High-resolution minisatellite-based typing as a portable approach to global analysis of Mycobacterium tuberculosis molecular epidemiology.
        Natl Acad Sci U S A. 2001; 98: 1901-1906
        • Cowan L.S.
        • Mosher L.
        • Diem L.
        • Massey J.P.
        • Crawford J.T.
        Variable-number tandem repeat typing of Mycobacterium tuberculosis isolates with low copy numbers of IS6110 by using mycobacterial interspersed repetitive units.
        J Clin Microbiol. 2002; 40: 1592-1602
        • Cowan L.S.
        • Diem L.
        • Monson T.
        • et al.
        Evaluation of a two-step approach for large-scale, prospective genotyping of Mycobacterium tuberculosis isolates in the United States.
        J Clin Microbiol. 2005; 43: 688-695
        • van Embden J.D.A.
        • Cave M.D.
        • Crawford J.T.
        • et al.
        Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology.
        J Clin Microbiol. 1993; 31: 406-409
        • Nguyen D.
        • Brassard P.
        • Menzies D.
        • et al.
        Genomic characterization of an endemic Mycobacterium tuberculosis strain: evolutionary and epidemiologic implications.
        J Clin Microbiol. 2004; 42: 2573-2580
        • Ijaz K.
        • Yang Z.
        • Matthews H.S.
        • Bates J.H.
        • Cave M.D.
        Mycobacterium tuberculosis transmission between cluster members with similar fingerprint patterns.
        Emerg Infect Dis. 2002; 8: 1257-1259
        • Cronin W.A.
        • Golub J.E.
        • Lathan M.J.
        • et al.
        Molecular epidemiology of tuberculosis in a low- to moderate-incidence state: are contact investigations enough?.
        Emerg Infect Dis. 2002; 8: 1271-1279
        • Braden C.R.
        • Onorato I.M.
        • Crawford J.T.
        Molecular epidemiology and tuberculosis control.
        JAMA. 2000; 284 (letter): 305-307
        • Malakmadze N.
        • Gonzalez I.M.
        • Oemig T.
        • et al.
        Unsuspected recent transmission of tuberculosis among high-risk groups: implications of universal tuberculosis genotyping in its detection.
        Clin Infect Dis. 2005; 40: 366-373
        • Cattamanchi A.
        • Hopewell P.C.
        • Gonzalez L.C.
        • et al.
        A 13-year molecular epidemiological analysis of tuberculosis in San Francisco.
        Int J Tuberc Lung Dis. 2006; 10: 297-304
        • Centers for Disease Control and Prevention
        Notice to readers: new CDC program for rapid genotyping of Mycobacterium tuberculosis isolates.
        MMWR Morb Mortal Wkly Rep. 2005; 54: 47
        • Daley C.L.
        Molecular epidemiology: a tool for understanding control of tuberculosis transmission.
        Clin Chest Med. 2005; 26: 217-231
        • Chin D.P.
        • DeRiemer K.
        • Small P.M.
        • et al.
        Differences in contributing factors to tuberculosis incidence in U.S.-born and foreign-born persons.
        Am J Respir Crit Care Med. 1998; 158: 1797-1803
        • Lillebaek T.
        • Anderson A.B.
        • Bauer J.
        • et al.
        Risk of Mycobacterium tuberculosis transmission in a low-incidence country due to immigration from high-incidence areas.
        J Clin Microbiol. 2001; 39: 855-861
        • Hirsch A.E.
        • Tsolaki A.G.
        • DeRiemer K.
        • Feldman M.W.
        • Small P.M.
        Stable association between strains of Mycobacterium tuberculosis and their human host populations.
        Natl Acad Sci U S A. 2004; 101: 4871-4876