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TB Notes Newsletter

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No. 2, 2006

HIGHLIGHTS FROM STATE AND LOCAL PROGRAMS

Molecular Genotyping of Mycobacterium tuberculosis in Connecticut

After more than a decade of use, molecular genotyping of Mycobacterium tuberculosis isolates is now a standard public health tool. Genotyping has been used in a variety of settings, including defining strains prevalent in the population, detecting outbreaks in institutions and the community, evaluating the completeness of contact investigations, and determining laboratory contamination.1-5

In 2005, CDC launched the Genotyping TB Program, making laboratory capacity available to state health departments interested in genotyping M. tuberculosis isolates. In New England, the six state health laboratories are now routinely forwarding all culture-confirmed isolates from patients with pulmonary TB to one of the program’s reference laboratories for genotyping. To accelerate the decline of TB in New England, the state health departments coordinate cross-jurisdictional investigations to prevent the transmission of TB across state lines. In this report, we describe one recent outbreak of TB in Fairfield County, Connecticut. This outbreak would not have been detected without the use of molecular genotyping.

Connecticut TB Outbreak

Since 2005, universal genotyping of pulmonary TB isolates has detected five clusters in Connecticut. One cluster, with cases diagnosed during February 2004–May 2005, consisted of four Hispanic males from one city in Fairfield County (Table 1). Risk factors included HIV infection (2), unemployment (2), and incarceration (2).

Table 1: Fairfield County, Connecticut TB Cluster, February 2004-May 2005

Age Groups (YTS) Occupation Country of Birth Date of entry into the U.S. HIV Status TB Risk Factors
15-24 Restaurant Mexico Unknown Negative Foreign born
25-44 Painter Mexico Post-2000 Negative Foreign born
24-44 Unemployed Mexico Pre-2000 Positive Foreign born: History incarceration, Excess alcohol
25-44 Unemployed U.S. N/A Positive History incarceration

Comment

In Connecticut, molecular genotyping is radically transforming TB control practices. Two methods based on polymerase chain reaction (PCR) are initially used. The first, spoligotyping, is a method for simultaneous detection and typing of M. tuberculosis strains. The second, mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) analysis, is a typing method that determines the number of repeated mycobacterial interspersed units at 12 independent loci.6 These methods provide faster turnaround times and produce digital results that make comparisons easier. A non-PCR technique, restriction fragment length polymorphism (RFLP), continues to be used to further define suspected outbreak strains. The population-based application of genotyping has revealed unsuspected transmission patterns that might not have been identified using conventional epidemiological techniques. Originally seven persons were identified in the Fairfield County cluster. Genotyping, using RFLP, showed that three strains were not identical to the dominant strain infecting the other four patients.

In response to this newly recognized cluster of four related TB cases, the DPH attempted a more intensive epidemiologic investigation with limited results, since two of the individuals had returned to Mexico. At this time, genotyping results are pending from another case potentially involved in this outbreak.

As more knowledge is gained about the use of molecular techniques and earlier detection of clusters, further investigations will continue to reveal previously unrecognized epidemiologic links between cases and define new settings where transmission occurred.7 We believe that the addition of molecular genotyping as a public health tool will augment TB control and accelerate the reduction of cases in Connecticut and the United States.

—Reported by T Condren, MPH, M Williams, RN,
TB Control Program
Connecticut Department of Public Health
G Budnick, MPS,
Connecticut Public Health Laboratory
J Hadler, MD, MPH, State Epidemiologist
M Lobato, MD, Division of TB Control, CDC

References

  1. Small PM, Hopewell PC, Singh SP, et al.  The epidemiology of tuberculosis in San Francisco. A population-based study using conventional and molecular methods.  N Engl J Med 1994; 330: 1703-9.
  2. Jereb JA, Burwen DR, Dooley SW, et al. Nosocomial outbreak of tuberculosis in a renal transplant unit: application of a new technique for restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolates. J Infect Dis 1993 168:1219-24.
  3. Daley CL, Small PM, Schecter GF, Schoolnik GK, McAdam RA, Jacobs WR Jr, Hopewell PC. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. An analysis using restriction-fragment-length polymorphisms. N Engl J Med 1992;326:231-5.
  4. Cronin WA, Golub JE, Lathan MJ, et al. Molecular epidemiology of tuberculosis in a low- to moderate-incidence state: are contact investigations enough? Emerg Infect Dis 2002;8:1271-9.
  5. CDC. Misdiagnoses of tuberculosis resulting from laboratory cross-contamination of Mycobacterium tuberculosis cultures--New Jersey, 1998. MMWR. 2000;49:413-6.
  6. Kwara A, Schiro R, Cowan, LS , et al. Evaluation of the epidemiologic utility of secondary typing methods for differentiation of Mycobacterium tuberculosis isolates. J Clin Micro, June 2003; 41: 2683-2685.
  7. Miller AC, Sharnprapai S, Suruki R, et al. Impact of genotyping of Mycobacterium tuberculosis on public health practice in Massachusetts. Emerg Infect Dis 2002;8:1285-9.

 

Last Reviewed: 05/18/2008
Content Source: Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

 

 
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