Molecular Epidemiology of Tuberculosis
We conducted a population-based study to assess demographic and risk-factor correlates for the most frequently occurring Mycobacterium tuberculosis genotypes from tuberculosis (TB) patients. The study included all incident, culture-positive TB patients from seven sentinel surveillance sites in the United States from 1996 to 2000. M. tuberculosis isolates were genotyped by IS6110-based restriction fragment length polymorphism and spoligotyping. Genotyping was available for 90% of 11,923 TB patients. Overall, 48% of cases had isolates that matched those from another patient, including 64% of U.S.-born and 35% of foreign-born patients. By logistic regression analysis, risk factors for clustering of genotypes were being male, U.S.-born, black, homeless, and infected with HIV; having pulmonary disease with cavitations on chest radiograph and a sputum smear with acid-fast bacilli; and excessive drug or alcohol use. Molecular characterization of TB isolates permitted risk correlates for clusters and specific genotypes to be described and provided information regarding cluster dynamics over time.

Since 1990, characterization of Mycobacterium tuberculosis isolates by molecular methods has been useful in confirming suspected laboratory contamination and as an adjunct to epidemiology-based contact investigation. Most studies used the restriction fragment length polymorphism (RFLP) technique, based on IS6110 and specific to the M. tuberculosis complex. This genetic element may be present in different positions on the chromosome, resulting in a unique genotype useful for characterizing the strain of M. tuberculosis infecting a patient. Although RFLP has disadvantages (e.g., cost, time required to culture the organism, and specialized training and laboratory equipment), IS6110-based RFLP is the established method considered most discriminatory for genetic characterization of M. tuberculosis strains worldwide.

In 1996, the Centers for Disease Control and Prevention (CDC) established seven sentinel surveillance sites in the United States (National Tuberculosis Genotyping and Surveillance Network) to assess the utility of molecular genotyping for improving tuberculosis (TB) prevention and control. The TB genotyping network used standardized protocols for molecular characterization of M. tuberculosis isolates from patients in all sentinel sites. The network was designed to address specific epidemiologic questions regarding the natural history, transmission, and potential applicability of molecular genotyping of M. tuberculosis strains to augment TB control activities. Two objectives were to identify and determine the prevalence of specific M. tuberculosis genotype clustering in populations of sentinel surveillance TB patients and to describe the demographic characteristics of these populations and the genotypic characteristics of M. tuberculosis strains in clustered and nonclustered TB cases. We describe demographic and risk factor correlates for the most frequently occurring M. tuberculosis genotypes in isolates collected from sentinel TB patients.