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In systematic studies of the molecular epidemiology of tuberculosis, DNA fingerprinting is used to estimate the fraction of incident cases attributable to recent transmission of Mycobacterium tuberculosis rather than reactivation disease and to identify risk factors for recent transmission. This approach is based on the premise that tuberculosis cases that share a DNA fingerprint are epidemiologically related while cases in which fingerprints are unique are due to remote infection that has reactivated. In this paper, the authors review the objectives and design of molecular epidemiologic studies of tuberculosis, describe current analytical approaches, and consider the impact of these different approaches on study results. Using data from a previously published investigation of the epidemiology of tuberculosis conducted from 1990 to 1993 among tuberculosis patients in New York City, New York, the authors show how selecting different measures of disease frequency, comparison groups, and sampling strategies may impact the results and interpretability of the study. They demonstrate ways to conduct sensitivity analyses of estimated results and suggest strategies that may improve the usefulness of this approach to studying tuberculosis. Am J Epidemiol 2002;155:565-71 [ABSTRACT FROM AUTHOR]

Background: The incidence of tuberculosis and drug resistance is increasing in the United States, but it is not clear how much of the increase is due to reactivation of latent infection and how much to recent transmission. Methods: We performed DNA fingerprinting using restriction-fragment-length polymorphism (RFLP) analysis of at least one isolate from every patient with confirmed tuberculosis at a major hospital in the Bronx, New York, from December 1, 1989, through December 31, 1992. Medical records and census-tract data were reviewed for relevant clinical, social, and demographic data. Results: Of 130 patients with tuberculosis, 104 adults (80 percent) had complete medical records and isolates whose DNA fingerprints could be evaluated. Isolates from 65 patients (62.5 percent) had unique RFLP patterns, whereas isolates from 39 patients (37.5 percent) had RFLP patterns that were identical to those of an isolate from at least 1 other study patient; the isolates in the latter group were classified into 12 clusters. Patients whose isolates were included in one of the clusters were inferred to have recently transmitted disease. Independent risk factors for having a clustered isolate included seropositivity for the human immunodeficiency virus (HIV) (odds ratio for Hispanic patients, 4.31; P = 0.02; for non-Hispanic patients, 3.12; P = 0.07), Hispanic ethnicity combined with HIV seronegativity (odds ratio, 5.13; P = 0.05), infection with drug-resistant tuberculosis (odds ratio, 4.52; P = 0.005), and younger age (odds ratio, 1.59; P = 0.02). Residence in sections of the Bronx with a median household income below $20,000 was also associated with having a clustered isolate (odds ratio, 3.22; P = 0.04). Conclusions: In the inner-city community we studied, recently transmitted tuberculosis accounts for approximately 40 percent of the incident cases and almost two thirds of drug-resistant cases. Recent transmission of tuberculosis, and not only reactivation of latent disease, contributes substantially to the increase in tuberculosis. (N Engl J Med 1994;330:1710-6). [ABSTRACT FROM AUTHOR]