Methodological problems in the molecular epidemiology of tuberculosis

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.