Methodological and Clinical Aspects of the Molecular Epidemiology of Mycobacterium tuberculosis and Other Mycobacteria

Abstract

Molecular typing has revolutionized epidemiological studies of infectious diseases, including those of a mycobacterial etiology. With the advent of fingerprinting techniques, many traditional concepts regarding transmission, infectivity, or pathogenicity of mycobacterial bacilli have been revisited, and their conventional interpretations have been challenged. Since the mid-1990s, when the first typing methods were introduced, a plethora of other modalities have been proposed. So-called molecular epidemiology has become an essential subdiscipline of modern mycobacteriology. It serves as a resource for understanding the key issues in the epidemiology of tuberculosis and other mycobacterial diseases. Among these issues are disclosing sources of infection, quantifying recent transmission, identifying transmission links, discerning reinfection from relapse, tracking the geographic distribution and clonal expansion of specific strains, and exploring the genetic mechanisms underlying specific phenotypic traits, including virulence, organ tropism, transmissibility, or drug resistance. Since genotyping continues to unravel the biology of mycobacteria, it offers enormous promise in the fight against and prevention of the diseases caused by these pathogens. In this review, molecular typing methods for Mycobacterium tuberculosis and nontuberculous mycobacteria elaborated over the last 2 decades are summarized. The relevance of these methods to the epidemiological investigation, diagnosis, evolution, and control of mycobacterial diseases is discussed.

FIG 1

Distribution of the three major types of genetic loci, i.e., mycobacterial interspersed repetitive units (MIRUs) (MIRU20 [1a] and MIRU40 [1b]), the direct-repeat (DR) locus (2), and IS6110 (3), within the chromosome of a hypothetical Mycobacterium tuberculosis strain.

FIG 2

Variation of LM-PCR methods used for molecular typing of M. tuberculosis strains. For details, see the text. (Adapted from reference with permission of the International Union against Tuberculosis and Lung Disease [copyright The Union].)

FIG 3

Worldwide distribution of lineages contained in the SITVIT2 database. AFRI, M. africanum; BOV, M. bovis; TUR, Turkey lineage; CAM, Cameroon lineage; Unk, unknown.