The use of restriction fragment length polymorphism (RFLP) analysis for epidemiological studies of tuberculosis in developing countries

Abstract

DNA fingerprinting, of which restriction fragment length polymorphism (RFLP) typing is the most common method used, has permitted novel investigations of the epidemiology and pathogenesis of tuberculosis. The use of IS6110, an insertion sequence which is present in Mycobacterium tuberculosis, is generally considered to be the standard RFLP method, but other molecular typing techniques may be used as adjuncts in selected circumstances. A number of epidemiologic studies using RFLP typing have been done in both industrialized and developing countries. The major findings include the confirmation or identification of chains of transmission (of both drug-sensitive and drug-resistant strains of tuberculosis), distribution of strain clusters within populations, differentiation of relapse from exogenous reinfection, better understanding of the pathogenesis of tuberculosis, identification of laboratory cross-contamination, and insight into the molecular evolution of the species. For developing countries, where the burden of tuberculosis is greatest, three major areas of investigation for the use of RFLP analysis in epidemiologic studies of tuberculosis have been identified: 1) community transmission, 2) nosocomial transmission, and 3) human immunodeficiency virus (HIV)-related tuberculosis. Elements of protocols are suggested which can be used by investigators to perform well-designed epidemiologic studies which will be relevant to developing countries and which are likely to have an impact on control programmes in these settings.