Utility of molecular epidemiology of tuberculosis

D. van Soolingen
1998 European Respiratory Journal  
Just 10 yrs ago it was still generally accepted that bacteria of the Mycobacterium tuberculosis complex were so highly conserved, that phage typing, which could distinguish about 20 different phage types, was all one needed to study the epidemiology of tuberculosis [1] [2] [3] [4] . From the late 1980s, repetitive deoxyribonucleic acid (DNA) sequences have been described, which are associated with different levels of genetic polymorphism [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]
more » ... ] . In 1990, the highly similar insertion sequences IS986 and IS6110 were found in the genome of M. tuberculosis [10, 13, 14] and, when these elements were applied in restriction fragment length polymorphism (RFLP) typing, they provided an unprecedented degree of discrimination between M. tuberculosis complex isolates. When IS986-based RFLP typing was used in 1990 to confirm for the first time a suspected outbreak of tuberculosis in the Netherlands [8], interest in the molecular epidemiology of tuberculosis was awakened. RFLP typing seemed ideal for studying small-scale transmission of M. tuberculosis, such as outbreaks in institutions, hospitals or among families [16, [18] [19] [20] [21] [22] . Within a remarkably short period of time the utility of fingerprinting for managing outbreaks was established. The RFLP typing technique was optimized and standardized to enable computer-assisted analysis of DNA fingerprints [23, 24] . This facilitated large-scale epidemiological studies. However, the utility and reliability of large-scale, or even routine, application of DNA fingerprinting in tuberculosis control is still debatable and hinges on whether clustering of DNA fingerprints among patients' isolates does truly reflect transmission of M. tuberculosis. If clustering of cases on the basis of DNA fingerprinting does indeed reflect recent transmission, then the results from the population-based studies in San Francisco [25], New York [26], the Netherlands [27] and Denmark [28] would suggest that ongoing transmission contributes much more to the overall tuberculosis disease incidence in de-veloped countries than has been assumed previously. However, how do the results of these studies fit with other findings of the transmission of M. tuberculosis between different groups? Both SMALL et al. [25] (in San Francisco, USA) and VAN DEUTEKOM et al. [29] (in Amsterdam, the Netherlands) found that only 5-10% of the links indicated by DNA fingerprinting, were also found by conventional contact tracing. Furthermore, in the molecular epidemiological study in Bern, Switzerland, conducted by GENEWEIN et al. [30] cases in totally different social groups were in the same DNA fingerprint clusters.
doi:10.1183/09031936.98.11040795 pmid:9623677 fatcat:4ynr6eibpjd57lhzwbmyzs2xcu