Molecular epidemiology of tuberculosis in Denmark in 1992

Abstract

The incidence of tuberculosis (TB) is increasing all over the world, including in countries with a high standard of living and good social security. Denmark represents such a region. Furthermore, it is a small country (5 million inhabitants) with a long tradition in TB control, including a centralization of the bacteriological diagnostic facility. The present study was intended to analyze the transmission of Mycobacterium tuberculosis in a country in which TB has low endemicity by a combination of conventional epidemiological approaches and DNA fingerprinting techniques, whereby individual bacterial strains can be traced. M. tuberculosis isolates from 92% of all new cases of bacteriologically verified TB in Denmark during 1992 were subjected to IS6110 DNA fingerprinting to visualize the DNA restriction fragment length polymorphism (RFLP) patterns of the isolated strains. The data obtained from the RFLP analyses were interpreted by using demographic data, such as age, sex, ethnicity, and residence, for the patients. The risk factors among the patients for being part of an active chain of transmission, as opposed to demonstrating reactivation of a previously acquired latent infection, were estimated by statistical analyses. The magnitude of TB transmission in 1992 in Denmark was determined, and transmitted infections were shown to comprise at least one quarter of the total number of cases. Almost half of the TB cases involved patients of foreign origin. However, most of these isolates showed unique DNA fingerprint patterns and were rarely part of an active chain of transmission. The major chains of recent transmission were localized to distinct geographical regions in the country. TB is frequent among immigrants, especially from Asia and Africa, but it is apparently readily suspected, diagnosed, and treated by the health care system. Danish patients with pulmonary symptoms are not primarily suspected to have TB and, therefore, play an important role in recent TB transmission in Denmark.

Comparison of Methods Based on Different Molecular Epidemiological Markers for Typing of Mycobacterium tuberculosis Complex Strains: Interlaboratory Study of Discriminatory Power and Reproducibility

“…This study shows that strain typing of M. tuberculosis complex strains by RFLP was reproducible for all 31 duplicate samples tested, irrespective of the DNA probe used. Recommendations for a standardized method of strain typing for M. tuberculosis were formulated in 1993 (48), and in virtually all published studies, investigators have complied with these recommendations (1,44,61). Therefore, the results of this study suggest that fingerprints generated in different laboratories can be compared, thus allowing the investigation of the prevalence of various types or genotypes in different regions and the trace of interregional transmission of M. tuberculosis.…”

“…Due to its apparent mobility and its common presence in, on average, large numbers of copies, IS6110 is widely used as a genetic marker to differentiate clinical M. tuberculosis isolates for epidemiological investigations. This includes investigations of the transmission of tuberculosis in hospitals (2,10), residential facilities for human immunodeficiency virus-infected people (7), prisons (19), and in larger populations (1,44,61). In contrast to IS6110, IS1081 is almost invariably present in five to seven copies per genome, and this IS has been found to be associated with limited DNA polymorphism (6,54).…”

False-positive results from cultures of Mycobacterium tuberculosis due to laboratory cross-contamination confirmed by restriction fragment length polymorphism

“…However, DNA fingerprinting of Danish TB isolates from 1992 to 1995 has now been completed. Though large clusters of identical strains are actually found (1,16,17), our data suggest that series of positive specimens exhibiting identical RFLP patterns are very unlikely. In 2 of the 38 cases, the identical patterns were most likely due to an epidemiological relation between the patients, thus sustaining the microbiological diagnosis.…”

Occupational tuberculosis following extremely short exposure

“…Since 1992 all first‐time culture‐confirmed TB cases in Denmark have been subjected to genotyping at the International Reference Laboratory of Mycobacteriology at Statens Serum Institut, Copenhagen, Denmark, using the IS 6110 ‐RFLP technique (7). The data and strain collection comprise The Danish TB Subtyping Database, containing >6000 DNA patterns from TB patients nationwide (2, 8, 9). The MT strain from this patient was subjected to genotyping and the DNA pattern of the isolate was compared to patterns in The Danish TB Subtyping Database using the software Bionumerics 4.61.…”