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[Findings and ongoing research in the molecular epidemiology of tuberculosis]
Dick van Soolingen1, Kristin Kremer
1National Institute for Public Health and the Environment, BA Bilthoven, The Netherlands. d.van.soolingen@rivm.nl
Settings:
While in The Netherlands the organization of tuberculosis (TB) control in the era of elimination is being discussed, worldwide TB is still a major problem.
Objectives:
To highlight findings and ongoing research in the molecular epidemiology of tuberculosis.
Findings:
In the past decade, many studies have pointed out the significance of the Beijing strains in the worldwide tuberculosis epidemic. In South-East Asia, as well as the former USSR Republics, the Baltic States and South Africa, Beijing strains are emerging and associated with (multi-drug) resistance. Recent research in China has pointed out that the average proportion of Beijing genotype strains in 10 provinces amounts 73%, but varies significantly by region. The highest density was observed in the Beijing region; 93%. Currently, research is focused on the evolutionary development of Beijing strains. Two evolutionary lineages were distinguished and the "modern" lineage seems associated with spread, despite BCG vaccination in Vietnam. A project of the European Union with 11 international partners is trying to disclose the evolutionary adaptation of M. tuberculosis in response to vaccination and exposure to anti-tuberculosis drugs. Also in Europe the interest in the Beijing genotype has recently been strongly awakened. While 6-7% of the susceptible isolates are of this genotype, 85% of the MDR-TB transmission in Europe can be attributed to the spread of Beijing strains. Moreover, one cluster of 174 MDR-TB cases has been detected and this re-emphasizes that particular genotypes are capable of gaining poly-resistance without losing fitness. It seems, therefore, important to have more studies on the dynamics in the population structure of M. tuberculosis worldwide. In the presentation examples of such studies will be discussed. Since 1993, IS6110 restriction fragment length polymorphism typing has gained recognition as the gold standard in the molecular epidemiology of tuberculosis. However, although the application of this method has brought significant new insights into the transmission of tuberculosis, it remains technically demanding and time-consuming. Therefore, recently a new standard typing method, the variable numbers of tandem repeat (VNTR) typing, has been proposed in a publication in the J. Clin. Microbiol. In the Netherlands, a large part of the collection of nearly 15,000 M. tuberculosis isolates are currently being retyped with VNTR typing. This is not only meant to evaluate the utility of the new 24 loci VNTR typing, but also to conserve the epidemiological trace of tuberculosis transmission in the past. The first results will be discussed. The role of non-tuberculous mycobacteria (NTM) in the diagnosis and treatment of tuberculosis-like diseases becomes increasingly important in the era of the HIV/AIDS pandemic. In Zambia it was recently shown that only in 50% of the cases diagnosed by Ziehl-Neelsen microscopy and X-ray, M. tuberculosis was isolated in a liquid culture system. In the other cases often only NTM can be cultured. In The Netherlands, particular NTM like M. avium, frequently cause lymphadenitis in children. This infection is normally indicated as "bird tuberculosis". However, with IS1245 RFLP typing it was pointed out that the M. avium isolates from lymphadenitis cases do not represent the bird type M. avium strains, but the M. avium strains typically found in humans and slaughtered pigs: Mycobacterium avium hominissuis.
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