A four-year nationwide molecular epidemiological study in Estonia: Risk factors for tuberculosis transmission

Abstract

T he smallest Baltic country, Estonia (population 1.3 million) suffers from a relatively high rate of tuberculosis (TB) in the European context, and is among the world's 27 high multidrug-resistant TB (MDR-TB) burden countries. 1 The TB incidence rate declined from 36.6 per 100 000 population in 2007 to 21.6/100 000 in 2012. However, a quarter (25.5%) of the 234 new cases reported in 2012 were MDR-TB (defined as resistance to at least isoniazid and rifampicin [RMP]), of which 6.6% were extensively drug-resistant TB (XDR-TB, defined as MDR-TB plus resistance to a fluoroquinolone and one of the three injectables). 2 Recent studies in Estonia showed that human immunodeficiency virus (HIV) infection, homelessness and alcohol abuse significantly increase the risk for XDR-TB. 3 However, the extent to which these determinants contribute to TB transmission is unknown.Molecular epidemiology has contributed significantly to our understanding of TB transmission. Studies using this approach have helped to determine what proportion of active TB is due to reinfection or reactivation and to identify risk factors for TB transmission within communities. 4 For such studies, the most commonly used methods for Mycobacterium tuberculosis DNA fingerprinting are insertion sequence (IS) 6110 restriction fragment length polymorphism (RFLP) 5 and 24-locus variable numbers of tandem repeat (VNTR) typing, 6 which were internationally standardised in 1993 and 2006, respectively. VNTR typing has various advantages over RFLP typing, including its ease of use, short turnaround time and digital output format. In addition, several population-based studies have shown that the predictive value of VNTR typing to study TB transmission is similar to that of RFLP typing in different Western European settings. 7,8 The current gold standard in molecular epidemiology of TB is therefore VNTR typing, which produces a numeric pattern enabling the identification of M. tuberculosis strains. 9 It is assumed that patients infected with M. tuberculosis isolates with identical DNA fingerprints are 1) infected with the same M. tuberculosis strain and 2) have infected each other, have a common source of infection or were independently infected by a highly prevalent strain circulating in the community. Conversely, it is assumed that patients who are infected with a strain with a unique DNA fingerprint in a population are either suffering from a reactivation of a previous infection or from infection with a strain that was newly introduced into the population by the patient. Investigators have thus used molecular clustering, defined as matching of identical DNA fingerprints, as an index of TB transmission.The first study to use RFLP DNA fingerprinting results conducted in Estonia showed high clustering rates among MDR-TB isolates, and suggested an association between the Beijing genotype of M. tuberculosis and drug resistance. 10 A later study that compared DNA fingerprints from MDR-TB cases reported in Europe during the years [2003][2004][2005][2006][2007] show...