title: Extent and origin of resistance to antituberculosis drugs in the Netherlands, 1993 to 2011.
abstract: The elimination of tuberculosis (TB) is threatened by an apparent increase in the level of resistance in Mycobacterium tuberculosis. In the Netherlands, where the majority of TB patients are migrants, resistance may also be increasing. We conducted a retrospective study, using 18,294 M. tuberculosis isolates from TB cases notified between 1993 and 2011. We investigated the trends in antituberculosis drug resistance, focusing on the country of birth of the patients and whether resistance had developed during treatment or was the result of transmission of resistant M. tuberculosis strains. For both scenarios, we determined whether this had happened in or outside the Netherlands. Antituberculosis drug resistance was found in 13% of all cases analysed and showed an increasing trend among patients who had been born in the Netherlands (p<0.001) and a decreasing trend among foreign-born (p=0.02) over the study period. Since 2005, the proportion of M. tuberculosis resistant strains among all strains tested has increased in both groups (p=0.03 and p=0.01, respectively). Overall, we found a significantly increasing trend when excluding streptomycin resistance (p<0.001). The trend was most markedly increased for isoniazid resistance (p = 0.01). Although resistance was mainly due to transmission of resistant strains, mostly outside the Netherlands or before 1993 (when DNA fingerprinting was not systematically performed), in some cases (n=45), resistance was acquired in the Netherlands. We conclude that antituberculosis drug resistance is increasing in the Netherlands, mostly related to migration from high TB-incidence countries, but also to domestic acquisition.
authors.affiliation: Epidemiology and Surveillance, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Ruesen
authors.forename: A B
authors.initials: AB
authors.lastname: van Gageldonk-Lafeber
authors.forename: G
authors.initials: G
authors.lastname: de Vries
authors.forename: C G
authors.initials: CG
authors.lastname: Erkens
authors.forename: J
authors.initials: J
authors.lastname: van Rest
authors.forename: H
authors.initials: H
authors.lastname: Korthals Altes
authors.forename: H
authors.initials: H
authors.lastname: de Neeling
authors.forename: M
authors.initials: M
authors.lastname: Kamst
authors.forename: D
authors.initials: D
authors.lastname: van Soolingen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000995:Antitubercular Agents / Q000627:therapeutic use; D016000:Cluster Analysis; D016172:DNA Fingerprinting; D005260:Female; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D009426:Netherlands / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D012959:Socioeconomic Factors; D013307:Streptomycin / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D013307:Streptomycin