Abstract
Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders.
Highlights
Tuberculosis (TB) and its multi- and extensively drugresistant forms (M/XDR-TB) are a major global public health concern
The investigation team consisted of the national TB contact points for World Health Organization (WHO) and European Centre for Disease Prevention and Control (ECDC) or representatives acting on their behalf, the National Reference Laboratories (NRLs) and the responsible local public health authorities in Austria, Romania and Germany
Cases were included without restriction in time when the isolate, collected in any of the three countries and recorded in any typing databases by the NRLs, shared the same spoligotype and 24-loci MIRU-VNTR pattern as in the initial cluster detected in Austria in March 2014
Summary
Tuberculosis (TB) and its multi- and extensively drugresistant forms (M/XDR-TB) are a major global public health concern. Where second-line drug susceptibility testing (DST) is available, (pre)XDR-TB is frequently detected [2,3]. These patients have a high risk of death [3]. TB transmission can be traced by classic and by molecular epidemiological methods. Classic methods include contact and source case investigations based on patient interviews. Molecular methods examine the genetic relationship between the isolates of the Mycobacterium tuberculosis complex. Common genotyping methods include spacer oligonucleotide typing (spoligotyping) and 24-loci mycobacterial interspersed repetitive units variable number of tandem repeats (24-loci MIRU-VNTR) analysis, both targeting specific small parts of the genome.
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