Abstract
SummaryBackgroundThe risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan.MethodsOn April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control.FindingsBetween Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation.InterpretationOur data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto.FundingThe Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG).
Highlights
WHO’s 2017 global tuberculosis report[1] contained the sobering news that the tuberculosis epidemic is larger than previously thought
We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five single nucleotide polymorphisms (SNPs) from the outbreak
We describe how a European response to a cluster of multidrug-resistant tuberculosis in patients from the Horn of Africa was jointly guided by rapid whole-genome sequencing (WGS) of Mycobacterium tuberculosis isolates, epidemiological investigations, and data sharing
Summary
WHO’s 2017 global tuberculosis report[1] contained the sobering news that the tuberculosis epidemic is larger than previously thought. Among an estimated 10·4 million new cases were 600 000 patients with rifampicin resistance or multidrug-resistant tuberculosis in 2016. The global burden of disease is unequally shared, population movement does lead to appearance of strains normally associated with one country or region in another country or region—a phenomenon historically linked to human migration, trade, and conquest.[2] War, government oppression, and economic inequality are the modern day forces driving people to Europe from its southern borders.[3] Climate change is likely to amplify these push factors in years to come.[4] In 2015 alone, more than 1 000 000 people did the dangerous journey to Europe in search of sanctuary or a better life than before.[5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
