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).

We present the case of a patient with catheter-related infection caused by Delftia tsuruhatensis, a newly described species closely related to Delftia acidovorans (formerly Comamonas acidovorans). To date, D. tsuruhatensis has not been described as a pathogen. To the best of our knowledge, this is the first report describing D. tsuruhatensis as the causative agent of a human infection. Case reportA 53-year-old woman with severe idiopathic pulmonary hypertension presented with flu-like symptoms, chills and a reduced general condition at our outpatient clinic. She had been treated for the past 18 months with continuous intravenous iloprost via a non-tunnelled central venous catheter (CVC) lying in the right vena subclavia. Her body temperature was 37.1 u C, heart rate was 86 beats min 21 , blood pressure was 140/83 mmHg, the respiratory rate was 15 breaths min 21 and the arterial oxygen saturation was 96 % while breathing 2 l oxygen min 21 via a transtracheal catheter. The lungs were clear on auscultation and there was no heart murmur. There was no erythema, pus or tenderness at the site of the CVC. Routine blood analyses were initially normal except for mild leukocytosis; the Creactive protein rose to a maximum of 47 mg l 21 within 3 days and declined thereafter. Blood cultures were obtained through the CVC and a peripheral line. The CVC was subsequently removed and its tip was sent for culture. Blood cultures drawn into BacT/ALERT FA/FN bottles were processed with the BacT/ALERT 3D system (bioMérieux). Aerobic bottles inoculated with blood from the catheter became positive after 11 h and those inoculated with blood from the peripheral line became positive after 28 h. Anaerobic bottles remained negative. A differential time to positivity of 17 h clearly pointed to a catheter-related infection at that point. Subcultures as well as cultures from the removed CVC tip on 5 % sheep blood agar and MacConkey agar showed growth of oxidasepositive, nonpigmented, lactose-nonfermenting colonies.Microscopy revealed long, straight, Gram-negative rods. Identification was attempted with the VITEK 2 colorimetric card (bioMérieux) and Delftia acidovorans was identified with a probability level of 98 %. To confirm identification according to in-house policies, 16S rRNA gene sequencing was done. The 59-end of the 16S rRNA gene was amplified using universal bacterial 16S rRNA gene primers as described before (Bosshard et al., 2004). The PCR product was sequenced and homology analysis was performed using SmartGene IDNS. A homology of .99 % with a minimum of 0.5 % difference with the second homologous species allows for identification at the species level according to Clinical and Laboratory Standards Institute (CLSI) approved guidelines for identification of bacteria by 16S rRNA gene target sequencing, which are widely used (Janda & Abbott, 2007). The obtained sequence of 747 bp located at the 59-end of the 16S rRNA gene showed 100 % identity to the type strains of Delftia tsuruhatensis (GenBank accession no. AB075017) and Delftia lac...

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Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin-transmission vs sporadic appearance-of these variants determines their impact on ART needs to be further explored.