Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.
Lancet Infect Dis. 2018 Apr;18(4):431-440. doi: 10.1016/S1473-3099(18)30004-5. Epub 2018 Jan 8.
The 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.
On 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.
Between 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.
Our 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.
The 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).
在欧洲，因逃避苦难而寻求避难的人群中结核病爆发的风险加剧。我们描述了欧洲对来自非洲之角和苏丹的患者中耐多药结核病爆发的跨国界应对措施。
2016 年 4 月 29 日和 5 月 30 日，在瑞士和德国国家分枝杆菌参考实验室分别对 4 例耐多药结核病患者确诊后，独立启动了暴发调查。在这项分子流行病学研究中，我们前瞻性地根据 24 位基因间散在重复单位-可变数量串联重复（MIRU-VNTR）谱、对异烟肼、利福平、乙胺丁醇、吡嗪酰胺和卷曲霉素的表型耐药性以及相应的耐药性突变，定义了暴发病例。我们对所有结核分枝杆菌分离株进行全基因组测序，并使用五个单核苷酸多态性（SNP）阈值对其进行聚类。我们从欧洲疾病预防与控制中心收集了宿主国家的流行病学数据。
2016 年 2 月 12 日至 2017 年 4 月 19 日期间，7 个欧洲国家共诊断出 29 例耐多药结核病患者。所有患者均来自非洲之角或苏丹，所有分离株相隔两个或更少的 SNP。22（76%）例患者报告了他们的旅行路线，路线之间存在明显的时空重叠。我们从非洲之角发现了另外 29 例与暴发相关的 MIRU-VNTR 相关病例，但所有病例与暴发相隔五个或更多的 SNP。然而，所有 58 株分离物均共享卷曲霉素耐药相关 tlyA 突变。
我们的数据表明，源病例与在索马里北部或吉布提流行的结核分枝杆菌克隆有关，并且可能在到达欧洲之前的途中发生了传播。我们假设共享的 tlyA 突变是一种耐药突变和系统发育标记，这是结核分枝杆菌 sensu stricto 中的首例。
瑞士联邦公共卫生办公室、苏黎世大学、惠康信托基金会、英国国家健康研究所（NIHR）牛津生物医学研究中心（BRC）、医学研究委员会、BELTA-TBnet、欧盟、德国感染研究中心和莱布尼茨肺部进化医学科学园区（EvoLUNG）。
