Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK.
Gastrointestinal Bacteria Reference Unit, Public Health England, London, UK.
Lancet Infect Dis. 2015 Aug;15(8):913-21. doi: 10.1016/S1473-3099(15)00002-X. Epub 2015 Apr 27.
Shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). Since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (MSM), in whom transmission is an important component of shigellosis epidemiology in high-income nations. We aimed to use sophisticated subtyping and international sampling to determine factors driving shigellosis emergence in MSM linked to an outbreak in the UK.
We did a large-scale, cross-sectional genomic epidemiological study of shigellosis cases collected from 29 countries between December, 1995, and June 8, 2014. Focusing on an ongoing epidemic in the UK, we collected and whole-genome sequenced clinical isolates of Shigella flexneri serotype 3a from high-risk and low-risk regions, including cases associated with travel and sex between men. We examined relationships between geographical, demographic, and clinical patient data with the isolate antimicrobial susceptibility, genetic data, and inferred evolutionary relationships.
We obtained 331 clinical isolates of S flexneri serotype 3a, including 275 from low-risk regions (44 from individuals who travelled to high-risk regions), 52 from high-risk regions, and four outgroup samples (ie, closely related, but genetically distinct isolates used to determine the root of the phylogenetic tree). We identified a recently emerged lineage of S flexneri 3a that has spread intercontinentally in less than 20 years throughout regions traditionally at low risk for shigellosis via sexual transmission in MSM. The lineage had acquired multiple antimicrobial resistance determinants, and prevailing sublineages were strongly associated with resistance to the macrolide azithromycin. Eight (4%) of 206 isolates from the MSM-associated lineage were obtained from patients who had previously provided an isolate; these serial isolations indicated atypical infection patterns (eg, reinfection).
We identified transmission-facilitating behaviours and atypical course(s) of infection as precipitating factors in shigellosis-affected MSM. The intercontinental spread of antimicrobial-resistant shigella through established transmission routes emphasises the need for new approaches to tackle the public health challenge of sexually transmitted infections in MSM.
Wellcome Trust (grant number 098051).
志贺菌病是一种急性、严重的细菌性结肠炎，在高收入国家，通常与前往高风险地区（非洲、亚洲和拉丁美洲）有关。自 20 世纪 70 年代以来，志贺菌病也被报道为男男性行为者（MSM）中的性传播感染，在这些国家，传播是志贺菌病流行病学的一个重要组成部分。我们旨在利用复杂的亚型分析和国际采样来确定与英国疫情相关的 MSM 中志贺菌病出现的驱动因素。
我们对 1995 年 12 月至 2014 年 6 月 8 日期间从 29 个国家收集的志贺菌病病例进行了大规模的、跨国家的基因组流行病学研究。我们专注于英国正在进行的疫情，从高风险和低风险地区（包括与旅行和男男性行为相关的病例）采集并全基因组测序了福氏志贺菌 3a 血清型的临床分离株。我们研究了地理、人口统计学和临床患者数据与分离株的抗生素敏感性、遗传数据和推断的进化关系之间的关系。
我们获得了 331 株福氏志贺菌 3a 血清型的临床分离株，其中 275 株来自低风险地区（44 株来自前往高风险地区的个体），52 株来自高风险地区，4 株来自外群样本（即密切相关但遗传上不同的分离株，用于确定系统发育树的根）。我们发现了一个最近出现的福氏志贺菌 3a 谱系，它在不到 20 年的时间里通过 MSM 的性传播在传统上低发地区跨越了各大洲。该谱系获得了多种抗生素耐药决定因素，流行的亚谱系与对大环内酯类抗生素阿奇霉素的耐药性密切相关。206 株来自 MSM 相关谱系的分离株中有 8 株（4%）来自以前提供过分离株的患者；这些连续分离株表明存在非典型感染模式（例如再感染）。
我们确定了促进传播的行为和感染的非典型过程（如再感染）作为受感染 MSM 中志贺菌病的诱发因素。通过既定的传播途径传播的耐抗生素志贺菌的洲际传播强调了需要采取新的方法来应对 MSM 中性传播感染的公共卫生挑战。
惠康信托基金会（098051 号赠款）。
