Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Lancet Microbe. 2021 Oct;2(10):e498-e507. doi: 10.1016/S2666-5247(21)00128-2.
has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England.
In this retrospective observational study, we analysed consecutive whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [SNPs]).
2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0·38). High-density phylogenetic clusters were randomly distributed over a wide geographical area. Most isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age (adjusted odds ratio 1·14 per 10 years, 95% CI 1·04-1·26), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis.
Previously identified widely disseminated dominant clones of are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis health-care-associated niche.
The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.
有报道称，在囊性纤维化患者的医疗机构中，很容易发生传播，这已成为一个重要的临床问题。我们将常规收集的全基因组测序和医疗保健使用数据进行了关联，旨在调查在英国，囊性纤维化患者和非囊性纤维化患者的感染中，这种传播解释了多大程度的感染。
在这项回顾性观察性研究中，我们分析了来自英格兰的连续全基因组测序数据（从 2015 年 2 月初到 2019 年 11 月 14 日），以识别基因组相似的分离株。通过与国家医疗保健使用数据库的链接，调查了患者之间可能的接触。多变量回归分析用于调查与获得基因组聚类株（基因组距离<25 个单核苷酸多态性[SNP]）相关的因素。
来自 906 名患者的 2297 个分离株作为英国公共卫生署常规诊断服务的一部分进行了全基因组测序。在包含 10 个或更多患者分离株的 14 个基因组簇中，除了一个外，均包含囊性纤维化患者和非囊性纤维化患者。囊性纤维化患者的聚类分离株与非囊性纤维化患者一样常见（431 名患者中有 258 名[60%]）（513 名患者中有 322 名[63%]；p=0·38）。高密度系统发育聚类随机分布在广泛的地理区域。大多数与潜在传播相一致的最接近遗传邻居的分离株没有可识别的相关流行病学接触。具有聚类分离株与年龄增加独立相关（调整后的优势比为每 10 年 1.14，95%CI 1.04-1.26），但与住院或门诊时间无关。我们发现了两对具有高度遗传差异的囊性纤维化同胞分离株和一对具有密切相关分离株的兄弟姐妹，以及 25 名未感染的囊性纤维化假定家庭接触者。
以前确定的广泛传播的优势克隆不是仅限于囊性纤维化患者，并且发生在其他慢性呼吸道疾病中。尽管我们的分析显示了一小部分病例无法排除人与人之间的传播，但它并不能支持这是在英格兰全国范围内传播的主要机制。总体而言，这些数据应使患者和临床医生放心，从医疗机构中的其他患者获得感染的风险相对较低，并促使未来的研究努力集中在确定囊性纤维化医疗保健相关利基之外的感染途径上。
英国国家卫生研究院、英国健康数据研究中心、惠康基金会、医学研究理事会和英国公共卫生署。
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