全基因组测序鉴定出多种艰难梭菌感染源。
Diverse sources of C. difficile infection identified on whole-genome sequencing.
机构信息
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
出版信息
N Engl J Med. 2013 Sep 26;369(13):1195-205. doi: 10.1056/NEJMoa1216064.
BACKGROUND
It has been thought that Clostridium difficile infection is transmitted predominantly within health care settings. However, endemic spread has hampered identification of precise sources of infection and the assessment of the efficacy of interventions.
METHODS
From September 2007 through March 2011, we performed whole-genome sequencing on isolates obtained from all symptomatic patients with C. difficile infection identified in health care settings or in the community in Oxfordshire, United Kingdom. We compared single-nucleotide variants (SNVs) between the isolates, using C. difficile evolution rates estimated on the basis of the first and last samples obtained from each of 145 patients, with 0 to 2 SNVs expected between transmitted isolates obtained less than 124 days apart, on the basis of a 95% prediction interval. We then identified plausible epidemiologic links among genetically related cases from data on hospital admissions and community location.
RESULTS
Of 1250 C. difficile cases that were evaluated, 1223 (98%) were successfully sequenced. In a comparison of 957 samples obtained from April 2008 through March 2011 with those obtained from September 2007 onward, a total of 333 isolates (35%) had no more than 2 SNVs from at least 1 earlier case, and 428 isolates (45%) had more than 10 SNVs from all previous cases. Reductions in incidence over time were similar in the two groups, a finding that suggests an effect of interventions targeting the transition from exposure to disease. Of the 333 patients with no more than 2 SNVs (consistent with transmission), 126 patients (38%) had close hospital contact with another patient, and 120 patients (36%) had no hospital or community contact with another patient. Distinct subtypes of infection continued to be identified throughout the study, which suggests a considerable reservoir of C. difficile.
CONCLUSIONS
Over a 3-year period, 45% of C. difficile cases in Oxfordshire were genetically distinct from all previous cases. Genetically diverse sources, in addition to symptomatic patients, play a major part in C. difficile transmission. (Funded by the U.K. Clinical Research Collaboration Translational Infection Research Initiative and others.).
背景
人们曾认为艰难梭菌感染主要在医疗环境中传播。然而，由于疾病的地方流行，确切的感染源难以确定，干预效果也难以评估。
方法
从 2007 年 9 月到 2011 年 3 月，我们对英国牛津郡医疗机构和社区中所有确诊艰难梭菌感染的有症状患者的分离株进行了全基因组测序。我们根据从 145 名患者的每一例患者的最早和最晚样本中估计的艰难梭菌进化率，比较了分离株之间的单核苷酸变异（SNV）。根据 95%预测区间，在相隔不到 124 天获得的传播性分离株之间，预计有 0 到 2 个 SNV。然后，我们根据住院和社区位置的数据，确定基因相关病例之间的可能流行病学联系。
结果
在评估的 1250 例艰难梭菌病例中，有 1223 例（98%）成功测序。在比较 2008 年 4 月至 2011 年 3 月期间与 2007 年 9 月以后获得的 957 个样本时，共有 333 个分离株（35%）与至少 1 个早期病例的 SNV 不超过 2 个，428 个分离株（45%）与所有早期病例的 SNV 超过 10 个。两组的发病率随时间的下降趋势相似，这表明针对从接触到发病的过渡阶段的干预措施有效。在 SNV 不超过 2 个的 333 例患者（符合传播条件）中，126 例（38%）与另一位患者有密切的医院接触，120 例（36%）与另一位患者没有医院或社区接触。在整个研究过程中，不断发现不同的感染亚型，这表明艰难梭菌有相当大的储存库。
结论
在 3 年期间，牛津郡的 45%艰难梭菌病例与所有以前的病例在基因上是不同的。除了有症状的患者之外，基因上不同的来源在艰难梭菌传播中也起着重要作用。（由英国临床研究合作组织转化感染研究倡议和其他组织资助）。
Zotero 插件