Dabritz Haydee A, Hill Karen K, Barash Jason R, Ticknor Lawrence O, Helma Charles H, Dover Nir, Payne Jessica R, Arnon Stephen S
Infant Botulism Treatment and Prevention Program, Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond.
Bioscience Division.
J Infect Dis. 2014 Dec 1;210(11):1711-22. doi: 10.1093/infdis/jiu331. Epub 2014 Jun 12.
Infant botulism (IB), first identified in California in 1976, results from Clostridium botulinum spores that germinate, multiply, and produce botulinum neurotoxin (BoNT) in the immature intestine. From 1976 to 2010 we created an archive of 1090 BoNT-producing isolates consisting of 1012 IB patient (10 outpatient, 985 hospitalized, 17 sudden death), 25 food, 18 dust/soils, and 35 other strains.
The mouse neutralization assay determined isolate toxin type (56% BoNT/A, 32% BoNT/B). Amplified fragment-length polymorphism (AFLP) analysis of the isolates was combined with epidemiologic information.
The AFLP dendrogram, the largest to date, contained 154 clades; 52% of isolates clustered in just 2 clades, 1 BoNT/A (n=418) and 1 BoNT/B (n=145). These clades constituted an endemic C. botulinum population that produced the entire clinical spectrum of IB. Isolates from the patient's home environment (dust/soil, honey) usually located to the same AFLP clade as the patient's isolate, thereby identifying the likely source of infective spores. C. botulinum A(B) strains were identified in California for the first time.
Combining molecular methods and epidemiological data created an effective tool that yielded novel insights into the genetic diversity of C. botulinum and the clinical spectrum, occurrence, and distribution of IB in California.
婴儿肉毒中毒(IB)于1976年在加利福尼亚首次被发现,是由肉毒梭菌孢子在未成熟肠道中发芽、繁殖并产生肉毒神经毒素(BoNT)所致。从1976年到2010年,我们建立了一个包含1090株产BoNT菌株的档案库,其中包括1012株IB患者菌株(10例门诊患者、985例住院患者、17例猝死患者)、25株食品菌株、18株灰尘/土壤菌株和35株其他菌株。
小鼠中和试验确定菌株的毒素类型(56%为BoNT/A型,32%为BoNT/B型)。对菌株进行扩增片段长度多态性(AFLP)分析,并结合流行病学信息。
AFLP系统树图是迄今为止最大的,包含154个分支;52%的菌株聚集在仅2个分支中,1个BoNT/A分支(n = 418)和1个BoNT/B分支(n = 145)。这些分支构成了一个地方性肉毒梭菌种群,产生了IB的整个临床谱。来自患者家庭环境(灰尘/土壤、蜂蜜)的菌株通常与患者的菌株位于同一AFLP分支中,从而确定了感染性孢子的可能来源。首次在加利福尼亚州鉴定出A(B)型肉毒梭菌菌株。
将分子方法和流行病学数据相结合,创造了一种有效的工具,对肉毒梭菌的遗传多样性以及加利福尼亚州IB的临床谱、发生情况和分布提供了新的见解。