2010年上海部分地区440例手足口病病例的病原谱及分子流行病学分析

摘要

本文旨在对上海部分地区2010年440例临床手足口病病例进行病原谱及分子流行病学特征分析,为上海地区手足口病防治工作提供依据.采集4所哨点医院440例手足口病病例的咽拭子、粪便和脑脊液标本,进行肠道病毒核酸检测、反转录-聚合酶链反应扩增、DNA测序和序列分子系统发生树分析.结果显示,引起手足口病的肠道病毒主要为肠道病毒71型(EV71)和柯萨奇病毒A组16型(CA16),其次为CA6和CA10.夏季(5～8月)为EV71和CA16感染的高发期.CA6和CA10阳性病例构成比随季节而变化,冬季达高峰.病毒的VP1基因序列分析显示,病例标本中的EV71均属CAa亚型,与国内近年各地流行株高度同源；而本研究中10例上海病例的CA6序列与2008年导致芬兰手足口病疫情的毒株有高度的核苷酸同源性(＞96％),CA10序列与2009年山东和2010年云南代表株最为接近,在系统发生树中分布于亚洲毒株基因簇.本研究提示,应重视对上海地区导致手足口病的非EV71非CA16肠道病毒的监测,深入分析CA6和CA10的流行趋势,以防范其快速传播.%The present paper aims to analyze the pathogenic spectrum and molecular epidemiology characteristics of 440 cases of hand, foot and mouth disease (HFMD) from certain areas of Shanghai in 2010, and to provide a basis for preventing and controlling HFMD in Shanghai. Throat swabs,stool samples and cerebrospinal fluid were collected from 440 HFMD cases. To detect and analyze the etiological agents involved in HFMD, reverse transcriptase-polymerase chain reaction (RT-PCR), DNA sequencing and phylogenetic tree analysis were performed. Enterovirus 71 (EV71) was detected most frequently, followed by coxsackievirus A16 (CA16), CA6 and CA10. The peak of detection rate of EV71 and CA16 appeared during the summer (May to August). However, the detection frequency of CA6 and CA10 changed along with the seasons, and reached the peak in winter. VP1 gene sequence analysis of these viruses showed that all EV71 strains belonged to C4a subtype, and highly homologous to the domestic epidemic strains circulating in China in recent years. The sequences of 10 Shanghai CA6 strains in this study had a high degree of nucleotide homology (more than 96%) with those strains leading to HFMD outbreak in Finland in 2008, while the phylogenetic tree based on CA10 sequences showed that there were close relationships among Shanghai strains, 2009 Shandong strains and 2010 Yunnan strains, all of which distributed in Asian evolutionary lineage. The study suggested that monitoring on the non-EV71 and non-CA16 enteroviruses which also cause HFMD should be strengthened, and further research on CA6 and CA10 should be carried out to prevent them from spreading quickly.