手足口病在亚太地区广泛流行，近4年在我国发病数始终位列法定报告传染病首位，严重威胁儿童健康。为阐述肠道病毒肠道病毒71型（EV71）和柯萨奇病毒A16型（CV-A16）所致手足口病的疾病负担，课题组将开展固定队列，基于人群的儿童血清流行病学前瞻性研究。研究内容包括：⑴建立1、2、3、4、5和6-9岁组6个队列，在2013年9月-2016年9月期间手足口病非流行季节开展7次血清学调查；⑵建立新生儿及其母亲配对队列，在出生时、2、4、6、12、24、36月龄进行血清学调查；⑶采用统一问卷收集研究对象信息，并采集流行高峰前后配对血清进行EV71和CV-A16中和抗体检测；⑷监测上述队列3年间手足口病发病情况，并采集病例粪便、肛拭子和咽拭子进行肠道病毒核酸检测。本研究将回答＜10岁儿童手足口病疾病负担、EV71和CV-A16的新感染发生率、中和抗体动力学变化和交叉保护水平等关键科学问题，为制定EV71疫苗免疫策略提供科学依据。

Hand, foot, and mouth disease (HFMD) is widespread across the Asia-Pacific region. Since 2009, the number of reported cases has been the 1st rank among the 39 notifiable infectious diseases in China. HFMD is an important public health issue, affecting millions of children's health every year. To illustrate the disease burden of HFMD caused by enterovirus 71 (EV71) and coxsackievirus A16 (CV-A16), a prospective population-based sero-epidemiological study will be conducted. First, 7 serological surveys will be conducted in non-epidemic seasons of HFMD between September 2013 and August 2016 among 6 cohorts. The 6 cohorts are 6 age groups of children which are 1, 2, 3, 4, 5 and 6-9 years old respectively. Second, a neonate-mother paired cohort will be established and sero-surveys will be undergone at the neonate born, 2, 4, 6, 12, 24 and 36 months separately. In each sero-survey, a standardized questionnaire will be administered to each study participant, and a serum sample will be collected to test EV71 and CV-A16 neutralizing antibody titer by neutralizing assays. Forth, the incidence of HFMD of the above cohorts will be monitored during the three years of follow-ups, and feces, rectal swabs and throat swabs of HFMD patients will be collected for enterovirus nucleic acid detection by real-time RT-PCR. This study aims to estimate the disease burden of HFMD in children younger than 10 years old and the sero-incidence rate of EV71 and CV-A16 infections after each HFMD epidemic, and explore dynamics of neutralizing antibody, and cross-protection between EV71 and CV-A16 infections. Our results will serve to provide scientific evidences for the formulation of EV71 immunization strategy.