2013～2018年泰安地区手足口病病原学构成及流行病学分析

近年来手足口病(Hand,foot,and mouth disease,HFMD)对我国儿童的健康造成了严重的危害。为了解山东省泰安地区HFMD的感染状况,本研究对2013～2018年度3 043份HFMD标本,应用实时荧光定量PCR进行肠道病毒A组71型(Enterovirus A71,EV-A71)、柯萨奇病毒A组16型(Coxsachievirus A16,CV-A16)和其他肠道病毒(其他EV)的病原体检测和分析。结果显示,肠道病毒检出阳性率为86.82%,确诊病例中其他EV所占比例最高,为42.92%,EV-A71和CV-A16分别占30.62%和26.46%。EV-A71是引起重症HFMD的主要病原,占73.09%。2013～2016年EV-A71和CV-A16为优势病原,占比例达50%以上,在2014年和2016年出现两个增长高峰。其他肠道病毒与EV-A71、CV-A16出现交替流行状况,2017年所占比例达到54.27%,2018年继续上升至77.78%。本地区HFMD夏季高发,集中在5～8月份,1～4岁幼儿易感,占确诊病例总人数的82.95%,特别是1～2岁年龄段发病...     

咸阳市2016-2019年手足口病病原学检测分析

本文通过对咸阳市2016-2019年手足口病(Hand,foot and mouth disease,HFMD)病原检测结果进行分析,阐明了咸阳市近四年HFMD病原谱的构成和流行特征,为HFMD防控工作提供依据.对2016-2019年收集的2711例HFMD病例标本进行荧光定量PCR检测确定肠道病毒型别,构建咸阳市HFMD病原谱并对阳性病例的流行特征进行描述性分析.2711例HFMD病例实验室确诊1444例(阳性率为53.26％),其中肠道病毒A组71型(Enterovirus 71,EV71)占病原谱构成的 12.74％、柯萨奇病毒 A组 16型(Coxsackievirus A16,CoxA16)占27.49％、柯萨奇病毒 A组 10型(Coxsackievirus A10,CoxA10)占5.19％、柯萨奇病毒 A 组6型(Coxsackievirus A6,CoxA6)占43.21％、其他肠道病毒(Enterovirus,EV)占11.36％.CoxA6和CoxA16交替居于咸阳市HFMD病原谱首位.咸阳市HFMD流行具有明显季节性和地区差异以及特定人群高发,夏季(5～7月)为发病主高峰,秋冬季(10～11月)为次高峰,主要集中在人口较多的市区,4岁以下散居儿童为易感人群,且男性发病率高于女性.今后的防控工作中应继续加强咸阳市HFMD监测,重视其他EV的监测工作,实时监测HFMD病原谱的变化.在高发季节,针对高发人群,采取积极有效干预措施,加强防控工作.     

2010—2019年滨州市手足口病流行病学特征分析

目的分析山东省滨州市2010—2019年手足口病(hand-foot-mouth disease, HFMD)流行特征,为科学制定防控策略提供依据。方法收集中国疾病监测信息系统中滨州市2010—2019年HFMD监测资料,采用描述流行病学方法对病例数据进行分析。结果滨州市2010—2019年共报告HFMD病例61 082例,年均发病率159.58/10万,疫情总体呈下降趋势,年度趋势变化差异有统计学意义(χ~2=4 576.81、P=0.001,P0.05);同时,不同年份发病率差异有统计学意义(χ~2=7 506.98、P=0.001,P0.05)。每年各月均有HFMD报告病例,报告病例呈明显单峰形式,6月达到顶峰,夏季(6—8月)报告病例最多,有38 693例,占63.35%。全市的7个县(市、区)均有报告病例,滨城区的报告发病数最多,有19 489例,占31.90%,不同地区构成比的差异有统计学意义(χ~2=17 085、P=0.001,P0.05);不同地区发病率也是滨城区最高,为288.96/10万,不同地区发病率的差异有统计学意义(χ~2=9 783.08、P=0.001,P0.05)。报告病例男女性别比为1.57∶1,男性高于女性,男女发病率的性别差异有统计学意义(χ~2=2 780.93、P=0.001,P0.05);1～5岁组报告病例49 172例,占80.50%;职业分布以散居儿童为主,有43 734例,占71.60%。RT-PCR检测出的3 413例HFMD阳性确诊病例中,其他肠道病毒感染最多,有1 356例,占比39.73%,但EV71、CoxA16仍是HFMD高强度流行的主要病原体,不同年份感染的优势菌株不尽相同。结论 2010—2019年滨州市HFMD发病率较高,并呈现明显的季节、地域、人群及不同年份优势菌株分布特征。需重点关注高发地区、1～5岁小年龄组散居儿童疾病预防和疫苗接种。滨州市疾病预防控制中心需及时对病原体的流行进行动态监测,尽早发现疫情苗头并采取相应措施。     

百色市2014年手足口病流行病学特征分析

目的分析百色市2014年手足口病流行特征,探讨该病的预防控制策略。方法采用描述流行病学方法对百色市2014年手足口病发病特征进行流行病学分析。结果 2014年百色市共报告手足口病44 520例,年发病率为1 258.05/10万,死亡17例,病死率为0.04%。病例报告有明显的季节性,4-6月为发病高峰;以0~5岁年龄组为主,占95.39%;男性发病率高于女性,男女发病比为1.44∶1;职业分布以散居儿童居多;病原学监测结果为EV71、Cox A16和其他肠道病毒混合感染;79.04%的重症病例(含死亡病例)由EV71感染所致。结论百色市手足口病流行情况严重,EV71仍是引起手足口病重症病例和死亡的主要病原体,今后仍需要采取综合性防治措施,开展健康教育,加强重症病人的筛查和救治,降低病死率。     

新疆维吾尔自治区2008～2017年手足口病流行病学及病原学监测分析

分析2008～2017年新疆维吾尔手足口病流行病学和病原学特征。采用描述性流行病学的方法,对2008～2017年国家疾病监测信息报告管理系统报告的手足口病例和新疆手足口病网络实验室数据的进行分析。2008～2017年新疆累计报告手足口病例68 820例,重症107例,死亡10例,年均发病率为31.33/10万;病例主要集中在乌鲁木齐市、伊犁州、昌吉州和塔城地区,占总病例数68.26%;5月～7月为发病高峰,病例以1岁～4岁儿童为主,占总病例数的74.46%,散居儿童和幼托儿童分别占51.52%和40.34%;对12 345例手足口病例标本进行核酸检测,阳性8 872例,阳性率71.87%,普通病例中肠道病毒71型(EV-A71)、柯萨奇病毒A组16型(CV-Al6)和其他肠道病毒分别占33.01%、40.33%和26.65%,重症和死亡病例的病原型别均以EV-A71为主,分别占91.03%和100%。新疆1岁～4岁的儿童为手足口病主要发病人群,不同地区发病水平不同,手足口病病原谱呈现EV-A71、CV-A16和其他EV交替流行态势。     

2010年海南省手足口病流行病学和病原学特征分析

为了探究2010年海南省手足口病(Hand-foot-and-mouth disease,HFMD)的流行病学及病原学特征,本研究对2010年海南省HFMD病例报告信息进行整理分析,并对2010年海南省18县市1346份HFMD病例临床标本进行肠道病毒(enterovirus,EV)实验室检测。核酸检测阳性标本进行EV分离和鉴定,对分离到的肠道病毒71型(Enterovirus 71,EV71)的VP1编码区全长基因进行扩增及序列测定,用Sequencher 5.0和MEGA 5.0等生物信息学软件基于VP1编码区进行EV71的分子流行病学分析。流行病学分析表明:全省18个县市均有病例报告,尤其以东北部县市高发,同时以4岁以下的婴儿为高发人群;而与全国大多省份流行规律不同的是其发病高峰期为9和10月份。实验室结果显示:EV71和CA16是引起2010年海南省HFMD流行的主要病原,但EV71感染在重症病例和死亡病例中占绝对优势。除此之外,还存在部分由其它EV感染引起的HFMD病例。分子流行病学分析提示:2010年海南省流行的EV71均属于C4a亚型,该亚型为我国近年来流行的优势基因型,同时进化分析提示至少存在3条传播链。本研究数据对阐明海南HFMD的流行传播规律,以进一步指导HFMD防控具有重要理论价值。     

湘潭地区2013-2014年手足口病病原监测结果分析

目的:分析2013-2014年湖南省湘潭市手足口病(HFMD)病原体型别及分布特征,为进一步完善HFMD的预防和治疗提供依据。方法:采用RT-PCR方法,对571例HFMD患儿进行肠道病毒通用型核酸(EV-RNA)、EV71及柯萨奇病毒A16(CA16)检测。结果:2013年除EV71及CA16外其他EV核酸阳性率75.30%,明显高于EV71的17.65%和CA16的7.05%(P0.05),2014年EV71型核酸阳性率为50.68%,明显高于CA16的19.93%和其他EV的29.39%(P0.05)。重症HFMD患儿EV71感染率明显高于轻症。结论:2013年湘潭地区HFMD患儿以除EV71及CA16外的其他EV病毒感染为主,2014年湘潭地区HFMD患儿以EV71感染为主。     

2011—2015年武鸣县手足口病流行特征分析

目的分析武鸣县2011—2015年手足口病(hand-foot-mouth disease,HFMD)流行病学特征,为武鸣县HFMD的预防和控制提供依据。方法收集并整理中国疾病监测信息报告管理系统中武鸣县2011—2015年HFMD病例资料,采用描述流行病学方法,对其流行病学特征进行分析。结果 2011—2015年,武鸣县共报告HFMD病例17 961例,发病率为648.42/10万,呈隔年高发。各月均有HFMD病例报告,报告病例数呈"双高峰"型,分别为4—6月7 308例(占40.69%),9—10月5 043例(占28.08%);报告病例最多的地区为武鸣县城4 266例,占总报告病例数的23.75%,高于其他乡镇;男性多于女性,男女性别比为1.51∶1;以<4岁儿童为主,占86.40%,其中散居儿童11 527例(占64.18%)。结论武鸣县HFMD具有发病率高、流行季节明显,以4岁以下散居儿童为主的流行病学特征;需加强重点地区、重点人群及HFMD病原学的监测。     

韶关市2008—2011年手足口病流行病学特征分析

目的了解韶关市2008—2011年手足口病流行特征,为降低该病的发病率提供决策依据。方法依据卫生部2008年版下发的手足口病诊断标准、防控指南,进行诊断、流行病学调查、标本采集。用描述流行病学方法对手足口病病例进行分析,并对人份标本进行逆转录酶反应(RT-PCR)核酸测定。结果韶关市4年共报告手足口病例14 076例,手足口病发病有明显的季节性,4～6月为发病高峰期,占全年报告总数的63.34%。发病人群以男性(男∶女=1.89∶1)5岁以下散居儿童为主,占总发病数的93.11%。4年的手足口病主要由EV71和其他肠道病毒混合感染引起,死亡病例主要由EV71感染引起。聚集性病例主要发生在个体托幼机构,占77.46%。散居或家庭聚集性病例占22.54%。结论当前手足口病是严重危害韶关市低年龄组儿童身体健康和生命安全的重要公共卫生问题,要不断加强环境及个人卫生条件的改善,普及健康教育。     

104例麻疹病例的流行病学分析

目的分析平顶山市麻疹病例发生的原因,为加速控制和消除麻疹提供科学依据。方法对平顶山市2013年法定传染病疫情报告资料和麻疹监测资料进行流行病学分析。结果平顶山市2013年共报告麻疹104例,年发病率为2.11/10万,2~4月为发病高峰;男女发病率差异有统计学意义,发病以3岁以下儿童居多,占发病总数的86.54%;其中8月龄~1岁者最多,占39.42%;14岁以上者9例,占8.65%,其他年龄组发病率随年龄增大而逐步下降。从病例就诊、住院时间上推断其感染方式可能以医院内感染为主。结论常规免疫接种率和首针及时接种率不高是麻疹高发的主要原因,医院内交叉感染是麻疹的传播因素,提高易感人群麻疹疫苗接种率,控制院内感染是控制、消除麻疹的有效手段。     

Seroprevalence of Human Enterovirus 71 and Coxsackievirus A16 in Guangdong,China, in Pre- and Post-2010 HFMD Epidemic Period

Background

Human Enterovirus 71 and Coxsackie A16 have caused many outbreaks in the last decade in mainland China, resulting in thousands of fatal cases. Seroepidemiology which provides important information to document population immunity is rare in China.

Methodology/Principal Findings

A cross sectional study of Enterovirus 71 (EV71) and Coxsackie A16 (CA16) seroprevalence was carried out in Guangdong, China, pre- and post- the 2010 hand, foot and mouth disease (HFMD) epidemic period. The levels of EV71 and CA16 specific antibodies were evaluated by a microneutralization test and the geometric mean titer (GMT) was calculated and compared. Our results indicated frequent infection by EV71 and CA16 in Guangdong before the 2010 epidemic. Only EV71 neutralizing antibody but not CA16 seroprevalence was significantly increased after the 2010 HFMD epidemic. Children less than 3 years old especially those aged 2 years showed the lowest positive rates for EV71 and CA16 NA before epidemic and the most significantly increased EV71 seroprevalence after epidemic. CA16 GMT values declined after the 2010 epidemic.

Conclusions

These results indicate EV71 was the major pathogen of HFMD in Guangdong during the 2010 epidemic. The infection occurs largely in children less than 3 years, who should have first priority to receive an EV71 vaccine.     

Epidemiological Characteristics and Spatial-Temporal Clusters of Hand,Foot, and Mouth Disease in Zhejiang Province,China, 2008-2012

Hand, foot and mouth disease (HFMD) is one of the major public health concerns in China. Being the province with high incidence rates of HFMD, the epidemiological features and the spatial-temporal patterns of Zhejiang Province were still unknown. The objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. The surveillance data of HFMD during 2008–2012 were collected from the communicable disease surveillance network system of Zhejiang Provincial Center for Disease Control and Prevention. The distributions of age, gender, occupation, season, region, pathogen’s serotype and disease severity were analyzed to describe the epidemiological features of HFMD in Zhejiang Province. Seroprevalence survey for human enterovirus 71 (EV71) in 549 healthy children of Zhejiang Province was also performed, as well as 27 seroprevalence publications between 1997 and 2015 were summarized. The spatial-temporal methods were performed to explore the clusters at county level. Furthermore, pathogens’ serotypes such as EV71 and coxsackievirus A16 (Cox A16) and meteorological factors were analyzed to explore the potential factors associated with the clusters. A total of 454,339 HFMD cases were reported in Zhejiang Province during 2008–2012, including 1688 (0.37%) severe cases. The annual average incidence rate was 172.98 per 100,000 (ranged from 72.61 to 270.04). The male-to-female ratio for mild cases was around 1.64:1, and up to 1.87:1 for severe cases. Of the total cases, children aged under three years old and under five years old accounted for almost 60% and 90%, respectively. Among all enteroviruses, the predominant serotype was EV71 (49.70%), followed by Cox A16 (26.05%) and other enteroviruses (24.24%) for mild cases. In severe cases, EV71 (82.85%) was the major causative agent. EV71 seroprevalence survey in healthy children confirmed that occult infection was common in children. Furthermore, literature summary for 26 seroprevalence studies during 1997–2015 confirmed that 0–5 years group showed lowest level of EV71 seroprevalence (29.1% on average) compared to the elder children (6–10 years group: 54.6%; 11–20 years group: 61.8%). Global positive spatial autocorrelation patterns (Moran’s Is>0.25, P<0.05) were discovered not only for mild cases but also for severe cases, and local positive spatial autocorrelation patterns were revealed for counties from the eastern coastal and southern regions. The retrospective space-time cluster analysis also confirmed these patterns. Risk factors analyses implied that more EV71 and less sunshine were associated with the clusters of HFMD in Zhejiang Province. Our study confirmed that Zhejiang Province was one of the highly epidemic provinces in China and that the epidemiological characteristics of HFMD were similar to other provinces. Occult infection in elder children and adults was one of the important reasons why most HFMD cases were children aged under-five. Combining the results of spatial autocorrelation analysis and the space-time cluster analysis, the major spatial-temporal clusters were from the eastern coastal and southern regions. The distribution of pathogens’ serotypes and the level of sunshine could be risk factors for, and serve as an early warning of, the outbreak of HFMD in Zhejiang Province.     

Characterization of an outbreak of hand, foot, and mouth disease in Nanchang, China in 2010

Recent outbreaks of human enterovirus 71 (EV71) infection and EV71-associated hand, foot, and mouth disease (HFMD) in China have affected millions and potentially lead to life-threatening complications in newborns. Furthermore, these outbreaks represent a significant global public health issue in the world. Understanding the epidemiology of HFMD and EV71 infection and their transmission patterns in China is essential for controlling outbreaks. However, no studies on the outbreaks of HFMD and EV71 infection in China during 2010 have been reported. In this report, we carried out an epidemiological analysis to study an outbreak of HFMD and EV71 infection in 2010 in the city of Nanchang in the Jiangxi province of People's Republic of China. From April 7 to May 11, 2010, a total of 109 HFMD cases were reported, and in this report the HFMD cases were studied by both epidemiological and laboratory analyses. The epidemiological study indicates that children aged younger than 8 years old represented more than 90% of the reported cases, with the age group of 1-3 years containing the highest number of cases. Laboratory studies detected a high prevalence of EV71 amongst the cases in our study, suggesting EV71 as a common enterovirus found in HFMD cases in Nanchang. Phylogenetic analysis of the sequence of the VP1 region of four EV71 isolates indicated that the Nanchang strains belong to the C4 subgenotype commonly found in China during outbreaks in 2008 but contain distinct variations from these strains. Our study for the first time characterizes the epidemiology of HFMD and EV71 infection in China in 2010 and furthermore, provides the first direct evidence of the genotype of EV71 circulating in Nanchang, China. Our study should facilitate the development of public health measures for the control and prevention of HFMD and EV71 infection in at-risk individuals in China.     

濮阳市2008—2012年手足口病流行病学特征分析

目的了解濮阳市手足口病流行病学特征,为制定防控策略提供科学依据。方法通过国家疾病监测信息管理系统收集的全市2008—2012年6月6日手足口病疫情资料进行描述和分析,并对部分病例和重症病例标本进行肠道病毒病原学检测。结果全市共报手足口病16 492例,发病高峰是每年的3-5月(第12～20周),呈典型的单峰型曲线;发病年龄以0～4岁居多;男性多于女性;散居儿童多于托幼机构儿童,爆发病例多发生在托幼机构,手足口病病原有EV71、CoxA16和其他肠道病毒,以EV71和CoxA16为主。结论手足口病发病有明显的季节性、年龄和性别差异,小年龄组儿童是手足口病预防控制重点人群,流行年度和流行季节的优势毒株为EV71,重症患者中EV71占到86.35%;非流行年和季节手足病例主要由CoxA16和其他肠道病毒引起。手足口病防控重点应体现在对病例分类管理上,同时应继续加强重症病例疫情监测和爆发控制。     

Monoclonal neutralizing antibodies against EV71 screened from mice immunized with yeast-produced virus-like particles

Periodic outbreaks of hand, foot and mouth disease(HFMD) occur in children under 5 years old, and can cause death in some cases. The C4 strain of enterovirus 71(EV71) is the main pathogen that causes HFMD in China. Although no drugs against EV71 are available, some studies have shown that candidate vaccines or viral capsid proteins can produce anti-EV71 immunity. In this study, female BABL/c mice(6–8 weeks old) were immunized with virus-like particles(VLPs) of EV71 produced in yeast to screen for anti-EV71 antibodies. Two hybridomas that could produce neutralizing antibodies against EV71 were obtained. Both neutralizing m Abs(D4 and G12) were confirmed to bind the VP1 capsid protein of EV71, and could protect 95% cells from 100 TCID50 EV71 infection at 25 μg/m L solution(lowest concentration). Those two neutralizing m Abs identified in the study may be promising candidates in development for m Abs to treat EV71 infection, and utilized as suitable reagents for use in diagnostic tests and biological studies.     

Cell surface sialylation affects binding of enterovirus 71 to rhabdomyosarcoma and neuroblastoma cells

ABSTRACT: BACKGROUND: Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD), and infection of EV71 to central nerve system (CNS) may result in a high mortality in children less than 2 years old. Although there are two highly glycosylated membrane proteins, SCARB2 and PSGL-1, which have been identified as the cellular and functional receptors of EV71, the role of glycosylation in EV71 infection is still unclear. RESULTS: We demonstrated that the attachment of EV71 to RD and SK-N-SH cells was diminished after the removal of cell surface sialic acids by neuraminidase. Sialic acid specific lectins, MAA and SNA, could compete with EV71 and restrained the binding of EV71 significantly. Preincubation of RD cells with fetuin also reduced the binding of EV71. In addition, we found that SCARB2 was a sialylated glycoprotein and interaction between SCARB2 and EV71 was retarded after desialylation. CONCLUSIONS: In this study, we demonstrated that cell surface sialic acids assist in the attachment of EV71 to host cells. Cell surface sialylation should be a key regulator that facilitates the binding and infection of EV71 to RD and SK-N-SH cells.     

Co-Circulation and Genomic Recombination of Coxsackievirus A16 and Enterovirus 71 during a Large Outbreak of Hand,Foot, and Mouth Disease in Central China

A total of 1844 patients with hand, foot, and mouth disease (HFMD), most of them were children of age 1–3-year-old, in Central China were hospitalized from 2011 to 2012. Among them, 422 were infected with coxsackievirus A16 (CVA16), 334 were infected with enterovirus 71 (EV71), 38 were co-infected with EV71 and CVA16, and 35 were infected with other enteroviruses. Molecular epidemiology analysis revealed that EV71 and CVA16 were detected year-round, but EV71 circulated mainly in July and CVA16 circulated predominantly in November, and incidence of HFMD was reduced in January and February and increased in March. Clinical data showed that hyperglycemia and neurologic complications were significantly higher in EV71-infected patients, while upper respiratory tract infection and C-reactive protein were significantly higher in CVA16-associated patients. 124 EV71 and 80 CVA16 strains were isolated, among them 56 and 68 EV71 strains were C4a and C4b, while 25 and 55 CVA16 strains were B1a and B1b, respectively. Similarity plots and bootscan analyses based on entire genomic sequences revealed that the three C4a sub-genotype EV71 strains were recombinant with C4b sub-genotype EV71 in 2B–2C region, and the three CVA16 strains were recombinant with EV71 in 2A–2B region. Thus, CVA16 and EV71 were the major causative agents in a large HFMD outbreak in Central China. HFMD incidence was high for children among household contact and was detected year-round, but outbreak was seasonal dependent. CVA16 B1b and EV71 C4b reemerged and caused a large epidemic in China after a quiet period of many years. Moreover, EV71 and CVA16 were co-circulated during the outbreak, which may have contributed to the genomic recombination between the pathogens. It should gain more attention as there may be an upward trend in co-circulation of the two pathogens globally and the new role recombination plays in the emergence of new enterovirus variants.