2007年北京地区儿童手足口病病原的初步筛查

2007年4～6月儿童手足口病流行期间,对北京地区51例皮损症状典型、伴/不伴发热、无重症合并症的手足口病患儿采样,建立RT-PCR方法,以5'非编码区(5'UTR)肠道病毒通用引物、CA16和EV71 VP1区特异性引物直接对82份临床标本进行了初步筛查,肠道病毒阳性率达70.6%。检测病例中CA16阳性25例(25/51)、EV71阳性4例(4/51)、非CA16和EV71的肠道病毒阳性病例7例(7/51),三者比例约为6:1:2。2007年北京地区儿童轻症手足口病主要病原包括CA16和EV71,同时还存在一定比例其它肠道病毒。部分EV71毒株经测序验证及系统进化分析显示为C4基因亚型。     

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—2016年上海地区手足口病病原谱及柯萨奇病毒A组6型不同基因型感染细胞的差异研究

本文旨在分析2011—2016年上海地区手足口病病原谱的构成和主要病原体流行规律,为手足口病的疫情防控和重症预警提供参考。采集2011—2016年哨点医院临床诊断为手足口病的患儿标本,首先进行肠道病毒通用型核酸和分型检测,其次对2012—2016年核酸检测为柯萨奇病毒A组6型(coxsackievirus A6,CA6)阳性样本进行基因型重组检测,分离重组型和非重组型CA6株,比较两者生物学特性。结果显示,2011—2012年秋季上海地区手足口病主要致病原为肠道病毒71型(enterovirus type 71,EV71)和CA16;2012年秋季起CA6成为主要病原体;2013—2014年重组型CA6(recombinant CA6,R CA6)占一定比例;2015—2016年非重组型CA6(non-recombinant CA6,NR CA6)成为优势流行株。R CA6和NR CA6代表株在RD细胞中增殖良好,在KB、MRC-5和HEp-2细胞中未见明显增殖。比较R CA6与NR CA6代表株接种于RD细胞后细胞活性下降的动态变化,未见显著差异。本研究证实,CA6为近年来上海地区手足口病的主要病原体,R CA6和NR CA6的构成比逐年变化,提示持续监测手足口病主要病原体并了解其生物学特性,对上海地区手足口病的防控预警及疫苗研发具有重要意义。     

炎琥宁联合痰热清治疗86例手足口病疗效观察及护理

近年来,手足口病的发病率有增多及严重的趋势,引起手足口病的肠道病毒包括肠道病毒71型（EV71）和A组柯萨奇病毒（CoxA）、埃可病毒（Echo）的某些血清型。EV71感染引起重症病例的比例较大,肠道病毒传染性强,可在短期内流行,我国小范围区域曾流行发病。临床上多采用病毒唑为主及加强对症治疗,为了寻找更有效的治疗方法,我科于2008年4～10月采用炎琥宁联合痰热清治疗手足口病86例,效果满意,现报告如下。     

2014-2018年辽宁省手足口病病原构成及其他肠道病毒基因进化特征

目的了解辽宁省2014-2018年手足口病病原构成以及其他(非EV71和非CA16的肠道病毒)肠道病毒基因进化特征。方法采用2014-2018年辽宁省14个市送检的手足口病确诊病例的阳性标本,通过细胞培养法分离肠道病毒,提取病毒RNA,采用RT PCR法对肠道病毒VP1区基因进行扩增和序列测定。利用BLAST对测序结果比对后确定病毒基因型别,并构建系统进化树。结果手足口病阳性标本病原构成以其他肠道病毒为主,构成比为51.96%,在重症病例中阳性标本构成比是59.29%。优势流行病原在2014和2016年以CA16为主,其他年份以其他肠道病毒为主。CA10、CA6和CA4肠道病毒的分离株与相应的原型株的亲缘关系较远,与国内的分离株的亲缘关系较近。结论EV71和CA16感染的构成比总体呈下降趋势,其他肠道病毒的构成比缓慢上升,是本地手足口病的优势病原,要加强对其他肠道病毒的检测和分型工作,有效预防和控制手足口病。     

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。     

手足口病的防治进展

手足口病（hand foot and mouth disease,HFMD）是由肠道病毒引起的常见急性传染病,主要为柯萨奇病毒A组16型（CoxA16）和肠道病毒71（EV71）,其传染性强,隐性感染比例大,多发生于学龄前儿童,尤以3岁以下年龄组发病率最高[1],近年有流行趋势[2],     

2012‒2013年浙江省手足口病流行病学和病原学特征分析

摘要：目的 了解2012?2013年浙江省手足口病流行特征和病原构成,为手足口病防控工作提供参考。方法 收集2012?2013年浙江省手足口病疑似患者粪便、咽拭子、疱疹液标本,采用实时荧光RT-PCR对收集样本进行HFMD病原体检测。结果 2012?2013年共采集样本1 792例,患者以5岁以下散居儿童为主;浙江省手足口病发病高峰期在5~6月份,9月份出现发病次高峰;肠道病毒总检出率为72.9%,其中2012年浙江省手足口病优势病原体为EV71（40.3%）,其次为CoxA16（31.3%）,2013年浙江省手足口病优势病原体为其他肠道病毒（77.2%） （非EV71和CoxA16）,以CoxA6为主（51.3%）。不同样本类型中,肠道病毒检出率依次为疱疹液（100.0%）、粪便（76.2%）和咽拭子（65.1%）。结论 手足口病的流行具有季节性和人群性,不同年份引起手足口病的优势病原体存在变化,持续地病原监测有助于预防和控制手足口病的流行暴发。     

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。     

肠道病毒71型分子流行病学研究进展

肠道病毒71型(Enterovirus type 71,EV71),自1974年首次报道以来,在世界范围内引起多次爆发与流行。EV71感染主要引起患者手足口病(hand,foot and mouth disease,HFMD),在临床上与柯萨奇病毒A16(Coxsakie A16,CA16)感染所引起的手足口病难以区别,但EV71还能够引起多种与神经系统相关的疾病。近年来,EV71病毒的流     

Genotypes of the Enterovirus Causing Hand Foot and Mouth Disease in Shanghai,China, 2012-2013

Sporadic HFMD (hand foot and mouth disease, HFMD) cases and outbreaks caused by etiologic agents other than EV71 and CA16 have increased globally. We conducted this study to investigate the prevalence and genetic characteristics of enteroviruses, especially the non-EV71 and non-CA16 enteroviruses, causing HFMD in Shanghai. Clinical specimens were collected from patients with a diagnosis of HFMD. A partial length of VP1 was amplified with RT-PCR and subjected to direct sequencing. Phylogenetic analyses were performed using MEGA 5.0. The ages of the HFMD cases ranged from 3 to 96 months, and the male/female ratio was 1.41. The median hospital stay was 2.96 days. Up to 18.0% of patients had neurologic system complications such as encephalitis, meningoencephalitis or meningitis. Of the 480 samples, 417 were positive for enterovirus (86.9%) with RT-PCR. A total of 13 enterovirus genotypes were identified. The most frequent genotypes were CA6 (31.9%), EV71 (30.6%), CA16 (8.8%) and CA10 (7.5%). Infections with CA6, EV71, CA16 and CA10 were prevalent throughout the years of study, while the proportion of CA6 notably increased from Sep. 2012 to Dec. 2013. Phylogenetic analyses showed that EV71 strains belonged to the C4a subgenogroup and CA16 was identified as B1b subgenogroup. The CA6 strains were assigned to genogroup F, whereas the CA10 strains were assigned to genogroup D. Patients infected with CA6 were typically younger, had a shorter hospital stay and had a lower incidence of neurologic system complications when compared to patients infected with EV71. Our study demonstrates that the enterovirus genotypes causing HFMD were diversified, and there was an increasing prevalence of the non-EV71 and non-CA16 enteroviruses from 2012 to 2013. CA6 was the most predominant pathogen causing HFMD from Sep. 2012 to Dec. 2013, and it often caused relatively mild HFMD symptoms. Most severe HFMD cases were associated with EV71 infection.     

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.     

热毒宁注射液治疗CoxA16、EV71肠道病毒感染手足口病的效果与安全性分析

目的探讨热毒宁注射液治疗CoxA16、EV71肠道病毒感染手足口病的效果与安全性。方法选择2015年10月~2016年5月在我院治疗的CoxA16、EV71肠道病毒感染的手足口病患儿96例,随机分为两组,其中对照组48例给予利巴韦林注射液治疗,研究组48例给予热毒宁注射液治疗,比较两组的治疗效果与安全性。结果研究组治疗总有效率(97.92%)明显高于对照组(83.33%),差异有统计学意义(P0.05);两组均无严重不良反应(P0.05)。结论热毒宁注射液治疗CoxA16、EV71肠道病毒感染手足口病患儿的效果显著,安全可靠,值得推广。     

Challenges to licensure of enterovirus 71 vaccines

Human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (EV71), which frequently involve neurological complications. EV71 vaccines are being evaluated in humans. However, several challenges to licensure of EV71 vaccines need to be addressed. Firstly, EV71 and coxsackievirus A (CA) are frequently found to co-circulate and cause hand-foot-mouth disease (HFMD). A polyvalent vaccine that can provide protection against EV71 and prevalent CA are desirable. Secondly, infants are the target population of HFMD vaccines and it would need multi-national efficacy trials to prove clinical protection and speed up the licensure and usage of HFMD vaccines in children. An international network for enterovirus surveillance and clinical trials is urgently needed. Thirdly, EV71 is found to evolve quickly in the past 15 years. Prospective cohort studies are warranted to clarify clinical and epidemiological significances of the antigenic and genetic variations between different EV71 genogroups, which is critical for vaccine design.     

A One-Step,Triplex, Real-Time RT-PCR Assay for the Simultaneous Detection of Enterovirus 71, Coxsackie A16 and Pan-Enterovirus in a Single Tube

The recent, ongoing epidemic of hand, foot, and mouth disease (HFMD), which is caused by enterovirus infection, has affected millions of children and resulted in thousands of deaths in China. Enterovirus 71 (EV71) and coxsackie A16 (CA16) are the two major distinct pathogens for HFMD. However, EV71 is more commonly associated with neurologic complications and even fatalities. Therefore, simultaneously detecting and differentiating EV71 and CA16 specifically from other enteroviruses for diagnosing HFMD is important. Here, we developed a one-step, triplex, real-time RT-PCR assay for the simultaneous detection of EV71, CA16, and pan-enterovirus (EVs) in a single tube with an internal amplification control. The detection results for the serially diluted viruses indicate that the lower limit of detection for this assay is 0.001–0.04 TCID₅₀/ml, 0.02 TCID₅₀/ml, and 0.001 TCID₅₀/ml for EVs, EV71, and CA16, respectively. After evaluating known HFMD virus stocks of 17 strains of 16 different serotypes, this assay showed a favorable detection spectrum and no obvious cross-reactivity. The results for 141 clinical throat swabs from HFMD-suspected patients demonstrated sensitivities of 98.4%, 98.7%, and 100% for EVs, EV71, and CA16, respectively, and 100% specificity for each virus. The application of this one-step, triplex, real-time RT-PCR assay in clinical units will contribute to HFMD surveillance and help to identify causative pathogen in patients with suspected HFMD.     

Phylogenetic Analysis of Enterovirus 71 Circulating in Beijing,China from 2007 to 2009

The major pathogens of hand, foot and mouth disease (HFMD) in Beijing, China from 2007 to 2009 were identified in this study. A total of 186 HFMD cases were included, and 136 cases (73%) were positive for enterovirus (EV). In 2007, 75% (27/36) were Coxsackievirus A16 (CA16) positive and 19% (7/36) were Enterovirus 71 (EV71) positive cases. However, EV71 was the predominant virus in 2008, when 56% (31/55) of the cases were positive for EV71 and 22% (12/55) were positive for CA16. In 2009, EV71 and CA16, with positive rates of 36% (16/45) and 29% (13/45), respectively, were still the major pathogens of HFMD. Phylogenetic analysis revealed that the dominant genotype of EV71 was C4, with co-circulation of genotype A in 2009. The prevalent cluster of the EV71 subgenotype C4 changed over time. A proposed new sublineage of EV71, C4a-2, was the predominant virus associated with the Beijing and nationwide HFMD outbreaks since 2008 and amino acid substitution, which possibly link to the central nervous system tropism of EV71, was found in genotype A viruses. Persistent surveillance of HFMD-associated pathogens is required for predicting potential emerging viruses and related disease outbreaks.     

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.