英山县手足口病爆发高峰期病原学及流行病学观察

目的:了解英山县2013-04-2013-05间手足口病爆发高峰期病原学及流行病学特征,为本地区手足口病的防治提供依据。方法:采集109例手足口病患者咽拭子标本,采用实时荧光定量PCR方法进行肠道病毒通用型、肠道病毒71型(EV71)和柯萨奇病毒A16型(CA16)的核酸检测。结果:肠道病毒通用型阳性81例,阳性率为74.3%;EV71病毒阳性63例,阳性率为57.8%;CA16阳性19例,阳性率为17.4%;其中EV71和CA16双阳性12例,阳性率为11.0%。此次爆发高峰期的发病患者年龄集中在1~4岁儿童,并且男性患儿明显多于女性,以散居儿童和幼托儿童为主,EV71亚型发热患者所占比率要显著高于CA16亚型。结论:英山县2013年手足口病高峰期的主要病原体是EV71亚型,了解患者手足口病感染的病原体亚型及流行病学特征。     

2011年天津市手足口病病原检测与基因特征分析

目的对天津市2011年手足口病(HFMD)进行病原学检测,并对引起HFMD的肠道病毒71型(EV71)和柯萨奇病毒A组16型(CVA16)进行基因特征分析,为天津市HFMD的防控提供基础资料。方法采用Real time RT-PCR方法对HFMD疑似病例标本进行检测,用人横纹肌瘤(RD)细胞对部分阳性标本进行病毒分离;随机挑取16株EV71病毒分离株和9株CVA16病毒分离株,进行VP1区基因扩增,并进行核苷酸序列和遗传进化关系分析。结果共检测HFMD疑似病例1 853例,总阳性率为70.91%(1314/1853),其中EV71占49.10%,CVA16占21.61%,EV71和CVA16双阳性占0.91%,其他肠道病毒(EV)占28.46%。16株EV71分离株与C4a亚型代表株具有最高的核苷酸序列同源性(97.3%～99.1%),属于C4a基因亚型;9株CVA16分离株与B1b亚型代表株具有最高的核苷酸序列同源性(94.9%～95.4%),属于B1b基因亚型。结论 2011年引起天津市HFMD的EV71型病毒流行株为C4a基因亚型,CVA16型病毒流行株为B1b亚型,并兼有一定比例的其他肠道病毒。     

实时荧光定量RT-PCR法检测安徽宿州市手足口病病原体结果分析

目的  了解宿州市手足口病肠道病毒谱及感染情况,为制订手足口病预防控制策略提供依据。 方法  采用实时荧光定量RT-PCR法对2012~2014年宿州市各县区哨点医院手足口病临床诊断病例进行病原学检测并分析。 结果  在962份样品中,肠道病毒核酸检测阳性384例,阳性率为39.92%;其中EV71、CoxA16分别为154例（占40.10%）、144例（占37.50%）,其他型肠道病毒共86例（占22.40%）。384例阳性病例中,男247例,女137例,阳性检出率在性别间差异无统计学意义（χ2=0.83,P＞0.05）;1岁组和2岁组手足口病毒核酸检测阳性占全部阳性者的73.18%。在3~4月和6~7月的发病高峰期间,病毒主要以CoxA16型和EV71型毒株为主,10~12月以EV71型病毒株为主。在人口密集的萧县和埇桥区,其手足口核酸阳性检出率最高,分别为50.21%和42.18%。 结论  宿州市手足口病病原体主要是EV71和CoxA16,主要发生在3岁以下儿童,发病时间以每年3~4月和6~7月为主,应加强在流行季节的防控工作及3岁以下手足口病患儿的病情监测与治疗。     

手足口病流行病学及其临床诊断与治疗

手足口病(hand-foot-mouth disease,HFMD),是由多种肠道病毒引起的常见传染病,以婴幼儿发病为主。大多数患者症状轻微,以发热和手、足、口腔等部位的皮疹或疱疹为主要特征。少数患者可并发无菌性脑膜炎、脑炎、急性弛缓性麻痹、呼吸道感染和心肌炎等,个别重症患儿病情进展快,可     

2012年天津市手足口病病原与分子流行病学分析

目的对天津市2012年的手足口病病例进行病原学检测,并对引起HFMD流行的肠道EV71型（EV71）和柯萨奇A组16型（CVA16）病毒进行分子生物学特征分析。方法利用Real—time PCR检测HFMD疑似病例标本,用人横纹肌肉瘤（RD）细胞对Real—time PCR检测阳性的部分病例标本进行病毒分离。随机挑取9株EV71病毒分离株和8株CVA16病毒分离株,采用PCR扩增VPl全基因,并进行核苷酸序列和遗传进化分析。结果共检测HFMD疑似病例1829例,肠道病毒总阳性率为81．30％（1487／1829）,其中EV71占39．88％,CVA16占38．33％,其他EV占21．79％。9株EV71分离株与C4亚型的C4a分支代表株的核苷酸序列同源性为97．3％～98．5％,均归属于C4a分支;8株CVA16分离株与B1亚型代表株的核苷酸序列同源性为92．9％～97．1％,其中7株属于B1b分支,1株属于B1a分支。结论导致天津市2012年HFMD流行的EV71为C4亚型中的C4a病毒株,CVA16为B1亚型的B1b病毒株。     

手足口病

1定义手足口病（Hand-foot—and—mouthdisease）是由肠道病毒引起的传染病,多发生于5岁以下儿童,可引起手、足、口腔等部位的疱疹,少数患儿可引起心肌炎、肺水肿、无菌性脑膜脑炎等并发症。个别重症患儿如果病情发展快,导致死亡。引发手足口病的肠道病毒有20多种（型）,柯萨奇病毒A组的16、4、5、9、10型,B组的2、5型,以及肠道病毒71型均为手足口病较常见的病原体,其中以柯萨奇病毒A16型（CoxA16）和肠道病毒71型（EV71）最为常见。     

山东省EV71和CoxA16所致手足口病重症病例流行病学及临床特征分析

目的比较EV71和CoxA16所致手足口病重症病例临床症状和体征,为手足口病的诊疗和防控提供依据。方法采用实时荧光定量RT-PCR对重症病例进行病原学分型;收集病例基本信息和临床资料,对2010年确诊的EV71和CoxA16所致手足口病重症病例的临床特征进行比较分析。结果 EV71与CoxA16所致手足口病重症患者主要为3岁以下儿童(占81.61%),患者平均年龄为2.30岁(0.20～16.39岁)。EV71所致重症患者最高体温为(38.75±0.04)℃,CoxA16所致重症患者为(38.60±0.07)℃,差异无统计学意义(t=-1.61,P>0.05);两种病毒所致重症患者口腔部位皮疹、咳嗽、流涕和心率加快发生率差异均有统计学意义(P<0.05),其他症状和体征均一致。结论 CoxA16与EV71所致重症手足口病患者临床特征基本一致,均引起严重并发症。应加强对CoxA16感染的监测和防控。     

手足口病临床诊疗措施初步探讨

目的探讨手足口病的临床诊断及治疗措施,为手足口病的防治提供理论依据。方法采用回顾性分析的方法对本院所收治的手足口病病例的相关信息进行分析。结果手足口病多发生于3岁以下的儿童,80％以上病例有发热,100％病例皮肤出现黏膜疹,部分病例出现AST、ALT、CK—MB、LDH和血糖升高。重症病例可并发中枢神经系统损伤,导致神经源性肺水肿和循环衰竭。轻型病例多于1周内痊愈。重症病例治疗困难,病死率达25．7％（9／35）。结论手足口病是一种自限性疾病,提高诊断警惕性和及时识别出重症病例的早期临床征象是降低病死率的关键环节。重症病例应采取以脱水、降颅压、大剂量激素和静脉用丙种球蛋白冲击及呼吸循环支持治疗为主的综合治疗措施。     

黄梅县手足口病临床分离株的基因型分析

目的:了解手足口病暴发高峰时段临床患者的咽拭子标本中分离出的人肠道病毒71型(EV71)和柯萨奇病毒A16型(CA16)的基因型,为手足口病的防治提供依据。方法:将手足口病高峰时期收集的咽拭子标本109份进行病毒分离鉴定,对分离到的4株EV71型病毒株的227bp VP3-VP1基因序列和3株CA16株的736bp VP1-2A基因序列进行基因测序,并进行系统进化分析。结果:检测到的4株EV71分离毒株均属C4a亚群,3株CA16分离毒株均属于B1b亚群。结论:2013年黄梅县手足口病暴发高峰时段的EV71流行株为C4a亚群,CA16流行株为B1b亚群。     

一起手足口病暴发的病原学诊断与分析

目的明确一起手足口病暴发的病原体并对其进行遗传性分析。方法收集部分病例和密切接触者的粪便标本,以及急性期与恢复期双份血清标本,同时应用传统的病毒分离与鉴定、双份血清中和抗体变化以及现代分子生物学诊断方法进行病因学诊断;并进一步针对病原体进行基因序列测定和遗传树图构建分析。结果应用RT-PCR及序列分析方法,从病例及密切接触者粪便标本直接扩增基因快速诊断为CAV16;8例病例中3例病毒分离阳性,应用RIVM肠道病毒组合血清均无法定型,而应用CAV16特异性引物RT-PCR诊断均为阳性,35例密切接触者标本中10例病毒分离阳性,6例(60%)为CAV16,同时EV71诊断均为阴性;用病例的分离株病毒对5个病例双份血清进行中和抗体检测,其中3例恢复期血清中和抗体效价呈4倍及以上增长;CAV16的本研究分离株和来源于GenBank中参考株,基于衣壳蛋白VP1基因同时进行遗传性分析,显示本研究分离株间同源性达99.7%~99.9%,具有直接的流行病学联系,在遗传树图中位于C基因型下相对独立的一分支,与同属于C基因型其它参考株核苷酸差异性达4.1%~5.1%。结论应用分子生物学方法结合传统的病毒分离与鉴定,既可快速又能准确鉴定引起本次手足口病暴发的病原为CAV16。     

Effect of enterovirus 71 vaccination on the epidemiological characteristics and etiology in hospitalized children with hand-foot-and-mouth disease: A retrospective study from a tertiary children’s hospital

Enterovirus 71 (EV71) vaccine for hand-foot-and-mouth disease (HFMD) prevention has been available for several years. However, as a new vaccine, the impact of EV71 vaccination on the epidemiology and etiology of HFMD is currently unclear. The purpose of this study was to compare and analyze the changes of epidemiological characteristics and etiology of HFMD patients after the introduction of EV71 vaccine. The data of hospitalized children with HFMD from 2014 to 2020 were collected from the case record department of a tertiary children hospital of Anhui Province. The changes of epidemiological characteristics, time distribution, disease severity and enterovirus serotypes in hospitalized children were analyzed. A total of 7373 cases of HFMD were reported during 2014 to 2020, including 634 (8.6%) severe cases. The number of cases reached the peak in 2016 (n = 1783) and decreased gradually after EV71 vaccination. The results of etiological test showed the positive rate was 80.5%, in which EV71 accounted for 1599 (21.7%) and CV-A16 accounted for 1028 (13.9%) respectively. The number of patients showed a bimodal distribution throughout the year, which were April to June and October to November. The age distribution changed significantly following the introduction of EV71 vaccine. The proportion of 1-year-old group of post-vaccination was significantly higher than that of pre-vaccination (61.9% vs 50.8%, P < .001). The proportion of HFMD caused by EV71 and severe cases decreased significantly after the vaccination (P < .001 for both). While the comparison of epidemiological characteristics and enterovirus serotypes between unvaccinated and vaccinated cases during 2017 to 2020 showed no significant difference. The dominant enterovirus serotypes of hospitalized HFMD changed significantly after the introduction of EV71 vaccine. The proportion of severe cases decreased significantly after the vaccination, but EV71 was still a major pathogen in patients with severe HFMD. More age-appropriate children are recommended to get vaccinated to establish stronger herd immunity in the population.     

2009年邯郸市手足口病血清流行病学调查

目的掌握2009年邯郸市0～15岁儿童EV71IgG和CoxA16IgG携带状况,探讨发病率与抗体的关系。方法采用酶联免疫吸附试验(ELISA)检测0～15岁儿童血清EV71IgG和CoxA16IgG,分析EV71IgG、CoxA16IgG阳性率随年龄的变化趋势及其与手足口病发病率间的关系。结果 2009年邯郸市报告HFMD病例19 457例,567例HFMD病例标本中450份肠道病毒核酸阳性,其中EV71 302份(占67.11%),CoxA16 75份(占16.67%)。采集856名儿童血清,EV71IgG阳性546例,阳性率63.79%;CoxA16IgG阳性579例,阳性率67.64%,差异无统计学意义(χ2=1.309,P>0.05)。儿童血清EV71IgG和CoxA16IgG阳性率呈负相关(r=-0.900),5岁以下儿童血清EV71IgG阳性率与2009年HFMD发病率呈正相关关系(r=0.852),CoxA16IgG阳性率与发病率呈负相关关系(r=-0.816)。结论 2009年邯郸市CoxA16和EV71均有流行,病例以EV71型为主。     

Safety and Immunogenicity of a Stable,Cold-Adapted,Temperature-Sensitive/Conditional Lethal Enterovirus A71 in Monkey Study

Enterovirus A71 (EV-A71) and coxsackievirus A16 (CA16) are major etiological agents of hand foot and mouth disease (HFMD) in children, which may result in fatal neurological complications. The development of safe, cost effective vaccines against HFMD, especially for use in developing countries, is still a top public health priority. We have successfully generated a stable, cold-adapted, temperature sensitive/conditional lethal EV-A71 through adaptive culturing in Vero cells at incrementally lower cultivation temperatures. An additional 40 passages at an incubation temperature of 28 °C, and a temperature reversion study at an incubation temperature of 37 °C and 39.5 °C, reveals the virus’s phenotypic and genetic stability at the predefined culture conditions. Six unique mutations (two in noncoding regions and four in nonstructural protein-coding genes) in combination may have contributed to its stable phenotype and inability to fully revert to its original wild phenotype. The safety and immunogenicity of this stable, cold-adapted, temperature sensitive/conditional lethal EV-A71 was performed in six monkeys. None of the inoculated monkeys developed any obvious clinical illness except one which developed a transient spike of fever. No gross postmortem lesion or abnormal histological finding was noted for all monkeys at autopsy. No virus was reisolated although EV-A71 specific RNA was detected in serum samples collected on both day 4 and day 8 postinoculation. Only EV-A71 RNA and viral antigen were detected in the spleen homogenate and peripheral blood mononuclear cells, respectively, collected on day 4. The two remaining monkeys developed good humoral immune response on day 14 and day 30 post-inoculation.     

2018年深圳市龙岗区手足口病流行病学分析

目的　了解2018年深圳市龙岗区手足口病流行病学特征,为制定针对性的防控措施提供科学依据。方法　采用描述性流行病学方法对2018年龙岗区手足口病流行的时间、空间、人群分布以及病原体流行状况进行分析。结果　2018年龙岗区共报告手足口病病例15 116例,发病率为311.45/10万。2018年龙岗区手足口病流行期为5—11月,全年高峰出现在5月。各街道均有病例报告。男女性别比为1.52∶1,发病人群中以5岁以下幼童为主,占发病总数的86.23%。病原体疫情监测显示阳性标本中以其他EV阳性率最高,占41.28%,其次为Cox A16型,占15.12%。结论　2018年龙岗区手足口病流行保持夏秋季节高发的特点,发病人群以0～5岁年龄组为主,病原体流行趋势为其他EV阳性率增加。因此,须加强手足口病监测,采取相关措施有效预防手足口病的流行或暴发。     

2010—2019年宝鸡市 手足口病流行特征及时空聚集分析

[摘要]　目的?分析陕西省宝鸡市2010—2019年手足口病流行特征及时空聚集性,为本市的手足口病防控提供理论依据。方法? 收集宝鸡市2010—2019年手足口病发病数据和病原学监测结果,建立数据库,分析手足口病流行特征及优势病原谱的变化,再应用ArcGIS 10.1系统对手足口病发病进行空间自相关及热点分析。结果?2010—2019年宝鸡市累计报告手足口病35 546例,平均发病率为94.62/10万,男性发病率高于女性（χ2=1031.484,P=0.000）;各年龄组发病率不同（χ2趋势=61 405.833,P=0.000）,其中1～2岁组年平均发病率最高（2572.65/10万）。宝鸡市手足口病病原谱的构成：2010年优势病原为Cox A16（65.14%）,2011年、2012年和2014年优势病原为EV-A71（82.67%、48.97%和54.87%）,2013年、2015—2018年均以其他肠道病毒为主（62.11%、49.34%、53.02%、42.29%、80.50%）,2019年Cox A16和其他肠道病毒比例相当（55.42% vs. 43.07%）,各年间优势病原分布不同（χ2=874.879,P=0.000）。全局自相关分析发现2014年、2017年、2018年、2019年具有空间聚集性,高值聚集区为本市南部地区及主城区。结论?陕西省宝鸡市手足口病发病存在时空聚集性,应加强重点地区疫情防控,制定针对性防控措施。　
     

Surveillance for Enteroviruses Associated with Hand,Foot, and Mouth Disease,and Other Mucocutaneous Symptoms in Spain, 2006–2020

Hand, foot, and mouth disease (HFMD) is a mild illness caused by enteroviruses (EV), although in some Asian countries, large outbreaks have been reported in the last 25 years, with a considerable incidence of neurological complications. This study describes epidemiological and clinical characteristics of EV infections involved in HFMD and other mucocutaneous symptoms from 2006 to 2020 in Spain. EV-positive samples from 368 patients were included. EV species A were identified in 85.1% of those typed EV. Coxsackievirus (CV) A6 was the prevalent serotype (60.9%), followed by EV-A71 (9.9%) and CVA16 (7.7%). Infections affected children (1–6 years old) mainly, and show seasonality with peaks in spring–summer and autumn. Clinical data indicated few cases of atypical HFMD as well as those with neurological complications (associated with the 2016 EV-A71 outbreak). Phylogenetic analysis of CVA6 VP1 sequences showed different sub-clusters circulating from 2010 to present. In conclusion, HFMD or exanthemas case reporting has increased in Spain in recent years, probably associated with an increase in circulation of CVA6, although they did not seem to show greater severity. However, EV surveillance in mucocutaneous manifestations should be improved to identify the emergence of new types or variants causing outbreaks and more severe pathologies.