湖南省祁阳县2012-2015年手足口病流行病学特征及防制策略研究

目的 分析湖南省祁阳县2012-2015年手足口病的流行病学特征,探索影响手足口病的影响因素,为调整控制策略提供依据.方法 运用SPSS 13.0软件对2012-2015年手足口病数据进行统计分析.结果 祁阳县2012-2015年共报告手足口病病例3 430例,年均发病率80.90/10万.病例发病时间集中分布在5-6月,占病例总数的44.99％.病例年龄最小的为3个月,最大的为17岁,0～5岁年龄组占发病数的94.08％,男女性别比为1.9:1.散居儿童占发病总数的91.05％.乡村高于城镇,其差异有统计学意义.致病病原体EV71、CoxA 16和其他肠道病毒同时存在,以EV71为主,占总数的50.49％.死亡病例2例均为EV71感染.结论 2012-2015年祁阳县手足口病发病水平呈逐年增高趋势,应重点加强对散居儿童的防控力度.     

Epidemiology and etiological characteristics of hand, foot and mouth disease in Huizhou City between 2008 and 2011

To study epidemiological features and etiological characteristics of hand, foot and mouth disease (HFMD), 42,012 cases were investigated from April 2008 to December 2011 in Huizhou, China. The average incidence rate was 21.16 per 10,000. The highest peak of HFMD incidence was detected between April and July each year, accounting for 55.93 % of all reported cases; another peak occurred in October through December, accounting for 24.17 % of the cases. Of the reported cases, 89.75 % were in children less than 4 years old, and there was a slight predominance of HFMD in boys and children living in rural and suburban areas. The major pathogens causing HFMD were enterovirus 71 (EV71) and coxsackievirus A16 (CA16). C4a was the most prominent EV71 subgenotype circulating in Huizhou. This founding provides insight for developing public-health interventions for the control and prevention of HFMD, especially for reducing the risk of HFMD in high-risk individuals by taking precautions against enterovirus infections.     

Simultaneous detection of human enterovirus 71 and coxsackievirus A16 in clinical specimens by multiplex real-time PCR with an internal amplification control

The recent and continuing HFMD outbreak caused by EV71 in several provinces of China since March 2008 has affected thousands of children and resulted in nearly 50 deaths. In this study, a sensitive and specific multiplex real-time RT-PCR assay has been developed for the rapid detection of EV71 and CV-A16. By using an internal amplification control, the real-time assay achieves detection of samples containing inhibitors and avoids false negatives. It should prove useful for clinical diagnosis of EV71 or CV-A16 infections.     

重庆市10102例手足口病疫情特征分析

目的分析重庆市手足口病流行特征,为制定防控措施提供科学依据。方法运用描述性流行病学方法,对重庆市手足口病发病资料进行分析。结果2008年5月至2009年6月共报告病例10102例,2008年5～6月、2009年4～6月出现发病高峰,2008年12月出现小高峰;5岁以下儿童发病占83.76%,2～4岁最多占49.89%;性别比男：女为1.55：1;主城区发病高于其它地区;实验室确诊病例344例,EV71阳性率52.91%;共报告10例以上的手足口病暴发疫情13起,均发生在小学和幼儿园,10起检出肠道病毒阳性,其中6起为EV71阳性。结论重庆市存在4～6月手足口病流行高峰;高危人群为2～4岁男孩;暴发疫情主要发生在小学和幼托机构;EV71肠道病毒是该市手足口病的主要病原体。     

深圳市重症手足口病临床与实验特征变化趋势及随访1年报告

目的比较2012与2008年深圳市重症手足口病临床和实验特征,探讨其变化趋势。方法深圳市第三人民医院2008年及2012年共收治778例手足口病住院患儿,重点分析其中260例手足口病重症患者（2008年64例,2012年196例）。通过RT—PCR检测CoxsackieA16（CoxA16,A16）及Enterovirus71（EV71）病毒核酸,出现神经系统症状或体征者检查脑脊液常规及生化,部分患儿行头颅MRI检查,同时比较临床表现、血液生化等变化趋势。所有患者随访12个月评估再发情况。结果与2008年相比,2012年手足口病重症患者发病高峰年龄下降,〈12月龄儿童分别占2008年和2012年重症的15％和40％。两个年度重症患者均以EV71感染为主;与2008年相比,2012年EV71感染所占比率有下降趋势;重症患者手、足皮疹出疹率下降,而口腔疱疹出疹率明显增高,疱疹性咽峡炎引起的重症病例数上升;外周血白细胞计数、中性粒细胞比值及CRP水平均明显增高;但并发脑干脑炎或神经源性肺水肿的病例数略有下降。随访1年结果显示,无论EV71或CoxA16型手足口病临床治愈后均可多次再发,轻症再发率高于重症。结论深圳市手足口病从2008年暴发至2012年,发病呈上升趋势,重症手足口病病例临床表现具有一些新的特征,应引起广大医护人员重视。     

2011年广州市手足口病病原谱分析

目的了解引起2011年广州市手足口病流行的病原体,确定其型别分布特征。方法收集手足口病疑似病例标本,用Real-time RT-PCR、巢式RT-PCR方法对其部分VP1基因进行扩增并测序,确定其病原谱构成,构建系统发育树。结果共收集2 067例疑似手足口病病例标本,其中实验室确诊肠道病毒阳性1 113份,包括EV71、CoxA16、CoxA6、CoxA10、CoxA9、HEV96、埃可病毒和柯萨奇B组等15种肠道病毒,其中EV71、CoxA16和CoxA6是主要病原体,分别占32.6%、39.2%和18.5%;死亡病例3例,全部由EV71引起;重症病例9例,6例由EV71引起,3例由CoxA6引起。VP1基因构建进化树分型发现,广州市2011年手足口病病原体属于HEV-A（97.2%）、HEV-B（2.5%）、HEV-C（0.3%）3个型别,未发现HEV-D型毒株。结论广州市2011年手足口病的流行主要由HEV-A型的EV71、CoxA16和CoxA6病毒引起,同时还存在HEV-B型和HEV-C型的CoxA9、EC、CoxB、CoxA24多种病毒。     

东莞市2009-2010年手足口病疫情分析及防治对策探讨

目的了解东莞市2009-2010年手足口病疫情的流行病学特点,为今后的防控工作提出对策。方法对东莞市2009-2010年手足口病疫情资料采用描述流行病学方法进行分析,对患者的咽拭子或粪便标本采用RT-PCR法进行肠道病毒核酸检测和病毒分型。结果东莞市2009年和2010年分别报告手足口病9263例和22721例,发病率分别为127.34/10万和373.28/10万。5岁以下婴幼儿分别占当年报告病例的91.68%和92.15%;散居儿童分别占当年报告病例的78.26%和73.58%;男性分别占当年报告病例的65.29%和65.27%;每年的4月份和10月份有2个发病高峰,前者为全年的发病高峰;暴发疫情均发生在托幼机构;分别有49.30%和53.65%的病例由EV71引起,所有死亡病例均由EV71引起。健康人群肠道病毒隐性感染率为11.67%,感染的主要病原体为其他肠道病毒（95.24%）。结论东莞市2010年手足口病流行强度大于2009年;应重点做好手足口病的病原学监测及5岁以下散居儿童和托幼机构的手足口病防治工作。     

惠州市重症手足口病病原谱及EV71型VP1区基因特征分析

目的分析惠州市手足口病重症病例的病原谱构成,了解惠州市肠道病毒71型分离株的VPl区基因特征．为科学防治手足口病提供科学依据。方法采集300例重症手足口病（HFMD）患者标本,采用实时荧光RT-PCR检测肠道病毒核酸,并对肠道病毒7l型（EV71）和柯萨奇病毒A16型（CoxA16）进行分型检测;选择8株EV71分离株进行VPl区基因全长序列测定,测序结果利用DNASTAR软件进行核苷酸、氨基酸序列分析和同源性比较。并用Mega5．0软件构建亲缘性进化树。结果通过实时荧光RT-PCR特异性检测,EV71阳性结果154份,阳性率为51．33％;CoxAl6阳性结果38份,阳性率为12．67％。测序结果表明,8株EV71之间的VPl基因核苷酸同源性为96．9％～99．2％。氨基酸同源性为99．3％～100％。VPI区基因遗传进化分析表明。8株EV71分离株与c4基因亚型的代表株处于同一分支,均属于C4基因亚型的C4a进化分支。结论惠州市手足口病疫情主要病原EV71病毒均属于C4a基因亚型,与2004年以来的中国大陆EV71病毒流行的基因型一致,未产生明显的抗原漂移及变异。     

广州市越秀区2008-2009年手足口病流行病学特征

目的探讨广州市越秀区手足口病的流行病学特征,为制定科学的防控措施提供依据。方法统计分析从国家疾病监测信息管理系统获得的越秀区手足口病病例资料。结果广州市越秀区2008-2009年共发生手足口病1331例,2008年发病率为3.96/万,2009年发病率为7.50/万,2009年手足口病的发病率明显上升（χ2=125.7,P〈0.001）。男女比为1.61：1,2～4岁组儿童发病率最高,4-6月为发病高峰,流动人口密集的地区发病率较高,流行期间易在托幼机构中引起暴发。2008年及2009年报告实验室确诊病例为61例和120例,分别占总报告例数的12.71%和13.78%,其中2008年EV71占优势,2009年则是CoxA16占优势。结论手足口病的发生有明显的地区、年龄和时间差异,掌握手足口病流行病学特征,将有助于更好地开展预防和控制工作。     

Cost-effectiveness of bivalent versus monovalent vaccines against hand,foot and mouth disease

ObjectivesEnterovirus 71 (EV71) and coxsackievirus A16 (CA16) were responsible for 43.3% (235 123/543 243) and 24.8% (134 607/543 243) of all laboratory-confirmed hand, foot and mouth disease (HFMD) cases during 2010–2015 in China. Three monovalent EV71 vaccines have been licensed in China while bivalent EV71/CA16 vaccines are under development. A comparative cost-effectiveness analysis of bivalent EV71/CA16 versus monovalent EV71 vaccination would be useful for informing the additional value of bivalent HFMD vaccines in China.MethodsWe used a static model parameterized with the national HFMD surveillance data during 2010–2013, virological HFMD surveillance records from all 31 provinces in mainland China during 2010–2013 and caregiver survey data of costs and health quality of life during 2012–2013. We estimated the threshold vaccine cost (TVC), defined as the maximum additional cost that could be paid for a cost-effective bivalent EV71/CA16 vaccine over a monovalent EV71 vaccine, as the outcome. The base case analysis was performed from a societal perspective. Several sensitivity analyses were conducted by varying assumptions governing HFMD risk, costs, discounting and vaccine efficacy.ResultsIn the base case, choosing the bivalent EV71/CA16 over monovalent EV71 vaccination would be cost-effective only if the additional cost of the bivalent EV71/CA16 compared with the monovalent EV71 vaccine is less than €4.7 (95% CI 4.2–5.2). Compared with the TVC in the base case, TVC increased by up to €8.9 if all the test-negative cases were CA16-HFMD; decreased by €1.1 with an annual discount rate of 6% and exclusion of the productivity loss; and increased by €0.14 and €0.3 with every 1% increase in bivalent vaccine efficacy against CA16-HFMD and differential vaccine efficacy against EV71-HFMD, respectively.ConclusionsBivalent EV71/CA16 vaccines can be cost-effective compared with monovalent EV71 vaccines, if suitably priced. Our study provides further evidence for determining the optimal use of HFMD vaccines in routine paediatric vaccination programme in China.     

A large outbreak of hand, foot, and mouth disease caused by EV71 and CAV16 in Guangdong, China, 2009

A large outbreak of hand, foot and mouth disease (HFMD) occurred in Guangdong, China, in 2009. A total of 92,749 cases were officially reported to the Center for Disease Control and Prevention of Guangdong (GDCDC). To clarify the pathogen causing the outbreak, 600 specimens, including stool, rectal swabs, vesicular swabs, cerebrospinal fluid, and throat swabs, were collected from 541 patients and subjected to one-step RT-PCR. Four hundred eighty-nine of 541 patient samples were positive for enterovirus. All positive samples were cultured on RD and Hep2 cells; 307 specimens displayed CPE. Sequence analysis of PCR fragment and typing real-time PCR indicated that these isolates included EV71 (56%), CAV16 (35.5%), CAV6 (2.0%), CAV10 (1.0%), CAV2 (0.7%), CAV4 (1.3%), Echo30 (0.7%), Echo25 (1.0%), Echo4 (0.3%), CBV5 (1.0%) and human rhinovirus (0.7%). 100% (12/12) of fatal cases and 97.2% (140/144) of severe cases carried EV71 and CAV16. The results implied that EV71 and CAV16 were mainly responsible for the outbreak. Comparison with the three global types of EV71 and the five clusters of genotype C showed that the sequences from mainland China (not including the Hong Kong region) are located in subgenogroup C-4 and originate from isolates from the Shenzhen area of Guangdong Province. Results from this study show that the C-4 genotype has been a prevalent pathogen in mainland China since 1998.     

轻型和重型手足口病临床和实验室特征分析

目的 研究2008年深圳市轻型和重型手足口病临床特点和实验室特征.方法 将深圳市东湖医院和儿童医院共145例手足口病住院患者作为研究对象,其中轻型124例,重型21例.收集患者临床和一般实验室资料,急性期与恢复期连续粪便和血标本,通过RT-PER检测EV71病毒核酸,分离和培养EV71肠道病毒,其中2例死亡患者行病理组织学检测.结果 与轻型患者比较,重型患者白细胞计数、血糖显著升高,但年龄显著降低,粪便中轻型和重型患者EV71基因检出率分别为35%与67%,重型患者EV71检出率显著高于轻型患者,从9例患者粪便中分离培养出肠道病毒,其中1例为死亡患者粪便标本.2例患者死于神经源性肺水肿和脑干脑炎.结论 EV71是重型患者和死亡患者的最主要病原体,神经源性肺水肿和脑干脑炎是EV71型手足口病的最主要死亡原因,对年龄小于4岁,高热、皮疹稀疏和高血糖的EV71型手足口病患者应警惕向重型发展.     

河北省手足口病病例的病原构成及EV71病毒基因特征分析

目的了解河北省不同地区、不同严重程度手足口病病例的病原构成情况及EV71病毒的基因特征。方法采集河北省不同地区的HFMD患者粪便、疱疹液、咽拭子标本进行核酸检测和病毒分离,同时结合所收集的HFMD患病例的居住地、疾病严重程度信息加以分析。选取18株EV71阳性分离株进行VP1编码区基因扩增和核苷酸序列测定和分析,与其它38株各基因型和基因亚型的EV71代表株构建系统发生树。结果2009年河北省HFMD临床诊断病例的EV阳性率为65．13％,其中以EV71为主,占阳性病例的58．0％（752／1296）。秦皇岛、邯郸、保定、邢台地区手足口病例以EV71感染为主,而衡水、沧州等地区则以CA16为主。轻型病例中EV71阳性率为37．74％,重症病例中EV71阳性率为80．64％,死亡病例检测13例,均为EV71阳性。18株EV71分离株的VP114核苷酸同源性为94．9％～99．8％,与C4亚型代表株的VP1区核苷酸同源性最高,为91．9％～99．6％。进化树结果显示,河北省EV71分离株与c4亚型代表株处于同一分支,并在C4a进化分支的不同簇中。结论2009年引起河北省手足口病流行的病原体主要为EV71和CA16。秦皇岛、邯郸、保定、邢台地区手足口病例以EV7I感染为主,而衡水、廊坊、沧州等地区则以CA16为主。EV71是重症病例的主要致病病原体。河北省EV71分离株为c4亚型C4a进化分支。     

Diagnosis of hand,foot, and mouth disease caused by EV71 and other enteroviruses by a one‐step,single tube,duplex RT‐PCR

Hand, foot, and mouth disease (HFMD) is caused mainly by enterovirus 71 (EV71) and other enteroviruses (EVs) such as Coxsackie A16 in China. EV71 infection can lead to severe clinical manifestations and even death. Other EVs, however, generally cause mild symptoms. Thus, early and accurate distinction of EV71 from other EVs for HFMD will offer significant benefits. A one‐step, single tube, duplex RT‐PCR assay is described in the present study to detect simultaneously EV71 and other EVs. The primers used for the duplex RT‐PCR underwent screening and optimization. The detection threshold was 0.001 TCID₅₀/ml for EV71 and 0.01 TCID₅₀/ml for other EVs. The positive rate of enterovirus detection in 165 clinical samples reached 68.5%, including 46.1% for EV71 and 22.4% for other EVs. Of all the severe HFMD cases, EV71 was responsible for 85.3% cases. The positive rate of EV71 fell markedly by day 8 after onset. In addition, sequencing of EV71 specific amplicons from duplex RT‐PCR revealed that C4a was the predominant subgenotype of EV71 circulating in Nanjing, China. The accuracy and reliability of the assay suggest strongly that the one‐step, single tube, duplex RT‐PCR will be useful for early diagnosis and monitoring of EV71 and other EV infections. J. Med. Virol. 84:1803–1808, 2012. © 2012 Wiley Periodicals, Inc.     

Clinicopathologic features and molecular analysis of enterovirus 71 infection: report of an autopsy case from the epidemic of hand, foot and mouth disease in China

A 15-month boy with fatal hand, foot, and mouth disease (HFMD) exhibited atypical symptoms and progressed rapidly to death. An autopsy was performed the next day and tissue sections were stained for histopathological examination. His intestinal samples were tested for enterovirus 71 (EV71), and the whole-genome sequence of EV71 was analyzed. An autopsy revealed that the central nervous system, lungs, and gut displayed severe meningitis and brainstem encephalitis, remarkable pulmonary congestion, edema, moderate inflammatory infiltration, and hemorrhage as well as intestinal mucosal congestion, epithelial necrosis, thinning intestinal wall, and submucosal lymphoid follicular hyperplasia. The heart showed myocardial interstitial congestion, myocardial edema, and some inflammatory infiltrates. There were no significant alterations in the architecture of other organs. EV71 antigen and apoptotic cells were detected in brain, lung and intestine by immunohistochemical staining and TUNEL (TdT-mediated dUTP nick-end labeling) respectively. Intestinal contents and intestinal autopsy samples of this case were positive for EV71, and the EV71 strain was classified as subgenogroup C4. In China, the severe forms of HFMD were mostly caused by EV71 subgenogroup C4 infection. Severe intestinal damages may relate to EV71 subgenogroup C4 infection. Thus, children with severe EV71 HFMD may have serious pathological changes in their central nervous system, lungs, and gut. Physicians should pay special attention to infants with atypical symptoms, particularly in EV71 epidemic areas for early diagnosis and treatment.     

西安地区2008年肠道病毒71型基因特征分析

目的 研究西安地区2008年引起手足口病病原构成及EV71的基因特征.方法 采集124例临床诊断手足口病病例标本,RT-PCR检测肠道病毒血清型别;挑选EV71阳性标本进行病毒分离,扩增7株EV71病毒,扩增其VP1区,测序并与EV71各血清型代表株序列比对,进行进化分析.结果 2008年西安地区手足口病（HFMD）的病原中CA16占49.45%,EV71占30.76%,其他肠道病毒占19.78%.7株EV71 VP1区与标准株序列比对,亲缘进化分析显示本地区EV71与中国大陆其他地区毒株相似.结论 2008年西安地区引起手足口病的病原以CA16为主,而EV71属于C4亚型.     

2008年深圳地区手足口病病原学调查

目的 研究2008年深圳地区手足口病病原体EV71和CoxA16感染情况,为手足口病的防治提供依据.方法 应用RT-PCR技术检测307例手足口病患儿标本病原体EV71、CoxA16基因,将PCR产物测序,并应用ChstaIW2在线分析软件进行序列分析、进化树分析.结果 不同标本中EV71的阳性率分别为:大便标本24.4%(75/307)、咽拭子为7.8%(24/307)、外周血12.5%(1/8);CoxA16的阳性率分别为,大便13.8%(28/203),咽拭子11.0%(20/181),其中EV71和CoxA16同时为阳性的有3份(0.98%);脑脊液标本未检测到EV71和CoxA16.与标准株BrCr序列比对分析,测序的14例标本中,8例的EV71新出现多个位点变异,其中2例标本的A2528G变异导致氨基酸改变,即N595D,1例标本的A2714G变异引起氨基酸改变,即1658V.进化树分析显示,有2例标本的病毒株与anhui毒株亲缘关系较近,与标准株BrCr及深圳株SHH02-6、SHZH02-40、SHZH03-58等亲缘关系较远;而其余12株与上述毒株亲缘关系较远.根据文献报道的EV71基因分型方法分析,测序的14株EV71基因型为C型.结论 在引起2008年深圳手足口病病原体中相当的比例是EV71,且可能部分是anhui病毒株的入侵.     

2010年安义县手足口病的流行特征分析

目的分析2010年安义县手足口病流行病学和病原学特征,为手足口病的防控工作提供依据。方法搜集手足口病资料,录入SPSS13.0,并进行统计分析。结果 2010年安义县共报告手足口病253例,发病率为104.76/10万,病死率为0.40%,发病年龄多集中在3岁以下儿童。男性多于女性,以散居儿童为主。全年均有病例发生,1-3月份为发病高峰。病原学检测结果,肠道病毒71型阳性率为28.30%,柯萨奇病毒A组16型阳性率为16.98%,其他肠道病毒阳性率为13.21%。结论 2010年安义县手足口病发病率较高,3岁以下散居儿童为重点人群。肠道病毒71型、柯萨奇病毒A组16型是引起安义县手足口病的主要病原体。