手足口病的流行现状及挑战

手足口病是由肠道病毒所致的全球性传染病.自20世纪90年代后期由肠病道毒所致的手足口病在亚太地区频繁暴发流行,其严重的神经系统并发症以及神经源性肺水肿致患者残疾和死亡.我国自2008年起每年发生全国范围的手足口病暴发流行,其中肠道病毒71型(EV71)是引起暴发而致死亡的主要病原体.目前手足口病已成为我国各类传染病中发病数最高的丙类传染病,给公共卫生带来严峻挑战.虽然绝大多数手足口病为自限性疾病,但约0.05％的患儿病情变化迅速并死亡,目前尚缺乏有效的抗病毒药物和疫苗来防治.因此,早期识别危重病例、早期进行合理临床管理和诊疗干预·以及采取及时有效的防控措施是降低手足口病所致危害的最主要策略.我国已在积极研发EV71疫苗,这将给手足口病流行暴发及其重症疾病的预防带来希望,并有望有效降低社会经济负担.     

493例手足口病的临床治疗体会

近年来,部分省市发生了手足口病的局部流行,该病为肠道病毒引起的以皮疹为主要临床特征的传染性疾病。手足口病在我国已经纳入了丙类传染病进行管理。我院自2007年3月至2009年10月共收治手足口病493例。经观察治疗,效果满意,现报告如下。     

手足口病的流行及防治研究进展

手足口病是由于感染肠道病毒所致的一种急性传染病,这种传染病常见于3岁左右的幼儿且有多种传播途径。手足口病的患病早期的表现与感冒症状很相似,不容易引起家长的重视,但是往往持续发热几天后小儿的手部、足部、臀部以及口腔等部位就会出现疱疹甚至溃破,病情严重的患儿可产生各种严重的并发症而导致死亡。本文对手足口病的流行进行了阐述,另外分析探讨了其疾病的防治研究的进展。     

深圳市南山区学校及托幼机构2010-2012年传染病暴发疫情分析

目的:分析南山区学校幼儿园2010-2012年传染病暴发疫情流行情况,探讨预防及控制疫情暴发的策略及方法.方法:以2010年南山区区级研究课题《学校传染病监测和预警系统研究》中开发的《学校传染病监测和预警系统》中的监测数据为基础数据,同时结合现场流行病学调查结果,采用MS Excel和SPSS对数据进行统计分析.结果:2010-2012年南山区学校及托幼机构共发生519起暴发疫情,其中甲类传染病疫情0起,乙类疫情56起,丙类传染病暴发疫情428起,其他传染病暴发疫情35起.暴发疫情种类以流感、手足口病、流行性出血热、感染性腹泻、水痘等为主,罹患人群共4227人,全区8个街道均有疫情发生,春秋季节暴发疫情较多,尤以3月份和9月份居多.结论:应重点加强学校和托幼机构等易感人群密集场所的传染病监测及疫情报告机制,落实晨检和因病缺课报告工作,提高疫情预警效率并及时采取防控措施,预防及控制流感、感染性腹泻、手足口病、水痘等常见传染病暴发疫情的发生,保护学生及幼儿的身体健康.     

2015年大连高新区传染病疫情分析

摘要：目的 对大连高新区2015年法定报告传染病进行分析,找出其流行规律,为降低和控制传染病发生提供依据。方法 采用描述流行病学分析方法。结果 2015年大连高新区共报告法定传染病13种499例,年发病率390.37/10万,同比上升了19.35%。发病数居前5位的是手足口病、梅毒、猩红热、其他感染性腹泻、肺结核,占发病总数的88.38%。结论 2015年大连高新区法定传染病以肠道传染病、呼吸道传染病、血源及性传播传染病为主,应针对高发传染病的流行特点采取有针对性的预防控制措施,以降低传染病的发病率。     

从手足口病的管理谈医院传染病的归口管理与集中收治

目的:从手足口病的管理探讨医院对传染病的归口管理与集中收治的相关问题.方法:2011年9月至2012年6月期间,共收治传染624例,占所有就诊患者的3.6％,其中手足口病患者66例,占所有传染病患者的10.58％,占所有就诊患者的3.81‰.积极相应我地区卫生管理部门的号召,召开全体员工大会,从思想上保证所有成员都全身心地投入到防止工作中去.根据卫生部门的相关要求,学校及幼儿园、车站、码头等人流密集地区也安排专业的医疗人员对过往行人进行检查,一旦发现疑似及确诊为手足口病的患者则马上加以隔离,并进行相关治疗.结果:经4-12周的治疗,所有患者均符合临床痊愈的标准,手足口病的传染源也得到了有效的控制.除此之外,本地未见其他手足口病被传染患者.结论:要健全并完善传染病的归口管理和集中收治体系,必须从法律、行政及执行多个层面共同入手,提升整个社会对于传染病的防范意识和救治能力,进而保证社会和谐化发展,人民的健康得到有效的保障.     

肠道病毒71型流行病学与病原学研究进展

肠道病毒71型（Enterovims71,Ev71）与柯萨奇病毒A组16型（CoxsackieA16,CA16）是婴幼儿常见传染病手足口病（Hand footmouth disease,HFMD）的主要病原,临床上以发热和口腔黏膜溃疡性疱疹及四肢末端水疱样皮疹为主要症状,个别患者可引起心肌炎、肺水肿、无菌性脑膜脑炎等致命性并发症,2种病原所致的手足口病临床难以区别,但EV71可引起严重中枢神经系统并发症,如无菌性脑膜炎（Aseptic Memnsitis）、脑干脑炎（Brainstem Encephalitis）和脊髓灰质炎样的麻痹（Poliomyelitis-like Paralysis）等。手足口病是全球性传染病,世界大部分地区均有此病流行的报道,已引起了全世界的普遍关注,其中由EV71引起的多种与神经系统相关的疾病严重威胁婴幼儿患者的生命,我国于2008年5月将其列入法定传染病中丙类进行管理。本文将从预防控制EV71感染的角度,对流行病学和病原学方面的资料进行整理和讨论。     

牛布鲁氏菌病阳性血清国家标准品的研制

手足口病是由多种肠道病毒感染导致的一种急性儿科传染病。近年来,我国肠道病毒71型 (EV71) 手足口病发病率急剧上升,重症病例时有报道,严重威胁儿童健康。临床上对于重症手足口病的治疗缺乏有效手段,主要以对症治疗和支持疗法为主。静脉注射人免疫球蛋白由健康献血员血浆提取纯化而来,含有包括EV71在内的多种肠道病毒的中和抗体,可作为重症手足口病被动免疫和免疫调节的重要手段,值得关注。     

许昌市小学生传染病知识知晓途径及行为情况调查分析

目的分析许昌市小学生了解传染病途径及行为,以期为进一步加强传染病预防控制及实践工作提供科学依据。方法采用两阶段分层整群抽样法,对许昌市6个区县18所小学2160名小学生,通过问卷调查小学生传染病获取途径、知晓率及行为情况。结果小学生传染病知识知晓率调查显示,女生流感预防措施、艾滋病传播途径、手足口病传染途径、乙肝传播途径、接种禁忌证、肺结核症状体征、狗咬伤处理方法知晓率高于男生(P0.05),城市流感预防措施、手足口病传染途径、麻疹预防方法、接种禁忌证、艾滋病传播途径、肺结核症状体征、狗咬伤处理方法高于郊区(P0.05)。经课堂教学、多媒体录像、电视及周围人群谈论知晓率分别为32.08%、26.44%、23.70%及17.78%,饭前便后洗手率、毛巾共用率、洗手使用肥皂率、吐痰至痰盂率、有疾病症状通知师长率分别为71.25%、35.79%、43.10%、90.32%、68.19%。结论许昌市小学生传染病知识知晓率仍有不足,通过前期调查了解,依据小学生掌握情况及特点,结合多种途径进行健康教育促进其健康行为提升。     

重症手足口病免疫球蛋白治疗的机理探讨

手足口病是由多种肠道病毒感染导致的一种急性儿科传染病.近年来,我国肠道病毒71型(EV71)手足口病发病率急剧上升,重症病例时有报道,严重威胁儿童健康.临床上对于重症手足口病的治疗缺乏有效手段,主要以对症治疗和支持疗法为主.静脉注射人免疫球蛋白由健康献血员血浆提取纯化而来,含有包括EV71在内的多种肠道病毒的中扣抗体,可作为重症手足口病被动免疫和免疫调节的重要手段,值得关注.     

Short-Term Effect of El Ni?o-Southern Oscillation on Pediatric Hand,Foot and Mouth Disease in Shenzhen,China

Hand, foot and mouth disease (HFMD) was an emerging viral infectious disease in recent years in Shenzhen. The underlying risk factors have not yet been systematically examined. This study analyzed the short-term effect of El Niño-Southern Oscillation on pediatric HFMD in Shenzhen, China. Daily count of HFMD among children aged below 15 years old, Southern Oscillation Index (SOI), and weather variables were collected to construct the time series. A distributed lag non-linear model was applied to investigate the effect of daily SOI on pediatric HFMD occurrence during 2008–2010. We observed an acute effect of SOI variation on HFMD occurrence. The extremely high SOI (SOI = 45, with 0 as reference) was associated with increased HFMD, with the relative risk (RR) being 1.66 (95% Confidence Interval [CI]: 1.34–2.04). Further analyses of the association between HFMD and daily mean temperature and relative humidity supported the correlation between pediatric HFMD and SOI. Meteorological factors might be important predictors of pediatric HFMD occurrence in Shenzhen.     

Early warning of hand,foot, and mouth disease transmission: A modeling study in mainland,China

BackgroundHand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model.MethodsThis study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, “epidemic acceleration week (EAW)” and “recommended warning week (RWW)”, were calculated to show the early warning time.ResultsThe mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R² > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions.ConclusionsThe disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD.     

Spatial-temporal mapping and risk factors for hand foot and mouth disease in northwestern inland China

BackgroundHand foot and mouth disease (HFMD) is becoming one of the common human infectious diseases in China. Previous studies have described HFMD in tropical or coastal areas of Asia-Pacific countries. However, limited studies have thoroughly studied the epidemiology and potential risk factors for HFMD in inland areas with complex environmental conditions.Methodology/Principal findingsUsing the data from 2009 to 2018 on reported cases of Xinjiang Uighur Autonomous Region, we characterized the epidemic features of HFMD. Panel negative binomial model was used to identify climate, geographical and demographic determinants for HFMD incidence. A total of 70856 HFMD cases (average annual incidence: 305 per million persons) were reported in Xinjiang during the 10-year study period, of which 10393 (14.7%) were laboratory-confirmed and 98 (0.1%) were severe. HFMD peaked in summer every year during the study period, and incidence in 2012, 2015, 2016 and 2018 had minor peaks in autumn. After adjusting the school or holiday month, multiple factors were found to affect HFMD epidemiology: urban area being major land cover type (incidence risk ratio, IRR 2.08; 95% CI 1.50, 2.89), higher gross domestic product per capita (IRR 1.14; 95% CI 1.11, 1.16), rise in monthly average temperature (IRR 1.65; 95% CI 1.61, 1.69) and monthly accumulative precipitation (IRR 1.20; 95% CI 1.16, 1.24) predicted increase in the incidence of HFMD; farmland being major land cover type (IRR 0.72; 95% CI 0.64, 0.81), an increase of percentage of the minority (IRR 0.91; 95% CI 0.89, 0.93) and population density (IRR 0.98; 95% CI 0.98, 0.99) were related to a decrease in the incidence of HFMD.Conclusions/SignificanceIn conclusion, the epidemic status of HFMD in Xinjiang is characterized by low morbidity and fatality. Multiple factors have significant influences on the occurrence and transmission of HFMD in Xinjiang.     

Prevalence of Multiple Enteroviruses Associated with Hand,Foot, and Mouth Disease in Shijiazhuang City,Hebei Province,China: Outbreaks of Coxsackieviruses A10 and B3

Hand, foot, and mouth disease (HFMD) has been one of the most common infectious diseases in Shijiazhuang City, as is the situation in China overall. In the National HFMD surveillance system, the pathogen detection was focused on EV-A71 and CVA16, and therefore, information on the other EVs is very limited. In order to identify the circulating EV serotypes in the HFMD outbreaks in Shijiazhuang City during 2010–2012, 4045 patients presented with HFMD were recruited in the study, and clinical samples were investigated. Typing of EV serotypes was performed using the molecular typing methods, and phylogenetic analyses based on entire VP1 sequences of human enterovirus 71 (EV-A71), coxsackievirus A16 (CVA16), CVA10 and CVB3 was performed. The results revealed that EV-A71 and CVA16 were the 2 most important pathogens but the circulating trends of the 2 viruses showed a shift, the spread of EV-A71 became increasingly weak, whereas the spread of CVA16 became increasingly stronger. CVA10 and CVB3 were the third and fourth most prevalent pathogens, respectively. Co-infection of two viruses at the same time was not found in these samples. Based on entire VP1 region sequences, the phylogenetic analysis revealed that C4a subgenotype EV-A71, B1a and B1b subgenotype CVA16 continued to evolve. The CVA10 strains were assigned to 4 genotypes (A–D), whereas the CVB3 strains were assigned to 5 genotypes (A–E), with clear geographical and temporal-specific distributions. The Shijiazhuang CVA10 sequences belonged to 4 epidemic lineages within genotype C, whereas the Shijiazhuang CVB3 sequences belonged to 2 epidemic lineages within genotype E, which may have the same origins as the strains reported in other part of China. CVA10 and CVB3, 2 pathogens that were previously infrequently detected, were identified as pathogens causing the HFMD outbreaks. This study underscores the need for detailed laboratory-based surveillances of HFMD in mainland China.     

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.     

National Epidemiology and Evolutionary History of Four Hand,Foot and Mouth Disease-Related Enteroviruses in China from 2008 to 2016

Hand, foot and mouth disease(HFMD) is a major public health concern in China. The most predominant enteroviruses that cause HFMD have traditionally been attributed to enterovirus A71(EVA71) and coxsackievirus A16(CVA16). Since its first large outbreak in 2008, the dominant HFMD pathogens are constantly changing. In 2013 and 2015, CVA6 exceeded both EVA71 and CVA16 to become the leading cause of HFMD in some provinces. However, there still lacks a comprehensive overview on the molecular epidemiology and evolution of HFMD-related enteroviruses at the national level. In this study, we performed systematic epidemiological analyses of HFMD-related enteroviruses using the data of 64 published papers that met the inclusion criteria, and conducted phylogenetic analyses based on 12,080 partial VP1 sequences identified in China before 31 st June 2018. We found that EVA71 prevalence has decreased sharply but other enteroviruses have increased rapidly from 2008 to 2016 and that one subtype of each enterovirus is represented during the epidemic. In addition, four genotypes EVA71_C4, CVA16_B1, CVA6_D and CVA10_C are the most predominant enterovirus strains and collectively they cause over 90% of all HFMD cases in China according to the phylogenetic trees using representative partial VP1 sequences. These four major enterovirus genotypes have different geographical distributions, and they may cocirculate with other genotypes and serotypes. These results suggest that more molecular epidemiological studies should be performed on several enteroviruses simultaneously, and such information should have implications for virological surveillance, disease management, vaccine development and policy-making on the prevention and control of HFMD.     

The Effect of Meteorological Variables on the Transmission of Hand,Foot and Mouth Disease in Four Major Cities of Shanxi Province,China: A Time Series Data Analysis (2009-2013)

Increased incidence of hand, foot and mouth disease (HFMD) has been recognized as a critical challenge to communicable disease control and public health response. This study aimed to quantify the association between climate variation and notified cases of HFMD in selected cities of Shanxi Province, and to provide evidence for disease control and prevention. Meteorological variables and HFMD cases data in 4 major cities (Datong, Taiyuan, Changzhi and Yuncheng) of Shanxi province, China, were obtained from the China Meteorology Administration and China CDC respectively over the period 1 January 2009 to 31 December 2013. Correlations analyses and Seasonal Autoregressive Integrated Moving Average (SARIMA) models were used to identify and quantify the relationship between the meteorological variables and HFMD. HFMD incidence varied seasonally with the majority of cases in the 4 cities occurring from May to July. Temperatures could play important roles in the incidence of HFMD in these regions. The SARIMA models indicate that a 1° C rise in average, maximum and minimum temperatures may lead to a similar relative increase in the number of cases in the 4 cities. The lag times for the effects of temperatures were identified in Taiyuan, Changzhi and Yuncheng. The numbers of cases were positively associated with average and minimum temperatures at a lag of 1 week in Taiyuan, Changzhi and Yuncheng, and with maximum temperature at a lag of 2 weeks in Yuncheng. Positive association between the temperature and HFMD has been identified from the 4 cities in Shanxi Province, although the role of weather variables on the transmission of HFMD varied in the 4 cities. Relevant prevention measures and public health action are required to reduce future risks of climate change with consideration of local climatic conditions.     

Characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern China

Human enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) has been a leading cause of childhood infection in China since 2008. Epidemic and molecular characteristics of HFMD have been examined in many areas of China, including the central and southern regions. However, clinical and genetic characterization of EV71 in the northeastern region of China is scarce. In this study, a series of analyses were performed on seven full-length EV71 sequences from HFMD patients who had either severe or mild disease. We have determined that these seven circulating EV71 viruses from Changchun, China are actually complex recombinant viruses involving multiple type A human enterovirus (HEV). Classified as EV71 subtype C4 (EV71 C4), these Changchun EV71 viruses contain genetic recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the structural protein region (P1) of these viruses resembled that of the prototype EV71 C1 strains. The non-structural protein domains (P2 and P3) showed a high degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5'UTR had unclassified recombination,while partial 3D region of these viruses showed a high degree of similarity to CA16. Phylogenetic analysis of full-length or partial sequences of isolates from severe or mild disease patients in Changchun always formed a single cluster in various phylogenetic analyses of different genomic regions, suggesting that all seven strains originated from one single common ancestor. There was no correlation between viral genomic sequence and virulence. Thus, we found that circulating recombinant forms of EV71 are prevalent among HFMD patients in Northeastern China. The existence of a unique cluster of EV71 related viruses in Northeast China has important implications for vaccine development that would address the increasing prevalence of HFMD.     

Serum Amyloid A and Clusterin as Potential Predictive Biomarkers for Severe Hand,Foot and Mouth Disease by 2D-DIGE Proteomics Analysis

Hand, foot, and mouth disease (HFMD) affects more than one million children, is responsible for several hundred child deaths every year in China and is the cause of widespread concerns in society. Only a small fraction of HFMD cases will develop further into severe HFMD with neurologic complications. A timely and accurate diagnosis of severe HFMD is essential for assessing the risk of progression and planning the appropriate treatment. Human serum can reflect the physiological or pathological states, which is expected to be an excellent source of disease-specific biomarkers. In the present study, a comparative serological proteome analysis between severe HFMD patients and healthy controls was performed via a two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy. Fifteen proteins were identified as differentially expressed in the sera of the severe HFMD patients compared with the controls. The identified proteins were classified into different groups according to their molecular functions, biological processes, protein classes and physiological pathways by bioinformatics analysis. The up-regulations of two identified proteins, serum amyloid A (SAA) and clusterin (CLU), were confirmed in the sera of the HFMD patients by ELISA assay. This study not only increases our background knowledge about and scientific insight into the mechanisms of HFMD, but also reveals novel potential biomarkers for the clinical diagnosis of severe HFMD.     

Spatiotemporal Cluster Patterns of Hand,Foot, and Mouth Disease at the County Level in Mainland China, 2008-2012

Background

Hand, foot, and mouth disease (HFMD) is known to be a highly contagious childhood illness. In recent years, the number of reported cases of HFMD has significantly increased in mainland China. This study aims at the epidemiological features, spatiotemporal patterns of HMFD at the county/district level in mainland China.

Methods

Data on reported HFMD cases for each county from 1 January 2008 to 31 December 2012 were obtained from the Chinese Center for Disease Control and Prevention. Cluster analysis, spatial autocorrelation, and retrospective scan methods were used to explore the spatiotemporal patterns of the disease.

Results

The annual incidences varied greatly among the counties, ranging from 0 to 74.31‰ with the median of 5.42‰ (interquartile range: 1.54‰–13.55‰) during 2008–2012 in mainland China. Counties close to provincial capital cities generally had higher incidences than rural counties. A seasonal distribution was observed between the northern and southern China, of which dual epidemic were shown in southern China and usually only one in northern China. Based on the global and local spatial autocorrelation analysis, we found that the spatial distribution of HFMD was presented a significant clustering pattern for each year (P<0.001), and hotspots of the disease were mostly distributed in coastal provinces of China. The retrospective scan statistic further identified the dynamics of spatiotemporal clustering areas of the disease, which were mainly distributed in the counties of eastern and southern China, as well as provincial capitals and their surrounding counties.

Conclusions

The spatiotemporal clustering areas of the disease identified in this way were relatively stable, and imminent public health planning and resource allocation should be focused within those areas.