手足口病(Hand foot mouth disease, HFMD) 是由肠道病毒引起的传染病，多发生于5岁以下的婴幼儿，可引起发热和手、足、口腔等部位的皮疹、溃疡，个别患者可引起心肌炎、肺水肿、无菌性脑膜脑炎等并发症。引发手足口病的肠道病毒有20多种，其中柯萨奇病毒(Cox Asckievirus) A16 型(Cox A16) 和肠道病毒71型（Enterovirus71.EV 71）最常见。hand-foot-mouth disease is a disease which is leaded by some kinds of Enterovirus, and normally is be found between some kidd below 5 years old, it can lead fever, some tetter or ulceration both in hand, foot, mouth, and some even in buttacks and knee, in some serious case, it can also cause carditis, pulmonary edema or aseptic meningitis, there are more than 20 kinds of virus which can cause hand-foot-mouth disease, the most comman are cox asckievirus A16, and Enterovirus71,

　　一、流行概况summary of epidemiology

　　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导。1957年新西兰首次报导，1958年分离出柯萨奇病毒，1959年提出HFMD 命名。早期发现的手足口病的病原体主要为Cox A16型，手足口病与EV 71感染有关的报导则始自20世纪70年代初，1972年EV 71在美国被首次确认。此后EV 71感染与Cox A16感染交替出现，成为手足口病的主要病原体。hand-foot-mouth disease is a global effectious disease, it was reported all over the world, and it is first reported in new zealand in 1957, and in 1958 fostered a virus name Cox Asckievirus, 1957 start named this microgam used HFMD method, at the begining of this disease, the main virus is Cox Asckievirus, and from  the early stage of 1970, such as in 1972, the Enterovirus was found in Americian, and from then on, the Cox asckievirus and enterovirus cause this disease alternately.

　　澳大利亚和美国、瑞典一样，是最早出现EV 71感染的国家之一。1972～1973 年、1986年和1999年澳大利亚均发生过EV 71流行，重症病人大多伴有中枢神经系统症状(CNS)，一些病人还有严重的呼吸系统症状。20世纪70年代中期，保加利亚、匈牙利相继暴发以CNS为主要临床特征的EV 71流行，仅保加利亚就超过750例发病，149人致瘫，44人死亡。英国1994年4季度暴发了一起遍布英格兰威尔士由Cox A16引起的手足口病流行，监测哨点共观察到952个病例，为该国有记录以来的最大一次流行，患者大多1～4岁，大部分病人症状平和。该国1963年以来的流行病资料数据显示，手足口病流行的间隔期为2～3年。其它国家如意大利、法国、荷兰、西班牙、罗马尼亚、巴西、加拿大、德国也经常发生由各型柯萨奇、埃可病毒和EV 71引起的手足口病。日本是手足口病发病较多的国家，历史上有过多次大规模流行，1969～1970年的流行以Cox A16感染为主，1973和1978年的2 次流行均为EV 71引起，主要临床症状为手足口病，病情一般较温和，但同时也观察到伴无菌性脑膜炎的病例。1997～2000年手足口病在日本再度活跃，EV 71、Cox A16均有分离，EV 71毒株的基因型也与以往不同。20世纪90年代后期，EV 71开始肆虐东亚地区。1997年马来西亚发生了主要由EV 71引起的手足口病流行，4～8月共有2628例发病，仅4～6月就有29例病人死亡。死者平均年龄1.5 岁，病程仅2天，100％发热，62％手足皮疹，66％口腔溃疡，28％病症发展迅速，17％肢软瘫，17例胸片显示肺水肿。australia, americian and sweden are the former country where found Enterovirus, during 1972-1973 and 1980-1999, Australia have this epidemic which just leaded by Enterovirus, and those serious disease all had symptom of center neural systom, and some also has serious symptom of respiratory system, from the history of hand-foot-mouth disease, the enterovirus is much more easier to cause some serious case and a higher mortality/ death rate, according to the data from 1963, the hand-foot-mouth disease can break out every 2-3 years, 1969-1970 the main microgam is Cox As, and from 1973 and 1978 is Enterovirus, and in 1997-2000 both Cox As and EV were found, and EV start to variance

　　我国自1981年在上海始见本病，以后北京、河北、天津、福建、吉林、山东、湖北、西宁、广东等十几个省市均有报导。1983年天津发生Cox A16引起的手足口病暴发流行，5～10月间发生了7 000余病例，经过2年散发流行后，1986年又出现暴发，在托儿所和幼儿园2次暴发的发病率分别达2.3％和1.9％。1995年武汉病毒研究所从手足口病人中分离出EV 71病毒，1998年深圳市卫生防疫站也从手足口病患者中分离出2株EV 71病毒。1998年EV 71感染在我国台湾省引发大量手足口病和疱疹性咽峡炎，在6月和10月两波流行中，共监测到129 106病例，重症病人405例，死亡78例，大多为5岁以下的儿童，并发症包括脑炎、无菌性脑膜炎、肺水肿或肺出血、急性软瘫和心肌炎。 2000年5～8月山东省省招远市暴发了小儿手足口病大流行，在3个多月里，招远市人民医院接诊患儿1698例，其中男1025例，女673例，男女之比为1.5:1，年龄最小5个月，最大14岁。首例发生于5月10日，7月份达高峰，末例发生于8月28日。128例住院治疗患儿，平均住院天数5.1d，其中3例合并暴发心肌炎死亡。the first case was reported in 1982 in shanghai, and later it was found in more than 10 provinces, and in 1983 and 1986 there were two times of break, and both are caused by Cox As, and 1995, the EV71 was fostered in wuhan, and 1998 EV also found in shenzhen and taiwan, in 2000, there is also a break in shandong province

　　二、流行环节及流行特征 the step and characteristic of epidemiology

　　（一）传染源 the source of infection,

　　手足口病的传染源是患者和隐性感染者。流行期间，患者是主要传染源。患者在发病1～2周自咽部排出病毒，约3～5周从粪便中排出病毒，疱疹液中含大量病毒，破溃时病毒即溢出。带毒者和轻型散发病例是流行间歇和流行期的主要传染源。the patient and virus taker is the source of infection, and during 1-2 week, the pharyngal can release virus and during 3-5 week, the stool can has virus, and liquid of the herpes can cantain lots of virus in it, when the herpes ulcerate, those virus come out, and during the diapause, the virus taker is the main part of infection source

　　（二）传播途径 the method of infection

　　主要是通过人群间的密切接触进行传播的。患者咽喉分泌物及唾液中的病毒可通过空气飞沫传播。唾液、疱疹液、粪便污染的手、毛巾、手绢、牙杯、玩具、食具、奶具以及床上用品、内衣等通过日常接触传播，亦可经口传播。接触被病毒污染的水源，也可经口感染，并常造成流行。门诊交叉感染和口腔器械消毒不严也可造成传播。it can spread by the closed contact with each other, the secretion from mouth can spread in the air, saliva, liquid of herpes, stool infected material such as hand, washcloth, wash tool for teeth, dishware, toy and bedding, intercloth with touch in our daily base, this can enter mouth so lead disease spread, in some case, they can get ill from contact infected water source, this can lead outbreak, and sometimes we also can get ths disease when using some medical mouth facility which was not disinfected strictly.

 

　　（三）易感人群 susceptibility group

　　人对引起手足口病的肠道病毒普遍易感，受感后可获得免疫力，各年龄组均可感染发病，但病毒隐性感染与显性感染之比为100:1，成人大多已通过隐性感染获得相应的抗体，因此，手足口病的患者主要为学龄前儿童，尤以≤3岁年龄组发病率最高，4岁以内占发病数85％～9 5％。据国外观察报告，在人群中，每隔2～3年流行一次，主要是非流行期间新生儿出世，易感者逐渐积累，达到一定数量时，便为新的流行提供先决条件。我国天津市1983年流行后，散发病例不断，1986年再次发生流行，而且两次均为Cox Al6引起。the human being is all easy to be infected by this disease, and when one catch this disease, he/ she can get the immunity of this disease, and as you know, each kind of virus can cause a particular immunity to this virus, so since there are more 20 kinds of virus lead Hand-foot-mouth disease, so one can't say one won't catch hand-foot-mouth disease even if he/ she caught it before, since it often break every 2-3 years, so lots of adult have immunity ability to this disease just because they got it before sometime in past but not cause some symptom, but through this process he/ she get the immunity to this disease, this disease mainly effect pre-shool age, and the kid below 4 years lod is 85-95%

　　（四）流行方式 the method of spread

　　手足口病分布极广泛，无严格地区性。四季均可发病，以夏秋季多见，冬季的发病较为少见。本病常呈暴发流行后散在发生，该病流行期间，幼儿园和托儿所易发生集体感染。家庭也有此类发病集聚现象。医院门诊的交叉感染和口腔器械消毒不严格，也可造成传播。天津市两次较大流行，托幼单位儿童发病率明显高于散居儿童。家庭散发，常一家一例；家庭暴发，一家多人或小孩子与成人全部感染发病。此病传染性强，传播途径复杂，流行强度大，传播快，在短时间内即可造成大流行。the disease can be found all over the world, and every season, and mainly in summer and autumn, and some less in winter, during outbreak, kidgardon can easy found lots of kids effected at the same time, and some family also can found several cases at the same time, if the hospital has not had strictly disinfect process, also can lead cross infection,

　　三、病原学pathegen

　　引起手足口病的病毒很多，主要为小RNA病毒科肠道病毒属的柯萨奇病毒、埃可病毒和新肠道病毒。CoxA组的16、4、5、7、9、10 型，CoxB组的2、5、13 型，以及EV 71型均为手足口病较常见的病原体，最常见为Cox Al6及EV 71型,有的报导埃可病毒及CoxB组某些型也可引起，但仍没获得到进一步证实。there are lots of virus can leas hand foot mouth disease, and mainly enterovirus such as Cox As and Ace and some new enterovirus, such as CoxA16. 4. 5. 7 .9 .10 and CoxB 2. 5. 13 and EV71 is the common pathogen, and most common microgen are CoxA16  and EV71,

肠道病毒目前有71型, 其中EV71是在1968年美国加州一名患儿的大便和脑组织中发现的, 在此前已经确定的肠道病毒有67种, 其中柯萨奇A组24个, 脊髓灰质炎病毒3个, 柯萨奇B病毒6个, 埃可病毒34个, 而其后发现的病毒就直接冠以EV68. 69, 70, 71等名, 目前肠道病毒最后一个为EV71. there are 71 types of enteroviruses having been found yet, and the EV71 was found in 1968 in Carlifornia in USA in the stool and brain tissue of a child case, and before this, there has been 67 types of enteroviruses been found in the world, and those includes 26 kinds of CoxA, 6 kinds of CoxB, and 3 kinds of poliomyelitis viruses, and 34 kinds of Aik Virus, and later when any other kind of enterovirus been found, they just name directly as EV68, 69, 70, 71, and then the last one is EV71

　　从有关资料表明，HFMD的病原体经历了较大的变迁。对药物具有抗性， 75％酒精，5％来苏对肠道病毒没有作用，对乙醚，去氯胆酸盐等不敏感。但对紫外线及干燥敏感，各种氧化剂(高锰酸钾、漂白粉等)、甲醛、碘酒都能灭活。病毒在50 ℃可被迅速灭活，但1mol浓度二价阳离子环境可提高病毒对热灭活的抵抗力，病毒在4 ℃可存活1年，在- 20 ℃可长期保存，在外环境中病毒可长期存活。

　　四、临床表现及病理 symptom and pathology

　　（一）临床表现 clinical symptom

　　手足口病是一种肠道病毒病，具有肠道病毒感染的共同特征。从最常见的无症状或仅有轻度不适，至严重的并发症甚至死亡均可发生。潜伏期一般3～7 d，没有明显的前驱症状，多数病人突然起病。约半数病人于发病前1～2d或发病的同时有发热，多在38℃左右。主要侵犯手、足、口、臀四个部位(四部曲)；因为疹子不像蚊虫咬、不像药物疹、不像口唇牙龈疱疹、不像水痘所以又称四不像；而且临床上更有不痛、不痒、不结痂、不结疤的四不特征。部分患者初期有轻度上感症状，如咳嗽、流涕、恶心、呕吐等等。由于口腔溃疡疼痛，患儿流涎拒食。口腔粘膜疹出现比较早，起初为粟米样斑丘疹或水疱，周围有红晕，主要位于舌及两颊部，唇齿侧也常发生。手、足等远端部位出现或平或凸的班丘疹或疱疹，皮疹不痒，斑丘疹在5d左右由红变暗，然后消退；疱疹呈圆形或椭圆形扁平凸起，内有混浊液体，长径与皮纹走向一致，如黄豆大小不等，一般无疼痛及痒感，愈合后不留痕迹。手、足、口病损在同一患者不一定全部出现。水疱和皮疹通常在一周内消退。it is a enterovirus disease, and has the general charactertic, and it can has not effect or just some kinds of discomfort to serious syndrome even death, the latent period nornally from 3-7 days, no evident symptom, and them sudden break with fever, the temperature normally not very high, for example about 38degree, and them herpes can be found in hand, foot, mouth, even in buttocks, not the samllar with rash such as bite by mouse, drug rash, or chicken pox,

　　（二）合并症 syndrome

　　手足口病表现在皮肤和口腔上，但病毒会侵犯心、脑、肾等重要器官。本病流行时要加强对患者的临床监测，如出现高热、白细胞不明原因增高而查不出其他感染灶时，就要警惕暴发性心肌炎的发生。近年发现EV 71较Cox Al6所致手足口病有更多机会发生无菌性脑膜炎，其症状呈现为发烧、头痛、颈部僵硬、呕吐、易烦燥、睡眠不安稳等；身体偶尔可发现非特异性红丘疹，甚至点状出血点。中枢神经系统症状多见于2岁以内患儿。the hand foot mouth disease mainly have some sympton in skin and mucous membrance, but the virus can effect the heart, brain, kedney, and normally this effect can endanger one's life, and the index about heart, brain and kidney will be monitored in clinic, if suddenly high fever, and white cell become high and no other infective source can be found, the carditis must to be considered, and recently we found that the enterovirus71 can be easier to lead meningitis without any bacteric than Cox, the patient will have fever, headache, cervical ragidity, vomiting, excitable, and not easy to fall into a deep sleep, there will be some no-characteristic rash, and even some bleeding point, and Center Neural System sympton normally is found in infant below 2 years old

　　五、诊断及鉴别诊断 diagnosis

　　（一）本病主要诊断依据 the main gist of diagnosis

　　流行病学资料、临床表现、实验室检查、确诊时须有病原学的检查依据。epidemic data, symptom of clininal, lab test, and pathogen test in lab

　　1、好发于夏秋季节；2、以儿童为主要发病对象，常在婴幼儿集聚的场所发生，呈流行趋势。3、临床主要表现为初起发热，白细胞总数轻度升高，继而口腔、手、足等部位粘膜、皮肤出现斑丘疹及疱疹样损害。4、病程较短，多在一周内痊愈。it can easy be pathogenetic in summer and autumn, and mainly effect child special infant, and can spread rapidly among the infant habitat, and the clinical sympton include: fever, a little high blood white cell, and subsequent have rash in mouth mucous membrance, hand and foot, and some on buttochs, the rash can be macula, papule or herpes, the the course of disease is about 1 week and automatic recovery

　　（二）实验室诊断 lab diagnosis

　　常用的分离方法有细胞接种和乳鼠接种。1998年人们开始用人肺系细胞(MRC-5)分离Cox A16等毒株，其敏感性好且接种病毒后出现细胞病变较快。人源细胞如W1-38、横纹肌瘤细胞(RD)也都可用于病毒分离。RD细胞支持大多数柯萨奇A组病毒复制，但一般要经过2次以上传代才出现明显病变，若在使用RD 细胞分离的同时再增加1株L20B或Hep-2细胞，可提高肠道病毒的分离率。为提高细胞对肠道病毒的敏感性，还可在细胞接种前用50μg/ml的5-碘脱氧尿嘧啶处理3天。对一些不能在细胞上生长的病毒，可用乳鼠接种分离病毒。埃可病毒一般不引起乳鼠发病,多由脑脊液分离,粪便中不易检出。the usually method is inoculate aimed tissue in a certain cell or rat,

　　肠道病毒型特异性鉴定主要靠血清中和实验，LMB组合血清可大大简化鉴定过程，但是有些毒株的中和作用不稳定，仍需由单价血清来鉴定，另一要注意的是病毒颗粒的集聚会影响中和效果，如EV 71的中和实验就需要使用单个分散的病毒。enterovirus charateristic differential diagnosis is mainly rely on blood serum test and lab test, and LMB set blood serum can make differential diagnosis easier,

　　近年来，PCR 技术已成为诊断肠道病毒感染最常用的一种方法。PCR测序技术则可用于肠道病毒分型。and recently, and technology of PCR is the most popular method of dignosis enterovirus, and this technology can get the virus grouping.

　　手足口病抗体检测的最常用方法目前仍是中和实验，该方法精确且具有型特异性。

　　六、预防原则 preventive principle

　　（一）加强监测，提高监测敏感性是控制本病流行的关键。及时采集合格标本，明确病原学诊断；enforce monitor, and the sensitivity of monitor is the key point of control the epidemic

　　（二）做好疫情报告，及时发现病人，积极采取预防措施，防止疾病蔓延扩散；and have good work in epidemic report, and find case in time, and make step to prevent the disease spread in time

　　（三）托幼机构做好晨间体检，发现疑似病人，及时隔离治疗；have a good work in morning check in kidgarden, and if there is a suspect case, insulate he/ she immediatelly

　　（四）被污染的日用品及食具等应消毒，患儿粪便及排泄物用3％漂白粉澄清液浸泡，衣物置阳光下暴晒，室内保持通风换气；disinfect daily facility and dashware, and disinfect patient stool and vomit with 3% chloride of lime, and the cloth of infant must put under the sun

　　（五）流行时, 做好环境、食品卫生和个人卫生during the epidemic, it is important to keep good hygiene habit, and have a good environment and food hygiene

　　（六）饭前便后要洗手，预防病从口入 wash hand before dinner and after defecate to prevent getting ill by the mouth

　　（七）家长尽量少让孩子到拥挤公共场所，减少被感染机会；avoid to go to crowded public as far as possible to ge reduce the opportunity to get ill

　　（八）注意婴幼儿的营养、休息，避免日光曝晒,防止过度疲劳，降低机体抵抗力；keep enough rest, nutrition, avoided excessive insolation, avoid fatigue to effect immunity

　　（九）医院加强预诊，设立专门诊室，严防交叉感染 enforce hospital pre-diagnosis and have special unit in clinic to avoid cross infection