Research progress on the epidemiology of hand, foot and mouth disease caused by Coxsackievirus A6
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摘要: 自2008年以来，柯萨奇病毒A组6型(Coxsackievirus A6, CVA6)在全球范围内引起了多次手足口病暴发，成为引发手足口病的主要病原体之一。作为导致手足口病流行的新病原体，目前尚无预防CVA6型手足口病的有效疫苗上市。CVA6易发生重组和变异，不仅小儿易感，也可对成年人造成感染，并常引起非典型症状，如脱甲等。因此，CVA6型手足口病已成为手足口病防控的重大挑战。本文就CVA6的病原学特征及其所致的CVA6型手足口病的流行特征、影响因素及防控措施等研究进展进行综述，为CVA6型手足口病预防控制措施的制定提供科学依据。Abstract: Since 2008, outbreaks of hand, foot and mouth disease caused by Coxsackievirus A6 (CVA6) were found worldwide. CVA6 has gradually become one of the predominant pathogens of hand, foot and mouth disease. As an emerging pathogen of hand, foot and mouth disease, there is no vaccine to prevent CVA6 effectively. Not only children but also adults are susceptible to CVA6, which is prone to recombination and mutation and often causes atypical symptoms, such as onychomadesis. Therefore, hand, foot and mouth disease caused by CVA6 has become a major challenge in the prevention and control of hand, foot and mouth disease. This article reviewed the research progress of its etiological and epidemic features, influencing factors, prevention and control measures of CVA6, in order to provide scientific basis for the prevention and control measures of hand, foot and mouth disease caused by CVA6.
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Key words:
- Coxsackievirus A6 /
- Hand, foot and mouth disease /
- Enterovirus /
- Epidemiology
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表 1 2008-2021年全球不同国家及地区CVA6型手足口病流行特征
Table 1. Characteristics of hand, foot and mouth disease caused by CVA6 outbreak globally from 2008 to 2021
国家/地区 时间(年) 病例数(例) 病原体 年龄范围 症状 芬兰[19-20] 2008 45 CVA6 0.3~10岁 脱甲 2009 317 肠道病毒阳性样本中，CVA6占71.0% 0.2~70岁 发热，头痛，喉咙痛，在手、足、口、面部和喉咙出现囊泡，有胃肠道症状，少数患者出现神经系统并发症 美国[21] 2011-2012 63 34个样本中，CVA6占74.0% CVA6型手足口病患者中，2岁以下占63.0%，18岁以上占24.0% 发热(76.0%)，手或足或口(67.0%)、手臂或腿(46.0%)、面部(41.0%)，臀部(35.0%)和躯干(19.0%)出现皮疹，70.0%的患者出现囊泡，65.0%的患者有疮痂，2名患者出现脱甲 新加坡[22] 2008 29 686 43个样本中，CVA6占23.5% 5岁以下为主，非EV71型患者集中在3~4岁(41.0%) 丘疹，口腔溃疡，发烧 法国[12, 23] 2010 222 肠道病毒阳性样本中，CVA10和CVA6分别占39.9%、28% CVA6阳性患者平均年龄2岁，年龄范围1~3岁 CVA6阳性患者中，82.5%出现发热，50.0%在手、足、膝盖、臀部出现水疱疹，70.0%有疱疹性咽峡炎症状 2014-2015 523 CVA6占53.9%，其次为CVA16(23.2%)，CVA10(7.3%) CVA6阳性患者平均年龄1.7岁 CVA6阳性患者中，76.9%出现发热，35.3%出现口腔溃疡，手(66.4%)、足(55.9%)、臀(59.8%)等部位出疹，非典型手足口病症状为68.5% 西班牙[24] 2010-2012 80 以CVA6为主，占60% 肠道病毒阳性患者平均年龄为1.7岁，CVA6阳性患者平均年龄7.9岁 手足口病症状(62.0%)、发热与皮疹(20.0%)、甲癣(12.0%) 日本[25] 2011 709 CVA6 - 发热，口腔粘膜轻度囊泡，手、足、四肢、臀部出现水泡 泰国[4] 2012 672 CAV6占32.9%，EV71占9.2%，CAV16占9.2% 5岁以下患者占93.1% 发热，流口水，拒绝进食，口腔软腭损伤，手、足、臀部、肛周、膝盖和手肘等多部位出疹 中国天津[27] 2013-2017 9 788 EV71、CVA16、CVA6和CVA10分别占肠道病毒阳性病例的23.9%、25.6%、29.6%和7.0% - - 中国厦门[31] 2009-2015 26 194 2009-2015年CVA6所占百分比分别为3.0%、2.6%、23.3%、19.9%、59.4%、29.9%、52.0% - - 中国广西[29] 2017 2 350 CVA6、EV71、CVA10分别占肠道病毒阳性病例的37.3%、36.4%、13.8% 5岁以下患者占90.0%以上 精神状况差，发烧，手、足、口、臀部、四肢、躯干部位出现皮疹，呕吐，部分患者出现四肢震颤和抽搐等症状 中国北京[5] 2013、2014、2015 33 144、47 440、25 111 2013-2015年CVA6分别占肠道病毒阳性病例的35.4%、3.1%、36.9% 2013年CVA6阳性患者平均年龄为35.5个月 发热(73.6%)，手(95.8%)、足(86.1%)、口(80.6%)、臀部(36.1%)出现皮疹，38.9%的患者出现脱皮，18.1%的患者出现甲廯 中国长春[6] 2013 1 125 CVA6检出率为66.9%，EV71检出率为19.2% 5岁以下为主 发热，手、足、口出现水疱疹 中国上海[11] 2012-2013 626 CVA6、EV71、CVA16分别占比46.6%、28.9%、15.3% 4~144个月 发热，手、足、口、臀部出现皮肤损害 
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表 2 EV71、CVA16及CVA6所致手足口病的流行病学特征、临床症状
Table 2. Epidemiological and clinical characteristics of hand, foot and mouth disease caused by EV71, CVA16 and CVA6
变量 EV71型手足口病 CVA16型手足口病 CVA6型手足口病 常见临床症状 与CVA16型手足口病相同 发热，手、足、口、臀等部位出现斑丘疹及疱疹[39] 与CVA16型手足口病相同 皮疹特点 咽峡部疱疹相对较少，皮疹多呈斑丘疹，直径较小[40] 口腔疱疹更广泛，多在2个以上口腔部位出现，且上颚、颊粘膜比EV71及CVA6相对更多；皮疹多呈斑丘疹、疱疹[40] 齿龈部疱疹相对少见，较多见于上颚及咽峡部，躯干皮疹多见，且皮疹更具多形性；皮肤损害相较EV71及CVA16更为严重；脱甲等特殊表现较为常见[2, 40] 流行年份 常隔年流行(如2010、2012、2016年)[41] 常隔年流行(如2010、2012、2016年)[41] 常隔年流行(如2013、2015、2017年)[26] 高发年龄 与CVA16型手足口病相同 5岁及以下儿童[1] 多为2岁左右，在成人中较EV71及CVA16更为常见[36] 导致重症及死亡 较易，尤其是3岁以下儿童，易导致重症及死亡病例 不易，多数具有自限性，预后相对较好 不易，但也可造成成人严重损害 高发季节 与CVA16型手足口病相同 南方多为秋冬季(9-10月)、夏季(5月)；北方多为夏季(6月)[42] 与CVA16型手足口病相同
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