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Article(id=1321169758255436023, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1321169735128043598, articleNumber=null, orderNo=null, doi=10.11847/zgggws1145247, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1723651200000, receivedDateStr=2024-08-15, revisedDate=1725206400000, revisedDateStr=2024-09-02, acceptedDate=1747152000000, acceptedDateStr=2025-05-14, onlineDate=1792921016514, onlineDateStr=2026-10-25, pubDate=1752076800000, pubDateStr=2025-07-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792921016514, onlineIssueDateStr=2026-10-25, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792921016514, creator=13701087609, updateTime=1792921016514, updator=13701087609, issue=Issue{id=1321169735128043598, tenantId=1146029695717560320, journalId=1319373219989389464, year='2025', volume='41', issue='7', pageStart='769', pageEnd='896', issueExtLink='null', onlineDate='null', pubDate='1752076800000', pubDateStr='2025-07-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792921011000, creator='13701087609', updateTime=1792921011000, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=776, endPage=781, ext={EN=ArticleExt(id=1321169758549037305, articleId=1321169758255436023, tenantId=1146029695717560320, journalId=1319373219989389464, language=EN, title=Epidemiologic characteristics of recurrent hand, foot, and mouth disease in Yunnan province, 2008 - 2022: a registry data analysis, columnId=1321169758473539832, journalTitle=Chinese Journal of Public Health, columnName=Special Report – Infectious Disease Surveillance, runingTitle=null, highlight=null, articleAbstract=
Objective

To describe the epidemiological characteristics of recurrent cases of hand, foot, and mouth disease (HFMD) in Yunnan province from 2008 to 2022 to inform the development of prevention and control strategies.

Methods

Records of HFMD cases diagnosed by various medical institutions in Yunnan province between May 8, 2008, and December 31, 2022, were collected via the Chinese Center for Disease Control and Prevention's Infectious Disease Information Reporting Management System. After cleaning and verifying the data, a database of recurrent HFMD cases was created. Then, we analyzed the temporal, regional, demographic, and pathogen distributions of the cases.

Results

A total of 899 455 HFMD cases were registered during the study period, including 54 138 recurrent cases (cumulative recurrence rate: 6.02%). Of these recurrent cases, 97.84% involved two episodes, with a male-to-female ratio of 1.61:1. The median age was 3.74 years for cases involving two episodes and 4.43 years for cases involving three episodes. The peak season occurred from May to July. Second episodes were prevalent in 15 counties and districts, while third episodes were concentrated in Kunming′s urban area. Most recurrences involved different pathogens; only 4.97% of cases involved two consecutive infections of the same pathogen. Patients with severe symptoms in the first episode were at an increased risk of recurrent HFMD compared to patients without severe symptoms (relative risk = 1.80, 95% confidence interval: 1.71 - 1.91).

Conclusions

The HFMD recurrence rate in Yunnan province was high and increased over time, exhibiting distinct temporal, demographic, and regional patterns. Improving pathogen surveillance is crucial for developing multivalent vaccines, and targeted measures should focus on severe cases and high-incidence areas.

, authors=Tian HUANG, Yuchen JIA, Erda ZHENG, Zeying LI, Jibo HE, Xiulian SHEN, authorsList=Tian HUANG, Yuchen JIA, Erda ZHENG, Zeying LI, Jibo HE, Xiulian SHEN, authorCompany=null, correspAuthors=Jibo HE, Xiulian SHEN, authorNote=null, correspAuthorsNote=
HE Jibo, E-mail:
SHEN Xiulian, E-mail:
, copyrightStatement=Copyright © 2025 Chinese Journal of Public Health. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1321169761195643136, articleId=1321169758255436023, tenantId=1146029695717560320, journalId=1319373219989389464, language=CN, title=2008—2022年云南省手足口病重复感染病例流行病学特征分析, columnId=1321169758632923386, journalTitle=中国公共卫生, columnName=专题报道——传染病监测, runingTitle=null, highlight=null, articleAbstract=
目的

描述2008—2022年云南省手足口病重复感染病例的流行病学特征，为制定云南省手足口病防控策略和措施提供科学依据。

方法

收集2008年5月8日—2022年12月31日云南省各级各类医疗机构诊断并通过“中国疾病预防控制中心传染病信息报告管理系统”报告的手足口病病例，经数据清洗、核对信息、整理获得重复感染手足口病病例数据库。描述重复感染手足口病病例的时间、地区、人群、病原分布等流行病学特征。

结果

2008—2022年云南省手足口病感染总数为899 455例，重复感染人数为54 138例，发生率为6.02%。重复感染发生率随观察时间延长而上升，2次感染占97.84%。男性重复感染发生率高于女性（性别比1.61:1）。第2次感染的年龄中位数为3.74岁，第3次感染为4.43岁。高发季节为5—7月，2次感染高发地区集中在15个县区，3次感染集中在昆明市城区。大多数重复感染为不同病原类型，连续两次感染为同一病原的病例仅占4.97%。首次感染出现重症的患者，重复感染风险是普通患者的1.80倍（95%CI=1.71～1.91）。

结论

云南省手足口病重复感染率较高，且随观察时间延长呈上升趋势，具有明显的时间、人群和地区特异性。完善病原学监测对研发多价疫苗具有重要意义，应针对重症患者和高发地区采取重点防控措施。

, authors=黄甜, 贾豫晨, 郑尔达, 李则颖, 何继波*, *, 沈秀莲*, *, authorsList=黄甜, 贾豫晨, 郑尔达, 李则颖, 何继波, 沈秀莲, authorCompany=null, correspAuthors=何继波, 沈秀莲, authorNote=

黄甜（1982—），副主任医师，硕士，研究方向：急性传染病预防与控制

, correspAuthorsNote=
何继波， E-mail：
沈秀莲，E-mail：
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Cumulative recurrent and total cases and cumulative recurrent incidence of hand, foot, and mouth disease by year in Yunnan province, China (2008 - 2022)

, figureFileSmall=null, figureFileBig=null, tableContent=
年份区间重复感染例数感染例数累计重复感染发生率/%
2008211 3960.02
2008—200912025 9430.46
2008—201072273 1800.99
2008—20111 905110 4521.72
2008—20123810169 4352.25
2008—20136531224 1462.91
2008—201410 523301 4233.49
2008—201515 583377 6204.13
2008—201621 251456 1674.66
2008—201725 860518 9414.98
2008—201832 384616 8275.25
2008—201940 062710 7745.64
2008—202043 911762 9965.76
2008—202148 004826 0955.81
2008—202254 138899 4556.02
), ArticleFig(id=1321169766593712429, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321169758255436023, language=CN, label=表1, caption=

2008—2022年云南省手足口病重复感染发生情况

, figureFileSmall=null, figureFileBig=null, tableContent=
年份区间重复感染例数感染例数累计重复感染发生率/%
2008211 3960.02
2008—200912025 9430.46
2008—201072273 1800.99
2008—20111 905110 4521.72
2008—20123810169 4352.25
2008—20136531224 1462.91
2008—201410 523301 4233.49
2008—201515 583377 6204.13
2008—201621 251456 1674.66
2008—201725 860518 9414.98
2008—201832 384616 8275.25
2008—201940 062710 7745.64
2008—202043 911762 9965.76
2008—202148 004826 0955.81
2008—202254 138899 4556.02
), ArticleFig(id=1321169766719541550, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321169758255436023, language=EN, label=Tab.2, caption=

Episode-specific total number of cases, proportions, male/female distribution (number/ratio/incidence rate), and overall incidence of recurrent hand, foot, and mouth disease (second to sixth episodes) in Yunnan province, 2008 - 2022

, figureFileSmall=null, figureFileBig=null, tableContent=
重复感染次数重复感染例数占比/%男性构成比/%男性重复感染发生率/%女性构成比/%女性重复感染发生率/%合计重复感染发生率/%
252 97497.8532 60961.606.2520 36538.405.395.89
31 0952.0270464.300.1339135.700.100.12
4650.124064.500.012538.500.010.01
530.01266.670.00133.330.000.00
610.001100.000.0000.000.000.00
合计54 138100.0033 35661.616.3920 78238.395.506.02
), ArticleFig(id=1321169766786650415, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321169758255436023, language=CN, label=表2, caption=

2008—2022年云南省手足口病重复感染病例人口学特征

, figureFileSmall=null, figureFileBig=null, tableContent=
重复感染次数重复感染例数占比/%男性构成比/%男性重复感染发生率/%女性构成比/%女性重复感染发生率/%合计重复感染发生率/%
252 97497.8532 60961.606.2520 36538.405.395.89
31 0952.0270464.300.1339135.700.100.12
4650.124064.500.012538.500.010.01
530.01266.670.00133.330.000.00
610.001100.000.0000.000.000.00
合计54 138100.0033 35661.616.3920 78238.395.506.02
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Number and proportion of recurrent cases of hand, foot, and mouth disease attributed to CVA16/EV71/other enterovirus infections, stratified by initial source of infection, among 1 187 laboratory-confirmed cases in Yunnan province, China (2008 - 2022)

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首次感染病原再次感染病原合计/例占比/%
CVA16感染例数占比/%EV71感染例数占比/%其他肠道病毒感染例数占比/%
CVA16221.8512410.4514712.3829324.68
EV711089.10373.121169.7726121.99
其他肠道病毒1179.86726.0744437.4163353.33
合计24720.8123319.6370759.561 187100.00
), ArticleFig(id=1321169766967005489, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321169758255436023, language=CN, label=表3, caption=

2008—2022年云南省重复感染手足口病连续2次感染病原特征

, figureFileSmall=null, figureFileBig=null, tableContent=
首次感染病原再次感染病原合计/例占比/%
CVA16感染例数占比/%EV71感染例数占比/%其他肠道病毒感染例数占比/%
CVA16221.8512410.4514712.3829324.68
EV711089.10373.121169.7726121.99
其他肠道病毒1179.86726.0744437.4163353.33
合计24720.8123319.6370759.561 187100.00
), ArticleFig(id=1321169767050891570, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321169758255436023, language=EN, label=Tab.4, caption=

Association between severe condition in the first episode and recurrence time of hand, foot, and mouth disease among reported cases in Yunnan province, China (2008 - 2022): a univariate logistic regression analysis

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感染次数首次感染重症数总数重症比率/%χ2值P值OR值95%CIχ2趋势值P值
18497850 5261.001.000403.72<0.05
297952 9741.85346.39<0.051.8661.745～1.995
3351 0953.2053.24<0.053.2722.335～4.585
44656.1512.63<0.056.4902.362～17.874
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2008—2022年云南省手足口病重复感染次数与首次感染是否出现重症的相关性

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感染次数首次感染重症数总数重症比率/%χ2值P值OR值95%CIχ2趋势值P值
18497850 5261.001.000403.72<0.05
297952 9741.85346.39<0.051.8661.745～1.995
3351 0953.2053.24<0.053.2722.335～4.585
44656.1512.63<0.056.4902.362～17.874
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2008—2022年云南省手足口病重复感染病例流行病学特征分析
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黄甜 , 贾豫晨 , 郑尔达 , 李则颖 , 何继波 *, * , 沈秀莲 *, *
中国公共卫生 | 专题报道——传染病监测 2025,41(7): 776-781
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中国公共卫生 |专题报道——传染病监测 2025 , 41 (7) : 776 -781
2008—2022年云南省手足口病重复感染病例流行病学特征分析
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黄甜, 贾豫晨, 郑尔达, 李则颖, 何继波*, * , 沈秀莲*, *
作者信息
  • 云南省疾病预防控制中心疫情监测/突发公共卫生事件处置中心，昆明 650500
通讯作者:
何继波， E-mail：
沈秀莲，E-mail：
作者简介:

黄甜（1982—），副主任医师，硕士，研究方向：急性传染病预防与控制

Epidemiologic characteristics of recurrent hand, foot, and mouth disease in Yunnan province, 2008 - 2022: a registry data analysis
Tian HUANG, Yuchen JIA, Erda ZHENG, Zeying LI, Jibo HE , Xiulian SHEN
Affiliations
  • Epidemic Surveillance/Emergency Public Health Disposal Center, Yunnan Center for Disease Control and Prevention, Kunming 650500, China
    • Corresponding Author:
    HE Jibo, E-mail:
    SHEN Xiulian, E-mail:
出版时间: 2025-07-10 doi: 10.11847/zgggws1145247
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摘要
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目的

描述2008—2022年云南省手足口病重复感染病例的流行病学特征，为制定云南省手足口病防控策略和措施提供科学依据。

方法

收集2008年5月8日—2022年12月31日云南省各级各类医疗机构诊断并通过“中国疾病预防控制中心传染病信息报告管理系统”报告的手足口病病例，经数据清洗、核对信息、整理获得重复感染手足口病病例数据库。描述重复感染手足口病病例的时间、地区、人群、病原分布等流行病学特征。

结果

2008—2022年云南省手足口病感染总数为899 455例，重复感染人数为54 138例，发生率为6.02%。重复感染发生率随观察时间延长而上升，2次感染占97.84%。男性重复感染发生率高于女性（性别比1.61:1）。第2次感染的年龄中位数为3.74岁，第3次感染为4.43岁。高发季节为5—7月，2次感染高发地区集中在15个县区，3次感染集中在昆明市城区。大多数重复感染为不同病原类型，连续两次感染为同一病原的病例仅占4.97%。首次感染出现重症的患者，重复感染风险是普通患者的1.80倍（95%CI=1.71～1.91）。

结论

云南省手足口病重复感染率较高，且随观察时间延长呈上升趋势，具有明显的时间、人群和地区特异性。完善病原学监测对研发多价疫苗具有重要意义，应针对重症患者和高发地区采取重点防控措施。

手足口病  /  重复感染病例  /  流行病学特征  /  云南省
Objective

To describe the epidemiological characteristics of recurrent cases of hand, foot, and mouth disease (HFMD) in Yunnan province from 2008 to 2022 to inform the development of prevention and control strategies.

Methods

Records of HFMD cases diagnosed by various medical institutions in Yunnan province between May 8, 2008, and December 31, 2022, were collected via the Chinese Center for Disease Control and Prevention's Infectious Disease Information Reporting Management System. After cleaning and verifying the data, a database of recurrent HFMD cases was created. Then, we analyzed the temporal, regional, demographic, and pathogen distributions of the cases.

Results

A total of 899 455 HFMD cases were registered during the study period, including 54 138 recurrent cases (cumulative recurrence rate: 6.02%). Of these recurrent cases, 97.84% involved two episodes, with a male-to-female ratio of 1.61:1. The median age was 3.74 years for cases involving two episodes and 4.43 years for cases involving three episodes. The peak season occurred from May to July. Second episodes were prevalent in 15 counties and districts, while third episodes were concentrated in Kunming′s urban area. Most recurrences involved different pathogens; only 4.97% of cases involved two consecutive infections of the same pathogen. Patients with severe symptoms in the first episode were at an increased risk of recurrent HFMD compared to patients without severe symptoms (relative risk = 1.80, 95% confidence interval: 1.71 - 1.91).

Conclusions

The HFMD recurrence rate in Yunnan province was high and increased over time, exhibiting distinct temporal, demographic, and regional patterns. Improving pathogen surveillance is crucial for developing multivalent vaccines, and targeted measures should focus on severe cases and high-incidence areas.

hand, foot, and mouth disease  /  recurrent infection cases  /  epidemiological characteristics  /  Yunnan province
黄甜, 贾豫晨, 郑尔达, 李则颖, 何继波, 沈秀莲. 2008—2022年云南省手足口病重复感染病例流行病学特征分析. 中国公共卫生, 2025 , 41 (7) : 776 -781 . DOI: 10.11847/zgggws1145247
Tian HUANG, Yuchen JIA, Erda ZHENG, Zeying LI, Jibo HE, Xiulian SHEN. Epidemiologic characteristics of recurrent hand, foot, and mouth disease in Yunnan province, 2008 - 2022: a registry data analysis[J]. Chinese Journal of Public Health, 2025 , 41 (7) : 776 -781 . DOI: 10.11847/zgggws1145247
正文
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手足口病（hand，foot and mouth disease, HFMD）是一种由肠道病毒感染引起的急性传染病，好发于<5岁儿童。我国作为该疾病的高发区域，全年均有病例报告且呈现明显地域性差异，其中云南省的发病率和重症病例比例长期位居全国前列[1–4]。手足口病由柯萨奇A组16型（coxsackievirus A16, CVA16））病毒和肠道病毒71型（enterovirus 71, EV71）等数十种血清型肠道病毒感染所致。因不同血清型的肠道病毒感染后无抗体的交叉保护，一种肠病毒感染后机体不能获得终身免疫，并且肠道病毒存在基因重组和变异，因此人群中存在重复感染手足口病的现象[5]。重复感染的发生也是手足口病发病率居高不下的重要原因之一。因此，本研究收集2008年5月8日—2022年12月31日“中国疾病预防控制中心传染病信息报告管理系统”报告的云南省手足口病病例，描述和分析手足口病重复感染病例的流行病学特征，为降低云南省手足口病重发感染的发生及防控工作提供防控建议。
1　资料与方法
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1.1　数据
来源通过中国疾病预防控制监测信息系统，收集自2008年5月8日—2022年12月31日云南省手足口病病例个案信息。运用MySQL 5.7数据库软件，根据患者姓名、证件号码、出生日期、家长姓名、联系电话、家庭住址等病例关键信息，初步筛选可能的手足口病重复感染的病例。由辖区疾病预防控制中心专业人员与患者家长电话联系或通过查询就诊医疗机构就诊记录的方式，确认为手足口病重复感染病例。
1.2　病例定义
由云南省各级各类医疗机构诊断并报告的手足口病病例，在此次诊断前14 d曾被诊断为手足口病轻症病例（2次诊断间隔时间>14 d），或在此次诊断前23 d曾被诊断为手足口病重症病例（2次诊断间隔时间>23 d）为手足口病重复感染病例[6]。以季节指数的大小变化反映重复感染病例数在不同月份的变化趋势和规律。采用直接平均季节指数法计算季节指数[7]，计算公式为：
$ \mathrm{季}\mathrm{节}\mathrm{指}\mathrm{数}=\frac{\mathit{\mathrm{\mathit{n}}}\mathrm{年}\mathrm{相}\mathrm{同}\mathrm{月}\mathrm{份}\mathrm{平}\mathrm{均}\mathrm{数}}{\mathrm{\mathit{n}}\mathrm{年}\mathrm{每}\mathrm{个}\mathrm{月}\mathrm{份}\mathrm{总}\mathrm{平}\mathrm{均}\mathrm{数}} $
如果季节指数>1，说明该时间段的数据高于整体平均水平，对应高流行季节；如果<1，则说明该时间段的数据低于整体平均水平，对应低流行季节。
1.3　统计分析
运用Excel 2019和SPSS 28.0对云南省手足口病重复感染的发生率、发生时间、人群特征、地区分布特征、病原感染特征及重复感染与重症的关联性等指标进行描述性统计分析。其中计数资料采用例数及百分位数进行描述，采用χ2检验进行组间比较，并采用趋势性χ2检验进行趋势分析。计算RR、OR值及95 %CI分析重复感染与重症的关联性，检验水准α=0.05（双侧检验）。将重复感染地均在同一县域辖区内的病例（因昆明市城区地理位置紧密关联，将五华区、盘龙区、官渡区、西山区和呈贡区视为同一辖区）进行地区分布描述。
2　结　果
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2.1　重复感染发生概况（表1）
2008—2022年云南省共报告手足口病发病数为899 455例，发生重复感染者为54 138例，累计重复感染发生率为6.02%。累计监测时间1、3、5和10年的重复感染发生率分别为0.46%、1.72%、2.91%和5.25%。重复感染发生率随着观察时间的延长逐渐升高。仅发生2次感染的病例为52 974例，发生率为5.89%，占重复感染病例97.84%。
2.2　时间分布（图1）
2018年发生重复感染人次最多，为6 696例次，占截至2022年发生重复感染总人次的12.09%（6696/55 375），重复感染从4月份开始快速上升，每年出现2次手足口病重复感染高峰，高峰月份为5—7月（季节指数分别为1.50、1.91、1.43），小高峰月份为11月（季节指数为1.11）。
2.3　人口学特征（表2）
发生第2次感染人群的最小年龄0.31岁，最大年龄39.69岁，年龄中位数为3.74岁（P10=2.01，P90=6.36），有10%的感染者年龄≤2.01岁，有90%的感染者年龄≤6.36岁，主要集中在2.01～6.36岁。发生第3次感染人群的最小年龄0.84岁，最大年龄16.23岁，年龄中位数为4.43岁（P10=2.61，P90=7.28），有10%的感染者年龄≤2.61岁，有90%的感染者年龄≤7.28岁，主要集中在2.61～7.28岁。发生≥第4次感染人群的最小年龄1.41岁，最大年龄15.82岁，年龄中位数为4.73岁（P10=3.18，P90=7.47），有10%感染者的年龄≤3.18岁，有90%感染者的年龄≤7.47岁，主要集中在3.18～7.47岁。发生重复感染的病例中男性病例占比61.61%，女性占比38.39%，男女性别比为：1.61:1。
2.4　地区分布
2008—2022年云南2次感染均发生在同一县区的病例共45 463例，涉及全省所有县区（129县区），其中重复感染2次手足口病病例数超过800例的县区共15个，为红塔区1 760例、蒙自市1 435例、新平县1 258例、嵩明县1 192例、弥勒市1 169例、通海县1 152例、芒市1 116例、元江县1 101例、江川区1 043例、盈江县1 004例、泸西县930例、开远市854例、思茅区827例、石林县811例、麒麟区808例。15个县区累计报告重复感染2次病例16 460例占报告病例总数的36.21%（16 460/45 463）。15个县区中，玉溪市有5个县区（红塔区、新平县、通海县、元江县、江川区）、红河州有4个县区（蒙自市、弥勒市、泸西县、开远市）、昆明市有2个县区（嵩明县、石林县）、德宏州有2个县区（芒市、盈江县）、普洱市有1个县区（思茅区）、曲靖市有1个县区（麒麟区）。2008—2022年云南重复感染3次手足口病病例数超过50例的县区为昆明市城区5个县区（西山区、盘龙区、五华区、官渡区和呈贡区）。2008—2022年云南3次感染均发生在同一县区的病例共925例，涉及全省103个县区，昆明市主城区累计报告重复感染3次病例120例占报告病例总数的12.97%（120/925）。
2.5　重复感染时间间隔
重复感染者第1次至第 2次发病间隔时间的中位数为1.41年（P10=0.50，P90=3.68）。重复感染者第 2次至第 3次发病间隔时间的中位数为1.31年（P10=0.44，P90=11.74）。重复感染者第 3次至第 4次发病间隔时间的中位数为1.20年（P10=0.58，P90=2.95）。
2.6　病原学特征（表3）
2008—2022年云南省报告的手足口病重复感染的病例，有连续2次感染病原学检测记录的病例共1 187例，其中连续两次感染均为CVA16者有22例（占1.85%），均为EV71者有37例（占3.12%），明确连续两次感染均为同一病原的病例仅有59例（占4.97%），明确连续2次感染为不同病原的病例有684例（占57.62%），大多数病例重复感染为不同病原类型。重复感染的病例中，首次感染以其他肠道病毒为主（633例，占53.33%），CVA16（293例，占24.68%）与EV71（261例，占21.99%）占比基本接近。CVA16重复感染病例的间隔感染时间中位数为597 d（P10=59，P90=1492）；EV71重复感染病例的间隔感染时间中位数为396 d（P10=56，P90=1087）。
2.7　重复感染次数与重症发生的关联（表4）
仅感染1次的患者重症发生率仅为1.00%，感染2、3和4次的患者首次感染重症发生率逐渐升高分别为1.85%、3.20%和6.15%。随着感染次数增加，重症发生率也呈现增加趋势，线性趋势χ2值为403.72，差异有统计学意义（P<0.05）。首次感染出现重症的患者，发生重复感染的风险是非重症患者的1.80倍（RR=1.80，95%CI=1.71～1.91）。
3　讨　论
收起
本研究结果显示，2008—2022年云南省手足口病重复感染的发生率为6.02%，观察期为1、2和3年的重复感染发生率仅为0.02%、0.46%和0.99%，观察期为5、10和15年的重复感染率则上升为2.25%，4.98%和6.02%。呈现随着观察时间延长，重复感染发生率逐渐上升的现象，这与黄娇[6]的研究结果一致。这与随着观察期的增加，累计发病率增加有关。有研究报告手足口病重复感染合并率为 2.25%（ 95%CI=1.59%～3.18%） [8]，各研究之间异质性较大。陕西省报道的 2008—2019年手足口病重复感染率为2.21%[9]低于云南省同期，北京朝阳区 2008—2014年手足口病重复感染发生率3.17%[10]，浦东新区2008—2012年手足口病重复感染发生率2.72%[11]，与云南省同期重复感染发生率接近。
手足口病重复感染发生的高发季节为5—7月[8]，与云南省手足口病高发季节基本一致，存在明显的季节性，这与目前国内研究一致[12–14]。发生2次感染的人群集中在2.0～6.3岁，3次感染的人群集中在2.6～7.3岁，4次感染的人群集中在3.2～7.5岁。本研究中手足口病重复感染者以2～7.5岁儿童为主，在其他地区研究中重复感染者以2～4岁儿童为主[9–15]，这可能与本次研究的观察时间较长有关，也可能与成年手足口病例有逐渐增多趋势有关[16]。本次研究中也呈现男性重复感染率高于女性的特点，与目前报道的研究结果一致[9，11–14]，这可能与男性手足口病发病率高于女性[1]有关，云南省手足口病病例男女性性别比约为1.7:1[17]。
2008—2022年云南重复感染2次的高发地区主要集中滇中的昆明市、玉溪市、曲靖市，滇东南的红河州，滇南的普洱市及滇西南的德宏州的部分县区，这与我省手足口病疫情聚集县区高度重合[18]。2008—2022年云南重复感染3次的高发地区则集中在昆明市城区，这可能与昆明市主城区的为云南省医疗服务资源最丰富的区域有关。
云南省重复感染患者第1、2次感染间隔中位数为1.41年，陕西省、海南省、北京市朝阳区、上海浦东区、重庆沙坪坝的研究报道第1、2次感染间隔时间中位数为0.98～1.34年[9–11，13–14]；云南省重复感染患者第2、3次感染间隔中位数为1.31年，陕西省、海南省、上海浦东区、重庆沙坪坝区研究报道第2、3次感染间隔时间中位数为是0.82～1.13年[9，11，13–14]；云南省重复感染患者第3、4次感染间隔中位数为1.20年，陕西省、海南省的研究报道第3、4次感染间隔中位数为1.88和0.86年[9，13]。各地监测发现的间隔感染时间稍有差异，但基本接近，这可能与各个研究的观察时间及观察样本量的大小有关。
大多数手足口病重复感染病例以感染不同病原类型为主，明确连续2次感染均为同一病原的病例仅占4.97%。原因是不同型别肠道病毒交叉免疫效果差，甚至不存在交叉免疫 [19]。2次感染病原均为CVA16的病例间隔感染时间中位数为1.63年，2次感染病原均为EV71病例的间隔感染时间中位数为1.08年。当前关于手足口病重复感染同一病原间隔感染时间的研究较少，仅上海市的一项研究中发现了2例两次感染EV71的手足口病重复感染病例，感染间隔期分别为7和15个月。该结果也在本次研究的重复感染EV71病毒的间隔感染时间区间内。分析感染CVA16和EV71的部分病例未能形成有效的持续免疫的原因，主要有2种可能：一是EV71和CVA16都具有相对稳定的抗原性，但一些病毒株可能由于表位的突变而具有抗原变异[20]，2次感染变异抗原性的毒株引起。二是与自然感染CVA16和EV71病毒，人群产生的抗体水平不均衡，个体差异很大，个体抗体水平高低不同有关[21]。
首次感染手足口病即发展为重症的病例发生再感染风险是普通手足口病病例的1.80倍，且重复感染次数越多的病例，重症的发生比率越高，仅感染1次的手足口病患者重症发生率仅为1.00%，2、3和4次重复感染手足口病患者，重复感染率上升至1.85%、3.20%、6.15%。陕西省、上海市浦东区开展的手足口病重复感染研究也表明重症重复感染率高于非重症重复感染率[9，11]。有研究认为，手足口病发展至危重症甚至死亡是病毒入侵人体后引发的宿主异常的神经内分泌调节以及产生的炎症因子风暴等共同作用的结果[22]。手足口病患者发生重症的危险因素是年龄<3岁、非母乳喂养、发热[23 – 24]，这些危险因素都与免疫状态炎症反应有关。
研发有效靶向手足口病相关主要病毒（EV71、CVA16、CVA10、CVA6）的多价疫苗是当前的防控手足口病的重点和难点。目前，我国对手足口病病原的监测仅仅限于区分EV71 、CVA16及其他肠道病毒，监测已发现我国手足口病病原谱已经出现了变化，由EV71和 CVA16的构成比呈现下降趋势，其他肠道病毒的构成比呈上升趋势[25]。本研究中受病原学检测结果的限制，无法明确除EV71 、CVA16以外感染的其他肠道病毒型别、无法完整分析手足口病重复感染的病原学特征。受手足口病威胁较大的地区应及早建立健全手足口病病原监测机制，将其他肠道病毒中占比较高的CVA6、CVA10等病原也纳入病原监测体系中，为选择针对性的疫苗研发提供依据[21]。此外，当前开展的手足口病重复感染相关危险因素的研究，其只包含传染病报告卡内涉及的病例年龄、性别、发病时间、是否发生重症等有限内容。当前研究尚未开展过旨在深入探究手足口病重复感染发生的影响因素的基于病例对照或队列研究，手足口病重复感染影响因素分析不全面。
综上所述， 2008—2022年云南省手足口病重复感染的发生率为6.02%，存在随着观察时间延长，重复感染发生率升高的现象。重复感染以2次感染为主，男性发生率高于女性，发生2次感染的年龄中位数是3.74岁，高发季节为5—7月，2次感染的高发地区聚集在15个县区，3次感染的高发地区则集中在昆明市城区。大多数手足口病重复感染病例以感染不同病原类型为主，预防重复感染发生的关键仍是研发安全有效的多价手足口病疫苗。首次感染出现重症的患者发生重复感染的风险是普通患者的1.8倍，需重点对重症手足口病患者及家长开展健康教育。

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doi: 10.11847/zgggws1145247
  • 接收时间：2024-08-15
  • 首发时间：2026-10-25
  • 出版时间：2025-07-10
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  • 收稿日期：2024-08-15
  • 修回日期：2024-09-02
  • 录用日期：2025-05-14
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    云南省疾病预防控制中心疫情监测/突发公共卫生事件处置中心，昆明 650500

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