Li Fajin, Wang Dan, Su Fei, Zhao Suye, Guo Jun, Zhang Fumin, Ran Xueqin, Wang Jiafu, Li Shijun
Key laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Collaborative Innovation Center for Mountain Ecology & Agro-Bioengineering (CICMEAB), College of Life Sciences/Institute of Agro-bioengineering, College of Animal Science, Guizhou University, Guiyang, Guizhou, China.
Laboratory Center, Institute of Infectious Disease Control, Guizhou Center for Disease Control and Prevention, Guiyang, Guizhou, China.
PLoS Negl Trop Dis. 2025 Aug 18;19(8):e0013394. doi: 10.1371/journal.pntd.0013394. eCollection 2025 Aug.
Hand, foot, and mouth disease (HFMD) is caused by more than 20 different enteroviruses (EVs). The predominant EV serotypes of HFMD have been continuously changing in recent years. Guizhou Province has reported higher rates of severe and fatal cases of HFMD. However, comprehensive studies on its epidemiology, etiology, and serological characteristics have remained limited in recent years.
We collected epidemiological and laboratory data from HFMD cases between 2008 and 2023, analyzing the data by age, gender, disease severity, and EV serotypes. Clinical samples from these cases were collected to isolate EVs. The VP1 gene was amplified from isolates of enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), coxsackievirus A6 (CV-A6), and coxsackievirus A10 (CV-A10), and the sequences were analyzed. We collected 432 serum samples from healthy individuals from 2019 to 2022 to assess antibodies against CV-A6, CV-A10, CV-A16, and EV-A71 of HFMD.
A total of 513,143 HFMD cases were reported in Guizhou Province from 2008 to 2023, including 9052 (1.76%) severe cases and 193 (0.038%) deaths. In laboratory-confirmed cases, EV-A71 was the dominant serotype from 2008 to 2012; other EVs became predominant from 2013 to 2018, and CV-A6 predominated in 2019, 2022, and 2023. Interestingly, novel epidemiological patterns of CV-A6 infection were observed, with a high incidence every other year in various cities since 2019. Among 432 healthy individuals, the overall seroprevalence rates of CV-A6, CV-A10, CV-A16, and EV-A71 were 62.04%, 54.17%, 54.63%, and 64.35%, respectively. Additionally, over 70% of the participants had neutralizing antibodies (NtAbs) against at least two types of these enteroviruses. Phylogenetic analysis revealed that CV-A16 isolates clustered into the B1a or B1b evolutionary branches, while EV-A71, CV-A6, and CV-A10 isolates belonged to the C4a, D3a, and C subgenotypes, respectively.
This results indicate differences in the incidence of major HFMD pathogens across years, regions, and populations. Other EVs, predominantly CV-A6, have become the main pathogens causing HFMD since 2019. CV-A6, CV-A10, CV-A16, and EV-A71 exhibited relatively high seroprevalence rates. Currently, there is an urgent need to develop multivalent vaccines and implement effective measures to reduce incidence of HFMD.
手足口病(HFMD)由20多种不同的肠道病毒(EV)引起。近年来,手足口病的主要肠道病毒血清型一直在不断变化。贵州省报告的手足口病重症和死亡病例发生率较高。然而,近年来关于其流行病学、病因学和血清学特征的综合研究仍然有限。
我们收集了2008年至2023年手足口病病例的流行病学和实验室数据,按年龄、性别、疾病严重程度和肠道病毒血清型进行数据分析。收集这些病例的临床样本以分离肠道病毒。从肠道病毒A71(EV-A71)、柯萨奇病毒A16(CV-A16)、柯萨奇病毒A6(CV-A6)和柯萨奇病毒A10(CV-A10)的分离株中扩增VP1基因,并对序列进行分析。我们收集了2019年至2022年432名健康个体的血清样本,以评估针对手足口病CV-A6、CV-A10、CV-A16和EV-A71的抗体。
2008年至2023年贵州省共报告手足口病病例513143例,其中重症病例9052例(1.76%),死亡193例(0.038%)。在实验室确诊病例中,2008年至2012年EV-A71是主要血清型;2013年至2018年其他肠道病毒成为主要血清型;2019年、2022年和2023年CV-A6占主导地位。有趣的是,观察到CV-A6感染的新的流行病学模式,自2019年以来在各个城市每隔一年发病率就很高。在432名健康个体中,CV-A6、CV-A10、CV-A16和EV-A71的总体血清阳性率分别为62.04%、54.17%、54.63%和64.35%。此外,超过70%的参与者对至少两种这些肠道病毒具有中和抗体(NtAbs)。系统发育分析表明,CV-A16分离株聚为B1a或B1b进化分支,而EV-A71、CV-A6和CV-A10分离株分别属于C4a、D3a和C亚型。
这些结果表明主要手足口病病原体在年份、地区和人群中的发病率存在差异。自2019年以来,其他肠道病毒,主要是CV-A6,已成为引起手足口病的主要病原体。CV-A6、CV-A10、CV-A16和EV-A71表现出相对较高的血清阳性率。目前,迫切需要开发多价疫苗并采取有效措施降低手足口病的发病率。