Clinical characteristics and severity of hand, foot, and mouth disease by virus serotype: A prospective hospital-based cohort study

The circulating enteroviruses (EVs) serotypes in hand, foot and mouth disease (HFMD) inpatients remained unclear. This study aimed to investigate the serotype-specific associations between clinical characteristics and severity of HFMD inpatients. The study utilised a prospective, hospital-based cohort design and a tiered diagnostic algorithm incorporating real-time RT-PCR and nested RT-PCR for serotyping. Clinical data were prospectively collected throughout hospitalization. Clinical severity was measured using diagnoses of central nervous system (CNS) complications and three other outcomes. A total of 1768 inpatients were enrolled consecutively between February 2017 and February 2018. The proportions of CNS complications varied by serotype (p < 0.001), with the highest for EV-A71 (40%), followed by CV-A4 (17%), CV-A2 (13%), CV-A10 (10%), CV-A6 (7%), and CV-A16 (4%). Children with CV-A2 and CV-A4 were less likely to have rashes on hands, feet, or buttocks and more likely to develop high fever, while those with EV-A71 had fewer mouth lesions. Of 230 lab-confirmed HFMD inpatients with CNS complications, EV-A71 accounted for 45% while CV-A6, CV-A16, CV-A4, CV-A10 and CV-A2 accounted for 35%. The logistic regression analysis revealed that non-CNS-specific symptoms such as cold limbs and vomiting, and clinical testing indicators including blood globulin, platelet, serum chloride and neutrophil counts, were associated with CNS complications. Non-EV-A71 EVs can also cause severe diseases, but those with EV-A71 infection are more likely to suffer CNS complications and other severe manifestations. The study highlighted the emergence of enterovirus serotypes, suggesting the need for future research on virus changes and associated disease burden.

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Publication Details

Journal
PLoS neglected tropical diseases
Published
2025-05-23
DOI
https://doi.org/10.1371/journal.pntd.0013039
Citations
2
Primary Topic
Viral Infections and Immunology Research
Type
article
Field-Weighted Citation Impact
2.78

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article

Clinical characteristics and severity of hand, foot, and mouth disease by virus serotype: A prospective hospital-based cohort study

Malik Peiris, Chongchen Zhou, Yibing Cheng, Peng Wu et al.
2 citations
PLoS neglected tropical diseases
Viral Infections and Immunology Research
2.78
article

Clinical characteristics and severity of hand, foot, and mouth disease by virus serotype: A prospective hospital-based cohort study

Malik Peiris, Chongchen Zhou, Yibing Cheng, Peng Wu, Qi Qiu, Tianchen Zhang, Mengyao Zeng, Yonghong Zhou, Junmei Yang, Hongjie Yu, Peng Cui, Benjamin J. Cowling, Lance C. W. Turtle, Lu Liang, Li Yu, Peng Li, Kai Wang, Yuanfang Shen, Chun Guo, Tom Solomon, Lü Long
article en
2 citations

Abstract

The circulating enteroviruses (EVs) serotypes in hand, foot and mouth disease (HFMD) inpatients remained unclear. This study aimed to investigate the serotype-specific associations between clinical characteristics and severity of HFMD inpatients. The study utilised a prospective, hospital-based cohort design and a tiered diagnostic algorithm incorporating real-time RT-PCR and nested RT-PCR for serotyping. Clinical data were prospectively collected throughout hospitalization. Clinical severity was measured using diagnoses of central nervous system (CNS) complications and three other outcomes. A total of 1768 inpatients were enrolled consecutively between February 2017 and February 2018. The proportions of CNS complications varied by serotype (p < 0.001), with the highest for EV-A71 (40%), followed by CV-A4 (17%), CV-A2 (13%), CV-A10 (10%), CV-A6 (7%), and CV-A16 (4%). Children with CV-A2 and CV-A4 were less likely to have rashes on hands, feet, or buttocks and more likely to develop high fever, while those with EV-A71 had fewer mouth lesions. Of 230 lab-confirmed HFMD inpatients with CNS complications, EV-A71 accounted for 45% while CV-A6, CV-A16, CV-A4, CV-A10 and CV-A2 accounted for 35%. The logistic regression analysis revealed that non-CNS-specific symptoms such as cold limbs and vomiting, and clinical testing indicators including blood globulin, platelet, serum chloride and neutrophil counts, were associated with CNS complications. Non-EV-A71 EVs can also cause severe diseases, but those with EV-A71 infection are more likely to suffer CNS complications and other severe manifestations. The study highlighted the emergence of enterovirus serotypes, suggesting the need for future research on virus changes and associated disease burden.

PLoS neglected tropical diseasesVol. 19(5)
University of Liverpool (GB), University of Electronic Science and Technology of China (CN), Chinese Center For Disease Control and Prevention (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Sichuan University (CN), Fudan University (CN), Peking Union Medical College Hospital (CN), Royal Liverpool University Hospital (GB), Walton Centre (GB), Zhengzhou University (CN), Zhengzhou Children's Hospital (CN), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (CN), Shanghai Institute of Planned Parenthood Research (CN), Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool (GB), Huazhong University of Science and Technology (CN), University of Hong Kong (HK)
Wellcome Trust, Total Foundation
Good health and well-being
Openalex Percentile: Top 10%
Viral Infections and Immunology Research
2.78
DOIOpen Access PDFOpenAlex
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