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Meta-Analysis
. 2022 Apr 28;17(4):e0267716.
doi: 10.1371/journal.pone.0267716. eCollection 2022.

Epidemiological characteristics, routine laboratory diagnosis, clinical signs and risk factors for hand, -foot -and -mouth disease: A systematic review and meta-analysis

Zhijie Yi  1 , Shujun Pei  2 , Wenshuai Suo  1 , Xiaoyang Wang  1 , Zengyuan Huang  3 , Aihua Yi  4 , Bohao Wang  5 , Zhiquan He  6 , Ruolin Wang  6 , Yi Li  6 , Wei Fan  6 , Xueyong Huang  1
Affiliations
Meta-Analysis

Epidemiological characteristics, routine laboratory diagnosis, clinical signs and risk factors for hand, -foot -and -mouth disease: A systematic review and meta-analysis

Zhijie Yi et al. PLoS One. .

Abstract

Background: For the past few years, only a few monovalent EV71 vaccines have been developed, while other enterovirus vaccines are in short supply. We conducted a quantitative meta-analysis to explore the epidemiological characteristics, routine laboratory diagnosis, clinical signs and risk factors for hand, foot and mouth disease (HFMD).

Methods: PubMed, Embase and the Web of Science were searched for eligible reports published before April 16, 2021, with no publication time or language restrictions. The primary outcome was the odds ratio of the epidemiological characteristics, routine laboratory diagnosis, and clinical signs associated with HFMD severity and death.

Results: After screening 10522 records, we included 32 articles comprising 781903 cases of hand, foot and mouth disease. Patients with severe illness developed some clinical signs (hypersomnia (OR = 21.97, 95% CI: 4.13 to 116.74), convulsion (OR = 16.18, 95% CI: 5.30 to 49.39), limb shaking (OR = 47.96, 95% CI: 15.17 to 151.67), and breathlessness (OR = 7.48, 95% CI: 1.90 to 29.40)) and had some changes in laboratory parameters (interleukin-6 levels standardized mean difference (SMD) = 1.57, 95%CI: 0.55 to 2.60), an increased neutrophils ratio (SMD = 0.55, 95%CI: 0.17 to 0.93), cluster of differentiation 4 (CD4+) (SMD = -1.38, 95%CI: -2.33 to -0.43) and a reduced lymphocytes ratio (SMD = -0.48, 95%CI: -0.93 to -0.33)) compared with patients with mild illness. The risk factors for death included cyanosis (OR = 5.82, 95% CI: 2.29 to 14.81), a fast heart rate (OR = 3.22, 95% CI: 1.65 to 6.30), vomiting (OR = 2.70, 95% CI: 1.33 to 5.49) and an increased WBC count (SMD = 0.60, 95% CI: 0.27 to 0.93).

Conclusions: China has the highest incidence of HFMD. Our meta-analyses revealed important risk factors that are associated with the severity and mortality of HFMD.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA flowchart used in the Study selection.
Fig 2
Fig 2. Forest plots of meta-analysis on a panel of clinical signs.
A Hypersomnia, B convulsion, C Limb shaking, D Breathlessness. *Data is converted from the original data.
Fig 3
Fig 3. Forest plots of meta-analysis on a panel of routine laboratory parameters.
A IL-6, B Neutrophils, C Lymphocytes, D CD4+. *Data is converted from the original data.
Fig 4
Fig 4. Forest plots on a panel of risk factors.
A Cyanosis, B Fast heart rate, C Vomiting, D WBC count, E Age. *Data is converted from the original data.
See this image and copyright information in PMC

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References

    1. Li ZQ, Qin ZQ, Tan HF, Zhang CH, Xu JX, Chen J, et al.. Analysis of the coverage of inactivated enterovirus 71 (EV71) vaccine and adverse events following immunization with the EV71 vaccine among children from 2016 to 2019 in Guangzhou. Expert Rev Vaccines. 2021:1–12. Epub 2021/05/27. doi: 10.1080/14760584.2021.1933451 . - DOI - PubMed
    1. Cai K, Wang Y, Guo Z, Yu H, Li H, Zhang L, et al.. Clinical characteristics and managements of severe hand, foot and mouth disease caused by enterovirus A71 and coxsackievirus A16 in Shanghai, China. BMC Infect Dis. 2019;19(1):285. Epub 2019/03/29. doi: 10.1186/s12879-019-3878-6 . - DOI - PMC - PubMed
    1. Kou Z, Jia J, Liu X, Luo T, Xin X, Gong J, et al.. Epidemiological characteristics and spatial-temporal clusters of hand, foot, and mouth disease in Qingdao City, China, 2013–2018. PLoS One. 2020;15(6):e0233914. doi: 10.1371/journal.pone.0233914 . - DOI - PMC - PubMed
    1. Wang Y, Li Y, Yang Y, Peng C, Fu X, Gu X, et al.. Virological investigation of genetic variation of enterovirus type 71 in hand, foot and mouth disease. Exp Ther Med. 2020;20(1):543–9. Epub 2020/06/17. doi: 10.3892/etm.2020.8728 . - DOI - PMC - PubMed
    1. He X, Dong S, Li L, Liu X, Wu Y, Zhang Z, et al.. Using a Bayesian spatiotemporal model to identify the influencing factors and high-risk areas of hand, foot and mouth disease (HFMD) in Shenzhen. PLoS Negl Trop Dis. 2020;14(3):e0008085. Epub 2020/03/21. doi: 10.1371/journal.pntd.0008085 . - DOI - PMC - PubMed

Publication types

Grants and funding

The funder of Henan Young and Middle-aged Health Science and Technology Innovation talent Project (YXKC2020006) is Xueyong Huang, who is involved study design and decision to publish. The funders of Natural Science Foundation of China (81773500) and study on the epidemiology had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The project leader of Natural Science Foundation of China (81773500) has retired for three years, and the project is being run temporarily by Xueyong Huang, the second project leader.