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

• Published in: PloS one 2022-04, Vol.17 (4), p.e0267716-e0267716
• Main Authors: Yi, Zhijie, Pei, Shujun, Suo, Wenshuai, Wang, Xiaoyang, Huang, Zengyuan, Yi, Aihua, Wang, Bohao, He, Zhiquan, Wang, Ruolin, Li, Yi, Fan, Wei, Huang, Xueyong
• Format: Article
• Language: English
• Subjects: Biology and Life Sciences; Blood Coagulation Tests; CD4 antigen; Complications and side effects; Coxsackievirus infections; Cyanosis; Cytokines; Diagnosis; Disease control; Disease prevention; Enterovirus A, Human; Enteroviruses; Epidemiology; Hand, Foot and Mouth Disease - diagnosis; Hand, Foot and Mouth Disease - epidemiology; Hand-foot-and-mouth disease; Health risks; Heart rate; Humans; Hypersomnia; Illnesses; Infectious diseases; Interleukin 6; Laboratories; Leukocytes (neutrophilic); Lymphocytes; Medical diagnosis; Medicine and Health Sciences; Meta-analysis; Mouth Diseases; Patients; People and Places; Physical Sciences; Public health; Research and Analysis Methods; Risk analysis; Risk Factors; Shaking; Sleep disorders; Systematic review; Vaccines; Vomiting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0267716

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