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

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.

Epidemiologic and clinical updates on viral infections in Saudi Arabia

“…HFMD viruses are ssRNAs belonging to the Picornaviridae family and Enterovirus genus ( Fig. 1 ) ( Zhao et al, 2020 ), which are mainly infected with enteroviruses 71 (EV71) and coxsackievirus-A16 (CoxA16) ( Yi et al, 2022 ). Usually, children under five years are highly susceptible and the viruses can be transmitted through the fecal–oral route or by personal contact ( Yi et al, 2022 ).…”

“…1 ) ( Zhao et al, 2020 ), which are mainly infected with enteroviruses 71 (EV71) and coxsackievirus-A16 (CoxA16) ( Yi et al, 2022 ). Usually, children under five years are highly susceptible and the viruses can be transmitted through the fecal–oral route or by personal contact ( Yi et al, 2022 ). HFMD causes mild symptoms, such as fever, vesiculation, and inappetence, and in some cases, it may progress to neurological complications that might lead to death ( Jiang et al, 2021 ), with an incubation period of 3–7 days ( Table 1 ) ( Yang et al, 2017 ).…”

Chinese parents’ intention to vaccinate their 0–5-year-old children with the EV-71 vaccine against hand, foot, and mouth disease and willingness-to-pay

“…The main clinical manifestations are fever, vesicular rashes on the hands, feet, and buttocks, and ulcers in the oral mucosa. Usually, HFMD is selflimiting, but a small proportion of children may experience severe complications such as meningitis, encephalitis, acute flaccid paralysis, and neurorespiratory syndrome (1)(2)(3).…”

Molecular epidemiology and clinical characteristics of enteroviruses associated HFMD in Chengdu, China, 2013–2022

“…While most cases of HFMD are mild and self-limiting, some cases can progress rapidly and result in severe central nervous system (CNS) complications. In such cases, the disease can deteriorate dramatically, leading to cardiopulmonary failure and even death [ 4 ]. For instance, enterovirus 71 (EV-A71) can cause serious neuropathology and cardiopulmonary complications, such as aseptic meningitis, acute flaccid paralysis, brainstem encephalitis, fatal myocarditis, and pulmonary edema, which can ultimately lead to death [ 5 ].…”