Mechanisms Underlying HFMD Clinical Pathology in Children

Hand, foot, and mouth disease (HFMD) is generally recognized as a contagious viral disease that commonly occurs in children worldwide, with a high incidence in Asia–Pacific regions in the past 20 years (Koh et al., Pediatr Infect Dis J 35(10):e285–e300, 2016; Puenpa et al., J Biomed Sci 26(1):75, 2019). Since 2000, major epidemics have emerged in East Asia (Huang et al., Emerg Infect Dis 24(3):432, 2018), and numerous large outbreaks have been reported in Taiwan (Chang et al., Pediatrics 109(6):e88, 2002), China; Anhui Province, mainland China; Australia (McMinn et al., Clin Infect Dis 32(2):236–242, 2001); and Southeast Asia (Khanh et al., Emerg Infect Dis 18(12):2002–2005, 2012). Several million HFMD cases have been reported in children. In approximately 1.5–2% of fatal cases, evidence of neurological disorders is identified (Koh et al., BMJ Glob Health 3(1):e000442, 2018; Gonzalez et al., Int J Mol Sci 20(20):5201, 2019), and in some cases, death may be potentially attributed to neurogenic pulmonary edema (PE) or cardiovascular complications occurring within a short time of damage to the nervous system (Wang et al., Pathology 48(3):267–274, 2016). Although cases of fatal HFMD account for only 0.1% of all cases, because HFMD primarily affects children under 2 years of age (Chan et al., Clin Infect Dis 31(3):678–683, 2000), HFMD, especially fatal HFMD, is a public health issue worthy of attention.