Enterovirus 71 infection

EV71 is an RNA virus classified as Enterovirus A71 within species A of the genus Enterovirus (family Picornaviridae) ^[1][2]. It was first isolated in California in 1969 from patients with neurological disease and subsequently spread to Europe, with documented outbreaks in Bulgaria (1975) and Hungary (1978), before becoming a recurrent cause of epidemics across Asia and, more recently, in Cambodia (2012) ^[1][2]. Because of its close relation to polioviruses, its capacity to cause neurological disease, and its evolving genotype structure (genogroups A–F, with B and C further subdivided into B0–B5 and C1–C5), EV71 is regarded as a distinct surveillance-relevant enterovirus entity ^[1][2].

EV71 infection most commonly manifests as hand, foot, and mouth disease, a generally mild illness affecting children; however, it can progress to severe and sometimes fatal complications including meningitis, brainstem encephalitis, acute flaccid paralysis, neurologic pulmonary edema, and systemic illness ^[3][1]. Specific viral receptors on white blood cells, respiratory and gastrointestinal epithelial cells, and dendritic cells are thought to underlie this broad tissue tropism and the potential for severe neurological and cardiopulmonary manifestations ^[1]. During the 2012 Cambodia outbreak, affected children under seven years of age presented with rapid clinical deterioration characterized by fever, respiratory illness, and generalized neurological abnormalities, with most fatalities occurring within 24 hours of admission ^[2].

EV71 was first identified in the United States in 1969 and subsequently caused outbreaks in Europe (notably Bulgaria in 1975 and Hungary in 1978) before becoming established as a major recurrent pathogen across the Asia-Pacific region ^[1][2]. Outbreaks in Asia occur in regular cycles, and the virus's rapid evolution in the absence of RNA proofreading means that different genogroups (A–F, with regional variants such as D in India and E/F in Africa) appear to differ in clinical and epidemiological properties ^[1][2]. Phylogenetic analyses suggest that clade C1b emerged around 1994 and C2b around 2002 in Europe, while more recent Asian outbreaks—including the 2012 Cambodia event in which at least 64 children died—illustrate the continuing public health burden of severe EV71 disease in young children ^[2].

EV71 spreads among young children via respiratory and gastrointestinal routes, consistent with the distribution of its specific receptors on cells of the respiratory tract, gut, white blood cells, and dendritic cells ^[2]. The virus spreads readily in close-contact settings such as households and childcare environments, and both intra- and inter-typic recombination are recognized to occur readily when multiple viral genomes co-infect the same host cell, facilitating ongoing diversification ^[2].

There are no specific antiviral agents approved for the treatment of EV71 infection, which underscores the importance of preventive measures ^[2]. Public health responses to outbreaks have relied on social distancing interventions, although the effectiveness of such measures has not been fully assessed ^[1]. Vaccination of children under five years of age has been recommended in areas of high virus susceptibility, and in December 2015 the China Food and Drug Administration approved the first EV71 vaccine following a large pediatric trial (approximately 10,000 children aged 6–35 months), in which vaccinated cohorts experienced substantially lower rates of HFMD and EV71-associated illness than placebo recipients ^[2]. Candidate vaccines under investigation include inactivated whole-virus, live-attenuated, subviral particle, and DNA formulations ^[1].

1. 1Solomon T et al. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis. 2010 Nov. PMID: 20961813. doi: 10.1016/S1473-3099(10)70194-8.PubMed: https://pubmed.ncbi.nlm.nih.gov/20961813/
2. 2Wikipedia contributors. Enterovirus 71 - Wikipedia [Internet]. Wikipedia. cited 4 Sept 2026.Available from: https://en.wikipedia.org/wiki/Enterovirus_71
3. 3Wei Y et al. Recent Advances in Enterovirus A71 Infection and Antiviral Agents. Lab Invest. 2024 Feb. PMID: 38008182. doi: 10.1016/j.labinv.2023.100298.PubMed: https://pubmed.ncbi.nlm.nih.gov/38008182/