The epidemiology of non-polio enteroviruses: recent advances and outstanding questions

Abstract

Purpose of review: There are over 100 serotypes of human enteroviruses, which cause a spectrum of illnesses, including meningitis, encephalitis, paralysis, myocarditis and rash. Increasing incidence of hand-foot-and-mouth disease in the Asia-Pacific region and recent outbreaks of enterovirus-associated disease, such as severe respiratory illness in the United States in 2014, highlight the threat of these viruses to human health.

Recent findings: We describe recent outbreaks of human enteroviruses and summarize knowledge gaps regarding their burden, spectrum of diseases and epidemiology.

Summary: Reported outbreaks of respiratory, neurological, skin and eye diseases associated with human enteroviruses have increased in frequency and size in recent years. Improved molecular diagnostics and genetic sequence analysis are beginning to reveal the complex dynamics of individual serotypes and genotypes, and their contribution to these outbreaks. However, the biological mechanisms underlying their emergence and transmission dynamics remain elusive. They are likely to involve changes in the virus, such as fitness, antigenicity, virulence or tropism, and in the human population, such as levels of sanitation and of homotypic and heterotypic immunity. Improvements in surveillance, serological surveys and detailed genetic and antigenic characterization of viral populations would help to elucidate these mechanisms. This will be important for the design of outbreak control and vaccine development strategies.

Figure 1

Schematic representation of the phylogenetic relationship between representative serotypes of the four species of human enteroviruses based on VP1 sequences reported in GenBank. A multiple sequence alignment was generated using Clustal Omega. A Neighbour-Joining tree was then created from this alignment, and visualised using FigTree v1.4.2 (http://tree.bio.ed.ac.uk/software/figtree/). Branch lengths are not to scale. Accession numbers were as follows: CV-A6, AF081297; CV-A10, AF081300; CV-A24, AF081311; E6; AF081321; E11, AF081326; E30, AF081340; EV-68, AF081348; EV-71, JN168790; EV-70, D00820 (nucleotides 2425–3339); PV1, V01149 (nucleotides 2480–3385); and CV-A16, U05876 (nucleotides 2446–3336). CV-A: coxsackievirus A; E: echovirus; EV: enterovirus; PV: poliovirus.

Figure 2

Number of annually reported echovirus 9 and coxsackievirus B4 detections in the United States. Based on data from [4].