Epidemiology of enterovirus 71 in the Netherlands, 1963 to 2008

Abstract

The incidence of enterovirus 71 (EV71) infection has greatly increased in the Asian Pacific region since 1997. Several large outbreaks, caused by different subgenogroups of EV71, occurred with high rates of morbidity and a substantial number of deaths. In 2007, 58 cases of EV71 infection requiring hospitalization were reported in The Netherlands after a period of low endemicity of 21 years. These events triggered a study on the epidemiology of EV71 in The Netherlands. Genetic analysis of the VP1 capsid region of 199 EV71 isolates collected from 1963 to 2008 as part of enterovirus surveillance activities revealed a change in the prevailing subgenogroups over time. From 1963 to 1986 infections were caused by three different and successive lineages belonging to subgenogroup B (the novel lineage designated B0, as well as B1 and B2). In 1987, following a major epidemic the previous year, the B genogroup was replaced by genogroup C strains of lineages C1 and, later, C2. Analyses of the clinical data suggested that there were differences between infection with genogroup B and with genogroup C strains in terms of the age groups affected and the severity of illness. From comparative analysis with genomic data available in the public domain, we concluded that EV71 strain evolution shows a global pattern, which leads to the question of whether the recently emerged C4 lineage strains will also spread outside of Asia.

FIG. 1.

Number of EV71 cases reported by members of the Weekly Sentinel Surveillance system of the Dutch Working group on Clinical Virology (1965 to 2008).

FIG. 2.

Phylogenetic analysis of EV71 isolates from the Netherlands (bold) and reference strains. The dendrogram was generated by the neighbor-joining method (bootstrap analysis with 1,000 pseudoreplicate data sets) on the basis of a multiple alignment of the nucleotide sequences of the VP1 region (891 nucleotides).

FIG. 3.

Successive appearance of EV71 subgenogroups in The Netherlands from 1963 to 2008.

FIG. 4.

Seasonal distribution of Dutch EV71 isolates, 1963 to 2008.

FIG. 5.

Age of Dutch children infected with EV71, 1963 to 2008.

FIG. 6.

Global presence of subgenogroups of EV71. Overview was made on the basis of an extensive literature review for the United Kingdom (2), Austria (35), Bulgaria (14), Hungary (30), Norway (45), the United States (3, 4, 36), Australia (4, 37, 39), Vietnam (42), China (11, 17, 18, 26), Singapore (6, 8, 29, 30, 40), Malaysia (1, 3, 5, 6, 13, 19, 29, 34, 36), Japan (3, 12, 31), and Taiwan (12, 22, 23, 25, 44). Black triangles represent single cases of subgenogroups other than the dominating subgenogroup in the period of time concerned.