Abstract
BackgroundHuman enterovirus 71 (EV71) is an important pathogen caused large outbreaks in Asian-Pacific region with severe neurological complications and may lead to death in young children. Understanding of the etiological spectrum and epidemic changes of enterovirus and population’s immunity against EV71 are crucial for the implementation of future therapeutic and prophylactic intervention.ResultsA total of 1,182 patients who presented with the symptoms of hand foot and mouth disease (67.3%) or herpangina (HA) (16.7%) and admitted to the hospitals during 2008-2013 were tested for enterovirus using pan-enterovirus PCR targeting 5′-untranslated region and specific PCR for viral capsid protein 1 gene. Overall, 59.7% were pan-enterovirus positive comprising 9.1% EV71 and 31.2% coxsackievirus species A (CV-A) including 70.5% CV-A6, 27.6% CV-A16, 1.1% CV-A10, and 0.8% CV-A5. HFMD and HA occurred endemically during 2008-2011. The number of cases increased dramatically in June 2012 with the percentage of the recently emerged CV-A6 significantly rose to 28.4%. Co-circulation between different EV71 genotypes was observed during the outbreak. Total of 161 sera obtained from healthy individuals were tested for neutralizing antibodies (NAb) against EV71 subgenotype B5 (EV71-B5) using microneutralization assay. The seropositive rate of EV71-B5 was 65.8%. The age-adjusted seroprevalence for individuals was found to be lowest in children aged >6 months to 2 years (42.5%). The seropositive rate remained relatively low in preschool children aged > 2 years to 6 years (48.3%) and thereafter increased sharply to more than 80% in individuals aged > 6 years.ConclusionsThis study describes longitudinal data reflecting changing patterns of enterovirus prevalence over 6 years and demonstrates high seroprevalences of EV71-B5 NAb among Thai individuals. The rate of EV71 seropositive increased with age but without gender-specific significant difference. We identified that relative lower EV71 seropositive rate in early 2012 may demonstrate widely presented of EV71-B5 in the population before account for a large outbreak scale epidemic occurred in 2012 with due to a relatively high susceptibility of the younger population.
Highlights
Human enterovirus 71 (EV71) is an important pathogen caused large outbreaks in Asian-Pacific region with severe neurological complications and may lead to death in young children
In agreement with previous findings, we demonstrated that a change in the prevailing subgenotypes and types occurred over time including the shift of EV71 to coxsackievirus species A (CV-A), which occurred in 2010 (EV71 subgenotype C4 to CV-A16) and 2012 (EV71-B5 to CV-A6)
While samples positive for EV71 and CV-A16 were relatively low in most years, we demonstrated that approximately 43% of enterovirus positive cases were CV-A6 infections, highlighting the predominant role of CV-A6 in this outbreak
Summary
Human enterovirus 71 (EV71) is an important pathogen caused large outbreaks in Asian-Pacific region with severe neurological complications and may lead to death in young children. The linear genome is organized in a single long open reading frame (ORF) flanked by the 5′ and short 3′-untranslated regions (UTR) with a polyadenylated tail. VP1 is the immune-dominant capsid protein and contains the most important neutralization epitopes. It shows a sequence divergence and has been used for molecular type assignment and evolutionary study. The incubation period for EV71 is assumed to be approximately 5 days (d) with the median duration of virus shedding period estimated to be 2 d in close contact group, 18 d in mild HFMD and 25 d for severe HFMD [20]. The median basic reproductive number for EV71 is 5.48, which is approximately two-fold higher than that of coxsackievirus (CV) type A16 infection (2.50 d) [21]
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