Risk Factors for Enterovirus A71 Seropositivity in Rural Indigenous Populations in West Malaysia

Abstract

Enterovirus A71 (EV-A71), which is transmitted by the fecal-oral route, causes hand, foot and mouth disease and, rarely, severe neurological complications. In Malaysia, the indigenous rural community (Orang Asli) has a high prevalence of parasitic diseases due to poor sanitation, water supply and hygiene practices. This cross-sectional study compared the seroepidemiology of EV-A71 among rural Orang Asli and urban Kuala Lumpur populations in West Malaysia, and determined the risk factors associated with EV-A71 seropositivity in rural Orang Asli. Seropositive rates were determined by neutralization assay. EV-A71 seropositivity was strongly associated with increasing age in both populations. Rural Orang Asli children ≤12 years had significantly higher EV-A71 seropositivity rates than urban Kuala Lumpur children (95.5% vs 57.6%, P < 0.001), and also higher rates in the age groups of 1–3, 4–6 and 7–12 years. Multivariate analysis confirmed that age ≤12 years (adjusted OR 8.1, 95% CI 3.2–20.7, P < 0.001) and using untreated water (adjusted OR 6.2, 95% CI 2.3–16.6, P < 0.001) were independently associated with EV-A71 seropositivity in the Orang Asli population. Supply of clean drinking water may reduce the risk of EV-A71 infection. With significantly higher EV-A71 seropositive rates, younger rural children should be a priority target for future vaccination programs in Malaysia.

Immune responses against enterovirus A71 infection: Implications for vaccine success

“…39 Children in rural villages had higher seropositive rates than urban children, reaching >80% seropositive by 3 years and >95% by 12 years. 38 High seroprevalence was observed recently in Cambodia, where EV-A71 seroprevalence among children was 88.8% although more stringent analyses were done with higher cut-off values. 34 In Singapore, there was very low overall seroprevalence rate of 26.9%, with the rate increasing from 14.3% in children aged 1 to 6 years to 38.8% in adolescents aged 13 to 17 years.…”

“…These variations are likely to reflect geography‐specific combinations of risk factors. Overall, children <5 years were shown to have lower seropositive rates of EV‐A71 antibody, except for children in rural villages of Malaysia, because of their poor living conditions and lifestyle compared with urban residents . This indicates that this age group is most susceptible to the infection, which is borne out by the higher rates of infection reported in younger children .…”

“…In Malaysia, the EV‐A71 seropositive rate in children <12 years was higher during epidemic years compared with nonepidemic years, with increasing seropositive rate as age increased . Children in rural villages had higher seropositive rates than urban children, reaching >80% seropositive by 3 years and >95% by 12 years . High seroprevalence was observed recently in Cambodia, where EV‐A71 seroprevalence among children was 88.8% although more stringent analyses were done with higher cut‐off values .…”

Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients

“…However, the OD values of PEP27 in non-HFMD children sera was higher than the remaining four IgM epitopes, suggesting that the cut-off could be improved. High population immunity to EV-A71 has been reported in Malaysian children, with EV-A71 seropositive rates in non-HFMD urban children increasing gradually from 47.1% at 1–3 years to 75.0% at 13–17 years [29], suggesting that true non-HFMD sera are required to establish a more reliable cut-off.…”

“…EV-A71 specific-IgM and -IgG antibodies in sera samples were detected using an EV-A71 IgM-capture enzyme-linked immunosorbent assay (ELISA; Beijing Wantai Biological Pharmacy Enterprise CO., Ltd., China) [28], and western blot and virion-based ELISA analyses, respectively. The neutralization activity of antibodies in sera specimens were tested in triplicate and analyzed by microneutralization assay as previously described [29,30]. A sample was considered positive if the neutralizing titer was ≥1:8.…”