Cyclical patterns of hand, foot and mouth disease associated with changes in childhood immunity levels in Malaysia
Recurring epidemics of childhood hand, foot and mouth disease are a major public health concern in Asia. In Malaysia one of the main infective agents is enterovirus A71, and the rate of disease spikes into epidemics approximately every 2-3 years. Researchers from the University of Malaya hypothesized that these recurrent epidemics were due to changes in the population immunity. They published their findings in the PLOS Neglected Tropical Diseases, showing associations between epidemic periods and immunity.
The researchers used Ministry of Health records for reporting the rates of hand, foot and mouth disease, and published reports for rates prior to 2006. Serum samples were taken from archived sera collected during routine childhood infection tests at the University of Malaya. Patients with suspected hand, foot and mouth disease were excluded. 1769 sera samples were used in total, with between 52 – 200 samples per year (with the exception of only 30 samples for 2009).
A neutralization assay was used to test for antibodies to the virus, and cross-sectional time series analysis to study the association between epidemic periods and seroprevalence rates. For this study, seroprevalence was defined as the proportion of sera samples with a neutralisation titre ?1:8. The results were adjusted for age and climactic variables.
The incidence of hand, foot and mouth disease was highest in patients under 2 years old, with 7-12 year olds showing the lowest incidence rate. The seroprevalence rate was highest in older children, with a rate of 71.6% for 7-12 year olds, and 52.8% for 1-6 year olds (p<0.001). Seroprevalence was also highest in epidemic years (67.4%) compared with non-epidemic years (36.6%) with p-value <0.001. The time series analysis showed that for every 10% increase in absolute monthly seroprevalence there were 45% higher odds of an epidemic, and that for every 10% decrease in seroprevalence between preceding and current months, there were 16% higher odds of an epidemic.
“This [research] suggests that epidemics lead to high levels of population seroprevalence; but during the 2-3 years between epidemics, the population of young children with no immunity is replenished and increases, making it more likely that a new epidemic will occur.” Explains Dr. Yoke Fun Chan from the University of Malaya. “This is the first study to show that the cyclical pattern of EV-A71 epidemics is associated with changes in EV-A71 seroprevalence.”
The study shows that changes in population immunity of children appear to be the major driving force of the cyclical hand, foot and mouth disease epidemics. This has important public health implications in directing vaccine planning, including timing and target populations for vaccines to prevent the spread of the disease.