title: Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia.
abstract: Enterovirus A71 (EV-A71) is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD) in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2-3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence). Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples collected from children ≤12 years old between 1995 and 2012 to determine the seroprevalence of EV-A71. Reported national HFMD incidence was highest in children <2 years, and decreased with age; in support of this, EV-A71 seroprevalence was significantly associated with age, indicating greater susceptibility in younger children. EV-A71 epidemics are also characterized by peaks of increased genetic diversity, often with genotype changes. Cross-sectional time series analysis was used to model the association between EV-A71 epidemic periods and EV-A71 seroprevalence adjusting for age and climatic variables (temperature, rainfall, rain days and ultraviolet radiance). A 10% increase in absolute monthly EV-A71 seroprevalence was associated with a 45% higher odds of an epidemic (adjusted odds ratio, aOR1.45; 95% CI 1.24-1.69; P<0.001). Every 10% decrease in seroprevalence between preceding and current months was associated with a 16% higher odds of an epidemic (aOR = 1.16; CI 1.01-1.34 P<0.034). In summary, the 2-3 year cyclical pattern of EV-A71 epidemics in Malaysia is mainly due to the fall of population immunity accompanying the accumulation of susceptible children between epidemics. This study will impact the future planning, timing and target populations for vaccine programs.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Malaysia.
authors.forename: Nmn
authors.initials: N
authors.lastname: NikNadia
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Malaysia.
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Sam
authors.affiliation: Department of Social and Preventive Medicine, Julius Centre University of Malaya, Faculty of Medicine, University of Malaya, Malaysia.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rampal
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Malaysia.
authors.forename: Wmz
authors.initials: W
authors.lastname: WanNorAmalina
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Malaysia.
authors.forename: Ghazali
authors.initials: G
authors.lastname: NurAtifah
authors.affiliation: National Public Health Laboratory, Ministry of Health, Selangor, Malaysia.
authors.forename: Khebir
authors.initials: K
authors.lastname: Verasahib
authors.affiliation: Kepong Health Office, Ministry of Health, Kuala Lumpur, Malaysia.
authors.forename: Chia Ching
authors.initials: CC
authors.lastname: Ong
authors.affiliation: Zoonosis Sector, Disease Control Division, Ministry of Health, Malaysia.
authors.forename: MohdAidinniza
authors.initials: M
authors.lastname: MohdAdib
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Malaysia.
authors.forename: Yoke Fun
authors.initials: YF
authors.lastname: Chan
mesh_terms: D002648:Child; D002675:Child, Preschool; D021821:Communicable Diseases, Emerging; D029821:Enterovirus A, Human; D006232:Hand, Foot and Mouth Disease / Q000097:blood / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D007223:Infant; D008296:Malaysia / Q000453:epidemiology; D013997:Time Factors