Factors that are associated with the risk of acquiringPlasmodium knowlesimalaria in Sabah, Malaysia: a case-control study protocol

IntroductionPlasmodium knowlesihas long been present in Malaysia, and is now an emerging cause of zoonotic human malaria. Cases have been confirmed throughout South-East Asia where the ranges of its natural macaque hosts andAnopheles leucosphyrusgroup vectors overlap. The majority of cases are from Eastern Malaysia, with increasing total public health notifications despite a concurrent reduction inPlasmodium falciparumandP. vivaxmalaria. The public health implications are concerning givenP. knowlesihas the highest risk of severe and fatal disease of allPlasmodiumspp in Malaysia. Current patterns of risk and disease vary based on vector type and competence, with individual exposure risks related to forest and forest-edge activities still poorly defined. Clustering of cases has not yet been systematically evaluated despite reports of peri-domestic transmission and known vector competence for human-to-human transmission.Methods and analysisA population-based case–control study will be conducted over a 2-year period at two adjacent districts in north-west Sabah, Malaysia. Confirmed malaria cases presenting to the district hospital sites meeting relevant inclusion criteria will be requested to enrol. Three community controls matched to the same village as the case will be selected randomly. Study procedures will include blood sampling and administration of household and individual questionnaires to evaluate potential exposure risks associated with acquisition ofP. knowlesimalaria. Secondary outcomes will include differences in exposure variables betweenP. knowlesiand otherPlasmodiumspp, risk of severeP. knowlesimalaria, and evaluation ofP. knowlesicase clustering. Primary analysis will be per protocol, with adjusted ORs for exposure risks between cases and controls calculated using conditional multiple logistic regression models.EthicsThis study has been approved by the human research ethics committees of Malaysia, the Menzies School of Health Research, Australia, and the London School of Hygiene and Tropical Medicine, UK.