title: Factors that are associated with the risk of acquiring Plasmodium knowlesi malaria in Sabah, Malaysia: a case-control study protocol.
abstract: BACKGROUND
  Plasmodium knowlesi has 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 and Anopheles leucosphyrus group vectors overlap. The majority of cases are from Eastern Malaysia, with increasing total public health notifications despite a concurrent reduction in Plasmodium falciparum and P. vivax malaria. The public health implications are concerning given P. knowlesi has the highest risk of severe and fatal disease of all Plasmodium spp 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
  A 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 of P. knowlesi malaria. Secondary outcomes will include differences in exposure variables between P. knowlesi and other Plasmodium spp, risk of severe P. knowlesi malaria, and evaluation of P. knowlesi case clustering. Primary analysis will be per protocol, with adjusted ORs for exposure risks between cases and controls calculated using conditional multiple logistic regression models.
  
  
  METHODS
  This 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.
authors.affiliation: Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Grigg
authors.affiliation: Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia Infectious Diseases Unit, Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia Sabah Department of Health, Kota Kinabalu, Sabah, Malaysia.
authors.forename: T
authors.initials: T
authors.lastname: William
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Drakeley
authors.affiliation: Sabah Department of Health, Kota Kinabalu, Sabah, Malaysia.
authors.forename: J
authors.initials: J
authors.lastname: Jelip
authors.affiliation: Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
authors.forename: L
authors.initials: L
authors.lastname: von Seidlein
authors.affiliation: Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia.
authors.forename: B E
authors.initials: BE
authors.lastname: Barber
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Fornace
authors.affiliation: Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia Royal Darwin Hospital, Darwin, Northern Territory, Australia.
authors.forename: N M
authors.initials: NM
authors.lastname: Anstey
authors.affiliation: Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
authors.forename: T W
authors.initials: TW
authors.lastname: Yeo
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Cox
mesh_terms: D000818:Animals; D000852:Anopheles; D016022:Case-Control Studies; D004199:Disease Vectors; D005260:Female; D065928:Forests; D006801:Humans; D008251:Macaca; D008288:Malaria / Q000209:etiology / Q000469:parasitology / Q000635:transmission*; D016778:Malaria, Falciparum; D016780:Malaria, Vivax; D008296:Malaysia; D008297:Male; D016790:Plasmodium knowlesi; D012107:Research Design; D012111:Residence Characteristics; D012307:Risk Factors
keywords: PARASITOLOGY