title: Plasmodium knowlesi invasion following spread by infected mosquitoes, macaques and humans.
abstract: Plasmodium knowlesi is increasingly recognized as a major cause of malaria in Southeast Asia. Anopheles leucosphyrous group mosquitoes transmit the parasite and natural hosts include long-tailed and pig-tailed macaques. Despite early laboratory experiments demonstrating successful passage of infection between humans, the true role that humans play in P. knowlesi epidemiology remains unclear. The threat posed by its introduction into immunologically naïve populations is unknown despite being a public health priority for this region. A two-host species mathematical model was constructed to analyse this threat. Global sensitivity analysis using Monte Carlo methods highlighted the biological processes of greatest influence to transmission. These included parameters known to be influential in classic mosquito-borne disease models (e.g. vector longevity); however, interesting ecological components that are specific to this system were also highlighted: while local vectors likely have intrinsic preferences for certain host species, how plastic these preferences are, and how this is shaped by local conditions, are key determinants of parasite transmission potential. Invasion analysis demonstrates that this behavioural plasticity can qualitatively impact the probability of an epidemic sparked by imported infection. Identifying key vector sub/species and studying their biting behaviours constitute important next steps before models can better assist in strategizing disease control.
authors.affiliation: Department of Disease Control,London School of Hygiene and Tropical Medicine,Keppel Street,London WC1E 7HT,UK.
authors.forename: Laith
authors.initials: L
authors.lastname: Yakob
authors.affiliation: Department of Mathematics,Biomathematics Graduate Program,Center for Quantitative Sciences in Biomedicine,North Carolina State University,Raleigh,NC 27695,USA.
authors.forename: Alun L
authors.initials: AL
authors.lastname: Lloyd
authors.affiliation: Institute of Biodiversity,Animal Health and Comparative Medicine,College of Medical Veterinary and Life Sciences,University of Glasgow,Glasgow G61 1QH,UK.
authors.forename: Rowland R
authors.initials: RR
authors.lastname: Kao
authors.affiliation: Institute of Biodiversity,Animal Health and Comparative Medicine,College of Medical Veterinary and Life Sciences,University of Glasgow,Glasgow G61 1QH,UK.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Ferguson
authors.affiliation: Institute of Biodiversity,Animal Health and Comparative Medicine,College of Medical Veterinary and Life Sciences,University of Glasgow,Glasgow G61 1QH,UK.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Brock
authors.affiliation: Immunology and Infection Department,London School of Hygiene and Tropical Medicine,Keppel Street,London WC1E 7HT,UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.affiliation: Mathematical Ecology Research Group,Department of Zoology,University of Oxford,Oxford OX1 3PS,Oxfordshire,UK.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bonsall
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology / Q000502:physiology*; D006790:Host-Parasite Interactions; D006801:Humans; D008251:Macaca; D008288:Malaria / Q000469:parasitology / Q000635:transmission* / Q000662:veterinary*; D008954:Models, Biological; D008992:Monkey Diseases / Q000469:parasitology / Q000635:transmission*; D009010:Monte Carlo Method; D000072138:Mosquito Vectors / Q000469:parasitology / Q000502:physiology*; D016790:Plasmodium knowlesi / Q000502:physiology*
keywords: 
                 Plasmodium knowlesi
              ; invasion analysis; mathematical model; vector behaviour; vector-borne disease