title: Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission.
abstract: Plasmodium vivax relapse infections occur following activation of latent liver-stages parasites (hypnozoites) causing new blood-stage infections weeks to months after the initial infection. We develop a within-host mathematical model of liver-stage hypnozoites, and validate it against data from tropical strains of P. vivax. The within-host model is embedded in a P. vivax transmission model to demonstrate the build-up of the hypnozoite reservoir following new infections and its depletion through hypnozoite activation and death. The hypnozoite reservoir is predicted to be over-dispersed with many individuals having few or no hypnozoites, and some having intensely infected livers. Individuals with more hypnozoites are predicted to experience more relapses and contribute more to onwards P. vivax transmission. Incorporating hypnozoite killing drugs such as primaquine into first-line treatment regimens is predicted to cause substantial reductions in P. vivax transmission as individuals with the most hypnozoites are more likely to relapse and be targeted for treatment.
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Michael T
authors.initials: MT
authors.lastname: White
authors.affiliation: Department of Infection and Immunity, Walter and Eliza Hall Institute, Melbourne, Australia.
authors.forename: Stephan
authors.initials: S
authors.lastname: Karl
authors.affiliation: Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Battle
authors.affiliation: Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Simon I
authors.initials: SI
authors.lastname: Hay
authors.affiliation: Department of Infection and Immunity, Walter and Eliza Hall Institute, Melbourne, Australia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Azra C
authors.initials: AC
authors.lastname: Ghani
mesh_terms: D000818:Animals; D004197:Disease Reservoirs / Q000469:parasitology*; D006790:Host-Parasite Interactions / Q000502:physiology; D006801:Humans; D008018:Life Cycle Stages; D016780:Malaria, Vivax / Q000469:parasitology* / Q000635:transmission*; D008954:Models, Biological; D010271:Parasites / Q000502:physiology; D010966:Plasmodium vivax / Q000254:growth & development* / Q000502:physiology*; D012008:Recurrence; D013997:Time Factors
keywords: epidemiology; global health; human; malaria; mathematical; model; relapse; vivax