title: Modeling the dynamics of Plasmodium vivax infection and hypnozoite reactivation in vivo.
abstract: The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear. In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine), or the blood and liver stages of infection (chloroquine + primaquine). In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG) where patients were treated with either artesunate, or artesunate + primaquine. Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand. Similar analysis revealed the around 70% of infections in the PNG cohort were due to hypnozoite reactivation. We show how the age of the cohort, primaquine drug failure, and seasonality may affect estimates of the ratio of primary P. vivax infection to hypnozoite reactivation. Modeling of P. vivax primary infection and hypnozoite reactivation provides important insights into infection dynamics, and suggests that 90-96% of blood stage infections arise from hypnozoite reactivation. Major differences in infection kinetics between Thailand and PNG suggest the likelihood of drug failure in PNG.
authors.affiliation: Centre for Vascular Research, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Adeshina I
authors.initials: AI
authors.lastname: Adekunle
authors.affiliation: Centre for Vascular Research, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Mykola
authors.initials: M
authors.lastname: Pinkevych
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Rose
authors.initials: R
authors.lastname: McGready
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
authors.forename: Christine
authors.initials: C
authors.lastname: Luxemburger
authors.affiliation: Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: White
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.affiliation: Centre for Vascular Research, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Cromer
authors.affiliation: Centre for Vascular Research, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
mesh_terms: D000368:Aged; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D000077332:Artesunate; D002738:Chloroquine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008099:Liver / Q000469:parasitology; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000453:epidemiology* / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D010219:Papua New Guinea / Q000453:epidemiology; D010966:Plasmodium vivax / Q000502:physiology*; D011319:Primaquine / Q000627:therapeutic use; D034101:Sporozoites / Q000502:physiology*; D013785:Thailand / Q000453:epidemiology; D064348:Torpor / Q000502:physiology*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D002738:Chloroquine; D011319:Primaquine