title: Decreased growth rate of P. falciparum blood stage parasitemia with age in a holoendemic population.
abstract: In malaria holoendemic settings, decreased parasitemia and clinical disease is associated with age and cumulative exposure. The relative contribution of acquired immunity against various stages of the parasite life cycle is not well understood. In particular, it is not known whether changes in infection dynamics can be best explained by decreasing rates of infection, or by decreased growth rates of parasites in blood. Here, we analyze the dynamics of Plasmodium falciparum infection after treatment in a cohort of 197 healthy study participants of different ages. We use both polymerase chain reaction (PCR) and microscopy detection of parasitemia in order to understand parasite growth rates and infection rates over time. The more sensitive PCR assay detects parasites earlier than microscopy, and demonstrates a higher overall prevalence of infection than microscopy alone. The delay between PCR and microscopy detection is significantly longer in adults compared with children, consistent with slower parasite growth with age. We estimated the parasite multiplication rate from delay to PCR and microscopy detections of parasitemia. We find that both the delay between PCR and microscopy infection as well as the differing reinfection dynamics in different age groups are best explained by a slowing of parasite growth with age.
authors.affiliation: Centre for Vascular Research, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Mykola
authors.initials: M
authors.lastname: Pinkevych
authors.forename: Janka
authors.initials: J
authors.lastname: Petravic
authors.forename: Kiprotich
authors.initials: K
authors.lastname: Chelimo
authors.forename: John
authors.initials: J
authors.lastname: Vulule
authors.forename: James W
authors.initials: JW
authors.lastname: Kazura
authors.forename: Ann M
authors.initials: AM
authors.lastname: Moormann
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage; D001769:Blood / Q000469:parasitology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology*; D008297:Male; D008853:Microscopy; D018512:Parasitemia / Q000453:epidemiology*; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000962:Antimalarials
keywords: Malaria; Plasmodium falciparum; blood stage; immunity; mathematical modeling