title: Impact of transmission intensity and age on Plasmodium falciparum density and associated fever: implications for malaria vaccine trial design.
abstract: To facilitate design of vaccine trials, malaria was studied in 6-month- to 6-year-old Kenyans during high (HI) and low intensity transmission seasons. During 84 days after cure, exposure to infected mosquitoes was 9-fold greater in the HI group, yet incidence of P. falciparum infection was increased only 2-fold, with no age effect. The density of recurrent P. falciparum was 14-fold greater in the HI group, and there was a striking association between age and parasitemia > or = 5000/microL. Fever was the only clinical manifestation attributable to parasitemia and only when the parasite density was > or = 5000/microL. Sixty-four percent of children with > or = 20,000 parasites/microL versus 10% with 1-4999/microL were febrile when parasitemic. Recurrent P. falciparum infection as a vaccine trial end point can be studied year-round among children < or = 6 years [corrected] in western Kenya. However, high-grade parasitemia (> or = 5000 or 20,000/microL) with or without elevated temperature will be optimally studied in the high transmission season among children < 2 years.
authors.affiliation: Malaria Program, Naval Medical Research Institute, Rockville, MD 20852, USA.
authors.forename: C
authors.initials: C
authors.lastname: Beadle
authors.forename: P D
authors.initials: PD
authors.lastname: McElroy
authors.forename: C N
authors.initials: CN
authors.lastname: Oster
authors.forename: J C
authors.initials: JC
authors.lastname: Beier
authors.forename: A J
authors.initials: AJ
authors.lastname: Oloo
authors.forename: F K
authors.initials: FK
authors.lastname: Onyango
authors.forename: D K
authors.initials: DK
authors.lastname: Chumo
authors.forename: J D
authors.initials: JD
authors.lastname: Bales
authors.forename: J A
authors.initials: JA
authors.lastname: Sherwood
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000367:Age Factors; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000962:Antimalarials / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000379:methods*; D015331:Cohort Studies; D018562:Disease Transmission, Infectious; D005334:Fever; D006801:Humans; D015994:Incidence; D007223:Infant; D007303:Insect Vectors / Q000469:parasitology; D007630:Kenya / Q000453:epidemiology; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology* / Q000635:transmission*; D018512:Parasitemia; D011739:Pyrimethamine / Q000627:therapeutic use; D012008:Recurrence; D012107:Research Design; D012189:Retrospective Studies; D012424:Rural Population; D012621:Seasons; D013413:Sulfadoxine / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D017780:Malaria Vaccines; D013413:Sulfadoxine; D011739:Pyrimethamine