title: Comparison of modeling methods to determine liver-to-blood inocula and parasite multiplication rates during controlled human malaria infection.
abstract: Controlled human malaria infection is used to measure efficacy of candidate malaria vaccines before field studies are undertaken. Mathematical modeling using data from quantitative polymerase chain reaction (qPCR) parasitemia monitoring can discriminate between vaccine effects on the parasite's liver and blood stages. Uncertainty regarding the most appropriate modeling method hinders interpretation of such trials. We used qPCR data from 267 Plasmodium falciparum infections to compare linear, sine-wave, and normal-cumulative-density-function models. We find that the parameters estimated by these models are closely correlated, and their predictive accuracy for omitted data points was similar. We propose that future studies include the linear model.
authors.affiliation: Jenner Institute, University of Oxford, UK. sandy.douglas@ndm.ox.ac.uk
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Douglas
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Edwards
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Duncan
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Thompson
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Sheehy
authors.forename: Geraldine A
authors.initials: GA
authors.lastname: O'Hara
authors.forename: Nicholas
authors.initials: N
authors.lastname: Anagnostou
authors.forename: Michael
authors.initials: M
authors.lastname: Walther
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Webster
authors.forename: Susanna J
authors.initials: SJ
authors.lastname: Dunachie
authors.forename: David W
authors.initials: DW
authors.lastname: Porter
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Draper
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
mesh_terms: D000818:Animals; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000469:parasitology*; D017780:Malaria Vaccines / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology / Q000469:parasitology* / Q000517:prevention & control; D008954:Models, Biological; D018512:Parasitemia / Q000235:genetics / Q000276:immunology / Q000469:parasitology* / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000276:immunology
chemical_list: D017780:Malaria Vaccines
keywords: Plasmodium falciparum; clinical trial; malaria; modeling; qPCR; vaccine