Comparison of modeling methods to determine liver-to-blood inocula and parasite multiplication rates during controlled human malaria infection

J Infect Dis. 2013 Jul 15;208(2):340-5. doi: 10.1093/infdis/jit156. Epub 2013 Apr 9.

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.

Keywords: Plasmodium falciparum; clinical trial; malaria; modeling; qPCR; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Liver / drug effects
  • Liver / immunology
  • Liver / parasitology*
  • Malaria Vaccines / blood
  • Malaria Vaccines / immunology
  • Malaria Vaccines / pharmacology*
  • Malaria, Falciparum / genetics
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / parasitology*
  • Malaria, Falciparum / prevention & control
  • Models, Biological*
  • Parasitemia / genetics
  • Parasitemia / immunology
  • Parasitemia / parasitology*
  • Parasitemia / prevention & control
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology

Substances

  • Malaria Vaccines