Comparison of clinical and parasitological data from controlled human malaria infection trials.
BACKGROUND
Exposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool to evaluate preliminary efficacy of malaria vaccines. To accommodate the demand of the malaria vaccine pipeline, controlled infections are carried out in an increasing number of centers worldwide. We assessed their safety and reproducibility.


METHODS
We reviewed safety and parasitological data from 128 malaria-naïve subjects participating in controlled malaria infection trials conducted at the University of Oxford, UK, and the Radboud University Nijmegen Medical Center, The Netherlands. Results were compared to a report from the US Military Malaria Vaccine Program.


RESULTS
We show that controlled human malaria infection trials are safe and demonstrate a consistent safety profile with minor differences in the frequencies of arthralgia, fatigue, chills and fever between institutions. But prepatent periods show significant variation. Detailed analysis of Q-PCR data reveals highly synchronous blood stage parasite growth and multiplication rates.


CONCLUSIONS
Procedural differences can lead to some variation in safety profile and parasite kinetics between institutions. Further harmonization and standardization of protocols will be useful for wider adoption of these cost-effective small-scale efficacy trials. Nevertheless, parasite growth rates are highly reproducible, illustrating the robustness of controlled infections as a valid tool for malaria vaccine development.
Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. M.Roestenberg@lumc.nl
Meta
M
Roestenberg
Geraldine A
GA
O'Hara
Christopher J A
CJ
Duncan
Judith E
JE
Epstein
Nick J
NJ
Edwards
Anja
A
Scholzen
André J A M
AJ
van der Ven
Cornelus C
CC
Hermsen
Adrian V S
AV
Hill
Robert W
RW
Sauerwein
D000328:Adult; D000704:Analysis of Variance; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D005260:Female; D006805:Human Experimentation / Q000592:standards* / Q000706:statistics & numerical data; D006801:Humans; D017780:Malaria Vaccines / Q000494:pharmacology* / Q000592:standards; D016778:Malaria, Falciparum / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D016133:Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric
D017780:Malaria Vaccines