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Clinical trials are an essential step in evaluation of safety and efficacy of malaria vaccines, and human experimental malaria infections have been used for evaluation of protective immunity of Plasmodium falciparum malaria. In this study, a quantitative real-time polymerase chain reaction was used to measure P. falciparum malaria parasitemia in non-immune volunteers who had been experimentally infected by mosquito bites. Based on a remarkably small variation in the kinetics of parasitemia, a statistical model was developed that provides detailed estimates of pre-patent periods and parasite multiplication of blood stages. Using this model, we could predict results on vaccine efficacy for 1) pre-erythrocytic vaccines in the asymptomatic incubation period and 2) asexual stage vaccines after a limited number of multiplication cycles. The model shows that stage-specific vaccines even with limited efficacy can be highly efficacious when used in combination. This P. falciparum challenge method significantly adds to the potential to evaluate efficacy of candidate malaria vaccines before going into field trials.
Received January 13, 2004. Accepted for publication March 16, 2004.
Acknowledgments: We thank M. van de Vegte-Bolmer for culturing malaria parasites, T. Arens and M. Sieben for skilled microscopy, J. van der Meer for clinical assistance, N. Nagelkerke for statistical advice, and W. Eling and A. Thomas for critical review and discussions.
Financial support: This project was supported by the European Union FP 5, contract number QLK2 -CT-1999-01293.
Authors’ addresses: Cornelus C. Hermsen, Geert Jan A. van Gemert, Denise S. C. Telgt, and Robert W. Sauerwein, Department of Medical Microbiology 188, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands, Telephone: 31-24-361-3663, Fax: 31-24-361-4666, E-mails: r.hermsen{at}ncmls.kun.nl, g.vangemert{at}mmb.umcn.nl, d.telgt{at}aig.umcn.nl, and r.sauerwein{at}mmb.umcn.nl. Sake J. de Vlas, Department of Public Health, Erasmus Medical Center, University Medical Center Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands, Telephone: 31-10-408-7985/8285, Fax: 31-10-408-9449, E-mail: s.devlas{at}erasmusmc.nl. Danielle F. Verhage, Department of Internal Medicine 541, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands, E-mail: d.verhage{at}aig.umcn.nl.
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