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MATHEMATICAL MODEL OF THE FIRST WAVE OF PLASMODIUM FALCIPARUM ASEXUAL PARASITEMIA IN NON-IMMUNE AND VACCINATED INDIVIDUALS

We present a dynamic model of the highly pathogenic first wave of Plasmodium falciparum asexual parasitemia in non-immune persons. The model was successfully fitted to malaria therapy data. This required four case-specific parameters: the basic two-day multiplication factor, the time of onset of adaptive immunity, and the effective dose 50 densities for the innate and adaptive immune responses, respectively. All four parameters show large case-dependent variation that is mainly attributable to host factors. According to the model, the maximum value of the first wave is controlled mainly by the innate immune response. We used the model to explore the expected effects of vaccines targeting the parasite’s asexual blood stages on the basis of what we consider to be the biologically most plausible assumptions concerning the parameter modifications induced by vaccination. According to our simulations, the benefit of antiparasitic vaccination is strongly host dependent and vaccine efficacy at low immunogenicity is much larger against severe disease than against fever. This has implications for the early testing of the protective efficacy of a vaccine in humans.

Received September 18, 2005. Accepted for publication May 8, 2006.

Acknowledgments: We gratefully acknowledge the provision of the malariatherapy data of the U.S. Public Health Service through Bill Collins and Geoffrey Jeffery. The detailed comments of an anonymous referee helped to clarify the presentation of our original submission.

^* Address correspondence to Klaus Dietz, Department of Medical Biometry, University of Tübingen, Westbahnhofstr. 55, 72070 Tübingen, Germany. E-mail: klaus.dietz{at}uni-tuebingen.de

Authors’ addresses: Klaus Dietz and Günter Raddatz, Department of Medical Biometry, University of Tübingen, Westbahnhofstr. 55, 72070 Tübingen, Germany, Telephone: 49-7071-297-2112, Fax: 49-7071-295-075; E-mails: klaus.dietz{at}uni-tuebingen.de and guenter.raddatz{at}tuebingen.mpg.de. Louis Molineaux, 46 Route de Peney Dessus, 1242 Satigny, Switzerland.

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