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AN EPIDEMIOLOGIC MODEL OF THE INCIDENCE OF ACUTE ILLNESS IN PLASMODIUM FALCIPARUM MALARIA

We propose a stochastic model for simulating malaria tolerance. The model relates the probability of a clinical attack of malaria to the peripheral parasite densities via a pyrogenic threshold that itself responds dynamically to the parasite load. The parameters of the model have been estimated by fitting it to the relationship between incidence of clinical episodes and the entomologic inoculation rate, using age-specific incidence data from two villages in Senegal and one village in Tanzania. The model reproduces the shifts in age distribution of clinical episodes associated with variation in transmission intensity, and in keeping with the data, predicts a slightly higher lifetime number of episodes in the mesoendemic village of Ndiop than in the holoendemic village of Dielmo. This model provides a parsimonious explanation of counter-intuitive relationships between the overall incidence of clinical malaria and transmission intensity. In contrast to the theory of endemic stability, recently proposed to apply to P. falciparum, it does not assume any intrinsic age dependence in the outcome of infection. This model can be used to explore the consequences for predictions of the effects of different anti-malarial interventions on the incidence of clinical malaria.

Received September 18, 2005. Accepted for publication February 7, 2006.

Acknowledgments: We thank Professor Klaus Dietz for his helpful comments on an earlier draft of this report and Dr. Timothy Haley for assistance with statistical analyses.

Financial support: The mathematical modeling study was supported by the Program for Appropriate Technology in Health (PATH) Malaria Vaccine Initiative and GlaxoSmithKline Biologicals S.A.

Disclaimer: Publication of this report and the contents hereof do not necessarily reflect the endorsement, opinion, or viewpoints of the PATH Malaria Vaccine Initiative or GlaxoSmithKline Biologicals S.A.

^* Address correspondence to Thomas Smith, Swiss Tropical Institute, Socinstrasse 57, PO Box, CH-4002, Basel, Switzerland. E-mail: Thomas-A.Smith{at}unibas.ch

Authors’ addresses: Thomas Smith, Amanda Ross and Nicolas Maire, Swiss Tropical Institute, Socinstrasse 57, PO Box, CH-4002, Basel, Switzerland, Telephone: 41-61-284-8273, Fax: 41-61-284-8105, E-mails: Thomas-A.Smith{at}unibas.ch, amanda.ross{at}unibas.ch, and nicolas.maire{at}unibas.ch. Christophe Rogier, Institut de Médecine Tropicale du Service de Santé des Armées, BP46, Parc du Pharo, 13998 Marseille-Armées, France; Telephone: 33-4-91-15-01-50/52, Fax: 33-4-91-01-64, E-mail: christophe.rogier{at}wanadoo.fr. Jean-François Trape, Institut de Recherche pour le Développement, 77 Paludologie Afrotropicale, BP 1386, CP 18524 Dakar, Senegal, Telephone: 221-849-3582, Fax: 221-832-4307, E-mail: Jean-Francois.Trape{at}ird.sn. Louis Molineaux, Peney-Dessus, CH-1242 Satigny, Geneva, Switzerland.

Reprints requests: Thomas Smith, Swiss Tropical Institute, Socinstrasse 57, PO Box, CH-4002, Basel, Switzerland.

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