Section: Application Domains

Intra-host models for malaria: analysis and estimation problems

We give a brief review of the biological features of malaria. Malaria in a human begins with an inoculum of Plasmodium parasites (sporozoites) from a female Anopheles mosquito. The sporozoites enter the liver within minutes. After a period of asexual reproduction in the liver, the parasites (merozoites) are released in the bloodstream where the asexual erythrocyte cycle begins. The merozoites enter red blood cells (RBC), grow and reproduce over a period of approximately 48 hours after which the erythrocyte ruptures releasing daughter parasites that quickly invade a fresh erythrocyte to renew the cycle. This blood cycle can be repeated many times, in the course of which some of the merozoites instead develop in the sexual form of the parasites : gametocytes. Gametocytes are benign for the host and are waiting for the mosquitoes. An important characteristic of Plasmodium falciparum, the most virulent malaria parasite, is sequestration. At the half-way point of parasite development, the infected erythrocyte leaves the circulating peripheral blood and binds to the endothelium in the microvasculature of various organs where the cycle is completed. A measurement of Plasmodium falciparum parasitaemia taken from a blood smear therefore samples young parasites only. Physician treating malaria use the number of parasites in peripheral blood smears as a measure of infection, this does not give the total parasite burden of the patient. Moreover antimalarial drugs are known to act preferentially on different stages of parasite development. Our work consists in developing tools for estimating the sequestered parasites and hence the total parasite burden of the patient.