Time of treatment influences the appearance of drug-resistant parasites in Plasmodium falciparum infections.
A deterministic mathematical model which predicts the probability of developing a new drug-resistant parasite population within the human host is reported. The model incorporates the host's specific antibody response to PfEMP1, and also investigates the influence of chemotherapy on the probability of developing a viable drug-resistant parasite population within the host. Results indicate that early treatment, and a high antibody threshold coupled with a long lag time between antibody stimulation and activity, are risk factors which increase the likelihood of developing a viable drug-resistant parasite population. High parasite mutation rates and fast PfEMP1 var gene switching are also identified as risk factors. The model output allows the relative importance of the various risk factors as well as the relationships between them to be established, thereby increasing the understanding of the conditions which favour the development of a new drug-resistant parasite population.
Gatton
M L
ML
Malaria Biology Laboratory, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Australia. michellG@qimr.edu.au
Hogarth
W
W
Saul
A
A
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000276:immunology; D000962:Antimalarials / Q000276:immunology / Q000627:therapeutic use*; D053626:Atovaquone; D003198:Computer Simulation; D004351:Drug Resistance / Q000235:genetics / Q000276:immunology; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000276:immunology; D008954:Models, Biological; D009154:Mutation; D009285:Naphthoquinones / Q000276:immunology / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D011739:Pyrimethamine / Q000276:immunology / Q000627:therapeutic use; D013997:Time Factors
D000913:Antibodies, Protozoan; D000962:Antimalarials; D009285:Naphthoquinones; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D053626:Atovaquone; D011739:Pyrimethamine