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Time of treatment influences the appearance of drug-resistant parasites in Plasmodium falciparum infections

Published online by Cambridge University Press:  06 February 2003

M. L. GATTON ,
W. HOGARTH  and
A. SAUL
M. L. GATTON
Affiliation:
Malaria Biology Laboratory, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Qld 4029, Australia
W. HOGARTH
Affiliation:
Faculty of Environmental Sciences, Griffith University, Kessels Road, Qld 4111, Australia
A. SAUL
Affiliation:
Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20852, USA
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Abstract

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.

Keywords

malariaPlasmodium falciparumdrug resistanceantibodiesPfEMP1mathematical modelling
Type
Research Article
Information
Parasitology , Volume 123 , Issue 6 , June 2001 , pp. 537 - 546
Copyright
© 2001 Cambridge University Press

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