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The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling

Published online by Cambridge University Press:  05 August 2002

S. PAGET-MCNICOL
Affiliation:
Malaria Biology Lab, Division of Infectious Diseases and Immunology, The Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Qld 4029, Australia
M. GATTON
Affiliation:
Malaria Biology Lab, Division of Infectious Diseases and Immunology, The Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Qld 4029, Australia
I. HASTINGS
Affiliation:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
A. SAUL
Affiliation:
Malaria Biology Lab, Division of Infectious Diseases and Immunology, The Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Qld 4029, Australia Present address: Malaria Vaccine Development Unit, NIAID/LPD, National Institutes of Health, Rockville MD 20852, USA.

Abstract

Recrudescing Plasmodium falciparum parasitaemia is attributed to the switching of PfEMP1, a variant antigen family encoded by the var gene repertoire, and the host's immune response. We have developed a mathematical model which incorporates var gene switching, and variant specific, non-variant specific and non-specific immunity. By conducting a sensitivity analysis of the model we have defined the parameter limits which produce chronic and recrudescing infections. We explore 3 switching mechanisms: ordered, random and uncoupled switching. We show that if var genes switch on and off independently at variable rates through the repertoire a chronic clinical infection is predicted. The fastest switching-on rate that produces a chronic infection is 0·03% per generation. The model predicts that non-variant specific immunity plays an important role in reducing disease severity. This work illustrates the complex relationship between the malaria parasite and its host and shows that var gene switching at rates substantially slower than 2% are essential for parasite survival.

Type
Research Article
Copyright
2002 Cambridge University Press

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