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

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Paget-McNicol, S., Gatton, M., Hastings, Ian ORCID: https://orcid.org/0000-0002-1332-742X and Saul, A. (2002) 'The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling'. Parasitology, Vol 124, Issue 3, pp. 225-235.

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Abstract

Recrudescing Plasmodium falciparum parasitacmia 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.

Item Type: Article
Uncontrolled Keywords: Plasmodium falciparum var gene switching rates switching mechanism disease severity mathematical modelling
Subjects: QU Biochemistry > Genetics > QU 475 Genetic processes
QW Microbiology and Immunology > QW 51 Morphology and variability of microorganisms. Microbial genetics.
QX Parasitology > Protozoa > QX 135 Plasmodia
QX Parasitology > Protozoa > QX 50 Protozoa
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1017/s0031182001001160
Depositing User: Sarah Lewis-Newton
Date Deposited: 02 Sep 2013 14:34
Last Modified: 06 Feb 2018 13:05
URI: http://archive.lstmed.ac.uk/id/eprint/2971

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