Research

Dynamics of immune response and drug resistance in malaria infection

David Gurarie^1,2 and F Ellis McKenzie²

¹  Department of Mathematics, Case Western Reserve University, Cleveland, OH. 44106, USA

²  Fogarty International Center, Building 16, National Institutes of Health, Bethesda, MD 20892, USA

author email corresponding author email

Malaria Journal 2006, 5:86doi:10.1186/1475-2875-5-86

Published:	11 October 2006

Abstract

Background

Malaria parasites that concurrently infect a host compete on the basis of their intrinsic growth rates and by stimulating cross-reactive immune responses that inhibit each others' growth. If the phenotypes also show different drug sensitivities ('sensitive' vs. 'resistant' strains), drug treatment can change their joint dynamics and the long-term outcome of the infection: most obviously, persistent drug pressure can permit the more resistant, but otherwise competitively-inferior, strains to dominate.

Methods

Here a mathematical model is developed to analyse how these and more subtle effects of antimalarial drug use are modulated by immune response, repeated re-inoculation of parasites, drug pharmacokinetic parameters, dose and treatment frequency.

Results

The model quantifies possible effects of single and multiple (periodic) treatment on the outcome of parasite competition. In the absence of further inoculation, the dosage and/or treatment frequency required for complete clearance can be estimated. With persistent superinfection, time-average parasite densities can be derived in terms of the basic immune-regulating parameters, the drug efficacy and treatment regimen.

Conclusion

The functional relations in the model are applicable to a wide range of conditions and transmission environments, allowing predictions to be made on both the individual and the community levels, and, in particular, transitions from drug-sensitive to drug-resistant parasite dominance to be projected on both levels.