%0 Journal Article
%T Dynamics of immune response and drug resistance in malaria infection
%A David Gurarie
%A F Ellis McKenzie
%J Malaria Journal
%D 2006
%I BioMed Central
%R 10.1186/1475-2875-5-86
%X 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.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.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.Since the 1920s it has been clear that interactions of immune-system and drug dynamics are critical to the elimination or persistence of drug-resistant malaria parasites in individual patients, but details and dynamic principles remain to be established [1,2]. Later, in the 1980s, it was found that an isolate from a malaria infection is typically a mixture of parasite genotypes, some of which differ in antigenic profile, growth rate and drug response, and show complex population dynamics in mixed cultures [3,4]. Here a mathematical model is developed to investigate the dynamics of parasite phenotypes in a malaria-infected host, with respect to critical interactions between their immune-mediated competition, relative drug sensitivities and persistent superinfection. The results characterize conditions under which a malaria infection dominated by relatively drug-sensitive parasites transitions to one dominated by relatively drug-resistant parasites.Antimalarial drugs taken prophylactically or early in infecti
%U http://www.malariajournal.com/content/5/1/86