%0 Journal Article
%T Clinically immune hosts as a refuge for drug-sensitive malaria parasites
%A Eili Y Klein
%A David L Smith
%A Maciej F Boni
%A Ramanan Laxminarayan
%J Malaria Journal
%D 2008
%I BioMed Central
%R 10.1186/1475-2875-7-67
%X The model is constructed as a two-stage susceptible-infected-susceptible (SIS) model of malaria transmission that assumes that individuals build up clinical immunity over a period of years. This immunity reduces the frequency and severity of clinical symptoms, and thus their use of drugs. It also reduces an individual's level of infectiousness, but does not impact the likelihood of becoming infected.Simulations found that with the introduction of resistance into a population, clinical immunity can significantly alter the fitness of the resistant parasite, and thereby impact the ability of the resistant parasite to spread from an initial host by reducing the effective reproductive number of the resistant parasite as transmission intensity increases. At high transmission levels, despite a higher basic reproductive number, R0, the effective reproductive number of the resistant parasite may fall below the reproductive number of the sensitive parasite.These results suggest that high-levels of clinical immunity create a natural ecological refuge for drug-sensitive parasites. This provides an epidemiological rationale for historical patterns of resistance emergence and suggests that future outbreaks of resistance are more likely to occur in low- or unstable-transmission settings. This finding has implications for the design of drug policies and the formulation of malaria control strategies, especially those that lower malaria transmission intensity.Malaria is the leading cause of death in children under five in sub-Saharan Africa [1]. Prompt treatment with effective antimalarial drugs could prevent much of the morbidity and mortality associated with clinical malaria, but the evolution of resistance has diminished the therapeutic efficacy of two previous first-line antimalarials, chloroquine (CQ) and sulphadoxine-pyrimethamine (SP). Historically, it has been suggested that resistance to both CQ and SP emerged from a limited number of de novo selection events in areas of low
%U http://www.malariajournal.com/content/7/1/67