The impact of heterogeneous transmission on the establishment and spread of antimalarial drug resistance.

TitleThe impact of heterogeneous transmission on the establishment and spread of antimalarial drug resistance.
Publication TypeJournal Article
Year of Publication2014
AuthorsKlein EY
JournalJ Theor Biol
Date Published2014 Jan 7
KeywordsAnimals, Antimalarials, Artemisinins, Computer Simulation, Culicidae, Drug Resistance, Humans, Malaria, Models, Statistical, Plasmodium falciparum, Poisson Distribution, Stochastic Processes, Time Factors

Despite the important insights gained by extending the classical models of malaria, other factors, such as immunity, heterogeneous biting, and differential patterns of drug use have not been fully explored due to the complexity of modeling multiple simultaneous malaria infections competing within a host. Understanding these factors is important for understanding how to control the spread of drug resistance to artemisinin which is just emerging in Southeast Asia. The emergence of resistance plays out at the population level, but is the result of competition within individuals for transmission events. Most studies of drug resistance evolution have focused on transmission between hosts and ignored the role of within-host competition due to the inherent complexity of modeling at multiple scales. To embed within-host competition in the model, we used an agent-based framework that was developed to understand how deviations from the classical assumptions of the Ross-MacDonald type models, which have been well-described and analyzed, impact the dynamics of disease. While structured to be a stochastic analog to classical Ross-Macdonald type models, the model is nonetheless based on individuals, and thus aspects of within-host competition can be explored. We use this framework to explore the role of heterogeneous biting and transmission on the establishment and spread of resistance in a population. We find that heterogeneous transmission slows the establishment of resistance in a population, but once resistance is established, it speeds the spread of resistance through the population. These results are due to the skewed distribution of biting which makes onward transmission a low probability and suggests that targeting the "core" group of individuals that provide the vast majority of bites could significantly slow the spread of resistance.

Alternate JournalJ. Theor. Biol.
PubMed ID24076451
PubMed Central IDPMC3864917
Grant ListDP1 OD003874 / OD / NIH HHS / United States
DP1OD003874 / OD / NIH HHS / United States
U01 GM070708 / GM / NIGMS NIH HHS / United States
U01GM070708 / GM / NIGMS NIH HHS / United States
U54 GM088491 / GM / NIGMS NIH HHS / United States
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