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Title: Probability of emergence of antimalarial resistance in different stages of the parasite life cycle
Authors: Wirichada Pongtavornpinyo
Ian M. Hastings
Arjen Dondorp
Lisa J. White
Richard J. Maude
Sompob Saralamba
Nicholas P. Day
Nicholas J. White
MacIej F. Boni
Mahidol University
Liverpool School of Tropical Medicine
Nuffield Department of Clinical Medicine
University of Oxford
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Feb-2009
Citation: Evolutionary Applications. Vol.2, No.1 (2009), 52-61
Abstract: Understanding the evolution of drug resistance in malaria is a central area of study at the intersection of evolution and medicine. Antimalarial drug resistance is a major threat to malaria control and directly related to trends in malaria attributable mortality. Artemisinin combination therapies (ACT) are now recommended worldwide as first line treatment for uncomplicated malaria, and losing them to resistance would be a disaster for malaria control. Understanding the emergence and spread of antimalarial drug resistance in the context of different scenarios of antimalarial drug use is essential for the development of strategies protecting ACTs. In this study, we review the basic mechanisms of resistance emergence and describe several simple equations that can be used to estimate the probabilities of de novo resistance mutations at three stages of the parasite life cycle: Sporozoite, hepatic merozoite and asexual blood stages; we discuss the factors that affect parasite survival in a single host in the context of different levels of antimalarial drug use, immunity and parasitaemia. We show that in the absence of drug effects, and despite very different parasite numbers, the probability of resistance emerging at each stage is very low and similar in all stages (for example per-infection probability of 10-10-10-9if the per-parasite chance of mutation is 10-10per asexual division). However, under the selective pressure provided by antimalarial treatment and particularly in the presence of hyperparasitaemia, the probability of resistance emerging in the blood stage of the parasite can be approximately five orders of magnitude higher than in the absence of drugs. Detailed models built upon these basic methods should allow us to assess the relative probabilities of resistance emergence in the different phases of the parasite life cycle. © 2009 Blackwell Publishing Ltd.
ISSN: 17524571
Appears in Collections:Scopus 2006-2010

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