Probability of emergence of antimalarial resistance in different stages of the parasite life cycle

Pongtavornpinyo, W; Hastings, I; Dondorp, A; White, L; Maude, R; Saralamba, S; Day, N; White, N; Boni, M

Journal article

Probability of emergence of antimalarial resistance in different stages of the parasite life cycle

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 10−10–10−9 if the per‐parasite chance of mutation is 10−10 per 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.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Pongtavornpinyo, W., Hastings, I., Dondorp, A., White, L., Maude, R., Saralamba, S., Day, N., White, N., & Boni, M. (2009). Probability of emergence of antimalarial resistance in different stages of the parasite life cycle. Evolutionary Applications, 2(1), 52–61.

MLA Style

Pongtavornpinyo, W, et al. “Probability of Emergence of Antimalarial Resistance in Different Stages of the Parasite Life Cycle.” Evolutionary Applications, vol. 2, no. 1, 2009, pp. 52–61.

Chicago Style

Pongtavornpinyo, W, I Hastings, A Dondorp, et al. 2009. “Probability of Emergence of Antimalarial Resistance in Different Stages of the Parasite Life Cycle.” Evolutionary Applications 2 (1): 52–61.
Print