LSTM Home > LSTM Research > LSTM Online Archive

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

Pongtavornpinyo, W., Hastings, Ian, Dondorp, A., White, L. J., Maude, R. J., Saralamba, S., Day, N. P., White, N. J. and Boni, M. F. (2009) 'Probability of emergence of antimalarial resistance in different stages of the parasite life cycle'. Evolutionary Applications, Vol 2, Issue 1, pp. 52-61.

Full text not available from this repository.

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.

Item Type: Article
Additional Information: 399VQ Times Cited:1 Cited References Count:34
Uncontrolled Keywords: artemisinin bottleneck de novo resistance drug resistance life cycle malaria population genetics resistance emergence severe falciparum-malaria elimination half-life plasmodium-falciparum drug-resistance pyrimethamine-sulfadoxine artesunate transmission spread combinations artemisinin
Subjects: WA Public Health > Preventive Medicine > WA 108 Preventive health services. Preventive medicine. Travel Medicine.
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
QV Pharmacology > QV 38 Drug action.
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by)
QW Microbiology and Immunology > QW 4 General works. Classify here works on microbiology as a whole.
QX Parasitology > QX 45 Host-parasite relations
QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 695 Parasitic diseases (General)
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids
QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 771 Standardization and evaluation of drugs
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General)
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
QX Parasitology > QX 4 General works
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1111/j.1752-4571.2008.00067.x
Depositing User: Mary Creegan
Date Deposited: 02 Jun 2010 17:06
Last Modified: 06 Feb 2018 12:59
URI: http://archive.lstmed.ac.uk/id/eprint/365

Statistics

View details

Actions (login required)

Edit Item Edit Item