Volume 9 Supplement 2

Parasite to Prevention: Advances in the understanding of malaria

Open Access

Antimalarial drugs: unexpected evolutionary consequences

  • Petra Schneider1,
  • Andy S Bell2,
  • Andrew F Read2 and
  • Sarah E Reece1, 3
Malaria Journal20109(Suppl 2):P45

https://doi.org/10.1186/1475-2875-9-S2-P45

Published: 20 October 2010

Background

For malaria parasites, exposure to drugs is now an integral, human-induced, part of their ecology that exerts substantial selective effects on their traits. Currently used drugs often do not eliminate transmission, which enables evolution of traits that are beneficial for parasites. The appearance and spread of resistance mutations that protect parasites through direct interactions with drug molecules are well documented and often assumed to underlie treatment failures. However, this is just one example of how parasites can minimise their vulnerability to drugs. Other parasite traits (e.g. growth rate, conversion rate, red blood cell preference) that parasites have evolved independently of drugs can also provide indirect protection from drugs. Both lab and field data suggest that such traits can influence parasite survival and transmission in drug treated malaria infections.

Methods

We used a rodent malaria model (Plasmodium chabaudi) to test if virulence can confer protection to parasites in drug-treated infections. Mice were infected with genetically similar virulent or avirulent genotypes (CWvir orCWavir), with or without an additional competing genotype (DK). Parasites were then exposed to drugs (control, pyrimethamine or artemisinin, across several doses and treatment regimes) and we compared parasite survival, production of gametocytes and, in a subset of infections, transmission to mosquitoes.

Results

We show virulent parasites better survived treatment with pyrimethamine1 or artemisinin, and produce more gametocytes than genetically related avirulent parasites. The survival and gametocyte production benefits for the virulent parasites held fora range of drug doses, duration of treatment and for drugs with different modes of action.

Conclusions

Drug sensitivity can be virulence dependent, leading to a survival and transmission advantage for virulent parasites. If these results are general across parasite genotypes and species, this has consequences for the evolutionary trajectories of parasites resulting from continued population-wide exposure to drugs2. I will discuss how to overcome the challenge of translating our laboratory findings to natural infections in humans and how to integrate our epidemiological and evolutionary findings into a framework for malaria control.

Authors’ Affiliations

(1)
Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh
(2)
Centre for Infectious Disease Dynamics, Departments of Biology and Entomology, Pennsylvania State University
(3)
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh

References

  1. Schneider P, Chan BH, Reece SE, Read AF: Does the drug sensitivity of malaria parasites depend on their virulence?. Malaria Journal. 2008, 7: 257-10.1186/1475-2875-7-257.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Stein WD, Sanchez CP, Lanzer M: Virulence and drug resistance in malaria parasites. Trends in Parasitology. 2009, 25: 441-443. 10.1016/j.pt.2009.07.003.View ArticlePubMedGoogle Scholar

Copyright

© Schneider et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Advertisement