Evolution and Epidemiology of Drug Resistance in Plasmodium (EVODRUG)

More than a century ago, the Nobel prize-winning scientist Paul Erlich predicted that pathogens subjected to drugs would evolve resistance. In the ensuing years, this worrying prediction has been proven to be true for a large number of pathogen-drug combinations. Today, drug resistance is both a major public health issue and one of the best documented examples of evolution in real time. Drug resistance is a major issue in the control of malaria. The evolution of drug resistance by malaria parasites is accepted as inevitable by the World Health Organization: Plasmodium parasites have evolved resistance to all classes of anti-malarials that have gone into widespread use. New front-line drugs are urgently needed, but so are evidence-based resistance management strategies. For this, however, the researchers need to understand the selective pressures involved in the evolution and spread of drug resistant mutations. The fate of drug resistant mutations depends on factors which may be controled, such as the rate and pattern of drug use. However, it also depends on factors over which cannot be controled, the most important of which is the biological cost that resistance imposes on the fitness of parasites. Drug resistance mutations are known to disrupt the parasite’s metabolism, generating fitness costs. In drug-treated hosts these costs are largely compensated by the benefits conferred by the resistance. In untreated hosts, however, the magnitude of these costs will determine whether these mutations will persist and spread in the population. Current views about the costs of drug resistance are almost entirely based on data regarding parasitic infections in vertebrate hosts. The costs of resistance in the mosquito vector have either been ignored entirely or been given only cursory attention. For the purpose of the aim of this projects, the researchers shall combine (i) an experimental approach using both artificially selected drug resistant strains of Plasmodium and an appropriate animal model , and field-collected drug resistant strains of P. falciparum, the aetiological agent of the most dangerous form of human malaria, (ii) an empirical approach in the field (Cameroun and Burkina Faso) that will allow the researchers to compare the frequency of different drug resistant mutations in both humans and mosquitoes at six different sites and (iii) a theoretical modelling approach that will integrate data from the field to make predictions about the evolution of drug resistance under different scenarios (different costs of drug resistance in mosquitoes and humans. The integration and feedback between these different approaches will provide the most complete picture to date of the transmission costs associated to drug resistance in Plasmodium and will potentially drastically alter predictions about the persistence and spread of drug resistance in the absence of treatment.

Project details

Drug Resistance

Sep 2016 — Mar 2020

$705,222

Burkina Faso
Cameroon
France