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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in drug development, deployment and resistance

Exploring the contribution of new genetic markers of drug resistance in human malaria parasites.

LSHTM investigators:
Gisela Henriques, Rachel Hallett, Colin Sutherland & Teun Bousema.
External collaborators:
Pedro Cravo (Universidade Federal de Goiás, Brazil); Paul Hunt (University of Edinburgh, UK); Halidou Tinto (Centre Muraz, Burkina Faso); Umberto D’Alessandro (Medical Research Council, The Gambia); Seif Shekalaghe (Kilimanjaro Christian Medical College, Tanzania).
Funding body:
Portuguese Foundation for Science and Technology.

Artemisinin derivatives form the cornerstone of anti-malarial drug therapy for the treatment of Plasmodium falciparum infection and recent evidence suggesting the possible development of resistance to this group of drugs is a significant public health concern.

The main aim of this PhD project is to investigate the genetic basis of the malaria parasite’s resistance to artemisinin derivatives. Using genome-wide strategies in the rodent malaria parasite Plasmodium chabaudi Drs Pedro Cravo and Paul Hunt, our collaborative research partners, have identified a number of novel genetic markers of antimalarial drug resistance. Now, using field isolates that were tested in vitro for their response to artemisinin derivatives as well as pre- and post- treatment samples from in vivo ACT trials, we are investigating the contribution that these new candidate genetic markers may be making to the development of artemisinin resistance in the human malaria parasite. Our preliminary results indicate that polymorphisms in a gene encoding the mu chain of the AP2 adaptor complex protein (pfap2-mu) are associated with varying degrees of in vitro and in vivo responses to artemisinin