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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in drug development, deployment and resistance

Identification and validation of candidate gene alleles associated with ACT resistant phenotypes of Plasmodium falciparum: part of the MALACTRES Consortium.

LSHTM investigators:
Colin Sutherland, Rachel Hallett, Nahla Gadalla, Khalid Beshir, Brighid O’Neill & Teun Bousema.
External collaborators:
Henk Schallig & Petra Mens (Royal Tropical Institute, The Netherlands), Umberto D’Alessandro (The Prince Leopold Institute of Tropical Medicine, Belgium), Aart van Amerongen (Biomolecular Sensing and Diagnostics, Agrotechnology & Food Innovations, The Netherlands), Chris Danks & Paul Meakin (Forsite Diagnostics Ltd, UK), Ehise Enato (Tropical Diseases Research Group, Nigeria), Halidou Tinto (Centre Muraz, Burkina Faso) & Seif Shekalaghe (Kilimanjaro Christian Medical Centre, Tanzania).
Funding body:
The European Union Seventh Research Framework Programme through the MALACTRES Consortium.

MALACTRES is a consortium of researchers aiming to tackle multi-drug resistance in malaria under combination therapy.

With partners in Europe and Africa, the overall objective is to assess specific genetic markers in Plasmodium falciparum for associations with artemisinin combination therapy (ACT) resistance and to develop innovative, rapid and simple diagnostics for malaria. Since the last Malaria Centre Report we have:

  • made progress in establishing SNP detection tests for new candidate genes pfubp1 and pfap2-mu (see report by Gisela Henriques).
  • produced good quality genotyping results from isolates with in vitro drug susceptibility data from Burkina Faso.
  • applied a novel molecular parasite clearance time assay to samples from a clinical trial in Kenya.
  • shown good evidence that slow parasite clearance by PCR is linked to post-treatment parasite recurrence and carriage of gametocytes.
  • revealed good evidence that pfmdr1 selection occurs in both Dihydroartemisinin-Piperaquine and Artemether-Lumefantrine (AL) treatment groups by day 3 after treatment, and thus is being selected by the artemisinin component.
  • validated the pfmdr1 N86Y SNP as a useful marker of parasite response to both artemisinin and lumefantrine.
  • expanded our large external network of collaborators, including groups who are running cross-sectional surveys and clinical trials from which parasite material can be used for a detailed analysis of known and candidate drug resistance markers.

For more information see the MALACTRES website.