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Analyze the spreading pattern and molecular mechanisms of malaria parasite chemoresistance (PI: A. Berry)

Regular monitoring of the levels of anti-malarial resistance of P. falciparum is an essential policy to adapt therapy and improve malaria control. In collaboration with IRD, we have assessed the impact of antimalarial treatments on the emergence and spread of resistant parasites in the field in Cameroon (Ménard et al, Malar J 2012). Artemisinin-derivatives (ART) are the last still effective antimalarial class but emergence of resistant P. falciparum raises dramatic public health problem. In collaboration with F. Benoit-Vical (LCC CNRS, Toulouse), we have demonstrated that F32-ART parasites, a highly ART-resistant, in vitro selected strain, survive toxic effect of ART through temporary growth arrest, as has been recently reported in malaria isolates from patients in Asia (Witkowski et al, AAC 2010 and AAC 2013). By sequencing the whole genome of F32-ART and its parental line in collaboration with the Pasteur Institutes of Paris and Cambodia, we found mutations which were also present in clinical ART-resistant malaria isolates from Southeast Asia. These findings allowed the identification of the first gene strongly associated with ART-resistance (Ariey et al, Nature 2014).

Based on this body of work, we are addressing 2 specific aims:
1- Monitor the emergence and spread of P. falciparum chemoresistance in Africa, with a particular focus on the K13 gene polymorphisms responsible for ART resistance (Sandie Ménard, PhD student)
2- Characterize the mechanisms underlying quiescence of ART-resistant P. falciparum and infer potential strategies to revert this quiescent state (Sandie Ménard, PhD student)

A quiescent Plasmodium falciparum parasite in a human erythrocyte following artemisinin treatment

Organisation de Coordination et de Coopération pour la lutte contre les grandes Endémies en Afrique Centrale (Yaoundé, Cameroun).

screening children for malaria infection in the Mfou district (Cameroun)

Last updated June 28, 2017

Centre de physiopathologie de Toulouse Purpan - CHU Purpan - BP 3028 31024 Toulouse Cedex 3
Inserm University of Toulouse Université Toulouse III - Paul Sabatier