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Review
. 2018:25:24.
doi: 10.1051/parasite/2018021. Epub 2018 Apr 20.

Plasmodium falciparum resistance to artemisinin-based combination therapies: A sword of Damocles in the path toward malaria elimination

Manel Ouji  1 , Jean-Michel Augereau  1 , Lucie Paloque  1 , Françoise Benoit-Vical  1
Affiliations
Review

Plasmodium falciparum resistance to artemisinin-based combination therapies: A sword of Damocles in the path toward malaria elimination

Manel Ouji et al. Parasite. 2018.

Abstract
in English, French

The use of artemisinin-based combination therapies (ACTs), which combine an artemisinin derivative with a partner drug, in the treatment of uncomplicated malaria has largely been responsible for the significant reduction in malaria-related mortality in tropical and subtropical regions. ACTs have also played a significant role in the 18% decline in the incidence of malaria cases from 2010 to 2016. However, this progress is seriously threatened by the reduced clinical efficacy of artemisinins, which is characterised by delayed parasitic clearance and a high rate of recrudescence, as reported in 2008 in Western Cambodia. Resistance to artemisinins has already spread to several countries in Southeast Asia. Furthermore, resistance to partner drugs has been shown in some instances to be facilitated by pre-existing decreased susceptibility to the artemisinin component of the ACT. A major concern is not only the spread of these multidrug-resistant parasites to the rest of Asia but also their possible appearance in Sub-Saharan Africa, the continent most affected by malaria, as has been the case in the past with parasite resistance to other antimalarial treatments. It is therefore essential to understand the acquisition of resistance to artemisinins by Plasmodium falciparum to adapt malaria treatment policies and to propose new therapeutic solutions.

Title: Résistance de Plasmodium falciparum aux combinaisons thérapeutiques à base d’artémisinine : une épée de Damoclès sur les stratégies d’éradication du paludisme.

Abstract: L’utilisation, dans le traitement du paludisme simple, de combinaisons thérapeutiques associant un dérivé de l’artémisinine et une molécule partenaire a largement contribué à une réduction significative de la mortalité due à cette pathologie dans les régions tropicales et subtropicales ainsi qu’une diminution de 18% de nombre de cas de 2010 à 2016. Cependant, ces progrès sont sérieusement menacés par la diminution de l’efficacité clinique des artémisinines caractérisées par des clairances parasitaires retardées et un taux de recrudescence élevé, signalés en 2008 à l’ouest du Cambodge. La résistance aux artémisinines s’est déjà étendue à plusieurs pays d’Asie du Sud-Est. De plus, il a été montré que la résistance aux molécules partenaires des artémisinines dans ces combinaisons thérapeutiques (ACT) a été facilitée suite à une diminution de la sensibilité à l’artémisinine. L’une des principales préoccupations est non seulement la propagation de ces parasites multi-résistants dans le reste de l’Asie, mais aussi leur apparition possible en Afrique subsaharienne, continent le plus touché par le paludisme, comme cela a été le cas dans le passé avec la résistance de parasites à d’autres traitements antipaludiques. Il est donc essentiel de comprendre l’acquisition de la résistance de Plasmodium falciparum aux artémisinines afin d’adapter les politiques de santé face au paludisme et de proposer de nouvelles solutions thérapeutiques.

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Figures

Figure 1
Figure 1
Mutations in the PfK13 protein involved in artemisinin resistance (WHO) [80].
See this image and copyright information in PMC

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