Prevalence of Mutations in the pfcoronin Gene and Association with Ex Vivo Susceptibility to Common Quinoline Drugs against Plasmodium falciparum

Océane Delandre (1, 2) , Mathieu Gendrot (1, 2) , Isabelle Fonta (1, 2) , Joel Mosnier (1, 2) , Nicolas Benoit (1, 2) , Rémy Amalvict (1, 2) , Nicolas Gomez (2, 1) , Marylin Madamet (1, 2) , Bruno Pradines (2, 1)

1 IRBA - Institut de Recherche Biomédicale des Armées [Antenne Marseille]
2 VITROME - Vecteurs - Infections tropicales et méditerranéennes

Background: Artemisinin-based combination therapy (ACT) was recommended to treat uncomplicated falciparum malaria. Unlike the situation in Asia where resistance to ACT has been reported, artemisinin resistance has not yet emerged in Africa. However, some rare failures with ACT or patients continuing to be parasitaemic on day 3 after ACT treatment have been reported in Africa or in travellers returning from Africa. Three mutations (G50E, R100K, and E107V) in the pfcoronin gene could be responsible for artemisinin resistance in Africa. Methods: The aims of this study were first to determine the prevalence of mutations in the pfcoronin gene in African P. falciparum isolates by Sanger sequencing, by targeting the 874 samples collected from patients hospitalised in France after returning from endemic areas in Africa between 2018 and 2019, and secondly to evaluate their association with in vitro reduced susceptibility to standard quinoline antimalarial drugs, including chloroquine, quinine, mefloquine, desethylamodiaquine, lumefantrine, piperaquine, and pyronaridine. Results: The three mutations in the pfcoronin gene (50E, 100K, and 107V) were not detected in the 874 P. falciparum isolates. Current data show that another polymorphism (P76S) is present in many countries of West Africa (mean prevalence of 20.7%) and Central Africa (11.9%) and, rarely, in East Africa (4.2%). This mutation does not appear to be predictive of in vitro reduced susceptibility to quinolines, including artemisinin derivative partners in ACT such as amodiaquine, lumefantrine, piperaquine, pyronaridine, and mefloquine. Another mutation (V62M) was identified at low prevalence (overall prevalence of 1%). Conclusions: The 76S mutation is present in many African countries with a prevalence above 10%. It is reassuring that this mutation does not confer in vitro resistance to ACT partners.

Mots clés: malaria; Plasmodium falciparum; antimalarial drug; pfcoronin; resistance; in vitro; molecular marker

Domaines: Bactériologie; Cardiologie et système cardiovasculaire; Maladies émergentes; Maladies infectieuses; Parasitologie; Virologie

Océane Delandre, Mathieu Gendrot, Isabelle Fonta, Joel Mosnier, Nicolas Benoit, et al.. Prevalence of Mutations in the pfcoronin Gene and Association with Ex Vivo Susceptibility to Common Quinoline Drugs against Plasmodium falciparum. Pharmaceutics, 2021, 13 (8), pp.1273. ⟨10.3390/pharmaceutics13081273⟩. ⟨hal-03429248⟩