EBioMedicine (Aug 2025)

Assessment of ex vivo antimalarial drug efficacy in African Plasmodium falciparum parasite isolates, 2016–2023: a genotype–phenotype association studyResearch in context

  • Jason Rosado,
  • Abebe A. Fola,
  • Sandrine Cojean,
  • Véronique Sarrasin,
  • Romain Coppée,
  • Justine Bailly,
  • Rizwana Zaffaroulah,
  • Azza Bouzayene,
  • Liliane Cicéron,
  • Ludivine Houzé,
  • Rebecca Crudale,
  • Lise Musset,
  • Marc Thellier,
  • Bruno Pradines,
  • Jérôme Clain,
  • Jeffrey A. Bailey,
  • Sandrine Houzé,
  • Ahmed Aboubacar,
  • Patrice Agnamey,
  • Abou-Bacar Ahmed,
  • Daniel Ajzenberg,
  • Adela Angoulvant,
  • Frédéric Ariey,
  • Benjamin Aubry,
  • Firouze Banisadr,
  • Sorya Belaz,
  • Ghania Belkadi,
  • Ghania Belkacem Belkadi,
  • Anne Pauline Bellanger,
  • Dieudonné Bemba,
  • Farida Benaoudia,
  • Martine Bloch,
  • Francoise Botterel,
  • Vincent Bouden,
  • Marie-Elisabeth Bougnoux,
  • Caren Brump,
  • Sophie Brun,
  • Julie Brunet,
  • Bernadette Buret,
  • Pauline Caraux-Paz,
  • Nourrisson Celine,
  • Sylvain Clauser,
  • Elodie Collin,
  • Naima Dahane,
  • Céline Damiani,
  • Eric Dannaoui,
  • Céline Dard,
  • Marie-Laure Darde,
  • Anne Debourgogne,
  • Thierry Delacour,
  • Jean-Marie Delarbre,
  • Anne Delaval,
  • Veronique Delcey,
  • Anne-Sophie Deleplancque,
  • Guillaume Desoubeaux,
  • Nathalie Desuremain,
  • Gisele Dewulf,
  • Rémy Durand,
  • Marie-Fleur Durieux,
  • Emmanuel Dutoit,
  • Odile Eloy,
  • Jean-François Faucher,
  • Loïc Favennec,
  • Albert Faye,
  • Odile Fenneteau,
  • Cécile Ficko,
  • Emilie Frealle,
  • Gilles Gargala,
  • Céline Garnaud,
  • Ludovic De Gentile,
  • Nadine Godineau,
  • Judith Gorlicki,
  • Yohann Le Govic,
  • Alain Gravet,
  • Nadia Guennouni,
  • Samia Hamane,
  • Thomas Hanslik,
  • Antoine Huguenin,
  • Jean-Pierre Hurst,
  • Fakhri Jeddi,
  • Leroy Jordan,
  • Luce Landraud,
  • Hélène Lapillonne,
  • Sébastien Larréché,
  • Rose-Anne Lavergne,
  • Jean Philippe Lemoine,
  • Cécile Leprince,
  • Elodie Lesteven,
  • Angèle Li,
  • Caroline Lohmann,
  • Basmaciyan Louise,
  • Marie-Claire Machouart,
  • Céline Malassigne,
  • Anthony Marteau,
  • Danièle Maubon,
  • Edith Mazars,
  • Bruno Megarbane,
  • Ana Mendes-Moreira,
  • Sylvain Mermond,
  • Gwénaël Le Moal,
  • Alicia Moreno,
  • Pierre Mornand,
  • Jean-Benjamin Murat,
  • René Nabias,
  • Jerome Naudin,
  • Gilles Nevez,
  • Céline Nourrisson,
  • Mouri Oussama,
  • Nathalie Parez,
  • Olivier Patey,
  • Pierre Patoz,
  • Gauthier Pean-De-Ponfilly,
  • Jean Yves Peltier,
  • Pascale Penn,
  • Alice Perignon,
  • Estelle Perraud-Cateau,
  • Alexander Pfaff,
  • Sorya Belaz,
  • Marc Pihet,
  • Jean-Etienne Pilo,
  • Isabelle Poilane,
  • Philippe Poirier,
  • Didier Poisson,
  • Denis Pons,
  • Lauren Pull,
  • Dorothée Quinio,
  • Didier Raffenot,
  • Matthieu Revest,
  • Gladys Robert,
  • Olivier Rogeaux,
  • Gabrielle Roosen,
  • Milène Sasso,
  • Françoise Schmitt,
  • Boualem Sendid,
  • Yaye Senghor,
  • Muriel Silva,
  • Jean-Yves Siriez,
  • Emilie Sitterlé,
  • Frédéric Sorge,
  • Maurellet Evrard Sylvie,
  • Ilhame Tantaoui,
  • Dominique Toubas,
  • Ali Cherif Touil,
  • Céline Tournus,
  • Hélène Yera

DOI
https://doi.org/10.1016/j.ebiom.2025.105835
Journal volume & issue
Vol. 118
p. 105835

Abstract

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Summary: Background: Given the altered responses to both artemisinins and lumefantrine in Eastern Africa, monitoring antimalarial drug resistance in all African countries is paramount. Methods: We measured the susceptibility to six antimalarials using ex vivo growth inhibition assays (IC50) for a total of 805 Plasmodium falciparum isolates obtained from travellers returning to France (2016–2023), mainly from West and Central Africa. Isolates were sequenced using molecular inversion probes (MIPs) targeting forty-three genes across the parasite genome, of which nineteen are drug resistance genes. Findings: Ex vivo susceptibility of all assessed antimalarial compounds was consistent with their potent activity. The median IC50 values for the six drugs were 1.1 nM [IQR: 0.8–1.7] for DHA, 16.7 nM [9.9–27.4] for LMF, 29.5 nM [19.1–45.5] for MFQ, 23.4 nM [17.1–39.0] for MDAQ, 26.7 nM [18.0–41.2] for CQ, and 18.5 nM [15.1–24.3] for PPQ. Only four isolates carried a validated pfkelch13 mutation. Multiple mutations in pfcrt and one in pfmdr1 (Asn86Tyr) were significantly associated with altered susceptibility to multiple drugs, and their frequencies decreased over time. Pfcrt and pfmdr1 mutations altered susceptibility to lumefantrine and mefloquine in an additive manner, with the wild-type haplotype (pfcrt K76-pfmdr1 N86) exhibiting the lowest susceptibility. Interpretation: Our study on P. falciparum isolates from West and Central Africa indicates a low frequency of molecular markers associated with artemisinin resistance and a modest but significant decrease (1.6–2.3X) in the frequency of multidrug resistance markers. These genotypic changes likely mark parasite adaptation to sustained drug pressure and call for intensifying the monitoring of antimalarial drug resistance in Africa. Funding: This work was supported by the French Ministry of Health (grant to the French National Malaria Reference Centre) and by the Agence Nationale de la Recherche (ANR-17-CE15-0013-03 to JC). JAB was supported by NIH R01AI139520. JR postdoctoral fellowship was funded by Institut de Recherche pour le Développement.

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