1. Baseline and multinormal distribution of ex vivo susceptibilities of Plasmodium falciparum to methylene blue in Africa, 2013–18
- Author
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Gendrot, Mathieu, Pradines, Bruno, Brouqui, P, Drancourt, Michel, Madamet, Marylin, Mosnier, Joel, Fonta, Isabelle, Amalvict, Rémy, Benoit, Nicolas, Briolant, Sébastien, Augis, V, Bastien, P, Berry, A, Chauvin, P, Cividin, M, Courtier, F, Delaunay, P, Delhaes, L, Dubosc, N, Gaillard, T, Genin, A, Garnotel, E, Javelle, E, L’ollivier, C, Lagier, J, Ledault, E, Leveque, M, Malvy, D, Marty, P, Ménard, G, Menu, E, Millet, P, Minodier, P, Picot, S, Pomares-Estran, C, Ranque, S, Receveur, M-C, Robin, A, Sappa, E, Savini, H, Sevestre, J, Simon, F, Sterkers, Yvon, Surcouf, C, Varlet, E, Wolff, A, Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, L'Oréal Recherche France (L'Oréal Recherche), L'OREAL, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Service de Santé des Armées, Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)
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0301 basic medicine ,Microbiology (medical) ,Veterinary medicine ,Plasmodium falciparum ,030231 tropical medicine ,030106 microbiology ,Drug Resistance ,Context (language use) ,Antimalarials ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Humans ,Distribution (pharmacology) ,Pharmacology (medical) ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Malaria, Falciparum ,ComputingMilieux_MISCELLANEOUS ,EC50 ,Pharmacology ,biology ,Bayes Theorem ,biology.organism_classification ,3. Good health ,Methylene Blue ,Infectious Diseases ,Reduced susceptibility ,chemistry ,Africa ,France ,Geometric mean ,Methylene blue ,Ex vivo - Abstract
Background Plasmodium falciparum resistance to most antimalarial compounds has emerged in Southeast Asia and spread to Africa. In this context, the development of new antimalarial drugs is urgent. Objectives To determine the baseline in vitro activity of methylene blue (Proveblue®) on African isolates and to determine whether parasites have different phenotypes of susceptibility to methylene blue. Methods Ex vivo susceptibility to methylene blue was measured for 609 P. falciparum isolates of patients hospitalized in France for malaria imported from Africa. A Bayesian statistical analysis was designed to describe the distribution of median effective concentration (EC50) estimates. Results The EC50 ranged from 0.16 to 87.2 nM with a geometric mean of 7.17 nM (95% CI = 6.21–8.13). The 609 EC50 values were categorized into four components: A (mean = 2.5 nM; 95% CI = 2.28–2.72), B (mean = 7.44 nM; 95% CI = 7.07–7.81), C (mean = 16.29 nM; 95% CI = 15.40–17.18) and D (mean = 38.49 nM; 95% CI = 34.14–42.84). The threshold value for in vitro reduced susceptibility to methylene blue was estimated at 35 nM using the geometric mean of EC50 plus 2 SDs of the 609 isolates. This cut-off also corresponds to the lower limit of the 95% CI of the methylene blue EC50 of component D. Thirty-five isolates (5.7%) displayed EC50 values above this threshold. Conclusions Methylene blue exerts a promising efficacy against P. falciparum and is a potential partner for triple combinations.
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- 2020
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