title: Confirmation of Plasmodium falciparum in vitro resistance to monodesethylamodiaquine and chloroquine in Dakar, Senegal, in 2015.
abstract: In response to increasing resistance to anti-malarial drugs, Senegal adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria in 2006. However, resistance of Plasmodium falciparum parasites to artemisinin derivatives, characterized by delayed parasite clearance after treatment with ACT or artesunate monotherapy, has recently emerged and rapidly spread in Southeast Asia. After 10 years of stability with rates ranging from 5.6 to 11.8%, the prevalence of parasites with reduced susceptibility in vitro to monodesethylamodiaquine, the active metabolite of an ACT partner drug, increased to 30.6% in 2014 in Dakar. Additionally, after a decrease of the in vitro chloroquine resistance in Dakar in 2009-2011, the prevalence of parasites that showed in vitro chloroquine resistance increased again to approximately 50% in Dakar since 2013. The aim of this study was to follow the evolution of the susceptibility to ACT partners and other anti-malarial drugs in 2015 in Dakar. An in vitro test is the only method currently available to provide an early indication of resistance to ACT partners.
  
  
  
  Thirty-two P. falciparum isolates collected in 2015 in Dakar were analysed using a standard ex vivo assay based on an HRP2 ELISA. The prevalence of P. falciparum parasites with reduced susceptibility in vitro to monodesethylamodiaquine, chloroquine, mefloquine, doxycycline and quinine was 28.1, 46.9, 45.2, 31.2 and 9.7%, respectively. None of the parasites were resistant to lumefantrine, piperaquine, pyronaridine, dihydroartemisinin and artesunate. These results confirm an increase in the reduced susceptibility to monodesethylamodiaquine observed in 2014 in Dakar and the chloroquine resistance observed in 2013. The in vitro resistance seems to be established in Dakar. Additionally, the prevalence of parasites with reduced susceptibility to doxycycline has increased two-fold compared to 2014.
  
  
  
  The establishment of a reduced susceptibility to monodesethylamodiaquine as well as chloroquine resistance, and the emergence of a reduced susceptibility to doxycycline are disturbing. The in vitro and in vivo surveillance of anti-malarial drugs must be implemented in Senegal.
authors.affiliation: Laboratoire d'étude de la Chimiosensibilité du Paludisme, Fédération des Laboratoires, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Silman
authors.initials: S
authors.lastname: Diawara
authors.affiliation: Unité Parasitologie et Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France.|Centre National de Référence du Paludisme, Marseille, France.
authors.forename: Marylin
authors.initials: M
authors.lastname: Madamet
authors.affiliation: Service des Urgences, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Mame Bou
authors.initials: MB
authors.lastname: Kounta
authors.affiliation: Centre Medical Inter-armées, Dakar, Senegal.|Laboratoire de Bactériologie Virologie, Université Cheikh Anta Diop, CHU Le Dantec, Dakar, Senegal.
authors.forename: Gora
authors.initials: G
authors.lastname: Lo
authors.affiliation: Service des Urgences, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Khalifa Ababacar
authors.initials: KA
authors.lastname: Wade
authors.affiliation: Service de Pédiatrie, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Aminata
authors.initials: A
authors.lastname: Nakoulima
authors.affiliation: Laboratoire d'Analyses Médicales, Institut Pasteur, Dakar, Senegal.
authors.forename: Raymond
authors.initials: R
authors.lastname: Bercion
authors.affiliation: Unité Parasitologie et Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France.|Centre National de Référence du Paludisme, Marseille, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Amalvict
authors.affiliation: Laboratoire d'étude de la Chimiosensibilité du Paludisme, Fédération des Laboratoires, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Mamadou Wague
authors.initials: MW
authors.lastname: Gueye
authors.affiliation: Laboratoire d'étude de la Chimiosensibilité du Paludisme, Fédération des Laboratoires, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Bécaye
authors.initials: B
authors.lastname: Fall
authors.affiliation: Chefferie, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Bakary
authors.initials: B
authors.lastname: Diatta
authors.affiliation: Laboratoire d'étude de la Chimiosensibilité du Paludisme, Fédération des Laboratoires, Hôpital Principal de Dakar, Dakar, Senegal. bruno.pradines@gmail.com.|Unité Parasitologie et Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France. bruno.pradines@gmail.com.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France. bruno.pradines@gmail.com.|Centre National de Référence du Paludisme, Marseille, France. bruno.pradines@gmail.com.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
mesh_terms: D000655:Amodiaquine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D010963:Plasmodium falciparum / Q000187:drug effects*; D012675:Senegal
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000655:Amodiaquine; C047386:desethylamodiaquine; D002738:Chloroquine; C031327:artemisinin
keywords: Anti-malarial drug; In vitro; Malaria; Plasmodium falciparum; Resistance; Senegal