Rachida Tahar1, Talleh Almelli2, Camille Debue2, Vincent Foumane Ngane3, Joseph Djaman Allico4, Solange Whegang Youdom3, Leonardo K Basco5. 1. Unité Mixte de Recherche 216 Mère et Enfant Face aux Infections Tropicales, Institut de Recherche pour le Développement (IRD), Unité de formation et de recherche de Pharmacie, Paris Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon. 2. Unité Mixte de Recherche 216 Mère et Enfant Face aux Infections Tropicales, Institut de Recherche pour le Développement (IRD), Unité de formation et de recherche de Pharmacie, Paris. 3. Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon. 4. Unité de Recherche Neurobiologie et Développement, Unité Propre de Recherche 3294, Centre National de la Recherche Scientifique, Université Paris-Sud XI, Orsay Laboratoire de Pharmacodynamie Biochimique, Unité de Formation et de Recherche Biosciences, Université de Cocody Département de Biochimie, Institut Pasteur de Côte d'Ivoire, Abidjan, Côte d'Ivoire. 5. Unité de Recherche 198, Unité de Recherche des Maladies Infectieuses et Tropicales Emergentes, IRD, Faculté de Médecine La Timone, Aix-Marseille Université, Marseille, France Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
Abstract
BACKGROUND:Artemisinin-based combination therapies (ACTs) are recommended for the treatment of acute uncomplicated falciparum malaria in many malaria-endemic countries. Despite the emergence of artemisinin resistance, few alternative non-ACTs, including atovaquone-proguanil, are currently available. METHODS:Plasmodium falciparum-infected Cameroonian children ≤5 years old (n = 338) were randomly assigned to artesunate-amodiaquine, atovaquone-proguanil, or artesunate-atovaquone-proguanil treatment groups and followed for 28 days, according to the standard World Health Organization protocol. In vitro response to atovaquone and cytochrome b sequence of clinical isolates were determined. RESULTS: Eight late failures and 16 failures (8 late and 8 early failures) were observed after artesunate-amodiaquine and atovaquone-proguanil therapies, respectively. Most late failures were due to reinfections. Artesunate-atovaquone-proguanil was not associated with any failure. After correction by genotyping, per-protocol analysis showed no difference in the efficacy of 3 drugs. However, the proportion of atovaquone-proguanil-treated patients with positive smears on day 3 was much higher (36.0%; P < .05) than that of the artesunate-amodiaquine (2.9%) and artesunate-atovaquone-proguanil (1.0%) groups. In vitro response and cytochrome b sequence did not indicate atovaquone resistance. CONCLUSIONS: Atovaquone-proguanil was characterized by a slow blood schizontocidal action and resulted in early treatment failure in a few patients. Artesunate-atovaquone-proguanil was a highly effective alternative treatment. CLINICAL TRIALS REGISTRATION: UMIN000003813.
RCT Entities:
BACKGROUND:Artemisinin-based combination therapies (ACTs) are recommended for the treatment of acute uncomplicated falciparum malaria in many malaria-endemic countries. Despite the emergence of artemisinin resistance, few alternative non-ACTs, including atovaquone-proguanil, are currently available. METHODS:Plasmodium falciparum-infected Cameroonian children ≤5 years old (n = 338) were randomly assigned to artesunate-amodiaquine, atovaquone-proguanil, or artesunate-atovaquone-proguanil treatment groups and followed for 28 days, according to the standard World Health Organization protocol. In vitro response to atovaquone and cytochrome b sequence of clinical isolates were determined. RESULTS: Eight late failures and 16 failures (8 late and 8 early failures) were observed after artesunate-amodiaquine and atovaquone-proguanil therapies, respectively. Most late failures were due to reinfections. Artesunate-atovaquone-proguanil was not associated with any failure. After correction by genotyping, per-protocol analysis showed no difference in the efficacy of 3 drugs. However, the proportion of atovaquone-proguanil-treated patients with positive smears on day 3 was much higher (36.0%; P < .05) than that of the artesunate-amodiaquine (2.9%) and artesunate-atovaquone-proguanil (1.0%) groups. In vitro response and cytochrome b sequence did not indicate atovaquone resistance. CONCLUSIONS:Atovaquone-proguanil was characterized by a slow blood schizontocidal action and resulted in early treatment failure in a few patients. Artesunate-atovaquone-proguanil was a highly effective alternative treatment. CLINICAL TRIALS REGISTRATION: UMIN000003813.
Authors: Lionel Almeras; Leonardo K Basco; Cheikh Sokhna; Stéphane Ranque; Philippe Parola; Christian Devaux; Philippe Brouqui; Michel Drancourt; Bruno Pradines Journal: New Microbes New Infect Date: 2018-07-04
Authors: Prabin Dahal; Umberto d'Alessandro; Grant Dorsey; Philippe J Guerin; Christian Nsanzabana; Ric N Price; Carol H Sibley; Kasia Stepniewska; Ambrose O Talisuna Journal: BMC Med Date: 2015-09-07 Impact factor: 8.775