Artesunate-amodiaquine versus artemether-lumefantrine for the treatment of acute uncomplicated malaria in Congolese children under 10 years old living in a suburban area: a randomized study.
BACKGROUND
The Republic of Congo adopted a new anti-malarial treatment policy in 2006, with artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) as the first- and second-line anti-malarial drugs, respectively. Only three clinical studies had been conducted before the policy change. A randomized study on these two artemisinin-based combinations was conducted, and the effect that sickle cell trait may have on treatment outcomes was evaluated in children under 10 years old followed during 12 months in Brazzaville in 2010-2011.


METHODS
A cohort of 330 children under 10 years of age living in a suburban area in the south of Brazzaville were passively followed for registration of malaria episodes. Uncomplicated Plasmodium falciparum episodes were randomly treated with co-formulated ASAQ (Coarsucam(®)) or AL (Coartem(®)). Patients were followed according to the 2009 World Health Organization protocol for the evaluation of anti-malarial drug efficacy. Plasmodium falciparum recrudescent isolates were compared to pre-treatment isolates by polymerase chain reaction (PCR) to distinguish between re-infection and recrudescence. PCR-uncorrected and PCR-corrected responses to treatment were determined using per protocol analysis. Haemoglobin type (AA, AS, SS) was determined by PCR.


RESULTS
Of 282 clinical malaria episodes registered during 1-year follow-up period, 262 children with uncomplicated malaria were treated with ASAQ (129 patients) or AL (133 patients). The PCR-corrected efficacy, expressed as the percentage of adequate clinical and parasitological response, was 97.0 % for ASAQ and 96.4 % for AL. Among ASAQ-treated patients, 112 (86.8 %) carried AA genotype and 17 (13.2 %) were AS carriers. The PCR-corrected efficacy was 96.4 % for AA-carriers and 100 % for AS-carriers treated with ASAQ [relative risk (RR) = 0.96; 95 % confidence interval, 0.93-1.00, p = 0.5]. Among 133 AL-treated children, 109 (82 %) carried AA, and 24 (18 %) AS genotypes. The PCR-corrected efficacy was 96.7 % among AA-carriers and 95.2 % among AS-carriers [RR = 1.01 (0.92-1.12), p = 0.6]. Nausea, jaundice, headache, dizziness, vomiting, pruritus, abdominal pain, and diarrhoea were registered as adverse events in both groups. ASAQ was associated with significantly more frequent adverse events (P < 0.05).


CONCLUSIONS
This first randomized study in Brazzaville confirmed the excellent efficacy of these co-formulated anti-malarial drugs in children. Sickle cell genotype did not influence the treatment efficacy of artemisinin-based combination therapy.
Unité de Recherche sur le Paludisme, Centre d'Etudes sur les Ressources Végétales (CERVE), BP 1249, Brazzaville, Republic of Congo. ngoualandounga@yahoo.fr.
Mathieu
M
Ndounga
Fondation Congolaise pour la Recherche Médicale (FCRM), BP 2672, Brazzaville, Republic of Congo. pmayengue@yahoo.fr.|Faculté des Sciences et Techniques, Université Marien Ngouabi, BP 69, Brazzaville, Republic of Congo. pmayengue@yahoo.fr.|Laboratoire National de Santé Publique, BP 120, Brazzaville, Republic of Congo. pmayengue@yahoo.fr.
Pembe Issamou Mayengue
Unité de Recherche sur le Paludisme, Centre d'Etudes sur les Ressources Végétales (CERVE), BP 1249, Brazzaville, Republic of Congo. pncasimiro@yahoo.fr.
Prisca Nadine
PN
Casimiro
Fondation Congolaise pour la Recherche Médicale (FCRM), BP 2672, Brazzaville, Republic of Congo. felixkoukouikila@yahoo.fr.
Félix
F
Koukouikila-Koussounda
Unité de Recherche sur le Paludisme, Centre d'Etudes sur les Ressources Végétales (CERVE), BP 1249, Brazzaville, Republic of Congo. michel_bitemo2008@yahoo.com.
Michel
M
Bitemo
Unité de Recherche sur le Paludisme, Centre d'Etudes sur les Ressources Végétales (CERVE), BP 1249, Brazzaville, Republic of Congo. brunellematondo@yahoo.fr.
Brunelle
B
Diassivy Matondo
Unité de Recherche sur le Paludisme, Centre d'Etudes sur les Ressources Végétales (CERVE), BP 1249, Brazzaville, Republic of Congo. leeaymar@gmail.com.
Lee Aymar
LA
Ndounga Diakou
Institut de Recherche pour le Développement (IRD), Unité Mixte de Recherche 198, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine La Timone, Aix-Marseille Université, Marseille, France. lkbasco@yahoo.fr.
Leonardo K
LK
Basco
Fondation Congolaise pour la Recherche Médicale (FCRM), BP 2672, Brazzaville, Republic of Congo. fntoumi@fcrm-congo.com.|Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany. fntoumi@fcrm-congo.com.|Faculté des Sciences et Techniques, Université Marien Ngouabi, BP 69, Brazzaville, Republic of Congo. fntoumi@fcrm-congo.com.
Francine
F
Ntoumi
D000655:Amodiaquine / Q000008:administration & dosage*; D000755:Anemia, Sickle Cell / Q000150:complications; D000962:Antimalarials / Q000008:administration & dosage*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003223:Congo; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D005838:Genotype; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012008:Recurrence; D013383:Suburban Population; D016896:Treatment Outcome
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D006454:Hemoglobins; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine