Persistence of High In Vivo Efficacy and Safety of Artesunate\u2013Amodiaquine and Artemether\u2013Lumefantrine as the First- and Second-Line Treatments for Uncomplicated Plasmodium falciparum Malaria 10 Years After Their Implementation in Gabon

Jacques M Ndong Ngomo,Pascal Ringwald,Bridy Moutombi Ditombi,Jeanne V Koumba Lengongo,Christelle L Offouga,Denise P Mawili-Mboumba,Thierry Fandeur,Guy J Ondzagha Megnie,Marielle K Bouyou-Akotet,Noé P M’Bondoukwé,Jean B Lekana-Douki

doi:10.2478/s11686-019-00115-y

Abstract

PurposeArtesunate–amodiaquine (AS–AQ) and artemether–lumefantrine (AL) have been widely used for the treatment of uncomplicated Plasmodium falciparum malaria since 2005 in Gabon. Since 2011, a rebound of malaria morbidity has been observed in this country, while no survey evaluating ACT efficacy was performed. During the same period, parasite resistance against artemisinin has been reported in Asia. The aim of this study was to assess the efficacy and tolerability of these two drugs in two sentinel sites of Gabon 10 years after their implementation.MethodsChildren aged from 12 to 144 months with uncomplicated malaria were recruited at the Regional Hospital of Melen, Libreville and in the Urban Health Center of Franceville between March 2014 and September 2015. The therapeutic efficacy was evaluated according to the WHO 2008 protocol of 28-day follow-up and PCR-uncorrected/corrected treatment outcomes were assessed.ResultsOne hundred and eighty-five children (98 ASAQ and 89 AL) were followed up until day 28. The PCR-corrected ACPR was 98.9% for AS–AQ and 96.4% for AL. Late therapeutic failure rate was 3.6% and 1.1% for AL and AS–AQ, respectively (p = 0.2). Adverse events and serious adverse events were rarely observed with both treatments.ConclusionAS–AQ and AL are still efficacious and well-tolerated for the treatment of uncomplicated malaria in Gabonese children.

Highlights

Since 2000, the majority of malaria-endemic countries substituted monotherapies by artemisinin-based combination therapies (ACTs) for uncomplicated malaria treatment [20]
This study presents the results of a clinical trial evaluating AS–AQ and AL efficacy and tolerability in two cities of Gabon (Libreville and Franceville), where both molecular markers of resistance as well as a rebound of malaria morbidity have been previously described [8, 12]
10 years after the implementation of AS–AQ and AL for the treatment of uncomplicated malaria in Gabon, it was necessary to re-evaluate the therapeutic efficacy of these combinations

Summary

Introduction

Since 2000, the majority of malaria-endemic countries substituted monotherapies by artemisinin-based combination therapies (ACTs) for uncomplicated malaria treatment [20]. Following ACTs use, a reduction of malaria mortality by 62% globally between 2000 and 2015, and by 29% between 2010 and 2015 was estimated [23]. Resistance to artemisinin and its spread are reported in South-East Asia. Extended author information available on the last page of the article region is known to have been focus of origin of antimalarial drug resistance before it reaches Africa [2, 6]. Almost all cases are due to P. falciparum, of which strains with molecular markers of artemisinin partner drugs are highly frequent in different areas of the country [11, 13]

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