In vivo efficacy of artesunate-amodiaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria: an open-randomized, non-inferiority clinical trial in South Kivu, Democratic Republic of Congo.
BACKGROUND
Between 2009 and 2012, malaria cases diagnosed in a Médecins sans Frontières programme have increased fivefold in Baraka, South Kivu, Democratic Republic of the Congo (DRC). The cause of this increase is not known. An in vivo drug efficacy trial was conducted to determine whether increased treatment failure rates may have contributed to the apparent increase in malaria diagnoses.


METHODS
In an open-randomized non-inferiority trial, the efficacy of artesunate-amodiaquine (ASAQ) was compared to artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in 288 children aged 6-59 months. Included children had directly supervised treatment and were then followed for 42 days with weekly clinical and parasitological evaluations. The blood samples of children found to have recurring parasitaemia within 42 days were checked by PCR to confirm whether or not this was due to reinfection or recrudescence (i.e. treatment failure).


RESULTS
Out of 873 children screened, 585 (67 %) were excluded and 288 children were randomized to either ASAQ or AL. At day 42 of follow up, the treatment efficacy of ASAQ was 78 % before and 95 % after PCR correction for re-infections. In the AL-arm, treatment efficacy was 84 % before and 99.0 % after PCR correction. Treatment efficacy after PCR correction was within the margin of non-inferiority as set for this study. Fewer children in the AL arm reported adverse reactions.


CONCLUSIONS
ASAQ is still effective as a treatment for uncomplicated malaria in Baraka, South Kivu, DRC. In this region, AL may have higher efficacy but additional trials are required to draw this conclusion with confidence. The high re-infection rate in South-Kivu indicates intense malaria transmission. Trial registration NCT02741024.
Médecins sans Frontières (MSF), Plantage Middenlaan 14, 1018 DD, Amsterdam, The Netherlands. marit.de.wit@amsterdam.msf.org.
Marit
http://orcid.org/0000-0002-1718-3347
M
de Wit
Médecins sans Frontières (MSF), Plantage Middenlaan 14, 1018 DD, Amsterdam, The Netherlands.
Anna L
AL
Funk
Médecins sans Frontières (MSF), Plantage Middenlaan 14, 1018 DD, Amsterdam, The Netherlands.
Krystel
K
Moussally
Médecins sans Frontières (MSF), Plantage Middenlaan 14, 1018 DD, Amsterdam, The Netherlands.
David Aksanti
DA
Nkuba
Manson Unit, Médecins Sans Frontières (MSF), 10 Furnival Street, London, EC4A 1AB, UK.
Ruby
R
Siddiqui
Médecins sans Frontières (MSF), Plantage Middenlaan 14, 1018 DD, Amsterdam, The Netherlands.
Karla
K
Bil
Médecins sans Frontières (MSF), Plantage Middenlaan 14, 1018 DD, Amsterdam, The Netherlands.
Erwan
E
Piriou
Academisch Medisch Centrum, Amsterdam, The Netherlands.
Aldert
A
Bart
Programme National de lutte contre le Paludisme, Kinshasa, South Kivu, Democratic Republic of the Congo.
Patrick
P
Bahizi Bizoza
London School of Hygiene and Tropical Medicine, London, UK.|Radboud university medical center, Nijmegen, The Netherlands.
Teun
T
Bousema
D000655:Amodiaquine / Q000008:administration & dosage*; D000962:Antimalarials / Q000008:administration & dosage*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage*; D002675:Child, Preschool; D015023:Democratic Republic of the Congo; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D016896:Treatment Outcome
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine
Artemether–lumefantrine; Artesunate–amodiaquine; Child; DR Congo; DRC; Plasmodium falciparum; Treatment efficacy; Uncomplicated malaria