Efficacy and safety of artemether + lumefantrine, artesunate + sulphamethoxypyrazine-pyrimethamine and artesunate + amodiaquine and sulphadoxine-pyrimethamine + amodiaquine in the treatment of uncomplicated falciparum malaria in Bangui, Central African Republic: a randomized trial

Abstract

BackgroundThe efficacy of artemisinin-based combination therapy (ACT) has been established. The objective of the present study was to compare the efficacy and safety in the Central African Republic (CAR) of three commercially available artemisinin-based combinations, artemether + lumefantrine (AL), artesunate + sulphamethoxypyrazine–pyrimethamine (AS-SMP) and artesunate + amodiaquine (AS-AQ), with those of sulphadoxine–pyrimethamine + amodiaquine (SP-AQ), which was the first-line reference treatment in the country from 2004, until it was replaced by ACT in 2006 in accordance with changes in international recommendations based on resistance identified in other regions.MethodsChildren aged six to 59 months with uncomplicated Plasmodium falciparum malaria were recruited in Bangui, the capital of the CAR. The 251 patients selected were randomly assigned to receive AL (n = 60), AS-SMP (n = 58), AS-AQ (n = 68) or SP-AQ (n = 65) and were followed up for 28 days. Clinical outcome was classified according to the standard 2003 World Health Organization protocol.ResultsAt day 28, the cure rates in a per-protocol analysis were 92% (48/52) with AL, 93% (50/54) with AS-SMP, 93% (55/59) with AS-AQ and 100% (57/57) with SP-AQ, with no statistically significant difference between the four treatments. Defervescence was significantly faster with AS-AQ than with AL (p <0.035). Fatigue was reported significantly more frequently by patients receiving AQ than by those treated with AS-SMP or AL (p = 0.006). All the other adverse events reported were mild, and no significant difference was noted by treatment.ConclusionThe three artemisinin-bsed combinations show similar, satisfactory results, comparable to that with SP-AQ. This evaluation is the first conducted in CAR since the official introduction of ACT. It should guide the National Malaria Control Programme in choosing the appropriate ACT for treatment of uncomplicated P. falciparum malaria in the future.

Impact of Antimalarial Treatment and Chemoprevention on the Drug Sensitivity of Malaria Parasites Isolated from Ugandan Children

“…Recent changes suggest that we should reconsider the use of aminoquinolines to treat malaria, including AS-AQ, which showed inferior efficacy to AL in Tanzania (54) and Uganda (55,56) some years ago but excellent recent efficacy in West and Central Africa (57-61); DP, which has shown excellent efficacy (7,(62)(63)(64)(65)(66); and perhaps combinations that include chloroquine (52,67). Further, we should be cautious regarding the long-term antimalarial efficacy of AL, as although both the clinical efficacy of AL (57)(58)(59)(60)(61)(64)(65)(66) and ex vivo activity of DHA and lumefantrine (31,42,(68)(69)(70) ies, current results suggest that the antimalarial potency of lumefantrine is decreasing. Our data show that antimalarial treatment regimens rapidly select for parasites with decreased drug sensitivity.…”

Fixed dose artesunate amodiaquine – a phase IIb, randomized comparative trial with non-fixed artesunate amodiaquine

“…As of 2014, ASAQ is available for use in 35 countries, including 32 in Africa [ 6 ]. Where tested in Africa, FD ASAQ has consistently achieved high efficacy, achieving Day 28 cure rates of ~93, 94 and 100% in children 60 months of age from Burkina Faso [ 6 ], Benin [ 5 ] and Central African Republic [ 10 ], respectively; ~98% in children <eight years of age in Cote D’Ivoire, Cameroon and Senegal [ 7 ] and <five years of age in the Democratic Republic of Congo (DRC) [ 8 ], as well as 100% in Nigerian children <12 years of age [ 9 ]. FD ASAQ was non-inferior to artemether-lumefantrine (AL) in two trials, achieving cure rates exceeding ~95% and non-inferiority margins of 3% [ 8 , 11 ].…”

Assessment of Clinical Pharmacokinetic Drug-Drug Interaction of Antimalarial Drugs α/β-Arteether and Sulfadoxine-Pyrimethamine

“…Artemisinin-based combination therapies (ACTs) are now recommended as the first-line treatment for falciparum malaria throughout the world, where malaria is endemic, and are now specifically recommended for the treatment of uncomplicated falciparum malaria (25). This is a pragmatic compromise, as ACTs may become the only available effective antimalarials and the evidence to date indicates that artemisinin derivatives are safe and effective (26).…”