A randomized trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated malaria among children in western Kenya

Abstract

BackgroundArtemether-lumefantrine (AL) was adopted as first-line treatment for uncomplicated malaria in Kenya in 2006. Monitoring drug efficacy at regular intervals is essential to prevent unnecessary morbidity and mortality. The efficacy of AL and dihydroartemisinin-piperaquine (DP) were evaluated for the treatment of uncomplicated malaria in children aged six to 59 months in western Kenya.MethodsFrom October 2010 to August 2011, children with fever or history of fever with uncomplicated Plasmodium falciparum mono-infection were enrolled in an in vivo efficacy trial in accordance with World Health Organization (WHO) guidelines. The children were randomized to treatment with a three-day course of AL or DP and efficacy outcomes were measured at 28 and 42 days after treatment initiation.ResultsA total of 137 children were enrolled in each treatment arm. There were no early treatment failures and all children except one had cleared parasites by day 3. Polymerase chain reaction (PCR)-uncorrected adequate clinical and parasitological response rate (ACPR) was 61% in the AL arm and 83% in the DP arm at day 28 (p = 0.001). PCR-corrected ACPR at day 28 was 97% in the AL group and 99% in the DP group, and it was 96% in both arms at day 42.ConclusionsAL and DP remain efficacious for the treatment of uncomplicated malaria among children in western Kenya. The longer half-life of piperaquine relative to lumefantrine may provide a prophylactic effect, accounting for the lower rate of re-infection in the first 28 days after treatment in the DP arm.

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.…”

Tailoring a Pediatric Formulation of Artemether-Lumefantrine for Treatment of Plasmodium falciparum Malaria

“…The longer half-life results in a longer posttherapeutic prophylactic effect and a decreased reinfection rate in the first 28 days compared with AL (38). However, theoretically, the longer half-life could also potentially increase the risk of selection of resistance to piperaquine (39).…”

Comparing the Impact of Artemisinin-Based Combination Therapies on Malaria Transmission in Sub-Saharan Africa

“…8 A variety of ACTs exists, such as artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), which vary in their efficacy profile against uncomplicated malaria, tolerability, and their ability to reduce infectivity to mosquitoes. 8,[11][12][13][14] The difference in efficacy between these ACTs may have important implications not only for the treatment of individual patients, but also for the population-level impact on malaria transmission. 11,13 The balance among these factors, which may themselves vary between communities, will determine whether AL or DP is optimal in different settings.…”

“…8,15,16 Comparative efficacy studies in multiple settings have consistently reported a longer duration to recurrent infection in individuals treated with DP as compared with AL. 13,14 At the population level, DP has drawbacks in terms of its relative effectiveness in reducing malaria transmission, compared with AL. A recent clinical trial conducted among Kenyan children has shown that despite the longer post-treatment prophylactic period of DP compared with AL, individuals treated with DP may have a longer infectious period and resultant higher malaria transmission potential to mosquitoes after treatment than those treated with AL.…”

“…For this purpose, we developed a mathematical model of P. falciparum malaria transmission and treatment in endemic communities using epidemiological and clinical findings on the efficacy of AL and DP. 8,11,13,14,17 We used this model to evaluate the potential reduction in prevalence and incidence of clinical episodes of malaria, comparing AL or DP as first-line treatment of malaria in different P. falciparum transmission intensity settings. To evaluate the effect of empirical uncertainty in the data surrounding epidemiological parameters on the predictions of our model, we used a Monte Carlo sampling approach.…”