Safety and efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Zambian children

Abstract

BackgroundMalaria in Zambia remains a public health and developmental challenge, affecting mostly children under five and pregnant women. In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL) that has proved to be highly efficacious against multidrug resistant Plasmodium falciparum.ObjectiveThe study objective was to determine whether dihydroartemisinin-piperaquine (DHA/PQP) had similar efficacy, safety and tolerability as AL for the treatment of children with uncomplicated P. falciparum malaria in Ndola, Zambia.MethodsBetween 2005 and 2006, 304 children (6-59 months old) with uncomplicated P. falciparum were enrolled, randomized to AL (101) or DHA/PQP (203) and followed up for 42 days. Outcome of treatment was defined according to the standard WHO classification, i.e. early treatment failure (ETF), late clinical failure (LCF, late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR). Recurrent infections were genotyped to distinguish between recrudescence and new infection.ResultsNo ETF was observed. At day 28, PCR-uncorrected ACPR was 92% in the DHA/PQP and 74% in the AL arm (OR: 4.05; 95%CI: 1.89-8.74; p < 0.001). Most failure were new infections and PCR-corrected ACPR was similar in the two study arms (OR: 0.69; 95%CI: 0.22-2.26; p = 0.33). Similar results were observed for day 42, i.e. higher PCR-uncorrected ACPR for DHA/PQP, mainly due to the difference observed up to day 28, while the PCR-corrected ACPR was similar: DHA/PQP: 93% (179/192), AL: 93% (84/90), (OR: 0.92; 95%CI: 0.30-2.64; p = 0.85). Except for cough, more frequent in the DHA/PQP arm (p = 0.04), there were no differences between treatment arms in the occurrence of adverse events. Two serious adverse events were probably associated to AL treatment.ConclusionDHA/PQP was as efficacious, safe and well tolerated in treatment of uncomplicated malaria as AL, though in the latter group more new infections during the follow up were observed. DHA/PQP seems a potential candidate to be used as an alternative first-line or rescue treatment in Zambia.Trial RegistrationISRCTN16263443, at http://www.controlled-trials.com/isrctn

Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Malaria in Children in Zaire and Uíge Provinces, Angola

“…The 28-day PCR-corrected efficacies for the AL Uíge arm and both DP arms are consistent with previously reported data for AL (24,25) and DP (26,27) and with high clinical efficacy estimates measured in African children prior to the widespread use of ACT. The point estimate for the 28-day PCR-corrected ACPR proportion in the AL Zaire arm of 88.4% is below the 90% WHO target efficacy for first-line treatment policy (12), but the 95% confidence interval of 78 to 95% is wide and includes the 95% secondary WHO target efficacy for ACTs.…”

Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso

“…In adults in Thailand, the protective efficacy of DHAPQ was 98% when DHAPQ was administered monthly and 86% when it was administered bimonthly (11). Despite extensive clinical evaluation and use of DHAPQ in Southeast Asia (12,13) and Africa (14)(15)(16), few studies have addressed pharmacokinetics of PQ in children (17)(18)(19). However, one of these studies suggested that children are underdosed with current regimens (17), which was also supported by a recent meta-analysis (20).…”

The Effects of ACT Treatment and TS Prophylaxis on Plasmodium falciparum Gametocytemia in a Cohort of Young Ugandan Children

“…Several studies using microscopic detection of gametocytes have shown no difference, 2,12,29 an increased risk of gametocyte detection after treatment with AL, 4,11 or more recently, an increased risk of gametocyte detection after treatment with ACT THERAPY, TS PROPHYLAXIS, AND P. FALCIPARUM DP. [14][15][16]30 These differences are likely caused by differences in analyses and the low sensitivity of microscopy for gametocytes. 30 A small study performed in western Kenya found no difference in microscopic gametocyte carriage between treatment with AL or DP.…”

“…[7][8][9][10] However, data comparing the effect of two leading ACTs in Africa-artemether-lumefantrine (AL) and dihyroartemesinin-piperaquine (DP)-on gametocytes have been mixed. 2,4,[11][12][13][14][15][16] Trimethoprim-sulfamethoxazole (TS), a drug routinely used to prevent opportunistic infections in human immunodeficiency virus (HIV) -infected individuals, has been shown to significantly reduce the incidence of malaria. [17][18][19][20][21] However, there is limited data on the association between the use of TS prophylaxis and gametocytes, and several studies have reported an association between exposure to sulfadoxinepyrimethamine (SP), another antifolate drug related to TS, and an increased prevalence and density of gametocytes.…”