Randomized non-inferiority and safety trial of dihydroartemisin-piperaquine and artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroonian children

Abstract

BackgroundArtemether-lumefantrine and artesunate-amodiaquine are first-line treatment for uncomplicated malaria in Cameroon. No study has yet compared the efficacy of these drugs following the WHO recommended 42-day follow-up period. The goal of this study was to compare the clinical efficacy, tolerability and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and dihydroartemisinin piperaquine (DHAP) among children aged less than ten years in two malaria-endemic ecological regions of Cameroon.MethodsA three-arm, randomized, controlled, non-inferiority trial was conducted among children of either gender aged six months (>5 kg) to ten years (n = 720) with acute uncomplicated Plasmodium falciparum infection. Parents/guardians of children provided consent prior to randomization to receive ASAQ, DHAP or AL in the ratio of 2:2:1, respectively. Treatment outcome was assessed based on standard WHO 2003 classification after 42 days of follow-up. The primary outcome was PCR-corrected day-42 cure rates. The non-inferiority, one-sided, lower limit asymptotic 97.5% confidence interval (CI) on the difference in PCR-corrected cure rates of ASAQ and DHAP when compared to AL was accepted if the lower limit of the CI was greater than −10%. Secondary outcomes were parasite and fever clearances and day 7 haemoglobin changes.ResultsPCR-corrected PP cure rates of 96.7, 98.1 and 96.3, respectively, for AL, ASAQ and DHAP was observed. The lower bound of the one-sided 97.5% CI calculated around the difference between day-42 cure rate point estimates in AL and ASAQ groups, AL and DHAP groups were, −6% and −4% respectively. There were no statistical significant differences in parasite or fever clearance times between treatments, although fever clearance pattern was different between ASAQ and DHAP. No statistical significant differences were observed in the occurrence of adverse events among treatment groups.ConclusionASAQ and DHAP are considered safe and tolerable and are not inferior to AL in the treatment of uncomplicated P. falciparum malaria in Cameroonian children.Trial registrationNCT01845701

Efficacies of DHA–PPQ and AS/SP in patients with uncomplicated Plasmodium falciparum malaria in an area of an unstable seasonal transmission in Sudan

“…DHA–PQQ was adopted as a second-line treatment in Kenya in 2009 [19]. Equally, research in west, south and central Africa has shown similar results [20–22]. Dihydroartemisinin has been identified as a potent derivative of the parent drug artemether [4].…”

Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria in Under-Five-Year-Old Nigerian Children Ten Years Following Adoption as First-Line Antimalarials

“…In Africa, where virtually all ACTs recommended as first-line treatments of uncomplicated infections by the World Health Organization (WHO) 14,15 are readily available, a commonly used ACT alongside AL and AA is dihydroartemisininpiperaquine (DHP) which has been shown to be an efficacious treatment of uncomplicated falciparum malaria in Africa and elsewhere. [16][17][18][19][20] The efficacies of AL, AA, and DHP in single studies have been less frequently evaluated exclusively in < 5year-old malarious children.…”

Clinical Efficacy and Safety of Artemisinin-based Combination Therapies in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Cameroon: A Systematic Review and Meta-Analysis from Individual Patient Data (2004-2020)

“…These ADRs were not serious enough to discontinue anti-malarial treatments except for individuals in studies that reported serious adverse events such as jaundice, haemoglobulinuria, anaemia, convulsion, severe fatigue, severe malaria and deaths. In the current review, 3 study participant died during treatment [26]. This rate of mortality was not related to the study drugs on patients included in the study with uncomplicated malaria.…”

“…The search of studies published from 2004 to 2020 identi ed 13 articles important to the topic under review [22][23][24][25][26][27][28][29][30][31][32][33][34], out of which 10 were RCTs [22-30, 33, 34] and 3 non-comparative clinical trials without randomisation [31, 32] (Additional le 1). Data from 3 unpublished studies that were conducted by the Cameroon National Malaria Control Programme and independent researchers were also included in this review.…”

“…A total of 12 (76.5 %) articles and unpublished data reported adverse events [23,24,26,[28][29][30][31]33]. The ACTs are well tolerated with few adverse events, the most reported across all studies being those of asthenia, diarrhoea, abdominal pain, anorexia, nausea, vomiting, headache and dizziness.…”