Efficacy of artemether–lumefantrine versus dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria among children in Rwanda: an open-label, randomized controlled trial

Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda

“…1 ; http://www.isrctn.com/ISRCTN63145981 ). The overall 42-day PCR-corrected efficacies of AL (95.2% (196 of 206); 95% CI, 91.3% to 97.7%) and DP (97.5% (212 of 217); 95% CI, 94.4% to 99.1%) were similar between both sites ( P = 0.17, log-rank test) 7 . The day 3 positivity rate (day 3 + ), defined as the proportion of patients who were still parasitemic on day 3 after initiation of treatment, was low for both treatments: 1 of 263 (0.4%) for AL and 0 of 264 for DP (Table 1 ).…”

“…Clinical drug efficacy trial oversight and blood sample collection. The clinical drug efficacy trial (ISRCTN63145981, http://www.isrctn.com/ISRCTN63145981) was conducted by the Rwanda National Malaria Program between 2013 and 2015 at two health facilities in Rwanda (Masaka and Ruhuha, in the Kicukiro and Bugesera districts, respectively) to assess the efficacy of AL or DP for the treatment of uncomplicated P. falciparum malaria in children 1-14 years of age, presenting with suspected uncomplicated P. falciparum malaria 7 . Patients at both sites were randomly assigned to receive a full course of AL (Co-artem, 20 mg artemether and 120 mg lumefantrine per tablet) or DP (Duo-cotecxin, 40 mg dihydroartemisinin and 320 mg piperaquine per tablet) according to the manufacturer's dosing schedule.…”

“…falciparum malaria in children 1–14 years of age, presenting with suspected uncomplicated P . falciparum malaria 7 . Patients at both sites were randomly assigned to receive a full course of AL (Co-artem, 20 mg artemether and 120 mg lumefantrine per tablet) or DP (Duo-cotecxin, 40 mg dihydroartemisinin and 320 mg piperaquine per tablet) according to the manufacturer’s dosing schedule.…”

“…Sample size calculations and clinical data management methods have been previously described 7 . PCR-adjusted clinical efficacy rates at day 42 were calculated using Kaplan–Meier survival analysis.…”

“… Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa 1 – 4 . Here we genotyped the P. falciparum K13 ( Pfkelch13 ) propeller domain, mutations in which can mediate artemisinin resistance 5 , 6 , in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda 7 . While cure rates were >95% in both treatment arms, the Pfkelch13 R561H mutation was identified in 19 of 257 (7.4%) patients at Masaka.…”