A randomized trial of the efficacy of artesunate and three quinine regimens in the treatment of severe malaria in children at the Ebolowa Regional Hospital, Cameroon

Abstract

BackgroundSevere malaria is a medical emergency with high mortality in children below 5 years of age especially in sub-Saharan Africa. Recently, quinine has been replaced by artesunate as the first-line drug in the treatment of severe malaria in Cameroon. No local data are yet available on the efficacy of artesunate with respect to the different quinine regimens used in this setting. This study was undertaken at the Ebolowa Regional Hospital (ERH), which is located in a region of perennial transmission of malaria.MethodsThis was a randomized, open-label trial in children aged 3 months to 15 years, admitted in the hospital with severe malaria due to Plasmodium falciparum confirmed on microscopy after informed parental consent. Patients were randomized into four groups. Group 1 (ARTES) received parenteral artesunate at 2.4 mg/kg at H0, H12, H24 and then once daily; Group 2 (QLD) received a loading dose of quinine base at 16.6 mg/kg followed 8 hours later by an eight-hourly maintenance dose of 8.3 mg/kg quinine base; Group 3 (QNLD3) received 8.3 mg/kg quinine base every 8 hours; and, Group 4 (QNLD2) received 12.5 mg/kg quinine base every 12 h. All patients invariably received a minimum of 24 h parenteral treatment, then, oral drugs were prescribed. The endpoints were fever clearance time, time to sit unsupported, time to eat, parasite clearance time, and parasitaemia reduction rate at H24. Survival analysis was used to compare the outcomes.ResultsOne-hundred and sixteen patients completed the study: 29 in ARTES arm, 28 in QLD arm, 30 in QNLD3 arm, and 29 in QNLD2 arm. There was no major differences in baseline characteristics in the treatment groups. On analysis of endpoints, fever clearance time and parasite clearance time were significantly shorter for artesunate-treated patients than for quinine-treated patients. Parasitaemia reduction rate at H24 was also significantly higher for artesunate. Time to sit unsupported and time to eat were shorter with artesunate, but the difference was not statistically significant.ConclusionArtesunate is more effective than quinine in the treatment of severe malaria in Cameroonian children.

Economic evaluation of artesunate and three quinine regimens in the treatment of severe malaria in children at the Ebolowa Regional Hospital-Cameroon: a cost analysis

“…The results of the clinical effectiveness of each treatment group measured in PRR 24 , is presented in Table 1 and have been previously reported in another publication [15]. Results show that ARTES had statistically significantly higher effectiveness than any of the quinine treatment alternatives.…”

“…Economic data was collected alongside clinical effectiveness data from each patient using a questionnaire administered by trained researchers. The result of the comparative effectiveness of the treatment alternatives has been previously reported and published [15]. …”

“…For each treatment regimen, parenteral treatment was relayed with an artemisinin-based combination (artemether–amodiaquine or artemether–lumefantrine) as soon as he could take oral treatment before being discharged from the hospital. The procedure for dilution and administration of the drugs and monitoring for clinical side-effects have been described in a previously published paper [15]. Malaria thick films were conducted on each patient at base case on admission and daily until discharge.…”

Review of malaria situation in Cameroon: technical viewpoint on challenges and prospects for disease elimination

“…All these studies concluded to the continuous efficacy of artemisinin base combination in Cameroon [128, 129, 131]. For diagnostic and treatment of malaria cases, several programmes have been conducted across the country in order to strengthen health care workers practices [132–134]. Additional case management programmes conducted include seasonal malaria chemoprevention in the North and Far-North regions.…”

Drug-induced hypersensitivity to artemisinin-based therapies for malaria

“…Hypersensitivity drug reactions (HDRs) are, in contrast to most other adverse drug reactions, mediated by specific immunological pathways and are considered largely independent of the administered dose or pharmacological action [27]. Cases of allergic reaction following treatment with artemisinin derivatives have consistently been reported since the first clinical trials systematically evaluating artemisinins [5,19,[28][29][30][31][32][33][34][35].…”