Clinical trial of beta-arteether versus quinine for the treatment of cerebral malaria in children in Yaounde, Cameroon.

Abstract

Abstract. One hundred and two children aged 0-10 years with cerebral malaria (Blantyre coma score of 2 or less) were randomly treated either with intramuscular arteether (3.2 mg/kg on Day 0, followed by 1.6 mg/kg on Days 1 to 4) or intravenous (IV) quinine dihydrochloride (20 mg of the salt/kg, followed by 10 mg of the salt/kg every 8 hr up to Day 6). Treatment with oral quinine sulfate (10 mg/kg every 8 hr) was substituted for IV quinine when the patient was able to take oral medicine. All patients were followed up in the hospital for 7 days; thereafter, they were treated as outpatients on Days 14, 21, and 28.Mortality rate, the main efficacy parameter, was 11.8% lower in the arteether treatment group than in the quinine group (15.7% versus 27.4%); however, the difference was not significant (P ϭ 0.25). Means for fever clearance time, coma resolution time, and parasite clearance time were similar in the 2 treatment groups (42.2 Ϯ 34.9 hr; 34.8 Ϯ 18.8 hr, and 46.3 Ϯ 28.5 hr, respectively for arteether, versus 45.0 Ϯ 26.7 hr; 30.3 Ϯ 18.9 hr, and 40.7 Ϯ 18.9 hr, respectively, for quinine). At 28 days, the cure rates were 73.2% and 64.9% for the arteether and quinine treatment groups, respectively.Arteether is safe and therapeutically at least as effective as quinine for the treatment of cerebral malaria in children in Cameroon. Because of its ease of administration, arteether appears to be suited for use in the rural zones where monitoring facilities do not exist.

Neurotoxicity and efficacy of arteether related to its exposure times and exposure levels in rodents.

“…9,58 The results contributed to a low therapeutic potential of intramuscular AE when compared with oral DQHS, oral and intravenous artesunate (AS), intramuscular AM, and even intramuscular ␣/␤-AE formulated with peanut oil in humans. 9,[59][60][61] Although far fewer undesirable side effects were reported in these trials, the lower efficacy limited the use of the drug in patients infected with P. falciparum malarias. Previous PK data demonstrated that the AM plasma concentration was more than three-fold higher than that of AE in rats at a same dose level and with the same sesame oil formulation.…”

“…20 It may be that AM has a less lipophilic property than AE that favors absorption from muscle. Better efficacy of ␣/␤-AE was found in a peanut oil formulation in India, [59][60][61] suggesting that peanut oil may also facilitate better absorption of this drug in humans. Therefore, further investigation on new intramuscular formulations needs to be done to increase efficacy and decrease toxicity of the oil-soluble antimalarial drug AE.…”

Artemisinin derivatives Versus quinine for severe malaria in children: A systematic review and meta-analysis

“…Seven trials reported fever clearance time, though three (8,11,12) presented data in a format that precluded meta-analysis; the remainder (9,(15)(16)(17) showed comparable results between all three artemisinin derivatives and quinine. All trials reported coma recovery time, though three (8,11,12) could not be included in meta-analysis.…”

“…The trials examined mortality, clinical outcomes (fever clearance time, coma recovery time, neurological sequelae), parasite clearance and some side effects. (Table II) was low for three trials (11,12,14), moderate for another three (8,10,17) and high for four trials (9,13,15,16). Only one trial(11) provided a sample size calculation.…”

“…Table I summarizes the trial characteristics. Two trials compared quinine with artesunate (8,9), six with artemether(10-15), and two with arteether (16,17). Four trials recruited only participants with cerebral malaria (10,11,13,14).…”