Efficacy of rectal artesunate compared with parenteral quinine in initial treatment of moderately severe malaria in African children and adults: a randomised study

• Published in: The Lancet (British edition) 2004-05, Vol.363 (9421), p.1598-1605
• Main Authors: Barnes, KI, Mwenechanya, J, Tembo, M, Mcllleron, H, Folb, PI, Ribeiro, I, Little, F, Gomes, M, Molyneux, ME
• Format: Article
• Language: English
• Subjects: Absorption; Administration, Rectal; Adolescent; Adult; Antimalarials - administration & dosage; Antimalarials - pharmacokinetics; Artemisinins - administration & dosage; Artemisinins - pharmacokinetics; Biological and medical sciences; Child; Child, Preschool; Clinical trials; Drug Combinations; Drug Therapy, Combination; Effectiveness; Female; General aspects; Human protozoal diseases; Humans; Infant; Infectious diseases; Infusions, Intravenous; Injections, Intramuscular; Malaria; Malaria, Falciparum - blood; Malaria, Falciparum - drug therapy; Malaria, Falciparum - parasitology; Male; Medical sciences; Medical treatment; Middle Aged; Parasites; Parasitic diseases; Pharmacokinetics; Prescription drugs; Protozoal diseases; Pyrimethamine - administration & dosage; Quinine - administration & dosage; Sesquiterpenes - administration & dosage; Sesquiterpenes - pharmacokinetics; Sulfadoxine - administration & dosage; Suppositories; Vector-borne diseases
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(04)16203-X

Many patients with malaria of increasing severity cannot take medicines orally, and delay in injectable treatment can be fatal. We aimed to assess the reliability of absorption, antimalarial efficacy, and tolerability of a single rectal dose of artesunate in the initial management of moderately severe falciparum malaria. 109 children and 35 adults were randomly assigned to rectal artesunate (single dose of about 10 mg/kg) or parenteral quinine treatment (10 mg/kg at 0, 4, and 12 h). The primary endpoint was the proportion of patients with peripheral asexual parasitaemia of less than 60% of that at baseline after 12 h. Secondary endpoints were clinical response and concentrations of drug in plasma. Analysis was by intention-to-treat. All artesunate-treated patients had pharmacodynamic or pharmacokinetic evidence of adequate drug absorption. 80 (92%) of 87 artesunate-treated children had a 12 h parasite density lower than 60% of baseline, compared with three of 22 (14%) receiving quinine (relative risk 0·09 [95% Cl 0·04–0·19]; p