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


METHODS
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.


RESULTS
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% CI 0.04-0.19]; p<0.0001). In adults, parasitaemia at 12 h was lower than 60% of baseline in 26 (96%) of 27 receiving artesunate, compared with three (38%) of eight receiving quinine (relative risk 0.06 [0.01-0.44]; p=0.0009). These differences were greater at 24 h. Clinical response was equivalent with rectal artesunate and parenteral quinine.


CONCLUSIONS
A single rectal dose of artesunate is associated with rapid reduction in parasite density in adults and children with moderately severe malaria, within the initial 24 h of treatment. This option is useful for initiation of treatment in patients unable to take oral medication, particularly where parenteral treatment is unavailable.
Barnes
K I
KI
Division of Pharmacology, University of Cape Town, South Africa.
Mwenechanya
J
J
Tembo
M
M
McIlleron
H
H
Folb
P I
PI
Ribeiro
I
I
Little
F
F
Gomes
M
M
Molyneux
M E
ME
D000285:Administration, Rectal; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000493:pharmacokinetics; D037621:Artemisinins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D011739:Pyrimethamine / Q000008:administration & dosage; D011803:Quinine / Q000008:administration & dosage*; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013413:Sulfadoxine / Q000008:administration & dosage; D013488:Suppositories
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; D013488:Suppositories; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011803:Quinine; D011739:Pyrimethamine