WHO Drug Information Vol. 18, No. 2, 2004 - World Health ...

Safety and Efficacy Issues
12 hours), and clinical improvement without
serious adverse reactions. In both study groups,
treatment was completed with the administration
of sulfadoxine-pyrimethamine according to
prevailing national policy.
Clinical outcome
Rectal artesunate, given as a single dose of
10 mg/kg, showed rapid antimalarial efficacy
within 24 hours of administration in moderately
severe falciparum malaria in children and adults
(Table 1). All patients had either pharmacodynamic
or pharmacokinetic evidence of absorption
of the drug. Clearance of asexual parasites from
the peripheral blood was consistently faster with
rectal artesunate than parenteral quinine, as is
expected when an artemisinin is absorbed
adequately (Table 2). The results were highly
Table 2: Parasite density over time by allotted treatment group
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WHO Drug Information Vol 18, No. 2, 2004
significant not only in the large study of children,
but also in the smaller study in adults, which was
powered to detect only large effects. The clinical
and parasitological responses show that rectal
artesunate provides effective initial management
of acute malaria in patients who cannot take
medication by mouth, particularly when parenteral
treatment is not available.
A faster decrease in peripheral parasitaemia does
not necessarily ensure improved clinical outcome.
In this study, the clinical success rate for rectal
artesunate was similar to that for parenteral
quinine. This is consistent with other studies
comparing intramuscular artemether with intravenous
quinine in severe malaria, where artemether
showed more rapid decrease in parasitaemia but
equivalent clinical outcomes (11).
Children Adults
Rectal Quinine p Rectal Quinine p
artesunate IM/IV artesunate IM
(n=87) (n=22) (n=27) (n=8)
Parasitaemia (ring forms per µL blood)
Baseline 185977 230738 0.69 56480 58340 0.666
(112 411- (170 078- (26 536- (45 110-
336 000) 325 029) 126 000) 118 230)
12 h 50596 210335