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Guidelines for the treatment of malaria – 2 edition

Box 8.1a
Recommendation: IV/IM artesunate treatment for severe P. falciparum malaria in adults

 intravenous artesunate should be used in preference to quinine for the treatment of severe
P. falciparum malaria in adults. Strong recommendation, high quality evidence
GRADE evaluation (see Annex 8, Table A8.1.1)
Intravenous artesunate has been shown to significantly reduce the risk of death from severe malaria compared
to intravenous quinine (6 trials, 1938 participants; RR 0.62, 95% CI 0.51–0.75; high quality evidence).
Intravenous artesunate was associated with a lower risk of hypoglycaemia (2 trials, 185 participants; RR
0.46, 95% CI 0.25–0.87; low quality evidence).
No difference has been shown in the risk of serious neurological sequelae (2 trials, 1253 participants, very
low quality evidence).
Other consideration
• Artesunate offers a number of programmatic advantages over quinine in terms of not requiring rate-
controlled infusion or cardiac monitoring.

Box 8.1b

Recommendation: IV/IM artesunate treatment for severe P. falciparum malaria in children
 intravenous artesunate should be used in preference to quinine for the treatment of severe
P. falciparum malaria in children. Strong recommendation, high quality evidence
Intravenous or intramuscular artesunate has been shown to reduce significantly the risk of death from severe
malaria compared to intravenous quinine (4 trials, 5765 participants; RR 0.76, 95% CI 0.65–0.90; high quality
evidence).
Intravenous artesunate was associated with a lower risk of hypoglycaemia (4 trials, 5765 participants;
RR 0.62, 95% CI 0.45–0.87; high quality evidence).
No difference has been shown in the risk of serious neurological sequelae at day 28 (3 trials, 5163 participants,
moderate quality evidence).
Other consideration
• Artesunate offers a number of programmatic advantages over quinine in terms of not requiring rate-
controlled infusion or cardiac monitoring.

8.4.2 Quinine
Quinine treatment for severe malaria was established before modern clinical trial
methods were developed. Several salts of quinine have been formulated for parenteral
use, but the dihydrochloride is the most widely used. Peak concentrations following
intramuscular quinine in severe malaria are similar to those following intravenous
infusion. Pharmacokinetic modelling studies suggest that a loading dose of quinine (i.e.
20 mg salt/kg body weight – twice the maintenance dose) reduces the time needed to
reach therapeutic plasma concentrations. The maintenance dose of quinine (10 mg salt/kg

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