Severe malaria results in over a million deaths every year, most of
them in children aged under five years and living in sub-Saharan Africa.
This review examines whether treatment with artesunate, instead of the
standard treatment quinine, would result in fewer deaths and better
To compare artesunate with quinine for treating severe malaria.
We searched the Cochrane Infectious Diseases Group Specialized
Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, LILACS, ISI
Web of Science, the metaRegister of Controlled trials (mRCT), conference
proceedings, and reference lists of articles to November 2010.
Randomized controlled trials comparing intravenous, intramuscular, or
rectal artesunate with intravenous or intramuscular quinine for treating
adults and children with severe malaria who are unable to take
medication by mouth.
Data collection and analysis
Two authors independently assessed the eligibility and risk of bias of
trials, and extracted and analysed data. The primary outcome was
all-cause death. Dichotomous outcomes were summarized using risk ratios
(RR) and continuous outcomes by mean differences (MD). Where
appropriate, we combined data in meta-analyses.
Eight trials enrolling 1664 adults and 5765 children are included in
Treatment with artesunate significantly reduced the risk of death both
in adults (RR 0.61, 95% Confidence Interval (CI) 0.50 to 0.75; 1664
participants, five trials) and children (RR 0.76, 95% CI 0.65 to 0.90;
5765 participants, four trials).
In children, treatment with artesunate increased the incidence of
neurological sequelae at the time of hospital discharge. The majority of
these sequelae were transient and no significant difference between
treatments was seen at later follow up.
The evidence clearly supports the superiority of parenteral artesunate
over quinine for the treatment of severe malaria in both adults and
children and in different regions of the world.
Plain Language Summary: Artesunate reduces death from severe malaria
Severe malaria occurs when infection with the malaria parasite is
complicated by serious failure of the body's major organs, and results
in over a million deaths every year. Sometimes severe malaria is
associated with coma and is known as cerebral malaria. Following
cerebral malaria a small proportion of children suffer with long-term
This review of trials assessed the effectiveness of artesunate compared
with the standard treatment quinine. Eight trials involving 1664 adults
and 5765 children were identified, from study sites in Asia and Africa.
Treating adults in Asia with artesunate instead of quinine would prevent
an extra 94 deaths for every 1000 patients treated. In trials involving
children, the proportion of deaths was lower than in the trials
involving adults. This lower risk of death results in a smaller benefit
in children than in adults, but would still save an extra 26 lives for
every 1000 children treated.
In the children who survived their illness, there were more neurological
problems at the time of hospital discharge in those treated with
artesunate than those treated with quinine. However, the majority of
these neurological problems had resolved when they were reviewed 28 days
later, and at this timepoint there was no difference between the two
Artesunate should be the drug of choice for adults and children with
severe malaria worldwide.
Sinclair, D.; Donegan, S.; Isba, R.; Lalloo, D.G. Artesunate versus quinine for treating severe malaria. Cochrane Database of Systematic Reviews (2012) (Issue 6) Art. No.: CD005967. [DOI: 10.1002/14651858.CD005967.pub4]