Artesunate versus quinine for treating severe malaria

Abstract

Background
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 treatment outcomes.

Objectives
To compare artesunate with quinine for treating severe malaria.

Search methods
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.

Selection criteria
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.

Main results
Eight trials enrolling 1664 adults and 5765 children are included in this review.

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.

Authors' conclusions
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 neurological disability.

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 treatment groups.

Artesunate should be the drug of choice for adults and children with severe malaria worldwide.

Citation

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]

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