Artesunate versus quinine for treating severe malaria
Abstract
Background
Severe malaria kills over a million people every year. We sought evidence of superiority of artesunate compared with the standard treatment quinine.
Objectives
To compare artesunate with quinine for treating severe malaria.
Search methods
We searched the Cochrane Infectious Diseases Group Specialized Register (July 2009), CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to July 2009), EMBASE (1974 to July 2009), LILACS (1982 to July 2009), ISI Web of Science (1945 to July 2009), the metaRegister of Controlled trials (mRCT), conference proceedings, and reference lists of articles. We contacted researchers and the World Health Organization.
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 assessed the eligibility and risk of bias of trials, extracted and analysed data, and drafted the review. The third author contributed to the design and writing of the review. Death was the primary outcome. Dichotomous outcomes were summarized using risk ratios (RR) and continuous outcomes by mean differences (MD). Where appropriate, we combined data in meta‐analyses. Heterogeneity was investigated for the primary outcome using subgroup analyses.
Main results
Six trials enrolling 1938 participants (1664 adults and 274 children) met our inclusion criteria. All six trials were conducted in Asia, and only one small trial enrolled only children. Five trials used intravenous artesunate and one trial intramuscular artesunate; all six used intravenous quinine. Treatment with artesunate significantly reduced the risk of death (RR 0.62, 95% CI 0.51 to 0.75; 1938 participants, 6 trials), reduced parasite clearance time (MD 8.14 h, 95% CI 11.55 to 4.73; 292 participants, 3 trials), and hypoglycaemia detected by routine monitoring (RR 0.46, 95% CI 0.25 to 0.87; 185 participants, 2 trials). There was no evidence of a difference in neurological sequelae, coma recovery time, time to hospital discharge, fever clearance time, or adverse effects other than hypoglycaemia.
Authors' conclusions
Intravenous artesunate is the drug of choice for adults with severe malaria, particularly if acquired in Asia. This review did not identify sufficient data to make firm conclusions about the treatment of children or the effectiveness of intramuscular artesunate. There is an urgent need to compare the effects of artesunate with quinine in African children with severe malaria. The applicability of these results to Asian children and the ethics of further research are points of debate.
PICO
Plain language summary
Artesunate reduces death from severe malaria in adults in Asia, but there is not enough evidence to say how effective artesunate is in children, people in Africa, or on potential adverse effects
Severe malaria kills over a million people every year. The annual death toll can be as high as one in a 100 children under the age of five. Severe malaria occurs when infection with the malaria parasite is complicated by serious failure of the body's major organs. Sometimes it is associated with coma (known as cerebral malaria). Following cerebral malaria a small proportion of children suffer with long‐term neurological disability.
Quinine, the standard treatment for severe malaria, often causes adverse effects. In most people symptoms are mild; less common but more serious adverse effects include low blood sugar and heart rhythm disturbances. Regular glucose measurement and a heart trace are therefore advised when quinine is given by injection. Lack of resources may not permit this monitoring in some settings.
Artesunate is generally well tolerated, safe, and does not require any monitoring. Artesunate comes from a family of drugs known as the artemisinin derivatives. Another drug from this group, artemether, has shown no reduction in death compared to quinine. Artemether absorption is erratic and unreliable. By contrast, artesunate levels peak reliably and predictably within an hour.
The review of trials assessed the effectiveness of artesunate versus quinine. Six trials involving 1938 people (1664 adults and 274 children) were identified, all undertaken in Asia. Treatment with artesunate significantly reduced the risk of death. It also reduced the time taken to clear parasites from the blood and reduced the number of people with low blood sugar during follow up in trials where this was routinely measured. There was no evidence to say if the drug is effective in children in Africa, in whom most deaths from severe malaria occur.
