Initial high dose of quinine to treat severe malaria

People with severe malaria are unconscious, have difficulty breathing, may convulse, and have low blood sugar. They need treating quickly.

Quinine given intravenously or intramuscularly has been used for some years to treat severe malaria. It is particularly helpful as it works against parasites resistant to chloroquine, which used to be an effective and commonly used drug.

The World Health Organization recommends that doctors give people with severe malaria an initial high dose (loading dose) of intravenous quinine followed by lower quinine maintenance doses. This is to get an effective drug concentration in the blood. Several different quinine loading doses, maintenance doses, and dose intervals have been examined. There are some concerns about adverse effects in children.

The authors of this review wanted to summarize the benefits and harms of different quinine dosing regimens. They identified four relevant trials with 144 participants. A high initial dose of quinine reduced fever clearance time and parasite clearance time, but there were too few data to describe the impact on death. No difference was detected for recovery of consciousness and other neurological symptoms, but there were probably too few participants to detect differences.

Authors' conclusions: 

Quinine loading dose reduced fever clearance time and parasite clearance time. Data are insufficient to directly demonstrate an impact of loading dose on risk of death.

Read the full abstract...

Quinine is used for treating severe malaria. There are arguments for giving an initial high dose. We examined the evidence for and against this policy.


To assess the clinical outcomes and adverse events of a high first (loading) dose regimen of quinine compared with a uniform (no loading) dose regimen in people with severe malaria.

Search strategy: 

We searched the Cochrane Infectious Diseases Group Specialized Register (February 2009), CENTRAL (The Cochrane Library Issue 1, 2009), MEDLINE (1966 to February 2009), EMBASE (1974 to February 2009), LILACS (1982 to February 2009), and conference proceedings for relevant abstracts. We also contacted researchers working in the field and checked the reference lists of all studies.

Selection criteria: 

Randomized controlled trials comparing a high first (loading) dose of intravenous quinine with a uniform (no loading) dose of intravenous quinine in people with severe malaria.

Data collection and analysis: 

Two reviewers independently assessed the risk of bias in the trials and extracted data (including adverse event data). We used Review Manager 5.0 to analyse the data: risk ratio (RR) for binary data and mean difference (MD) for continuous data with 95% confidence intervals (CI). We contacted study authors for additional information.

Main results: 

Four trials (n = 144) met the inclusion criteria. Loading dose was associated with fewer deaths, but this was not statistically significant (RR 0.62, 95% CI 0.19 to 2.04; 3 trials). Loading dose was associated with faster clearance of parasites (WMD -7.44 hours, 95% CI -13.24 to -1.64 hours; 2 trials), resolution of fever (WMD -11.11 hours, 95% CI -20.04 to -2.18 hours; 2 trials). No statistically significant difference was detected for recovery of consciousness, neurological sequelae, or convulsions, but the numbers were small.