Summary of findings for the main comparison.
Artemether compared with quinine for treating children with severe malaria | |||||
Patient or population: Children with severe malaria Settings: Malaria‐endemic countries Intervention: Intramuscular artemether Comparison: Intravenous or intramuscular quinine | |||||
Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (trials) | Quality of the evidence (GRADE) | |
Assumed risk | Corresponding risk | ||||
Quinine | Artemether | ||||
Death | 170 per 1000 | 164 per 1000 (129 to 204) | RR 0.96 (0.76 to 1.2) | 1447 (12 trials) | ⊕⊕⊕⊝ moderate1,2,3,4 |
Coma resolution time | The mean coma resolution time ranged across control groups from 17.4 to 42.4 hours | The mean coma resolution time in the intervention groups was 5.45 hours shorter (7.90 to 3.00 shorter) | ‐ | 358 (6 trials) | ⊕⊕⊝⊝ low3,5,6,7 |
Neurological sequelae at discharge | 220 per 1000 | 185 per 1000 (145 to 235) | RR 0.84 (0.66 to 1.07) | 968 (7 trials) | ⊕⊕⊝⊝ low 1,2,3,8 |
Parasite clearance time | The mean parasite clearance time ranged across control groups from 22.4 to 61.25 hours | The mean parasite clearance time in the intervention groups was 9.03 hours shorter (11.43 to 6.63 shorter) | ‐ | 420 (7 trials) | ⊕⊕⊕⊝ moderate1,3,7,9 |
Fever clearance time | The mean fever clearance time ranged across control groups from 18 to 61.25 hours | The mean fever clearance time in the intervention groups was 3.73 shorter (6.55 to 0.92 shorter) | ‐ | 457 (8 trials) | ⊕⊕⊝⊝ low3,10,11,12 |
*The assumed risk is the median control group risk across studies. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio. | |||||
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. |
1 No serious risk of bias: Trials were variable in their risk of bias, but exclusion of the trials at high or unclear risk of selection bias did not change this result. 2 No serious inconsistency: None of the individual trials found statistically significant effects, and there was no statistical heterogeneity between trials. 3 No serious indirectness: Trials were from West Africa, East Africa and one from India. All were in children with severe malaria (aged under 15 years), and most compared the standard dose of intramuscular artemether with the WHO recommended dose of intravenous quinine. 4 Downgraded by 1 for serious imprecision: These trials, and the overall meta‐analysis are underpowered to detect a difference or to prove equivalence. 5 Downgraded by 2 for serious risk of bias: Four of the six trials were at unclear risk of selection bias. When these four trials are excluded the result becomes non‐significant. 6 No serious inconsistency: Statistically significant differences were only seen in two of the six trials. However, statistical heterogeneity between trials was low and the overall meta‐analysis is statistically significant. 7 No serious imprecision: The result is statistically significant and the overall meta‐analysis is adequately powered to detect this effect. 8 Downgraded by 2 for very serious imprecision: These trials, and the overall meta‐analysis are underpowered to detect a difference or to prove equivalence. The 95% CI is very wide and includes clinically important differences and no effect. 9 Downgraded by 1 for serious inconsistency: The mean difference in parasite clearance time ranged from a two hour increase with artemether to a 15 hour decrease. 10 Downgraded by 1 for serious risk of bias: Four of the seven trials were at unclear risk of selection bias. When these four trials are excluded the result becomes non‐significant. 11 Downgraded by 1 for serious inconsistency: The mean difference in fever clearance time ranged from a 25 hour increase with artemether to an 18 hour decrease. 12 No serious imprecision: The overall meta‐analysis is powered to detect this effect. The result is statistically significant but may not be clinically important.