Artemisinin derivatives versus quinine in treating severe malaria in children: a systematic review

Abstract

Background: The efficacy of intravenous quinine, which is the mainstay for treating severe malaria in children, is decreasing in South East Asia and Africa. Artemisinin derivatives are a potential alternative to quinine. However, their efficacy compared to quinine in treating severe malaria in children is not clearly understood. The objective of this review was to assess the efficacy of parenteral artemisinin derivatives versus parenteral quinine in treating severe malaria in children.

Methods: All randomized controlled studies comparing parenteral artemisinin derivatives with parenteral quinine in treating severe malaria in children were included in the review. Data bases searched were: The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2007), MEDLINE (1966 to February 2008), EMBASE (1980 to February 2008), and LILACS (1982 to February 2008). Dichotomous variables were compared using risk ratios (RR) and the continuous data using weighted mean difference (WMD).

Results: Twelve trials were included (1,524 subjects). There was no difference in mortality between artemisinin derivatives and quinine (RR = 0.90, 95% CI 0.73 to 1.12). The artemisinin derivatives resolved coma faster than quinine (WMD = -4.61, 95% CI: -7.21 to -2.00, fixed effect model), but when trials with adequate concealment only were considered this differences disappeared. There was no statistically significant difference between the two groups in parasite clearance time, fever clearance time, incidence of neurological sequelae and 28th day cure rate. One trial reported significantly more local reactions at the injection site with intramuscular quinine compared to artemether. None of the trials was adequately powered to demonstrate equivalence.

Conclusion: There was no evidence that treatment of children with severe malaria with parenteral artemisinin derivatives was associated with lower mortality or long-term morbidity compared to parenteral quinine. Future studies require adequately powered equivalence trial design to decide whether both drugs are equally effective.

Figure 1

Meta-analysis of effect of artemisinin derivatives versus quinine on mortality (fixed effect model). Weight of study was expressed by size of square.

Figure 2

Subgroup meta-analysis of effect of β-arteether, artemether and artesunate versus quinine on mortality (fixed effect model). Weight of study was expressed by size of square.

Figure 3

Meta-analysis of effect of artemisinin derivatives versus quinine on parasites clearance time (random effect model). Weight of study was expressed by size of square.

Figure 4

Meta-analysis of effect of artemisinin derivatives versus quinine on fever clearance time (random effect model). Weight of study was expressed by size of square.

Figure 5

Meta-analysis of effect of artemisinin derivatives versus quinine on coma resolution time (fixed effect model). Weight of study was expressed by size of square.

Figure 6

Meta-analysis of effect of artemisinin derivatives versus quinine on incidence of neurological sequelae (fixed effect model). Weight of study was expressed by size of square.

Figure 7

Meta-analysis of effect of artemisinin derivatives versus quinine on 28^th day cure rates (random effect model). Weight of study was expressed by size of square.