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Guidelines for the treatment of malaria – 2 edition

Benefits
Two systematic reviews (6,7) and three subsequent RCTs (8–10). The first review (search
date not reported, seven RCTs, 1919 adults and children) analysed individual participant
data (6). It found no significant difference in mortality between IM artemether and
quinine given by IV infusion or IM injection (the latter in one RCT only) in severe
falciparum malaria (mortality 136/961 (14%) with artemether, 164/958 (17%) with quinine;
odds ratio 0.80, 95% CI 0.62–1.02). Parasite clearance was faster with artemether than
with quinine (OR 0.62, 95% CI 0.56–0.69). The review found no significant difference
in the speed of coma recovery, fever clearance time or neurological sequelae between
artemether and quinine (coma recovery time OR 1.09, 95% CI 0.97–1.22; fever clearance
time OR 1.01, 95% CI 0.90–1.15; neurological sequelae, OR 0.82, 95% CI 0.59–1.15).
The second review (search date: 1999, 11 RCTs, 2142 people) found a small significant
reduction in mortality for IM artemether compared with IV quinine (OR 0.72, 95% CI
0.57–0.91) (7). However, more rigorous analysis excluding three poorer quality trials found
no significant difference in mortality (OR 0.79, 95% CI 0.59–1.05). The review found no
significant difference in neurological sequelae at recovery between the artemether and
quinine groups (OR 0.8, 95% CI 0.52–1.25).
The first subsequent RCT (105 people aged 15–40 years with cerebral malaria in
Bangladesh) compared IM artemether (160 mg initially, then 80 mg/kg once daily)
with IV quinine (loading dose 20 mg/kg, then 10 mg/kg every 8 h) (8). It found no
significant difference in death rates between the artemether and quinine groups (9/51
(18%) compared with 10/54 (19%), OR 0.94, 95% CI 0.35–2.55). Mean fever clearance
time and coma recovery time were significantly longer for artemether than for quinine
(fever clearance time 58 h compared with 47 h, WMD 11.0 h, 95% CI 1.6–20.4 h; coma
recovery time 74 h compared with 53 h, WMD 20.8 h, 95% CI 3.6–38.0 h). There was no
significant difference in mean parasite clearance time between artemether and quinine
(52 h compared with 61 h, WMD −8.6 h, 95% CI −22.5 h to +5.3 h).

The second subsequent RCT (41 children with severe malaria in Sudan, 40 analysed)
compared IM artemether (3.2 mg/kg loading dose, then 1.6 mg/kg once a day) with IV
quinine (loading dose 20 mg/kg, then 10 mg/kg every 8 h) (11). It found that artemether
significantly increased fever clearance time but found no significant difference between
artemether and quinine in time to parasite clearance (mean fever clearance time 30.5 h
with artemether, 18 h with quinine, P = 0.02; mean parasite clearance time 16 h compared
with 22.4 h, P > 0.05). There were no deaths in the artemether group, one child died with
quinine (0/20 (0%) compared with 1/21 (5%), P value not reported).
The third subsequent RCT (77 comatose children aged 3 months–15 years with cerebral
malaria) compared IM artemether (1.6 mg/kg every 12 h) with IV quinine (10 mg/kg
every 8 h) (10). It found no significant difference in death rates between the artemether
and quinine groups (3/38 (8%) compared with 2/39 (5%), P value not reported). There

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