Table 1.
Randomized trials of anti-inflammatory and antioxidant therapies in severe malaria with neurological complications
| Reference | Design and regimena | Patients | Outcomes |
|---|---|---|---|
| Corticosteroids | |||
| Warrell et al. (1982)44 |
RDPCT of dexamethasone (1.5–2.0 mg/kg over 48 h) |
100 Thai children and adults with cerebral malaria |
Dexamethasone prolonged DoC (63 h vs 47 h in placebo group); complications in 26% of dexamethasone group versus 11% of placebo group |
| Hoffman et al. (1988)71 |
RDPCT of dexamethasone (11.4 mg/kg per 48 h) |
38 Indonesian children and adults with impaired consciousness |
No significant difference in FCT, PCT and DoC |
| Rampengan (1991)72 |
Randomized trial of dexamethasone (4.5 mg/kg per 72 h) versus heparin (300 U/kg intramuscularly daily for 3 days) versus neither |
62 Indonesian children and adults with impaired consciousness |
No significant difference between groups in mortality or neurological sequelae |
| Immunomodulatory therapy | |||
| Taylor et al. (2002)81 |
RDPCT of HIG purified from plasma of local semi-immune blood donors (400 mg/kg by intravenous infusion over 3 h) versus placebo (albumin and sucrose infusion) |
31 Malawian children with cerebral malaria |
No difference in mortality: 5 of 16 patients given HIG died compared with 1 of 15 receiving placebo; no differences in DoC, FCT or PCT |
| van Hensbroek et al. (1996)80 |
RDPCT of monoclonal antibody (B-C7) against TNF |
610 Gambian children with cerebral malaria |
No difference in mortality; neurological sequelae in 15 (6.8%) of survivors in B-C7 group compared with 5 (2.2%) survivors in the placebo group (adjusted odds ratio 3.35, 95% CI 1.08–10.4) |
| Iron-chelation therapy | |||
| Gordeuk et al. (1992)73 |
RDPCT of deferoxamine (100 mg/kg per day infused for a total of 72 h) |
83 Zambian children (<6 years old) with cerebral malaria |
Shorter DoC in deferoxamine group (20 h) versus in placebo group (43 h); rapid PCT in deferoxamine group |
| Thuma et al. (1998)74 |
RDPCT of deferoxamine (100 mg/kg per day infused for a total of 72 h) |
352 Zambian children (<6 years old) with cerebral |
No significant effect on mortality or DoC |
| Mohanty et al. (2002)99 |
RDPCT of oral deferiprone (75 mg/kg) | 45 indian patients | Deferiprone improved FCT, PCT and DoC |
| Pentoxifylline | |||
| Di Perri et al. (1995)78 |
RDPCT of pentoxifylline (10 mg/kg continuous infusion) |
56 Burundian children with cerebral malaria |
Shorter median DoC in pentoxifylline group (6 vs 46 h); trend towards reduced mortality in pentoxifylline group |
| Looareesuwan et al. (1998)100 |
Randomized trial of low-dose pentoxifylline (0.83 [mg/kg]/h) versus high-dose pentoxifylline (1.67 [mg/kg]/h) versus placebo |
45 Thai adults, 18 of whom had cerebral malaria |
No difference in DoC or mortality |
| Das et al. (2003)79 |
RDPCT of pentoxifylline (10 mg/kg intravenously) for 3 days |
52 Indian adults with cerebral malaria |
Shorter DoC in pentoxifylline group (22 h) versus placebo group (64 h); decrease in TNF levels by day 3 and trend towards reduced mortality in pentoxifylline group |
a
All patients were given the antimalarial drug quinine, except for some patients in the van Hensbroek study, who were given artemether. Abbreviations; DoC, duration of coma after treatment; FCT, fever clearance time; HIG, hyperimmune immunoglobin; PCT, parasite clearance time; RDPCT, randomized, double-blind, placebo-controlled trial; TNF, tumor necrosis factor.