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Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria
P E Thuma1, G F Mabeza, G Biemba
1Pennsylvania State University, Hershey Medical Center, USA.
Insights
This study investigated iron chelation therapy for cerebral malaria in children. Deferoxamine added to quinine did not significantly reduce mortality, with a trend towards increased risk in the urban setting.
Area of Science:
- Pediatric Infectious Diseases
- Hematology
- Malariology
Background:
- Cerebral malaria is a severe complication of Plasmodium falciparum infection, particularly in young children.
- Iron dysregulation is implicated in the pathogenesis of cerebral malaria.
- Deferoxamine is an iron chelator with potential therapeutic benefits.
Purpose of the Study:
- To evaluate the efficacy of deferoxamine, an iron chelator, in reducing mortality in children with cerebral malaria.
- To assess the impact of deferoxamine on coma recovery in pediatric cerebral malaria patients.
Main Methods:
- A randomized controlled trial involving 352 children under 6 years old with cerebral malaria in Zambia.
- Participants received standard quinine therapy with either deferoxamine or placebo for 7 days.
- Mortality rates and coma recovery times were compared between the two groups.
Main Results:
- Overall mortality was 18.3% in the deferoxamine group versus 10.7% in the placebo group (adjusted odds ratio 1.8; P=0.074).
- At the urban site, mortality was higher in the deferoxamine group (24.1%) compared to placebo (6.8%; P=0.061).
- No significant difference in coma recovery was observed between groups.
Conclusions:
- Adding deferoxamine to quinine therapy did not demonstrate a beneficial effect on mortality in children with cerebral malaria.
- The study suggests a potential for increased mortality risk with deferoxamine in urban settings.
- Further research is needed to understand the role of iron chelation in cerebral malaria management.
Abstract:
To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age < 6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18.3% (32/175) in the deferoxamine group and 10.7% (19/177) in the placebo group (adjusted odds ratio 1.8; 95% confidence interval 0.9-3.6; P = 0.074). At the rural study site, mortality was 15.4% (18/117) with deferoxamine compared to 12.7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24.1% (14/58) with deferoxamine and 6.8% (4/59) with placebo (P = 0.061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1.2; 95% confidence interval 0.97-1.6; P = 0.089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.
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