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Iron chelating agents for treating malaria.

BACKGROUND
Researchers are exploring the effects of adding treatments to the main antimalarial regimens in an attempt to reduce mortality from Plasmodium falciparum. Iron chelation is one potential chemotherapeutic adjuvant treatment. Before advocating adjunctive therapy, the effects of iron chelators in improving patient outcomes need to be examined.


OBJECTIVES
To assess the effects of iron-chelating agents combined with antimalarial drugs, or iron chelators alone, for treating Plasmodium falciparum malaria in adults and children, in relation to mortality, coma recovery time, parasite clearance, and adverse effects.


SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group trials register (up to January 2003), the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 1, 2003), MEDLINE (January 1966 to January 2003), EMBASE (January 1980 to November 2002), and reference lists of retrieved studies. We also contacted organisations, experts and researchers in the field.


SELECTION CRITERIA
All randomised controlled trials comparing iron chelating agents with placebo, or comparing iron chelating agents in conjunction with other antimalarials with antimalarial treatment alone in adults or children with falciparum malaria.


DATA COLLECTION AND ANALYSIS
Two reviewers independently applied inclusion criteria and assessed trial quality. One reviewer (HS) extracted data from included studies. Study authors were contacted for missing and additional data.


MAIN RESULTS
Seven trials involving 570 participants were included. Two trials involving 435 children compared the iron chelator DFO with placebo and standard treatment. No evidence of benefit or harm was shown in relation to mortality, but studies were small. The risk of experiencing persistent seizures was lower with DFO compared to placebo treatment (RR 0.80, 95% CI 0.67 to 0.95), but adverse effects were more common in the DFO group. One trial involving 45 adults and children compared the orally active iron chelator (deferiprone) with placebo and standard treatment; coma recovery (WMD -27 hrs; 95%CI -34.20 to -19.80) and parasite clearance (WMD -24 hrs; 95%CI -35.27 to -12.73) were significantly faster in the deferiprone group compared to placebo, but clinical significance cannot be assumed from this small trial. The authors reported no side effects during the study.


REVIEWER'S CONCLUSIONS
There are insufficient data for any conclusions for both agents tested. There are non-significant trends towards harm (death) and potential benefit (fewer seizures) with DFO. With deferiprone, results suggest possible benefit (shorter coma recovery and parasite clearance). If this topic is considered a priority for further research, larger trials are needed to detect an effect on clinical outcomes; and these trials should also include carefully evaluate adverse effects.