Iron-chelating agents for treating malaria

Abstract

BACKGROUND: Mortality from Plasmodium falciparum malaria remains high; death and sequelae occur in even in patients treated with antimalarial drugs. Researchers are exploring the effects of adding treatments to the main antimalarial regimens in an attempt to reduce mortality. Iron chelation is one potential chemotherapeutic adjuvant treatment. Before advocating adjunctive therapy, the effects of iron chelators in improving patient outcomes needs 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: Electronic searches of the Cochrane Library, MEDLINE, and EMBASE, using the standard Cochrane search strategy. Bibliographies of retrieved studies were scrutinized in order to identify further relevant trials. Organisations, experts and other individuals in malaria research were contacted for unpublished studies. SELECTION CRITERIA: All randomised controlled trials of adults or children with P.falciparum malaria. DATA COLLECTION AND ANALYSIS: Trials were identified and extracted by a single reviewer (HS) and checked by a second (MM). Inclusion criteria were applied, and data were extracted independently by both reviewers. Authors were contacted for missing and additional data. Meta-analysis used Relative Risk (RR) and 95% Confidence Intervals. MAIN RESULTS: No evidence of benefit or harm were shown in relation to mortality, but studies were small, and one trial was tending towards more deaths with the intervention when it was stopped. The risk of experiencing persistent seizures was significantly lower with desferrioxamine compared to placebo treatment (RR 0.80, 95% CI 0.67 to 0.95). Many adverse effects were more common in participants treated with desferrioxamine. REVIEWER'S CONCLUSIONS: Trends suggestive of both harm (death) and potential benefit (fewer seizures) are demonstrated in this review. It is not possible to comment on time to event outcomes that include coma recovery or parasitaemia as we are clarifying data with the trialists. Whether to conduct further trials will depend on a judgement about potential benefit.