Iron-chelating agents for treating malaria

Malaria is a major health problem that particularly affects people living in sub-Saharan Africa and other tropical parts of the world. It often causes considerable morbidity and high mortality, especially in children under five, and is passed by mosquito bites from infected female mosquitoes. Several drugs are available to treat malaria infections, and there are also additional drugs that can be used to increase effectiveness. Since parasites require iron to reproduce, drugs that withhold available iron (ie iron-chelating drugs) from the parasite could inhibit the parasite reproduction rate and may be used as adjuncts to traditional antimalarial drugs. However, the agents may also reduce the availability of iron to the individual, and this may contribute to or exacerbate anaemia. There are a number of different iron-chelating agents, such as desferrioxamine (DFO) and deferiprone, and all were considered in the review of trials, although DFO has to be given intravenously and so will be of little use in most malarious areas. The drugs may also display adverse effects like headaches, dizziness, muscle pain, and tiredness. The review found seven trials of DFO and deferiprone involving 570 participants. Although the drugs may have helped in part with parasite levels, there seemed to be adverse effects including concerns about possibility of an increase in death. There is insufficient evidence to support the use of iron-chelating agents as adjuncts in the treatment of malaria, and further trials are not expected.

Authors' conclusions: 

There are insufficient data to draw any conclusions for DFO and deferiprone. There are nonsignificant trends towards fewer seizures but overall harm (death) with DFO, and results from one small trial of deferiprone suggest shorter coma recovery and parasite clearance.

2008: We do not plan to update this review given the paucity of recent trials in this area and other priorities in malaria treatment research.

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Background: 

It is still unclear whether iron-chelating agents, such as intravenous desferrioxamine (DFO) and oral deferiprone, given alone or added to standard antimalarial treatment would reduce malaria deaths.

Objectives: 

To evaluate iron-chelating agents alone or combined with standard antimalarial drugs for treating P. falciparum malaria.

Search strategy: 

In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, mRCT, and reference lists. We also contacted researchers in the field.

Selection criteria: 

Randomized controlled trials comparing iron-chelating agents with placebo, or comparing iron-chelating agents plus standard antimalarial drugs with antimalarial drugs alone in adults or children with P. falciparum malaria.

Data collection and analysis: 

We independently applied inclusion criteria and assessed trial methodological quality, and one author extracted data. We contacted trial authors for additional data. We combined dichotomous data using risk ratios (RR) and continuous data with weighted mean differences (MD), and presented both with 95% confidence intervals (CI).

Main results: 

Seven trials involving 570 participants met the inclusion criteria. Two small trials compared DFO with placebo (plus standard antimalarial drugs in both groups). No evidence of benefit or harm was shown in relation to death, but the trials were small (435 participants). The risk of experiencing persistent seizures was lower with DFO compared with placebo (RR 0.80, 95% CI 0.67 to 0.95; 334 participants, 1 trial), but adverse effects were more common with DFO. One small trial involving 45 adults and children compared deferiprone with placebo (plus standard antimalarial drugs in both groups). Participants in the deferiprone group had significantly faster coma recovery (MD -27 h, 95% CI -34.20 to -19.80) and parasite clearance (MD -24 h, 95% CI -35.27 to -12.73). No adverse effects were reported for this trial.

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