Intervention Review

Iron-chelating agents for treating malaria

  1. Helen J Smith1,*,
  2. Martin M Meremikwu2

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 22 APR 2003

Assessed as up-to-date: 16 FEB 2003

DOI: 10.1002/14651858.CD001474


How to Cite

Smith HJ, Meremikwu MM. Iron-chelating agents for treating malaria. Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD001474. DOI: 10.1002/14651858.CD001474.

Author Information

  1. 1

    Liverpool School of Tropical Medicine, International Health Group, Liverpool, Merseyside, UK

  2. 2

    University of Calabar Teaching Hospital, Department of Paediatrics, Calabar, Cross River State, Nigeria

*Helen J Smith, International Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, Merseyside, L3 5QA, UK. cjdhel@liv.ac.uk.

Publication History

  1. Publication Status: Stable (no update expected for reasons given in 'What's new')
  2. Published Online: 22 APR 2003

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

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 methods

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.

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.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

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.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

針對治療瘧疾所用的鐵離子螯合劑

像是靜脈注射的desferrioxamine(DFO)與口服的 deferiprone,當這類的鐵離子螯合劑採取單獨給藥或是添加到標準的抗瘧治療方法當中時,是否可以減少瘧疾造成的死亡數目,目前還不清楚。

目標

對於治療惡性瘧原蟲瘧疾而言,鐵離子螯合劑類的藥物應該要單獨給藥,或是與標準的抗瘧疾藥物合併使用,必須要進行評估。

搜尋策略

2007年5月我們搜尋Cochrane Infectious Diseases Group Specialized Register, CENTRAL (Cochrane Library 2007, Issue 2)、MEDLINE、EMBASE、LILACS、mRCT,以及參考文獻清單。我們也與本領域研究人員聯絡。

選擇標準

惡性瘧原蟲瘧疾之成人或兒童之隨機對照試驗將鐵離子螯合劑類的藥物與安慰劑進行比較,或是將鐵離子螯合劑類的藥物加上標準的抗瘧疾藥物與單獨使用的抗瘧疾藥物進行比較。

資料收集與分析

我們獨立地使用了收集的標準,並評估過試驗方法上的品質,而且有1位作者擷取出了資料。為了取得更多的資料,我們與試驗的作者們進行過聯繫。我們使用了相對風險(RR)與帶著加權平均差(WMD)的連續性資料,將二元性資料合併起來,並且將這2者都以95%信賴區間(CI)來表示。

主要結論

當中共有包含了570名參與者在內的7項試驗符合了收集的標準。有2項小型的試驗將DFO與安慰劑進行了比較(在2組當中都有添加標準的抗瘧疾藥物)。就死亡方面來說,並沒有證據顯示相關的優點或是危害,但是這些試驗都屬於小型的(435名參與者)。跟安慰劑比較起來,使用DFO的時候,遇到持續性發作的風險較低(RR 0.80,95% CI 0.67到0.95;334名參與者,1份試驗),但是DFO卻會帶來較多的副作用。有1項包含了45名成年人與兒童的小型試驗曾經將deferiprone與安慰劑(在2組當中都有添加標準的抗瘧疾藥物)進行比較。在deferiprone組當中的參與者,明顯地比較快從昏迷當中恢復過來(WMD −27 h,95% CI −34.20到−19.80),而且也能夠較快地將寄生蟲排除乾淨(WMD −24 h,95%CI −35.27到−12.73)。這項試驗並未報告有不良的作用。

作者結論

並沒有足夠的資料可針對DFO與deferiprone作出任何結論。對於DFO而言,有某些不是很明顯的趨勢說明它可以讓發作的情形減少,但不包括整體危害(死亡),同時也有1項小型的deferiprone試驗結果認為它可以讓昏迷恢復的時間與寄生蟲清除時間都縮短。本篇回顧中缺乏了近期的試驗,而且也沒有研究瘧疾治療其他重點,因此我們並沒有更新本篇回顧的計畫。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

以鐵離子螯合劑治療瘧疾。瘧疾是1種重大的健康問題,特別是它會影響那些撒哈拉以南之非洲區域中的居民,以及世界上住在其他熱帶地區裡的人們。它通常會引起相當多的致病人數以及很高的死亡率,尤其是對於那些不到5歲的兒童,而且它會從受到感染的雌性蚊子那兒開始,藉由蚊子叮咬來進行傳播。有幾種藥物可以用來治療瘧疾感染,而且還有許多輔助藥物可以用來增強功效。因為寄生蟲需要鐵才能進行再生,若是有藥物能夠從寄生蟲當中阻斷鐵的供應(也就是鐵質螯合劑的藥物),就有可能抑制寄生蟲的再生速率,而且或許也可以被用來當作傳統之抗瘧疾藥物的佐劑。然而,這些藥物也可能會降低人體所取得的鐵質供應量,而這樣的情況就可能會造成貧血或是讓貧血的症狀加劇。市面上有很多不同的鐵質螯合劑藥物,例如desferrioxamine(DFO)與deferiprone,雖然DFO必須要採用靜脈注射的給藥方式,因此在大多數的瘧疾區域中,它的實用性並不高,但是在本篇的試驗回顧當中,這些藥物仍然都是本研究考量之對象。這些藥物也可能會帶來某些不良反應,像是頭痛、暈眩、肌肉疼痛,以及疲倦。本篇回顧發現,有7篇屬於DFO與 deferiprone的試驗,其中包含了570名參與者。雖然說在某些情況下,這些藥物可能會有助於減少寄生蟲的數量,但是也有某些不良的作用,包括可能會提高死亡比率的顧慮。目前還沒有充分的證據可支持以鐵質螯合劑藥物當作療瘧疾之佐劑,我們也不對更深入的試驗抱持著期待。