Artesunate plus mefloquine versus mefloquine for treating uncomplicated malaria

  • Review
  • Intervention

Authors


Abstract

Background

Using a pilot system we have categorised this review as: “Historical question – no update intended: monotherapy no longer recommended" (see published notes).

Multiple-drug-resistant malaria is widespread, and in South-East Asia resistance is high against nearly all single therapy antimalarial drugs. Here, and in other areas with low malaria transmission, the combination of artesunate and mefloquine may provide an effective alternative.

Objectives

To compare artesunate plus mefloquine with mefloquine alone for treating uncomplicated Plasmodium falciparum malaria.

Search methods

We searched the Cochrane Infectious Diseases Group Specialized Register (May 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1988 to May 2005), LILACS (May 2005), BIOSIS (1985 to June 2005), conference proceedings, and reference lists. We also contacted researchers, organizations, and pharmaceutical companies.

Selection criteria

Randomized and quasi-randomized controlled trials comparing artesunate plus mefloquine with mefloquine alone for treating uncomplicated malaria.

Data collection and analysis

Two authors independently applied the inclusion criteria, extracted data, and assessed methodological quality. The primary outcome was treatment failure by day 28, defined as evidence of parasitaemia with or without clinical failure between days zero (start of treatment) and 28. For dichotomous data we calculated risk ratios (RR) and 95% confidence intervals (CI).

Main results

Eight trials involving 1996 participants met the inclusion criteria. All were conducted in areas with low malaria transmission, seven in South-East Asia and one in the Peruvian Amazon. The doses and dosing regimens of artesunate and mefloquine varied across trials. The trials using a total dose of 25 mg/kg mefloquine and 10 mg artesunate reported fewer treatment failures with the combination at all time points: day 28 (RR 0.17, 95% CI 0.06 to 0.47; 824 participants, 4 trials), day 42 (RR 0.23, 95% CI 0.14 to 0.39; 298 participants, 1 trial), and day 63 (RR 0.26, 95% CI 0.09 to 0.77; 501 participants, 2 trials). The results for parasitaemia showed a similar trend. Trials using a lower dose of artesunate tended to favour the artesunate plus mefloquine combination. Overall, adverse events were similar across treatment arms.

Authors' conclusions

Artesunate plus mefloquine performs better than mefloquine alone for treating uncomplicated falciparum malaria in areas with low malaria transmission. A total dose of 25 mg/kg mefloquine and at least 10 mg artesunate leads to higher cure rates. Better reporting of methods and standardisation of outcomes would help the interpretation of future trials.

2008: As monotherapy is no longer recommended by the World Health Organization for malaria treatment, the authors do not intend to update this review.

摘要

背景

比較以Artesunate加上mefloquine 與mefloquine治療無併發症之瘧疾

具有多重藥物抗藥性的瘧疾頗為普遍,而且在東南亞地區幾近全部的單1療法型之抗瘧疾藥物均有很高的抗藥性。在此地,以及在其他瘧疾傳播程度並不高的區域,artesunate與mefloquine的組合或許能夠成為1種有效的替代選項。

目標

為了比較以artesunate加上mefloquine 與單獨使用mefloquine治療無併發症之瘧疾。

搜尋策略

我們搜尋Cochrane Infectious Diseases Group Specialized Register (2005年5月)、CENTRAL (Cochrane Library Issue 2, 2005)、 MEDLINE (1966年−2005年5月)、 EMBASE (1988 年−2005年5月)、 LILACS (2005年5月)、 BIOSIS (1985 – 2005年年6月)、研討會手冊,以及參考資料清單。我們也與本領域藥廠、相關機構以及研究人員聯絡。

選擇標準

針對比較將artesunate加上mefloquine與單獨使用mefloquine治療無併發症瘧疾之隨機與半隨機對照試驗

資料收集與分析

兩位作者獨立地採用了收集的標準、擷取出資料,並且評估了方法學的品質。主要的結果為第28天之前所發生治療失敗情況,並將它定義為第0天(治療的起點)與第28天之間無論有或無發生臨床失敗的寄生蟲血症。針對二元性的資料,我們計算了相對風險(RR)與95%信賴區間(CI)。

主要結論

共有包含了1996名參與者在內的8項試驗符合了收集的標準。所有的試驗都是在具有低度瘧疾傳播的區域當中所進行的,當中有7項是在東南亞,另外還有1項是在秘魯亞馬遜地區。這些artesunate與mefloquine的劑量以及療法,在各個試驗之中都有所不同。使用了總劑量為每公斤25毫克的mefloquine以及10毫克的artesunate得試驗報告在所有的時間點上均有治療較少失敗的情形,而這些時間點為:第28天(RR 0.17,95% CI 0.06到0.47;824名參與者,4份試驗)、第42天(RR 0.23,95% CI 0.14到0.39;298名參與者,1份試驗),以及第63天(RR 0.26,95% CI 0.09到0.77;501名參與者,2份試驗)。不同試驗顯示這項結果有類似的趨勢。使用較低劑量之artesunate的試驗,傾向組合artesunate加上mefloquine。整體來說,這些治療組之間副作用均類似。

作者結論

在瘧疾傳播程度較低的區域,對於治療無併發症的瘧原蟲瘧疾而言,將Artesunate加上mefloquine會比單獨使用mefloquine具有更好的療效。總劑量為每公斤25毫克的mefloquine,以及10毫克以上的artesunate,可以帶來更高的治癒率。如果研究方法與結果標準化作到更好,將可以對未來試驗的闡述有所幫助。

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

對於治療因為惡性瘧原蟲所引起的無併發症瘧疾而言,在具有低度瘧疾傳播的區域當中所測試過的Artesunate加上mefloquine可以比單獨使用mefloquine具有更好的效果。瘧疾是1種寄生蟲所造成的疾病,它會藉由蚊子來散布,而且奪去了全世界成千上萬人的性命。具有多重抗藥性的瘧疾已經很普遍了,而且在東南亞地區當中,對於幾近全部的單1療法型之抗瘧疾藥物而言,都有了很高的抗藥性。在此地,以及在其他瘧疾傳播程度並不高的區域當中,將artesunate與mefloquine組合起來,或許能夠成為1種有效的替代選項。本篇回顧中包含了8項試驗,而且大部分都是來自於東南亞,針對無併發症瘧疾的治療,這些試驗將artesunate加上mefloquine與單獨使用mefloquine進行了比較。對於消滅血液中的寄生蟲與減少高燒情況發生而言,Artesunate加上mefloquine可以比單獨使用mefloquine具有更好的效果。這2種治療方法的副作用是類似地。

Plain language summary

Artesunate plus mefloquine in areas with low malaria transmission performed better than mefloquine alone for uncomplicated P. falciparum malaria

Using a pilot system we have categorised this review as: “Historical question – no update intended: monotherapy no longer recommended" (see published notes).

Malaria is a parasitic disease spread by mosquitoes that kills thousands of people worldwide. Multiple-drug-resistant malaria is widespread, and in South-East Asia resistance is high against nearly all single therapy antimalarial drugs. Here, and in other areas with low malaria transmission, the combination of artesunate and mefloquine may provide an effective alternative. The review includes eight trials, mainly from South-East Asia, that compared artesunate plus mefloquine with mefloquine alone for treating uncomplicated malaria. Artesunate plus mefloquine performed better at destroying blood parasites and reducing fever. Adverse events were similar with both treatments.