Atovaquone-proguanil for treating uncomplicated malaria

  • Review
  • Intervention

Authors


Abstract

Background

Many conventional treatments for uncomplicated malaria are failing because malaria parasites develop resistance to them. One way to combat this resistance is to treat people with a combination of drugs, such as atovaquone-proguanil.

Objectives

To compare atovaquone-proguanil with other antimalarial drugs (alone or in combination) for treating children and adults with uncomplicated Plasmodium falciparum malaria.

Search methods

We searched the Cochrane Infectious Diseases Group Specialized Register (June 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), LILACS (1982 to June 2005), reference lists, and conference abstracts. We also contacted relevant pharmaceutical manufacturers and researchers.

Selection criteria

Randomized controlled trials comparing atovaquone-proguanil with other antimalarial drugs for treating children and adults confirmed to have uncomplicated P. falciparum malaria.

Data collection and analysis

Three authors independently assessed trial eligibility and the risk of bias in the trials, and extracted data for an intention-to-treat analysis (where possible). We used risk ratio (RR) and 95% confidence intervals (CI) for dichotomous data. We contacted trial authors for additional information where needed.

Main results

Ten trials, with a total of 2345 participants, met the inclusion criteria. The trials were conducted in four geographical regions and were often small, but they included comparisons across eight drugs. Nine trials were funded by a pharmaceutical company, only three carried out an intention-to-treat analysis, and allocation concealment was unclear in seven. Atovaquone-proguanil had fewer treatment failures by day 28 than chloroquine (RR 0.04, 95% CI 0.00 to 0.57; 27 participants, 1 trial), amodiaquine (RR 0.22, 95% CI 0.13 to 0.36; 342 participants, 2 trials), and mefloquine (RR 0.04, 95% CI 0.00 to 0.73; 158 participants, 1 trial). There were insufficient data to draw a conclusion for this outcome from comparisons with sulfadoxine-pyrimethamine (172 participants, 2 trials), halofantrine (205 participants, 1 trial), artesunate plus mefloquine (1063 participants, 1 trial), quinine plus tetracycline (154 participants, 1 trial), and dihydroartemisinin-piperaquine-trimethoprim-primaquine (161 participants, 1 trial). Adverse events were mainly common symptoms of malaria and did not differ in frequency between groups.

Authors' conclusions

Data are limited but appear to suggest that atovaquone-proguanil is more effective than chloroquine, amodiaquine, and mefloquine. There are insufficient data for comparisons against sulfadoxine-pyrimethamine, halofantrine, artesunate plus mefloquine, quinine plus tetracycline, and dihydroartemisinin-piperaquine-trimethoprim-primaquine in treating malaria. There are not enough data to assess safety, but a number of adverse events were identified with all drugs. Large trials comparing atovaquone-proguanil with other new combination therapies are needed.

摘要

背景

以Atovaquoneproguanil治療無併發症之瘧疾

對於無併發症的瘧疾而言,有很多傳統的治療方法都失敗了,因為瘧疾的寄生蟲會對它們產生抗藥性。對抗抗藥性的方法之一就是使用組合式藥物,例如atovaquoneproguanil。

目標

比較以atovaquoneproguanil與其他抗瘧疾藥物(單獨使用或是採取合併型式)對於治療兒童與成年人無併發症之惡性瘧原蟲瘧疾。

搜尋策略

我們搜尋Cochrane Infectious Diseases Group Specialized Register (2005年6月)、 CENTRAL (Cochrane Library Issue 2, 2005)、MEDLINE (1966年−2005年6月)、 EMBASE (1980年 – 2005年6月)、 LILACS (1982年−2005年6月)、 參考資料清單,以及研討會摘要。我們也與本領域相關藥廠以及研究人員聯絡。

選擇標準

比較atovaquoneproguanil與其他的抗瘧疾藥物治療兒童與成年人經確認患無併發症之惡性瘧原蟲瘧疾的隨機對照試驗。

資料收集與分析

有3位作者獨立地評估了試驗的合格度以及方法面的品質,並擷取出資料及儘可能的做意圖性治療的分析。針對二元性的資料,我們使用了相對風險(RR)與95%信賴區間(CI)。在有必要的時候,我們為了更多的資訊而與試驗的作者們取得過聯繫。

主要結論

共有包含總數為2345名參與者的10項試驗符合了收集的標準。這些試驗是在4個地理區域當中所完成的,而且通常都是小型的,但是它們收集了跨越8種藥物之間的比較。有1家藥廠贊助了其中的9項試驗,只有3項試驗完成了某種意圖性治療的分析,至於在7份試驗當中,分配工作的隱藏狀況都是不清楚的。直到第28天之前,Atovaquoneproguanil的治療失敗情形比chloroquine(RR 0.04,95% CI 0.00到0.57;27名參與者,1項試驗)、 amodiaquine(RR 0.22,95% CI 0.13到0.36;342名參與者,2項試驗),以及mefloquine(RR 0.04,95% CI 0.00 到0.73;158 名參與者,1項試驗)都還要少。在跟sulfadoxinepyrimethamine(172名參與者,2項試驗)、 halofantrine(205名參與者,1項試驗)、artesunate加上mefloquine(1063名參與者,1項試驗)、quinine加上tetracycline(154名參與者,1項試驗),以及dihydroartemisininpiperaquinetrimethoprimprimaquine(161名參與者,1項試驗)等項目所進行的比較當中,並沒有充分的資料能夠針對這樣的結果歸納出任何結論。當中的不良事件大部分都是常見瘧疾的症狀,而且在各個組別之間,這些事件的發生頻率也沒有什麼不同。

作者結論

資料雖然是有限的,但是看起來卻可以認定 atovaquoneproguanil會比chloroquine、amodiaquine,以及mefloquine更為有效。對於治療瘧疾而言,關於與sulfadoxinepyrimethamine、halofantrine、artesunate加上mefloquine、quinine加上tetracycline,以及dihydroartemisininpiperaquinetrimethoprimprimaquine之間的比較,並沒有充足的資料。並沒有足夠的資料可以評估安全性,但是在使用所有的這些藥物時,的確發生了很多不良事件。還需要有大型的試驗來將atovaquoneproguanil與其他種新式的組合型療法進行比較。

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

對於治療無併發症的瘧疾而言,Atovaquoneproguanil看起來會比個別的藥物更有效,但是只有少數的資料曾經將atovaquoneproguanil與其他的組合型療法進行過比較。對於無併發症的瘧疾而言,許多傳統的治療方法都失敗了,因為瘧疾的寄生蟲會對它們產生抗藥性。若是以atovaquoneproguanil之類的組合型藥物來治療的話,就可以減少這樣的狀況。本篇回顧發現了10項試驗,大多數在方法面的品質都不高,而且大多數都是由某1家單獨的藥廠所贊助的。除此之外,這些試驗都是小型的,而且其中的參與者都不多,因此,若是想要減少血液當中的惡性瘧原蟲瘧疾之寄生蟲,雖然證據認為atovaquoneproguanil會比很多種單1藥物治療來得更有效,但是這些證據都是有限地。只有少數具有良好品質的資料曾經將atovaquoneproguanil與其他新式的組合型療法進行過比較。並沒有足夠的資料可以評估不良的事件,但是所有的試驗都曾經記錄過某些不良的事件。

Plain language summary

Atovaquone-proguanil appears to be more effective than individual drugs for treating uncomplicated malaria, but there are few data comparing atovaquone-proguanil to other combination therapies

Many conventional treatments for uncomplicated malaria are failing because malaria parasites develop resistance to them. This can be reduced by treating people with combination drugs such as atovaquone-proguanil. The review found 10 trials, most of low methodological quality and most funded by a single pharmaceutical company. In addition, trials were small and had few participants thus evidence suggesting atovaquone-proguanil as more effective than a number of single drug treatments at eliminating the Plasmodium falciparum malaria parasite from the blood was limited. There were few good quality data comparing atovaquone-proguanil with other new combination therapies. There were not enough data to assess adverse events, but all trials recorded some adverse events.