Chemoprophylaxis and intermittent treatment for preventing malaria in children

 

Abstract

Background

Malaria causes repeated illness in children living in endemic areas. Policies of giving antimalarial drugs at regular intervals (prophylaxis or intermittent treatment) are being considered for preschool children.

Objectives

To evaluate prophylaxis and intermittent treatment with antimalarial drugs to prevent malaria in young children living in malaria-endemic areas.

Search methods

We searched the Cochrane Infectious Diseases Group Specialized Register (August 2007), CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (1966 to August 2007), EMBASE (1974 to August 2007), LILACS (1982 to August 2007), mRCT (February 2007), and reference lists of identified trials. We also contacted researchers.

Selection criteria

Individually randomized and cluster-randomized controlled trials comparing antimalarial drugs given at regular intervals (prophylaxis or intermittent treatment) with placebo or no drug in children aged one month to six years or less living in a malaria-endemic area.

Data collection and analysis

Two authors independently extracted data and assessed the risk of bias in the trials. We used risk ratio (RR) or mean difference with 95% confidence intervals (CI) for meta-analyses. Where we detected heterogeneity and considered it appropriate to combine the trials, we used the random-effects model (REM).

Main results

Twenty-one trials (19,394 participants), including six cluster-randomized trials, met the inclusion criteria. Prophylaxis or intermittent treatment with antimalarial drugs resulted in fewer clinical malaria episodes (RR 0.53, 95% CI 0.38 to 0.74, REM; 7037 participants, 10 trials), less severe anaemia (RR 0.70, 95% CI 0.52 to 0.94, REM; 5445 participants, 9 trials), and fewer hospital admissions for any cause (RR 0.64, 95% CI 0.49 to 0.82; 3722 participants, 5 trials). We did not detect a difference in the number of deaths from any cause (RR 0.90, 95% CI 0.65 to 1.23; 7369 participants, 10 trials), but the CI do not exclude a potentially important difference. One trial reported three serious adverse events with no statistically significant difference between study groups (1070 participants). Eight trials measured morbidity and mortality six months to two years after stopping regular antimalarial drugs; overall, there was no statistically significant difference, but participant numbers were small.

Authors' conclusions

Prophylaxis and intermittent treatment with antimalarial drugs reduce clinical malaria and severe anaemia in preschool children.

 

Plain language summary

Preschool children taking antimalarial drugs regularly are less likely to get malaria or severe anaemia, but more trials are needed to show whether survival is improved

Most children in areas where malaria is endemic are semi-immune against serious malaria by the age of seven, but for children under five the disease can be serious, and a million worldwide die each year from malaria. The review of 21 trials found that children taking regular antimalarial prophylaxis or intermittent treatment were less likely to get malaria, severe anaemia, or be admitted to hospital, but there was no change in the overall death rate. The benefits are similar in intermittent treatment of infants and prolonged prophylaxis, but long-term deleterious effects, including the possibility that it may interfere with the development of children's immunity to malaria, are unknown for either regimen. Further trials with long-term follow up are needed.

 

摘要

背景

化學性預防及間歇性治療對於兒童防止瘧疾的效果

瘧疾會導致居住在風土病地區的兒童反覆發病。對於學齡前兒童定期(預防或間歇性治療)給予抗瘧疾藥物是可以納入考慮的政策。

目標

評估使用抗瘧藥物做為化學性預防以及間歇性治療，對居住在瘧疾流行地區的幼童罹患瘧疾的預防效果。

搜尋策略

我們搜尋了the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), 以及所找到試驗的文章中的參考文獻。也與研究學者聯繫。

選擇標準

以隨機及準隨機對照臨床試驗，對象是1個月大到6歲的兒童，或是較少住在瘧疾流行區者，比較規律時間間隔(預防或是間歇性治療)投予抗瘧藥物及安慰劑或不給藥物。

資料收集與分析

我們獨立擷取數據及評估方法學質量。使用相對風險(relative risk, RR)或是具95%信任區間(confidence intervals, CI)的加權平均差(weighted mean difference)做整合性分析(metaanalyses)。其中我們檢測到異質性，但認為其合適用來結合所有的試驗，我們使用了隨機效應模式(randomeffects model, REM)。

主要結論

19個試驗(14,393個受試者)符合納入條件。接受抗瘧藥作預防或是間歇性治療的兒童有較少的臨床瘧疾事件發生(RR 0.52, 95% CI 0.35 to 0.77, REM; 4051個受試者，8個試驗)，且嚴重貧血較不常發生(RR 0.54, 95% CI 0.42 to 0.68; 2727個受試者，8個試驗)。 未偵測到死亡數有差異性，無論其死亡原因為何(RR 0.82, 95% CI 0.65 to 1.04; 7929個受試者，9個試驗)，但是信任區間(confidence intervals)顯示無法排除潛在的重大差異。無任何試驗報告有嚴重的不良事件。有3個試驗測量停止規律使用抗瘧藥後6個月至2年內之罹病率及死亡率；整體來說，並無統計上的差異，但是受試者的樣本數過小。

作者結論

使用抗瘧藥物預防及間歇性治療減少了學齡前幼童的瘧疾及嚴重貧血的發生。但並無足夠證據可看出在死亡率上的效果。

翻譯人

本摘要由三軍總醫院洪乃勻翻譯。

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

總結

學齡前的幼童定期使用抗瘧藥物似乎較少得到瘧疾或是嚴重的貧血，但需要更多試驗來證明是否能改善存活率。住在瘧疾區的兒童到7歲時，對於嚴重瘧疾大部分是半免疫的，但對5歲以下的兒童來說，一旦罹患瘧疾會很嚴重。全世界每年有一百萬人死於瘧疾。這些試驗回顧發現規律使用抗瘧藥物作預防或間歇性治療的幼童似乎比較不會得到瘧疾、嚴重貧血、或住院，但整體死亡率則無改變。在嬰兒期的間歇性治療與延長預防的效益相似，但長期使用的危害，例如幼童對於瘧疾產生免疫力上的可能干擾，在所有的療程上都還不清楚，這部分有賴更多試驗的長期追蹤。