Artesunate combinations for treatment of malaria:: meta-analysis
Artesunate combinations for treatment of malaria:: meta-analysis
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DOI：
10.1016/s0140-6736(03)15162-8
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发表时间：
2004-01-03
期刊：
影响因子：
168.9
通讯作者：
White, N
中科院分区：
文献类型：
--
作者：
Adjuik, M;Agnamey, P;White, N
背景在现有的疟疾药物方案中加入青蒿素衍生物可以减少治疗失败和传播潜力。我们从随机对照试验中评估了这一假设的证据。方法我们对来自16个随机试验(n=5948)的单个患者的数据进行了荟萃分析，这些试验研究了在标准治疗恶性疟疾的基础上加入青蒿琥酯的效果。我们估计了第14天和第28天(青蒿琥酯联合治疗与标准治疗相比)寄生虫性失败的优势比(OR)，并使用标准方法计算了合并的汇总OR。所有试验合并后，第14天(OR 0.20，95%CI 0.17-0.25，n=4504)和第28天(排除新感染，0.23，0.19-0.28，n=2908；包括再感染，0.30，0.26-0.35，n=4332)寄生虫性失败的发生率较低。青蒿琥酯治疗后寄生虫清除明显加快(Ratio Ratio 1.98，95%CI 1.85~2.12，n=3517)。在基线没有配子细胞的参与者中，青蒿琥酯在第7天减少了配子细胞数量(OR 0.11，95%CI 0.09-0.15，n=2734)，在第14天和第28天的影响更大。加入青蒿琥酯1d(6次试验)与第14天(0.61，0.48-0.77，n=1980)和第28天(调整为排除新感染0.68，0.53-0.89，n=1205；未调整包括再感染0.77，0.63-0.95，n=1958)的失败相关。在这些试验中，配子体在第7天减少(在基线为0.11，0.09-0.15的参与者中，n=2734)。青蒿琥酯和安慰剂的严重不良事件的发生率没有显著差异。解释说，在标准抗疟疾治疗的基础上增加3天的青蒿琥酯，大大减少了治疗失败、复发和配子体携带。
Background Addition of artemisinin derivatives to existing drug regimens for malaria could reduce treatment failure and transmission potential. We assessed the evidence for this hypothesis from randomised controlled trials.Methods We undertook a meta-analysis of individual patients' data from 16 randomised trials (n=5948) that studied the effects of the addition of artesunate to standard treatment of Plasmodium falciparum malaria. We estimated odds ratios (OR) of parasitological failure at days 14 and 28 (artesunate combination compared with standard treatment) and calculated combined summary ORs across trials using standard methods.Findings For all trials combined, parasitological failure was lower with 3 days of artesunate at day 14 (OR 0.20, 95% CI 0.17-0.25, n=4504) and at day 28 (excluding new infections, 0.23, 0.19-0.28, n=2908; including re-infections, 0.30, 0.26-0.35, n=4332). Parasite clearance was significantly faster (rate ratio 1.98, 95% CI 1.85-2.12, n=3517) with artesunate. In participants with no gametocytes at baseline, artesunate reduced gametocyte count on day 7 (OR 0.11, 95% CI 0.09-0.15, n=2734), with larger effects at days 14 and 28. Adding artesunate for 1 day (six trials) was associated with fewer failures by day 14 (0.61, 0.48-0.77, n=1980) and day 28 (adjusted to exclude new infections 0.68, 0.53-0.89, n=1205; unadjusted including reinfections 0.77, 0.63-0.95, n=1958). In these trials, gametocytes were reduced by day 7 (in participants with no gametocytes at baseline 0.11, 0.09-0.15, n=2734). The occurrence of serious adverse events did not differ significantly between artesunate and placebo.Interpretation The addition of 3 days of artesunate to standard antimalarial treatments substantially reduce treatment failure, recrudescence, and gametocyte carriage.