Adjuik M, Babiker A, Garner P, Olliaro P, Taylor W, White N
Lancet. 2004 Jan 3;363(9402):9-17. doi: 10.1016/s0140-6736(03)15162-8.
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.
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.
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.
The addition of 3 days of artesunate to standard antimalarial treatments substantially reduce treatment failure, recrudescence, and gametocyte carriage.
在现有的疟疾治疗方案中添加青蒿素衍生物可降低治疗失败率和传播可能性。我们从随机对照试验中评估了这一假设的证据。
我们对16项随机试验（n = 5948）中个体患者的数据进行了荟萃分析，这些试验研究了在恶性疟原虫疟疾标准治疗中添加青蒿琥酯的效果。我们估计了第14天和第28天寄生虫学失败的比值比（OR）（青蒿琥酯联合用药与标准治疗相比），并使用标准方法计算了各试验的合并汇总OR。
对于所有合并的试验，第14天使用3天青蒿琥酯时寄生虫学失败率较低（OR 0.20，95%CI 0.17 - 0.25，n = 4504），第28天（不包括新感染，0.23，0.19 - 0.28，n = 2908；包括再感染，0.30，0.26 - 0.35，n = 4332）。青蒿琥酯使寄生虫清除明显更快（率比1.98，95%CI 1.85 - 2.12，n = 3517）。在基线时无配子体的参与者中，青蒿琥酯在第7天降低了配子体计数（OR 0.11，95%CI 0.09 - 0.15，n = 2734）,在第14天和第28天效果更大。添加1天青蒿琥酯（六项试验）与第14天（0.61，0.48 - 0.77，n = 1980）和第28天（调整后排除新感染0.68，0.53 - 0.89，n = 1205；未调整包括再感染0.77，0.63 - 0.95，n = 1958）的失败率降低有关。在这些试验中，第7天配子体减少（在基线时无配子体的参与者中0.
