Bukirwa H, Orton L
Uganda Malaria Surveillance Project, Mulago Hospital Complex, Kampala, Uganda, PO BOX 24943.
Cochrane Database Syst Rev. 2005 Oct 19;2005(4):CD004531. doi: 10.1002/14651858.CD004531.pub2.
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.
To compare artesunate plus mefloquine with mefloquine alone for treating uncomplicated Plasmodium falciparum malaria.
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.
Randomized and quasi-randomized controlled trials comparing artesunate plus mefloquine with mefloquine alone for treating uncomplicated malaria.
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 relative risks (RR) and 95% confidence intervals (CI).
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.
多重耐药性疟疾广泛存在，在东南亚，几乎对所有单药治疗的抗疟药物耐药性都很高。在疟疾传播率低的此地及其他地区，青蒿琥酯与甲氟喹联合使用可能是一种有效的替代疗法。
比较青蒿琥酯加甲氟喹与单用甲氟喹治疗非复杂性恶性疟的疗效。
我们检索了Cochrane传染病组专业注册库（2005年5月）、Cochrane系统评价数据库（2005年第2期）、MEDLINE（1966年至2005年5月）、EMBASE（1988年至2005年5月）、LILACS（2005年5月）、BIOSIS（1985年至2005年6月）、会议论文集及参考文献列表。我们还联系了研究人员、组织和制药公司。
比较青蒿琥酯加甲氟喹与单用甲氟喹治疗非复杂性疟疾的随机和半随机对照试验。
两名作者独立应用纳入标准、提取数据并评估方法学质量。主要结局为第28天的治疗失败，定义为在第0天（治疗开始）至28天之间出现寄生虫血症证据，无论有无临床失败。对于二分数据，我们计算了相对危险度（RR）和95%置信区间（CI）。
八项涉及1996名参与者的试验符合纳入标准。所有试验均在疟疾传播率低的地区进行，七项在东南亚，一项在秘鲁亚马逊地区。各试验中青蒿琥酯和甲氟喹的剂量及给药方案各不相同。使用25mg/kg甲氟喹和10mg青蒿琥酯总剂量的试验在所有时间点报告联合用药的治疗失败情况较少：第28天（RR 0.17，95%CI 0.06至0.47；824名参与者，4项试验）、第42天（RR 0.23，95%CI 0.14至0.39；298名参与者，1项试验）和第63天（RR 0.26，95%CI 0.09至0.77；501名参与者，2项试验）。寄生虫血症结果显示出类似趋势。使用较低剂量青蒿琥酯的试验倾向于支持青蒿琥酯加甲氟喹联合用药。总体而言，各治疗组的不良事件相似。
在疟疾传播率低的地区，青蒿琥酯加甲氟喹治疗非复杂性恶性疟的效果优于单用甲氟喹。25mg/kg甲氟喹和至少10mg青蒿琥酯的总剂量可提高治愈率。更好地报告方法和统一结局标准将有助于未来试验的解读。
