Olliaro P, Nevill C, LeBras J, Ringwald P, Mussano P, Garner P, Brasseur P
UNDP/World Bank/WHO Special Programme for Training and Research in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland.
Lancet. 1996 Nov 2;348(9036):1196-201. doi: 10.1016/S0140-6736(96)06217-4.
Opinion and policy over the use of amodiaquine for treating malaria vary. Amodiaquine is more palatable than chloroquine and may be more effective but serious adverse events have been reported in travellers taking it as prophylaxis. It is not recommended as first-line treatment. In the light of the global debate over the use of this drug, we conducted a systematic review of the effectiveness and tolerability of amodiaquine in the treatment of uncomplicated falciparum malaria.
This is a systematic review of published and unpublished randomised or pseudorandomised trials of amodiaquine. Observational reports were also systematically identified and reviewed to access evidence of serious adverse events.
40 trials met the inclusion criteria. Symptomatic patients were enrolled in 24 studies in comparisons of amodiaquine (n = 1071) with chloroquine (n = 1097). Amodiaquine was significantly more effective than chloroquine, with odds ratios and 99% confidence intervals (OR [99% CI]) of 4.29 (3.30-5.58) on day 7 and 6.00 (3.97-9.06) on day 14. Time to parasite clearance was significantly shorter with amodiaquine and fever clearance times were marginally faster. Eight studies compared amodiaquine with chloroquine in asymptomatic parasitaemia, with effects on parasitological outcomes similar to those for symptomatic malaria. At twelve sites, 692 amodiaquine and 679 sulfadoxine/pyrimethamine (S/P) recipients were enrolled. The two drugs did not differ significantly on day 7 (OR 0.74 [0.48-1.15]) but the odds ratios favoured S/P on day 14 (OR 0.51 [0.28-0.93]) and on day 28 (OR 0.30 [0.16-0.55]). The time to parasitological clearance was similar in the two groups; fever clearance times were significantly shorter with amodiaquine. Tolerability was assessed for both comparative and non-comparative trials. The rates of adverse events in controlled trials were 10.7%, 8.8%, and 14.3% with amodiaquine, chloroquine, and S/P, respectively. No life-threatening adverse events and no significant shifts in laboratory indices were reported.
This systematic review of published and unpublished trials supports the use of amodiaquine in the treatment of uncomplicated malaria. However, there is partial cross-resistance between chloroquine and amodiaquine, and monitoring of the effectiveness of this drug and surveillance for evidence of toxicity must continue.
关于使用阿莫地喹治疗疟疾的观点和政策各不相同。阿莫地喹比氯喹口感更好，可能更有效，但有报告称服用它作为预防药物的旅行者出现了严重不良事件。不建议将其作为一线治疗药物。鉴于全球对该药物使用的争论，我们对阿莫地喹治疗非复杂性恶性疟的有效性和耐受性进行了系统评价。
这是一项对已发表和未发表的阿莫地喹随机或伪随机试验的系统评价。还系统地识别和审查了观察性报告，以获取严重不良事件的证据。
40项试验符合纳入标准。在24项研究中，有症状的患者被纳入阿莫地喹（n = 1071）与氯喹（n = 1097）的比较研究。阿莫地喹比氯喹显著更有效，第7天的优势比和99%置信区间（OR [99% CI]）为4.29（3.30 - 5.58），第14天为6.00（3.97 - 9.06）。阿莫地喹使寄生虫清除时间显著缩短，发热清除时间略快。8项研究在无症状带虫者中比较了阿莫地喹与氯喹，对寄生虫学结果的影响与有症状疟疾相似。在12个地点，纳入了692名服用阿莫地喹和679名服用磺胺多辛/乙胺嘧啶（S/P）的受试者。两种药物在第7天无显著差异（OR 0.74 [0.48 - 1.15]），但在第14天（OR 0.51 [0.28 - 0.93]）和第28天（OR 0.30 [0.16 - 0.55]）优势比有利于S/P。两组的寄生虫学清除时间相似；阿莫地喹的发热清除时间显著更短。对比较性和非比较性试验的耐受性进行了评估。对照试验中，阿莫地喹、氯喹和S/P的不良事件发生率分别为10.7%、8.8%和14.3%。未报告危及生命的不良事件，实验室指标也无显著变化。
这项对已发表和未发表试验的系统评价支持使用阿莫地喹治疗非复杂性疟疾。然而，氯喹和阿莫地喹之间存在部分交叉耐药性，必须继续监测该药物的有效性并监测毒性证据。
