Amodiaquine alone, amodiaquine plus sulfadoxine-pyrimethamine, amodiaquine plus artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial
Amodiaquine alone, amodiaquine plus sulfadoxine-pyrimethamine, amodiaquine plus artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial
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DOI：
10.1016/s0140-6736(05)66417-3
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发表时间：
2005-04-23
期刊：
影响因子：
168.9
通讯作者：
Whitty, CJM
中科院分区：
文献类型：
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作者：
Mutabingwa, TK;Anthony, D;Whitty, CJM
背景 由于耐药性增加，许多非洲国家正在考虑改变恶性疟疾的联合治疗。然而，这些组合的有效性数据很少。我们的目的是研究已在东非证明有效的三种药物组合与阿莫地喹单药疗法相比的有效性。方法我们在坦桑尼亚穆赫扎（该地区对磺胺多辛-乙胺嘧啶和氯喹耐药率很高的地区）对患有单纯性疟疾的儿童（4-59 个月）进行了抗疟药物组合的随机试验。儿童被随机分配接受 3 天的阿莫地喹 (n=270)、阿莫地喹 + 磺胺多辛-乙胺嘧啶 (n=507) 或阿莫地喹 + 青蒿琥酯 (n=515)，或为期 3 天的六剂蒿甲醚-本芴醇治疗方案 (n=519)。药物是在家里口服的，医务人员没有观察到。主要终点是第 14 天时对治疗分配进行盲法评估的寄生虫学失败。次要终点包括第 28 天的随访和配子体携带。按意向治疗进行分析。结果 在筛选的 3158 名儿童中，1811 名被随机分配治疗，1717 名（95%）达到了 14 天的随访。阿莫地喹组被数据和安全监测委员会提前叫停。到第14天，阿莫地喹的寄生虫学失败率为248例中的103例（42%），阿莫地喹+磺胺多辛-乙胺嘧啶的476例中有97例（20%），阿莫地喹+青蒿酯的491例中有54例（11%），蒿甲醚-本芴醇的502例中有7例（1%）。到第 28 天，寄生虫学失败率分别为 239 例中的 182 例（76%）、476 例中的 282 例（61%）、472 例中的 193 例（40%）和 485 例中的 103 例（21%）。各个治疗组和次佳治疗组合之间的差异显着 (p
Background Many countries in Africa are considering a change to combination treatment for falciparum malaria because of the increase in drug resistance. However, there are few effectiveness data for these combinations. Our aim was to study the effectiveness of three drug combinations that have proven efficacious in east Africa compared with amodiaquine monotherapy.Methods We undertook a randomised trial of antimalarial drug combinations for children (aged 4-59 months) with uncomplicated malaria in Muheza, Tanzania, an area with a high prevalence of resistance to sulfadoxine-pyrimethamine and chloroquine. Children were randomly allocated 3 days of amodiaquine (n=270), amodiaquine +sulfadoxine-pyrimethamine (n=507), or amodiaquine+artesunate (n=515), or a 3-day six-dose regimen of artemether-lumefantrine (n=519). Drugs were taken orally, at home, unobserved by medical staff. The primary endpoint was parasitological failure by day 14 assessed blind to treatment allocation. Secondary endpoints included day 28 follow-up and gametocyte carriage. Analysis was by intention to treat.Findings Of 3158 children screened, 1811 were randomly assigned treatment and 1717 (95%) reached the 14-day follow-up. The amodiaquine group was stopped early by the data and safety monitoring board. By day 14, the parasitological failure rates were 103 of 248 (42%) for amodiaquine, 97 of 476 (20%) for amodiaquine+sulfadoxine-pyrimethamine, 54 of 491 (11%) for amodiaquine+artesunate, and seven of 502 (1%) for artemether-lumefantrine. By day 28, the parasitological failure rates were 182 of 239 (76%), 282 of 476 (61%), 193 of 472 (40%), and 103 of 485 (21%), respectively. The difference between individual treatment groups and the next best treatment combination was significant (p