Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have been reported in Plasmodium falciparum in north-eastern Tanzania, and the identification of a suitable antimalarial to replace SP is now a high priority. We conducted a trial in July 2000 to determine the efficacy of proguanil (PG) plus dapsone (DS), compared with that of SP, for the treatment of asymptomatic falciparum infection. A total of 220 children with parasitaemia > or = 2000 per microL completed the study; 112 had received a single dose of SP (dosage calculated for pyrimethamine 1.25 mg/kg and sulfadoxine 25 mg/kg) and 108 had taken PG 10 mg/kg with DS 2.5 mg/kg each day for 3 days. Clearance of asexual parasites at day 7 was 14.3% with SP, but 93.5% with PG-DS. The remarkably high failure rate with SP was not associated with occurrence of leucine substitution at position 164 of the dhfr gene. Both treatment regimens were well tolerated. Compared with available data on another antifolate combination, chlorproguanil-dapsone ('Lapdap'), PG-DS was slightly but significantly inferior in achieving parasite clearance (99.5% versus 93.5%). The estimated cost of a 3-day course of PG-DS treatment for a child weighing 18 kg is US $0.15. With the rising incidence of SP-resistant P. falciparum infection, PG-DS could provide an effective, affordable and already available therapeutic alternative for malaria in East Africa at least until chlorproguanil-dapsone is registered.

译文

据报道,在坦桑尼亚东北部的恶性疟原虫中,对磺胺多辛-乙胺嘧啶 (SP) 的耐药性相当高,现在确定合适的抗疟药来替代SP是当务之急。我们2000年7月进行了一项试验,以确定与SP相比,丙胍 (PG) 加氨苯砜 (DS) 治疗无症状恶性疟原虫感染的疗效。共有220名寄生虫血症> 或 = 2000名儿童完成了研究; 112接受了单剂量的SP (对于乙胺嘧啶1.25 mg/kg和磺胺多辛25 mg/kg计算的剂量),108每天服用PG 10 mg/kg和DS 2.5 mg/kg,持续3天。在第7天,无性寄生虫的清除用SP 14.3%,但用PG-DS 93.5%。SP极高的失败率与dhfr基因164位亮氨酸取代的发生无关。两种治疗方案均具有良好的耐受性。与另一种抗叶酸药物组合氯丙胍-氨苯砜 ('Lapdap') 的可用数据相比,PG-DS在获得寄生虫清除方面略有下降,但明显逊色 (99.5% 比93.5%)。对于体重18千克的儿童,为期3天的PG-DS治疗的估计费用为0.15美元。随着抗SP的恶性疟原虫感染发病率的上升,PG-DS可以为东非的疟疾提供一种有效,负担得起且已经可用的治疗替代品,至少直到氯丙胍-氨苯砜注册为止。

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