A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania
A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania
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DOI：
10.1016/s0035-9203(01)90207-x
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发表时间：
2001-07-01
影响因子：
2.2
通讯作者：
Curtis, CF
中科院分区：
文献类型：
--
作者：
Mutabingwa, TK;Maxwell, CA;Curtis, CF
据报告，坦桑尼亚东北部的恶性疟原虫对磺胺嘧啶-乙胺嘧啶（SP）有相当程度的抗药性，目前的一个高度优先事项是确定一种合适的抗疟药来取代SP。我们于2000年7月进行了一项试验，以确定氯胍（PG）加氨苯砜（DS）与SP治疗无症状恶性疟原虫感染的疗效。共有220名寄生虫血症大于或等于2000/穆尔的儿童完成了研究; 112名儿童接受了SP单次给药（根据乙胺嘧啶1.25 mg/kg和磺胺嘧啶25 mg/kg计算的剂量），108名儿童每天服用PG 10 mg/kg和DS 2.5 mg/kg，持续3天。第7天，SP的无性寄生虫清除率为14.3%，而PG-DS为93.5%。SP的显著高失败率与dhfr基因164位亮氨酸取代的发生无关。两种治疗方案均耐受良好。与另一种抗叶酸剂组合氯丙胍-氨苯砜（“Lapdap”）的现有数据相比，PG-DS在实现寄生虫清除方面略差但显著差（99.5%对93.5%）。对于体重18 kg的儿童，PG-DS治疗3天疗程的估计费用为0.15美元。随着抗SP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、负担得起和已经可用的治疗替代品，至少在氯丙胍胺-氨苯砜注册之前。
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 greater than or equal to 2000 per muL 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.