Pudney M, Gray J S
Department of Molecular Sciences, Wellcome Foundation Limited, Beckenham, Kent, U.K.
J Parasitol. 1997 Apr;83(2):307-10.
This study demonstrates the activity of the hydroxynaphthoquinone (HNQ), atovaquone, against Babesia divergens, the cause of a rare but lethal form of human babesiosis. In vitro studies showed that unlike other anti-malarial drugs, the HNQs studied have a high level of anti-babesial activity and atovaquone was more active than imidocarb, the most effective compound used so far for human B. divergens babesiosis and also used routinely for the treatment of bovine babesiosis. Atovaquone also proved to be extremely active against B. divergens in gerbils (Meriones unguiculatus). Acute fulminating infections were effectively treated with as little as 1.0 mg/kg with increasing effectiveness up to 10 mg/kg, which compares well with the activity of imidocarb. Although immunosuppression with dexamethasone slowed the decline of parasitemias after treatment with atovaquone, gerbil survival was unaffected. Pretreatment of gerbils with 4 daily low doses of atovaquone did not have any effect on the development of subsequent infections. However, if treatment was continued after infection, daily doses as low as 0.5 mg/kg effectively suppressed the parasites.
本研究证明了羟基萘醌(HNQ)阿托伐醌对分歧巴贝斯虫的活性,分歧巴贝斯虫是一种罕见但致命的人类巴贝斯虫病的病原体。体外研究表明,与其他抗疟药物不同,所研究的羟基萘醌具有高水平的抗巴贝斯虫活性,且阿托伐醌比咪唑苯脲更具活性,咪唑苯脲是迄今为止用于治疗人类分歧巴贝斯虫病最有效的化合物,也常用于治疗牛巴贝斯虫病。阿托伐醌在沙鼠(长爪沙鼠)体内也被证明对分歧巴贝斯虫极具活性。急性暴发性感染用低至1.0毫克/千克的剂量即可有效治疗,剂量增至10毫克/千克时效果更佳,这与咪唑苯脲的活性相当。尽管用 dexamethasone 进行免疫抑制会减缓阿托伐醌治疗后寄生虫血症的下降,但沙鼠的存活率不受影响。用4天低剂量的阿托伐醌对沙鼠进行预处理对随后感染的发展没有任何影响。然而,如果在感染后继续治疗,低至0.5毫克/千克的每日剂量就能有效抑制寄生虫。