Efficacy of atovaquone against Babesia gibsoni in vivo and in vitro

Efficacy of atovaquone against Babesia gibsoni in vivo and in vitro
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DOI:
10.1016/j.vetpar.2004.07.005
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发表时间:
2004-09-20
影响因子:
2.6
通讯作者:
Higuchi, S
Higuchi, S
中科院分区:
农林科学2区
文献类型:
--
作者:
Matsuu, A;Koshida, Y;Higuchi, S

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在日本青森县实验性感染吉氏巴贝斯虫的三只狗中,研究了阿托伐醌对吉氏巴贝斯虫的治疗效果,这些狗是从日本青森县自然感染的狗中分离出来的。一旦出现寄生虫血症。达到 10% 时,口服阿托伐醌(30 mg/kg,每天两次,持续 7 天)。阿托伐醌治疗后 2 天内,寄生虫从血涂片中消失,且没有任何临床副作用。所有狗的贫血和血小板减少症均得到显着改善。然而,聚合酶链反应检测显示,在阿托伐醌治疗后,外周血中间歇性存在吉布氏拟杆菌标记基因,表明该生物体尚未被消除,并且在最后一次治疗后33天,寄生虫在血涂片中重新出现。为了研究对阿托伐醌敏感性的变化,使用从感染原始寄生虫分离株的未治疗狗以及两只实验感染和阿托伐醌治疗的动物获得的外周血进行体外敏感性测试(血液在治疗后吉布氏杆菌感染复发时采集)。将阿托伐醌添加至培养基中,终浓度为 0.1、1、10、100 和 1000 nM。对于未经处理的寄生虫,在 1000 nM 阿托伐醌下发生完全生长抑制,而在该浓度下孵育 48 小时后,复发寄生虫仅受到 39.52 +/- 18.34% 和 31.31 +/- 8.14% 的抑制。
The therapeutic efficacy of atovaquone against Babesia gibsoni was examined in three dogs experimentally infected with B. gibsoni isolated from naturally infected dogs in Aomori Prefecture, Japan. Once parasitemia. reached 10%, atovaquone was administered orally (30 mg/kg twice daily for 7 days). Within 2 days of atovaquone treatment, the parasite disappeared from blood smears without any clinical side effects. Anemia and thrombocytopenia were significantly improved in all the dogs. However, a polymerase chain reaction assay revealed that a B. gibsoni marker gene was intermittently present in peripheral blood after atovaquone therapy, indicating that the organism had not been eliminated, and parasites reappeared in blood smears 33 days after the last treatment. To investigate the change in sensitivity against atovaquone, an in vitro sensitivity test was performed using peripheral blood obtained from an untreated dog that was infected with the original parasite isolate, and from two of the experimentally infected and atovaquone-treated animals (blood was collected at the time of the post-treatment recurrence of the B. gibsoni infection). Atovaquone was added to the culture medium to final concentrations of 0.1, 1, 10, 100, and 1000 nM. For the untreated parasites, complete growth inhibition occurred at 1000 nM of atovaquone, whereas the recurrent parasites were inhibited by only 39.52 +/- 18.34% and 31.31 +/- 8.14% at this concentration after 48 h of incubation.