Tafenoquine Is a Promising Drug Candidate for the Treatment of Babesiosis
Tafenoquine Is a Promising Drug Candidate for the Treatment of Babesiosis
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DOI：
10.1128/aac.00204-21
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发表时间：
2021-07-01
影响因子：
4.9
通讯作者：
Xuan，Xuenan
中科院分区：
文献类型：
--
作者：
Liu，Mingming;Ji，Shengwei;Xuan，Xuenan
由于耐药性，常用的抗巴贝虫药物对巴贝虫病的疗效有限，并造成严重的副作用。他非诺喹（TAF）于2018年被美国食品和药物管理局批准用于根治间日疟原虫感染和预防疟疾。在此，我们评估了TAF治疗巴贝虫感染的有效性，并阐明了TAF抗巴贝虫的可能机制。以巴贝斯虫感染BALB/c和SCID小鼠的寄生虫血症和存活率为指标，探讨TAF治疗后免疫应答在巴贝斯虫感染中的作用。寄生虫血症、存活率、体重、生命体征、全血细胞计数和B的血液生化。用吉氏巴贝斯虫感染的脾切除犬，观察TAF的抗巴贝斯虫活性和毒副作用。然后，为了理解TAF活性的机制，使用过氧化氢作为短期B的氧化剂。采用B.通过逆转录-定量PCR（qRT-PCR）检测microti感染的小鼠。阿克特湾罗德海年湾给予TAF可迅速消除Gibsoni感染。仍然需要重复给予TAF或与其他抗菌药物联合治疗，以避免免疫功能低下宿主的潜在致命性复发。TAF治疗巴贝虫感染时应注意高钾血症。TAF具有杀巴贝斯作用，可能与药物诱导的氧化应激有关。考虑到与人类相比，动物中葡萄糖-6-磷酸脱氢酶缺乏症的发生率较低，迫切期望TAF用于感染巴贝虫的农场动物和宠物。
Due to drug resistance, commonly used anti-Babesiadrugs have limited efficacy against babesiosis and inflict severe side effects. Tafenoquine (TAF) was approved by the U.S. Food and Drug Administration in 2018 for the radical cure of Plasmodium vivax infection and for malaria prophylaxis. Here, we evaluated the efficacy of TAF for the treatment ofBabesiainfection and elucidated the suspected mechanisms of TAF activity againstBabesiaparasites. Parasitemia and survival rates of Babesia rodhaini-infected BALB/c and SCID mice were used to explore the role of the immune response inBabesiainfection after TAF treatment. Parasitemia, survival rates, body weight, vital signs, complete blood count, and blood biochemistry of B. gibsoni-infected splenectomized dogs were determined to evaluate the anti-Babesiaactivity and side effects of TAF. Then, to understand the mechanism of TAF activity, hydrogen peroxide was used as an oxidizer for short-term B. rodhaini incubationin vitro, and the expression levels of antioxidant enzymes were confirmed using B. microti-infected mice by reverse transcription-quantitative PCR (qRT-PCR). AcuteB. rodhainiandB. gibsoniinfections were rapidly eliminated with TAF administration. Repeated administration of TAF or a combination therapy with other antibabesial agents is still needed to avoid a potentially fatal recurrence for immunocompromised hosts. Caution about hyperkalemia should be taken during TAF treatment forBabesiainfection. TAF possesses a babesicidal effect that may be related to drug-induced oxidative stress. Considering the lower frequency of glucose-6-phosphate dehydrogenase deficiency in animals compared to that in humans, TAF use onBabesia-infected farm animals and pets is eagerly anticipated.