Development of an effective alternative model for in vivo hypnozoite-induced relapse infections: a Japanese macaque (Macaca fuscata) model experimentally infected with Plasmodium cynomolgi
Development of an effective alternative model for in vivo hypnozoite-induced relapse infections: a Japanese macaque (Macaca fuscata) model experimentally infected with Plasmodium cynomolgi
复制标题
开发体内催眠体诱导的复发感染的有效替代模型：实验性感染食蟹猴疟原虫的日本猕猴（Macaca fuscata）模型
DOI：
10.1016/j.parint.2020.102096
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发表时间：
2020
影响因子：
1.9
通讯作者：
Chigusa Y.
中科院分区：
文献类型：
--
作者：
Kawai S;Annoura T;Araki T;Shiogama Y;Shogo S;Sato MO;Kaneko O;Yasutomi Y;Chigusa Y.
在本研究中，我们证明，日本猕猴（Macaca fuscata）可以作为一个有效的替代在vivomodel研究催眠虫诱导的复发感染引起的食蟹猴疟原虫B株，该模型是可比的恒河猴模型。实验使用两只雌性日本猕猴（JM-1和JM-2; 5岁;体重约4.0 kg）。为了在蚊子体内产生子孢子，血液感染了P。从供体猴JM-1收集食蟹猴B菌株，并使用标准人工膜饲养方法饲养约200只蚊子。将分离的子孢子（2 × 105个）经静脉接种JM-2猴，于感染后第8天检测血吸虫期。从第12天开始，将硫酸氯喹（CQ）以6.0 mg/kg的剂量肌肉注射到JM-2猴体内，连续6天，之后寄生虫从外周血中消失。第一次复发发生在第26天，再次用CQ治疗。然后，第二次复发发生在第44天，其通过CQ治疗治愈，随后以1.0 mg/kg/天的剂量给予磷酸伯氨喹（PQ）15天。观察JM-2猴直至PQ给药后69天，在整个随访期间未复发。我们建议日本猕猴模型不仅有助于抗催眠虫活性的药物筛选，而且还可以用作研究催眠虫生物学的有力工具。
In the present study, we demonstrate that the Japanese macaque (Macaca fuscata) can be used as an effective alternativein vivomodel for investigating hypnozoite-induced relapsing infection caused byPlasmodium cynomolgiB strain, and that this model is comparable to the rhesus macaque model. Two female Japanese macaques (JM-1 and JM-2; aged 5 years; weighing about 4.0 kg) were used for the experiment. To produce sporozoites in mosquitoes, blood infected withP. cynomolgiB strain was collected from the donor monkey JM-1 and fed to approximately 200 mosquitoes using the standard artificial membrane feeding method. The isolated sporozoites (2 × 105) were intravenously inoculated into the JM-2 monkey, and the blood stage of the parasite was detected on day 8 after the infection. Chloroquine sulfate (CQ) was intramuscularly administered at a dosage of 6.0 mg/kg into the JM-2 monkey for 6 consecutive days from day 12 onward, after which the parasites disappeared from the peripheral blood. The first relapse occurred on day 26, which was treated again with CQ. Then, the second relapse occurred on day 44, which was cured by CQ treatment followed by the administration of primaquine phosphate (PQ) at a dosage of 1.0 mg/kg/day for 15 days. The JM-2 monkey was observed until 69 days after PQ administration, and there was no relapse during the entire follow-up period. We propose that the Japanese macaque model could contribute not only to drug screening for anti-hypnozoite activity, but could also be used as a powerful tool for investigating hypnozoite biology.