In the present study, we demonstrate that the Japanese macaque (Macaca fuscata) can be used as an effective alternative in vivo model for investigating hypnozoite-induced relapsing infection caused by Plasmodium cynomolgi B 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 with P. cynomolgi B 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.

在本研究中，我们证明了日本猕猴（Macaca fuscata）可以用作调查由食蟹猕猴B株引起的次殖子诱发的复发性感染的有效替代体内模型，并且该模型与恒河猴模型相当。实验使用了两只雌性日本猕猴（JM-1和JM-2；年龄5岁；重约4.0千克）。为了在蚊子中产生子孢子，从供体猴JM-1收集被食蟹猕猴B株感染的血液，并使用标准的人工膜喂养方法喂养大约200只蚊子。分离的子孢子（2×10 ⁵）静脉内接种到JM-2猴子中，并在感染后第8天检测到该寄生虫的血液阶段。从第12天起连续6天以6.0 mg / kg的剂量肌内注射硫酸氯喹（CQ），该寄生虫从外周血中消失。第一次复发发生在第26天，再次接受CQ治疗。然后，第二次复发发生在第44天，通过CQ治疗治愈，然后以1.0 mg / kg / day的剂量施用磷酸伯氨喹（PQ）15天。观察到JM-2猴子直到PQ给药后69天为止，并且在整个随访期间均未复发。我们建议，日本猕猴模型不仅可以用于药物筛查次生子活性，