Development of an effective alternative model for in vivo hypnozoite-induced relapse infection: A Japanese macaque (Macaca fuscata) model experimentally infected with Plasmodium cynomolgi. (June 2020)

• Record Type: Journal Article
• Authors: Kawai, Satoru; Annoura, Takeshi; Araki, Tamasa; Shiogama, Yumiko; Soma, Shogo; Takano, Jun-ichiro; Sato, Marcello Otake; Kaneko, Osamu; Yasutomi, Yasuhiro; Chigusa, Yuichi
• Is Part Of: Parasitology international. Volume 76(2020)
• Publication Date: 2020-06
• Subjects: Plasmodium cynomolgi -- Japanese macaque -- Hypnozoite -- Relapse -- Primate model; Parasitology -- Periodicals; Parasites -- Periodicals; Parasitic Diseases -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; 571.99905
• DOI: 10.1016/j.parint.2020.102096
• Languages: English
• ISSNs: 1383-5769

Abstract

Abstract: 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 × 10 5 ) 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. Graphical abstract: Unlabelled Image Highlights: Two Japanese macaques ( Macaca fuscata ) were used for the experiment. P. cynomolgi B-sporozoites were inoculated intravenously into the monkeys. The relapse pattern was similar to that observed in the rhesus macaque model. The Japanese macaque model could contribute to the study on hypnozoite biology.