A PRIMATE MODEL FOR SEVERE HUMAN MALARIA WITH CEREBRAL INVOLVEMENT - PLASMODIUM-COATNEYI INFECTED MACACA-FUSCATA

A PRIMATE MODEL FOR SEVERE HUMAN MALARIA WITH CEREBRAL INVOLVEMENT - PLASMODIUM-COATNEYI INFECTED MACACA-FUSCATA
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DOI:
10.4269/ajtmh.1993.48.630
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发表时间:
1993-05-01
影响因子:
3.3
通讯作者:
SUZUKI, M
SUZUKI, M
中科院分区:
医学4区
文献类型:
--
作者:
KAWAI, S;AIKAWA, M;SUZUKI, M

文献摘要

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为了建立人类重症疟疾动物模型,我们对感染革内疟原虫的日本猕猴(Macaca fuscata)进行临床和病理观察。实验中使用了两只8个月和9个月大的猴子。接种该寄生虫后,两只猴子均出现高寄生虫血症(20-28.2%)的暴发性急性感染,并伴有典型的严重疟疾症状而死亡。在切除脾脏的日本猴子中,隔离的受感染红细胞阻断了脑毛细血管。脑组织的电镜研究显示,受感染红细胞的膜上突出了电子致密的突起,这些突起与脑毛细血管内皮细胞形成局灶性连接。这些发现与在人类病例中看到的非常相似。感染红细胞明显隔离,均匀分布于肺和心脏毛细血管。未切除脾的日本猴出现急性贫血,细胞堆积量为6%,但脑毛细血管阻塞最小。然而,在这只动物的心脏和肺部的毛细血管中,明显存在被隔离、感染的红细胞。本研究表明,日本猴对柯氏疟原虫感染高度敏感,该系统为人类重症疟疾的研究提供了模型。
To develop an animal model for severe human malaria, we carried out clinical and pathologic observations of Japanese monkeys (Macaca fuscata) infected with Plasmodium coatneyi. Two monkeys, eight and nine months of age, were used in this experiment. After inoculation with the parasite, both monkeys developed a fulminating acute infection with high parasitemia (20-28.2%) and became moribund with typical signs of severe malaria. In the splenectomized Japanese monkey, sequestered infected erythrocytes blocked brain capillaries. Electron microscopic studies on brain tissues revealed electron-dense knobs protruding from the membrane of infected erythrocytes that formed focal junctions with the cerebral capillary endothelial cells. These findings were remarkably similar to those seen in human cases. Prominent sequestration of the infected erythrocytes was uniformly distributed in capillaries of the lungs and heart. The nonsplenectomized Japanese monkey developed acute anemia with a packed cell volume of 6%, but blockage of brain capillaries was minimal. However, sequestered, infected erythrocytes were evident in capillaries of the heart and lungs of this animal. Our study showed that the Japanese monkey is highly susceptible to P. coatneyi infection and that this system provides a model for the study of severe human malaria.