Human malaria in immunocompromised mice: New in vivo model for chemotherapy studies
Human malaria in immunocompromised mice: New in vivo model for chemotherapy studies
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DOI：
10.1128/aac.45.6.1847-1853.2001
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发表时间：
2001-06-01
影响因子：
4.9
通讯作者：
Druilhe, P
中科院分区：
文献类型：
--
作者：
Moreno, A;Badell, E;Druilhe, P
我们最近设计了一种新的恶性疟原虫小鼠模型，并记录了其免疫效应机制的研究潜力，为了确定其药物研究的价值，我们评估了其对现有抗疟药物的反应与在人类中观察到的反应相比。免疫受损的BXN（bg/bg xid/xid nu/nu）小鼠用敏感的NF 54菌株或多重抗性T24菌株感染，然后用氯喹、奎宁、甲氟喹或双氢青蒿素治疗。在先前报道的人类反应和恶性疟原虫寄生的人红细胞（huRBC）-BXN小鼠对经典抗疟药物的反应之间观察到平行性，根据寄生虫血症的降低速度和寄生虫的形态学改变来测量。感染敏感菌株的小鼠在用氯喹或甲氟喹治疗后成功治愈。感染了多重抗性菌株的小鼠不能被氯喹或奎宁治愈，但此后对双氢青蒿素治疗有反应。每种药物的寄生虫清除速度和诱导的形态学改变不同，并且与先前报道的观察结果相匹配，因此强调了模型的相关性，因此，这些数据表明，恶性疟原虫-huRBC-BXN小鼠可以提供有价值的体内系统，并且应该包括在可用于评价恶性疟原虫对药物的反应的动物的短列表中。
We have recently designed a new Plasmodium falciparum mouse model and documented its potential for the study of immune effector mechanisms, In order to determine its value for drug studies, we evaluated its response to existing antimalarial drugs compared to that observed in humans. Immunocompromised BXN (bg/bg xid/xid nu/nu) mice were infected with either the sensitive NF54 strain or the multiresistant T24 strain and then treated with chloroquine, quinine, mefloquine, or dihydroartemisinin. A parallelism was observed between previously reported human responses and P, falciparum-parasitized human red blood cell (huRBC)-BXN mouse responses to classical antimalarial drugs, measured in terms of speed of decrease in parasitemia and of morphological alterations of the parasites, Mice infected with the sensitive strain were successfully cured after treatment with either chloroquine or mefloquine, In contrast, mice infected with the multiresistant strain failed to be cured by chloroquine or quinine but thereafter responded to dihydroartemisinin treatment, The speed of parasite clearance and the morphological alterations induced differed for each drug and matched previously reported observations, hence stressing the relevance of the model, These data thus suggest that P. falciparum-huRBC-BXN mice can provide a valuable in vivo system and should be included in the short list of animals that can be used for the evaluation of P. falciparum responses to drugs.