Triggering of high-level resistance against Schistosoma mansoni reinfection by artemether in the mouse model

Triggering of high-level resistance against Schistosoma mansoni reinfection by artemether in the mouse model
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DOI:
10.4269/ajtmh.2004.71.774
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发表时间:
2004-12-01
影响因子:
3.3
通讯作者:
Tanner, M
Tanner, M
中科院分区:
医学4区
文献类型:
--
作者:
Bergquist, R;Utzinger, J;Tanner, M

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蒿甲醚是双氢青蒿素的甲醚衍生物,不仅具有抗疟疾特性,而且对可引起血吸虫病的寄生虫的未成熟阶段-童虫具有很强的活性。为了测试在诱导免疫保护反应方面是否与辐射的效果相似,将小鼠组感染曼氏血吸虫尾蚴,并在感染后1-3周用蒿甲醚治疗。对照组小鼠感染正常尾蚴或暴露于辐射的尾蚴,允许早期发育,但不成熟的寄生虫。在初始感染后6周对小鼠进行攻击,并且在攻击后8周解剖时计算各组中回收的染色体的平均数目。初次感染后两周给予蒿甲醚的保护率为58%,而感染后三周给予蒿甲醚的保护率为81%。这种保护水平与通常用辐照尾蚴免疫获得的保护水平一样高(在本研究中为84%),并且上级于迄今为止报道的用任何单个单体型疫苗候选抗原获得的抗性水平。
Artemether, a methyl ether derivative of dihydroartemisinin, not only exhibits antimalarial properties, but also possesses strong activity against schistosomula, the immature stages of a parasitic worm that can cause schistosomiasis. To test if the effect would be similar to that of irradiation with respect to the induction of immunologic protective responses, groups of mice were infected with Schistosoma mansoni cercariae and treated with artemether at 1-3 weeks post-infection. Control mice were either infected with normal cercariae or with cercariae exposed to radiation that permitted early development but not maturation of the parasites. The mice were challenged six weeks after the initial infection, and the mean numbers of schistosomes recovered in the various groups were calculated upon dissection eight weeks post-challenge. The administration of artemether two weeks after the initial infection resulted in 58% protection, while giving the drug three weeks post-infection increased the level of protection to 81%. This level of protection is as high as that normally obtained by immunization with irradiated cercariae (84% in the present study) and is superior to the level of resistance obtained with any individual schistosome vaccine candidate antigen thus far reported.