Court J P, Stables J N, Lees G M, Martin-Short M R, Rankin R
Department of Biochemical Microbiology, Wellcome Reserach Laboratories, Beckenham, Kent, England.
J Helminthol. 1988 Mar;62(1):1-9. doi: 10.1017/s0022149x00011123.
Transplanted infections of Dipetalonema viteae and Brugia pahangi have been evaluated as tools for experimental chemotherapy. Attempts were made to establish these filariae in similar pharmacokinetic sites within the same host, so that direct comparisons of in vivo drug susceptibilities could be made. Unfortunately, it was not possible to establish B. pahangi in the subcutaneous tissues, the preferred site of D. viteae. Therefore, intraperitoneal B. pahangi and subcutaneously implanted D. viteae in gerbils were used for the study. D. viteae infections were significantly enhanced by concomitant infections with B. pahangi, while B. pahangi infection rates were unaffected by the presence of D. viteae. Experiments with amoscanate, CGP6140 and Mel W demonstrated the importance of employing both B. pahangi and D. viteae for antifilarial discovery work and the fundamental effect of parasite location on drug efficacy. D. viteae rapidly migrate from the peritoneal cavity of gerbils following implantation; twenty one hours after infection 73% of transplanted worms were found in the subcutaneous tissues. It was shown that the migration response could be used as a stringent parameter for demonstrating antifilarial activity. D. viteae were exposed to antifilarial drugs for 24 hours in vitro, washed and implanted into the peritoneal cavity of gerbils. At autopsy, 5 days later, 10(-8)M ivermectin and milbemycin D had prevented migration; CGP6140, amoscanate, suramin, flubendazole and furapyrimidone were also detected at less than 10(-6)M using this parameter. In all cases the migration response was more sensitive to drugs than parasite kill. Ivermectin's ability to inhibit worm migration through the tissues is discussed, with respect to the role of itinerant males in the reproductive cycle of Onchocerca volvulus.
已对移植感染的魏氏双瓣线虫（Dipetalonema viteae）和彭亨布鲁线虫（Brugia pahangi）作为实验化疗工具进行了评估。人们试图在同一宿主的相似药代动力学部位建立这些丝虫，以便能够直接比较体内药物敏感性。不幸的是，无法在皮下组织中建立彭亨布鲁线虫，而皮下组织是魏氏双瓣线虫的首选部位。因此，本研究使用了在沙鼠腹腔内感染的彭亨布鲁线虫和皮下植入的魏氏双瓣线虫。魏氏双瓣线虫感染会因同时感染彭亨布鲁线虫而显著增强，而彭亨布鲁线虫的感染率不受魏氏双瓣线虫存在的影响。使用氨甲酰苯胺、CGP6140和Mel W进行的实验证明了在抗丝虫发现工作中同时使用彭亨布鲁线虫和魏氏双瓣线虫的重要性，以及寄生虫位置对药物疗效的根本影响。魏氏双瓣线虫植入后会迅速从沙鼠腹腔迁移；感染21小时后，73%的移植虫体出现在皮下组织中。结果表明，迁移反应可作为证明抗丝虫活性的严格参数。将魏氏双瓣线虫在体外暴露于抗丝虫药物24小时，冲洗后植入沙鼠腹腔。5天后尸检发现，10^(-8)M的伊维菌素和米尔倍霉素D可阻止迁移；使用该参数还检测到CGP6140、氨甲酰苯胺、苏拉明、氟苯达唑和呋喃嘧啶酮的浓度低于10^(-6)M。在所有情况下，迁移反应对药物的敏感性都高于杀死寄生虫。文中讨论了伊维菌素抑制虫体在组织中迁移的能力，以及游走雄虫在盘尾丝虫（Onchocerca volvulus）生殖周期中的作用。
