Lok J B, Knight D H, Selavka C M, Eynard J, Zhang Y, Bergman R N
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, USA.
Trop Med Parasitol. 1995 Dec;46(4):235-40.
Normal adult Dirofilaria immitis from a microfilaremic donor dog and D. immitis from donors rendered microfilaria (MF) negative by seven consecutive monthly doses of milbemycin oxime (500 micrograms/kg) were transplanted into three previously uninfected and untreated dogs. Two dogs received reciprocal combinations of treated and untreated D. immitis and the third received untreated adults of both sexes. A fourth dog served as an infected, milbemycin treated, non-transplanted control. Eleven weeks after pairing treated female with untreated male worms, a low-level microfilaremia developed in the recipient. Two of the three treated female worms recovered from this dog were non-fertile, and the third contained a small number of elongate and coiled embryos but no mature intrauterine (stretched) microfilariae (MFF). The dog receiving treated male and untreated female worms became microfilaremic after two weeks. Microfilaremia peaked at 37,000/ml 16 weeks after transplantation and declined over the next 20 weeks to 7,200/ml. Untreated females paired with treated males either became non-fertile or exhibited low numbers of developing embryos and MFF scattered throughout their reproductive tracts. Pairing of untreated male and female worms produced a mcirofilaremia during the second post-operative week, which plateaued around 15,000 MFF per ml. Females recovered after this pairing contained a normal pattern of embryonic development, including stretched MFF. There were no significant differences in the percentage composition or absolute numbers of developing and mature sperm in the reproductive tracts of treated and untreated male worms. However, the resumption of MF production in one milbemycin treated female worm after pairing with normal males and failure of treated males to sustain MF production in untreated female worms suggest that milbemycin oxime impairs the sexual competence of male D. immitis. This may explain the ability of this drug to bring about long term suppression of microfilaremia without immediate adulticidal activity.
将来自一只微丝蚴血症供体犬的正常成年犬恶丝虫以及通过连续七个月每月剂量的米尔贝肟（500微克/千克）使微丝蚴（MF）呈阴性的供体犬的犬恶丝虫，移植到三只先前未感染且未治疗的犬体内。两只犬接受了经处理和未经处理的犬恶丝虫的相互组合，第三只犬接受了雌雄两性的未经处理的成虫。第四只犬作为感染、经米尔贝肟治疗、未进行移植的对照。在将经处理的雌虫与未经处理的雄虫配对11周后，受体犬出现了低水平的微丝蚴血症。从这只犬体内回收的三只经处理的雌虫中有两只不育，第三只含有少量细长且盘绕的胚胎，但没有成熟的子宫内（伸展的）微丝蚴（MFF）。接受经处理的雄虫和未经处理的雌虫的犬在两周后出现了微丝蚴血症。微丝蚴血症在移植后16周达到峰值37,000/毫升，并在接下来的20周内降至7,200/毫升。未经处理的雌虫与经处理的雄虫配对后，要么不育，要么在其生殖道中出现少量发育中的胚胎和分散的MFF。未经处理的雄虫和雌虫配对在术后第二周产生了微丝蚴血症，每毫升稳定在约15,000个MFF左右。此次配对后回收的雌虫胚胎发育模式正常，包括伸展的MFF。经处理和未经处理的雄虫生殖道中发育和成熟精子的百分比组成或绝对数量没有显著差异。然而，一只经米尔贝肟处理的雌虫与正常雄虫配对后恢复了微丝蚴的产生，而经处理的雄虫在未经处理的雌虫中未能维持微丝蚴的产生，这表明米尔贝肟损害了雄性犬恶丝虫的性能力。这可能解释了这种药物能够在没有立即杀成虫活性的情况下实现对微丝蚴血症的长期抑制的能力。
