Studies of reproductive competence in male Dirofilaria immitis treated with milbemycin oxime

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.