In vitro efficacy of anti-protozoal compounds against Tritrichomonas foetus

Abstract

Bovine trichomoniasis is a sexually transmitted disease caused by Tritrichomonas foetus, an obligate parasite of the reproductive tract of cows and the surface of the bull’s penis and prepuce. Significant economic losses occur annually in both beef and dairy cattle occur annually due to this disease. In 1991, annual losses approached $650 million (Speer and White, 1991) in the United States and have continued with some producers reporting income losses of up to 22% (Rae et al., 2004; Villarroel et al., 2004). Infected bulls are asymptomatic carriers of T. foetus, but are capable of transmitting the organism to cows during coitus (BonDurant, 1997). Infection in cows results in endometritis, cervicitis, and vaginitis, which may lead to embryonic death, abortion, pyometra, fetal maceration, or infertility (Felleisen, 1999a). The major economic losses associated with T. foetus include reduced calf crop due to early embryonic loss or abortion, reduced weaning weights due to delayed conception, and culling and replacement of infected cattle. Producers invest significant time and expense testing bulls prior to the breeding season. Weekly sampling for six weeks prior to introduction of the bull into a herd is recommended but rarely performed. Vaccination has been considered to be of limited value for protecting the cattle herd (Bondurant, 2005; Herr et al., 1991; Soto and Parma, 1989). Cattle operations currently infected with T. foetus struggle with eliminating the pathogen from the herd. With the lack of an effective FDA approved treatment, current recommendations are labor intensive, costly as infected bulls must be slaughtered, and rely heavily upon accurate diagnosis of trichomoniasis. With the use of simple and accurate testing methods that can reliably screen for infection combined with a safe, effective, and approved treatment for T. foetus, all bulls found within an infected herd could be treated. The ability to treat all bulls within an infected herd would eliminate the need to cull valuable animals and/or risk transmission during subsequent breeding seasons via undetected carrier bulls. Use of nitromidazoles, which have previously proven to be efficacious in clearing infected bulls, has been banned in the United States. Very little research has been conducted with other potential pharmaceuticals for treatment of T. foetus infections in bulls. Benzimidazoles, specifically oxibendazole and oxfendazole, and ponazuril are anti-protozoal drugs that are legal for use in food animals and were found to be the most efficacious of a panel of agents tested against T. foetus by this research team in a limited in vitro replication study. In this study, ponazuril and oxibendazole combined with a polymer enhancer eliminated 100% of T. foetus organisms. Based on these promising results, further investigation of the efficacy and safety of these formulations is warranted and could result in future treatment options for this economically devastating disease of cattle. In this study we formulated an oxibendazole, oxfendazole and ponazuril topical-enhanced were used to establish a dosage for treatment of T. foetus infection in bulls and determined the efficacy of the formulations in vitro. Assays were evaluated at predetermined time points using Neubauer hemocytometers to determine the number of viable trophozoites and the induction of the pseudocyst form. Cultures were examined for reversibility to the motile trophozoite form or continued replication of organisms following the administration of the drug. In our final study, complete kill of the organism was achieved and all replicates remained negative for reemergence of trophozoites or pseudocysts following 5 days of culture.