Lowell A. Miller

Review of issues concerning the use of reproductive inhibitors, with particular emphasis on resolving human-wildlife conflicts in North America.

This manuscript provides an overview of past wildlife contraception efforts and discusses the current state of research. Two fertility control agents, an avian reproductive inhibitor containing the active ingredient nicarbazin and an immunocontraceptive vaccine, have received regulatory approval with the Environmental Protection Agency and are commercially available in the USA. OvoControl G Contraceptive Bait for Canada Geese and Ovo Control for pigeons are delivered as oral baits. An injectable immunocontraceptive vaccine (GonaCon Immunocontraceptive Vaccine) was registered with the Environmental Protection Agency for use in female white-tailed deer in September 2009. An injectable product (GonaCon Immunocontraceptive Vaccine) is registered for use in female white-tailed deer. Both products are labeled for use in urban/suburban areas where these species are overabundant. Several other compounds are currently being tested for use in wildlife in the USA, Europe, Australia and New Zealand that could have promise in the future. The development and use of reproductive inhibitors for resolving human-wildlife conflicts will depend on a number of factors, including meeting the requirements of regulatory agencies for use in the environment and on the biological and economical feasibility of their use. Use will also be dependent on health and safety issues and on public acceptance of the techniques.

No adverse effects of simultaneous vaccination with the immunocontraceptive GonaCon and a commercial rabies vaccine on rabies virus neutralizing antibody production in dogs.

Parenteral vaccination campaigns are integral to the elimination of canine rabies. To maximize herd immunity in dogs, immunocontraception provided at the time of rabies vaccination should reduce fecundity and dog abundance. GonaCon has been used successfully as an immunocontraceptive in a variety of mammals, and by inference, the dog would be an ideal candidate for testing. As an initial step in evaluating a combination-vaccination program, we assessed the effects of GonaCon on rabies virus neutralizing antibody production in dogs after administration of a veterinary rabies vaccine. Eighteen feral/free ranging dogs were included in this initial study: six were given GonaCon only, six were given rabies vaccination only, and six received GonaCon and rabies vaccination. Antibody levels were evaluated over 82 days. The use of the immunocontraceptive GonaCon did not affect the ability of dogs to seroconvert in response to the rabies vaccine. Thus, GonaCon provides a potential immunocontraceptive for use in combination with rabies vaccine to increase herd immunity and address dog population over abundance to better manage rabies.

Nonsurgical fertility control for managing free-roaming dog populations: A review of products and criteria for field applications

About 75% of dogs worldwide are free to roam and reproduce, thus creating locally overabundant populations. Problems caused by roaming dogs include diseases transmitted to livestock and humans, predation on livestock, attacks on humans, road traffic accidents, and nuisance behavior. Nonsurgical fertility control is increasingly advocated as more cost-effective than surgical sterilization to manage dog populations and their impact. The aims of this review were to 1) analyze trends in numbers of scientific publications on nonsurgical fertility control for dogs; 2) illustrate the spectrum of fertility inhibitors available for dogs; 3) examine how differences between confined and free-roaming dogs might affect the choice of fertility inhibitors to be used in dog population management; and 4) provide a framework of criteria to guide decisions regarding the use of nonsurgical fertility control for dog population management. The results showed that the 117 articles published between 1982 and 2011 focussed on long-term hormonal contraceptives, such as gonadotropin-releasing hormone agonists, immunocontraceptives, and male chemical sterilants. The number of articles published biennially increased from one to five papers produced in the early 1980s to 10 to 20 in the past decade. Differences between confined dogs and free-roaming dogs include reproduction and survival as well as social expectations regarding the duration of infertility, the costs of sterilization, and the responsibilities for meeting these costs. These differences are likely to dictate which fertility inhibitors will be used for confined or free-roaming dogs. The criteria regarding the use of fertility control for dog population management, presented as a decision tree, covered social acceptance, animal welfare, effectiveness, legal compliance, feasibility, and sustainability. The review concluded that the main challenges for the future are evaluating the feasibility, effectiveness, sustainability, and effects of mass nonsurgical sterilization campaigns on dog population size and impact as well as integrating nonsurgical fertility control with disease vaccination and public education programs.

Comparison of immune and adverse effects induced by AdjuVac and Freund's complete adjuvant in New Zealand white rabbits (Oryctolagus cuniculus).

Though Freunds complete adjuvant effectively increases immune response to vaccines in various species, its potentially severe inflammatory effects have led many animal researchers to seek alternative immunological adjuvants. In a study of New Zealand white rabbits, the authors compared the immune and adverse effects of Freunds complete adjuvant with the effects of two formulations of AdjuVac, an immunological adjuvant previously developed by their group. All three adjuvants improved humoral immune response but also caused inflammation. Inflammatory reactions caused by AdjuVac, however, tended to be less severe than those caused by Freunds complete adjuvant.

Nicarbazin OvoControl G Bait Reduces Hatchability of Eggs Laid by Resident Canada Geese in Oregon

Abstract Expanding populations of resident Canada geese (Branta canadensis) are resulting in increased conflicts with humans. Nonlethal and humane means are needed for managing Canada goose flocks at a variety of sites, including golf courses, industrial parks, government sites, and city parks. Decreased egg production and hatching are side effects of nicarbazin, a veterinary drug used to treat coccidiosis in chickens. Capitalizing on these effects, we developed nicarbazin as a reproductive inhibitor for Canada geese and conducted a field efficacy study. We recruited study sites in 2002 and 2003. Following laboratory testing, we conducted a field efficacy trial of nicarbazin for reducing the hatchability of Canada goose eggs in spring 2004 in Oregon, USA. The study began in February 2004 at 10 sites in Oregon, with 2 control and 3 treated sites on each side of the Cascades. We fed bait daily to resident Canada geese for approximately 6 weeks. We located and monitored nests until hatching or ≥5 days beyond the expected hatching date to determine hatchability. We completed data collection in May 2004. Geese consumed 8,000 kg of bait, with 5,100 kg of OvoControl G® (Innolytics, LLC, Rancho Santa Fe, CA) 2,500-ppm nicarbazin bait consumed among 6 treated sites and 2,900 kg of untreated bait consumed among 4 control sites. We monitored 63 nests at treated sites and 46 nests at control sites to determine hatching success of eggs. There was a 62% reduction in the percentage of nests with 100% hatchability at treated sites as compared to controls. There was a 93% increase in the percentage of nests at treated sites with 0% hatchability as compared to nests with no eggs hatching at control sites. Hatchability from treated sites versus control sites was reduced 36% (F = 5.72, P = 0.0622). We submitted results from this study to support Environmental Protection Agency registration of nicarbazin as a reproductive inhibitor for use in Canada geese. We have shown that treatment of resident Canada geese with OvoControl G 2,500-ppm nicarbazin bait by licensed, trained applicators immediately prior to and during the breeding season can reduce hatchability of eggs laid by treated geese, thereby reducing recruitment of goslings into problem resident Canada goose populations.

Concomitant administration of GonaCon™ and rabies vaccine in female dogs (Canis familiaris) in Mexico.

Mexico serves as a global model for advances in rabies prevention and control in dogs. The Mexican Ministry of Health (MMH) annual application of approximately 16 million doses of parenteral rabies vaccine has resulted in significant reductions in canine rabies during the past 20 years. One collateral parameter of rabies programs is dog population management. Enhanced public awareness is critical to reinforce responsible pet ownership. Surgical spaying and neutering remain important to prevent reproduction, but are impractical for achieving dog population management goals. GonaCon™, an anti-gonadotropin releasing hormone (GnRH) vaccine, was initially tested in captive female dogs on the Navajo Nation, 2008. The MMH led this international collaborative study on an improved formulation of GonaCon™ in captive dogs with local representatives in Hidalgo, Mexico in 2011. This study contained 20 bitches assigned to Group A (6 control), Group B (7 GonaCon™), and Group C (7 GonaCon™ and rabies vaccine). Vaccines were delivered IM. Animals were placed under observation and evaluated during the 61-day trial. Clinically, all dogs behaved normally. No limping or prostration was observed, in spite of minor muscle atrophy post-mortem in the left hind leg of dogs that received GonaCon™. Two dogs that began the study pregnant give birth to healthy pups. Dogs that received a GonaCon™ injection had macro and microscopic lesions consistent with prior findings, but the adverse injection effects were less frequent and lower in intensity. Both vaccines were immunogenic based on significant increases in rabies virus neutralizing antibodies and anti-GnRH antibodies in treatment Groups B and C. Simultaneous administration of GonaCon™ and rabies vaccine in Group C did not affect immunogenicity. Progesterone was suppressed significantly in comparison to controls. Future studies that monitor fertility through multiple breeding cycles represent a research need to determine the value of integrating this vaccine into dog rabies management.

Use of a GnRH vaccine, GonaCon™, for prevention and treatment of adrenocortical disease (ACD) in domestic ferrets

Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets.

Efficacy of ERL-4221 as an ovotoxin for feral pigs (Sus scrofa).

Context The expansion of feral pig populations across the United States has increased the occurrence of damage and damage complaints. New techniques are needed to more effectively manage feral pig damage, including the development of fertility control agents. Aims We aimed to assess the ovotoxic properties of ERL-4221 as a candidate fertility control agent for feral pigs. Methods We conducted two palatability trials to determine ERL-4221 acceptance and one experimental trial with ERL-4221 at the captive wildlife facility of Texas A&M University-Kingsville during 2008. Our experimental trial had three treatments, a control containing no ERL-4221, baits containing 16.0 mg ERL-4221 kg–1 bodyweight for 10 days, and baits containing 16.0 mg ERL-4221 kg–1 bodyweight for 20 days. Key results Final body mass, total ovary mass, number of follicles and number of corpora lutea did not differ between treatments. Conclusions We did not find it efficacious to orally deliver ERL-4221 to feral pigs to reduce fertility. Oral delivery is the most practical, cost-effective means of delivering fertility control agents to feral pigs and development of additional fertility control strategies are needed. Implications Unless ovotoxic effects of ERL-4221 can be identified in feral pigs, along with a successful means of administration, other fertility control strategies may need to be explored, such as oocyte-secreted proteins that regulate follicular development.