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Contraception offers potential as a tool for managing certain diseases in wildlife, most notably venereally transmitted diseases or diseases transmitted at parturition. Brucellosis is an excellent example of an infectious disease present in wild populations that could potentially be managed through immunocontraception. Previous studies in bison (Bison bison) suggest that a single injection of GonaCon (National Wildlife Research Center, U.S. Department of Agriculture/Animal and Plant Health Inspection Service/Wildlife Services, Fort Collins, Colorado 80521, USA) results in 3 or more yr of infertility. Ongoing studies will determine if the use of GonaCon in bison decreases shedding of Brucella abortus from infected animals and will better define the duration of infertility following a single injection

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., (Copyright © 2013. Published by Elsevier Inc.)

The uncontrolled reproduction of free-roaming feral cats contributes to overpopulation and associated concerns regarding their welfare and impact on public health and the environment. Nonsurgical fertility control that could be administered to feral cats in the field would be a powerful tool for cat population control. The objective was to test the efficacy and duration of activity of a single-dose GnRH immunocontraceptive vaccine (GonaCon™) on the fertility of adult female laboratory cats. Vaccinated cats (n = 15) received a single injection of vaccine containing a GnRH-KLH conjugate (200 μg) emulsified in a mycobacterial and oil adjuvant on study Day 0. Sham-treated cats (n = 5) received a single injection containing all vaccine components except the GnRH-KLH conjugate. A breeding trial started on study Day 120. Vaccinated cats had a longer time to conception (median 39.7 mo) compared to sham-treated cats (4.4 mo; P < 0.001). A total of 93% of vaccinated cats remained infertile for the first year following vaccination, whereas 73, 53, and 40% were infertile for 2, 3, and 4 y, respectively. At study termination (5 y after a single GnRH vaccine was administered), four cats (27%) remained infertile. The GnRH antibody titers declined more rapidly in short-term responding cats with < 2 y of infertility (n = 4), compared to long-term responding cats that experienced fertility control for >2 y (n = 11) (P < 0.05). Non-painful but persistent late-onset granulomatous injection site masses appeared 2 y after initial vaccination in five cats. We concluded that GnRH immunocontraception is an ideal candidate for further development for feral cat control., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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., (© 2010 ISZS, Blackwell Publishing and IOZ/CAS.)

Resident populations of two exotic deer species, fallow deer and axis deer, are having adverse impacts on their habitat and on native plant and animal communities at Point Reyes National Seashore (PRNS) in California. These non-native cervids were released intentionally for recreational hunting on the property now known as PRNS during the period 1942-1954. Approximately 860 fallow deer and 250 axis deer now inhabit PRNS. Under an approved non-native deer management plan, fallow and axis deer populations will be removed from PRNS by 2021 via culling of animals by sharpshooting and by treatment of some of the female fallow deer with GonaCon™ Immunocontraceptive Vaccine. During July-August 2007, 69 fallow does were captured, equipped with numbered ear tags and radiotelemetry collars, and injected with GonaCon™ vaccine before being released. Control animals include 10 does that were captured, marked, and given “sham” injections during July-August 2007, and 19 does that were captured and marked (but not injected) during 2005. Reproductive activity, as indicated by lactation and fecal concentrations of progesterone among the GonaCon™-treated and control does, will be monitored and compared for two years, and will be used to determine the efficacy of GonaCon™ as a cervid contraceptive agent. Traditional methods of population control, such as regulated harvest by licensed hunters, often are impractical or illegal in settings such as national and state parks, and the use of firearms may be prohibited in some urban and suburban environments. The development of safe and effective wildlife contraceptives such as GonaCon™ is needed to control locally overabundant populations in situations where traditional management tools cannot be employed.

The term “vaccine” has traditionally been associated with establishing immunity (antibodies) to a disease. This immunity is usually developed following administration of killed microorganisms. Disease vaccines typically require 1 to 3 injections, depending on the antigen design and efficacy of the vaccine. The effectiveness of the disease vaccine depends on the immune response developed by the host following exposure to the disease organism. The immunocontraceptive vaccine GonaCon™ is designed to produce immunity to the “self” hormone (GnRH), which is essential to reproductive activity in the mammal. Antibodies to GnRH reduce its biological activity resulting in infertility of both sexes. GonaCon™’s effectiveness as a single-injection immunocontraceptive wildlife vaccine depends on 4 factors. The first is the use of a large foreign mollusk protein in the GnRH conjugate. Second is the design of mollusk/GnRH protein conjugate that presents the GnRH antigen in a repetitious fashion. This design mimics the “danger signal” found in bacterial pathogens to which the animal has been previously exposed. Third is the addition to the vaccine of micrograms of Mycobacterium avium, which is ubiquitous in the environment and activates memory cells. The fourth factor is use of a water-in-oil emulsion, which provides a depot at the injection site, allowing a slow release of the vaccine. With this formulation, the vaccine is presented to the body as a “chronic infection”, even though it is not infectious. The granuloma that normally develops at the injection site plays a prime role in the host’s defense against this “chronic infection”. A WHO report on the use of the alum adjuvant in human vaccines states that “development of a small granuloma is inevitable with vaccines adjuvanted with aluminum, and is to be considered necessary to the efficacy of the adjuvant.” Researching GonaCon™ for use in companion animals, NWRC has looked at many different adjuvants intended to reduce the injection site reaction while at the same time retaining an effective vaccine. This paper reports on the role of the adjuvant and the injection site on the effectiveness of the vaccine.

Recently, wildlife contraception became a reality with the registration of OvoControl for geese and pigeons. A data submission to the Environmental Protection Agency for the registration of GonaCon™ for white-tailed deer is forthcoming. The question that is now facing wildlife managers is if, and how, to implement contraception as part of an overall management plan. Population models offer a method of predicting the long-term efficacy of management actions without investing time and money in expensive field studies. Black-tailed prairie dogs were used as a target species for the purposes of these models. Four different management options were modeled for a 100-year period including no control, lethal control only, fertility control only, or a combination of lethal and fertility control. Yearly culling resulted in a more rapid rate of population decline than yearly contraception. Culled populations (50-90% culling) went extinct more quickly than populations contracepted at the same rate. Populations could be stabilized at their current size with 12.79% yearly culling or 33.25 % yearly contraception. Populations also remained relatively stable over 100 years when 50% of the population was culled initially, followed by 85.8% contraception once every 3 years. These models will help provide a scientific basis for further discussion on the usefulness of wildlife contraceptives, and will help highlight the areas that need further research.

Greater demand for non-lethal means of alleviating human-wildlife conflict has led to an interest in contraception as a wildlife management tool. The development of a single-injection Gonadotropin-Releasing Hormone (GnRH) contraceptive vaccine by the USDA National Wildlife Research Center reduces logistical limitations and the cost of using a vaccine that requires 2 injections. This study assesses the efficacy of different GnRH-KLH (keyhole limpet hemocyanin) vaccine designs. Forty-two captive female black-tailed deer were divided into 3 groups. A control group was injected with saline solution, and 2 treated groups were given either GonaCon™, a GnRH vaccine paired with AdjuVac™ (an adjuvant containing 175 µg of killed Mycobacterium avium), or GnRH vaccine without AdjuVac™ (instead substituting DEAE-dextran/oil (DD) as the adjuvant). Pregnancy rates in deer treated with GonaCon™ were significantly reduced as compared to saline controls (P = 0.006). There was no significant difference between GnRH-DD compared to saline (P = 0.297). Significant difference was found between GonaCon™ and GnRH-DD (P = 0.055). Vaccinated does that remained fertile received booster injections according to treatment group and were administered either GonaCon™ containing 87 µg M. avium or GnRH-KLH conjugate bound to DEAE-dextran. Deer that received booster injections regardless of the adjuvant were 100% contracepted for 1 year. Six out of 10 deer that received a prime injection of GonaCon™ remained 100% contracepted for 3 years, suggesting that the killed M. avium in the adjuvant is essential for the success of GonaCon™ as a single-injection GnRH vaccine.

Despite the fact that many wildlife species have become overabundant both in North America and other parts of the world, the public is increasingly unwilling to manage wildlife populations with traditional techniques such as trapping or lethal methods. A growing segment of the public is urging the use of contraceptives to reduce populations of overabundant free-ranging wildlife. In spite of public pressure, the development and use of wildlife fertility control techniques has been slow to occur, partially because of the difficulty in developing efficient, cost-effective methods, and partially because of misconceptions about these potential techniques. The regulatory authority for contraceptives has recently been moved from the Food and Drug Administration (FDA) to the Environmental Protection Agency (EPA); the extensive EPA registration process is both rigorous and costly. Only one wildlife contraceptive is currently registered and available: the National Wildlife Research Center (NWRC) worked to develop a product for reducing the hatchability of Canada goose eggs in cooperation with Innolytics, LLC, who holds the registration for OvoControl® G. Development is continuing for additional experimental products. Another product developed by the NWRC, the single-shot GonaCon™ Immunocontraceptive Vaccine is poised to begin the registration process. A third product, DiazaCon™, will be soon tested for field efficacy and should begin the registration process within the year. No single wildlife contraceptive technique would be applicable for use in all wildlife species and for all management situations for a particular species. Differences in animal physiology and behavior, as well as differences in the ecology of the damage, affect which contraceptives will be most effective. Therefore, contraceptives with different modes of action will need to be developed for different species and uses. Wildlife contraceptives will not replace other management tools and will probably have a limited use, primarily in urban/suburban areas. In most species, wildlife contraceptives will not rapidly reduce populations. Populations of short-lived species such as rodents could be rapidly reduced with contraceptives; however, in long-lived species such as deer and horses, it would take years to reduce populations with fertility control alone, and damage caused by those species will continue to occur. This manuscript will discuss what contraceptive techniques are being developed by the USDA Wildlife Services NWRC, and when, where, and for what species they may be applicable.

Controlling fertility of feral horses through the use of long-acting contraceptives or sterilization approaches has been championed as a reasonable and humane solution for addressing overpopulation problems in several western states. However, methods to accomplish long-term contraceptive efficacy of horses following a single treatment have been lacking. In fall 2002 and spring 2003, we initiated a study to compare the long-term efficacy of a single-shot contraceptive vaccine directed at gonadotropin releasing hormone (GonaCon™) to that of a single-shot vaccine directed at the zona pellucida (SpayVac) and to the use of intrauterine contraceptive devices (IUD). Both vaccines were administered with AdjuVac™, an adjuvant developed at the National Wildlife Research Center. The objectives of the study were to determine: 1) 3-year efficacy for preventing pregnancy, 2) whether the contraceptive effects are reversible, and 3) whether there are contraindications. The Nevada Department of Agriculture provided the feral mares, which were maintained at the Nevada State Penitentiary, Carson City, facility. Mares were dewormed and given health vaccinations annually. Eight untreated control mares were compared to 12 mares treated with SpayVac, 16 mares treated with GonaCon™, and 15 mares treated with copper-containing IUDs. Only 25% (2/8) of the control mares were not pregnant or infertile in the first year. All mares in the SpayVac group were infertile, and 94% (15/16) were infertile in the GonaCon™ group during the first breeding season. In Year 2, 80% (10/12) of the SpayVac-treated mares and 60% (9/15) of the GonaCon™-treated mares were infertile. In Year 3, 80% of the SpayVac mares and 53% (8/15) of the GonaCon™-treated mares were infertile. For IUD-treated mares, 80% (12/15) were infertile after Year 1, but only 29% (4/14) and 14% (2/14) were infertile after Years 2 and 3, respectively. For IUD mares that were infertile, it was possible to visualize the IUD by ultrasonography, leading us to conclude that mares that became pregnant had lost their IUDs. For mares given SpayVac, uterine edema was commonly observed. In Years 2 and 3, antibody titers for SpayVac were progressively lower compared to titers observed in Year 1.

High deer densities increase vehicle collisions, damage agricultural crops, and amplify the spread of zoonotic and animal diseases, intensifying human-deer conflict. In addition, deer impact on forest vegetation can influence the distribution and abundance of other wildlife species. Greater demand for non-lethal means of animal damage control has led to an interest in contraception as a wildlife management tool. The development of a single-injection Gonadotropin-Releasing Hormone (GnRH) contraceptive vaccine by NWRC reduces logistical limitations and cost of using immunocontraception as compared to a vaccine that requires two injections. This study assessed the efficacy of two different GnRH-KLH (keyhole limpet hemocyanin) vaccine designs in a single-injection study, to determine if Mycobacterium avium bacterium in the adjuvant is necessary for the success of a single-injection contraceptive vaccine. Forty-two captive female black-tailed deer were divided into 3 groups. Control deer were injected with saline solution, one treatment group received GonaCon™ (a GnRH-KLH vaccine paired with AdjuVac™ adjuvant that contains a small quantity of killed M. avium bacterium), and the second treatment group received GnRH-KLH vaccine with DEAE-Dextran/oil as the adjuvant. Contraceptive success was evaluated by monitoring progesterone, pregnancy specific protein, antibodies to GnRH-KLH conjugate and to Johne’s bacterium (M. avium), and actual pregnancy rates. Pregnancy rates were significantly different based on treatment (X² = 9.389; df = 2; P = 0.009). Pregnancy rates in deer treated with GonaCon™ were significantly reduced as compared to saline controls (P = 0.006), but there was no significant difference between GnRH-DD compared to saline (P = 0.297). Significant difference was found between GonaCon™ and GnRH-DD (P = 0.055). Results suggest that M. avium in the AdjuVac™ adjuvant is essential for the success of the single-injection GnRH vaccine GonaCon™. The development of a single-injection vaccine will increase the practicality and lower the cost of using immunocontraception as a tool to control deer populations.

Locally overabundant deer herds, particularly those inhabiting fenced or other enclosed areas in urban or suburban settings, are presenting serious problems for wildlife managers, landowners, and the general public. Traditional methods of population control, such as regulated harvest by licensed hunters, often are impractical or illegal in such settings. The development of safe and effective wildlife contraceptives is needed to control locally overabundant populations in situations where traditional management tools cannot be employed. During July 2004, we initiated a field study of GonaCon™ Immunocontraceptive Vaccine, developed by research scientists at the National Wildlife Research Center in Fort Collins, Colorado. This vaccine had previously been tested successfully as a contraceptive in captive animals including white-tailed deer, feral and domestic swine, and wild horses. The two-year field study was prompted by the need to manage an enclosed, overabundant population of white-tailed deer that had caused considerable ecological damage to a 662-acre, federally-owned, forested site in Silver Spring, Maryland. The U.S. General Services Administration, which manages the property, conducted an environmental assessment, which concluded that sharpshooting followed by immunocontraception would be the most appropriate deer management strategy. After 214 deer were removed from the site by sharpshooters, we set up and tested an automated radio telemetry system for tracking deer and monitoring their mortality. Twenty-eight does were then captured, equipped with ear tags and radio telemetry collars, and injected with GonaCon™ vaccine. Fifteen additional does were captured, marked, and released without vaccination as untreated control animals. Reproductive behavior and fawn production by the vaccinated and unvaccinated does will be monitored and compared for two years, and will be used to determine the efficacy of GonaCon™ as a wildlife contraceptive agent. Data from this study will be used to support EPA registration of GonaCon™ as a wildlife contraceptive agent.

Overpopulation of feral horses in several western states is an unquestioned problem. Current management strategies of removal and adoption are expensive, logistically challenging, and ineffective as a means of population control. We are testing three long-acting contraceptive approaches on feral Nevada mares. Modified reversible immunocontraceptive vaccines for gonadotropin releasing hormone (GnRH) and porcine zona pellucida (PZP) (SpayVac), and intrauterine contraceptive devices (IUDs), are being evaluated to determine: 1) their safety and efficacy for preventing pregnancy for multiple years, 2) whether the effects are reversible, and 3) whether there are notable contraindications. Preliminary data after 1 year suggest that IUD- and PZP-treated mares continue to exhibit breeding and estrus, while GnRH-treated mares are less likely to cycle. All mares in the GnRH and PZP treatments were infertile for the breeding season. Eighty percent of the IUD-treated mares were infertile; those mares that became pregnant likely failed to retain the IUD. A notable contraindication was that uterine edema normally observed in mares in the follicular phase of the estrous cycle was commonly observed in PZP-treated mares. Because administration of each contraceptive approach is different, and each has different effects and expected duration, one approach or a combination of approaches may be best suited for specific field applications. Subsequent years of this study should establish the efficacy and safety of one or more long-acting contraceptive approaches for feral horse population control.

Populations of wildlife, such as California ground squirrels, can grow to the extent that they come in conflict with humans. Contraception is a method of population management under investigation that may be useful in situations where neither leaving the animals uncontrolled nor lethal control are apropos. In this study, we tested the use of a single-injection gonadotropin releasing hormone (GnRH) immunocontraceptive vaccine in urban California ground squirrels. We monitored the effects of treatment for two breeding seasons. Immunization reduced the proportion of females lactating by 91% the first year and 96% in the second year. Testicular development was inhibited 35% the first year and 89% the second year. There is a delay of several months from the time of injection to inhibition of testes development. Reduction in the number of juveniles born per adult as determined by a visual count index was 9% the first year and 66% the second year. This study shows that the single-shot GnRH vaccine is over 90% effective for at least 1.5 years and requires several months after immunization for contraceptive effect. Because the immunization requires injection, it is labor intensive, but it is much more practical than treatments requiring multiple administrations to the same animal. GnRH immunocontraception may be a useful tool in rodent population management in certain circumstances.

BACKGROUND: The grey squirrel, Sciurus carolinensis Gmelin, is an invasive alien species introduced into Great Britain in the late nineteenth century and into Northern Italy during the early twentieth century. Grey squirrels have displaced the native European red squirrel, Sciurus vulgaris L., throughout much of Great Britain and have a significant impact on trees and woodlands through bark-stripping activity. In Britain, eradication is no longer an option at a regional scale, but fertility control offers a non-lethal approach to reducing negative impacts. The cholesterol mimic DiazaCon™ has been successfully used to inhibit reproduction in some species. These studies aimed to evaluate whether DiazaCon™ is effective in inhibiting reproduction in grey squirrels. RESULTS: DiazaCon™ reduced serum cholesterol levels in female grey squirrels at a range of doses. The period of effect increased with increasing dose. Reproduction rate was not significantly different between treatment and control groups owing to a lack of breeding in controls. CONCLUSIONS: DiazaCon™ has potential to reduce serum cholesterol levels enough and for a sufficient period to reduce fertility in female grey squirrels. Information on baseline physiology and blood chemistry of grey squirrels is required to inform interpretation of the level of significance of the effect. © Crown copyright 2012. Reproduced with permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Management of prairie dogs in the past has included poisoning, fumigants, barriers, and relocation. Because of the diverse attitudes related to prairie dog management, nonlethal methods that allow the existence of prairie dogs but help minimize damage related to population growth need to be developed. GonaCon™ is an immunocontraceptive vaccine that elicits antibodies to native GnRH; this prevents the secretion of reproductive hormones necessary for sperm and oocyte production. Prairie dogs were vaccinated with 0.1, 0.2, or 0.4mL of the GonaCon™ emulsion intramuscularly in the upper thigh containing 100, 200, or 400μg GnRH conjugate, respectively. Control animals were vaccinated with 0.4mL saline emulsion in the upper thigh. Blood samples (≤1mL) were taken from the femoral vein once pretreatment and at 1, 2, 3, 4, 6, and 15 months post-vaccination. Age (adult or juvenile) did not affect immune response to GonaCon™. Antibody titers were higher in the 200 and 400μL GonaCon™ groups than in the 100μL group, and there was no difference between the 200 and 400μL GonaCon™ groups. No adverse effects of GonaCon™ were noted on weight or blood chemistry parameters during the study. GonaCon™ will likely contracept prairie dogs for ≥1 year in the field using either 200 or 400μg conjugate. GonaCon™ could be incorporated into management plans to help maintain prairie dog populations while reducing habitat degradation due to overpopulation. [ABSTRACT FROM AUTHOR]

Problem An effective, single-injection, multi-year, GnRH contraceptive agent is needed to control reproduction in overabundant white-tailed deer populations. Method of study Two GnRH conjugates, GonaCon™ (GnRH–KLH) and GonaCon-B™ (GnRH–blue protein), were prepared in emulsion form as one-injection and two-injection immunocontraceptive vaccine formulations. In addition, the GnRH–KLH protein conjugate was lyophilized and suspended in AdjuVac™ adjuvant to produce a fifth vaccine formulation. Each formulation was administered to a group of five captive adult female white-tailed deer. Reproductive performance of treated female deer was monitored for 5 years to determine the comparative efficacy of the various treatments. Results The longevity of the contraceptive response (2–5 years) was strongly influenced by the design of the conjugate antigen, the adjuvant used, and the delivery form of the vaccine. Conclusion One-injection and two-injection formulations of GonaCon™ and GonaCon-B™ produced multi-year contraception in adult female white-tailed deer. GonaCon-B™ provided a longer lasting contraceptive effect. [ABSTRACT FROM AUTHOR]

Urbanization and associated landscaping has increased the abundance of year-round habitat for waterfowl, resulting in vegetation damage, loss of recreational activities, air transportation mishaps and health hazards. As part of a research program to develop socially acceptable techniques for management of pest bird populations, we are evaluating nicarbazin as a contraceptive in pest and surrogate avian species. As reproductive studies with Canada Geese (Branta canadensis) are tedious due to the difficulty of conducting controlled field studies and/or breeding geese in captivity, we evaluated the effects of oral nicarbazin administration on the production and hatchability of chicken eggs. Blood plasma and egg DNC concentrations were correlated to contraceptive efficacy. Subsequent studies are being conducted with geese to determine the diet nicarbazin concentration required to produce the desired blood and plasma DNC concentrations. This approach permits the expeditious evaluation of formulations and dosing regimes by simply monitoring blood DNC concentrations in target species. [ABSTRACT FROM AUTHOR]