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Alliance of Wild Horse Advocates

SITUATION REPORT

Trials Begin for 3-4 year
PZP Fertility Control



Issue: Alternatives to removing horses to provide stable populations

Situation: Fertility study team starts trials of PZP formula that should provide three to four years of fertility control.

Location: Carson City, NV

Date: March 15, 2011

Report by: Willis Lamm

At the March 10-11 meeting of the National Wild Horse and Burro Advisory Board an announcement was made that trials would soon begin on a three to four year fertility control vaccine.

The following week, on a cloudy Tuesday morning in Carson City, a field trial started that could potentially change the parameters for managing free-roaming horses on public lands. Dr. John W. Turner, Jr. (University of Toledo College of Medicine, Health and Science) and Dr. Irwin K. Liu (U.C. Davis School of Veterinary Medicine) initiated a trial on 105 wild mares that could validate such a breakthrough. Volunteer Palomino Armstrong and I were able to witness, assist and learn a great deal about this process.

Why pursue fertility control?

Although the Wild Free-roaming Horses and Burros Act calls for agencies to utilize designated herd areas principally for the welfare of free-roaming horses and burros, the Act and other laws place some constraints on horse populations. For example, agencies have to manage for multiple uses and to achieve thriving ecological balance, and horses are a dominant species on the range.

While it has been argued that various alternative management models could be applied, the current reality is that some alternatives to present management strategies would require changes in federal law before they could occur. Furthermore, huge sums of money are presently required to support tens of thousands of horses in long term holding and little money is available to implement new models or to collect data and monitor the effectiveness of alternative management models. Therefore as a practical matter the two choices presently available to BLM are removal of excess horses and controlling the rate of fertility within the herds.

The greatest advantage of applying fertility control is that it has the least negative impact on the genetic viability of a given herd. The numbers of breeding members of the herd are not dramatically reduced every few years. This broader "genetic platform" is allowed to continue to exist however each mare would simply produce fewer offspring over her lifetime. Genetic diversity would remain robust while the horse population would more likely remain within its resource limits.

Conversely, removing members of the breeding population is disruptive, reduces genetic diversity, and there is evidence to suggest that large reductions of ungulate populations actually stimulate compensatory reproduction. Thus overdependence on removals as a means to manage horse populations is in several ways counterintuitive.

What is PZP?

PZP is an abbreviation for Porcine Zona Pellucida Vaccine. It is actually a vaccine that inhibits fertilization of eggs in mares. Here is a simple explanation as to how it works.

Every mammallian egg is coated with a membrane called the zona pellucida which is basically a sperm receptor. The PZP vaccine produces antibodies in the horse that bind to the zona pellucida and prevents conception.

The PZP vaccine is derived from pig's eggs. It is harmless to the horse when injected however it produces an specific immune response. Zona pellucida antibodies bind to the zona pellucida membrane during ovulation. This immune response is much the same as how harmless cowpox vaccine produces an immune response in humans that will protect humans against deadly smallpox.

PZP does not affect egg production, mares' cycles or seasonal ovulation. It simply prevents the eggs that the mare releases from being fertilized. Physiologically, when the effects of the vaccine wear off the mare will simply stop producing antibodies and normal conception will resume without any specific intervention.

How can one vaccination provide three to four years of fertility control?

Time release medications have been around since the early 1960s, the most commonly known being SmithKline French's "Contac 12 Hour Cold Medicine" with its "tiny time-release capsules." As this technology evolved, a variety of polymers were developed within which specific medications could be encapsulated and that had specific degradation properties. Medicines and vaccines could be released anywhere from a few hours to multiple years. Presently the use of polymers to control the release of materials that they contain have been used in thousands of applications including the delivery of medications, fertilizers and insect controls.

Polymers containing PZP are tiny, about the size of a shard of mechanical pencil lead. A handful of tiny "pellets" release PZP at varying intervals. They are injected into a large muscle using a "jab stick." Typically a mare receives a liquefied "primer" vaccination that triggers an immediate immune response that will last until the vaccine in the pellets starts to be absorbed. The mare's immune system would be expected to prevent conception following the dosage received from each time release pellet.

The two greatest advantages of this formula and delivery system over their predecessors are that each mare only needs a single treatment and fertility control should be expected to last three to four years. Disruption of free-roaming bands due to catch, treat and release is minimal.

How the study will work.

A primary purpose of this study is to compare two versions of three to four year PZP with the two year formulation currently being used and also compare the effective of PZP formulations with untreated control mares. Periodic blood work will be done on the mares to track the biological efficacy of the vaccine as well as any side effects that might appear. PZP has been in use for decades, so what would be significant is how consistently this delivery method provides fertility control over long periods of time.

Approximately 100 breeding age mares have been selected for this trial. One-fifth received the current 2-year vaccine. One-fifth received one version of the 3-4 year vaccine. One-fifth received the other 3-4 year version. One-fifth received no vaccinations and will serve as a negative control group. One fifth is a "positive" control group that will receive the original two-injection vaccine upon which all subsequent PZP vaccines have been based. Of the two-shot protocol, the first shot is the primer and the second shot, which they receive three weeks later, is the booster. All the horses have been identified for tracking purposes and blood was drawn to provide a baseline for hematological study.

The mares were distributed into six large holding pens, each pen receiving an assortment of mares from all five study groups. The pens are sufficiently large to allow the mares to socialize, establish band hierarchies and to accommodate foals produced by the control mares. Stallions will be introduced (one per band) once the mares have settled and established social order.

One of the "bands" of mares from the various study groups.
At predetermined intervals the stallions will be rotated from one study band to another to ensure that the possibility of lack of virility in one or more of the stallions would not skew the study results.

Dr. Gerald Peck will monitor the health and condition of the mares and will do periodic blood work.

The delivery system.

The methodology to deliver PZP has improved dramatically over the years. It has evolved from crude darting of horses to "jab stick" technology. The most current version of the jab stick, as was demonstrated by Alan Shepherd, is a relatively sophisticated spring loaded device that simply requires the user to tap the horse in a large muscle, in this case in the medial glutial (rump) muscle. The spring mechanism injects the capsules into the muscle. The process is no more invasive than injecting an annual booster vaccine and actually takes a fraction of the time. The horses showed little if any reaction to being "jabbed."

The vaccination and monitoring process.

The Stewart Conservation Camp horse program has a large, modern horse preparation facility where several hundred horses are maintained. It includes specially designed chutes and alleys that allow for the quiet and orderly movement of horses and a padded veterinary squeeze for safely confining horses to draw blood, provide vaccinations, hoof care and other veterinary treatment. The Camp Manager is Tim Bryant who has decades of livestock experience and the horses are handled by Hank Curry's inmate horse training crew.

Each study group of horses, except for the control group, was brought into the chute area and went through the vetting squeeze one horse at a time. The ID of each horse was checked and recorded. Then Dr. Peck took a blood sample and Dr. Liu and Dr. Turner injected the primer and time release capsules. From there the horses were disbursed to their respective study bands.

Dr. Liu injects the primer.
Dr. Turner positions the jab stick.

Dr. Peck will monitor the horses through the test period.

Facts and myths.

There have been a number of concerns expressed among advocates with respect to possible unintended effects of PZP. In fact a number of bizarre theories have emerged. The following information is based on years of observations, including our direct observations of hundreds of Virginia Range horses, and from a better understanding of how PZP actually works.

PZP simply causes an immune response that affects the zona pellucida and prevents conception. It has no affect whatsoever on any embryo that the mare might already be carrying or any other ovarian or uterine tissue. Since PZP is a vaccine rather than some chemical agent, there should be no issues that would otherwise be generally associated with chemical exposure to sensitive tissues.

PZP does not affect a mare's cycle or season. It simply prevents conception of those eggs normally produced. There is some anecdotal evidence that some mares that haven't conceived could release one additional egg before seasonal shutdown but this effect is not significant.

There is a very small percentage of mares who ovulate out of season. In the wild we will see an occasional December, January and February foal from mares that have never received fertility control. Since PZP does not effect ovulation, it can neither decrease or increase incidences of mid winter conception and foaling.

Most horses' lives revolve around the social structure in which the horses engage. Our observations of fertility controlled horses showed relatively consistent trends before, during and after fertility control. Lead mares remained lead mares. The social order remained intact. The social associations between mares appeared to be unaffected. (This was an important element for us to witness in order to be comfortable with this population control approach.)

Mares do get bred more often. In observing free-roaming bands with fertility controlled members the increased breeding seemed to be somewhat distracting, however most free-roaming stallions are pretty calm about this business when they have a decent sized harem. Consequently the mares appeared to come to no harm. Conversely immature two year old fillies weren't becoming pregnant and older mares that during prior years constantly presented with a gaunt appearance were regaining lost weight and behaving more robustly. Aside from reducing the need for removals, the general health of the bands appeared to improve when mares were able to "rest" between producing foals.

We are also keenly aware that interrupting the production of foals is far less disruptive to the horses than the alternative of permanently snatching them off the range.

With respect to rotating stallions during the test, such activity will likely produce some social disruption. However on the range more dominant stallions commonly displace less dominant stallions. So long as the harem of mares stays intact, the mares seem to have little concern about stallion displacement, oftentimes not even stopping reciprocal grooming or foal care while rather intensive stallion battles took place nearby. "We're supposed to go with you now? OK, then."

While stallion replacement during the test would be more frequent than natural changes that would take place on the range, it is not likely to seriously disrupt the mares' social fabric. Furthermore any stallion that exhibits aggressive breeding tendencies or demonstrates threatening behavior towards foals will be immediately removed from the trial.

Conclusions.

This activity is an efficacy test. How well these vaccines work will be established at the end of the test.

The test is being conducted by some of the leading experts in the field. There is high confidence that the conclusions produced will be valid and useful.

The Stewart Conservation Camp is a safe, suitable facility with sufficient staff to carry out the day to day objectives of the study.

The inclusion of study groups that are being given earlier versions of the PZP formula will expand the knowledge base with respect to those formulations. More data is always useful. The greater the amount of relevant data, the more reliable the conclusions are likely to be.

Equine fertility control is an advancing science. This study is an important step in producing safer, longer lasting population management techniques.

Equine fertility control allows for more proactive herd population management. If we are to achieve any significant improvements in herd management methods and ecosystem management models, we will likely have to relieve the significant drain on financial resources produced by accumulating and warehousing horses. To use an ER metaphor, we have to stop the bleeding before we can cure the patient. This test is an important step toward reducing the financial bleeding that impedes BLM's ability to test and properly evaluate new range and horse management models.

Willis Lamm
March 15, 2011


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