One BIG HAIRY DEAL

USDA grants conditional licensing for controversial hairy footwart vaccine

On March 17, Hygieia Biological Laboratories received a conditional license from USDA to sell its Serpens species Bacterin for the prevention and treatment of papillomatous digital dermatitis (PDD), commonly known as hairy footwarts.

While the vaccine may sound like a godsend to dairy herds plagued by hoof warts, the vaccine is embroiled in controversy. For starters, the bacteria that the vaccine stimulates immunity to has never been identified as causative agent of hairy warts by noncompany researchers. And, to date, no independent, peer-reviewed university study has been made public that demonstrates the vaccine actually works.

Still, USDA issued its conditional license earlier this spring for nationwide sales. State veterinarians in 39 states have allowed the sale of the vaccine in their jurisdictions for at least the next 10 months.

In order to qualify for a conditional USDA license, Hygieia had to satisfy requirements for safety, purity and "a reasonable expectation of efficacy." (For full licensing, the company must also document efficacy and potency.)

Safety refers to freedom from undue adverse reactions-both local and systemic-when the product is used as directed. Purity incorporates strain identity. A vaccine is pure if it is made from a correctly identified and completely purified master seed bacteria and the final product contains only that bacteria, and no viable contaminants.

"Reasonable expectations of efficacy" simply stated means: Does the vaccine work?

"Hygieia doesn't currently have trial data with a high degree of confidence relative to efficacy. However, we have a reasonable degree of confidence that the vaccine does what the manufacturer claims it to do regarding prevention and treatment of footwart lesions and lameness," says Dr. David Espeseth, director of USDA's Center for Veterinary Biologics, Licensing and Policy Development. "We grant a conditional license with the reasonable expectation that the product will produce the results for which it is offered."

According to Dale Wallis, Hygieia's senior staff veterinarian and the co-developer of the vaccine, USDA has completed evaluation of only two preliminary trials.

"We have correspondence documenting the USDA statistician's conclusion of a sevenfold reduction in the incidence of new warts in vaccinates compared to controls (non-vaccinates), with a probability of error of only .006," Wallis says.

"We believe healing of lesions of vaccinates when controls do not improve means the vaccine is efficacious."

USDA's conditional license requires Hygieia to secure written permission from the state veterinarian before the vaccine can be shipped to any particular state. In many states, specific sales restrictions apply, so it's best to ask your veterinarian for details.

As we go to press, the states that have not yet responded to Hygieia are Alaska, Arizona, Delaware, Georgia, North Carolina, Rhode Island and South Carolina.

Thus far, four states have denied permission for footwart vaccine sales. "We were told that footwart vaccine field trials are currently underway in Illinois, so the state vet didn't want the product sold commercially, at least for now.

"Vermont requested updated USDA labeling information on the vaccine before it can be sold there," Wallis explains.

Nevada and New Jersey don't want any conditionally licensed products sold in their states.

Serpens species Bacterin has been licensed in California for over-the -counter (OTC) sales since July 1996, having satisfied the same four criteria (safety, purity, efficacy and potency) for the California Department of Food and Agriculture. Since, then, Hygieia has sold some 65,000 doses of the vaccine.

Field trials. To test Serpens species Bacterin, Hygieia conducted field trials at five commercial dairies¾four in California and one in Utah. A total of 3,450 cows were involved in the studies, which were conducted from March 1996 to the present.

Leen and Paula deSnayer volunteered their 500 cows for a one-year footwart vaccine trial that was completed on March 15, 1998. Prior to starting the trial, the Lodi, Calif., herd was divided into three groups based on age, lactation number and days in milk.

Each group included both animals with active PDD lesions and clinically normal cows. The deSnayers didn't know which animals were included in which group. Vaccination or control status was assigned to each group randomly.

The deSnayers discontinued foot baths during the trial. They did continue to apply antibiotic powder and bandages to infected footwart lesions. That treatment included 210 different cows, and about 20 cows were bandaged twice. At the end of the trial, more non-vaccinated cows had been bandaged than vaccinates.

"We saw a big difference, especially after the second vaccination. Since the trial began, we've had less incidence of footwarts in the herd as a whole," Leen relates. He did notice that footwarts reoccurred in the herd in August and December of last year.

"I feel the vaccine is working, but not for as long as we had hoped," Leen says. "After three months, the effects taper off." The reoccurrence helped Hygieia to determine booster recommendations.

Hygieia also received permission from the Utah state veterinarian to conduct a study at Ray Gilbert's dairy in Lewiston, Utah. About 25% of Gilbert's 650 Holsteins were infected with footwarts prior to the trial. Upon completion, analysis indicated more than an 80% reduction in lesions for vaccinated cows, according to Gilbert's veterinarian, Larry Mitchell.

"It seems to me, that in the field, we've seen a response to the vaccine and it has made a significant impact," Mitchell says. "I recommend it to producers who are having problems with footwarts."

Columbus, Wis., dairy producer John Winter acquired Serpens species Bacterin from his nutritionist, who won some doses in Hygieia's door prize drawing at the 1997 World Dairy Expo.

Winter launched his career in dairying just last April. He purchased three-fourths of a Holstein herd, plus additional cows at auction, for a total of 50 head. "I bought a hornets' nest," Winter says. "From the time I started milking, more than half of my cows had chronic sore feet because of footwarts. Tank average was only 30 lb. of milk per cow per day."

Winter tried the widely accepted treatment protocols¾footbaths, antibiotic sprays and bandaging. "I was wrapping feet on five or six cows each day," he says.

Starting November 20, 1997, Winter discontinued all previous treatments and gave his entire herd three initial doses of Hygieia's vaccine at four-week intervals, according to label directions. He followed with a booster after four months in mid-March.

"Footwart lesions started clearing up gradually after the third dose," Winter reports. "Now all the lesions are completely healed. Since we started vaccinating, we haven't had any new cases of footwarts, and tank average had increased to 68 to 70 lb. per cow per day."

Despite the glowing testimonials many scientists and veterinarians in the field remain skeptical. While approximately 15 groups of researchers throughout the world are investigating PDD, Hygieia is the only known lab to have isolated the Serpens species bacteria in PDD lesions.

Researchers with the Hairy Footwarts Task Force at the University of California at Davis (UCD) are investigating the role of spirochetes in PDD because they are one of the predominant bacteria types that are found deep in the PDD lesions.

Like many professionals in the dairy world, UCD researchers Richard Walker, David Hird, Deryck Read and Steven Berry all question Serpens species Bacterin because there are as yet no published results in peer-reviewed journals describing vaccine studies conducted at major universities or other non-commercial laboratories.

"In fact, there is no conclusive evidence in any peer-review literature that identifies the definite etiologic agent of PDD," says Walker. "A number of bacteria have been associated with PDD; however, the casual role is yet to be proven for any of the organisms."

Last summer, Berry and Tom Graham, a herd health veterinarian in private practice, led a randomized controlled study to test the efficacy of Hygieia's footwart vaccine in a commercial herd. As we go to press, Berry and Graham are still waiting to hear if their study will be accepted for publication in the Journal of the American Veterinary Medical Association. Until their manuscript is accepted, trial design details and official results are unavailable for publication elsewhere.

Until more research is available, Graham suggests that "dairy producers work with their veterinarians to examine the efficacy and cost effectiveness of any new product to ensure its usefulness."

Wallis says that over the last 12 to 15 months, Hygieia has offered to sponsor vaccine studies at several major universities. Thus far, only one school has responded. As a result, a new field trial involving Serpens species Baterin was recently initiated at a U.S. veterinary college. However, the exact location and protocol are confidential. It is typical for university studies to remain confidential until the results are in and the data analyzed.

While the world waits for more peer-reviewed data, industry professionals are formulating opinions on the future of Serpens species Bacterin and hairy footwarts.

"There's nothing I'd like better than to see a vaccine that works for footwarts," says University of Florida Extension Veterinarian Jan Shearer.

"I'm as undecided as anyone might be at this point, because most of Hygieia's research has not been subjected to peer review. All I have to go on right now is information from the manufacturer," Shearer says.

"It would be irresponsible for me to recommend something that hasn't withstood the scrutiny of peer review," Shearer continues. "So for that reason I've got to be very careful about any recommendations I would make regarding the vaccine," he says.

In recent years, Shearer has been advising commercial dairy producers throughout Florida about footwart treatment. He has advocated topical antibiotic sprays alone, or combined with bandaging.

"Producers are spending a lot of money on things that are ineffective for footwarts," he says. "I don't see topical sprays, with or without bandaging, as solutions, [but] merely stopgap measures.

"We need a solution for footwarts. A vaccine combined with proper environmental management [is] part of what will likely be a solution," he projects.

James Jarrett, executive vice president of the American Association of Bovine Practitioners (AABP), says the vaccine "receives mixed reviews" from "five or six" AABP board members, who are veterinarians working in various parts of the country. "Some veterinarians in our organization are concerned about the lack of peer-reviewed research data," Jarrett adds.

Hygieia's conditional license expires March 17, 1999. The company has until that date to prove to USDA that is has made adequate strides to satisfy the efficacy and potency requirements for full licensing of Serpens species Bacterin.

When the conditional license expires, Hygieia will either be granted a full permanent license, its conditional license will be extended for one more year, or it will be denied further licensing until acceptable data are filed.

The current labeled protocol for prevention includes three 5-cc doses administered subcutaneously (under the skin) at four week intervals (0, 4 and 8 weeks), with a single booster dose four months after the third dose and every four to six months thereafter.

For treatment of PDD-affected animals, three 5-cc doses are administered subcutaneously at four week intervals (0, 4 and 8 weeks) in conjunction with appropriate management practices, which may include footbaths or wraps. After healing, another dose should be given, followed by single booster doses every four to six months.

The retail OTC price per dose is about $4.00 to $4.50, so in a normal prevention program, the cost is $20 to $27.00 per cow per year.

For more information about Serpens species Bacterin, contact: Hygieia Biological Laboratories, 1785 E. Main St., No. 4, P.O. Box 8300, Woodland, Calif. 95776; phone: (916)-661-1442; fax: (916)-661-1633; e-mail: Hygieia@Com-puserv.com

Sidebar:

Footwart Disease Characteristics

Disease characteristics:

• First-calf heifers most often affected
• Feet only affected, usually hind feet
• Severe lameness, walking on toes, clubbed toes, loss of body weight, decreased milk yield and reproductive efficiency
• Little or no digital swelling (in contrast to foot rot)