Biologic and Therapeutic Options Discussed
The Biologic and Therapeutic Agents Forum at the 2006 AAEP Convention was facilitated by Craig Barnett, DVM, Intervet Senior Equine Technical Services Specialist, and co-facilitator Carol Clark, DVM, Dipl. ACVIM, of Peterson & Smith Equine Hospital in Ocala, Fla.
The first topic of discussion was the equine viral arteritis (EVA) outbreak in 18 states and two Canadian provinces in 2006. The outbreak was the first in the Quarter Horse industry. (In 2007, EVA reared its head again in the Quarter Horse population, see www.TheHorse.com/emag.aspx?ID=7745).
It was noted by Kevin Hankins of Fort Dodge Animal Health (which makes a vaccine against EVA) that the vaccine available to protect horses from EVA has been used minimally in the Quarter Horse industry in recent years. Once this outbreak started, however, the number of doses produced was upped from 2,000 to 18,0000 to try and meet the demand.
The AAEP Vaccination Guidelines recommendations can be found at http://aaep.org/pdfs/AAEP_vacc_guide.pdf.
The AAEP recommendations state that intact colts intended to be breeding stallions should be given one dose at six to 12 months of age with annual boosters. Document the seronegative nature of these colts prior to vaccination.
For open mares that are seronegative, vaccinate annually before breeding to carrier stallions. Isolate these mares for 21 days after breeding to a carrier stallion. Vaccinated mares do not develop clinical signs even though they become transiently infected and might shed virus for a short time.
For breeding stallions and teasers, vaccinate annually 28 days before start of breeding season. Note that virus might be shed in semen for up to 21 days.
The Forum group also discussed quarantine, since horses can shed the virus for up to 21 days through the respiratory route, and stallions can become affected for longer terms (years) and shed the virus in semen. Veterinarians also warned that while the vaccine is not labeled for use in pregnant mares, thousands of pregnant mares have been vaccinated without problem. The decision to use the vaccine off-label is up to the horse owner and veterinarian.
Young colts should be tested to determine whether they have been exposed, then vaccinated to protect them from becoming carriers when they are sexually mature.
It was noted that if a mare is to be vaccinated, a blood should be drawn from her nursing foal to show it is negative prior to the vaccination. The baby will seroconvert (show positive antibodies to equine arteritis virus) either through his dam's nasal shedding or through ingesting antibodies in the mare's milk.
"You can't tell the difference in titers (of antibodies) whether it's from vaccine or natural exposure," noted one vet.
There was a warning that many horses can become seropositive and never show clinical signs. With the Quarter Horse outbreak in 2006, about 50% of exposed horses developed clinical signs, from abortion to stocking up.
Mary Beth Evans, DVM, MS, senior staff veterinarian, Center for Veterinarian Biologics (CVB), USDA/APHIS Veterinary Services, spoke on proposed regulations on viral strain changes in equine vaccines. The point that has been discussed for the past couple of years is that there needs to be a policy change to better allow for influenza products to be updated with new strains in a timely manner when change occurs due to significant antigenic drift in the field.
Her division has worked to develop guidelines for vaccine manufacturers to allow them to update killed virus vaccines without having to go through new product licensing.
Influenza has a variety of subtypes, and is known to have antigenic drift (changes in the genetics of the virus that make current vaccines not work as well or at all). The decision was that there need to be a mechanism in place to add strains fast due to outbreaks or the potential of an outbreak. Also needed is the ability for vaccine manufacturers to delete a strain no longer causing disease from a licensed vaccine.
The current "Draft VS Memo on Viral Strain Changes in Inactivated Equine and Swine Influenza Vaccines" has been out for public comment and revised and is going through USDA revision. It assumes that replacing/adding strains shouldn't result in substantial production changes in vaccines. The new policy would allow manufacturers to substitute or add strains without repeating efficacy and field safety studies if there is justification of strain replacement/selection. There will be no more than three strains of a subtype per licensed product allowed.
The USDA will allow up to two strain substitutions within each of the subtypes present in the currently licensed vaccine. The antigen/dose of each new strain must be equal to or greater than that of the original strain unless justified by a host challenge study. Manufacturers cannot decrease the antigen/dose of the original strains unless justified by a host challenge study.
Based on adequate justification, strains of new subtypes may be added to a licensed vaccine. For an entirely new product or new process, efficacy and field safety data will be required.
Conditional licensure may be considered for an entirely new flu product or manufacturing process. Where there's a reasonable expectation of efficacy and adequate field safety data, efficacy studies can be pending. In other words, this is a fast-track licensing procedure that requires proof of purity and safety and a reason to expect efficacy. This would mean a vaccine could be on the market in about one-third the time it takes today. This means eight months to one year versus three years without this policy. This is modeled after the human regulations, although human challenge studies are not required.
There is one modified live flu vaccine (Fluavert), and that is not covered in this policy change. Neither are any vectored vaccines.
Josie Traub-Dargatz, DVM, Dipl. ACVIM, of Colorado State University, gave an update on the National Animal Health Monitoring System (NAHMS) 2005 report, which had information released starting in late 2006. She said in early 2007 the group will use event organizers in six states to do a survey on equine events, including testing requirements and procedures.
There is a tremendous amount of information available to the public, and more is being compiled and released. This information can be found at www.aphis.usda.gov/vs/ceah/ncahs/nahms/equine. (To find articles written from the NAHMS report on www.TheHorse.com, simply type in NAHMS in the keyword search box at the top of any page.)
Traub-Dargatz said horse owners should let the federal government know that a seven-year gap between reports of the equine industry are too broad. Horse owners should request more frequent studies since the information is being used and is helpful.
The question was raised by Rob Holland, DVM, a private practitioner in Kentucky and a senior veterinarian with Pfizer Animal Health, whether horse owners should vaccinate against strangles in the face of an outbreak?
The consensus of the group was no, because a horse can become a carrier or might be sick already and develop additional problems such as purpura. A horse that is exposed and asymptomatic that is then vaccinated could have an immune-mediated crisis.
One vet said he was comfortable vaccinating in the face of a strangles outbreak. Rocky Bigbie, DVM, of Fort Dodge Animal Health, said that the adjuvant in vaccines that makes them work better could cause a problem if the horse is vaccinated at the wrong time; the vaccine could actually make the horse worse.
It was noted that reporting of adverse reactions to the USDA by veterinarians is very low. "If an owner or vet thinks there was an adverse reaction, report it either to USDA or to the manufacturer" was the consensus. This can be done on the USDA web site http://www.aphis.usda.gov/vs/cvb/html/adverseeventreport.html.
Equine infectious anemia (EIA) was reported for the first time in Ireland in 2006. The source was an illegal plasma product. This brought up the discussion of unregulated plasma in the United States, a source of heated controversy for several years in this forum. One veterinarian in the audience said there is a concern this type of disease outbreak could happen in the United States because several distributors of equine serum are not USDA licensed and the products are not tested.
There are USDA-licensed plasma products that are tested for the presence of EIA, noted Tim Cordes, DVM, of USDA/APHIS. Non-licensed plasma products are not regulated.
"Normal" plasma and serum that does not make disease claims does not have to be tested, said Evans of the Center for Veterinary Biologics. She noted that the USDA/APHIS does not have staff or budget to inspect all of these products. If there is a claim on the product that it is a treatment for failure of passive transfer, R. equi, or West Nile virus, the FDA would be responsible for it because it would be considered a new animal drug.
In response to a question from the audience on how veterinarians and those in the horse industry could push for testing of all equine plasma products, Evans said the group could petition the government. "If you are aware of a manufacturer making claims, we'd like to hear about them," said Evans. "If we have evidence, we can generally investigate."
Barnett said the EIA outbreak in Ireland sends a strong message regarding the potential for disease outbreaks as it relates to unregulated equine plasma products, and that the industry needs to take a stand. Another vet brought up the potential problem of liability when using a product not licensed by the USDA.
A recommendation from the Forum was sent to the AAEP Board recommending, "That the AAEP petition USDA Veterinary Services regarding the need to regulate unlicensed, unregulated products."
The Forum also send the AAEP Board a recommendation stating, "That the AAEP utilize the Guardian and Spur of the Moment (newsletters), possibly through assistance from the Education Committee, to educate and heighten the awareness of the membership regarding the use of licensed and unlicensed plasma products."
The Forum also sent a recommendation to the AAEP Board, "That a quick reference list of equine medications be provided to the membership outlining those are approved, generics, and those for which veterinarians may need to utilize legally compounded products." And the Forum also recommended, "That an updated article with brief and specific compounding guidelines be placed in the Guardian and/or Spur of the Moment."
About the Author
Kimberly S. Brown was the Publisher/Editor of The Horse: Your Guide To Equine Health Care from June 2008 to March 2010, and she served in various positions at Blood-Horse Publications since 1980.