First published in "Bellwether" #45
The Newsmagazine of the School of Veterinary Medicine, University of Pennsylvania
Spring/Summer 1999

In the late 1980s and through the early 1990s, Dr. Mattie Hendrick, associate professor of pathology, noticed an increase in incidence in feline fibrosarcomas seen in the pathology department of the School. Pennsylvania had recently enacted a law that made rabies vaccinations mandatory for all cats, and new, powerful rabies vaccines as well as feline leukemia vaccines had just been introduced. A retrospective analysis of the cases found that these sarcomas had occurred at sites typically used for injections, and a microanalysis of some of the tumor sites revealed measurable amounts of aluminum hydroxide, a commonly used adjuvant in vaccines surrounding the tumors. Clinicians worldwide were made aware of the possible connection between vaccines and feline sarcomas.

Many vaccines cause a lump or an inflammatory reaction in cats one to two weeks after vaccination. Dr. Hendrick said that it has been hypothesized that in some cases, something during the inflammatory reaction causes the local cells at these reaction sites to "change from normal cells that proliferate in response to injury or wounding to become tumor cells." Some investigators are looking at the role of growth factors and oncogenes in the proliferation of the sarcomas.

Feline vaccine-associated sarcomas have occurred in cats that received all different types of vaccines, including those with and without adjuvants. The clear majority of the tumors in one study, however, was associated with the FeLV and rabies vaccines. The effect of vaccines has been found to be additive, that is, the more vaccines injected simultaneously into one site, the greater the tumor risk.

Although the cats that experienced these sarcomas were of all ages, the mean age was eight years and most of the tumors appeared two months to 10 years after vaccination. No breed of cat was particularly susceptible. Females and males were equally affected. Neither feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) infections were factors in incidence. To approximate an accurate rate of prevalence, 2,000 cats vaccinated in one practice were followed for five years. Five developed sarcomas / all at rabies vaccination sites.

One study showed that vaccine-associated sarcomas have a recurrence rate as high as 62%; most tumors recurring two to five times in the period six months to two years after the initial occurrence. Metastasis, however, is uncommon.

The tumors themselves are characterized as grey-white, firm, and usually well demarcated, often with central areas of necrosis. One of the reasons that the sarcomas have such a poor prognosis and high rate of recurrence is that this characteristic demarcation can be extremely deceptive. There are often tumor "fingers" that stretch out along the fascial plane and can be very difficult to excise completely. Excision of the tumor "fingers" is vital and provides the cat with the best chance of prolonged survival. "Most people believe that aggressive surgery with wide margins is the best treatment," said Dr. Hendrick, "and 'aggressive' is the important part." The results of radiation and chemotherapy remain largely unclear.

In 1996, the Vaccine-Associated Feline Sarcoma Task Force (VAFSTF) was formed. One of the first achievements of the VAFSTF was the issuance of a list of recommendations to veterinarians, recommending, among other things, that veterinarians keep complete vaccination records, vaccinate at separate sites, and keep those sites distal. The group has also funded a number of ongoing studies in the epidemiology, etiology and pathogenesis, and treatment of vaccine-associated feline sarcomas. The ultimate goal of all research is, as Dr. Hendrick pointed out, prevention or cure of this condition. P.C.

Too much of a good thing is bad? This statement seems custom-made for the subject of vaccination. Dr. Nicola Mason, lecturer in medicine at the School, presented relevant immunological principles and made a compelling case for the conservative approach to canine vaccination.

The aim of vaccination, Dr. Mason explained, is to prime the immune system to respond rapidly and efficiently to antigenic challenge. The first puppy and kitten vaccinations will stimulate the primary immune response that is characterized by a relatively slow increase in antibody titers. The puppy and kitten booster vaccinations and thereafter annual vaccinations stimulate an anamnestic response during which the antibody titers rise more rapidly and to a greater extent than is seen with the initial introduction to the vaccine antigen.

Vaccines may contain either killed or attenuated antigen. Killed vaccines require parenteral administration and usually contain high levels of antigen together with an adjuvant. Killed vaccines will not revert to virulence. Modified live vaccines (MLV) are generally more potent, and are formulated in lower antigenic doses without the necessity for adjuvants. MLV's may be administered locally (i.e. intranasally) and reversion to virulence is possible.

Whether they are administered subcutaneously, intramuscularly, intranasally or orally, vaccines are not entirely benign. The most immediate adverse effects of vaccination are anaphylaxis and anaphylactoid responses. These responses are very uncommon, but when they do occur the effects are often seen within minutes to hours of vaccination and appear to be more frequently seen with the use of killed vaccines.

Dr. Mason also addressed the topical issue of vaccine-induced hemolytic anemia. "Retrospective studies have demonstrated a temporal relationship between vaccination and the onset of immune-mediated hemolytic anemia. Although suggestive, a true cause and effect relationship between vaccination and immune-mediated hemolytic anemia has not yet been demonstrated," Dr. Mason said.

The potential adverse effects of vaccination underscore the need to tailor vaccination protocols on an individual basis. Canine "core" vaccinations include rabies, distemper, adenovirus, parvovirus and parainfluenza. Use of "non-core" vaccines such as Lyme, leptospirosis, coronavirus and broadtail should be determined based on the risk-to-benefit ratio of administration for each individual patient. Dr. Mason did not support the use of the Lyme vaccine stating that most cases of "Lyme disease" in the dog are often self-limiting or readily responsive to antibiotic therapy (Lyme nephropathy was the exception).

Typically canine vaccination protocols call for DA2LPPi immunizations every 3-4 weeks between the ages of 6-8 weeks and 16 weeks. Rabies vaccines are usually administered at 13 weeks of age. The frequency of booster vaccinations is controversial. Most of the U.S. veterinary schools advocate annual revaccination with DA2LPPi; however, some are now recommending booster vaccinations every three years.

"Although vaccination protocols and vaccines are under increasing scrutiny with respect to adverse effects, we should not forget that the frequency of adverse effects is extremely low and because of vaccination, we are able to protect our pet population from a number of potentially fatal diseases," Dr. Mason said. J.C.

Vaccination protocols have prompted considerable controversy in recent years, as veterinarians have begun to reevaluate vaccination strategy on a risk-benefit basis. "We began to see that there were some adverse effects to vaccination / that these vaccines weren't as benign as experts have led us to believe," said Dr. Diane Eigner, president-elect of the American Association of Feline Practitioners (AAFP).

New data and fresh reanalysis of key therapeutic issues have prompted the AAFP to revise its feline vaccination guidelines. Dr. Eigner, who operates the Philadelphia-based veterinary practice, The Cat Doctor, discussed the key issues regarding vaccination and presented the current vaccination guidelines.

To address the issue of adverse reactions to vaccines, the AAFP modified its recommendations regarding which vaccines to administer and the frequency at which they should be given. Core antigens were defined as those for which the consequences of infection are severe, public health issues are involved, and infection is prevalent. The AAFP listed the following as core antigens: rabies, feline panleukopenia (FPL), feline viral rhinotracheitis (FVR) and feline calicivirus.

The AAFP classified as non-core antigens: feline leukemia virus (FeLV), feline infectious peritonitis (FIP), chlamydia and Microsporum canis, and recommended that FeLV and FIP be given only to at-risk cats.

Based on clinical studies that revealed durations of vaccine immunity to exceed one year, the AAFP recommended that vaccinations not be given annually, as has been the convention. They advocated vaccinating kittens for the three core antigens, and revaccinating at one year of age and then every three years thereafter (annually in high-risk populations, such as breeding colonies and cats being boarded). The rabies vaccine should be administered at three months of age, one year of age, and then every three years thereafter, unless local law mandates greater frequency. For FeLV, at-risk cats should be vaccinated according to manufacturers' recommendations (generally annually).

The AAFP also made suggestions regarding vaccine type (killed vs. attenuated), composition (single antigen vs. multivalent) and administration route.

Dr. Eigner encouraged owners to learn about vaccination issues and participate in making decisions regarding the vaccination of their cats. "We want people to look at the benefits as well as the risks." J.C.

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