Notes from ACVIM 2000

In the 1970’s, non-adjuvanted modified-live virus (MLV) led the market. Cats typically received 2 MLV vaccinations per year. In the mid 1980’s, killed rabies, feline leukemia, and combination vaccines were introduced, but an adjuvant was needed to activate the immune response.

When a major outbreak of the rabies virus swept the northeast US in 1987, many states enacted legislation requiring rabies vaccinations for household pets. Widespread use of the newer, safer vaccine followed. But another development soon called the use of adjuvanted vaccines into question.

Early in the 1990’s, injection site neoplasms began to be observed and received increasing attention in the veterinary community. The Journal of the American Veterinary Medical Association (JAVMA) reported on injection site reactions. In a letter to the editor of that publication that same year, the question of sarcomas in cats caused by vaccines was posed.

There followed articles in Cancer Research, 1992, on the correlation of aluminum adjuvants to these sarcomas, and other articles suggesting that more than aluminum was involved..

A seminal epidemiology study suggested a causal relationship between vaccination and sarcomas in cats. Other products and materials have been associated with these tumors which have been observed most commonly in cats and to a lesser extent in other animals.

In 1996 the Vaccine Associated Feline Sarcoma Task Force (VAFSTF) was formed sponsored by the American Animal Hospital Association (AAHA), the Veterinary Cancer Society (VCS), The American Association of Feline Practitioners (AAFP), and the American Veterinary Medical Association (AVMA). An advisory panel on feline vaccines of the AAFP and the Academy of Feline Medicine (AFM) recommended a move to triannual vaccinations instead of annual vaccinations in 1998. This recommendation has proven to be controversial but has definitely initiated a dialog on vaccination programs and injection site sarcomas.

Continuing study of epidemiology, pathogenesis, and treatment, sponsored by the VAFSTF with financial support from the animal health community, will help to make the practice of vaccination medically sound.

One thing is clear—change us not an option for the veterinary profession. As new technologies are introduced, it is the obligation of the veterinary community to understand and learn how these technologies can be safely incorporated into the practice of medicine to best meet the needs of clients and patients.

Vaccine-associated sarcoma (VAFS) is a malignant tumor that is bigger, faster growing, and has a higher rate of recurrence that fibrosarcomas occurring elsewhere in the body. Major epidemiological studies have linked previous vaccination and the incidence of VAFS.

Inflammation has been shown to be important in the pathogenesis of some sarcomas in cats and other species and vaccine adjuvants and adjuvanted rabies and FeLV vaccines produce chronic injection site inflammation. The mutagenicity of adjuvants has been linked to free radical formation, a factor in tissue damage.

P53 (tumor suppressor gene) expression is up-regulated in response to DNA damage, not only in vaccine-associated sarcomas but in adjacent tissues, suggesting a "field carcinogenesis effect" similar to that observed in the mouth in people who use tobacco products.

Postvaccination lumps are relatively common in cats and are frequently diagnosed as benign granulomas; however, lumps persisting for 3 months or longer should be biopsied. These tumors have a characteristic histological appearance and can be distinguished from non-injection site tumors.

The use of non-adjuvanted vaccines that do not produce chronic local injection site inflammation should reduce the incidence of vaccine-associated sarcomas in genetically susceptible cats.

Feline sarcoma is a disease to prevent—not treat. When this is not the case, most authors recommend surgical removal as soon as possible after a tumor has been discovered. Diagnosis for suspected malignancy and to determine the extent of the lesion may include routine radiography, biopsy, computed tomography (CT), and magnetic resonance imaging (MRI).

The surgical procedure is to remove the skin and the tumor from at least 3 to 5 cm surrounding the margins of the mass. This means that part of the dorsal spinous processes of the thoracic vertebrae along with associated muscle must be removed.

Because these tumors are so aggressive, chemotherapy plus radiation therapy is recommended when available. Recurrence of these tumors is common, mandating aggressive wide-excision surgery.

A monthly recheck for the first 3 months, followed by one at least ever 3 months for one year is recommended.

Most vaccination-site reactions in cats appear to have a benign course and usually resolve themselves within 3 months. However, in some cats (somewhere between 1:1000 and 1:10,000), vaccine administration has been associated with sarcoma development at the site of vaccination. The frequency of vaccination has been implicated in the formation of malignant neoplasms and suggests to some that cats have become an over-vaccinated population.

While no one is recommending against vaccination, it is important to assess need and risk before administering a vaccine. Core vaccines (rabies, rhinotracheitis, calicivirus, panleukopenia virus), are considered mandatory for animal health.

Rabies vaccination has been required by law in many states for human health because of previous outbreaks. However, vaccination beyond these core antigens should be administered with discrimination after careful evaluation, including consultation with the owner.

Recombinant (genetically engineered) vaccines are among the newest responses to the need for a safe vaccine technology. Gene-sized fragments of the DNA proteins responsible for infection are isolated and spliced together (recombined) within the genome of another organism, usually an avian poxvirus. When the new augmented virus is administered to a cat, it develops an immunity to the original virus. The whole virus is never introduced, allowing for the administration of a product that not only eliminates the possibility of infection, but is free of inflammation-producing adjuvants. That, and more conservative immunization schedules, should go a long way toward eliminating vaccination site neoplasms.

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