Having worked in the veterinary profession for the past six years, I was aware of Vaccine Associated Fibrosarcoma, but had not seen any of the practices that I worked in make any changes to their vaccine recommendations. I hoped that in compiling the available information on this disease, I might be able to propose changes to the current vaccine protocol based on all of the available information and provide a comprehensive source of current information for concerned cat owners.

I was surprised to find the scientific information to be very one sided. The controversy is not scientific as I had believed, but rather it is a political and ethical debate within a dramatically changing profession. As a cat owner myself, I was very disappointed with what I discovered in researching this disease.

I was extremely fortunate to have the assistance and support of some wonderful veterinarians in my quest for information:

• Gregory Ogilvie, DVM, Diplomate ACVIM, Professor of Oncology
• Dennis Macy, DVM, Diplomate ACVIM,
• Larry J. Swango, DVM, PhD, Professor of Virology at Auburn University
• Felicia Neuman, DVM
• Jamie Molinelli, DVM
• Timothy Slajchert, DVM
• Kevin Doherty, VMD
• Steven Shipley, DVM
• Edwin Kriel, DVM

I am especially grateful to Dr. Ann Minihan, Diplomate of the American College of Veterinary Surgeons, of Chesapeake Veterinary Referral Surgery for allowing me to photograph the removal of a VAS and for sharing so much information about the surgical aspects of treating this type of cancer. I am also grateful to the Animal Emergency Center for allowing me to photograph Bouf, a cat with a very advanced fibrosarcoma tumor on his back. It is my hope that this report will accomplish something good for all of the other "Bouf"s and their owners.

I also want to express my gratitude to Jeff and Coleen Kremer, who not only provided me with endless resources, but also inspired me to be as thorough and accurate as possible. They have served as a strong reminder that this disease is not about statistics and studies, but about people and the pets that they love

Although broad changes have not yet been made in feline vaccination programs, the openness and honesty that I encountered as I searched for answers and information is very encouraging. Any changes that occur will likely be attributable to veterinarians such as those listed above. Their dedication towards excellence in their profession and their commitment to providing the best possible care for their patients should not go unnoticed

The only appropriate dedication for the work that I have put into this project is to the cats that suffer from this disease, past, present, and future. During the process of researching and writing this report, I was blessed to have met several cats suffering from vaccine-associated fibrosarcoma. Nothing in this report does justice to their suffering, and no statistic conveys the urgency of this issue for the victims.

As a member of the veterinary profession, I am ashamed to say that we have let these animals down. The only thing that I can offer to the cats that still have a chance is a voice and a personal commitment to educating as many cat owners as possible about the risks of overvaccination. Below is a photograph of a cat named Bouf, taken on the last day of his life. He never received treatment for the VAS that caused his owners to euthanize him on Wednesday, November 3, 1999.

My hope is that through education and dissemination of information, Bouf will not have died in vain, but that his experience will serve as a warning to both veterinary professionals and cat owners everywhere.

Vaccine Associated Fibrosarcoma became an issue in the early 1990’s. Since then, hundreds of thousands of dollars have been poured into researching the cause and treatment of this disease. Despite the efforts to understand this disease, many questions remain unanswered. The answer that is the most clear is not pleasant. The prognosis for cats diagnosed with VAS is very poor with only 5-6% surviving for more than two years after diagnosis.

Although there is no conclusive evidence as to the way in which vaccines cause fibrosarcoma, many theories have been postulated. There are three basic theories regarding how vaccines induce fibrosarcoma tumors: vaccine adjuvants, inflammatory response, and a genetic predisposition. The most likely explanation is a combination of all three. Despite the lack of answers, the fact that this cancer represents a serious threat to the companion cat population is undisputed. Estimates of the incidence of this disease are as high as 1:1000 vaccinated cats.

Current vaccine protocol, as recommended by the vaccine manufacturers, involves annual revaccination for all cats, regardless of their likelihood of exposure to disease. Although the incidence of infectious diseases has decreased and animals are more likely to be examined yearly, there are still many disadvantages to yearly vaccination. These disadvantages include failure to address individual situations and needs and the risk of fibrosarcoma.

Recommendations for a revised vaccination schedule include triennial revaccination for cats that are not at a high risk of exposure, elimination of FeLV vaccination for cats in lower risk categories, and standardizing the injection sites to facilitate both early diagnosis and treatment if a fibrosarcoma should develop.

Some veterinarians have voiced objections to changes in vaccine protocol, particularly to changing frequency recommendations. Other objections include concerns about legal liability, loss of revenue, and reduced compliance with annual exam recommendations. Overcoming these obstacles will involve a changing legal picture, changing the focus of the annual visit, better communication between veterinarian and client, and re-educating pet owners as to the benefits and risks of annual vaccinations and exams. There is not likely to be a satisfactory resolution to this problem without the cooperation of the veterinary community, vaccine manufacturers, government regulatory agencies, and, most importantly, the active participation of concerned cat owners.

Figure 1. Photograph of a Cat with an Untreated Fibrosarcoma Tumor…………… 3

Figure 2. Vaccine Associated Feline Sarcoma Task Force…………………………….. 4

Figure 3. Removal of a Vaccine Associated Fibrosarcoma Tumor……………………. 6

Figure 4. Survival Rates……………………………………………………………………. 7

Figure 5. Photograph Illustrating 3 cm Surgical Margins…………………………….. 8

Figure 6.Photograph of a Surgical Wound……………………………………………….. 9

Figure 7. Photograph of Closed Surgical Site……………………………………………. 9

Figure 8. Chart Illustrating Recommended Vaccine Schedule for Cats …………….. 11

Figure 9. Diagram Illustrating Recommended Vaccine Sites…………………………. 16

Figure 10. Chart Illustrating Efficacy and DOI of Feline Vaccines…………………... 22

Figure 11. Chart Indicating Vaccine Cost, Price, and Mark-up………………………. 23

Between 1987 and 1991, veterinary pathologists noted an alarming increase in the number of fibrosarcoma tumors observed in feline biopsy samples submitted for pathology. The pathologists also discovered vaccine components in the tissue submitted. At the same time, the veterinarians submitting the samples noticed that the tumors were increasingly appearing in vaccination sites. As reports of these findings trickled in to veterinary colleges and organizations, oncologists and internal medicine specialists began research projects to see if the observations were merely anecdotal or were a significant medical finding. Joined by feline practitioners and immunologists, the investigation into the suspected vaccine connection began in full force.

In 1996, the American Veterinary Medical Association, the American Animal Hospital Association, the American Association of Feline Practitioners, and the Veterinary Cancer Society created a task force to define the scope of the problem, determine causes and prognosis of the syndrome, and educate and inform both veterinarians and members of the public. As the first multi-organizational task force ever convened by the veterinary profession, the Vaccine Associated Feline Sarcoma Task Force (VAFSTF) combined all relevant areas of expertise in order to make comprehensive and accurate recommendations to the veterinary community.

Although the VAFSTF, the AVMA, and the AAFP have recommended initial changes to vaccine protocol, very few practicing veterinarians have complied with them. Despite the broad changes veterinary teaching hospitals have made in their vaccine programs and recommendations, many private practice veterinarians have treated the probable connection between vaccines and fibrosarcoma with disbelief and have discounted the available information as misleading and alarmist. Veterinary medicine is largely self-regulating and sometimes unregulated. In conjunction with the large percentage of clinic revenue tied to current vaccine protocol, there is a very hostile environment in which to research this potentially explosive subject. All of the concerns expressed by practicing veterinarians must be addressed in order to bring about any significant change in feline vaccination programs.

The following report examines the history and scientific evidence of Vaccine Associated Fibrosarcoma, current vaccination protocols, recommendations for future vaccination protocols, anticipated objections to those recommendations, and responses to those concerns. A glossary is included for words in bold type and can be found at the conclusion of this report.

Fibro comes from the Latin word fibra. In the combining form, it means fibrous matter or structure. Sarcoma comes from the Modern Latin sarcoma, which was derived from the Greek word sarx, meaning flesh. It identifies any of the many malignant tumors that originate in connective tissue, or tissue developed from the mesoderm. Therefore, a fibrosarcoma is a fibrous tumor originating from connective, vascular, skeletal, muscular, or other mesodermic tissue.

Although this type of cancer occurs in many species, this report will only address how this cancer manifests itself in felines in association with vaccinations.

Since the early nineties, there has been speculation about a connection between the development of fibrosarcoma tumors and vaccinations. Multiple studies have been conducted at veterinary colleges nationwide yielding some surprising and disturbing results.

A letter to the editor published in the Journal of the American Veterinary Association in 1991 was the first report proposing a connection between vaccination and the subsequent development of fibrosarcoma. This letter, written by Drs. Hendrick and Goldschmidt from the University of Pennsylvania, detailed their observation that an increase in the diagnosis of fibrosarcomas had coincided with a Pennsylvania law requiring rabies vaccination in cats. A study at the University of California performed by Dr. Phillip Kass confirmed the initial hypothesis that rabies vaccines were a cause, but also implicated feline leukemia vaccines (Kass 539).

The first step in connecting vaccines with fibrosarcoma involved an intense microscopic examination of feline biopsy specimens. When pathologists at the University of Pennsylvania examined these specimens, some cells in the tissue samples contained a "gray-brown globular material," later documented to be aluminum, a common vaccine adjuvant (Hendrick). Later studies by Tufts University and Dr. J. A. Ellis showed both adjuvanted and non-adjuvanted vaccines to be associated with the development of this type of cancer, thus ruling out aluminum adjuvants as the sole cause (Hendrick).

A study by Dr. Mattie Hendrick and Tufts University, performed in the early 1990’s indicated that tumors related to vaccination developed in younger cats and were larger and more aggressive with higher rates of recurrence in comparison with non-vaccine related sarcomas (Hendrick). Figure 1 illustrates a vaccine-associated fibrosarcoma that was left untreated in a six year old cat. His tumor developed approximately three months post-vaccination and although a biopsy was performed, the owners elected not to attempt surgical removal of the tumor.

FIGURE 1. Photograph of a Cat with an Untreated Fibrosarcoma Tumor

An epidemiological study performed by Dr. Kass in 1993 demonstrated an increased risk of fibrosarcoma that compounded with the number of vaccines administered simultaneously in the same location (Ogilvie, "Vaccine" 416). One vaccine administered into the intrascapular region created a 50% greater risk of developing a fibrosarcoma. A second vaccination in the same area increased the risk to 127%, and a third or fourth vaccination to 175% (LaRue and Kitchell 391).

With growing evidence of a problem, tension began to form between different groups and specialties within the profession. Occasional reports were available in journals and a presenter at a conference might lecture on the topic, but, overall, practicing veterinarians still had very little information available to them. Perhaps some thought that the problem was going to go away; certainly many wished that it would, especially the sales representatives from the vaccine manufacturers.

In November 1996, the veterinary community took the unprecedented step of convening a multi-disciplinary task force to investigate this problem. Never before had such a broad based initiative been taken with only animal health at risk. This task force represents a combined effort of the American Veterinary Association, the American Animal Hospital Association, the American Association of Feline Practitioners, the Veterinary Cancer Society, veterinary researchers and clinicians, the Animal Health Institute, and representatives of the USDA. The task force is divided into four subgroups, each having a different set of goals and areas of exploration, as shown in Figure 2. Although the task force has made preliminary recommendations for vaccine protocol (Richards, "Feline"), their final report is not expected until 2001

There are currently several theories being explored as to why vaccinations are causing fibrosarcomas. Earliest theories, which have already been discounted, centered only on the rabies vaccine. Later theories blamed adjuvants, inflammatory response, genetic predisposition, or a combination of these factors.

Although the aluminum particles found in early tumors appeared incriminating, later studies have suggested that adjuvants cannot be the only factor involved in tumor development. In studies performed by Dr. Dennis Macy at the University of Colorado, the same degree of inflammation was produced using non-adjuvanted vaccines as those containing aluminum (Hendrick). A current study including six collaborating centers aims to firmly establish the role adjuvants and other variables play in vaccine associated fibrosarcomas (Richards, "Vaccine").

In both humans and animals, a connection between inflammation and the subsequent development of tumors has been established, and this theory might explain VAS. However, other species have not developed the same cancer despite a similar inflammatory response to vaccines and some cats have developed no detectable inflammation, but still develop fibrosarcoma. Nevertheless, this is the strongest theory to date, as scientists have been able to observe microscopic areas of transition between inflammation and tumors (Macy, "Vaccine" 380).

The third theory is the most difficult to prove, although there is strong anecdotal evidence for it. Because cats breed locally, a genetic predisposition to development of fibrosarcoma could account for the varied rates of incidence in different geographical locations. In a roundtable discussion published in Veterinary Forum in March 1999, Dr. Macy notes that related cats have developed sarcomas despite growing up in different households ("Feline").

Although there have already been numerous studies documenting a link between vaccination and the subsequent development of fibrosarcomas, many gray areas remain to be explored. Incidence of VAS from vaccine administration is estimated between 1:10,000 and 3.6:10,000 (Wolf 682). Other reports are as high as 1:1000 cases of vaccine related fibrosarcoma per number of cats vaccinated (LaRue and Kitchell 391). Based on these figures, an estimated 22,000 cats developed feline fibrosarcoma in 1991 alone (Couto and Macy, "Review").

The problem with firmly establishing the incidence of this or any other animal illness is the lack of a central reporting agency for disease management. Unlike the Centers for Disease Control for human medicine, veterinary medicine has no repository for disease information. Because the only disease that veterinarians are required to report is rabies, it is difficult to establish the impact that vaccine associated fibrosarcoma or any other feline illness has on the companion cat population. The retrospective studies currently cited for statistics reflect the cases seen at a particular institution rather than nationwide.

Several current studies attempt to account for geographical differences and better establish an overall incidence of Vaccine Associated Fibrosarcoma. The United States Pharmacopeia (USP) in Rockville, Maryland is conducting one of these studies. Between 1994 and August 1998, 169 cases of VAS from around the country were reported to the Veterinary Practitioners Reporting Program at USP (Meyer). Unfortunately, the percentage of cases reported remains low, hindering the efforts of investigators.

Dr. Leslie Fox of the University of Florida describes VAS as being locally aggressive and having a propensity towards metastasizing to the lungs (Fox). Dr. Fox goes on to explain that the complexity of complete surgical excision of these tumors results from the branching out of the tumor along the fascia, the thin layer of tissue that covers and supports the muscles and internal organs of the body (Fox). VAS can also involve skeletal tissue making adequate surgical margins of three centimeters an impossibility. Treatment typically involves surgical removal of the tumor (Illustrated in Figure 3) followed by radiation and/or chemotherapy. The prognosis is poor even with aggressive treatment. Unfortunately, even in the best circumstances, treatment appears to be more valuable in prolonging the life of the animal rather than in curing the disease.

According to a retrospective study by the University of Missouri, cats that receive treatment lived an average of 11.5 months. Cats without treatment averaged less than one month. The survival rate and length of time depended heavily on several factors, the first being whether the tumor was completely excised. Cats that had complete excisions averaged greater than sixteen months survival while cats with incomplete excisions were likely to survive only nine months. Of twenty-four cats that had only surgery without adjuvant therapy, only two were long term survivors suggesting that chemotherapy will play a large role in the successful treatment of VAS (Henry 399). Figure 4 illustrates the differences in survival time and recurrence with relation to surgical treatment.

A more recent study, presented at the annual symposium of the American College of Veterinary Surgeons (ACVS) in October 1999, studied 61 cases of VAS from 1986 to 1996. The study was a collaborative effort between the University of Wisconsin and the University of Pennsylvania to evaluate the disease free period and overall survival time of cats treated with surgery. The researchers concluded that only radical first excisions followed by either chemotherapy or radiation gives cats a chance of long-term survival (Brakeman, "VAFS" 18).

Researchers established a median survival time of less than two years (576 days) with only eleven percent of the cats that received only surgical treatment surviving. There was a tremendous discrepancy in disease free intervals between cats that had surgery at a referral center and cats whose surgery was performed by the referring hospital. Cats having surgery at a referral center had a disease free interval of 274 days while cats having surgery at the referring clinic had a disease free interval of only 66 days. This dramatic difference was attributed to the likelihood of the referral hospital performing a radical first excision rather than a marginal one (Brakeman, "VAFS" 18).

Although metastasis occurs in only about 24% of cases, recurrence of a tumor has been reported to be 86% within six months of surgery, 22% recurring multiple times at either the same site or the perimeter of the surgical incision (Henry 399). Treatment and prognosis are based on tumor grading and staging. Despite the seemingly low rate of metastasis, this cancer results in a high mortality rate due to its extremely invasive nature. When the tumors occur in the intrascapular region, the area most often used to administer vaccines, the cancer often infiltrates adjacent tissue and strangles both nerves and blood supply.

Several universities and organizations are evaluating the most effective treatment protocol for VAS. The recommendations at this time are surgical excision of the tumor with wide and deep surgical margins (>3 cm), possibly with pre-surgical radiation therapy (Ogilvie, "Diabolical" 398). Figure 5 illustrates the surgical margins used in removing an actual VAS tumor. If the margins were found to be inadequate, additional radiation therapy would be indicated. Some of the chemotherapeutic agents showing promise in treating this disease are carboplatin and adriamycin. Although these have proven to be the most effective drugs for preventing metastasis, modifications to the treatment plan would be made to adjust for the individual patient (LaRue and Kitchell 392-394).

One issue currently being studied is the length of time that a veterinarian should observe an area of inflammation before performing a biopsy. Dr. Lawrence McGill, a pathologist at Animal Reference Pathology in Salt Lake City suggests waiting four to six weeks before surgical excision is attempted ("Feline"). Dr. Meyer of USP stated in the summary of data from the VPR that one forth of the cats in their database developed sarcomas within three months with nearly one third of those developing a tumor within one month of vaccination. She went on to say that pending further investigation of that information, veterinarians may want to re-evaluate how long they observe suspect lumps before removing them (Meyer). Although Dr. Macy reports cell doubling times for fibrosarcoma to be as little as twelve hours ("Feline"), he also recommends surgical excision of lumps persisting for greater than three months (Meyer).

One of the biggest concerns facing veterinarians and cat owners in treating this disease is quality of life. With such a poor prognosis, the long-term value of repeated surgical excision or continued chemotherapy is questionable at best. As with human medicine, the side effects of chemotherapy can be debilitating and severe, and the recovery from the removal of large blocks of soft-tissue is painful and difficult. Figures 6 and 7 illustrate the large excision area, even for a less advanced case. The tumor in the photograph measured a mere 2.5 centimeters but the closed incision was just under six inches long. In most cases of VAS, the pet owner will face the difficult and painful decision of euthanasia.

Because this disease by its very nature affects cats that have been well cared for, many of the pet owners facing this decision have the financial resources to try at least some degree of treatment. Their struggle then becomes a question of when to stop. Owners must look ahead and keep the best interests of the cat at heart. Although this method may be very difficult psychologically, it is most beneficial to both the pet and person when the time comes to say goodbye. Jeff and Coleen Kremer have created a website called "Sylvia’s Journey of New Hope" which chronicles their cat’s battle with "the sarcoma monster." (See Appendix C for more information on the Kremers and their website.) They suggest owners make a list of their healthy cat’s activities and characteristics before it becomes seriously ill. The cat owner then has objective criteria by which to evaluate the cat’s quality of life when it begins to deteriorate (Kremer).

Since 1978, vaccination protocol has been essentially the same for every cat in North America and most of the world. Figure 8 is a chart that shows the vaccines traditionally recommended and their frequency. See Appendix A for a description of the specific diseases.

*Some states allow a three-year rabies vaccine to be used and thus require vaccination only every three years. Most veterinarians use the three-year vaccine even if they recommend vaccinating annually. In the states that require rabies every three years, the initial vaccine is to be given between 12 and sixteen weeks of age, then again a year later, followed by a three-year schedule.

All vaccines other than rabies require at least two boosters three to four weeks apart. This serves an important purpose in establishing effective immunity in a kitten. When kittens are born and nurse, they receive maternal antibodies from their mother’s colostrum. These antibodies help protect the kitten from infectious disease while its own immune system is developing. Unfortunately, these same antibodies interfere with a vaccine’s ability to stimulate the kitten’s immune system. Vaccines are given in a series beginning between 6 and 9 weeks to minimize the lapse between the maternal antibodies and the kitten’s immune response to the vaccine. Usually the maternal antibodies have dissipated by twelve weeks of age, at which time a rabies vaccine is usually administered (American).

One indisputable fact about feline vaccinations is that they have drastically improved the quality and length of life for many cats. The past twenty years have seen a dramatic drop in every infectious disease for which veterinarians currently vaccinate. Indeed, it is because of the effectiveness of the public education campaigns involving vaccination that many animals are no longer significantly at risk for developing these diseases. Dr. Richard Ford of North Carolina State University credits vaccines with reducing some major feline health threats to rare or non-existent within vaccinated populations (Ford 535).

Veterinarians commonly vaccinate for diseases that range in severity from inconvenient and uncomfortable to fatal. FVRCP is a multivalent vaccine, often referred to as a distemper shot. This vaccine protects against Chlamydiosis, Panleukopenia (also known as feline distemper), Rhinotracheitis, and Calicivirus. The FIP or feline infectious peritonitis vaccine is relatively new. Introduced within the past decade, it is available as both an intranasal vaccine and an injectable. Also recommended is FeLV, or feline leukemia virus vaccination. This disease inevitably results in death, although the time an animal can live with this virus varies considerably. The incidence of these diseases has been drastically reduced in the companion cat population as a direct result of increased vaccination compliance. Unfortunately, despite the drastic reduction in new infections, feline leukemia is still the number two cause of death in cats, second only to automobile accidents.

The current vaccination protocol has been very effective in accomplishing its goal of eradicating infectious disease in felines. The only cats still considered at greater risk for developing any of the aforementioned diseases would be strays, outdoor cats, and cats in shelters, catteries with a high turnover, and holding facilities. These cats are consistently exposed to other cats with unknown disease exposure and vaccination histories. In addition, many of the cats in shelters and holding facilities are too young to have been fully vaccinated or may not have received sufficient colostrum from their mothers, or may have received colostrum lacking sufficient maternal antibodies to protect them (American).

The current vaccine protocol practiced by most veterinary hospitals today has several significant disadvantages. These include, but are not limited to, uncertainty about the duration of immunity and the efficacy of common feline vaccinations, failure to address individual risk factors and needs, and the risk of vaccine related complications.

Although vaccines have changed and, in the opinions of the manufacturers, improved over the past twenty years, the recommended frequency of booster vaccination is the same. This is because manufacturers are not required to prove duration of immunity to any degree of certainty (Small). The only vaccine that has ever been studied extensively for duration of protection is the rabies vaccine, due to the public health risk of this disease (Macy, "Feline").

Most of the information available to practicing veterinarians regarding the effectiveness of a given vaccine comes from the manufacturer and is more anecdotal than scientific. Although the benefits of vaccinating are clear, there was never any scientific basis for annual revaccination. In fact, the USDA has only required Duration of Immunity (DOI) data for most vaccines since 1995 and no biologics companies have studies that show a DOI of only one year. (Wolf 682-686)

In analyzing whether to vaccinate and how often, the veterinarian and cat owner should examine several risk factors, including likelihood of exposure, previous history of response to vaccination, health status, and ability to monitor post vaccination health.

The most important factor is the likelihood of exposure. Indoor cats in single cat households are highly unlikely to be exposed to any infectious diseases and should require less frequent vaccination. The current manufacturer labeling and vaccination protocol do not make any allowances for this most important factor.

The second factor to consider would be previous response to vaccination. If a cat has had a negative response to vaccination, the administering veterinarian should carefully weigh the benefits of vaccinating that animal with the risk of another more severe reaction. Anaphylaxis is a sometimes-fatal allergic response and is not uncommon with vaccine administration.

The third factor, often overlooked but extremely important, is the overall health status of the patient before vaccination. To understand the importance of this issue, one must first understand the mechanism by which a vaccine works (see Appendix B). If the patient is immuno-compromised or in poor health due to stress, nutritional status, or another disease process, a vaccine will not be effective because the body will not be able to mount an appropriate immune response to the antigen. It is during this period of additional stress that an animal can become infected with another pathogen.

The final factor to consider in making vaccination decisions is the ability of the pet owner or clinician to monitor the animal after the vaccination is administered. Some side effects from vaccination are sudden and severe while others may take months or even years to fully manifest. Veterinarians often do not take the time to discuss possible adverse effects with their clients severely affecting the clients’ ability to recognize potential problems in their pets before they become life threatening.

There are many complications that can occur from vaccination, one of the most severe being fibrosarcoma. Dr. Gregory Ogilvie, Diplomate of the ACVIM and a recognized specialist in the field of Oncology, lists the following other side effects ranging from mild to severe: "Fever, sore joints, neurologic disorders (encephalitis), elevated liver enzymes, renal failure, bone marrow suppression, immune mediated hemolytic anemia and thrombocytopenia, anaphylaxis, immune mediated thyroiditis, and post vaccinal thyroiditis" (Ogilvie, "Diabolical" 397). Dr. Macy reports an association between rabies vaccination and autoimmune disease, anaphylaxis, granuloma formation, soreness at the injection site, and tumor development (Macy, "Has").

Macy believes that recommendations for vaccination should reflect the risk of infection, an understanding of current vaccine products, and scientific information (Macy, "Feline"). When the risk of contracting an infectious disease is lower than the risk of a potentially fatal vaccine side effect, responsible veterinarians and owners alike should reconsider the wisdom of continued annual vaccinations.

The AVMA and VAFSTF have made specific recommendations regarding sites of administration for various vaccines. They believe that following the general guidelines for vaccination that they have recommended will assist in both characterizing a cause and facilitating treatment (Richards, "Feline").

1. Vaccination and other injection protocols should be standardized within each practice. Careful documentation of the location of the injection, type of vaccine or other injectable administered, the manufacturer, and the serial number should be kept in each patient’s permanent file.
2. Other recommendations include
1. Vaccines containing panleukopenia, calicivirus, and Rhinotracheitis should be administered on the right shoulder according to the recommendations of the manufacturer.
2. Vaccines containing rabies antigen should be given in the right rear leg as distally (far from the trunk) as possible according to the recommendations of the manufacturer
3. Vaccines containing feline leukemia virus antigen should be administered in the left rear leg as distally as possible, according to the manufacturers recommendations
4. Injection sites of all other medications should be carefully documented (Richards, "Feline").

Figure 9 illustrates both the recommended vaccination sites and the site most commonly used in the past. Careful documentation of both injection sites and product information will help investigators determine trends in the development of VAS. Manufacturer, vaccine components, killed or modified live vaccines, and serial number can be used to characterize this information. Another anticipated benefit of these protocols is to facilitate treatment. This is accomplished in two ways: early preliminary diagnosis and treatment decisions can be made if a growth appears at an injection site and locating injection sites as distally as possible allows for amputation of the affected limb, effectively removing the tumor and all adjacent tissue.

Veterinarians also have another option for the FVRCP injectable vaccine. This product is an intranasal vaccine manufactured by Heska™. This vaccine is administered into the cat’s nose and eyes, the sites at which the viruses enter the cat. The most frequent complication of this type of vaccine is sneezing. Currently, this is the only intranasal FVRCP vaccine marketed for cats; however, in response to the VAS issue, Heska™ and other manufacturers are actively seeking alternatives to other traditionally injectable vaccines.

Many clinicians and teaching hospitals have made preliminary recommendations with regard to changing the frequency of vaccination. Most of the suggestions indicated that a move to three-year revaccination intervals would be the most appropriate. In 1998, seven U.S. veterinary colleges had extended their vaccination intervals. Kittens receive two sets of shots three to four weeks apart. One year later they receive a booster and then are put on a rotating three-year schedule. This allows a vaccine to be given once a year with the exam (Wolf 685). Dr. Gregory Ogilvie similarly recommends vaccinating every three years for FVRCP and rabies, where allowed by law. For the typical indoor cat not exposed to FeLV, vaccinations for this disease would discontinue after age two (Wolf 687). In an interview with Dr. Ogilvie, he suggests that most cats never need to be vaccinated for FeLV unless they fall into a high risk category.

A truth that, unfortunately, is seldom shared with veterinary clients is that not all animals need all vaccines (American). Many factors should be considered when deciding whether or not to vaccinate and for what diseases. Some variables that should have an affect on this decision include: overall health and nutritional status of the patient, age, likelihood of exposure, previous vaccine history, medications the animal is currently taking, and recent or forthcoming stressful situations.

Overall health and nutritional status have a strong affect on the body’s ability to respond effectively to a vaccine. A depressed immune system will not be able to produce an adequate response to any pathogen, especially not one that bypasses the body’s natural front-line defenses. We see this phenomenon in people with poor diets who are more vulnerable to a host of illnesses and secondary infections. This is especially important for veterinarians to remember when dealing with recently adopted cats and kittens. With questionable histories, it can be difficult to get a clear picture of the cat’s overall status. Postponing vaccination until the pet has a chance to adjust to a new environment and diet would be in the cat’s best interest.

The age of a pet is also critical in making an intelligent decision about vaccination. Older pets, like aging humans, face different health issues than their younger counterparts. Organ systems are wearing out and can tolerate less stress. Although immune systems are not as strong, natural immunity to pathogens in the environment is well established. As cats age, vaccination becomes less effective and more risky. At the same time, the cat’s likelihood of being exposed to a pathogen that it does not have some degree of immunity to is very unlikely.

Another important factor to consider is the opportunity for infection. A cat living indoors in a single cat household is highly unlikely to be exposed to any of the diseases for which veterinarians currently vaccinate. Conversely, the risk for a cat or kitten residing in a shelter or a multi-cat household might be much greater. Outdoor cats are also far more likely to be exposed to a variety of pathogens (and a number of other dangers). Cats falling into the high-risk categories would probably benefit from a more frequent vaccination schedule.

Dr. Richard Ford, Diplomate of the ACVIM and a professor at North Carolina State University has also expressed concern that vaccines are given to meet "perceived demand rather than the need to stop widespread or endemic infections" (Ford). Due to the lack of available information and definitive diagnosis for many of the infectious diseases cats are currently vaccinated for, ascertaining the true risk of infection may prove to be impossible.

A cat’s previous vaccine history should also have some bearing on the decision to vaccinate. It is likely that a cat that has been vaccinated would have a sufficient duration of immunity to extend the interval between vaccines by an additional two or three years (Wolf 682). Human medicine refrains from recommending yearly vaccination and there is little difference in the immune systems of animals. Dr. Wolf further hypothesizes that "If immunity persists for the seventy plus average year life span of a human being, then it is reasonable to assume that immunity will persist the lifespan of a companion animal" (682).

Another important piece of the puzzle involves other medications the pet may be taking. Certain drugs can suppress the immune system and affect the ability of the vaccine to induce the desired response. These drugs include corticosteroids, which are used frequently in companion animals to treat allergies, lameness, autoimmune disorders and other problems that require either an anti-inflammatory or immuno-suppressive effect. It is frivolous and potentially dangerous to vaccinate an animal that has been given an immune suppressant.

The final factor to consider in deciding whether to vaccinate is stress. Many people are intimately familiar with the concept of getting sick when stressed. This concept holds true for cats as well. A cat changing households, entering or leaving a new environment, gaining or losing a housemate, or going through any significant change will be in a weakened state and less able to mount a sufficient immune response to any challenges, natural or manmade. When vaccinating, the veterinarian and pet owner should consider recent changes such as these as well as forthcoming stressful periods. For example, it would not be a good idea to vaccinate an animal immediately before boarding or a long trip.

Although considering these factors requires time and thought, the benefits of vaccinating intelligently can be felt by pet, owner, and veterinarian. Pets are less likely to have undesirable responses to vaccination. Owners are likely to be very pleased at the concern shown by their veterinarian and the continued good health of their pets. Veterinarians displaying this degree of dedication to the health and well being of their clients are likely to be rewarded with strong client loyalty and a large number of referrals.

One of the largest and most legitimate concerns that veterinarians have regarding a change in their vaccine protocol is legal liability. Veterinarians are currently in a very difficult position. Although the manufacturers’ labels indicate annual revaccination, current professional literature indicates that close attention should be given to vaccination procedures and many professional organizations have begun to mention longer intervals between vaccines. Because under malpractice statutes veterinarians are held to their level of education and training and to the standard of practice in their geographical area, the correct course of action in this situation can be difficult to identify.

The most significant problem with regard to legal liability is the fact that the manufacturer labels vaccines to be administered every year. Using products in an extra-label manner is common in veterinary medicine, but still very controversial. Certainly, the veterinarian would be at risk for a lawsuit if the less frequently vaccinated cat became infected with one of those viruses. Even more importantly, the veterinarian would have taken on that risk individually since the manufacturer would quickly point out that the vaccine was not given as frequently as recommended on the label.

One aspect of the manufacturers’ role in this problem is lack of adequate standards for vaccine licensure. Dr. Dennis Macy, a professor and researcher at the University of Colorado, and one of the most outspoken veterinarians on the topic of VAS is one of the harshest critics of the veterinary vaccine industry. His criticisms include lack of proof of duration of immunity, arbitrary booster recommendations, and lack of truth in labeling. According to Dr. Macy, "(t)he booster recommendation could just as well be every leap year or full moon!" (Macy, "Feline")

Many veterinarians will not feel comfortable changing their vaccine recommendations before the manufacturers change their labels. Because of the

strong profit motive, change in labeling is unlikely to occur without intervention on the part of the USDA. Macy advocates raising the standards for both the vaccine manufacturers and the USDA. He and many other prominent veterinarians feel that "it is not my responsibility…to show the lack of need for annual vaccination, rather,

it is the multi-billion dollar vaccine industry’s responsibility to provide convincing evidence, … and to establish a medical need to administer feline vaccines annually to adult cats to maintain health" (Macy, "Feline").

Even though changes to vaccine labels seem far in the future, veterinarians must still address the issue of annual vaccination in their practices today. Although there is a risk of liability from breakthrough infection and vaccine failure, veterinarians face much greater penalties for cases of willful negligence. Not informing a client of the potential risks involved in vaccinating is negligent and willfully denies the clients right to make medical decisions on the part of their pet.

Despite the labels, veterinary oncologists, internal medicine specialists, immunologists, and feline specialists are changing their opinions and protocols. Teaching hospitals around the country have already made changes and as the graduates of those schools enter private practice, the standard of care will change. The safest way to guard against liability in this case will be to adhere to the standards of practice not only in a geographical community, but also in the veterinary community as a whole and begin to make changes.

Other factors working against liability in administering vaccines less frequently than the label indicates are previous legal decisions. According to Colorado State University, booster recommendations have been determined arbitrarily and "extra-label use of vaccines was found to be appropriate when supported by scientific principles" (Small).

The December 1999 issue of DVM Magazine reported that a California veterinarian has been named defendant in a suit brought by a client whose cat was diagnosed with VAS. Dr. Macy, considered a leading expert on VAS, is one of the only members of the veterinary community who has been able or willing to comment on this case. He postulated, "he [the veterinarian named in the lawsuit] was in deep water because, from what I have read, the veterinarian is considered to be the ‘learned intermediary’ between the vaccine manufacturer and the client. If you fail to get written proof that you have warned a client of the risks involved in vaccination, you are on the hot seat" (Blakeman, "Client").

The best option for the general practice veterinarian would be an informed consent to be signed by clients who choose to vaccinate as well as those who opt for triennial vaccinations after educating themselves and discussing their options with the doctor. This form would release the veterinarian from liability if he or she has carefully disclosed the risks and benefits of vaccination. If this mechanism is used as a tool for clear and accurate communication with clients, rather than a substitute for it, a consent form might be an acceptable compromise.

Although the VAFSTF has not developed owner consent forms, the American Association of Feline Practitioners and the Academy of Feline Medicine have published "Guidelines for Writing Owner Consent Forms" which can be found in the Journal of the American Veterinary Medical Association, January 15, 1998, Vol. 212, No. 2, page 241 (Brakeman, "Client").

Another very legitimate concern regarding changes in vaccination protocol is the issue of vaccine efficacy and duration of immunity. Currently, no vaccine manufacturer has produced scientific evidence that supports or undermines the assumption that vaccines can be given less frequently without compromising safety.

Efficacy is the ability of a product to produce the effect or consequence that it is designed to produce. In the case of vaccines, they are designed to produce an immune response that will protect the recipient from exposure to the real disease. Vaccine manufacturers must prove that their vaccine works in order to market the product. They do not under current USDA regulations have to prove the length of time that the vaccine is effective (Macy, "Feline").

The crux of this issue is to define how well current vaccines protect from disease and for how long. Unfortunately, proving the duration of immunity is cost prohibitive and time consuming. Because the USDA does not require these studies, manufacturers have implied that this responsibility rests with the veterinary community. Dr Dennis Macy vehemently disagrees and believes that the time has come to re-examine the long-standing practice of annual vaccination (Macy, "Feline").

Some practicing veterinarians remember seeing viral epidemics in the companion animal population and younger veterinarians have not forgotten the horror stories they heard in veterinary school. A major area of concern for everyone involved is addressing the VAS issue without reintroducing an epidemic of infectious disease.

Dr. Macy recommends that conscientious veterinarians examine criteria other than label recommendations to establish vaccination frequency. Several approaches recommended by Macy include prevalence of a disease in cats that have ever been vaccinated and the duration of immunity provided by natural infection, titering, and challenge studies. He recommends using all of the methods to come to a solid and scientifically based conclusion (Macy, "Feline").

In examining the prevalence of a disease in cats that have ever been vaccinated at any point in their lives, a vaccine that mimics the disease process may be expected to provide similar protection as the natural infection. Because some infectious diseases provide lifelong immunity to re-infection for survivors, it is logical to assume that a modified live vaccine that mimics the disease process would provide the same degree of protection (Macy, "Feline").

Titering studies conducted by immunologists at veterinary schools around the country have indicated that immunity can be established based on an antibody titer (Small). Animals with protective titers have adequate protection from infection and do not require revaccination. This allows veterinarians the option of a blood test to determine the necessity of vaccination for each individual cat. The drawbacks of attempting to use an antibody titer to establish immunity are that the type of vaccination used must be known, titers do not necessarily reflect mucosal or cellular immunity, and that negative titers do not necessarily indicate susceptibility in animals that have been previously vaccinated (Macy, "Feline").

The third option is DOI studies determined by challenge data. Challenge studies involve deliberately exposing an animal with a known vaccination history to the pathogen for which it was vaccinated. Ability to resist developing the disease despite certain exposure through inoculation is the most believable evidence. Unfortunately, these studies can be quite expensive and time consuming (Macy, "Feline"). Figure 10 illustrates an analysis of feline infectious disease as proposed by Dr. Macy.

Vaccines have long been the "cash cow" of the veterinary profession. Most people know about the importance of vaccinating. Indeed, many have seen the effects of the diseases for which we now have vaccines. Unfortunately, many clients also mistakenly think that the most important part of the annual visit is the vaccination.

Many clients associate a trip to the veterinarian with vaccinations. The bread and butter of a standard day practice is the annual exam and vaccination visit. Figure 11 illustrates the both the actual cost of feline vaccines to the veterinarian and the average mark-up paid by the veterinary client.

According to Veterinary Economics Magazine, in 1990 vaccines represented twenty percent of the total revenue of the average veterinary practice. Medications and examinations represented nearly equal proportions of total practice revenue, with all other services, including surgery and diagnostics representing a much smaller percentage (Tumblin and Wutchiett 44).

Although these statistics appear to be strong motivation not to alter current vaccination protocol, handling changes in protocol appropriately allows the money normally spent on vaccinations to be redirected to other more neglected areas of preventative care rather than lost. Dr. Alice Wolf of Texas A&M suggests that not only can lost revenue be replaced, but that it can be replaced by providing higher quality medical care for the patient. Some of the ways she suggests for better use of a client’s resources are dental care, earlier tumor removal, diagnostic radiographs and laboratory work, and geriatric screens for older pets. As evidence, Dr. Wolf offers that during the first year of Texas A&M’s reduced frequency vaccination program, their total revenue increased by 27% (Wolf 686).

Another issue Dr. Wolf addresses is the fierce competition that exists in some markets. There are always going to be differences in the recommendations two clinics make for their clients (Wolf 685). In changing vaccine protocol, a clinic might be scrutinized by clients and colleagues alike, and there is potential for competitors to attempt to exploit any uncertainty or distrust that clients of that clinic might have. The best way to address this issue is to communicate clearly with every client about the changes being implemented.

Broad policy changes could be handled through a letter to each cat owner outlining the changes in policy and the reasons behind them. Offering references to other resources where the client can gather their own information on the topic would also show great concern for the well being of the cat and respect for the owner’s ability to participate in health care decisions. It would also be essential to encourage clients to contact the clinic if there are any questions. The normally scheduled annual exam would then give each client an opportunity to further discuss the issue with his or her doctor.

Veterinarians complete an undergraduate degree, plus an additional four years in veterinary school. They are familiar with radiology, biochemistry, neurology, oncology, immunology, hematology, internal medicine, orthopedics, pharmacology, ophthalmology, and microbiology. Moreover, unlike human medicine, they are familiar with the anatomy and physiology of many species rather than just one.

This extensive training and expertise too often goes unnoticed or underrated. Veterinarians themselves are, in some ways, responsible for the popular misconceptions the public has developed regarding their abilities, and changing them will be challenging. Clear communication will be the hallmark of the successful veterinary practice of the future. As people become more educated about medicine in general, and as pets become more and more part of the family, the only practices that will survive are those that thoroughly and clearly address the concerns of their clients and provide the most responsible care for their pets.

Practicing veterinarians are also concerned that clients will not bring their pets in for annual examinations without vaccines as a motivation to do so. Although this argument has some merit, the attitude of clients towards physical exams has developed over many years of miseducation on the part of the entire veterinary community.

For years now, the incredibly high mark-up on vaccines has allowed for vaccine "sales" and promotions. Many practitioners discount their examination fee with the purchase of all available vaccines. Others offer a free exam with vaccinations. Meanwhile, vaccine companies spend millions of dollars on advertising the dangers of infectious diseases and the importance of vaccination in preventing them. The information given to clients in the past has strongly supported the erroneous assumption that the most important thing a veterinarian does is vaccinate.

The most valuable resource any veterinarian has to offer is his or her expertise and experience. Because their patients cannot clearly communicate their symptoms, veterinarians possess amazing observation skills. In palpating an animal’s abdomen, most skilled veterinarians can assess the kidneys, liver, spleen, and intestines for gross abnormalities. Listening to the heart, lungs, and abdomen give an adept veterinarian a good idea of how the heart, lungs and gastro-intestinal tract are functioning. A thorough physical examination can detect problems before they become life threatening. For example, it is not unusual for heart problems to be detected during an annual exam and thus treated before the animal becomes symptomatic yielding both a longer and more comfortable life.

Some clients, because of the misinformation they have received for so many years, may not want to bring their cat in yearly if they are not being vaccinated. Even these clients can be enticed to bring their cat in annually if the vaccinations are rotated. For example, if rabies is required every third year, FVRCP can be given the first year of the new program, followed by FeLV the second, followed by rabies the third. In areas where rabies is required annually by law, this should not be an issue.

Rather than focusing on the vaccination aspect of the annual veterinary visit, practitioners have an opportunity to completely re-educate their clientele. If veterinarians are concerned that pets will suffer because their owners will not bring them in for physicals if they do not need a vaccine, they should share that concern with their clients. Concerned cat owners will appreciate the sincere interest in the well-being of their pets and are likely to comply with the recommendation for annual examinations if they understand its importance.

The most effective tool for changing the focus of the annual visit is client education, an area that is sorely lacking in the average veterinary practice. Many vets do not talk to the client as they are conducting a physical examination. If a client were better informed on what, precisely, the veterinarian was assessing and why, cat owners would place more value on the physical exam.

One way that veterinarians can better educate and involve their clients is to thoroughly explain every aspect of the physical exam. Typically, a physical exam is grouped into systemic categories. For example, integumentary, muscular, circulatory, respiratory, digital, urogenital, ocular, aural, mucosa, gastrointestinal, and general observations should be recorded (Cornelius 1-3). As each system is evaluated, certain criteria are used to determine the status of the patient. Sharing both the criteria and the findings might take more time but involving the client in their pets care, creates a more conscientious and observant pet owner and allows the client to develop respect for the expertise that permits a veterinarian to evaluate a patient so thoroughly and quickly.

The benefits to having knowledgeable clients are plentiful. A client who is more informed is more likely to catch problems early and bring them to their veterinarian’s attention. They are also more likely to seek treatment and to comply with instructions regarding medications and home care. A client who understands the medical significance of periodontal disease, for example, is far more likely to allow their veterinarian to provide routine dental care.

Another aspect of client education should focus on other neglected areas of preventative care. As the pet population ages, it is subject to the same health problems that aging people are. Arthritis, heart disease, kidney and liver problems, glaucoma, and cataracts are among the problems that animals and people share as they age. Money saved from omitting unnecessary vaccines could be used for medications to treat arthritis, EKGs to measure heart function, and blood screens to assess organ function and overall health.

The most important thing for a veterinarian to remember as he or she evaluates changing their vaccine protocol is that the clients who come in every year without fail do so because they have the best interests of their pet at heart. Allowing those clients to be more proactive in caring for their pets will benefit both the pet and the practice.

The most important aspect of any relationship is communication. Veterinarians who have not established a pattern of open communication with their clients will be at a severe disadvantage in trying to change their vaccination recommendations. Dr. Alice Wolf addresses the communication issue by first pointing out that clients are better educated and informed than they are given credit for. She recommends an honest personal discussion aided by carefully and thoroughly prepared reading materials (Wolf 685).

The first step that general practitioners must make is to increase the perceived value of the annual physical exam. This means no more free exams with the purchase of vaccines, no more discounted exams with the purchase of vaccines, and no more vaccines without a thorough physical. Not only do the pets suffer when thorough physicals are not performed, but veterinarians are selling themselves short by not emphasizing the skill required to perform one. The ability to feel an abnormality in an organ as small as the kidney of a cat through the abdominal wall while your patient is trying to jump off the table is truly admirable!

In changing the attitude that clients have towards the physical exam, it is imperative for the veterinarian to send a clear message that he or she takes his or her ability to make accurate observations seriously. If the veterinarian does not tell the client that he or she is feeling the size, shape and texture of the liver, kidneys, and spleen, the client is likely to think they are just feeling the belly of their cat. If the veterinarian has never talked to the client about the importance of healthy teeth and gums to overall health, and if they have never told the client that abscessed teeth can lead directly to heart disease, the client is far less likely to understand the significance of tarter build up on their cats teeth.

The physical exam is the most valuable and important part of the client’s annual visit. Not only is a thorough physical essential to maintaining a pets good health, but it is also the best time to market additional services to the client. The physical exam is the most valuable service a veterinarian performs and clients do not have that perception when they receive the exam free with the purchase of vaccines. In order for the perceived value of the physical exam to increase, the price will have to be based on the actual value of the service.

In anticipation of the expected vaccine recommendations, veterinarians should consider immediately reducing the prices of vaccines and raising the price of the physical. The extremely high mark-up on vaccines, particularly the rabies vaccine, implies a very high value. Reducing that mark-up would send the message that vaccines are merely an adjunct to the annual visit rather than the purpose of it.

Veterinarians have quite a bit to offer their clients, from preventative medicine to surgery to behavioral advice. Many clients are searching for ways to make their pets happier, healthier and more involved in their lives. This is the ideal time for veterinarians to develop other areas of their practices and begin to offer their clients the comprehensive care for which they are searching.

Vaccine Associated Fibrosarcoma is a multifaceted problem that bears close scrutiny on the part of veterinarians, vaccine manufacturers, government regulatory agencies, and, most importantly, cat owners. Because of the clear evidence of a connection between vaccines and the development of this cancer, the difficulty in treating fibrosarcoma, and the poor prognosis for cats developing this disease, immediate action must be taken.

Veterinarians can begin addressing this problem by closely adhering to the recommendations of the VAFSTF and by communicating with their clients regarding the risks of vaccination. Veterinarians also need to be committed to keeping themselves updated as new information on this disease becomes available.

Vaccine manufacturers must address the insufficiency of arbitrary recommendations for the administration of the vaccines they produce and market. They will play a pivotal role in the expediency of resolving this problem. These manufacturers should also be called upon to individually research the safety of their products and should label vaccines according to both safety and efficacy.

Government regulatory agencies, specifically the USDA, must be more aggressive in addressing the safety issues in question with regard to vaccines. Although animal welfare issues have received little attention from this agency to date, the changing view of pets in society requires this agency to be more forceful in dealing with issues such as these that affect not only the health of many animals, but also the hearts and pocketbooks of their owners.

Finally, and most importantly cat owners must take direct action to help resolve this issue in a timely manner. Education, information, and communication are the keys to making responsible and intelligent medical decisions for cats. Open communication with the veterinarian treating the pet is essential and should be demanded. Thanks to the increasing availability of information on VAS as well as a wide range of other topics that can affect the health of companion animals, pet owners now have the ability to gather information on their own and then discuss this information with their veterinarian. Owners also have the option to choose another veterinary hospital if they feel that their needs and the needs of their pets are not being adequately addressed.

Cat owners possess a great deal of power in this situation if they arm themselves with knowledge. Being an active participant in their cat’s medical treatment will bring about more conscientious care on the part of the veterinarians, which will in turn put pressure on both the USDA and the vaccine manufacturers to make the changes necessary to better ensure the health and safety of our feline friends.

Adjuvant: a component used in killed vaccines to stabilize the parts of the virus needed to create an immune response in the animal, also a person or thing that helps, as in chemotherapy as an adjuvant to surgical excision.

Anaphylaxis: an allergic response to an allergenic substance that an animal has been exposed to previously. This response can result in shock and even death.

Antibody Titer: a measure of a specific type of antibody in a person or animals immune system (see also protective titer)

Bone Marrow Suppression: bone marrow suppression involves a non-regenerative anemia. If the bone marrow is suppressed, there will be fewer platelets and few new red blood cells being created.

Colostrum: the fluid secreted by the mothers mammary glands for the first several days after giving birth, contains high levels of protein and maternal antibodies.

Corticosteroids: a class of drugs which includes Beclomethasone, Flunisolide,and Prednisone. These drugs can be used to treat a variety of ailments from adrenal disease to skin rash to cancer. Prednisone has a strong anti-inflammatory effect and is used to reduce muscular, skeletal and joint inflammation as well as suppress the immune system in diseases of auto-immune origin. Prednisone is frequently used in veterinary medicine to treat allergies, irritable bowel syndrome, shock, and a variety of other ailments.

Distally: As far from the trunk of the body as possible, far from the origin

Encephalitis: an inflammation of the brain caused by bacterial or viral agents

Endemic: a disease that is constantly present but is generally under control

Euthanasia: causing a painless death with an injection of Sodium Pentobarbital, putting to sleep.

Excision: cutting out or away diseased or damaged tissue

FeLV: Feline leukemia virus, a common disease of outside cats spread through blood, saliva, and from mother to kittens

FVRCP: A multivalent vaccine that immunizes against Chlamydia, Rhinotracheitis, Calicivirus, and panleukopenia (see Appendix A)

FIP: Feline infectious peritonitis (see Appendix A)

Grading: using objective criteria to establish the malignancy of a tumor and its ability to metastasize.

Granuloma: a firm, tumor like granulation formed in reaction to chronic inflammation (from a foreign body, bacteria, etc)

Immune Mediated Hemolytic Anemia: a disease in which the body attacks its own red cells causing severe anemia and often resulting in death.

Integumentary: of or pertaining to the skin

Intranasal vaccines: vaccines that are given into the nose of an animal rather than injected. They typically allow a faster immune response by targeting the entry point of the pathogen.

Mesoderm: The middle of three layers of embryonic cells from which skeletal, muscular, vascular, connective, etc. tissue develops.

Metastasis: the spread of cancer from one part of the body to another unrelated part of the body (i.e. from skin and muscle tissue to the liver) by way of the blood stream or lymphatic system

Multivalent: a vaccine having many parts, designed to create an immune response to more than one disease simultaneously

Protective titer: the level of antibodies that will protect and animal or person from infection if exposed to the real disease (challenged)

Pathogen: any disease-causing organism, particularly viruses and bacteria

Renal Failure: kidney failure

Retrospective Study: a study that reviews cases of a specific diagnosis to analyze similarities, identify trends and develop hypotheses on disease origin

Staging: see grading

Surgical Margins: the edge of a surgical excision. Pathologists closely examine them for evidence of cancer cells to ensure adequate excision of a tumor.

Thrombocytopenia: A decrease in the number of platelets (round nonnucleated disks associated with the clotting process)

Thyroiditis: an inflammation of the thyroid gland that often results in temporary or permanent hypo or hyperthyroidism

Vaccine failure: the inability of a vaccine to create the desired immune response; caused by either a defective vaccine, inappropriate administration of a vaccine, or failure of an animal to respond as anticipated due to maternal antibodies or immune dysfunction

In a sense, vaccines work the same way an infection does. The most efficient way to understand how both work is to understand the immune response.

Immune responses fall into two basic categories; however, they are overlapping and interconnected to a large degree. The first exposure to an antigen triggers a non-specific event. This non-specific event triggers components of the specific system. Lymphocytes, part of the specific response, are trained to react with a precise protein sequence or shape. Normally an animal has billions of lymphocytes, each specific for a single protein sequence. When a lymphocyte encounters its particular protein, it divides and produces memory cells (T cells) and cells to produce antibody (B cells).

B-lymphocytes are programmed to produce antibody when they meet their programmed protein. The importance of the immune response in understanding the mechanism of vaccination is that the lymphocytes react with a single protein and continue to react with it; and they amplify themselves when they meet it.

As far as the immune system is concerned, a vaccine is, in a sense, just another antigen. The main difference is that vaccines push the immune response through the initial steps, creating a strong and amplified specific response lying in wait for the real thing.

The difference between vaccines and the real thing, ostensibly, is that natural exposure carries a high risk of infection. Vaccines instead take the natural, disease-causing agent and modify it. There are two basic ways of accomplishing this. A modified live virus is either a harmless version of the virus or just a part of the virus that will still create an immune response to the real thing. A killed virus is just what it sounds like. The virus itself is inactivated but the proteins remaining are still able to create the desired immune response.

Most immunologists view killed vaccines as safer than modified live vaccines, but also somewhat less effective. Killed vaccines use adjuvants, agents that tend to enhance the immune response, to make them more effective. Aluminum is the most common adjuvant used in animal vaccines at this time. Adjuvants allow a slow release of the virus setting up persistent antigen exposure and thus a more effective immune response.

In summary, a vaccine attempts to mimic the natural disease process without the risks of a natural infection.

In December 1997, a very special cat succumbed to vaccine-associated fibrosarcoma. Unfortunately, she was not special because her disease was so rare or because so few die from it. Sylvia was special because her parents, Jeff and Coleen Kremer have created a legacy in her name.

Although Sylvia lost her battle against vaccine-induced fibrosarcoma, she has not lost the war. The Kremer’s have created an accurate and informative website recognized by animal organizations all over the country and dedicated to assisting other pet owners in surviving or avoiding a similar plight through education. They have allied themselves with noted researchers and organizations to provide the most accurate and up to date information available to the public.

This site bears mentioning for several reasons. The first is the motive behind it. The Kremers are dedicated to sharing Sylvia’s story in order to encourage people to educate themselves about the health care of their cats. The second is the time and effort that Jeff and Coleen have put into developing this site and ensuring that the information appearing on it is accurate. The third and most important reason for highlighting their web page is Sylvia. This report listed many numbers and statistics related to this disease. Despite a dedicated effort to provide comprehensive and accurate information, the loss, anger and frustration of a pet owner who has gone through this devastating illness with one of their cats cannot be adequately conveyed.

Sylvia’s Journey includes information on treatment protocols, fact sheets, published technical papers, studies from the AAFP and VAFSTF, information on reporting cases of VAS, information on intranasal vaccines, and, perhaps most importantly, an area for cat owners dealing with fibrosarcoma in their own cats to meet each other and share information and resources.

Jeff and Coleen Kremer are a force to be reckoned with in the battle against VAS and with the resources they have gathered thus far, it appears that Sylvia’s war is far from over.

Their website can be viewed at:

http://catshots.com & http://www.catshots.com

TO: Marilyn Julius

FROM: Heather Lord

SUBJECT: Interview Summary

DATE: October 15, 1999

On October 5, 1999, I had the opportunity to interview Dr. Gregory Ogilvie by telephone. Dr. Ogilvie is a Diplomate of the American College of Veterinary Internal Medicine and he teaches Internal Medicine and Oncology at Colorado State University. He is a recognized expert in the area of vaccine related fibrosarcoma,

In an attempt to keep my interview as brief as possible out of respect for Dr. Ogilvie’s busy schedule, I limited myself to four basic questions which I had already forwarded to him in my letter of inquiry. Below is an outline of the information that he provided for me:

• He felt that the resistance to making changes in vaccine protocol was due to concern over losing revenue, misinformation about the prevalence of viral diseases and the ability of vaccines to prevent them, and concern about professional liability.
• Dr. Ogilvie outlined his recommendations for the FeLV vaccine for both high and low risk cats.
• After explaining the obstacles to completing efficacy results for vaccines, Dr. Ogilvie went on to cite studies completed by the larger vaccine manufacturers. He feels that changes in manufacturers’ labels will have a greater impact on general practice vets than more studies would.
• Dr. Ogilvie feels that it is still a bit premature to take the decision of vaccine protocol out of the hands of the veterinarian. Pending the task force’s findings which will be released in less than two years, he feels it most prudent to wait for their recommendations

I thanked Dr. Ogilvie profusely for taking the time out of his schedule to talk with me. He also gave me the names of some other experts that he felt might be helpful to me in completing the research for my formal report. He also offered to forward me some other articles via e-mail. I will be sending him a copy of my report when it is complete, and he said he would be happy to read it and might like to forward it to some of his colleagues.

I was very pleased to have had the opportunity to speak with such as esteemed veterinarian. The interview went very well, despite the fact that I was very nervous and felt a little ridiculous asking a well-respected scientist such simplistic questions. The information he gave me was very useful in clarifying some gray areas in my report that secondary research had failed to illuminate.

P.O. Box 832

Sparks, Maryland 21152

September 13, 1999

Gregory K. Ogilvie, DVM, Diplomate ACVIM

Comparative Oncology Unit, Colorado State University

College of Veterinary Medicine and Biomedical Sciences

Ft. Collins, Colorado 80523

Dear Dr. Ogilvie:

I am preparing a report on vaccine-induced fibrosarcomas in cats for my Report and Technical Writing class at Villa Julie College in Stevenson, Maryland. As a veterinary technician, this is a problem that I would like to explore in greater depth. After reviewing two of your articles, "Diabolical Dilemma: Vaccine Associated Sarcomas: Big Problems!?" and "Vaccine Associated Sarcomas: Where do we go from here?", I would be very grateful to get your input on more specific questions in either an interview or a letter.

These are some of the questions that I am interested in developing:

1. Why do you feel there has been so much resistance within the general veterinary population to shift to the recommendations that you outlined in the TNAVC 1999 Proceedings? Do you feel that their objections have merit from a medical standpoint?

2. You recommended annual boosters for FeLV, which I understand to be strongly implicated as a causative factor of fibrosarcomas. Is there a specific reason that these vaccines are unable to adequately protect for three years as was recommended for most other vaccines? Do you feel that protocol should be more flexible for cats that are at low risk of exposure?

3. Do you feel that adequate testing has been done to establish longevity of the vaccine's effectiveness? If not, do you feel that doing so would be an important step in making recommendations that general practice veterinarians feel comfortable with?

4. Do you feel that a more intensive public education effort should be initiated so that cat owners can make informed decisions about their pets?

Thank you very much for taking the time to read this letter. I know that you have a very busy schedule. I hope that you might have a chance to respond to my questions by mail, phone, or e-mail at your convenience. Would it be possible to schedule something by October 10 in order to complete my research? You can contact me via e-mail at Heather-VJC@msn.com, or via telephone at (410) 472-9099. Thank you again for your time and patience.

Sincerely,

Heather L. Lord