Feline vaccination in 2008: Progressive practices for progressive practices (Proceedings)

Dramatic changes have occurred in the past 10 years regarding the way veterinarians view vaccines and vaccination practices. The concepts of core and non-core vaccines, disease risk assessment, extended inter-vaccination intervals, and using products that minimize the risks of vaccine-associated sarcoma (VAS) are currently mainstream veterinary medicine. There are now a number of publications that document the long duration of immunity provided by most feline viral vaccines. The third revision of the American Association of Feline Practitioners (AAFP) Vaccination Guidelines for cats was published in late 2006. This very through document is exhaustively referenced and is an outstanding resource for veterinary practitioners as they change vaccination practices.

The AAFP vaccine guidelines specifically recommend avoiding vaccines that cause persistent local tissue inflammation and which might lead to VAS development. This means a general rule of avoiding adjuvanted vaccines and using non-adjuvanted vaccines whenever possible.

Core Vaccines for Cats

Core vaccines should be given to every patient regardless of lifestyle. For cats, the core vaccines include: parvovirus (panleukopenia), herpesvirus (feline viral rhinotracheitis), calicivirus (FVRCP), and rabies.

Modified live (MLV) FVRCP vaccines are recommended because they are not adjuvanted and do not carry the same risk of inducing chronic vaccine site inflammation that can produce VAS. In addition, a recent study has shown more rapid development of immunity against feline parvovirus in kittens given MLV FVRCP compared to those given killed FVRCP vaccine.

Feline leukemia virus (FeLV) vaccine is still on the AAFP non-core list but I consider it a core vaccine for pediatric patients with the caveat that a non-adjuvanted FeLV vaccine that does not carry the risk of post-vaccinal inflammation that could lead to VAS should be used. The reason for recommending universal kittenhood protection against FeLV is because cats under a year of age are at greatest risk for acquiring this disease. Virtually 100% of kittens infected with FeLV at 6 weeks of age or less will remain persistently infected for life. At 6 months of age, the risk of persistent infection drops to 30% and this decreases further to 5% or less after 12 months due to the development of natural resistance to this disease with age. When we ask clients about their kitten's environment, they may tell us that the kitten will be kept only indoors. However, the kitten may escape to the outside or the client may begin allowing the cat outside. The owner may not return the kitten for FeLV vaccination after the pediatric vaccination series has been completed even though the kitten's risk of exposure to FeLV has changed. By vaccinating the most susceptible individuals (young kittens) we will provide the best possible protection during the period of highest susceptibility to the disease. After a year of age, if the cat truly is kept only indoors without exposure to FeLV-infected cats, we do not need to continue FeLV vaccine administration.

What about virulent systemic calicivirus? See attached FAQ sheet about this virus.

I do not recommend giving Chlamydophila or Bordetella bacterins to household pet cats even though these vaccines remain on the AAFP non-core list. Both of these diseases are very uncommon causes of upper respiratory disease and these vaccines are reactive and have a short duration of immunity. Chlamydophila or Bordetella bacterins may be helpful for short-term use in shelter or cattery situations where an outbreak of upper respiratory disease has occurred if these agents are cultured from a number of cats and confirmed as a major component of the respiratory syndrome.

The feline infectious peritonitis (FIP coronavirus) vaccine and feline Giardia vaccines are on the AAFP not recommended list for reasons of lack of efficacy.

In my opinion, the currently available FIV vaccine is also not acceptable because of poor to minimal efficacy. This vaccine is adjuvanted which means that it carries the risk of VAS. FIV-vaccinated cats will also test falsely positive on antibody-based tests (ELISA, Western Blot, IFA) for at least a year post-vaccination. FIV PCR testing is not yet sufficiently accurate to help us differentiate vaccinated from naturally-infected cats.

Pediatric Vaccination

The goal of pediatric vaccination is to stimulate active and solid immunity before the susceptible kitten is exposed to pathogenic disease. In the words of the famous Civil War general, Nathan Bedford Forrest, we need to "Get there firstest, with the mostest". This means that we must start our vaccination program early enough to prevent active disease as maternal antibody wanes and we must use the safest, most efficacious vaccine products available.

The pediatric Core FVRCP vaccine series should be started when the kitten is seen for its first pediatric examination at 6-8 weeks of age. Core vaccines should be repeated at 3-4 week intervals until the kitten is 16 weeks of age. Although some biologics manufacturers have experimental studies that demonstrate good protection by 12 weeks of age, recent research using conventional kittens indicates that maternal antibody interference with vaccination may persist in some kittens beyond 14 weeks of age. Therefore, I recommend administering the final pediatric vaccination at 16 weeks of age or older. Rabies vaccine should be given at 12 weeks of age or older as per the Rabies Compendium and local ordinances. A non-adjuvanted rabies vaccine is recommended.

Kittens should be tested negative for FeLV prior to vaccination. In addition to the other serious consequences of infection, there is no demonstrated benefit of giving an FeLV vaccine to an FeLV-infected cat. A non-adjuvanted FeLV vaccine should be use according to the manufacturer's instructions.

What if a client is late for revaccination during the pediatric series or comes back at 6 months of age for neuter without having completed the pediatric series? Must I start the vaccination series all over again?

No. If the last core FVRCP vaccine was given at 12 weeks of age or older, one more MLV vaccine should suffice to ensure solid protection. If the last vaccine was at less than 12 weeks, a series of two MLV vaccines is recommended.

Similarly, if you are evaluating an older cat of unknown vaccination status, a series of two MLV FVRCP vaccines, in addition to one RV is recommended to assure a solid basis of protection. After that, for adults, the revaccination interval for FVRCP is 3 years, RV at one year and then as per manufacturer's instructions or local ordinance thereafter.

Re-Vaccination Intervals

FVRCP, FeLV, and RV should be repeated at one year of age. FVRCP is given every 3 years after that time. RV should be re-admininstered according to the manufacturer's licensing approval (1 year or 3 years) and according to local ordinance. FeLV vaccination may be continued according to manufacturer's instructions if the cat is at risk of exposure after 1 year of age.

Is it better to use an adjuvanted 3-year licensed RV or a non-adjuvanted 1-year licensed RV in cats?

The most important factor in induction of VAS is inflammation at the injection site. Experimental histologic studies of vaccination sites show that non-adjuvanted vaccines produce little to no inflammation, whereas adjuvated vaccines cause inflammatory changes at the site that may last for months to years. In my opinion, it is safer to use a non-adjuvated vaccine more frequently rather than any adjuvanted vaccine, regardless of the frequency of use.

What if I change the vaccine products I am using? Must I start the vaccine series all over again?

No. The body does not recognize vaccine brand names. The important protective antigens will be present in a product produced by a different manufacturer. All approved veterinary vaccines have been tested and licensed for efficacy by the USDA.

Vaccine Adverse Events

Systemic Adverse Events

It is fairly common for cats to exhibit some malaise, low grade fever, and anorexia for 12-36 hours post-vaccination. These signs are more frequent when adjuvanted vaccines and/or multiple vaccines are given at the same visit. We see this adverse event so commonly that most veterinarians warn cat owners that this will occur.

"Limping kitten syndrome" is a post-vaccinal, febrile, non-erosive polyarthritis syndrome associated with calicivirus vaccine administration. As the name suggests, this syndrome is most common in young cats. The polyarthritis is a self-limited and usually lasts less than a week. NSAID or other analgesic treatment will provide relief and shorten the duration of clinical signs.

Immune-mediated hematologic disorders including immune-mediated anemia, thrombocytopenia, and/or pancytopenia have occasionally been associated with vaccine administration in cats. Post-vaccinal anterior uveitis has been reported in a few cats. This appears to be an Arthus-like immunologic reaction similar to the "blue-eye" reactions seen with canine CAV-1 vaccine. These immune-mediated disorders usually appear within 3-4 weeks post-vaccination.

The most critical, life-threatening adverse vaccine reaction is systemic anaphylaxis. Cats may exhibit a shock-like event with collapse, panting, vomiting, and/or diarrhea. Intravenous fluids, rapid-acting corticosteroids and anti-histamines should be administered as soon as possible. The lung is a major shock organ in cats and an enriched oxygen environment may be helpful. Avoid over-aggressive fluid administration because pulmonary edema can result.

Cats with a history of adverse vaccine events should be carefully assessed for the need for any vaccines in the future. In general, we try to avoid revaccination whenever possible. If additional vaccines must be given they should be given individually and separated by a 3-4 week interval. A different brand/type of vaccine should be used and the cat should receive antihistamine and corticosteroid pre-medication. I recommend that pre-treatment and vaccination be given as early in the day as possible and the cat should remain at the veterinary hospital for observation for the remainder of the day.

Vaccine-associated sarcoma (VAS):

The issue that galvanized the veterinary community and stimulated us to reassess vaccination practices, particularly in cats, has been the emergence of vaccine-associated sarcomas. This often fatal consequence of vaccination has been strongly linked to adjvanted vaccines because this problem did not appear in cats in significant numbers until killed, adjuvanted rabies and feline leukemia virus vaccines were introduced. The World Health Organization (WHO) in 1999 classified veterinary vaccine adjuvants as Class III/IV carcinogens with Class IV being the highest risk. All vaccine adjuvants induce chronic inflammation at injection sites that can lead to sarcoma development in genetically predisposed cats. Aluminum is not the only component that is associated with VAS, however, aluminum serves as the "smoking gun" in injection-site tumors because no other injectable agents contain this material. The histologic appearance of VAS is classical because they have a significant lymphocytic and plasmacytic infiltrate. The etiology can be further confirmed with immunohistochemical studies.

There is probably a genetic component that predisposes some cats to tumor development at sites of chronic inflammation. At present we are not able to test for this genetic predisposition. Mechanical influences such as the temperature of the vaccine, the size of the needle used for injection, and the site of injection (subcutaneous versus intra-muscular) have been ruled out as causal factors.

There are several significant problems with using retrospective epidemiologic studies to attempt to determine which specific products or adjuvant components are of most concern. First, veterinarians often change products and may not keep accurate records about which product brands and lot numbers were used. Second, tumors may develop many years after a vaccine was given. Therefore, if a VAS tumor develops in a 10 year old cat that has been vaccinated yearly, we cannot know whether it was the vaccine given this year, 5 years ago, or 9 years ago that produced neoplastic transformation.

The occurrence of VAS in cats has been listed in various reports to be between 1.3:1000 and 1:10,000. Cats tend to breed locally, not nationally or internationally. Local populations may have genetic variations that may predispose a cat to developing VAS. Thus, the incidence of VAS seen in a particular practice may be different from another practice 10 or 100 miles away that uses the same vaccines and protocols.

How do you I know whether my patient has a VAS and what should I do if I diagnose one?

A local reaction at the site of vaccination is relatively common in cats, especially when adjuvanted vaccines are used. This site reaction usually subsides within 3-4 weeks without incident. If the site lesion is still present 4 weeks post-vaccination, you should perform fine needle aspiration cytology. If only inflammation is seen, the site can be watched for an additional 4 weeks. If the local reaction is still present 8 weeks post-vaccination, it should be biopsied and if not neoplastic, the affected area should be excised. If there is neoplastic transformation at a vaccination site, the cat should be referred for imaging and radical surgical removal of the mass. Complete first excision is the best treatment and may be curative. Further adjunctive therapy for VAS might include radiotherapy (brachytherapy, etc.), chemotherapy, and/or immunotherapy. The specifics of these adjunctive treatments are beyond the scope of this discussion.

Using the AAFP recommended sites for vaccination gives us a better chance to remove vaccination-site sarcomas completely should they occur. However, the best ways to reduce the incidence of site reactions and VAS are to use non-adjuvanted feline vaccines whenever possible and to give feline vaccines on an appropriate, reduced frequency schedule as recommended by the AAFP, ACVIM Infectious Disease study group, AAHA, and academic infectious disease specialists.

Lymphocytic nephritis from parenteral feline vaccines grown in Crandall Rees kidney cells

Chronic progressive renal disease (CPRD) is the most common cause of morbidity and mortality in older cats. Lymphocytic/plasmacytic nephritis is a common histologic finding in cats with CPRD. A pilot study by Dr. Mike Lappin and his research group several years ago demonstrated that Crandall Rees kidney cell (CRCK) antigen from viral cell cultures used to produce feline vaccines caused the development of anti-renal antibody in cats vaccinated with parenteral FVRCP vaccines. A further report from this research group demonstrated lymphocytic/plasmacytic inflammation in the kidneys of CRKC-sensitized cats. While the long-term significance of these findings is not yet known, it is another reason to modify our vaccination protocols to reduce the number of vaccines and vaccinations given to cat to the fewest needed to maintain good disease protection and good health.

Reporting Adverse Events

Veterinarians should keep accurate records of the brand, lot, serial number and injection site of all vaccines administered to their patients. The peel-off vaccine labels are very useful for those practices using paper records. Data should be entered in the electronic record for paperless practices. Any suspected adverse event should be reported to the Professional Services veterinarians of the biologics manufacturer involved. Adverse events should also be reported to the USDA Adverse Event reporting site at: http://www.aphis.usda.gov/vs/cvb/html/adverseeventreport.html If entering this long string is cumbersome, you can "Google": USDA adverse event, and the reporting site will be the first entry on the search results list. The USDA online reporting form is very easy to fill out and submit.

References

AAFP Feline Vaccine Advisory Panel Report 2006: JAVMA 2006; 229(9), 1405

Rassnick KM: Vaccine-associated sarcomas: The problem is not over yet. ACVIM Proc 2006

Levy JK et al: Responses of Feral Cats to Vaccination in Trap-Neuter-Return Programs. ACVIM Proc. 2006

Levy JK et al: The Effect of Anesthesia and Surgery on Serological Responses to Vaccination in Kittens. ACVIM Proc 2006

Lappin MR, et al: Interstitial nephritis in cats inoculated with Crandell Rees feline kidney cell lysates. J Fel Med Surg 2006;8:353.

Gore TC et al: Three-year duration of immunity in cats following vaccination against FVR, FCV, and FPL. Vet Therapeutics 2006:7(3):213.

Shultz RD: Duration of immunity of canine and feline vaccines: A review. Vet Microbiol 2006; 117(1):75

Kirpensteijn J: Feline injection site-associated sarcoma: Is it a reason to critically evaluate our vaccination policies? Vet Microbiol 2006;117(1):59

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Volume 74, World Health Organization, International Agency for Research on Cancer, Feb 23-Mar 2, 1999, p 24, 305, 310.