Current vaccine controversies (Proceedings)

Vaccination is a key component of preventing infectious disease in individuals as well as reducing the risk of exposure to (and by) others. Testing for the presence of feline leukemia virus (FELV), feline immunodeficiency virus (FIV) in our patients is also crucial in prevention of the spread of preventable diseases between cats.

Vaccination Guidelines Immunization is a method of enhancing or influencing the immune system and to develop resistance to infectious disease by inducing the production of antibodies and/or immunologically sensitized cells. A vaccine consists of material administered to induce immunity and is a preparation of weakened (attenuated), killed or immunologically active subunits of active virus or bacteria, which are unable or unlikely to cause the disease against which they are designed to protect. Vaccines are usually administered parenterally by injection or by mucosal route.

In 1998, the American Association of Feline Practitioners (AAFP) released Feline Vaccination Guidelines intending to review, update and summarize vaccine-related issues affecting how a practicing veterinarian chooses to formulate vaccination strategies for cats. Controversy arose as some practitioners feared that reducing the frequency of vaccine administration might result in outbreaks of well controlled infectious diseases and that clients would visit veterinary clinics less frequently thereby preventing early detection of disease and implementation of medically valuable preventative care opportunities as well as threaten a cornerstone of practice revenue.. This resulted in much beneficial discussion within the profession. An update was published in 2006. Both documents are available at www.catvets.com in the Guidelines section.

The following is an attempt to summarize the key points of the 2006 document.

1. Vaccines continue to play an important role in the control of feline infectious diseases in an overall preventative health care program for cats.

2. Vaccinations should be selected for each patient based on risk of exposure to specific pathogenic agents.

3. Core vaccines are those recommended for administration to every cat because of a) severity of disease, b) transmissibility between animals and/or c) zoonotic potential. As such, panleukopenia (FPV), feline viral rhinotracheitis virus (FHV-1), feline calicivirus (FCV) and rabies are considered core vaccines for cats. In the newest version of the Guidelines, FELV is highly recommended in kittens.

4. Non-core vaccines are those whose use should be restricted to individual cats deemed to be at a reasonable risk of exposure based on their lifestyle or environment. These would include FELV in adult cats, chlamydophyla, feline infectious peritonitis (FIPV), FIV, bordetella and giardia vaccines.

5. While vaccine administration is not an innocuous procedure, the benefits of vaccination far outweigh the risks for the majority of cats. We must continue to vaccinate our patients to prevent recrudescence of infectious diseases we now control. The objective of feline vaccination protocols should be to vaccinate more cats in the population, vaccinate individuals less frequently, and only for the diseases for which there is a risk of exposure and disease.

In other words, rather than being viewed as a routine, annual requirement and the driving force behind the annual exam, vaccination should be a carefully considered medical procedure discussed thoroughly with the client. At each visit, vaccination requirements should be revisited as the risk factors for that patient change through life.

When developing a vaccination protocol for an individual cat, the following questions may be considered. Is this individual at risk for this disease? Does this disease have high morbidity? Is it readily treatable? Realistically, could this agent cause fatal illness? It may be inappropriate to use a vaccine against a disease that is rare or against a disease that is not associated with a high morbidity. What kind of protection do I expect from this vaccine (prevention vs. decreased severity of illness)? What side effects or adverse reactions might this vaccine cause? How long does immunity last and when did this cat receive this vaccine last? Each infectious agent is different; in general those that cause severe systemic disease result in lifelong immunity (e.g., panleukopenia) whereas those that cause superficial infections produce more transient immunity or a carrier state following recovery (e.g., FHV-1).

Risk assessment

Host factors, environmental factors and agent factors

Many factors affect the ability of the host to respond to immunization. These include genetics, maternal immunity, age at time of exposure to the agent, stress (husbandry or concurrent illness), nutritional status and medication/therapies. In general, kittens younger than 6 months of age are the most susceptible to infection, and interference with vaccination antigen by maternal Ab is the single most common cause of vaccination failure. Population density, sanitation, and ventilation impact not only the opportunity for exposure to the pathogen but also the dose of the agent that an individual is exposed to. The virulence and mutation of the pathogen will also play a role. The result of these three groups of factors will significantly impact the interaction between the pathogen and individual cats. These aspects should be re-evaluated as often as annually or as host and environmental factors change.

How often should an individual be vaccinated?

With the exception of rabies vaccines, determination of duration of immunity (DOI) has not been required by the American licensing body, the US Department of Agriculture (USDA) for vaccine licensing until recently. This means that only new products whose licensing applications have received recently have required DOI data. The recommendation for annual revaccination was, from the start, an arbitrary recommendation, not based on scientific data. For most vaccines (e.g., FVRCP), annual revaccination is excessive, for others (e.g., chlamydophila) it is inadequate.

Why should we have concerns about over-vaccinating? Arguably, the most alarming one is the risk of vaccine site associated sarcoma (VAS) development, however, valid concerns have been raised that over-exposure of the immune system to antigens may over-sensitize a predisposed individual to the risks of hypersensitivity reactions. Administration of any vaccine or other "medication" is never completely without risk. The benefits of the procedure must be weighed against the possible risks. The most common vaccine reactions are local ones such as pain, local swelling or hair loss at the site of injection. Malaise with low-grade fever and lethargy are not uncommon. Hypersensitivity reactions may occur from the most severe and life-threatening, anaphylaxis (Type I, more common with killed vaccines), a local inflammatory reaction (Type III), or a Type IV reaction with granuloma formation. The use of multiple antigens may also cause a transient immunosuppression during the post vaccinal period, the same period during which one is attempting to induce immunity!

The incidence of soft tissue sarcomas has increased in cats since the late 1980s and parallels the introduction of widespread FELV vaccination as well as the mandatory use of longer acting, more potent rabies vaccines. In epidemiological studies it was shown that cats receiving FELV vaccines had a 5.5 fold increased likelihood of developing a sarcoma at an injection site and that cats receiving rabies vaccine had a twofold increase in risk compared to cats receiving no vaccines. It was calculated in the initial study by Kass, that one to three sarcomas developed per 10,000 doses of FELV and rabies vaccine administered. Other studies place the rate of risk lower or higher but numerous studies have confirmed the causal relationship between vaccination and sarcoma formation in cats. Additionally it was observed that the risk increased with the number of doses of vaccine administered to a given cat at one time: a 50% increase following one vaccine, a 127% increase after two doses and a 175% increase following three or four vaccines given simultaneously. It should not be concluded that only FELV and rabies are involved, however, as other antigens have been implicated as well. The Vaccine Associated Fibrosarcoma Task Force (VAFSTF) investigated the pathogenesis of these dreadful reactions. One component appears to be malignant transformation of reactive fibroblasts in the presence of adjuvant. Meticulous investigation has confirmed that neither FELV, FIV nor feline sarcoma viruses are present in these tumours. Nevertheless, the risks of developing a VAS are still lower than the risk of developing FELV or rabies if exposed. Clients have a right to be informed of the risks of vaccinating and of not vaccinating. The following websites are helpful for informing the concerned client about VAS: www.catshots.com, www.avma.org/vafstf

What guidelines can we use to minimize the risk of the development of a VAS and what protocol can be used in their management?

1. Use a minimum number of vaccines for an individual and base the selection on risk assessment.

2. Use the least reactive products available, i.e. use MLV, recombinant or other non-adjuvanted products.

3. Follow the AAFP vaccine administration site recommendations (FVRCP: lower R fore limb, rabies lower R hind limb, FELV lower L hind limb).

4. Use single dose vials rather than multidose tanks to ensure that all doses of vaccine are uniform.

5. Follow the "3-2-" guidelines of the, for handling post vaccination masses. Biopsy any post vaccination mass if it continues to be present three months after vaccination, if it is larger than 2 cm in diameter, or if it is increasing in size one month after vaccination.

6. Biopsy, rather than remove the mass initially because if the mass turns out to be a sarcoma, then excision of the mass is not sufficient, and the opportunity for an aggressive first surgery has been missed (survival is highly associated with the completeness of the first attempt at surgical excision).

FIV vaccination

Each situation must be carefully evaluated but vaccination is not routinely recommended. FIV vaccination is considered to be a non-core vaccine reserved for cats at high risk of infection. This might include cats that roam outdoors, particularly those cats that fight a lot. Cats residing with FIV-infected cats are also at increased risk of infection. Although we tend to believe that the risk of transmission between cats that live peacefully together is low, there are reports of transmission between cats without evidence of fighting. The extent of protection offered by the vaccine in the field is unknown, but protection was less than 100% in cats experimentally challenged with a laboratory strain during licensing studies. Thus, it is reasonable to assume that not all vaccinated cats will be protected against all strains of FIV. Once a cat at high risk of FIV infection is vaccinated, it will become very difficult to know if it has subsequently become infected. Antibody titers induced by vaccinating appear to cause false positive results for at least four year. Commercially available polymerase chain reaction (PCR) tests cannot be used with confidence. Virus isolation remains the gold standard for differentiating between an infected vs. a vaccinated cat.

Virulent strain calicivirus

What about the virulent strain feline calicivirus (VS-FCV) vaccine? The American Association of Feline Practitioners suggests in the Virulent Calicivirus Information Brief that veterinarians consider the information provided in the Feline Vaccine Advisory Panel Report and the following information when making a decision concerning use of FCV containing vaccines:

• The incidence of VS-FCV associated disease in the United States or other countries is unknown.

• In part because of the difficulties associated with achieving a clinical diagnosis, it is currently unknown whether VS-FCV outbreaks are increasing over time.

• VS-FCV strains appear to arise from mutations; so far, each of the outbreak strains appears to be genetically and antigenically distinct from others.

• It is currently unknown whether administration of CaliciVax? results in protection against heterologous VS-FCV strains on challenge.

• The maximal duration of immunity of CaliciVax? for homologous or heterologous VS-FCV strains is unknown.

• Use of multiple FCV strains in feline vaccines may increase cross-protection capabilities but results of serum neutralization tests of FCV strains in vitro may not necessarily correlate to protection on challenge.

• Inactivated vaccines may induce protection more slowly than modified live vaccines and so if an inactivated FCV containing vaccine is to be used in the primary immunization period for cats at high risk of exposure to feline panleukopenia virus, it should be used in combination with a parentally administered modified live feline panleukopenia virus containing vaccine.

Unfortunately, the length of these notes precludes the inclusion of the Vaccine Advisory Panel Summary Table, which the author recommends that you download and print it from www.catvets.com => Veterinary Professionals => Practice Guidelines => Guidelines Publications.

Aafp feline retrovirus management, key points from the 2008 guidelines document

FELV and FIV are among the most common infectious diseases of cats. Although vaccines are available for both viruses, form the cornerstone for preventing new infections. Currently, the majority of cats are never tested for FELV or FIV during their lifetime, resulting in thousands of new cases each year.

Testing for FELV and FIV: All cats should be tested at appropriate intervals based on risk assessment

• Test new cats entering a household or group housing as in shelter or cattery settings. Test again at least 60 days later, limiting exposure to other cats if possible during that time.

• Test if exposed to a retrovirus infected cat at least once, 60 days after exposure.

• Test all sick cats, regardless of previous test results.

• Test before initial vaccination for FELV or FIV.

• Consider annual retesting of cats that remain at risk for infection, regardless of vaccination status.

• Always confirm an initial positive retrovirus test.

• Cats that donate blood or tissue should be tested for FELV by real-time PCR to rule out regressive infection that may be transmissible via transfusion or transplantation.

• Testing healthy feral cats in trap–neuter–return programs is optional depending on resources and program goals.

Vaccination and other preventative measures ??

When to consider FELV vaccination

• Vaccination of all kittens is highly recommended.

• Vaccinate cats that have direct contact with cats of known positive or uncertain status, such as outdoor cats and group housing foster or shelter situations.

When to consider FIV vaccination

• Cats living with FIV-positive cats, particularly if there is fighting.

• Cats that go outside and fight.

• It is unknown whether the vaccine provides cross protection against the many heterologous strains of the virus.

• NOTE! Cats vaccinated with the current FIV vaccine will test positive for FIV antibodies. Visible (collar) and permanent (microchip) identification is recommended for all cats to facilitate reunification should cats become lost. This especially important for cats vaccinated against FIV since a positive test in an animal shelter may result in euthanasia.

Isolation of infected cats using screen or chain link fence barriers is adequate to prevent the transmission of retroviruses. Detergents and common hospital disinfectants effectively inactivate retroviruses. Using sterile or single-use items will deter iatrogenic infections. All blood donors should be tested at least annually.

Management considerations

Retrovirus-positive cats may live many years without related illness. A decision about euthanasia should not be made based on a positive test alone.

• Retrovirus-positive cats should be evaluated by a veterinarian twice a year. In addition to a thorough physical exam, a minimum database including a complete blood count, chemistry panel and urinalysis should be performed at least yearly. Cats with FELV may have complete blood counts performed twice yearly due to their increased risk of hematological diseases.

• Utilize aggressive diagnostic and treatment plans early in the course of any illness.

• Retrovirus positive cats should be spayed or neutered, housed indoors, and should avoid raw food diets.

• Few large controlled studies have been performed using antiviral or immunomodulating drugs for the treatment of naturally infected cats. More research is needed to identify best practices to improve long-term outcomes following retroviral infections in cats.

Recommendations specific to cattery, shelter and rescue situations may be found within the full text of the guidelines. The author recommends that you download and print them from www.catvets.com => Veterinary Professionals => Practice Guidelines => Guidelines Publications.