Top eight questions about virulent hemorrhagic feline calicivirus (Proceedings)

Feline calicivirus (FCV) is best known for its role in causing acute upper respiratory disease and oral ulceration in kittens and cats. Although morbidity in routine respiratory infections is high, these infections are rarely fatal. Most recovered kittens do develop a chronic carrier state characterized by continuous shedding of virulent virus from the oral cavity and respiratory tract that may last for months to years. The caliciviruses are comprised of a variety of small, non-enveloped, single-stranded RNA viruses that are regarded as being somewhat more resistant than feline herpesvirus-1 when outside the host. Unlike herpesvirus-1, however, over 40 strains of calicivirus have been identified and are known to vary significantly in virulence and antigenicity. Despite widespread vaccination against FHV-1 and FCV, these viruses are still known to occur in large numbers in the domestic cat population, particularly in multiple cat households and animal shelters.

Since 1998, however, at least 6 outbreaks of a virulent feline calicivirus have been reported. [REF #1] In these outbreaks, virulent, systemic strains of feline calicivirus (referred to as VS-FCV or hemorrhagic feline calicivirus) were recovered. Unlike FCV associated with routine, acute upper respiratory infection in kittens, infection with a virulent systemic strain of calicivirus has resulted in high mortality among previously healthy kittens and cats. Associated clinical signs include high fever, oculonasal discharge, alopecia, cutaneous ulcers involving the face and limbs, and subcutaneous edema. Infection causes epithelial cell cytolysis and systemic vascular compromise in susceptible cats. VS-FCV viruses appear to be highly contagious and are easily transmitted to other cats by way of eating utensils, hands, and even clothing.

Although the incidence of infection is quite low within the cat population, new vaccines are being developed to protect cats against the emerging strains of virulent FCV. This column is a 'first look' at the clinical aspects of hemorrhagic feline calicivirus and will facilitate decisions regarding the use of these new vaccines as they enter the market in 2007.

What is virulent systemic feline calicivirus?

Virulent systemic calicivirus is a newly recognized feline calicivirus variant that causes severe systemic disease with up to 60% mortality in affected populations of cats. Clinical signs include upper respiratory disease (oculo-nasal discharge, oral ulcers), pneumonia, peripheral edema and skin sloughing (especially on the face and limbs) due to cutaneous vasculitis, and systemic vasculitis with DIC that causes multiple organ/system failure which may lead to death.

Which cats are most likely to be affected?

Virulent systemic calicivirus has occurred almost exclusively in populations of group housed cats. In each documented outbreak, the disease seems to have spontaneously appeared in the population, most likely by mutation from caliciviruses already circulating in the group of cats. This is supported by genomic analysis of the virulent strains - they are unique, rather than clonal, and have no common mutations that could easily explain the change in virulence. Outbreaks of virulent calicivirus have been isolated and are very rare. Shelter and rescue catteries are the most commonly affected populations. Several epizootics in veterinary facilities have occurred because of the introduction of a sick shelter cat into the veterinary hospital. Because this calicivirus variant is so pathogenic, the disease usually burns itself out in the affected population over several weeks and general spread to and among household pets in the surrounding community has not been reported. However, in at least one case, veterinary personnel handling cats in an affected population have carried the disease to their own pets at home.

How can I recognize this disease?

Virulent systemic calicivirus is a very rare disease that most often affects group housed cats. Typically, the disease emerges as an apparent epizootic of upper respiratory disease that causes severe respiratory symptomatology but progresses to produce cutaneous and systemic complications with a higher than expected mortality rate among affected cats. The incubation period for VS-FCV is 1-5 days. Older cats often have more severe disease than younger cats with this unusual calicivirus variant. Keep in mind that this is a very rare variant of feline calicivirus and that the vast majority of cats with clinical signs of upper respiratory disease will have infection caused by the much more common feline upper respiratory disease agents.

How is virulent systemic calicivirus spread among cats?

Like other caliciviruses, hemorrhagic calicivirus is present in the secretions and excretions of affected cats. Once the virulent mutant appears, spread may occur by direct contact among cats, transfer by hospital personnel handling cats, and via fomites. If an outbreak of VS-FCV is suspected, strict quarantine and isolation of affected cats, and scrupulous cleaning procedures must be initiated to contain the infection and avoid spread of the disease. Hospital personnel should wear protective clothing (gowns, caps, shoe covers) and disposable gloves when handling affected cats. Food bowls, medical equipment, and supplies used in the isolation area should remain there and not be moved in and out of the isolation area. Personnel should wash exposed body parts well and change their clothing and footwear prior to returning home to avoid transmission of the disease to their own household cats. Ideally, the hospital should avoid admitting new feline patients until the disease outbreak is under control.

What should I do if I suspect that I have a patient affected with virulent systemic calicivirus?

If you suspect that you have a patient with virulent systemic calicivirus, you should immediately institute the isolation and sanitation procedures described previously. Contact Dr. Janet Foley at the School of Veterinary Medicine, University of California at Davis. Dr. Foley is conducting an ongoing investigation of this disease and may be contacted at: jefoley@ucdavis.edu or (530) 754-7355 for additional information and for recommendations regarding sample submission for testing to definitively diagnose this disease. No new cats should be introduced into the environment unless testing does not identify the presence of hemorrhagic calicivirus or until the disease has run its course in the affected population. Recovered cats may shed infectious virus for several weeks to months post-infection so they should not be commingled with susceptible cats during this time.

How can I prevent this disease from being introduced into my veterinary hospital?

Virtually all nosocomial cases of this disease occurring in veterinary hospitals have occurred because of the introduction of a sick shelter or rescue cat into the hospital environment. The best method to prevent the introduction of this disease is to avoid hospitalizing sick cats from these types of shelter and rescue facilities. If such cats must be admitted into your hospital, they should be kept in strict isolation under barrier conditions as described above to prevent spread to other cats in the hospital population.

Does VS-FCV occur in well-vaccinated cats?

The traditional upper respiratory calicivirus vaccines (containing calicivirus strain F9 or others) do not protect cats against the virulent systemic calicivirus variant. One killed, adjuvanted VS-FCV vaccine is now available. Several other biologics manufacturers are developing feline vaccines that will include the virulent systemic calicivirus antigen and these products should be available later this year.

When virulent systemic calicivirus vaccines are available, should I change my vaccination protocol for cats to include this antigen?

There are several important criteria to consider when making any decision about whether or not to change your current feline vaccination protocol or the products you are using. Risk assessment is an important part of this decision making process.

Is virulent systemic calicivirus a disease that commonly produces significant morbidity and/or mortality among cats, particularly among household pets? The answer to this question is, no. Although the mortality rate is high, the disease is very rare and outbreaks have almost always involved shelter or rescue cats, not household pets.

The second point to consider is whether the risk of exposure to or infection with this disease is greater than the risk of potential harm from a vaccine product containing this antigen. As you are undoubtedly aware, the American Association of Feline Practitioners Vaccination Protocol recommends limiting the number of antigens administered to cats to those that commonly cause significant morbidity and mortality. This document also recommends using the least reactive vaccine products available (MLV or other non-adjuvanted products) to reduce the risk of vaccine-associated sarcomas (VAS) in cats. The risk of VAS from chronic post-vaccinal inflammation reported in the literature is 1.3:1000 to 1:10, 000.

At the present time, the total number of cats reportedly diagnosed with VS-FCV disease in the past 9 years is less than several hundred. The risk of exposure to or infection with hemorrhagic calicivirus is much less than the potential for chronic inflammation that can lead to sarcoma development with an aduvanted vaccine. Therefore, if a new VS-FCV vaccine product contains adjuvant, we do not recommend using it. If a non-adjuvanted VS-FCV vaccine product becomes available it would not carry the same risk of VAS development. Such a vaccine would be recommended because it may be beneficial to add this additional antigen to broaden the spectrum of calicivirus protection for your feline patients.

References

1. Foley J, Hurley K, Pesavento PA, Poland A, Pedersen NC. Virulent systemic feline calicivirus infection: local cytokine modulation and contribution of viral mutants. J Feline Med Surg 2006 Feb;8(1):55-61.

2. Pedersen NC, Elliott JB, Glasgow A, Poland A, Keel K. An isolated epizootic of hemorrhagic-like fever in cats caused by a novel and highly virulent strain of feline calicivirus. Vet Microbiol. 2000;73(4):281-300

3. Coyne KP, Jones BRD, Kipar A, et al. Lethal outbreak of disease associated with feline calicivirus infection in cats. Vet Rec. 2006;158(16):544-50.

4. Abd-Eldaim M, Potgieter L, Kennedy M. Genetic analysis of feline caliciviruses associated with a hemorrhagic-like disease. J Vet Diagn Invest. 2005;17(5):420-9.

5. Hurley KF, Pesavento PA, Pedersen NC, Poland AM, Wilson E, Foley JE. An outbreak of virulent systemic feline calicivirus disease. J Am Vet Med Assoc. 2004;224(2):241-9.

6. Schorr-Evans EM, Poland AM, Johnson WE, Pedersen NC. An epizootic of highly virulent feline calicivirus disease in a hospital setting in New England. J Feline Med Surg. 2003;5(4):217-26.

7. Hurley KF, Sykes JE. Update on feline calicivirus: new trends. Vet Clin North Am Small Anim Pract. 2003;33(4):759-72.