Virulent systemic feline calicivirus (Proceedings)

1) Overview

a) The VS-calicivirus is a mutant strain of the common feline calicivirus.

b) It causes disease that is much more severe and usually fatal, especially to adults.

c) Common calicivirus vaccines offer no protection, but they do not predispose the cat to getting a VS-calicivirus infection.

d) The common calicivirus disease

i) It is an upper respiratory infection primarily affecting the nose.

ii) Clinical signs

(1) Sneezing, fever (mild), lethargy, anorexia, nasal discharge (serous to purulent), and oral ulcers (primarily on the tongue.). The distinguishing feature (from a Herpesvirus infection) is oral ulceration. The feline Herpesvirus often causes corneal ulceration.

2) First outbreak

a) Occurred in 1998 in Northern California.

b) Occurred in a veterinary practice and a research laboratory.

c) 33 and 50% of infected cats died.

d) It was spread by contaminated fomites.

e) Clinical signs

i) Began with typical URI signs then ...

ii) Fever, facial and limb edema, hair loss and ulcerative dermatitis of the face and feet, sudden death.

3) Southern California (Los Angeles) outbreak

a) Occurred in three veterinary practices and one rescue organization. They were located geographically close to each other and employed many common staff members, who circulated between the four facilities.

b) Transmission between the four facilities was due principally to fomites and cat-to-cat contact involving cats with clinical and subclinical infections.

c) Involved 54 cases.

d) The common clinical signs were fever (81%), nasal discharge (30%), oral ulcers (46%), and limb or facial edema (52%).

e) The less common signs were dyspnea (17%), dermatitis of the face and feet (17%), conjunctivitis (11%), icterus (11%), and pleural effusion, diarrhea, vomiting, and hemorrhage in the skin.

f) 15% of the cats had mild clinical signs; 15% of the cats had moderate clinical signs; and 70% of the cats had severe clinical signs that included edema, dyspnea, and death. 63% of the cats with severe clinical signs died.

g) The time from exposure to the onset of clinical signs averaged four days (1-12 days).

h) 59% of the cats over one year of age died; the fatality rate of cats less than six months old was in frequent.

4) Common components of the VS-Calici outbreaks

a) An index case could be identified (5/6), usually a shelter or rescue cat.

b) They have occurred principally in adult, vaccinated cats that had received herpes-calici vaccine.

c) Spread has occurred rapidly be a fomites on employees or clients.

d) They have not spread out of the facility into the community.

e) Each outbreak has resolved in about two months.

5) VS-Calici Shedding

a) In feces

b) In sloughed skin and hair

c) In nasal, ocular, and oral secretions

d) Viral shedding occurs intermittently for ~4 months after resolution of clinical signs.

6) Typical Clinical Signs

a) Begins with classic calicivirus URI signs

i) Sneezing

ii) Nasal and ocular discharge

iii) Oral ulceration

iv) Anorexia

v) Lethargy

vi) Fever

b) More severe signs

i) Frequent

(1) Fever > 105

(2) Cutaneous edema: head and limbs; fluid oozes through the skin

(3) Alopecia

(4) Ulcerative dermatitis: pinnae, lips, nose, around eyes

ii) Less Frequent

(1) Severe dyspnea due to pulmonary edema, pleural effusion, pneumonia

(2) Icterus

(3) Vomiting and diarrhea

(4) Coagulopathy: ecchymoses in skin

(5) Sudden death

7) Unique Features of the VS-Calici (vs. the Common Calici)

a) Induces systemic vascular compromise leading to swelling, edema, and hemorrhage.

b) Rapidity of involvement of visceral organs (~4 days)

i) Lungs, pancreas, liver

ii) Resulting in death.

8) Stopping an outbreak

a) Clean contaminated exam rooms. Wash surfaces with detergent. Treat with bleach (1:32 solution) or potassium peroxymonosulfate (Trifectant®). Other commonly used disinfectants are not effective.

b) Cleaned every surface in the hospital, especially objects frequently touched such as telephones, keyboards, doorknobs, etc.

c) Treat bedding and clothing. Discard (preferably) OR wash with hot water, detergent, and bleach or discard.

d) Wear isolation clothing when touching these cats. Close the facility for at least two weeks.

e) Isolate sick and exposed cats using individual wards and separate equipment and clothing. Limit staff exposure.

f) Close your hospital for disinfection for at least 2 weeks.

9) Confirmation

a) Simplistic approach

i) Above clinical signs +

ii) Positive isolation for feline calicivirus

(1) Moisten swab with transport media and collect samples from the nares and oral cavity.

(a) Viral transport media: 10 mg injectable amoxicillin or ampicillin + 6 mg of gentamicin sulfate in 500 ml of sterile saline.

(2) Freeze the samples.

(3) Transport to the lab overnight with dry ice or ice packs.

(4) More likely to be VS-calici if a positive isolation occurs from a sample taken from a skin lesion.

iii) False positive isolations

(1) Up to 25% of clinically normal cats will have FCV in their oral cavities

(2) Recent FVRCP vaccine – modified live only.

iv) False negative isolations

(1) Some clinically affected cats do not shed calicivirus (Veterinary Microbiology, January 2006). Thus, isolation rates of 30-50% are typical in outbreaks, especially one week after onset of clinical signs.

b) Currently, immunohistochemical staining of affected tissues demonstrating the presence of the virus in the viscera and its association with lesions is the Gold Standard. However, it is only available through specialized laboratories.

10) Calicivirus Isolation

a) Many commercial veterinary labs will not do it.

b) Texas Veterinary Medical Diagnostic Laboratory; (888) 646-5623; (979) 845-3414

i) Charge: Texas residents: $17.00; Non-Texas Residents: ~ $28.00

ii) Sample: Oral + nasal swab and/or skin lesions

iii) No transport media

iv) Iced at 40 degrees and shipped overnight

v) Frozen at -17 degrees and stored for "good period of time"

(1) If frozen, must be shipped frozen.

vi) Turn around time varies depending on the amount of virus, etc. It can be as short as 24 hours or up to 1 month. They inoculate cultures once per week.

11) Vaccination

a) CaliciVax by Fort Dodge is the only product containing VS-Calici.

i) Requires 2 doses 3-4 weeks apart for kittens or adults

b) Safety

i) The FD safety study showed 3% incidence of "adverse events"

(1) Adverse events includes "reaction" and "response"

ii) MLV vaccines

(1) Cats receiving MLV products feel normal for 3-10 days.

(2) During that time the virus replicates up to an immunizing dose.

(3) But, the cat's response is spread over several days and is not noticeable.

(4) Thus, there are very few "reactions."

iii) Killed vaccines

(1) The antigen mass and adjuvant confront the immune system within hours after vaccination.

(2) The immune system is upregulated rapidly and forcefully.

(3) This causes fever/lethargy/etc. in the 24-48 hour timeframe post vaccination.

(4) This constitutes a good "response" rather than a "reaction."

(5) Advantages: No reversion to virulence and no long-term infections.

c) Cross protection

i) Any answer to the issue of cross protection is speculation because not all strains have been used in challenge studies.

ii) But, present calicivirus vaccines do not have cross protection to all strains of common calicivirus disease. There are literally dozens of strains, and all US vaccines only contain one strain. But, we use these vaccines without question.

iii) CaliciVax is a combination of one common calici strain and one VS-calici strain.

(1) 37 calicivirus isolates were collected from outbreaks in European shelters. Cross neutralization tests were performed on each of the 37 strains to determine the likelihood of cross protection.

(a) Group 1 cats received a vaccine with one common Calici strain: 24% cross neutralization.

(b) Group 2 cats received CaliciVax: 73% cross neutralization

(c) Protection tripled by using a dual-strain vaccine.

(2) Therefore, even if you do not protect against all strains of VS-calici, CaliciVax will greatly increase protection against common calicivirus strains.

(3) No other calici (FVRCP) vaccine can do that.

iv) PU R, Coleman J, Omori M, Arai M, Hohdatsu T, Huang C, Tanabe T, Yamamoto JK. Dual-subtype FIV vaccine protects cats against in vivo swarms of both homologous and heterologous subtype FIV isolates. AIDS. 2001;15:1225-1237.

(1) This study on the FIV shows that combining two strains of virus into the same vaccine will increase efficacy against the two strains as well as against other strains.

v) All current calicivirus vaccines are single strain vaccines.

(1) "Unfortunately, there is an increasing number of strains against which vaccination does not even provide limited protection ('vaccine resistant strains'). That same tendency to mutate that results in so many different clinical manifestations of FCV means that vaccine resistant strains are constantly emerging, and most FCV vaccines contain strains that have not been updated in decades. Although new vaccine strategies, such as polyvalent vaccines, are under investigation at this point it is prudent to assume that even vaccinated cats will be susceptible to infection and severe disease from some strains of calicivirus." UC Davis Koret Shelter Medicine Program website; http://www.sheltermedicine.com/portal/is_vsfcv.shtml

(2) Your choices

(a) Current single strain calicivirus vaccines with limited protection against common calicivirus strains and no protection against VS-calicivirus strains.

(b) CaliciVax, a dual strain vaccine with increased protection against common calicivirus strains and some protection against VS-calicivirus strains.

12) Summary

a) The VS-calici is a mutant strain of the feline calicivirus.

b) It has occurred spontaneously at least 9 times since 1998.

c) It is spread by fomites and contact.

d) Many cats become infected.

e) Most of the adults die.

f) Prevention is available: CaliciVax by Fort Dodge.

References(In order of occurrence)

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 Microbio. 2002;73:281-300.

Hurley KF, Pesavento PA, Pedersen NC, et. al. An outbreak of virulent systemic-feline calicivirus disease. J Amer Vet Med Assoc. 2004;224(2);241-246.

Foley JE. Calicivirus: Spectrum of Disease. In: August JA, ed. Consultation in Feline Internal Medicine, 5th ed. 2006:1-7.

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

Pu R, Coleman J, Omori M, et. al., Dual-subtype FIV vaccine protects cats against in vivo swarms of both homologous and heterologous subtype FIV isolates, AIDS, 2001, Vol. 15, pp. 1225-1237.