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Discussion

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Authored by Mia McKenzie

Feline Calicivirus

This paper discusses Feline Calicivirus in the shelter environment. It uses evidence based research and experiences from shelters who have successfully contained the Feline Calicivirus, and to determine the most humane and effective management of Feline Calicivirus suspect cats and infected cats in animal shelters. This paper is written in support of Nathan Winograd's No Kill Equation. What is it? The Feline Calicivirus (FCV), commonly labelled as 'cat flu', is a part of the Caliciviridae family, and is a RNA virus (Newsham, 2011). Compared to a DNA virus, an RNA virus has a higher mutation rate. It can change its hereditary information, structure and size at a quicker rate and it offers a better chance of survival (Newsham, 2011). Human Norovirus NoV, commonly labelled as 'gastro', is also a member of the Caliciviridae family. NoV has not been successfully grown in cell culture and this has hindered studies on its environmental persistence (Cannon et al 2006). FCV can be propagated in cell culture and has been significantly studied as a surrogate for NoV (Cannon et al 2006). Due to this research, there is extensive information about FCV studies freely available to the public.
Feline Calicivirus, microscopic

Is there only one strain? FCV has multiple strains that offer a wide variety of clinical signs ranging from asymptomatic cats, to cats that have severe symptoms and death (Newsham, 2011). To complicate it further, two strains can combine that can increase the efficacy of the infectivity of a group of cats (Coyne et al 2006). This is because FCV strain combinations allow faster rates of mutation which allows the virus to avoid host immune responses (Coyne et al 2006). Coynes' study of a colony of FCV infected cats showed:
“At the beginning of the study, the colony was found to be infected with one strain. Later, tests showed that a second FCV strain entered the colony. Further tests showed that a combination strain, some parts of the first strain and some parts of the second strain was circulating within the colony.”

Shelters that have a large population of cats within a confined space, it is suggested that this environment offers optimal conditions for strain evolution (Newsham, 2011).

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What are the signs and symptoms? The Koret Shelter Medicine Program (KSMP) list some symptoms that can be associated with an FCV infection:
Fever Ulceration of the oral cavity (Including tongue & palate) and nasal planum Rhinitis Conjunctivitis Acute & chronic gingivostomatis Acute arthritis or 'limping kitten syndrome' Pneumonia Systemic vasculitis with multi organ involvement

Symptoms can be mild or severe and can include all or a combination of the above. Oral ulceration is a common symptom, but is not present in every case (KSMP, 2010). Also, each symptom of FCV can be a symptom of another pathogen. For example, tongue ulceration can be caused by FCV, incorrectly diluted ammonium or feline herpes virus (KSMP, 2010). The images A, B and C are taken from the KSMP Information sheet on Feline Calicivirus and show the similarity between the same symptoms, but are caused by a different pathogen.

A. tongue ulceration caused by FCV

B. tongue ulceration caused by

ammonium toxicity

C. tongue ulceration caused by

feline herpes virus

It is important to rule out other organisms prior to pursuing the diagnosis for FCV, especially with cats that have a severe illness and have an incomplete vaccination history. Quimby discusses a variety of pathogens that can cause the same or similar clinical symptoms as FCV. (Quimby 2010)
feline herpesvirus bordetella bronchiseptica chlamydophilia felis panleucopaenia chronic rhinosinusitis mycoplasma spp.

Also something to consider it that FCV rarely works alone (KSMP, 2010). It is suggested that it can appear in combination with Bordetella Bronchiseptica and Feline Panleukopenia. So even a mild strain of FCV in combination with these other diseases can cause a severe illness, or even death (KSMP, 2010).
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The good news is high mortality outbreaks caused by a pathogen like Panleukopenia can be controlled within a shelter environment, by using a vaccine and there is no carrier involvement that will effect other cats. How is it spread? FCV is shed predominantly with oral and nasal secretions in the acute phase. FCV shedding is not induced by stress. A source of infection in a shelter can be caused by asymptomatic carrier cats that continuously shed (Little 2011). On recovery, many cats will shed for at least 30 days post infection and some cats will shed even for a few years (ABCD, 2012). It is obviously difficult to identify these cats when they are admitted to the shelter. Cats can be infected with FCV via the nasal, oral or conjunctival route. The oropharynx is the primary site of replication. (ABCD, 2012) There has been much discussion about the four feet rule, keeping cats at least four feet a part to prevent droplet transmission via sneezing. Little states that sneezed macro droplets do not travel more than four feet (Little 2011). KSMP states that true aerosol transmission is unlikely due to cats not having the tidal volume ability to generate an effective aerosol. KSMP discusses a study; “In one study, naïve cats were placed in a small room in an open wire cage at least four feet away from the
sick cats, with strict handling order such that uninfected cats were always handled before sick cats. No transmission of FCV occurred. As soon as this order was reversed, however, the naïve cats quickly became infected.”

This indicates that fomites are the primary means of spread of FCV. This is also supported in Coyne's study which demonstrated that cross infection was common if infection and fomite control were not practised (Coyne, 2006). Fomites are nonliving materials, such as bed linen, pens, benches that are capable of transmitting infectious organisms from one individual to another (Glanze et al, 1990). The transfer of the organism to the fomite occurs when a person fails to wash their hand, or wash their hand effectively and are not practising good standards of infection and fomite control. There has been extensive research done of the survival of FCV on fomites. This has been completed by medical research, using FCV as a surrogate for Norovirus studies. Clay studied FCV survivability of fomites (Clay, 2006). These were some of the results. FCV survived:
up to 3 days on telephone buttons up to 2 days on computer mouse up to 12 hours on a keyboard

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Vaccination ABCD (European Advisory Board on Cat Diseases) recommends that all healthy cats should be vaccinated against FCV and on admission to a shelter if the cat does not have a vaccination record. It provides good protection, but note that is does not prevent cats from becoming infected and from shedding FCV after an illness (Radford et al, 2006). Vaccination will reduce the severity of the clinical symptoms and will shorten the duration of the shedding (Little, 2011). The current vaccines for FCV only offers protection from limited strains and does not not offer broad spectrum cover, also it does not protect the cat from virulent strains of FCV (Little, 2011). Vaccination will therefore decrease treatment, resources, quarantine time and will allow for quicker adoption of cats. The Australian and Pesticides and Veterinary Medicines Authority (APVMA) agrees with the Australian Veterinary Association (AVA) that evidence based research has shown that core vaccinations should be given every three years, not annually as previously administered in Australia. However, the APVMA supports the ABCD in recommendations that cats in high risk of FCV should receive an annual re-vaccination (APVMA, 2010). Disease Control Disease control is essential to prevent FCV from further spread within the shelter. A single case does not mean an outbreak is inevitable (KPMS, 2010). All suspect cats must be isolated from healthy cats. This can be accomplished by using a different room, building or advanced foster carer. KPMS states that shelters that have had an FCV out break and have successfully contained the infection without a separate air supply for isolation rooms. For all strains of FCV, from mild to severe, strict fomite control must be practised. When attending suspect cats: . use disposable gowns, gloves and shoe covers in between attending
sick cats, and sick cats and healthy cats . attend to healthy cats prior to sick cats . effective mechanical removal of FCV with detergent via hand washing in between cats. The use of alcohol based hand gel is not
reliable. But an ethanol concentration of greater than 70 percent appears to be most effective (KPMS, 2012).

It is known that FCV is inactivated by heat at 60 degrees Celsius and by Sodium Hypochlorite (bleach) at 1000 parts per million, 0.1% (CDNA, 2010).

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The chemical agent must be fresh and be diluted just before using (CDNA, 2010). The surface must be free of faecal or organic matter as it will inactivate the chemical agent. The chemical agent needs at least 10 minutes of contact time to kill the virus. Quaternary ammonium, detergent and ethanol does not inactivate FCV (CDNA, 2010). To clean fomites, it is recommended to first clean with a detergent to remove organic matter, dirt and oil which will improve the efficacy of the cleaning agent. Cleaning fomites a few times a day is recommended during a suspect case of FCV, as it can persist in a dried state at room temperature for up to 28 days (KPMS, 2010). Having dedicated items and reducing items in isolated areas will reduce the chances of transmission. Flea treatment is vital in disease control for FCV. A study showed that FCV remained infectious in flea faeces for up to 8 days (Mencke et al, 2009). Since FCV is shed in the oral and nasal secretions, you could expect that due to self grooming, an infected cat would spread the virus over their hair follicles. This is why wearing disposable gloves when handling suspect cats is important. Isolation There is little literature on the length of quarantine time for cats with FCV. KPMS states that the exact length of time is unknown. Even though a cat can shed FCV for weeks to months after its illness, there have been no studies on how long FCV maintains its virulence. KPMS discusses adoption after FCV.
“In a few known cases, cats shedding a formerly virulent systemic strain of FCV have been released to homes or adopted out after 10 weeks or more following resolution of an outbreak and no further transmission of disease was seen. In these cases, it appears that although the cats were still carriers, the virus had lost the mutation conferring increased virulence.”

The Department of Primary Industries in Victoria,states that all shelters must provide an isolation for animals suspected of having an infectious disease (SGOV, 2011). Any quarantine area must be easy to decontaminate, spacious and comfortable. It is inhumane to house a cat in a small space or cage while in quarantine. KPMS states that FCV infected cats leave shelters every single day and there is no possible way to avoid sheltering or adopting out cats with FCV. From the evidence, it appears that each case needs to be treated individually to determine an appropriate risk assessment for quarantine time and specifics of adoption. This will depend on:
if the strain produces mild or severe symptoms if FCV effected healthy cats, not just immunosuppressed cats and kittens if severe symptoms effected well vaccinated cats (KMPS suggests a three month quarantine for a strain of FCV that effected well vaccinated cats) Page 5 Discussion: Feline Calicivirus

Treatment There is no specific treatment for FCV and therefore its focus is on supportive therapy (ABCD, 2012).
Hydration Correcting electrolyte disturbances Correcting acid base disturbances

Supporting appetite with warm high flavoured meals. If
necessary a nasogastric tube for enteral feeding may be required. Non-steroidal anti inflammatory medications to reduce fever and decrease pain Antibiotics for a secondary bacterial infection

Antiviral medications used in Veterinary medicine only inhibits the DNA virus, not an RNA virus like FCV (ABCD, 2012) However, a recent study using an antiviral medication called Phosphorodiamidate Morpholine Oligomer (PMO) has shown promising results. Not only did 47 out of 59 cats that received PMO survive, but PMO also reduced viral shedding and hastened clinical recovery (Smith et al 2008). Diagnosis FCV cannot be diagnosed by clinical signs alone (KPMS, 2010). As discussed previously, FCV can produce a variety and combination of clinical symptoms and every symptom can possibly be a result of another pathogen. Diagnosis should be formulated around the cats history, clinical symptoms and tests.
A cats history includes vaccination, recent exposures to sick cats or multi cat environments or even a recent trip to the vet. A cats clinical symptoms have been discussed. Samples of bodily fluids of effected areas and oropharyngeal swabs.

FCV can be detected by a viral culture or RT-PCR (reverse transcription polymerase chain reaction, see image below) and both methods are equally sensitive (KPMS, 2010). Samples from the oropharnyx are most common because it is the primary site of FCV replication (ABCD, 2012). Other sites or bodily fluids that appear to be effected during the acute phase should also be tested to provide a definitive diagnosis.

Image: RT-PCR, swabbing the back of the cats throat Page 6 Discussion: Feline Calicivirus

Interpreting Results Caution should be taken in interpreting tests due to false positives. This can occur due to:
virus in live vaccines may be shed post vaccination (Ruch-Gallie et al, 2011) samples can be contaminated during collection or during analysis (Little, 2011) up to 25% of clinically well cats will test positive for FCV from an oropharyngeal swab (KPMS). This is why testing multiple sites and/or tissues and/or serum would determine a definitive result. Recovering or chronically infected cats that constantly or intermittently shed will test positive for FCV

KMPS discussed a case of false negatives. KMPS collected oropharyngeal swabs during an outbreak. During the acute phase of the illness, 90% of cats tested positive and a week after the onset of clinical symptoms, only 30% of cats tested positive. This suggests that a false negative can occur if a cat is infected with FCV but is in the recovery stage. RT-PCR tests have the ability to identify the FCV strain (ABCD, 2012). This would be useful in outbreak situations to differentiate between cats infected with different strains causing different symptoms, but both positive for FCV.

Conclusion The Feline Calicivirus has a high mutation rate, has many strains and is common amongst cats, especially cats from multi cat environments. It is even suggested that shelters can never eradicate FCV. Evidence based research and shelters that have had a successful experience in containing FCV outbreaks prove that the common practise of killing suspect or infected cats or groups of cats with FCV, is not necessary. It appears that humans are the primary reason FCV is spread in a shelter environment. This alone raises ethical questions about shelters who kill a group of cats that are suspect of being infected with FCV when it was the staff who transmitted the disease through lack of infection and fomite control. Adoption of cats that have recovered from FCV has been accomplished using risk assessment and appropriate placements.

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Discussion Killing shelter cats that are suspect or infected with FCV for infection control purposes can be deemed useless. It will only solve the shelters immediate issues of an infected cat in the shelter. But most importantly, it will not prevent the next cat, and the next cat after that from entering the shelter from being a carrier or being infected with FCV. The evidence based research discredits the common practise of killing suspect or infected FCV shelter cats, and it appears that the kill method is most likely due to a combination of laziness and lack of knowledge about FCV. Nathan Winograd discusses effective medical management in the no kill equation (Winograd, 2009). A shelter medical program that keeps animals healthy within the shelter but fails to meet the goals and the mission of the organisation like reduced killing, high quality animal services and increased adoptions cannot be considered a successful shelter medical program. Considering that the first book solely dedicated to the care of animals in shelters was published in 2004, effective and humane shelter medicine is relatively new (Miller, Hurley, 2009) With the introduction of the no kill equation, the humane, intelligent and effective shelter management has been brought to light. There is a great amount of evidence based research on FCV due to its surrogate research for NoV. Shelter medicine should take advantage of this already funded and resourced literature and use it to help guide best practises for shelter animal care, rehabilitation and rehoming. There is no reason why the same principles of evidence based medicine that is applied in other settings, like hospitals, cannot be applied in shelter medicine and management. In keeping with increasing community expectations about how our displaced pets are managed, it is obvious that implementing evidence based research into shelter management is a must for preventing the suffering and the mass killing of shelter cats with suspect or infections of Feline Calicivirus.

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References
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ABCD, European Advisory Board on Cat Diseases (2012) http://abcd-vets.org/guidelines/guidelines_pdf/1201-FCV_Guideline.pdf . AVPMA (2010) Australian Pesticides and Veterinary Medicines Authority, Australian Government. http://www.apvma.gov.au/use_safely/vaccination.php . Cannon J et al (2006) Surrogates for the study of norovirus stability and inactivation in the environment: A comparison of murine norovirus and feline calicivirus. Journal of Food Protection 2006;69:2761-2765. . CDNA, Communicable Diseases Network Australia (2010) Australian Government, Department of health and Ageing, Barton, ACT http://www.health.gov.au/internet/main/publishing.nsf/content/F2A4C351C705B6C6CA 257783000C24CA/$File/norovirus-guidelines.pdf . State Government of Victoria SGOV (2011) Code of Practice for the Management of Dogs and Cats in Shelters and Pounds (Revision1). Department of Primary Industres, Victoria, Australia. http://www.dpi.vic.gov.au/pets/about-pets/legislation-and-regulation/management-of-dogs-and-cats-inshelters-and-pounds/code-of-practice-for-the-management-of-dogs-and-cats-in-shelters-and-pounds . Clay S et al (2006) Survival on uncommon fomites of feline calicivirus, a surrogate of noroviruses. Am J Infection Control 2006;34:41-43. . Coyne, K.P. et al (2006) Recombination of feline calicivirus within an endemically infected cat colony. The Journal of General Virology 87:921-926. . Glanze et al (1990) Mosby's Dictionary: Medical, Nursing, & Allied Health. The C.V. Mosby Company, Missouri. Printed in the United States of America. . Little, S (2011) Feline herpesvirus and calicivirus infections: What's new? Presented at 63rd CVMA Convention, July 6-9 2011, World Trade & Convention Centre, Canada. . Mencke, N et al (2009) Tranmission of feline calicivirus via the cat flea (Ctenocephalides felis). Parasitol Res 105(1):185-189. . Miller L, Hurley, K (2009) Infectious disease management in animal shelters. WileyBlackwell, Iowa. Printed in Singapore. Page xi. . Newsham E (2011) The molecular pathogenesis of feline calicivirus infection. Infection Biology, School of Veterinary Science, University of Liverpool. . Radford, A.D. (2006) The challenge for the next generation of feline calicivirus vaccines. Vet Microbiology 2006;117(1):14-18. . Ruch-Gallie R.A. et al (2011) Results of molecular diagnostic assays targeting feline herpesvirus-1 and feline calicivirus in adult cats administered modified live vaccines. J Feline Med Surg 13(8):541-545. . Smith AW, Iverson PL, O'Hanley PD, et al. Virus-specific antiviral treatment for controlling severe and fatal outbreaks of feline calicivirus infection. Am J Vet Res 2008;69:23-32. . UC-Davis Koret Shelter Medicine Program (2010) Shelter health Portal, Information Sheets http://sheltermedicine.com/node/5 . Winograd, N. (2009) Redemption: the myth of pet overpopulation and the no kill revolution in America. Second edition. Almaden Books. Printed in the United States of America.