• Introduction
• Overview
• Session 1: Background to FCoV/FIP
• Session 2: Diagnosis & Treatment of FIP
• Session 3: Epidemiology of FCoV Infection
• Session 4: Pathogenesis and Immunopathogenesis of FIP
• Session 5: Prevention of FCoV Infection/FIP
• Workshop Results
  • Workshop 1: Recommendations for Diagnosing FIP (especially with regard to RT-PCR Tests) and Treatment.
  • Workshop 2: Recommendations for Minimizing Disease Spread in Breeding, Rescue, and Boarding Catteries, in Veterinary Practices, and at Cat Shows.
  • Workshop 3: Recommendations for Priority Areas of Future FCoV Research.
• Glossary

WORKSHOP RESULTS

Workshop 1:
Recommendations for Diagnosing FIP (especially with regard to RT-PCR Tests) and Treatment.
Chair: S. Paltrinieri

DIAGNOSIS:

Serology and Fecal Analysis

• Evaluate clinical signs carefully; some signs are classically associated with FIP (i.e., effusions) and some signs are atypical (i.e., orchitis, enteritis, pericarditis).
• When FIP is part of a differential diagnosis, testing should be targeted to rule in or rule out other diseases, for there is no specific test for FIP.
• Although not specific, AGP (alpha 1-acid glycoprotein) is a good new supportive test for a diagnosis of FIP; however, it may not be widely available and is a non-specific test that identifies an inflammatory response.
• Do not diagnose FIP on the basis of a high coronavirus antibody titer. It is only suggestive of FIP when considered together with the cat's history and clinical signs. For example, a high antibody titer in a cattery cat has less significance than a high antibody titer in a cat from a single-cat household.
• Currently, there is no commercially available test that differentiates between the mutated (i.e., FIPV) and non-mutated forms of FCoV.
• A positive PCR test on blood or effusions is poorly specific for FIP. Coronavirus can be found in the blood of healthy cats as well as cats with FIP. Coronavirus can be present in effusions in cats with diseases other than FIP.
• Choice of the laboratory that is used for testing can be critical as there are currently no standards for either coronavirus PCR testing or immunofluorescent antibody titers (IFA).

Pathology

• Effusions are generally fibrinous exudates.
• Lesions in organs are generally pyogranulomatous foci and are often perivascular.
• Cytological evaluation of effusions can often support a diagnosis of FIP.
• Histology may be more accurate earlier in the disease.
• A large sample size may be required to detect coronavirus in tissues by immunohistochemistry because there may be few cells that are positive for virus by immunofluorescence.

TREATMENT

• Once diagnosis is confirmed, no treatment has been proved effective.
• Severely affected animals (i.e., an animal whose survival is estimated to be less than one month) should be considered for euthanasia.
• Less severely affected animals may be treated with non-specific supportive therapy including interferon or other immunomodulating drugs. It is unknown how effective these drugs are and more research into potential treatment is needed.

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Workshop 2:
Recommendations for Minimizing Disease Spread in Breeding, Rescue, and Boarding Catteries, in Veterinary Practices, and at Cat Shows.
Chair, Dr. Niels Pedersen

Dr. Niels Pedersen, University of California at Davis chairing Workshop 2

Given the time constraints, the group in this session decided to eliminate the discussion of disease spread at veterinary practices and cat shows, as they believed these areas were the least likely sources of infection.

Recommendations include:

• Keep the overall numbers in a cattery or multi-cat environment low; it is recommended that "living" groups stay small (i.e., four to six cats per group).
• The cleanliness of litter boxes and how they are cleaned can be a key to minimizing the spread of the virus in either a cattery or shelter. Dry dirty litter can be a source of aerosolized virus from fecal matter.
• Isolate queens two weeks prior to birthing in catteries or other multi-cat environments. This gives the queen time to get over any stress-induced coronavirus shedding.
• Isolation of queens and early weaning:
  • If you have had no cases of FIP, you probably can continue to raise your kittens as you always have.
  • If you are experiencing losses to FIP, isolation and early weaning may be an option. Its effectiveness depends on the caretaker's ability to control the spread f the virus. In home-based situations, this can be difficult, for it involves strict barrier nursing techniques.
  • The isolation of the queen and her kittens is a good idea. It minimizes the spread of FIP and other diseases by decreasing the exposure of the kittens to a variety of viruses.
• Concerns were recognized with early weaning including eating, socialization, and related behavioral issues. If the kittens are already shedding coronavirus by six to eight weeks, there is no point in early weaning. A question was raised that can only be answered by further research: "If you early wean kittens and thus there is no exposure to FCoV, do you then create a susceptible population.(i.e., are naïve kittens more at risk)?" Studies have shown that this happens with feline calicivirus.
• The younger the kittens are exposed to FCoV, the higher the lever of viral replication and shedding. Therefore, the older they are before they are exposed, the less they will shed and replicate and the lower the risk of a successful mutant virus (FIPV) developing. Resistance to FIPV/FCoV increases with the animal's age. Kittens between six and 16 weeks of age are highly susceptible. A key to managing the disease is the development of a standardized, fast, reliable, and inexpensive test to determine viral shedding.
• In shelters, improve husbandry to decrease virus spread and to lower stress levels. Control efforts should target the younger cats (i.e., kittens). The stress of entering a shelter can lead to a major increase in viral shedding. Therefore, the younger kittens should be isolated or placed in foster care to minimize exposure.
• Existing studies indicate that high antibody titers (> 1:400) are probably indicative of high rates of shedding.
• There is a need to develop better tests to aid in FCoV control:
  • Cheap and accurate serology.
  • Cheap and accurate tests for viral shedding in feces.

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Workshop 3:
Recommendations for Priority Areas of Future FCoV Research.
Chair, Dr. Diane Addie

1. In the absence of an effective vaccine, it was considered a priority to prevent cats becoming infected with FCoV at all. It was considered important to look at ways of minimizing virus dose. Existing cat litters need to be checked for their ability to limit FCoV transmission by biocidal action and/or good clumping. The effect of flushing litter trays on FCoV spread needs to be investigated.

2. The ideal vaccine should protect against FIP, give good mucosal immunity to prevent infection, and reduce virus shedding. Development of a therapeutic vaccine should also be considered, both to treat cats with FIP and to attempt to stop carrier cats from shedding. For the latter, it is essential to establish where the virus is in carrier cats (the ileum and colon are the most likely areas) so that immune clearance of virus from this area is taken into consideration in vaccine development.

3. The group was concerned about antibody-dependent enhancement (ADE) being a laboratory artifact and that experimental vaccines that might have worked perfectly well in the field had been rejected because in experimental infections they caused ADE. A reasonable challenge virus needs to be defined. The 79-1146 strain is probably not a good choice, since it is extremely virulent and also is a Type II FCoV. The working group called for standardization of vaccine challenge protocols worldwide, using a constant virus dose, strains more representative of natural infection (including Types I and II), and natural exposure challenge (i.e., challenge not given parenterally). The virus dose threshold over which FIP develops would need to be established. A challenge virus stock should be made and stored in two or three locations worldwide and supplied from there to those working on novel vaccines.

4. It is claimed that mutated FCoVs that cause FIP (i.e., FIPVs) do not transmit to other cats. However, many investigators had seen "outbreaks" of FIP. The group considered it important to establish whether FIPVs are transmissible.

5. More molecular work needs to be undertaken in the following areas:

   • To establish whether all FIPVs have 3c deletions.
   • To define the functions of non-structural proteins 3a, b, c, and 7a and b.
   • To do a worldwide phylogenetic study so that future vaccines will cover as many natural FCoV strains as possible.

6. More work needs to be undertaken to grow the Type I FCoV in cell culture. Different cell lines should be tried, and if that fails, the Type I receptor needs to be found and cloned into a cell line.

7. More work is required to understand exactly what FIPV does in the infected macrophage. In addition, the cytokine profiles of naturally infected cats need to be determined.

8. The phenomenon of resistant cats requires further investigation. Might it be possible to breed cats resistant to FCoV infection? Could resistant cats simply have been exposed very early in life (in the first week) and therefore become immune-tolerant?

9. Since the research community in FCoV is small, it is important that we exchange ideas more often and work together. An email newslist will be established and the www.felinecoronavirus.com website will continue as a place where researchers can list available reagents.

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