Feline infectious peritonitis

An infectious disease caused by a coronavirus that causes disseminated immune-mediated pyogranulomatous vasculitis. Infection can take one of two forms: wet or dry. Following oronasal infection, the virus can begin to replicate in the monocyte/macrophage system. This triggers an immune-mediated pathogenesis in which the humoral response (antibodies) leads to the formation of immune complexes that are deposited on the vascular walls. These deposits trigger a type III hypersensitivity reaction that causes disseminated vasculitis and pyogranulomas.

• Wet form. Vasculitis increases permeability of the vascular serosa of the body cavities. Levels of fibrin-rich exudate increase and accumulate in these cavities. This form is considered 2-3 times more frequent than the dry form.
• Dry form. Characterized by the presence of pyogranulomas in different organs.

FIP is generally associated with low morbidity (<1% annually) and high mortality. In large cat communities, the prevalence of some type of feline coronavirus is estimated to be 80%-90% and in cats living alone, between 10% and 40%. Around 20% of infected cats develop the disease (mainly those under 3 and over 11 years of age). Once developed, it has a high mortality rate, depending on the virulence and tissue tropism of the strain, the magnitude of the infection, the age of the animal, the quality of its immune response, and the route of viral entry. If cellular immunity is high, the disease may not develop; if it is low, the wet form will develop, and if it is intermediate, the dry form. Spontaneous remission has been described and confirmed in autopsy findings, and in some cases the infection has been cured. It is now believed that feline enteric coronavirus, which multiplies in mature columnar cells of the intestinal epithelium, can mutate or recombine, acquiring the ability to enter the body. If this mutant virus begins to replicate in the monocyte/macrophage system, it could become the virus that causes FIP. The non-mutated intestinal virus remains, and is shed in the faeces to become a source of new infections. However, it is known that 95% of cats with FeCoV also have the virus in their blood. The source of infection is thought to be symptomatic cats that shed the virus for a short period of time and FeCoV carriers that shed it intermittently for long periods of time. Feline coronaviruses are currently considered a group of viruses. There are different strains of FIPV and FeCoV. All have a similar antigenic composition in the same geographical area, but very different pathogenicity.

Symptoms

Usually nonspecific, presenting with anorexia, weight loss, lethargy, vomiting, diarrhoea and fluctuating fever of unknown origin that does not respond to treatment. FeCoV can sometimes cause severe gastroenteritis. The wet form is characterized by painless abdominal distension that may be accompanied by pleural effusion (fibrinous pleuritis) and dyspnoea. Pericardial effusions may also occur. Vomiting, jaundice secondary to liver and pancreatic inflammation, and a tendency to bleed may also occur if DIC sets in (FIP is a feline pathology that is often associated with DIC). The dry form usually has an insidious onset and nonspecific symptoms that are later complicated by the symptoms of the organs affected by pyogranulomatous inflammation. The virus has a predilection for the liver, spleen and lymph nodes, due to their high macrophage content. Ocular symptoms, if present, develop earlier than any other systemic symptoms, and can take the form of unilateral or bilateral uveitis, chorioretinitis, hyphaemia, miosis, corneal oedema, etc.. In 50% of cases of FIP, progressive nervous symptoms develop such as ataxia, seizures, vestibular signs, posterior third paralysis, tetraparesis, etc., as a result of pyogranulomatous multifocal meningoencephalitis. These symptoms are more frequent in animals under 2 years of age. The kidneys may appear large and irregular on palpation, similar to a renal lymphoma. The lungs can also be affected. FeLV and FIV coinfection is common, and this phenomenon can promote the development of FIP and complicate the symptoms. Cases of FIP associated with Hemobartonella felis have also been observed. Sometimes, the only symptom may be the enlargement of a single lymph node, similar to a tumour.

Interpretation of laboratory tests

General Tests

• Complete blood count: Non-regenerative, normocytic, normochromic anaemia (50%). Neutrophil-induced leucocytosis (some leukocytes may present inclusion bodies), with a shift to the left, lymphopaenia and monocytosis. In cases of fulminant FIP, panleukopaenia may occur.
• Serum protein: In more than 40% of affected cats, total protein is high and an electrophoretic pattern of polyclonal hyperglobulinaemia (increased α2, β, and γ) with hypoalbuminaemia is observed, indicating chronic inflammation and antibody production.

• Blood biochemistry: Changes will depend on the organs affected. TBIL is increased in 25% of cases and in 17% of cases ALP, CRE and GPT may also be increased.
• Serology: Coronavirus antibodies are detected. Positive titres should be interpreted with caution, as they may be due to FeCoV or FIPV, whereas negative titres generally rule out the possibility of FIPV infection. A positive titre in a symptomatic adult cat that does not have contact with other cats is more indicative of disease than a positive tire in a group of animals. Very high titres usually indicate dry FIP and lower titres indicate wet FIP. Both FeCoV and PIFV can give high or low titres.
  Positive titres without symptoms should be re-titred after two months to check progress.
  A significant decrease is a value ≥ 4 times lower than the initial titre (e.g., a decrease from 1/640 to 1/80). If the titre is unchanged, it means that contact with the virus continues or the disease is developing. In the final stages of the disease, the titre may be negative, particularly if drainage has been performed. This negativisation is possibly due to the formation of immune complexes that reduce the number of circulating antibodies. Titres may also be negative in cats with symptomatic FIP that are also highly immunoexpressed (due to other pathologies such as FIV).

Specific tests

• CSF analysis, Aseptic inflammation with numerous neutrophils, macrophages and lymphocytes (leukocytes >100 cells/μL, with >70% neutrophils) and a very high protein concentration >200 mg/dL. CSF serology. IgG positive.
• Abdominal fluid examination: Transparent to cloudy, yellowish, viscous exudate with flocculent material that usually coagulates (or forms fibrin chains) on contact with air. Specific gravity > 1018, protein > 4 g/dL (if globulins ≥ 50% and γ ≥ 32%, highly suspicious for FIP; if albumin > 48% or A/G stone > 0.81, highly NOT suspicious for FIP), low WBC count (1000-2000 cells/mL), with nondegenerated lymphocytes, macrophages, and neutrophils (differential diagnosis with septic peritonitis and pyothorax). These results are common to lymphocytic cholangitis.
• Biopsy: Make sure the animal has not developed DIC before performing a biopsy. Post-mortem detection of virus outside the gastrointestinal tract, such as in a lymph node, abdominal mass, or affected organ, is useful for diagnosing FIP.
• Clotting: In some cases (fulminant FIP) an increase in fibrinogen (> 400 mg/dl) may be found, and if the animal has developed DIC, thrombocytopaenia and increased prothrombin and activated thromboplastin times may be observed.

Prophylaxis

Intranasal vaccination stimulates cellular immunity. Vaccinating kittens between 6 and 16 weeks old may decrease the incidence of symptomatic FIP. However, there is no cross-protection between different virus strains.

Efforts should be made to reduce the prevalence of feline enteric coronavirus, since it is the source of the virus that causes FIP. It is estimated that 33% of seropositive animals shed viruses; therefore, it is advisable to remove them from the cat community, and to remove seropositive mothers from their kittens. The virus is highly labile in the environment and very sensitive to disinfectants.

It is easily inactivated with a 0.5 g/L chlorhexidine solution or 0.2% formol.

Bibliography

• ADDIE, D.D. (2000) The Veterinary Journal, Vol. 159, nº1, pg. 8-9.
• ADDIE, D.D. (1995) American Journal of Veterinary Research, Vol 56, nº 4, pg. 429-434.
• ADDIE, D.D. (1990) The Veterinary Record, Enero 1990. pg. 14-18.
• APPEL, M.J. (1987) Virus Infections of Vertebrates. Elsevier. pg. 267-285.
• BONAGURA, J.D. (1995) Kirk Current Veterinary Therapy XII. (W.B. Saunders) pg.1125.
• EVERMANN, J.F. (1995) Journal of Veterinary Medical Association, Vol. 206, nº 8, pg. 1130-1134.
• FRADIN-FERME, M. (1999) Pratique Médicale et Chirurgicale de l’Animal de Compagnie, T. 34, S3, pg. 309-318.
• FOLEY, J.E. (1998) Journal of Veterinary Internal Medicine, Vol. 12, pg. 415-423.
• GONON, V. (1995) Recueil de Médicine Vétérinaire, Vol. 171 (01), pg. 33-38.
• GREEN, C.E. (1999) A.V.E.P.A. XXXIV Congreso Nacional, pg. 149.
• GREEN, C.E. (1990) Infectious diseases of the dog and cat ,W.B. Saunders, pg. 42, 207-208, 300-307.
• GUNN-MOORE, D.A. (1999) Veterinary Microbiology, Vol. 69, pg. 127-130.
• GUNN-MOORE, D.A. (1998) Veterinary Microbiology, Vol. 62, pg. 193-205.
• HARPOLD, L.M. (1999) Journal of American Veterinary Medical Association, Vol 215, nº 7, pg. 948-951.
• HERREWEGH, A.A.P.M. (1995) Journal of Clinical Microbiology, Vol 33,nº 3 pg. 684-689.
• HOHDATSU, T.(1994). Archives of Virology, 139: 237-285.
• KENNEDY, M.A. (1998) Journal of Veterinary Diagnostic Investigation, nº 10, pg.93-97.
• KIPAR, A. (1999) Veterinary Microbiology, Vol. 69, pg. 131-137.
• KIPAR, A. (1999) Veterinary Record, Vol 144, pg. 118-122.
• KIPAR, A. (1998) Journal of Comparative Pathology, Vol 119, pg. 1-14.
• KISS, I. (2000) The Veterinary Journal, Vol. 159, nº1, pg. 64-70.
• LI, X. (1994) Veterinary Microbiology, Vol. 42, pg. 65-67.
• NELSON, R.W. (1995) Pilares de Medicina Interna en Animales Pequeños (Mosby Year Book) pg 725-726, 892,913,919-921.
• PEDERSEN, N.C. (1987) Virus infections of carnivores. Max J.Appel (Elsevier) pg. 267-285.
• PRÉLAUD, M. (1999) Pratique Médicale et Chirurgicale de l’Animal de Compagnie, T. 34,nº 5, pg. 609-610.
• RICHARDS, J.R. (1995) Feline Practice, Vol 23 nº 3, pg. 52-55.
• ROTTIER, P.J.M. (1999) Veterinary Microbiology, Vol. 69, pg. 117-125.
• VENNEMA, H. (1999) Veterinary Microbiology, Vol. 69, pg. 139-141.
• WILLS, J. (1993) Manual de medicina felina. (Acribia) pg 416-420.
• ZENGER, E. (2000) Feline Practice Vol.28, nº 1, pg. 16-18.