Medizinische Kleintierklinik
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Pathogenesis, diagnosis, and treatment of feline infectious peritonitis

Michele Bergmann1, Kirsten Kuehner1, Sandra Felten1, Laura Sangl1, Sonja Brodmann1, Stephanie Gründl1, Stephanie Doenges1, Friederike Riemer1, Yvonne Fischer1, Susanne Ritz1, Lara Matiasek1, Andrea Fischer1, Karin Weber1, Carola Sauter-Louis2, Kaspar Matiasek3, Monir Majzoub3, Walter Hermanns3, Robert Fux4, Gerd Sutter4, Katrin Hartmann1

1Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Faculty of Veterinary Medicine, LMU, Munich
2Clinic for Ruminants, Centre for Clinical Veterinary Medicine, Faculty of Veterinary Medicine, LMU, Munich
3Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, Faculty of Veterinary Medicine, LMU, Munich
4Institute for Infectious Diseases and Zoonoses, Centre for Clinical Veterinary Medicine, Faculty of Veterinary Medicine, LMU, Munich

Background

Feline infectious peritonitis (FIP) is one of the leading infectious causes of death in cats. Diagnosing FIP ante mortem can be extremely challenging, and the pathogenesis of FIP is still not fully understood. The current hypothesis states that FIP is caused by feline coronavirus (FCoV) which, in affected cats, spontaneously mutates from a minimally pathogenic virus to an aggressive, lethal virus. To date the most reliable diagnostic test is the detection of FCoV antigen in macrophages by immunostaining. However, in cats with certain forms of disease, all noninvasive clinical tests have limitations. In addition, treatment of cats with FIP remains frustrating, and all cats that have developed FIP eventually die with a median survival time of nine days after diagnosis. Currently, no drug has proven efficacious in curing FIP, and there is urgent need for the detection of effective drugs.

Research highlights

Diagnosis of feline infectious peritonitis
A specific diagnostic tool to definitively diagnose the disease would be extremely important as the diagnosis of FIP commonly leads to euthanasia. However, few reliable non-invasive tools exist to definitively diagnose FIP intra vitam. A recent study from our group focused on the diagnostic accuracy of the Rivalta test, which has been used routinely in Europe to diagnose FIP in cats with effusions. Sensitivity and specificity of the Rivalta test, however, were lower than previously reported, except when used in young cats. The components in effusions that lead to a positive Rivalta test remain unknown, but it has been shown that the positivity is not simply related to high total protein concentrations.

Another study evaluated the sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of FCoV in different body fluids. In addition, the diagnostic value of the RT-PCR in a macrophage-enriched peripheral blood mononuclear cell fraction was investigated. Although this RT-PCR did not specifically detect the mutated virus, it had a high specificity for the detection of FIP in this study, but lacked sensitivity.

A current study now focusses on testing for the presence of FCoV antigen in macrophages in various body fluids, including effusion, cerebrospinal fluid, and aqueous humor, using different immunohistochemisty staining techniques.

Treatment of feline infectious peritonitis
As FIP is a very common disease and the prognosis is very poor, there is an urgent need for new treatment options that lead to a prolonged survival time. Our reaserch group performed several placebo-controlled double-blind studies in the last years treating cats with FIP with specific compounds and comparing their survival times, as well as other variables, to those of untreated cats. In a recently performed randomized placebo-controlled double-blind treatment trial, the effect of feline interferon-omega was investigated, but there was no significant difference in the survival time of cats treated with FeIFN-omega versus placebo or in any other variable evaluated. The cats survived between three and 200 days (median, nine days).

Another randomized, placebo-controlled double-blind study evaluated the effect of propentofylline on survival time and quality of life of cats with FIP, but this drug was not found to be efficacious either. Other treatment approaches are currently under investigation.

Future perspectives

The pathogenesis of FIP is still not fully understood. The current hypothesis states that FIP is caused by a mutation in the spike protein of FCoV leading to inability of the virus to replicate in enterocytes. We are currently evaluating a novel PCR that has been designed to detecte the crucial mutation in the spike protein, which confers the inability to replicate in enterocytes. If this PCR proves to be specific, it will be modified into a bed-side diagnostic tool that can be used in practice. Another focus of interest is the epidemiology and the concern of excretion of the mutated virus. The risk of the mutated virus to be excreted and potentially infect other cats is still debated. Since FIP is most common in multi-cat environments, ability to specific detect the mutated virus significantly contributes to an improvement of FIP prevention in multi-cat institutions. In addition, new therapeutic approaches, such as treatment with human gammaglobulins in cats with FIP, are under investigation.

Selected references

  • Fischer Y, Sauter-Louis C, Hartmann K: Diagnstic accuracy of the Rivalta test for feline infectious peritonitis. Vet Clin Pathol 2012;41:558-567
  • Hartmann K, Ritz S: Treatment of cats with feline infectious peritonitis. Vet Immunol Immunopathol 2008;123:172-175
  • Fischer Y, Ritz S, Weber K, Sauter-Louis C, Hartmann K: Randomized, placebo controlled study of the effect of propentofylline on survival time and quality of life of cats with feline infectious peritonitis. J Vet Intern Med 2011;25:1270-1276

Funding

  • MSD, Haar, Deutschland

External collaborations

Herman Egberink, Institute of Virology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands
Karin Möstl, Institut für Virologie, Veterinärmedizinische Universität Wien, Österreich
Annette Lister, Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, Indiana, USA