Feline infectious peritonitis
The Feline Infectious Peritonitis (FIP ) is triggered by the feline coronavirus infectious disease that infects only cats ( Felidae ). The name is derived from the most common clinical manifestation of peritonitis ( peritonitis). However, even only be affected the pleura, which is why often the name Feline Infectious polyserositis used. In addition, a disease without any involvement of the serosa may ( lining of the body cavities ) may occur. If there is even a clinical manifestation of the disease, this is fatal in most cases. The disease occurs worldwide.
- 3.1 "Wet Form"
- 3.2 "dry form "
Cause and Epidemiology
The cause for FIP is a highly virulent coronavirus. The today as feline coronavirus (FCoV ) designated virus was until the late 1990s, divided into two different viruses: the little pathogenic, so-called " Feline Enteric Coronavirus " ( FECV ) and the highly pathogenic " Feline infectious peritonitis virus " ( FIPV ). The latter is merely a mutation of the " FECV " within the carrier animal. Both are currently classified as a subtype or isolate of the virus species Alpha coronavirus 1.
The mutation consisting of a deletion in the viral gene 3C, which does not always takes place at the same location. Is favored the change from inaccurate work of the viral RNA polymerase, through which it comes to an improperly installed nucleotide per 1,000 to 10,000 nucleotides during replication. With a total length of viral RNA of about 30,000 nucleotides that is already three mutations in the genetic material of the virus replication per "normal".
The FCoV occurs worldwide, but only about five to ten percent of seropositive ( infected ) cats breaks the FIP disease from. Based on the total cat population has the FIP, a frequency of occurrence ( prevalence) of one to two percent. There are serologically two virus types, which occurs mainly in Europe and the U.S. Type 1 is propagatable in cell cultures, which is not possible with the occurring mainly in Japan Type 2.
The incubation period is probably up to four months. Already on the second day after infection, the animals excrete the virus via feces, nasal secretions and saliva. The first of the harmless virus is transmitted primarily through contact with infected feces or through contaminated objects. Also a mouth -to- mouth or mouth - to-nose transfer is possible. Moreover, people may carry the virus, and transferred to the cat. Often infect virus -bearing mother cats their fetuses already during pregnancy. The transfer of the already mutated form probably plays no role in the spread of the disease.
In principle, all kinds of cats and for FIP ages are susceptible. Most commonly, the disease attacks animals aged six months to five years and older animals aged 14 and over. Since wild cats are usually loners without solid excrement-places, wild animals are much less likely to become infected. Captured feral cats are seropositive to about 10%, after a few weeks in a shelter, however, almost 90 % of the animals. For large cats particularly sizeable populations in zoos are also at risk, leopards are considered to be particularly susceptible.
Pathogenesis and forms
The pathogenesis of the disease is not yet completely understood. The mutation of the first harmless FcoV variant the so-called " FIP virus " is made in the gut and can be years after infection. With the mutation, the virus acquires the ability to bind to ribosomes in phagocytes of the immune system (monocytes and macrophages) and to proliferate in these ( replication). By multiplication of the virus it comes to the disintegration of phagocytes and the released virus particles are taken up by other macrophages, which the virus spreads in the body. With the release of cell mediators in activation of the cells lining the blood vessels ( endothelial cells) and thus to an inflammation. Certain cell messengers also lead to cell death of other immune cells such as lymphocytes. The non-mutated variant multiplies is mainly expressed in the epithelial cells of the jejunum.
It is believed today that whether and in what form the disease is ultimately, is the immune status of the individual animal dependent.
In some of the animals, the disease breaks in spite of a virus mutation not due to a strong cell-mediated immune response. The immune system is thus able to keep the infected blood cells under control. These animals remain without clinical symptoms, but differ as latent carriers of the virus from this further. In some of the animals a complete elimination of the virus is suspected, making them susceptible for infections had declined again.
Clinically manifest is a FIP probably only in immune dysfunction, such as stress or other conditions that lead to an increased virus replication in the gut. A bearing on the pathogenesis of the formation of antibodies, as they may not neutralize the virus. With increased formation of antibodies also increases macrophages are activated, in which there is thus a further virus propagation. The paradox that the antibodies actually formed to combat pathogens lead to an exacerbation of the disease ( " antibody-dependent enhancement of virus infection," engl. Antibody -dependent enhancement ) is, ( eg AIDS, dengue fever) also observed in viral diseases of man. However, this antibody -dependent enhancement is believed to play a role only in experimental infections.
In the past, the disease ( "wet" and " dry form ") was divided into two main types. However, the boundaries between the two main forms are fluid, almost every infected animal shows components of both forms, one of which temporarily can dominate. Therefore, this classification is considered in the recent literature increasingly obsolete.
"Humidity form "
In a weak cell-mediated immune response, there is a persistent virus replication in the blood ( viremia ) and massive formation of immune complexes, complement activation and phagocytic cells ( macrophages). This leads to blood vessel inflammation ( vasculitis) and a lymphoplasmacellular perivasculitis ( marked by lymphocytes and plasma cells inflammation around the blood vessels) of the serous membranes, leading to a tissue death (necrosis ) results. However, some authors are of the opinion that it is in the changes to a true granulomatous vasculitis and perivasculitis, so one dominated by phagocytes inflammation of the vessels and their surroundings. The lymphoplasmacytic perivasculitis then provides a late stage dar. Macroscopically, these inflammatory foci as whitish nodules dar. Due to the inflammation it also comes at a discharge of serum and proteins in the body cavities and fibrin deposits on internal organs.
"Dry form "
In the " dry form " dominate larger nodes that occur predominantly within the institutions. It is fused to inflammation arising as the wet form of vasculitis / perivasculitis. They are sometimes referred to changes as " granulomatous ", but it is not is a true granulomatous inflammation. The liquid outlets are not reproduced in this form. It is believed that this form developed in a less severely weakened cell-mediated immune response and it is a milder, protracted course form. It accounts for about 17 percent of FIP cases, but here is due to the heavy diagnosability (see below) to expect a substantial underreporting.
Symptoms
A clinically manifest FIP begins with reduced feed intake (anorexia), emaciation, and for relapsed, refractory fever. The other symptoms are dependent on the form of the expression, which can smooth transitions between the two forms occur. The division into wet and dry form is strictly speaking a description of the macroscopic findings. Microscopically both forms usually form from an identical image.
"Humidity form "
The classic " wet form " manifests itself in fluid accumulation in the abdominal cavity ( ascites, ascites ) and / or chest cavity ( pleural effusion). The accumulation of fluid in the abdominal cavity can be diagnosed as increase in size with fluctuation usually clinically. Accumulation of fluid in the chest cavity can cause severe shortness of breath. A puncture provides a yellowish, stringy, viscous liquid. The fact that this is a protein-rich exudate, which is quite typical in its appearance, is a major diagnostic criterion.
"Dry form "
The " dry form " is expressed in nodular changes, especially in the abdomen. The brain, the eyes, the organs of the thoracic cavity or only the skin may be affected. Depending on the organ localization can occur jaundice, eye diseases ( uveitis, corneal changes, retinitis ), anemia or neurological symptoms (convulsions, seizures, disorientation, nystagmus, paralysis ).
Diagnosis
A clinical suspicion is at any given fever (less than six years) at a younger cat that does not respond to antibiotic treatment.
Accumulation of fluid in the body cavities ( " wet form ") and an increased content of globulins in the blood ( hyperglobulinemia ) are already clear indications. Certain changes in the blood picture ( moderate to severe anemia, neutrophilia and leukopenia ) are further suspicions.
The following further diagnostic testing methods are possible:
Thread pulling end consistency of Punktatflüssigkeit
Measuring the density of a Bauchhöhlenpunktats FIP cat refractometer
A combination of different methods increases the diagnostic value. A determination of the liberated by hemolysis lactate dehydrogenase ( an enzyme that converts lactate to pyruvate ) may be a further indication of the disease, as well as the determination of the in cats caused mostly by FIP increase of pancreatic enzyme alpha -amylase.
While an antigen detection in the effusion is considered conclusive, which is only difficult to detect " dry form ". The detection methods 4-7 are also possible, however, applies so far only the pathohistological evidence as significant for the presence of the FIP. A detection of antibodies in tissue samples ( bioptate ) of lung, liver, kidney and lymph nodes is considered to be conclusive, but there are cross-reactions with the harmless FCoV variant and other coronaviruses ( Canines coronavirus, TGE virus ) for which cats are indeed in principle susceptible but do not trigger any FIP. A PCR virus detection in tissues is also commercially available.
Since 2012 there is a detection method that promises a unique molecular characterization of two coronavirus variants. Here, mutations in two spike proteins are detected by PCR, which has a direct relationship with the mutated variant and thus the FIP. This test is also commercially available since 2013, and can be done at aspirates from effusions, cerebrospinal fluid and aqueous humor as well as EDTA blood.
Differential Diagnosis
In the wet form fairly typical of other causes of ascites and / or pleural effusion should be excluded. These mainly include heart disease, lack of protein in the blood ( hypoproteinemia ), Stauungsergüsse by cancer, bleeding, or a bacterial pleuritis or peritonitis; a rare Streptotrichose ( purulent bacterial pleurisy, the liquid is here but brownish cloudy) or a rupture of the thoracic duct ( chylothorax ). A majority of these disorders can be quite simple excluded due to the caused by this relatively low protein content of the effusion ( transudate ) and the absence of tumor cells or bacteria.
In refractory fever and / or nodular changes Feline leukemia, immune deficiency syndrome of cats, panleukopenia, lymphosarcoma, yersiniosis and Tyzzersche disease must be considered.
Therapy and prophylaxis
A clinically manifest FIP inevitably leads to death within a few weeks, as there is no treatment. Only symptomatic therapy combined with immunosuppression is possible. Evidence that an addition to immunosuppressive therapy treatment carried out with feline interferon may have a beneficial effect on the survival time could not be confirmed in a recent study. A therapeutic trial with high-dose glucocorticoids may be possibly taken in combination with the thromboxane synthase inhibitor Ozagrel. Against secondary bacterial infection, an antibiotic is indicated.
Vaccination against FIP is controversial. Fundamental problem here is that a systemically administered vaccine ( vaccine) in the strains used entails the risk of creating a FIP vaccine virus in itself, the vaccine virus with the field virus can be mixed and can antibody-dependent immune enhancement occur. The purpose of the available vaccine is therefore the creation of a local immune response at the cellular level and on the basis of local IgA in the portal of entry of the virus in the nasopharyngeal area. Therefore, the vaccine is dripped into the nose. The only local effect of the vaccine here is ensured, since the vaccine strain can grow only at a temperature of 31 ° C. With already FCoV -positive animals (including through the harmless variant ) fails the principle of vaccination. It is therefore only partly recommendable. It makes sense she is in seronegative cats in larger flocks and individually held animals in homes that would be overwhelmed in their immune response by accidental contact with eingeschlepptem virus material (eg faeces on the shoes of the owner) as a result of the massive " viral loads ". The protective effect of the vaccine ( Primucell FIP ®) resulted in clinical trials very different results. Depending on the study, an efficiency between 0 (for no protective effect ) and 75 percent is specified.
The attempt to prevent the spread of the harmless output variant of the virus, based on the concept of "Early Weaning " (English, early weaning), which was introduced in 1992 by Addie & Jarrett. Here, the pregnant mother cat isolated two weeks before the birth of other cats and subjected to the birth and rearing kittens strict hygiene conditions. With five to six weeks the kittens are deducted from the mother and separated from it because they are only protected up to this point by maternal antibodies and then could get from it transmit the virus. In contrast to successes in Great Britain, where all kittens were then FCoV - seronegative, this result was not reproduced in a German study.
A more practical strategy is to reduce the infection pressure within the cat population. The principle is simply thin out the potentially pathogenic FCoV virus as much as possible and with simple hygienic methods already feasible. Possible measures are recommended:
- Setting up as many Kotkisten, which should be cleaned several times a day
- If possible using always the same drinking and food vessels and their daily cleaning
- Attitude of the cats in small groups of 3 to 4 animals
- Removing heavy Virusausscheidern from the group
- Remove dams two weeks before throwing from the group and separate rearing of pups.
History
The FIP was observed from 1954 grown in the U.S., although anecdotal reports of suspected FIP cases can be found as early as 1914. 1963 wrote Jean Holzworth for the first time a detailed work, 1966 reported Wolfe and Griesemer the infectious nature of the disease after and gave a more detailed description. In 1968, Zook et al. in experimentally infected with the disease cats the virus first detected by electron microscopy. The fact that it is at the pathogen to a coronavirus, has been suspected since 1970, but only in 1976 succeeded the detection of the pathogen ( Osterhaus et al. ) And its growth in cell culture ( Pedersen ). Starting in 1977, the exciting first " FIP virus " was called ( FIPV ). 1979, the first ELISA test for the detection of antibodies has been developed. 1981 described Pedersen et al. the first time the widespread occurrence of feline enteric coronavirus ( FECV ) and showed the great similarity to FIPV. In 1987, Pedersen on the hypothesis that FECV and FIPV represent a common virus spectrum and differ only in their virulence. 1998 succeeded his working group ( Vennema et al. ) Proof that the FIPV is merely a mutation of the FECV. From 2000, the term feline coronavirus (FCoV ) sat by designation as a pathogen.
First experimental trials for vaccine development date back to the early 1980s. Experiments with different vaccine strains ( heterologous virus, 1979, 1984.1988; homologous virulent virus, 1983; homologous attenuated virus, 1983; vaccinia virus recombinants, 1990, 1992 ) produced no detectable protective effect and even led to Impferkrankungen which partially located terms of antibody-dependent immune enhancement (see below) manifested. The first safe commercial vaccine was produced in 1991 by Pfizer.
With the emergence of Severe Acute Respiratory Syndrome (SARS) and the discovery in 2003 made that it is the causative agent is a coronavirus that FCoV and other animal coronaviruses were suspected to be responsible for this severe respiratory disease in humans. The FCoV shows the nucleotide sequence of great matches for SARS virus. These assumptions, however, have not been confirmed.