FIP treatment research: targeting viral replication

Kim Y, Mandadapu SR, Groutas WC and Chang KO. Potent inhibition of feline coronaviruses with peptidyl compounds targeting coronavirus 3C-like protease. Antiviral research. 2013; 97: 161-8. 

Feline coronavirus is associated with development of feline infectious peritonitis (FIP), a lethal disease of cats. Development of effective drugs to treat FIP has been frustrating, and currently there is no specific treatment approved. Research projects are now focusing on new strategies to combat this virus. 

In this study, researchers focused on a particular viral protein to target with an inhibitor. The target they selected is an enzyme (3C-like protease). During viral replication, the coronavirus produces a polyprotein that must be processed into a mature protein by this and other enzymes. Compounds (peptidyl inhibitors) were developed that inhibited the function of the 3C-like protease. In cell culture, these compounds did inhibit feline coronavirus replication. When combined with another similar compound, virus replication was dramatically affected. These drugs offer hope for development of future treatments for FIP. [MK]


See also: Kim Y, Lovell S, Tiew KC, et al. Broad-spectrum antivirals against 3C or 3C-like proteases of picornaviruses, noroviruses, and coronaviruses. Journal of virology. 2012; 86: 11754-62.

Related blog articles:
FIP: a new treatment approach: Winn grant W12-026 (April 2012)
Development of new therapies for FIP: Winn grant W10-037 (March 2012)

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Join us on Google+

Kim Y, Mandadapu SR, Groutas WC and Chang KO. Potent inhibition of feline coronaviruses with peptidyl compounds targeting coronavirus 3C-like protease. Antiviral research. 2013; 97: 161-8. 

Feline coronavirus is associated with development of feline infectious peritonitis (FIP), a lethal disease of cats. Development of effective drugs to treat FIP has been frustrating, and currently there is no specific treatment approved. Research projects are now focusing on new strategies to combat this virus. 

In this study, researchers focused on a particular viral protein to target with an inhibitor. The target they selected is an enzyme (3C-like protease). During viral replication, the coronavirus produces a polyprotein that must be processed into a mature protein by this and other enzymes. Compounds (peptidyl inhibitors) were developed that inhibited the function of the 3C-like protease. In cell culture, these compounds did inhibit feline coronavirus replication. When combined with another similar compound, virus replication was dramatically affected. These drugs offer hope for development of future treatments for FIP. [MK]


See also: Kim Y, Lovell S, Tiew KC, et al. Broad-spectrum antivirals against 3C or 3C-like proteases of picornaviruses, noroviruses, and coronaviruses. Journal of virology. 2012; 86: 11754-62.

Related blog articles:
FIP: a new treatment approach: Winn grant W12-026 (April 2012)
Development of new therapies for FIP: Winn grant W10-037 (March 2012)

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Join us on Google+

Read More

Value of tests to diagnose FIP

Jeffery U, Deitz K and Hostetter S. Positive predictive value of albumin: globulin ratio for feline infectious peritonitis in a mid-western referral hospital population. J Feline Med Surg. 2012; 14: 903-5. 
 
The definitive method to diagnose feline infectious peritonitis (FIP) is biopsy and histopathology. A previous report has indicated that a low serum albumin to globulin (A:G) ratio has a high positive predicative value for FIP in cats with clinical signs highly suggestive of the disease. Yet, FIP can present with more vague clinical signs. Predictive values (positive and negative) depend significantly on the prevalence of the disease in the tested population. The positive predictive value is the probability that an animal with a positive test truly has the target disease. When prevalence of the disease is high, the positive predictive value of a test will be greater than when prevalence is low. The authors of this retrospective study investigated the performance of low A:G ratio as a diagnostic test for cats with vague signs of illness consistent with a possible diagnosis of FIP. They wanted to establish the positive predictive value of A:G less than 0.8 and less than 0.6 for FIP in a referral hospital in a mid-west population of cats with one or more clinical signs compatible with FIP (lethargy and inappetance, along with weight loss, pyrexia, effusion, neurological signs, diarrhea, mild upper respiratory tract signs, ocular lesions, and jaundice).

The findings of this study show the importance of determining diagnostic test performance in relation to the population in which the test will be performed. In this study’s results, a cat with an A:G of 0.6 or more was highly unlikely to have FIP. Also, in this population of cats (those visiting a referral hospital in mid-west United States) where the prevalence of FIP is low, a low A:G is of little value in confirming FIP. Therefore, using an A:G of less than 0.8 or less than 0.6 to support a diagnosis of FIP in a patient from a population where FIP would be one of several differential diagnoses carries a high risk of a false-positive diagnosis. [VT]

See also: Fischer Y, Sauter-Louis C and Hartmann K. Diagnostic accuracy of the Rivalta test for feline infectious peritonitis. Vet Clin Pathol. 2012; 41: 558-67. 

Related blog posts:
Diagnosis of FIP (May 2011)
Development of new therapies for FIP (March 2012)

Jeffery U, Deitz K and Hostetter S. Positive predictive value of albumin: globulin ratio for feline infectious peritonitis in a mid-western referral hospital population. J Feline Med Surg. 2012; 14: 903-5. 
 
The definitive method to diagnose feline infectious peritonitis (FIP) is biopsy and histopathology. A previous report has indicated that a low serum albumin to globulin (A:G) ratio has a high positive predicative value for FIP in cats with clinical signs highly suggestive of the disease. Yet, FIP can present with more vague clinical signs. Predictive values (positive and negative) depend significantly on the prevalence of the disease in the tested population. The positive predictive value is the probability that an animal with a positive test truly has the target disease. When prevalence of the disease is high, the positive predictive value of a test will be greater than when prevalence is low. The authors of this retrospective study investigated the performance of low A:G ratio as a diagnostic test for cats with vague signs of illness consistent with a possible diagnosis of FIP. They wanted to establish the positive predictive value of A:G less than 0.8 and less than 0.6 for FIP in a referral hospital in a mid-west population of cats with one or more clinical signs compatible with FIP (lethargy and inappetance, along with weight loss, pyrexia, effusion, neurological signs, diarrhea, mild upper respiratory tract signs, ocular lesions, and jaundice).

The findings of this study show the importance of determining diagnostic test performance in relation to the population in which the test will be performed. In this study’s results, a cat with an A:G of 0.6 or more was highly unlikely to have FIP. Also, in this population of cats (those visiting a referral hospital in mid-west United States) where the prevalence of FIP is low, a low A:G is of little value in confirming FIP. Therefore, using an A:G of less than 0.8 or less than 0.6 to support a diagnosis of FIP in a patient from a population where FIP would be one of several differential diagnoses carries a high risk of a false-positive diagnosis. [VT]

See also: Fischer Y, Sauter-Louis C and Hartmann K. Diagnostic accuracy of the Rivalta test for feline infectious peritonitis. Vet Clin Pathol. 2012; 41: 558-67. 

Related blog posts:
Diagnosis of FIP (May 2011)
Development of new therapies for FIP (March 2012)

Read More

Evolving insights into FIP virulence

Terada Y, Shiozaki Y, Shimoda H, et al. Feline infectious peritonitis virus with a large deletion in the 5'-terminal region of the spike gene retains its virulence for cats. The Journal of general virology. 2012; 93: 1930-4. 

The acquisition of macrophage tropism appears to be an essential step in the transformation of feline enteric corona virus (FECV) to feline infectious peritonitis virus (FIPV).This is a transformation from a largely non-pathogenic and localized enterocyte pathogen to a highly virulent and systemic monocyte/macrophage pathogen. Therefore, determining the critical genetic mutation(s) leading a change in tropism is required for understanding the pathogenic phenomena of feline coronavirus (FCoV) infections. Although various viral proteins such as 3c and 7b have been considered to be involved in the transformation, the spike (S) protein may also play a role in a switch toward macrophage tropism and enhanced virulence. 

In coronaviruses, the S protein functions in cell entry and is responsible for receptor attachment and membrane fusion. While the receptor-binding site is located in the N-terminal part of the protein, fusion is mediated by its membrane proximal part. Surprisingly, previous studies have suggested virulence mutation(s) in the S protein occur in the membrane-proximal domain of the protein and not in the N-terminal region. 

In the present study, a type I FCoV strain, C3663, was found to have a large deletion of 735 bp within the gene encoding for the S protein, resulting in an estimated 245 amino acid loss in the N-terminal region of the protein. FIP developed in three out of four cats that were infected with strain C3663, suggesting that the 5’-terminal region of the S gene is not essential for pathogenic transformation. If the S protein is indeed involved in the transformation and development of FIP, then this result is consistent with the localization of the determinant for macrophage tropism lying in the domain responsible for membrane fusion suggesting a role for fusion function rather than for receptor binding. [GO]

See also: Rottier PJ, Nakamura K, Schellen P, Volders H and Haijema BJ. Acquisition of macrophage tropism during the pathogenesis of feline infectious peritonitis is determined by mutations in the feline coronavirus spike protein. J Virol. 2005; 79: 14122-30. 

Related blog articles:
Understanding FIP virulence (October 2012)
Development of new therapies for FIP (March 2012)

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Join us on Google+

Terada Y, Shiozaki Y, Shimoda H, et al. Feline infectious peritonitis virus with a large deletion in the 5'-terminal region of the spike gene retains its virulence for cats. The Journal of general virology. 2012; 93: 1930-4. 

The acquisition of macrophage tropism appears to be an essential step in the transformation of feline enteric corona virus (FECV) to feline infectious peritonitis virus (FIPV).This is a transformation from a largely non-pathogenic and localized enterocyte pathogen to a highly virulent and systemic monocyte/macrophage pathogen. Therefore, determining the critical genetic mutation(s) leading a change in tropism is required for understanding the pathogenic phenomena of feline coronavirus (FCoV) infections. Although various viral proteins such as 3c and 7b have been considered to be involved in the transformation, the spike (S) protein may also play a role in a switch toward macrophage tropism and enhanced virulence. 

In coronaviruses, the S protein functions in cell entry and is responsible for receptor attachment and membrane fusion. While the receptor-binding site is located in the N-terminal part of the protein, fusion is mediated by its membrane proximal part. Surprisingly, previous studies have suggested virulence mutation(s) in the S protein occur in the membrane-proximal domain of the protein and not in the N-terminal region. 

In the present study, a type I FCoV strain, C3663, was found to have a large deletion of 735 bp within the gene encoding for the S protein, resulting in an estimated 245 amino acid loss in the N-terminal region of the protein. FIP developed in three out of four cats that were infected with strain C3663, suggesting that the 5’-terminal region of the S gene is not essential for pathogenic transformation. If the S protein is indeed involved in the transformation and development of FIP, then this result is consistent with the localization of the determinant for macrophage tropism lying in the domain responsible for membrane fusion suggesting a role for fusion function rather than for receptor binding. [GO]

See also: Rottier PJ, Nakamura K, Schellen P, Volders H and Haijema BJ. Acquisition of macrophage tropism during the pathogenesis of feline infectious peritonitis is determined by mutations in the feline coronavirus spike protein. J Virol. 2005; 79: 14122-30. 

Related blog articles:
Understanding FIP virulence (October 2012)
Development of new therapies for FIP (March 2012)

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Join us on Google+

Read More

Revealing more about FIP

Pedersen NC, Liu H, Scarlett J, et al. Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats. Virus Research 2012;165:17-28. 
  
Feline infectious peritonitis (FIP) is a complex disease involving a mutant coronavirus. The specific mutation that occurs allowing this normally innocuous virus to cause a fatal disease remains unclear. A particular virus protein, the 3c protein, has been investigated as a possible viral mutational site contributing to disease development. These investigators found that this protein appears to be involved with the ability of the virus to replicate in the intestines. Mutations in the gene for this protein lead to the virus being unable to replicate in the intestinal tract and thus unable to be shed in feces. More than half of the FIP viruses they analyzed had a mutation in the 3c gene. This may explain why FIP outbreaks with cat-to-cat transmission of the mutant virus rarely occurs – it is simply no longer shed in feces once this mutation occurs. While we still don’t know what makes the FIP virus so nasty, we have gained a better understanding of its strange epidemiology. [MK]

See also: Brown MA. Genetic determinants of pathogenesis by feline infectious peritonitis virus. Vet Immunol Immunopathol 2011;143:265-268.

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+

Pedersen NC, Liu H, Scarlett J, et al. Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats. Virus Research 2012;165:17-28. 
  
Feline infectious peritonitis (FIP) is a complex disease involving a mutant coronavirus. The specific mutation that occurs allowing this normally innocuous virus to cause a fatal disease remains unclear. A particular virus protein, the 3c protein, has been investigated as a possible viral mutational site contributing to disease development. These investigators found that this protein appears to be involved with the ability of the virus to replicate in the intestines. Mutations in the gene for this protein lead to the virus being unable to replicate in the intestinal tract and thus unable to be shed in feces. More than half of the FIP viruses they analyzed had a mutation in the 3c gene. This may explain why FIP outbreaks with cat-to-cat transmission of the mutant virus rarely occurs – it is simply no longer shed in feces once this mutation occurs. While we still don’t know what makes the FIP virus so nasty, we have gained a better understanding of its strange epidemiology. [MK]

See also: Brown MA. Genetic determinants of pathogenesis by feline infectious peritonitis virus. Vet Immunol Immunopathol 2011;143:265-268.

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+

Read More

FIP: a new treatment approach

Winn grant W12-026, a Bria Fund project
Anti-immune evasive therapy in the treatment of FIP - a randomized,
controlled clinical trial
Investigators: Hans Nauwynck, Sabine Gleich; Ghent University, Belgium

This project is a continuation of a previous Winn grant (W10-039): Development of a novel treatment strategy to inhibit the immune evasion mechanism of feline infectious peritonitis virus

 

Feline coronavirus exists in two forms: a less harmful (avirulent) strain that can cause mild enteritis and a highly pathogenic (virulent) strain that causes a progressive and usually fatal disease known as feline infectious peritonitis (FIP). Cats living in multi‐cat environments (e.g., shelter cats or cats in breeding catteries) are at a particularly high risk to develop FIP. An effective therapy is currently not available and affected cats usually succumb to their disease. Previous research has shown that FIP virus can evade the host’s immune system and that a specific blocking agent can inhibit this evasion mechanism. It has been shown in a previous project that this agent is well tolerated when administered to healthy cats and that the desired plasma concentration can be achieved with different administration routes.

In this project, the investigators will evaluate the efficacy of the inhibitor as a treatment for FIP in 10 naturally infected cats. In addition, the pharmacological behavior of the compound will be determined in the first 6 cats that enter this study. If the results of this pilot study are promising, the project will be expanded into a randomized, controlled trial. The goal of this project is to improve the quality of life and survival of cats with FIP by enabling the host’s immune system to recognize and destroy infected cells.

This project is available for sponsorship. When you sponsor a project, your name will be added to the list of the project's supporters on our website and in any publications we produce about the project. You will receive exclusive pre-publication reports on the progress of your chosen project as they become available, and a final report at its conclusion.

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+

Winn grant W12-026, a Bria Fund project
Anti-immune evasive therapy in the treatment of FIP - a randomized,
controlled clinical trial
Investigators: Hans Nauwynck, Sabine Gleich; Ghent University, Belgium

This project is a continuation of a previous Winn grant (W10-039): Development of a novel treatment strategy to inhibit the immune evasion mechanism of feline infectious peritonitis virus

 

Feline coronavirus exists in two forms: a less harmful (avirulent) strain that can cause mild enteritis and a highly pathogenic (virulent) strain that causes a progressive and usually fatal disease known as feline infectious peritonitis (FIP). Cats living in multi‐cat environments (e.g., shelter cats or cats in breeding catteries) are at a particularly high risk to develop FIP. An effective therapy is currently not available and affected cats usually succumb to their disease. Previous research has shown that FIP virus can evade the host’s immune system and that a specific blocking agent can inhibit this evasion mechanism. It has been shown in a previous project that this agent is well tolerated when administered to healthy cats and that the desired plasma concentration can be achieved with different administration routes.

In this project, the investigators will evaluate the efficacy of the inhibitor as a treatment for FIP in 10 naturally infected cats. In addition, the pharmacological behavior of the compound will be determined in the first 6 cats that enter this study. If the results of this pilot study are promising, the project will be expanded into a randomized, controlled trial. The goal of this project is to improve the quality of life and survival of cats with FIP by enabling the host’s immune system to recognize and destroy infected cells.

This project is available for sponsorship. When you sponsor a project, your name will be added to the list of the project's supporters on our website and in any publications we produce about the project. You will receive exclusive pre-publication reports on the progress of your chosen project as they become available, and a final report at its conclusion.

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+

Read More

Coronavirus in California shelter cats

Final report, Winn grant W10-036, a Bria Fund project
Molecular prevalence and viral load of replicating feline coronavirus in the bloodstream of healthy shelter cats in southern California
Investigators: Pedro Paulo Diniz, Yvonne Drechsler, Linda Kidd, Frank Bossong, Ellen Collisson; Western University of Health Science, Pomona, CA

Feline infectious peritonitis (FIP) remains a serious disease affecting cats, and while much remains unknown, research supported by Winn Feline Foundation is helping to shed light on this enigmatic disease. One of the major challenges of FIP is often the diagnosis; since a diagnosis of FIP is currently essentially a death sentence, accurate appraisal is vital. Unfortunately, the disease often presents with vague signs, and laboratory testing seldom offers any conclusive information. FIP is associated with feline coronavirus infection. However, the majority of cats infected with this virus never suffer any significant disease; thus, testing for the virus in suspected cases is also inconclusive, regardless of the result.

In order to better understand all parameters associated with disease production, these researchers wanted to examine characteristics of virus infection in otherwise healthy cats. Perhaps distinctions from those suffering from FIP could be identified to aid diagnosis. To do this, they assessed the amount of virus actually replicating in the blood of over 200 shelter cats in California.

Interestingly, they found that the incidence of actual replicating virus was quite low in the blood, even in cats that were actively shedding virus in their feces. The level of viral replication in cats with FIP is frequently fairly high, but in healthy cats, at least in the population tested by these investigators, actively replicating virus in the blood is quite low despite known infection. Thus, detecting high levels of replicating virus in the blood may be a useful diagnostic tool for FIP cases, and would allow distinction of harmless coronavirus infection from FIP. In order to validate these results, the investigators plan to test all cats for the presence of antibodies to the virus which would provide a picture of how prevalent infection, past or present, is among this population. [MK]

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+

Final report, Winn grant W10-036, a Bria Fund project
Molecular prevalence and viral load of replicating feline coronavirus in the bloodstream of healthy shelter cats in southern California
Investigators: Pedro Paulo Diniz, Yvonne Drechsler, Linda Kidd, Frank Bossong, Ellen Collisson; Western University of Health Science, Pomona, CA

Feline infectious peritonitis (FIP) remains a serious disease affecting cats, and while much remains unknown, research supported by Winn Feline Foundation is helping to shed light on this enigmatic disease. One of the major challenges of FIP is often the diagnosis; since a diagnosis of FIP is currently essentially a death sentence, accurate appraisal is vital. Unfortunately, the disease often presents with vague signs, and laboratory testing seldom offers any conclusive information. FIP is associated with feline coronavirus infection. However, the majority of cats infected with this virus never suffer any significant disease; thus, testing for the virus in suspected cases is also inconclusive, regardless of the result.

In order to better understand all parameters associated with disease production, these researchers wanted to examine characteristics of virus infection in otherwise healthy cats. Perhaps distinctions from those suffering from FIP could be identified to aid diagnosis. To do this, they assessed the amount of virus actually replicating in the blood of over 200 shelter cats in California.

Interestingly, they found that the incidence of actual replicating virus was quite low in the blood, even in cats that were actively shedding virus in their feces. The level of viral replication in cats with FIP is frequently fairly high, but in healthy cats, at least in the population tested by these investigators, actively replicating virus in the blood is quite low despite known infection. Thus, detecting high levels of replicating virus in the blood may be a useful diagnostic tool for FIP cases, and would allow distinction of harmless coronavirus infection from FIP. In order to validate these results, the investigators plan to test all cats for the presence of antibodies to the virus which would provide a picture of how prevalent infection, past or present, is among this population. [MK]

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+

Read More

Development of new therapies for FIP

Final report, Winn grant W10-037
Development of FIP Therapeutics in a Mouse Model
Investigator: Gary R. Whittaker, Cornell University

Feline infectious peritonitis (FIP) is a lethal systemic infection in cats, caused by a virulent biotype (FIPV) of feline coronavirus (FCoV). Infection by FCoV normally causes mild and often inapparent enteritis, in which case the virus is referred to as feline enteric coronavirus. Like many other viral systems, coronaviruses are activated by host cell proteases, and mutations on the viral spike protein can lead to changes in the activating protease and increased pathogenicity. FIPV is highly dependent on cathepsin B, an activating protease, for cell entry and replication.

Young cat with dry (non-effusive) FIP

 Therefore, these investigators have focused on testing cathepsin B as an effective anti-viral treatment for FIPV. The researchers developed a mouse model for FIP development and tested the new therapeutic using that model. They utilized two different types of the virus inhibitor, and found that the second one tried, known as MDL21870, worked well in the mouse model. This is an important first step in development of effective FIP therapeutics. [MK]

Related articles: Legendre AM and Bartges JW. Effect of polyprenyl immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis. J Feline Med Surg. 2009; 11: 624-6.

Winn’s 33rd Annual Symposium on Feline Health (2011) – Focus on FIP: lecture notes and audio recordings

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+

Final report, Winn grant W10-037
Development of FIP Therapeutics in a Mouse Model
Investigator: Gary R. Whittaker, Cornell University

Feline infectious peritonitis (FIP) is a lethal systemic infection in cats, caused by a virulent biotype (FIPV) of feline coronavirus (FCoV). Infection by FCoV normally causes mild and often inapparent enteritis, in which case the virus is referred to as feline enteric coronavirus. Like many other viral systems, coronaviruses are activated by host cell proteases, and mutations on the viral spike protein can lead to changes in the activating protease and increased pathogenicity. FIPV is highly dependent on cathepsin B, an activating protease, for cell entry and replication.

Young cat with dry (non-effusive) FIP

 Therefore, these investigators have focused on testing cathepsin B as an effective anti-viral treatment for FIPV. The researchers developed a mouse model for FIP development and tested the new therapeutic using that model. They utilized two different types of the virus inhibitor, and found that the second one tried, known as MDL21870, worked well in the mouse model. This is an important first step in development of effective FIP therapeutics. [MK]

Related articles: Legendre AM and Bartges JW. Effect of polyprenyl immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis. J Feline Med Surg. 2009; 11: 624-6.

Winn’s 33rd Annual Symposium on Feline Health (2011) – Focus on FIP: lecture notes and audio recordings

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+

Read More

Birman cats and FIP

Final report, Winn grant 08-036
Blood parameters potentially associated with susceptibility to feline coronavirus in Birman cats
Investigators: Saverio Paltrinieri; University of Milan

This research project examined the increased susceptibility of Birman cats to FIP. The investigators specifically focused on various blood parameters to correlate with immune status and FIP susceptibility. Blood and/or feces were initially collected from 233 cats in 25 breeding catteries or colonies; 57 cats were excluded due to insufficient data or presence of disease within the cattery. Of the 176 cats tested, 5 were diagnosed with FIP. Birman cats were not found to be feline coronavirus seropositive at a higher rate than other breeds. However, the percentage of cats with detectable virus in feces was higher in breeds other than the Birman. Populations of both Birman cats and cats of other breeds had a high prevalence of FCoV infection; there was no statistical difference between the two groups. While differences in some blood parameters were noted, all, both Birman and non-Birman, were within normal reference ranges. The researchers speculate that these differences are breed related, but do not seem to correlate with FCoV infection.

No differences of biologic significance were noted among the various lymphocyte populations in any group of cats, whether Birman or non-Birman. Individual variations in cytokine levels were noted, but did not correlate with FIP development. Birman cats seemed to have a higher capability for cell-mediated immunity, which is critical for protection against FIP. The researchers speculate that poor cell-mediated immunity could induce the persistence of the virus in the host and ultimately this could increase the probability of mutation of the virus and subsequent development of FIP. [MK]

Related articles: Paltrinieri S, Comazzi S, Spagnolo V and Giordano A. Laboratory changes consistent with feline infectious peritonitis in cats from multicat environments. J Vet Med A Physiol Pathol Clin Med. 2002; 49: 503-10.

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+
 

Final report, Winn grant 08-036
Blood parameters potentially associated with susceptibility to feline coronavirus in Birman cats
Investigators: Saverio Paltrinieri; University of Milan

This research project examined the increased susceptibility of Birman cats to FIP. The investigators specifically focused on various blood parameters to correlate with immune status and FIP susceptibility. Blood and/or feces were initially collected from 233 cats in 25 breeding catteries or colonies; 57 cats were excluded due to insufficient data or presence of disease within the cattery. Of the 176 cats tested, 5 were diagnosed with FIP. Birman cats were not found to be feline coronavirus seropositive at a higher rate than other breeds. However, the percentage of cats with detectable virus in feces was higher in breeds other than the Birman. Populations of both Birman cats and cats of other breeds had a high prevalence of FCoV infection; there was no statistical difference between the two groups. While differences in some blood parameters were noted, all, both Birman and non-Birman, were within normal reference ranges. The researchers speculate that these differences are breed related, but do not seem to correlate with FCoV infection.

No differences of biologic significance were noted among the various lymphocyte populations in any group of cats, whether Birman or non-Birman. Individual variations in cytokine levels were noted, but did not correlate with FIP development. Birman cats seemed to have a higher capability for cell-mediated immunity, which is critical for protection against FIP. The researchers speculate that poor cell-mediated immunity could induce the persistence of the virus in the host and ultimately this could increase the probability of mutation of the virus and subsequent development of FIP. [MK]

Related articles: Paltrinieri S, Comazzi S, Spagnolo V and Giordano A. Laboratory changes consistent with feline infectious peritonitis in cats from multicat environments. J Vet Med A Physiol Pathol Clin Med. 2002; 49: 503-10.

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Read the Cat Health News Weekly
Join us on Google+
 

Read More

Diagnosis of FIP

Giori L, Giordano A, Giudice C et al: Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases, J Small Anim Pract 52:152, 2011. 

Feline infectious peritonitis (FIP) can be difficult to diagnose, especially in cases without abdominal fluid accumulation (‘dry’ or non-effusive FIP). The gold standard for diagnosis is through tissue analysis of involved organs, which is difficult and potentially dangerous in an ill cat. These researchers evaluated the usefulness of several non-invasive assays for diagnosis of FIP. Twelve cases suspicious for FIP, of which eight were confirmed, were evaluated retrospectively. The levels of certain inflammatory proteins were elevated significantly and consistently in cats with FIP. While not confirmatory, measurement of alpha-1-acid glycoprotein (AGP) can be used to support a diagnosis of FIP. [MK]

Related articles:

Duthie S, Eckersall PD, Addie DD et al: Value of alpha 1-acid glycoprotein in the diagnosis of feline infectious peritonitis, Vet Rec 141:299, 1997.

More on cat health: Winn Feline Foundation Library

Join us on Facebook

Follow us on Twitter

Giori L, Giordano A, Giudice C et al: Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases, J Small Anim Pract 52:152, 2011. 

Feline infectious peritonitis (FIP) can be difficult to diagnose, especially in cases without abdominal fluid accumulation (‘dry’ or non-effusive FIP). The gold standard for diagnosis is through tissue analysis of involved organs, which is difficult and potentially dangerous in an ill cat. These researchers evaluated the usefulness of several non-invasive assays for diagnosis of FIP. Twelve cases suspicious for FIP, of which eight were confirmed, were evaluated retrospectively. The levels of certain inflammatory proteins were elevated significantly and consistently in cats with FIP. While not confirmatory, measurement of alpha-1-acid glycoprotein (AGP) can be used to support a diagnosis of FIP. [MK]

Related articles:

Duthie S, Eckersall PD, Addie DD et al: Value of alpha 1-acid glycoprotein in the diagnosis of feline infectious peritonitis, Vet Rec 141:299, 1997.

More on cat health: Winn Feline Foundation Library

Join us on Facebook

Follow us on Twitter

Read More

Feline Coronavirus Persistence in Healthy Cats

Kipar A, Meli ML, Baptiste KE, et al. Sites of feline coronavirus persistence in healthy cats. J Gen Virol March 17, 2010.

Feline coronavirus (FCoV), the agent of FIP, is transmitted by the fecal-oral route. Some cats infected with FCoV do not clear the virus, and shed the virus either persistently or intermittently. These cats are important sources of the virus in cat populations. These investigators examined the tissues of infected cats in order to identify the organ site of viral persistence in healthy carriers. Overall, the colon tested positive for virus more than any other tissue over time. Interestingly, all organs, including brain and skin, tested positive for virus in at least one cat during the investigatory period, indicating that FCoV infection disseminates to many organs during infection, even in healthy cats. Cats shedding the virus were found to be infected not only in the colon, but also in the small intestine (jejunum and ileum); in addition, the amount of virus present was an important determinant of shedding in feces, with higher amounts leading to viral shedding as one would expect. While the colon was the primary site for viral persistence and the source of continued shedding over the long-term, spread of the virus to the small intestines appears to be necessary for detectable fecal shedding. This would explain the intermittent nature of virus shedding in carrier cats. In addition, it was found that other tissues outside the gut may remain persistently infected as well, and could serve as a source for recurrent viremia. Most commonly, the mesenteric, or abdominal lymph nodes, and liver were sites of viral persistence. In these tissues, it appears that the resident macrophages are the specific cells involved. Thus, even cats that clear the virus from the intestines may remain virus-infected. [MK]

Related articles:
Goodson TL, Randell SC, Moore LE. Feline infectious peritonitis. Compend Contin Educ Vet 2009;31.

More on cat health: Winn Feline Foundation Library
Join us on Facebook
Follow us on Twitter

Kipar A, Meli ML, Baptiste KE, et al. Sites of feline coronavirus persistence in healthy cats. J Gen Virol March 17, 2010.

Feline coronavirus (FCoV), the agent of FIP, is transmitted by the fecal-oral route. Some cats infected with FCoV do not clear the virus, and shed the virus either persistently or intermittently. These cats are important sources of the virus in cat populations. These investigators examined the tissues of infected cats in order to identify the organ site of viral persistence in healthy carriers. Overall, the colon tested positive for virus more than any other tissue over time. Interestingly, all organs, including brain and skin, tested positive for virus in at least one cat during the investigatory period, indicating that FCoV infection disseminates to many organs during infection, even in healthy cats. Cats shedding the virus were found to be infected not only in the colon, but also in the small intestine (jejunum and ileum); in addition, the amount of virus present was an important determinant of shedding in feces, with higher amounts leading to viral shedding as one would expect. While the colon was the primary site for viral persistence and the source of continued shedding over the long-term, spread of the virus to the small intestines appears to be necessary for detectable fecal shedding. This would explain the intermittent nature of virus shedding in carrier cats. In addition, it was found that other tissues outside the gut may remain persistently infected as well, and could serve as a source for recurrent viremia. Most commonly, the mesenteric, or abdominal lymph nodes, and liver were sites of viral persistence. In these tissues, it appears that the resident macrophages are the specific cells involved. Thus, even cats that clear the virus from the intestines may remain virus-infected. [MK]

Related articles:
Goodson TL, Randell SC, Moore LE. Feline infectious peritonitis. Compend Contin Educ Vet 2009;31.

More on cat health: Winn Feline Foundation Library
Join us on Facebook
Follow us on Twitter

Read More

Potential Treatment for FIP

Legendre, A.M. and J.W. Bartges, Effect of polyprenyl immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis. Journal of Feline Medicine & Surgery, 2009. 11(8): p. 624-626.

Feline infectious peritonitis (FIP) is a baffling and clinical important disease of cats caused by a virulent biotype of feline coronavirus. Despite the fact that the disease is relatively common, veterinarians are faced with a frustrating dilemma because there are no individual tests that are reliable for the diagnosis of FIP, the clinical picture is highly variable, and there is no known effective treatment. Polyprenyl immunostimulant (PI) is an investigational veterinary biologic manufactured by Sass & Sass, Inc and is comprised of a mixture of phosphorylated, linear polyisoprenols. This case series from the University of Tennessee describes three cats with the dry (non-effusive) form of FIP treated with PI. The cats were treated with varying doses of the drug, and by both subcutaneous and oral routes. Two of the three cats were still on treatment and were alive and well 2 years after diagnosis. The third cat survived 14 months but was treated for only 4.5 months. The investigators conclude that further studies to assess the therapeutic efficacy of PI for the treatment of FIP are warranted. [SL]
>> PubMed Abstract

Related Articles:
Addie, D., et al., Feline infectious peritonitis ABCD guidelines on prevention and management. J Feline Med Surg, 2009. 11(7): p. 594-604.
>> Full text article

Pedersen, N.C., A review of feline infectious peritonitis virus infection: 1963-2008. Journal of Feline Medicine & Surgery, 2009. 11(4): p. 225-258.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library
Join us on Facebook

Legendre, A.M. and J.W. Bartges, Effect of polyprenyl immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis. Journal of Feline Medicine & Surgery, 2009. 11(8): p. 624-626.

Feline infectious peritonitis (FIP) is a baffling and clinical important disease of cats caused by a virulent biotype of feline coronavirus. Despite the fact that the disease is relatively common, veterinarians are faced with a frustrating dilemma because there are no individual tests that are reliable for the diagnosis of FIP, the clinical picture is highly variable, and there is no known effective treatment. Polyprenyl immunostimulant (PI) is an investigational veterinary biologic manufactured by Sass & Sass, Inc and is comprised of a mixture of phosphorylated, linear polyisoprenols. This case series from the University of Tennessee describes three cats with the dry (non-effusive) form of FIP treated with PI. The cats were treated with varying doses of the drug, and by both subcutaneous and oral routes. Two of the three cats were still on treatment and were alive and well 2 years after diagnosis. The third cat survived 14 months but was treated for only 4.5 months. The investigators conclude that further studies to assess the therapeutic efficacy of PI for the treatment of FIP are warranted. [SL]
>> PubMed Abstract

Related Articles:
Addie, D., et al., Feline infectious peritonitis ABCD guidelines on prevention and management. J Feline Med Surg, 2009. 11(7): p. 594-604.
>> Full text article

Pedersen, N.C., A review of feline infectious peritonitis virus infection: 1963-2008. Journal of Feline Medicine & Surgery, 2009. 11(4): p. 225-258.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library
Join us on Facebook

Read More

Pathogenesis of Feline Coronavirus Infection

Pedersen, N.C., C.E. Allen, and L.A. Lyons, Pathogenesis of feline enteric coronavirus infection. Journal of Feline Medicine & Surgery, 2008. 10(6): p. 529-541.

The importance of feline enteric coronavirus (FECV) as a primary intestinal pathogen is considered minimal. The importance of FECV is that this virus can mutate in vivo. At least one mutant form causes the highly fatal disease called feline infectious peritonitis (FIP). Initially, this study had been designed to demonstrate that resistance and susceptibility to FECV infection were under genetic control, just as genetics appear to play a significant role in FIP resistance. With more than 3 years of study results, it became apparent that genetics would not readily define this initial goal. The investigators made a decision to concentrate their efforts on what was learned about FECV pathogenesis. A distinct primary stage of infection was identified that lasted from 7 to 18 months, with the highest level of virus shedding during this phase. This primary stage resolved in one of the three following ways: 1) recovery, 2) persistent shedding, or 3) recurrent or intermittent shedding. During the primary phase, shedding levels were significantly higher in kittens than in adult cats. As kittens might be infected before their immune systems mature, FECV replication would be more frequent and increase the potential for FECV to FIP mutations. FIP is known to be more common in kittens than adult cats. The investigators also looked at the role of stress on reactivating latent or subclinical infection, or increasing virus shedding. They evaluated the role natural stress such as pregnancy, parturition, and lactation might play. Stress was also simulated by giving a series of corticosteroid injections using methylprednisolone acetate. No increase in virus shedding was reported in any of the scenarios. Virus shedding and serum antibody titers had a significant relationship to each other. Cats shedding virus usually had titers of 1:100 or higher. Cats that were not shedding virus usually had titers of 1:25 and lower. Additional observations on immunity to FECV infection found that immunity during the primary phase of infection was slow to develop, intermittent, and tenuous in duration. Immunity during re-infection tended to mirror that occurring during primary infection, indicating this immunity lacks memory. This pattern of infection and immunity is strongly influenced by environmental factors. [MK]
>> PubMed Abstract

Related articles:
Pedersen, N.C., A review of feline infectious peritonitis virus infection: 1963-2008. Journal of Feline Medicine & Surgery, 2009. 11(4): p. 225-258.
>> PubMed Abstract

Addie, D., et al., Feline infectious peritonitis ABCD guidelines on prevention and management. J Feline Med Surg, 2009. 11(7): p. 594-604.
>> Free full text article

More on cat health: Winn Feline Foundation Library
Join us on Facebook

Pedersen, N.C., C.E. Allen, and L.A. Lyons, Pathogenesis of feline enteric coronavirus infection. Journal of Feline Medicine & Surgery, 2008. 10(6): p. 529-541.

The importance of feline enteric coronavirus (FECV) as a primary intestinal pathogen is considered minimal. The importance of FECV is that this virus can mutate in vivo. At least one mutant form causes the highly fatal disease called feline infectious peritonitis (FIP). Initially, this study had been designed to demonstrate that resistance and susceptibility to FECV infection were under genetic control, just as genetics appear to play a significant role in FIP resistance. With more than 3 years of study results, it became apparent that genetics would not readily define this initial goal. The investigators made a decision to concentrate their efforts on what was learned about FECV pathogenesis. A distinct primary stage of infection was identified that lasted from 7 to 18 months, with the highest level of virus shedding during this phase. This primary stage resolved in one of the three following ways: 1) recovery, 2) persistent shedding, or 3) recurrent or intermittent shedding. During the primary phase, shedding levels were significantly higher in kittens than in adult cats. As kittens might be infected before their immune systems mature, FECV replication would be more frequent and increase the potential for FECV to FIP mutations. FIP is known to be more common in kittens than adult cats. The investigators also looked at the role of stress on reactivating latent or subclinical infection, or increasing virus shedding. They evaluated the role natural stress such as pregnancy, parturition, and lactation might play. Stress was also simulated by giving a series of corticosteroid injections using methylprednisolone acetate. No increase in virus shedding was reported in any of the scenarios. Virus shedding and serum antibody titers had a significant relationship to each other. Cats shedding virus usually had titers of 1:100 or higher. Cats that were not shedding virus usually had titers of 1:25 and lower. Additional observations on immunity to FECV infection found that immunity during the primary phase of infection was slow to develop, intermittent, and tenuous in duration. Immunity during re-infection tended to mirror that occurring during primary infection, indicating this immunity lacks memory. This pattern of infection and immunity is strongly influenced by environmental factors. [MK]
>> PubMed Abstract

Related articles:
Pedersen, N.C., A review of feline infectious peritonitis virus infection: 1963-2008. Journal of Feline Medicine & Surgery, 2009. 11(4): p. 225-258.
>> PubMed Abstract

Addie, D., et al., Feline infectious peritonitis ABCD guidelines on prevention and management. J Feline Med Surg, 2009. 11(7): p. 594-604.
>> Free full text article

More on cat health: Winn Feline Foundation Library
Join us on Facebook

Read More

Understanding FIP

Regan, A.D., R.D. Cohen, and G.R. Whittaker, Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells. Virology, 2009. 384(1): p. 135-43.

Feline infectious peritonitis (FIP) is a fatal disease of cats associated with feline coronavirus (FCoV) infection, a common enteric virus of cats. How this virus leads to the lethal disease is not clear, as most infected cats do not develop disease. Cytokines are proteins secreted from cells, including cells of the immune system, that are important in mediating an effective immune response. Cats with FIP have abnormal cytokine production that may contribute to the disease FIP. In this study, the investigators examined the effects of the FIP virus on certain white blood cells collected from cats, in a laboratory environment. These cells are the target of the FCoV in cases of FIP. The investigators showed that an important cellular pathway responsible for inducing inflammation is activated by the virus, and is a key contributor to the disease observed in cats with FIP. The raises the possibility that inhibitors of this pathway may be beneficial in the treatment of FIP. [MK]
>> PubMed Abstract

Related articles:
Takano, T., et al., Neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF) produced by macrophages in cats infected with feline infectious peritonitis virus contribute to the pathogenesis of granulomatous lesions. Arch Virol, 2009.
>> PubMed Abstract

Giordano, A. and S. Paltrinieri, Interferon-gamma in the serum and effusions of cats with feline coronavirus infection. Vet J, 2009. 180(3): p. 396-8.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library
Join us on Facebook

Regan, A.D., R.D. Cohen, and G.R. Whittaker, Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells. Virology, 2009. 384(1): p. 135-43.

Feline infectious peritonitis (FIP) is a fatal disease of cats associated with feline coronavirus (FCoV) infection, a common enteric virus of cats. How this virus leads to the lethal disease is not clear, as most infected cats do not develop disease. Cytokines are proteins secreted from cells, including cells of the immune system, that are important in mediating an effective immune response. Cats with FIP have abnormal cytokine production that may contribute to the disease FIP. In this study, the investigators examined the effects of the FIP virus on certain white blood cells collected from cats, in a laboratory environment. These cells are the target of the FCoV in cases of FIP. The investigators showed that an important cellular pathway responsible for inducing inflammation is activated by the virus, and is a key contributor to the disease observed in cats with FIP. The raises the possibility that inhibitors of this pathway may be beneficial in the treatment of FIP. [MK]
>> PubMed Abstract

Related articles:
Takano, T., et al., Neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF) produced by macrophages in cats infected with feline infectious peritonitis virus contribute to the pathogenesis of granulomatous lesions. Arch Virol, 2009.
>> PubMed Abstract

Giordano, A. and S. Paltrinieri, Interferon-gamma in the serum and effusions of cats with feline coronavirus infection. Vet J, 2009. 180(3): p. 396-8.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library
Join us on Facebook

Read More

Skin Lesions Associated with FIP

Declercq, J., H. De Bosschere, et al. (2008). "Papular cutaneous lesions in a cat associated with feline infectious peritonitis." Vet Dermatol 19(5): 255-8.

This paper describes unusual lesions associated with a case of feline infectious peritonitis (FIP)– slightly raised intradermal papules that were not painful nor itchy. The 7 month old intact male domestic shorthair cat also had other indicators of FIP, such as fever, anterior uveitis, respiratory distress, and kidney abnormalities. The skin lesions were on the neck and thorax and difficult to see in these haired areas. Histopathologic analysis of these lesions along with immunohistochemistry revealed typical FIP lesions. If detected early in the disease process, analysis of similar skin lesions may help provide a diagnosis. [MK]
>> PubMed Abstract

Related articles:
Cannon, M. J., M. A. Silkstone, et al. (2005). "Cutaneous lesions associated with coronavirus-induced vasculitis in a cat with feline infectious peritonitis and concurrent feline immunodeficiency virus infection." J Feline Med Surg 7(4): 233-6.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library
Join us on Facebook

Declercq, J., H. De Bosschere, et al. (2008). "Papular cutaneous lesions in a cat associated with feline infectious peritonitis." Vet Dermatol 19(5): 255-8.

This paper describes unusual lesions associated with a case of feline infectious peritonitis (FIP)– slightly raised intradermal papules that were not painful nor itchy. The 7 month old intact male domestic shorthair cat also had other indicators of FIP, such as fever, anterior uveitis, respiratory distress, and kidney abnormalities. The skin lesions were on the neck and thorax and difficult to see in these haired areas. Histopathologic analysis of these lesions along with immunohistochemistry revealed typical FIP lesions. If detected early in the disease process, analysis of similar skin lesions may help provide a diagnosis. [MK]
>> PubMed Abstract

Related articles:
Cannon, M. J., M. A. Silkstone, et al. (2005). "Cutaneous lesions associated with coronavirus-induced vasculitis in a cat with feline infectious peritonitis and concurrent feline immunodeficiency virus infection." J Feline Med Surg 7(4): 233-6.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library
Join us on Facebook

Read More

Immunity and Feline Infectious Peritonitis

Giordano, A. and S. Paltrinieri (2009). "Interferon-gamma in the serum and effusions of cats with feline coronavirus infection." Vet J 180(3): 396-8.

Investigators from the University of Milan studied and compared the quantity of interferon-gamma concentrations in the serum of clinically normal cats infected with feline coronavirus (FCoV) with the concentrations in the sera and effusions of cats with feline infectious peritonitis (FIP), a disease associated with infection with a mutated form of FCoV. Interferon-gamma is a cytokine and an important modulator of cell mediated immunity. Cats with strong cell mediated immunity (CMI) either do not become infected with FCoV or develop the non-effusive form of FIP. Investigators divided cases into two major groups: Group A included cats with clinical FIP and Group B included FCoV infected clinically normal animals. Group A was further subdivided into two groups, those with non-effusive FIP (A1) and effusive FIP (A2). Group B was also subdivided into 2 groups where subgroup B1 included cats from catteries with a high prevalence of FIP and group B2 included cats from catteries with a low prevalence of FIP. Clinically normal FCoV-infected cats from catteries with a high prevalence of FIP had the highest level of serum interferon-gamma. The serum concentration of interferon-gamma was not significantly different in cats with FIP and the clinically normal FCoV-infected cats from catteries with a low prevalence of FIP. The effusions from cats with FIP had a significantly higher level (40 fold) of interferon-gamma than the serum in these cats. This suggests that cells within FIP lesions produce the interferon-gamma present in effusions. The investigators believe the results indicate that CMI is also likely to be involved in the pathogenesis of FIP, and interferon-gamma prevents the onset of FIP in some instances and could contribute to development of disease in others. [VT]
>> PubMed Abstract

Related articles:
Kipar, A., M. L. Meli, et al. (2006). "Natural feline coronavirus infection: differences in cytokine patterns in association with the outcome of infection." Vet Immunol Immunopathol 112(3-4): 141-55.
>> PubMed Abstract

Paltrinieri, S., C. Metzger, et al. (2007). "Serum alpha1-acid glycoprotein (AGP) concentration in non-symptomatic cats with feline coronavirus (FCoV) infection." J Feline Med Surg 9(4): 271-7.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library

Giordano, A. and S. Paltrinieri (2009). "Interferon-gamma in the serum and effusions of cats with feline coronavirus infection." Vet J 180(3): 396-8.

Investigators from the University of Milan studied and compared the quantity of interferon-gamma concentrations in the serum of clinically normal cats infected with feline coronavirus (FCoV) with the concentrations in the sera and effusions of cats with feline infectious peritonitis (FIP), a disease associated with infection with a mutated form of FCoV. Interferon-gamma is a cytokine and an important modulator of cell mediated immunity. Cats with strong cell mediated immunity (CMI) either do not become infected with FCoV or develop the non-effusive form of FIP. Investigators divided cases into two major groups: Group A included cats with clinical FIP and Group B included FCoV infected clinically normal animals. Group A was further subdivided into two groups, those with non-effusive FIP (A1) and effusive FIP (A2). Group B was also subdivided into 2 groups where subgroup B1 included cats from catteries with a high prevalence of FIP and group B2 included cats from catteries with a low prevalence of FIP. Clinically normal FCoV-infected cats from catteries with a high prevalence of FIP had the highest level of serum interferon-gamma. The serum concentration of interferon-gamma was not significantly different in cats with FIP and the clinically normal FCoV-infected cats from catteries with a low prevalence of FIP. The effusions from cats with FIP had a significantly higher level (40 fold) of interferon-gamma than the serum in these cats. This suggests that cells within FIP lesions produce the interferon-gamma present in effusions. The investigators believe the results indicate that CMI is also likely to be involved in the pathogenesis of FIP, and interferon-gamma prevents the onset of FIP in some instances and could contribute to development of disease in others. [VT]
>> PubMed Abstract

Related articles:
Kipar, A., M. L. Meli, et al. (2006). "Natural feline coronavirus infection: differences in cytokine patterns in association with the outcome of infection." Vet Immunol Immunopathol 112(3-4): 141-55.
>> PubMed Abstract

Paltrinieri, S., C. Metzger, et al. (2007). "Serum alpha1-acid glycoprotein (AGP) concentration in non-symptomatic cats with feline coronavirus (FCoV) infection." J Feline Med Surg 9(4): 271-7.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library

Read More

Diagnosis of FIP

Winn funded research

Kennedy, M. A., M. Abd-Eldaim, et al. (2008). "Evaluation of antibodies against feline coronavirus 7b protein for diagnosis of feline infectious peritonitis in cats." American Journal of Veterinary Research 69(9): 1179-1182.

Feline infectious peritonitis (FIP) is a lethal, complex, and clinically important disease of cats caused by feline coronavirus (FCoV). FCoV occurs in two biotypes: one that is virulent and causes FIP, and one that is nonvirulent. FIP occurs in an effusive form characterized by pleural effusion or ascites, as well as a granulomatous form that may affect several organs. No consistent genetic difference has been identified that can distinguish all virulent from nonvirulent FCoVs. As a result, antemortem diagnosis of FIP is difficult because no test that is specific and sensitive for the FIP virus is available. It has been suggested that the product of the 7b gene is a virulence factor. If expression of the 7b protein consistently leads to FIP, cats infected with virulent FCoV would be expected to have measurable antibodies against this protein, whereas cats infected with the nonvirulent FCoV would not. This would allow differentiation of cats infected with virulent FCoV from those infected with a nonvirulent strain. The purpose of this study was to determine specific antibody concentrations against the 7b protein in cats with FIP or other diseases and healthy cats. Serum samples from 95 cats submitted for various diagnostic tests as well as 20 samples from specific pathogen free cats used as negative controls were tested for antibodies against the 7b protein. Serum from cats with FIP had antibodies against the 7b protein. However, some healthy cats, as well as cats with other diseases, were seropositive for the 7b protein. The researchers conclude that seropositivity for the 7b protein is not specific for the FCoV virulent biotype or a diagnosis of FIP.
>> PubMed abstract

Related articles:
Hartmann, K., C. Binder, et al. (2003). "Comparison of different tests to diagnose feline infectious peritonitis." J Vet Intern Med 17(6): 781-90.
>> PubMed abstract

More on cat health: Winn Feline Foundation Library

Winn funded research

Kennedy, M. A., M. Abd-Eldaim, et al. (2008). "Evaluation of antibodies against feline coronavirus 7b protein for diagnosis of feline infectious peritonitis in cats." American Journal of Veterinary Research 69(9): 1179-1182.

Feline infectious peritonitis (FIP) is a lethal, complex, and clinically important disease of cats caused by feline coronavirus (FCoV). FCoV occurs in two biotypes: one that is virulent and causes FIP, and one that is nonvirulent. FIP occurs in an effusive form characterized by pleural effusion or ascites, as well as a granulomatous form that may affect several organs. No consistent genetic difference has been identified that can distinguish all virulent from nonvirulent FCoVs. As a result, antemortem diagnosis of FIP is difficult because no test that is specific and sensitive for the FIP virus is available. It has been suggested that the product of the 7b gene is a virulence factor. If expression of the 7b protein consistently leads to FIP, cats infected with virulent FCoV would be expected to have measurable antibodies against this protein, whereas cats infected with the nonvirulent FCoV would not. This would allow differentiation of cats infected with virulent FCoV from those infected with a nonvirulent strain. The purpose of this study was to determine specific antibody concentrations against the 7b protein in cats with FIP or other diseases and healthy cats. Serum samples from 95 cats submitted for various diagnostic tests as well as 20 samples from specific pathogen free cats used as negative controls were tested for antibodies against the 7b protein. Serum from cats with FIP had antibodies against the 7b protein. However, some healthy cats, as well as cats with other diseases, were seropositive for the 7b protein. The researchers conclude that seropositivity for the 7b protein is not specific for the FCoV virulent biotype or a diagnosis of FIP.
>> PubMed abstract

Related articles:
Hartmann, K., C. Binder, et al. (2003). "Comparison of different tests to diagnose feline infectious peritonitis." J Vet Intern Med 17(6): 781-90.
>> PubMed abstract

More on cat health: Winn Feline Foundation Library

Read More

Seizures in Cats with FIP

Timmann, D., S. Cizinauskas, et al. (2008). "Retrospective analysis of seizures associated with feline infectious peritonitis in cats." J Feline Med Surg 10(1): 9-15.

Seizures have been reported frequently in feline infectious peritonitis (FIP) but have not been studied in detail in association with this disease. The purpose of this study was to perform a retrospective analysis of neurological signs in a population of 55 cats with a histopathologically confirmed neurological form of FIP. Seizure patterns were determined and it was attempted to relate occurrence of seizures with age, breed, sex and neuropathological features. Fourteen cats had seizure(s), while 41 cats had no history of seizure(s). Generalised tonic-clonic seizures were seen in nine cats; and complex focal seizures were observed in four patients. The exact type of seizure could not be determined in one cat. Status epilepticus was observed in one patient but seizure clusters were not encountered. Occurrence of seizures was not related to age, sex, breed or intensity of the inflammation in the central nervous system. However, seizures were significantly more frequent in animals with marked extension of the inflammatory lesions to the forebrain (P=0.038). Thus, the occurrence of seizures in FIP indicates extensive brain damage and can, therefore, be considered to be an unfavourable prognostic sign.
>>PubMed abstract

Related articles:
Winn funded research
Foley, J., C. Rand, et al. (2003). "Inflammation and changes in cytokine levels in neurological feline infectious peritonitis." J Fel Med Surg 5(6): 313-322.
>>PubMed abstract

More on cat health: Winn Feline Foundation Library

Timmann, D., S. Cizinauskas, et al. (2008). "Retrospective analysis of seizures associated with feline infectious peritonitis in cats." J Feline Med Surg 10(1): 9-15.

Seizures have been reported frequently in feline infectious peritonitis (FIP) but have not been studied in detail in association with this disease. The purpose of this study was to perform a retrospective analysis of neurological signs in a population of 55 cats with a histopathologically confirmed neurological form of FIP. Seizure patterns were determined and it was attempted to relate occurrence of seizures with age, breed, sex and neuropathological features. Fourteen cats had seizure(s), while 41 cats had no history of seizure(s). Generalised tonic-clonic seizures were seen in nine cats; and complex focal seizures were observed in four patients. The exact type of seizure could not be determined in one cat. Status epilepticus was observed in one patient but seizure clusters were not encountered. Occurrence of seizures was not related to age, sex, breed or intensity of the inflammation in the central nervous system. However, seizures were significantly more frequent in animals with marked extension of the inflammatory lesions to the forebrain (P=0.038). Thus, the occurrence of seizures in FIP indicates extensive brain damage and can, therefore, be considered to be an unfavourable prognostic sign.
>>PubMed abstract

Related articles:
Winn funded research
Foley, J., C. Rand, et al. (2003). "Inflammation and changes in cytokine levels in neurological feline infectious peritonitis." J Fel Med Surg 5(6): 313-322.
>>PubMed abstract

More on cat health: Winn Feline Foundation Library

Read More

Feline Interferon as a Treatment for FIP

Ritz, S., H. Egberink, et al. (2007). "Effect of feline interferon-omega on the survival time and quality of life of cats with feline infectious peritonitis." J Vet Intern Med 21(6): 1193-7.

Feline infectious peritonitis (FIP) is a devastating disease of young cats with no known effective treatment. Feline interferon-omega (Virbagen Omega, Virbac) has been used in Europe and other parts of the world to treat FIP, but its efficacy is unknown. The drug is currently not available in North America. This study evaluated the efficacy of feline interferon-omega on the survival time and quality of life in 37 privately owned cats with naturally occurring FIP. The study was designed as a placebo-controlled double-blind trial. There was no statistical difference in the survival time or other variables in cats receiving feline interferon-omega compared to cats receiving placebo.
>> PubMed abstract

Winn Feline Foundation funds 3 new studies on FIP in 2008

Bria Fund for FIP Research

More on cat health: Winn Feline Foundation Library

Ritz, S., H. Egberink, et al. (2007). "Effect of feline interferon-omega on the survival time and quality of life of cats with feline infectious peritonitis." J Vet Intern Med 21(6): 1193-7.

Feline infectious peritonitis (FIP) is a devastating disease of young cats with no known effective treatment. Feline interferon-omega (Virbagen Omega, Virbac) has been used in Europe and other parts of the world to treat FIP, but its efficacy is unknown. The drug is currently not available in North America. This study evaluated the efficacy of feline interferon-omega on the survival time and quality of life in 37 privately owned cats with naturally occurring FIP. The study was designed as a placebo-controlled double-blind trial. There was no statistical difference in the survival time or other variables in cats receiving feline interferon-omega compared to cats receiving placebo.
>> PubMed abstract

Winn Feline Foundation funds 3 new studies on FIP in 2008

Bria Fund for FIP Research

More on cat health: Winn Feline Foundation Library

Read More