Author: LM

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Evaluation of a commercial test for genetic resistance to feline infectious peritonitis

Original article: Evaluation of a commercial test for genetic resistance to feline infectious peritonitis, year 2015

Niels C. Pedersen, DVM PhD,
Professor Emeritus,
Center for Pet Health,
School of Veterinary Medicine,
University of California, Davis

The laboratory called AnimalLabs © in Zagreb, Croatia, offers a test that they say identifies cats that carry a genetic marker of resistance to FIP (http://www.animalabs.com/feline-infectious-peritonitis-dna-test-for-resistance/, accessed 7 October 2015). The same test is offered by Genimal Biotechnologies in France (https://www.genimal.com/dna-tests/cat/feline-infectious-peritonitis-resistance/, accessed 29 October 2015). AnimalLabs © has provided two links, one to a research article describing this marker1 , and the second review article on the FIP, which I published in 2009.2 The first article is freely available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041894/pdf/1297-9716-45-57.pdf. A summary of my 2009 review article is available at: https://sockfip.org/wp-content/uploads/2019/04/FIP_Synopsis_Jan13_09-1.pdf. I want to assure you that listing my review article does not support this test. In fact, I believe that the research behind this test was flawed in several respects and should be considered preliminary at best.

I would like to summarize the research that Hsieh and his colleagues did in the article.1 The researchers hypothesized that interferon-gamma is involved in protecting against FIP, a reasonable assumption based on previous research by other scientists. They sequenced the feline interferon-gamma gene (fIFNG) and identified differences between cats (i.e., genetic polymorphisms) at three different positions, which they designated 401, 408, and 428B. These polymorphisms included a single nucleotide polymorphism (SNP) at each of these positions. These SNPs were not located in the parts of the genes that code for the fIFNG protein (i.e., exons) but rather in the regions that surround the exons (i.e., introns). Intron regions are known to contain both nonsense sequences and genetic elements that regulate the level of protein expression by the gene. They then collected DNA from 66 healthy cats and 60 cats with FIP. They found no relationship between the differences in SNPs at positions +401 and +408, but there was a relationship with disease status for the SNP at position +428B. I quote their work – “of all SNPs tested; only fIFNG + 428C/T was shown to be significantly associated with infection outcome. At position +428, there was a higher frequency of the CT genotype in asymptomatic control cats (19.5 %) than in cats with FIP (6.3 %) and the data showed a significant correlation with disease resistance (p = 0.03) (Table 2).” It is noteworthy that among the 66 healthy and 60 cats with FIP, only cats that had CC or CT were present; no cats that had TT were present in either population. The table showing the relevant findings is given below:

Healthy catsFIP cats
+428 SNPs(% of cats)(% of cats)
CC66 (80.5)60 (93.8)
CT16 (19.5) 4 (6.3)
TT0 (0.0)0 (0.0)

The authors concluded that the difference between 16 healthy cats with CT (19.5 % healthy cats) was significantly different from the 4 FIP cats with CT (6.3 % cats with FIP). Using the odds ratio (OR), they calculated that the odds of CC in FIP cats were 3.6 times higher than in CT cats, and concluded that the T SNP is dominant over C. There were two problems with this conclusion, however. First, no cat in their study was TT, and given the fact that 20 cats in both populations carried the T SNP (20/126=15.8 %), one would expect 9 % (0.158 x 0.158=.092), or 11 cats out of 126 cats to be TT. This suggests that either TT is embryonic lethal or, more likely, the populations studied were not a random representation of all cats. Statistical comparisons are only valid when the populations are randomly selected, and special care should be taken when the significance level approaches the minimum P value of P ≤ 0.05 and the number of cases and controls is small. The null value for TT cats in the population also made it impossible to assess whether cats containing two copies of the “protective allele” also had significantly higher resistance than cats that were CC. One would expect that if T is dominant and CT is protective, TT would also be protective. Knowledge of the incidence of cats that are TT at +428 is crucial to the use of the test, because the only way to breed to the CT genotype, if it is the only genotype associated with resistance to FIP, is to maintain CC cats in the population. If TT cats are shown to have a similar degree of resistance to FIP as CT cats, then it is theoretically possible to breed for the T allele alone (CT and TT) assuming that the T allele is indeed associated with resistance. Therefore, the value of the test depends on the prevalence of the CC, CT and TT genotypes in the populations in which it will be used. It is likely that some breeds will be homozygous for the common C allele and therefore will not be covered by the test. Although unlikely, some breeds may have a high prevalence of T and again assuming that both CT and TT are protective, testing may not be cost-effective. If the prevalence of T is low, positive selection for T carries a risk of inbreeding (see discussion below). The bottom line is that breeders should not pay for this test until they have the information they need to use it properly in their breeding programs.

The authors had the biggest problem explaining the biological significance of the T SNP polymorphism. Most significant genetic mutations are found in exons (protein coding regions) and not in introns (non-protein coding regions). To provide biological relevance, the authors had to demonstrate that an intron mutation caused an increase in fIFNG production. The usual way to do this would be to isolate a normal gene with a CC SNP and an alternative gene with a CT SNP and show that there was a difference in the expression level of fIFNG between the two genes in a test system (ie in-vitro). The simplest test would be to identify a large group of cats that are CC, CT or TT, isolate their blood lymphocytes, stimulate them to produce IFNG, and then compare the levels of either specific RNA (by qRT-PCR) or the actual protein by ELISA or other assay. If their observations are correct, cat lymphocytes that are CT or TT should express more fIFNG than cats that are CC. Instead of this complex experiment, the authors decided to only measure fIFNG levels in the plasma of cats with FIP, arguing that cats with FIP and CT SNPs would have higher plasma levels of fIFNG than cats with FIP and CC SNPs. They found that 12/12 cats with FIP with CC SNP had very low levels of fIFNG, while all three cats with FIP with CT mutation had high levels. The conclusion was that the CT mutation allows for higher expression of fIFNG. There are several serious problems with this conclusion. First, it is paradoxical to conclude that a CT mutation confers resistance to FIP and that this resistance is associated with increased fIFNG expression, but then to prove this using plasma from CT cats that have suffered from FIP. The second problem is that there were only three cats in the CT group and 12 cats in the CC group, which makes any statistical comparison irrelevant. Finally, there is no good evidence that cats develop FIP because they are unable to produce sufficient levels of fIFNG. Several FIP studies have measured cytokine expression in cats with FIP.3 These studies were more concise when they showed an increase in FIFNG in the serum of cats with FIP and an increased production of blood lymphocytes in cats with FIP after stimulation. In fact, the general conclusion is that IFNG is stimulated rather than inhibited in cats with FIP.

Up to this point, I assume that this research is justified and that further research is needed. The problem is to make a huge leap from some weak research findings to practical applications. There is already ample evidence that FIP resistance cannot be attributed to a single polymorphism in a single gene. Our attempts to find the only gene responsible for FIP resistance in field studies with Burmese cats4 and randomly bred cats in our own experimental breeding program5 did not allow us to identify a single genetic marker of FIP resistance / susceptibility that we would consider significant. In fact, the only genetic risk factor we were able to identify for FIP resistance was kinship crossing itself.6 Breeding resistant cats with resistant cats did not increase the resistance of their offspring, but rather made them even more susceptible. This is exactly what you would expect from a genetic trait that includes many different genes and gene pathways. The more you try to select a single resistance factor, the more you inadvertently limit the role of multiple genes and gene pathways. Interestingly, the current recommendation is still the best, ie to avoid inbreeding and not keep cats that have fathered kittens with FIP. This recommendation is based on the theory that such cats carry a greater proportion of susceptibility factors than cats that do not produce kittens that have developed FIP and will produce kittens with an even higher proportion of risk factors when bred together. Based on these findings, selection for resistance to FIP using a single genetic marker is more likely to favor inbreeding and, in fact, increase the incidence of FIP. Finally, it should be recalled that heredity explains only 50 % susceptibilities to FIP, 7 the remainder being attributed to epigenetic (genetic changes that occur after birth) and environmental factors.

Although a simple genetic test that would significantly reduce the risk of FIP does not seem realistic, there is reason to continue to look for genetic explanations for why some cats may appear to be resistant to FIP and others succumb to it, and why some cats develop a wet form of FIP and in others a chronic dry form. These studies should focus on farms where FIP exists, where pedigrees are known and where genetic traits can be easily traced. However, the cost of such research should not be at the expense of breeders who order the test. The normal procedure for placing a genetic test for a disease trait on the market is to verify it before it is offered to the public. I don't think this test has been sufficiently researched.

Cited literature

  1. Hsieh LE, Chueh LL. Identification and genotyping of feline infectious peritonitis-associated single nucleotide polymorphisms in the feline interferon-γ gene. Vet Res. 2014, 45:57.
  2. Pedersen NC. A review of feline infectious peritonitis virus infection: 1963-2008. J Feline Med Surg. 2009, 11 (4): 225-58.
  3. Pedersen NC. An update on feline infectious peritonitis: virology and immunopathogenesis. Vet J. 2014, 201 (2): 123-32
  4. Golovko L, Lyons LA, Liu H, Sørensen A, Wehnert S, Pedersen NC. Genetic susceptibility to feline infectious peritonitis in Birman cats. Virus Res. 2013, 175 (1): 58-63.
  5. Pedersen NC, Liu H, Gandolfi B, Lyons LA. The influence of age and genetics onnatural resistance to experimentally induced feline infectious peritonitis. Vet Immunol Immunopathol. 2014, 162 (1-2): 33-40.
  6. Pedersen NC, et al. Immunity to feline infectious peritonitis virus infection is diminished rather than enhanced by positive selection for a resistant phenotype over three generations.Manuscript in preparation.
  7. Foley JE, Pedersen NC: Inheritance of susceptibility of feline infectious peritonitis in purebred catteries. Feline Practice, 1996, 24 (1): 14-22
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DR. PEDERSEN’S AUTOBIOGRAPHY

Original article: DR. PEDERSEN'S AUTOBIOGRAPHY
Published 18.3.2014, Translation 29.1.2021

I was born in 1943. My father was a Danish emigrant and my mother was the daughter of Danish emigrants. However, I learned that I also have Swedish roots after my father's line. I spent the first 14 years of my life in Southern California (Azusa and San Dimas), where my parents rented and then owned several family poultry farms. Although wholesale and retail eggs were their main business, they also raised ducks, geese and turkeys for the holidays. My father liked cats, but not pets. He always kept a large number of them on the farm to keep the rodent population low and their diet was supplemented by blood eggs. I loved all sorts of animals and bred pigeons, pheasants, wild ducks. As a pet, I even had a goat and a rabbit. However, my greatest love was the cats.

My first feline companion was a white, short-haired female with brownish ears, called MoMo (the mother of a cat in my child's tongue). She lived with me for 14 years and regularly and later irregularly gave me kittens. I also befriended many wild cats and one of my tasks was to sit with a box of kittens when customers came to buy eggs. I found homes for many kittens and once in a while I got 25 or 50 cents. I got to know the character and personality of cats more than anyone else. My life changed in 1956, when a huge summer fire in the hills around our San Dimas farm caused the temperature around the chickens to rise to more than 53 ° C and we lost all the water used to cool them. Sixty thousand chickens died within a week as a result of the sunburn. This unfortunate incident was, in fact, a blessing, as small family poultry farms in Southern California were rapidly becoming unprofitable, and this event forced my father to leave poultry after 30 years. He monetized all the property, which had some value, and exchanged it for a small warm spring resort in southern Nevada, and since then my family has been a real middle class. The resort was located in a valley called Upper Muddy, which also housed a large cattle ranch. The high school was 20 miles from Overton and the school started by 6:30. I started high school as a freshman with great tremor and on the first day of school I immediately fell in love with my future wife (Gerie). A small high school and living in a Mormon farming community have given me all sorts of experiences I wouldn't have had if I attended a much larger high school in Southern California. Every capable boy competed in sports and there were many interesting courses and extracurricular activities. Each student had to participate in several activities. My greatest high school experience was with Future Farmers of America, and I eventually became an FFA civil servant.

In 1961, I was accepted to the University of Nevada in Rene for scholarships from the Union Pacific Railroad and the Max E. Fleishman Foundation with the intention of becoming a teacher of professional agriculture. I soon realized that this was probably not the best career choice, but I had no idea about anything else. At the end of the first year, however, I switched to Animal Sciences and in the second year I began to attend much more demanding subjects in preparation for a possible Ph.D. in this field. My life changed again when I enrolled in a veterinary course led by one of the two veterinarians who were responsible for the small veterinary program at UNR. I have never had any direct experience with veterinarians before. Dr. Marble started my interest in veterinary medicine and even allowed me to help him with some of his experimental operations. I was immediately caught up in it and at the last minute I applied to three veterinary schools, UC Davis, WSU and CSU. I was accepted to all three schools, but I decided to go to UC Davis, California, which was closer to my home. I'm a native Californian (and an adapted Nevada). I was also fortunate that my tuition was paid by the state of Nevada under the Western Interstate Compact for Higher Education (WICHE).

I entered veterinary school in September 1963 with the intention of becoming a general practitioner for cattle (my second and third loves are cows and poultry). I worked on several science projects over the weekends and holidays, and I fell even more in love with research. In August 1964, I married my high school love Gerie. In my spare time, I worked with one of the graduate pathology students on a new feline disease called feline peritonitis and co-authored my first scientific article on FIP in 1964. I was horrified by a lack of knowledge about cats and their diseases, but that didn't stop me. After graduating from veterinary school, I graduated in internal medicine for small animals and surgery at Colorado State University, which significantly affected my future life and career. Once again, I realized how little we knew about cat diseases, and I became even more aware of my lifelong affinity and understanding with this species. Prior to my internship in 1967, I was accepted as a graduate student at the John Curtin School of Medical Research (JCSMR), Australian National University, Canberra, ACT, Australia. Australia has fascinated me all my life and JCSMR has given me not only a great research experience, but also my first experience with this vast and beautiful country. After graduating, I worked briefly as a celebrity practitioner in Hollywood to earn money to get my family (I already had a daughter) to Australia. Studying research at the Department of Experimental Pathology at JCSMR was unmatched, but not entirely related to my future career. But I learned about experimental methods. In 1972 I received my Ph.D. from experimental pathology and immunology with honors in. My love for Australia, which I cultivated in books as a child, became a lifelong passion. My hobby is identifying and photographing Western Australian plants. At our house in Winters, California, I have a large collection of photos of the flowering shrubs of Western Australia.

Dr. As longtime director of the Center for Pet Health (CCAH), Pedersen led a team that raised money and designed his current home. The CCAH building was completed in 2006 at a cost of $ 16 million, all of which was obtained from private sources. It is considered one of the most beautiful and functional buildings in the complex and is home to five clinical services and four major research programs.

In early 1972, I returned to the United States for a research position at the School of Veterinary Medicine at UC Davis, where I studied animal cancer associated with retroviruses. This was my first experience with the feline leukemia virus, which we saw during my studies in many cats, but whose cause was unknown at the time. My first year in research did not go well for me and I was considering moving to a postdoctoral position in transplant immunology at the University of Washington. Before formalizing this position, however, the dean of the Veterinary School called me and asked me if I would consider accepting a position at an internal medicine clinic for small animals. Dean Pritchard was tired of hiring doctors with rich clinical experience but weak scientific skills. He decided to try to admit to the clinic people with great research experience and good clinical potential. I became the first of a large number of employees at UC Davis with a professional background of this kind. It turned out to be a very wise decision, as the clinical program at UC Davis soon became world famous not only for its high clinical level but also high level of research.

I have worked at UC Davis since 1972 and retired in October 2013 as Professor Emeritus. I spent the first 17 years in clinics, teaching and working in research. For the rest of my time at Davis, my career was much more about administration and research. After serving as chair of the department, I became the founder and director of the Center for Pet Health and a few years later the director of the Laboratory for Veterinary Genetics. This latter function has rekindled my interest in the role of genetics in disease. Research into infectious and immunological diseases in cats and dogs has accompanied me throughout my career. I am still working and continuing my first love, research. I have no plans to retire if my health allows it, because for me, retirement in research is much better than retirement.

Although I have studied many infectious diseases of cats, FIP remains my first love, if the term can be called a disease that is still so widespread and almost always fatal. I learned to look at the FIP as a "worthy adversary." It is undoubtedly one of the most complex and challenging infectious diseases in existence, and trying to find prevention and treatment is what drives me the most. I realize that the answers don't just come. It's not like researching human diseases that have no problems with funding, whether from individuals or organizations that have a personal interest in discovering treatments. I hope that I will continue to strive to keep the disease at the center of attention, and I can say that I am not alone. I have recently reviewed more than 100 clinical and scientific publications on FIP submitted by research groups around the world since 2008. No other cat disease has received so much attention.

I enclose a more detailed biography of my career with an emphasis on FIP research, which still engulfs me. My biggest career achievements have been in the field of feline infectious diseases such as FeLV, FIV, FCV, FECV and FIPV. My textbook on diseases in a multi-cat environment, which has become a classic today, is perhaps my best creative work. However, my wife, three daughters, a son and 7 (soon to be 8) grandchildren, all successful so far, are my greatest legacy. But I hope that at least for a while, my "paw prints" will remain visible through the literature on cat diseases. And something like pets I've always had cats - always only two and always males.

–Niels C. Pedersen

Note: When Dr. Pedersen mentions a more detailed career CV, meaning mainly a number of published articles that you will find in scientific journals.

This is a 1991 photo when I received the first Jean Holzworth Cat Research Award. Dr. Holzworth was for me the best feline medicine expert he had ever lived. She graduated from DVM at Cornell University and spent her entire life at Angell Memorial Animal Hospital in Boston. She wrote the first modern textbook on cat diseases and I considered her a good friend and inspiration. She convinced me of something I've always believed in - you can't be a great veterinarian for cats without deep and confidential knowledge of this species, including everything from anatomy and physiology to behavior. -DR. P.

Wife of Dr. Pedersen Gerie with the newest members of the SOCK FIP family - recently adopted two brothers Piper (right) and Frodo (left). Frodo and Piper are among the many former experimental cats that the Pedersen have adopted over the past 40 years.

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Detection of Ascitic Feline Coronavirus RNA from Cats with Clinically Suspected Feline Infectious Peritonitis

Original article published on the portal National Center for Biotechnology Information
13.10.2013

Abstract

Ascitic feline coronavirus (FCoV) RNA was examined in 854 cats suspected of having feline infectious peritonitis (FIP) by RT-PCR. Positivity was significantly higher in purebreds (62.2%) than in hybrids (34.8%) (P <0.0001). Among purebred breeds, the positives of the Norwegian Forest Cat (92.3%) and the Scottish Fold cat (77.6%) were significantly higher than the average of purebred breeds (P = 0.0274 and 0.0251, respectively). Positivity was significantly higher in males (51.5%) than in cats (35.7%) (P <0.0001), whereas the prevalence of anti-FCoV antibodies generally showed no gender difference, suggesting that FIP in males infected with FCoV is more common, so males are more likely to break FIP. Genotyping was performed on 377 gene positive samples. Type I (83.3%) was detected much more frequently than type II (10.6%) (P <0.0001), similar to previous serological and genetic surveys.

See for more information original article. Among other things, it is mentioned that the incidence of FIP shows seasonal changes, and most often occurs in the autumn and winter months, while in summer the incidence is significantly lower.

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History of FIP research

Original article: History of FIP research; 19.10.2010; Translation 1.2.2021

Probably the oldest recorded case of FIP (Utrecht State Veterinary School, 1912/13); retrospective diagnosis is likely from the description of chronic exudative peritonitis, dyspnoea (pleurisy?), fever and eye symptoms. (Jacob, 1914).

The sudden occurrence of FIP in the late 1950s has been documented in long-term and thorough autopsy records at the hospital. Angell Memorial Animal Hospital in Boston. Therefore, the existence of FIP as a major disease before this time is questionable. The mention of a cat with a disease reminiscent of the FIP was published half a century earlier (1914 Jakob-Groot and Horzinek), but whether it was really the FIP is uncertain given the absence of reports of a similar disease in the following decades. The incidence of the disease has steadily increased since the 1960s and is currently one of the leading infectious causes of death in young cats from shelters and kennels. The reason for the sudden onset of FIP is unknown, but there are at least three possible explanations. First, coronaviruses may have specialized in cats over the last half century. Remarkably, FIP emerged ten years after the first mentions of porcine gastroenteritis (TGE) in North America. The causative FIP virus is closely related to porcine TGE virus and CCV (Canine Corona Virus), although they are still genetically distinguishable. However, recombinants are known to occur between these three viruses. At least one CCV strain can cause mild enteritis in cats and exacerbate subsequent FIPV infection, suggesting a strong resemblance to feline coronaviruses. Therefore, in this scenario, CCV may be a more likely precursor to FECV. Recombinant events are favored by the ease with which transcription units (RNAs) can be gained or lost during the divergent development of coronaviruses. Second, the FIP mutation may be selective for the FECV variant that emerged in the 1950s. This variant could also arise due to intraspecific and interspecific mutability of coronaviruses in general, and in this case FCoV in particular. The third explanation may include changes in the understanding of cats as pets and their breeding in this modern age. After World War II, there was a dramatic shift when cats began to behave like pets. The numbers of domestic cats have increased significantly, the breeding of purebred animals and cat breeding has become more popular, and more and more cats, especially kittens, have found themselves in shelters. These large, multi-cat enclosures are known to be a breeding ground for feline enteric coronavirus (FECV) and FIP infection. Interestingly, feline leukemia virus infection also spread among domestic cats during this period. FeLV infection was an important cofactor for FIP until it was pushed back into the wild in the 1970s and 1980s by testing, elimination / isolation, and possible vaccination.

Genetic relationships between different genotypes of feline and canine coronaviruses (FCoV and CCoV). Feline sequences are colored blue, canine sequences are colored orange, and porcine sequences are colored purple. Arrows indicate predicted recombination sites. Genes encoding polymerase polyprotein (Pol), structural peak (S), envelope (E), membrane (M) and nucleocapsid (N) proteins are indicated. Genes encoding helper proteins are indicated by numbers.

Sources:

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Prevalence of feline infectious peritonitis in specific cat breeds

Original article: Prevalence of feline infectious peritonitis in specific cat breeds; 1.2.2006; Translation 28.2.2021

Loretta D. Pesteanu-Somogyi, DVM †, Christina Radzai, DVM Bar, Barrak M. Pressler, DVM, DACVIM

Abstract

Although purebred cats are known to be more likely to develop feline infectious peritonitis (FIP), previous studies have not examined the prevalence of the disease in individual breeds. During 16 years, all cats diagnosed with FIP were identified at the University Veterinary Hospital. The breed, sex and reproductive status of the affected cats were compared with the general cat population and with mixed cat breeds evaluated during the same period. As in previous studies, sexually intact cats and purebred cats were significantly more likely to be diagnosed with FIP; the prevalence of the disease was also higher in males and young cats. Abesian, Bengal, Burmese, Himalayan, Ragdoll and Rex cats showed a significantly higher risk, while Burmese, Exotic Shorthair, Manx, Persian, Russian Blue and Siamese cats did not show an increased risk of developing FIP. Although other factors undoubtedly affect the relative prevalence of FIP, this study provides further guidance in prioritizing differential diagnoses in sick purebred cats.

Feline infectious peritonitis (FIP) is a progressive systemic disease with a wide range of clinical symptoms and high mortality (Hartmann 2005). It is caused by a mutation in feline enteric coronavirus, a common feline pathogen that may not cause any clinical signs or only transient diarrhea (Pedersen 1995; McReynolds and Macy 1997; Hartmann 2005). The mutated FIP virus spreads through the monocyte phagocytic system, and variations in the immune response of individual cats cause one of two recognized forms of the disease (Pedersen 1995, McReynolds and Macy 1997, Hartmann 2005). The "wet" form of FIP, which is observed in approximately 75% cases, is caused by complement-mediated vasculitis initiated by deposition of the immune complex in the vessel walls and usually leads to effusions in the body cavity (Pedersen 1995; McReynolds and Macy 1997, Hartmann 2005.). The "dry" form of FIP, identified in other cases, arises when a cell-mediated immune response dominates and granulomas form in various organs (Pedersen 1995; McReynolds and Macy 1997; Hartmann 2005).

Epidemiological studies of cats with FIP have identified several risk factors for developing the disease. The highest prevalence is in young cats (aged 3 months to 3 years), with most cases (75%) being in an environment with numerous cats (Kass and Dent 1995, Pedersen 1995, Foley et al. 1997a, McReynolds and Macy 1997, Rohrbach et al., 2001). Males and sexually intact cats are also at increased risk of developing FIP (Robison et al. 1971; Rohrbach et al. 2001). Other factors that are mentioned less frequently, associated with an increased prevalence of the disease, include seasonal (more cases are usually diagnosed in winter) FeLV infection, increased factors associated with "stress", high titers of coronavirus antibodies, regular feeding of new cats. to kennels and increased coronavirus excretion (Kass and Dent 1995, Pedersen 1995, McReynolds and Macy 1997, Foley et al. 1997a, Rohrbach et al. 2001).

Two studies report that FIP is more common in purebred cats (Robison et al. 1971; Rohrbach et al. 2001). Although the relative prevalence of FIP in different breeds of cats has been the subject of at least one study, statistical differences have not been calculated (Scott 1991). Therefore, to the authors' knowledge, it has never been thoroughly examined whether there is a specific predisposition to FIP depending on the breed. The purpose of this study was to determine whether such a preference for the cat breed actually exists. The sex and age of the affected cats were also examined to allow some comparison between the current population in the study and the populations from previous studies.

Materials and methods

The final diagnosis was checked for all cats entered into the computer database of patients at North Carolina State University College of Veterinary Medicine (NCSU-CVM) between December 22, 1986 and December 22, 2002. Cats with FIP were identified using coding terms. "Feline infectious peritonitis" or "FIP". In all cases, the final diagnosis was made by the attending physician; diagnostic criteria and the results of anti-mortem or post-mortem diagnostic test results have not been reviewed.

The breed, sex, and reproductive status of all cats examined at NCSU-CVM during the 16-year study period were assessed; all cats of unknown breed were excluded. Mixed breeds of cats of all coat lengths (domestic short-haired, medium and long-haired) were considered as a single breed (called "mixed breed") for data analysis purposes. Descriptive statistics were calculated for each variable studied for the FIP population and for the total cat population. Descriptive statistics on the age of cats at the time of evaluation were calculated only for cats affected by the FIP. Differences in breed, sex, and reproductive status were compared using Fisher's exact test; P values less than or equal to 0.05 were considered significant. The odds ratio (OR) and 95% confidence interval (CI) were also calculated for each variable.

The results

During the 16-year study period, 11,535 cats of known breeds were examined at the NCSU-CVM. The cats studied included mixed breeds of cats (9511 cats) and 36 different purebred breeds (2024 cats). Sixty cats (0.52%) had a definitive diagnosis of FIP; the breed was intended for all affected cats. Gender and reproductive status information was available for 57 of the 60 FIP cats and 11303 of the 11475 FIP negative cats. Age information was available for 58 of the 60 FIP cats.

Cats diagnosed with FIP included mixed breeds of cats (33 cats) and 13 different purebred breeds (27 cats). The prevalence of FIP in the mixed cat breed population was 0.35% versus 1.3% in the purebred cat population (Fig. 1). Purebred cats showed a significantly higher probability of developing FIP than mixed breeds (OR 4.5, CI 2.7-7.5; P <0.001). Breeds with a FIP prevalence significantly higher than that of mixed cat breeds included the Abyssinian, Bengal, Birman, Himalayan, Ragdoll and Rex breeds (including Cornish and Devon varieties) (Table 1, Figure 2). The prevalence of FIP in Burmese, exotic shorthair, Manx, Persian, Russian blue and Siamese cats did not differ significantly from mixed breed cats. Although two Havana cats evaluated at NCSU-VTH during the study period were diagnosed as FIP positive, this small number precluded statistical analysis.

Figure 1: Prevalence of FIP by group of cats
Figure 2: Prevalence of feline infectious peritonitis (FIP) in mixed breeds of cats and in breeds with a prevalence of FIP significantly different (P <0.05) from mixed breeds of cats.
TribeandCats diagnosed with FIP / total number of cats (% affected by FIP)Odds ratioConfidence intervalP value (Fisher's exact test)
Abesín cat3/99 (3.0%)8.982.71-29.770.006
Bengal cat1/8 (12.5%)41.034.91-342.850.028
Burma4/18 (22.2%)82.0626.66-262.44<0.001
Burmese cat1/37 (2.7%)7.981.06-59.910.124
Exotic shorthair cat1/62 (1.6%)4.710.63-34.980.199
Havana cat2/2 (100%)_b_b_b
Himalayan cat4/364 (1.1%)3.191.12-9.060.046
Manx1/67 (1.5%)4.350.59-32.290.213
Persian cat4/481 (0.5%)2.410.85-6.830.101
Ragdoll
2/13 (15.3%)52.2211.14-244.790.001
Rex (Cornish and Devon)2/17 (11.7%)38.298.42-174.150.002
Russian blue1/39 (2.6%)7.561.01-56.680.130
Siamese cat1/536 (0.2%)0.540.07-3.931.00
Table 1: Prevalence, odds ratios and confidence intervals in purebred cats with FIP
and Breeds with 0.0% prevalence of feline infectious peritonitis are not listed.
b Insufficient number of cats for statistical calculations.

The prevalence of FIP was zero in 23 cat breeds. These included Angora (11 cats evaluated during the study period), Balinese (25 cats), Belgian (two cats), Bombay (four cats), British Blue (two cats), British Shorthair (three cats), Carthusian (four cats) , Colorpoint Shorthair (one cat), Egyptian Mau (one cat), Japanese bobtail (six cats), Korat (five cats), Maine Coon (151 cats), Maltese (two cats), Norwegian Forest (five cats), Ocicat ( 16 cats), Ragamuffin (one cat), Scottish Fold (15 cats), Siberian (one cat), Snowshoe (two cats), Somali (three cats), Sphinx (one cat), Tonkin (18 cats) and Turkish Van ( two cats). Unfortunately, the low prevalence of FIP in the population of mixed cat breeds has prevented the determination of significance or relative risk in these purebred cat varieties.

FIP was significantly more likely in sexually intact cats compared to the general cat population, regardless of gender (intact male versus neutered male, P <0.001; intact female versus neutered female, P = 0.002; all intact cats versus all neutered cats, P < 0.001, the prevalence of intact cats in the general population was 15.8%, compared to 45.6% in the FIP population). Although FIP was more numerous in males than in females, the difference in prevalence was not statistically significant (P = 0.425; 53.6% from the total cat population were males, compared to 59.6% from the FIP population). At the time of the last evaluation, the median age of cats with FIP was 0.96 years (25th percentile 0.5 years, 75th percentile 2.0 years). 67% cats with FIP were less than 2 years old.

Discussion

Although an increased prevalence of FIP in purebred cats has been reported previously, this is the first time that the predisposition of specific breeds to disease development has been investigated (Robison et al. 1971; Rohrbach et al. 2001). Our results show that some breeds may in fact be more likely to develop FIP, especially Biri, Ragdoll, Bengal, Rex, Abesian and Himalayan breeds. Other cat breeds, Burmese, Exotic Shorthair, Manx, Persian, Russian Blue and Siamese, do not appear to be at increased risk compared to mixed cats. Our results regarding the effect of gender, reproductive status, and age on the relative prevalence of FIP are similar, although not identical, to previous studies (Robison et al. 1971, Horzinek and Osterhaus 1979; Kass and Dent 1995; Rohrbach et al. 2001).

Previous evidence supports the influence of host genetics on the mutation of feline enteric coronavirus or on susceptibility to FIP. Cheetahs, whose genomes have become more homozygous with minimal allelic diversity due to evolutionary narrowing, have a very high prevalence of FIP (O'Brien et al. 1985). Similarly, the increased prevalence we found in some purebred variations could be due to the concentration of inherited factors through breeding or small founder populations. Given the shared environment and virus strain, Foley and Pedersen (1995) calculated that slightly more than 50% of the susceptibility to FIP in purebred cats from six breeds could be attributed to inherited differences between individuals. Interestingly, in this study, one of the kennels with numerous closely related cats suffering from FIP was the Biriem kennel (Foley and Pedersen 1995). In this study, Birmans were by far the most commonly affected, and therefore we may not be the first to point out an increased susceptibility to FIP in this breed.

Other researchers have questioned whether the increased prevalence of FIP in purebred cats could not actually be due to misleading factors. Purebred cats are bred more frequently in kennels, which can be inherently more stressful due to the environment with numerous cats, the regular arrival of new cats and frequent breeding (Kass and Dent 1995, Pedersen 1995). In addition, kennel cats are likely to face higher exposure to feline enteric coronavirus (a condition for FIP development) due to increased population density (Foley et al. 1997a, 1997b, McReynolds and Macy 1997). Finally, the possible increased willingness of owners of expensive purebred cats to perform advanced diagnosis and supportive care at a recommended veterinary facility, such as NCSU-VTH, may skew the apparent prevalence of the disease. However, these factors are expected to falsely increase the prevalence of FIP in all purebred cats, and not only in those breeds that we report have an increased risk of developing the disease.

We have decided to include in this report cases based on the final diagnosis entered in our computerized medical database, and not on the control of records and histopathological reports. As a result, we must recognize that future investigations, which will be limited to cases with a confirmed diagnosis, may yield different results. However, because the pre-death diagnosis of FIP in our tertiary care hospital is expected to be similar to the diagnostic algorithms proposed by other authors, we feel that our results, especially in breeds with more or a particularly strong association with the disease, are unlikely to conflict with future studies. (Sparkes et al. 1991, Rohrer et al. 1993, Addie and Jarrett 1998).

A multivariate analysis of the variables studied here would further define the susceptibility of a specific breed to FIP. For example, it is not known whether breeds with an increased FIP prevalence actually had a higher number of intact cats, which affected our calculations. Furthermore, very few individuals were examined in some breeds and the large CI reflected inaccuracy in risk determination. We doubt that the absence of cats diagnosed with FIP in 23 breeds indicates absolute disease resistance, although it is possible that some of these breeds (such as the Maine Coon cat, which were observed in relatively large numbers at NCSU-VTH) have unrecognized protective factors. which affect susceptibility to FIP. Unfortunately, due to the low prevalence of FIP in all cats, a much larger population will need to be examined to determine if the low incidence of the disease in these breeds is statistically significant.

The predisposition of certain breeds to the development of FIP demonstrated here requires further research. Our results suggest that in some sick purebred cats, the suspected FIP index is likely to increase. A multicenter study, which includes cases from both primary and recommended facilities with multivariate analysis, is probably necessary to definitively answer the question of the sensitivity of individual breeds to FIP.

Thanks

We thank Cavell Brownie, PhD (Department of Statistics, State University of North Carolina) for performing statistical analyzes, and Malcolm Roberts, BVSc, PhD, MPH, FRCVS, FACVSc (Department of Clinical Sciences, State University of North Carolina) for reviewing the manuscript.

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