Feline infectious peritonitis (FIP) is a progressive. Prevalence of feline infectious peritonitis in specific cat breeds *

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Journal of Feline Medicine and Surgery (2006) 8, 1e5 doi:10.1016/j.jfms.2005.04.003 Prevalence of feline infectious peritonitis in specific cat breeds * Loretta D Pesteanu-Somogyi DVM 1y, Christina Radzai DVM 1z, Barrak M Pressler DVM, DACVIM 2 * 1 Veterinary Teaching Hospital, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27506, USA 2 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27506, USA Date accepted: 14 April 2005 Although known that purebreed cats are more likely to develop feline infectious peritonitis (FIP), previous studies have not examined the prevalence of disease in individual breeds. All cats diagnosed with FIP at a veterinary teaching hospital over a 16-year period were identified. Breed, sex and reproductive status of affected cats were compared to the general cat population and to mixed breed cats evaluated during the same period. As with previous studies sexually intact cats and purebreed cats were significantly more likely to be diagnosed with FIP; males and young cats also had a higher prevalence of disease. Abyssinians, Bengals, Birmans, Himalayans, Ragdolls and Rexes had a significantly higher risk, whereas Burmese, Exotic Shorthairs, Manxes, Persians, Russian Blues and Siamese cats were not at increased risk for development of FIP. Although additional factors doubtlessly influence the relative prevalence of FIP, this study provides additional guidance when prioritizing differentials in ill purebreed cats. Ó 2005 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved. Feline infectious peritonitis (FIP) is a progressive systemic disease with a wide spectrum of clinical signs and high mortality (Hartmann 2005). It is caused by a mutation in the feline enteric coronavirus, a common pathogen of cats that may cause no clinical signs or transient diarrhea (Pedersen 1995, McReynolds and Macy 1997, Hartmann 2005). The mutated FIP virus disseminates via the monocyte phagocytic system, and variations in an individual cat s immune response produce one of two recognized forms of disease (Pedersen 1995, McReynolds and Macy 1997, Hartmann 2005). The wet form of FIP, seen in approximately 75% of cases, is caused by complement-mediated vasculitis initiated by immune complex deposition in vessel walls, and typically results in body cavity effusions (Pedersen 1995, McReynolds and Macy 1997, Hartmann 2005). The dry form of FIP, * Drs Pesteanu-Somogyi and Radzai contributed equally to this work as senior veterinary students. *Corresponding author. E-mail: barrak_pressler@ncsu.edu y Current address: Bay Ridge Animal Hospital, 6803 5th Avenue, Brooklyn, NY 11220, USA. z Current address: Boiling Springs Animal Hospital, 550 Park Drive, Boiling Springs, PA 17007, USA. found in the remainder of cases, results when a cell-mediated immune response dominates and granulomas form in various organs (Pedersen 1995, McReynolds and Macy 1997, Hartmann 2005). Epidemiologic studies of cats with FIP have identified several risk factors for development of disease. The highest prevalence is in young cats (3 months to 3 years of age) with the majority of cases (75%) in multi-cat environments (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 for development of FIP (Robison et al 1971, Rohrbach et al 2001). Other factors that have been less commonly reported to be associated with an increased disease prevalence include season (more cases are typically diagnosed in winter), FeLV infection, an increase in factors associated with stress, high coronavirus antibody titer, regular introduction of new cats to a cattery, and increased frequency of coronavirus shedding (Kass and Dent 1995, Pedersen 1995, McReynolds and Macy 1997, Foley et al 1997a, Rohrbach et al 2001). 1098-612X/05/010001+05 $30.00/0 Ó 2005 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

2 LD Pesteanu-Somogyi et al Two studies have reported that FIP is more common in purebreed cats (Robison et al 1971, Rohrbach et al 2001). Although the relative prevalence of FIP in different cat breeds has been reported in at least one study, statistical differences were not calculated (Scott 1991). Therefore, to the authors knowledge, whether a specific breed predisposition exists has never been thoroughly investigated. The purpose of this study was to determine whether such a breed predilection exists in cats. Sex and age of affected cats were also examined in order to allow some comparison between the current study population and those in previous studies. Materials and methods The final diagnosis was reviewed for all cats entered in the computerized patient database of the North Carolina State University College of Veterinary Medicine (NCSU-CVM) between December 22, 1986 and December 22, 2002. Cats with FIP were identified using the coding terms feline infectious peritonitis or FIP. Final diagnosis in all cases had been determined by the attending clinician; criteria used for diagnosis and results of antemortem or post-mortem diagnostic test results were not reviewed. Breed, sex, and reproductive status of all cats evaluated at the NCSU-CVM during the 16-year study period were reviewed; all cats of unknown breed were excluded. Mixed breed cats of all hair lengths (domestic shorthair, mediumhair and longhair) were considered a single breed (termed 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 for cat age at time of evaluation were calculated only for FIP-affected cats. Breed, sex, and reproductive status differences were compared using the Fisher s exact test; values of P less than or equal to 0.05 were considered significant. Odds ratios (OR) and 95% confidence intervals (CI) were also calculated for each variable. Results During the 16-year study period, 11,535 cats of known breed were examined at the NCSU-CVM. Cats examined included mixed breed cats (9511 cats) and 36 different purebreed varieties (2024 cats). Sixty cats (0.52%) had a final diagnosis of FIP; breed was known for all affected cats. Sex and reproductive status information was available for 57 of the 60 FIP cats and 11,303 of the 11,475 non-fip cats. Age information was available for 58 of the 60 FIP cats. Cats diagnosed with FIP included mixed breed cats (33 cats) and 13 different purebreeds (27 cats). Prevalence of FIP in the mixed breed cat population was 0.35% versus 1.3% in the purebreed cat population (Fig 1). Purebreed cats were significantly more likely to be diagnosed with FIP than were mixed breed cats (OR 4.5, CI 2.7e7.5; P! 0.001). Breeds with a prevalence of FIP significantly greater than mixed breed cats included the Abyssinian, Bengal, Birman, Himalayan, Ragdoll, and Rex (including Cornish and Devon varieties) breeds (Table 1, Fig 2). The prevalence of FIP in Burmese, Exotic Shorthair, Manx, Persian, Russian Blue, and Siamese cats was not significantly different from mixed breed cats. The two Havana Brown cats evaluated at the NCSU-VTH during the study period were both diagnosed with FIP, but this small number precluded statistical analysis. Twenty-three cat breeds had an FIP prevalence of zero. These included the Angora (11 cats evaluated during study period), Balinese (25 cats), Belgian (two cats), Bombay (four cats), British Blue (two cats), British Shorthair (three cats), Chartreux (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 Cat (five cats), Ocicat (16 cats), Ragamuffin (one cat), Scottish Fold (15 cats), Siberian (one cat), Snowshoe (two cats), Somali (three cats), Sphinx (one cat), Tonkinese (18 cats), and Turkish Van (two cats) breeds. Unfortunately, the low prevalence of FIP in the mixed breed cat population prevented determination of significance or relative risk in these purebreed cat varieties. Prevalence of FIP ( ) 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 All Cats Mixed Breed Cats Purebred Cats Fig 1. Prevalence of feline infectious peritonitis (FIP) in cats by cat group. *Statistically significant difference from mixed breed cats. *

Prevalence of FIP 3 Table 1. Prevalence, odds ratios, and confidence intervals for purebreed cats with feline infectious peritonitis (FIP) Breed a Cats diagnosed with FIP/total number cats seen (% affected with FIP) Odds ratio Confidence interval P-value (Fisher s exact test) Abyssinian 3/99 (3.0%) 8.98 2.71e29.77 0.006 Bengal 1/8 (12.5%) 41.03 4.91e342.85 0.028 Birman 4/18 (22.2%) 82.06 26.66e262.44!0.001 Burmese 1/37 (2.7%) 7.98 1.06e59.91 0.124 Exotic Shorthair 1/62 (1.6%) 4.71 0.63e34.98 0.199 Havana Brown 2/2 (100%) e b e b e b Himalayan 4/364 (1.1%) 3.19 1.12e9.06 0.046 Manx 1/67 (1.5%) 4.35 0.59e32.29 0.213 Persian 4/481 (0.5%) 2.41 0.85e6.83 0.101 Ragdoll 2/13 (15.3%) 52.22 11.14e244.79 0.001 Rex (Cornish and Devon) 2/17 (11.7%) 38.29 8.42e174.15 0.002 Russian Blue 1/39 (2.6%) 7.56 1.01e56.68 0.130 Siamese 1/536 (0.2%) 0.54 0.07e3.93 1.00 a Breeds with 0.0% prevalence of feline infectious peritonitis not listed. b Insufficient number of cats to allow statistical calculations. Cats with FIP were significantly more likely to be sexually intact when compared to the general cat population, regardless of whether the cats were male or female (intact male versus castrated male, P! 0.001; intact female versus spayed female, P Z 0.002; all intact cats versus all altered cats, P! 0.001; prevalence of intact cats in the general population was 15.8%, versus 45.6% in the FIP population). Although more cats with FIP were male than female, the difference in prevalence was not statistically significant (P Z 0.425; 53.6% of the total cat population was male, versus 59.6% of the FIP population). At the time of last evaluation the median age of cats with FIP was 0.96 years (25th percentile 0.5 years, 75th percentile 2.0 years). Sixty-seven percent of cats with FIP were less than 2 years of age. Discussion Although the increased prevalence of FIP in purebreed cats has been previously reported, this is the first time that a predisposition of specific breeds to the development of disease has been examined (Robison et al 1971, Rohrbach et al 2001). Our results show that certain breeds may in fact be more likely to develop FIP, particularly the Birman, Ragdoll, Bengal, Rex, Abyssinian, and Himalayan breeds. Other breeds of cats, the Burmese, Exotic Shorthair, Manx, Persian, Russian Blue, and Siamese, did not appear to be at increased risk as compared to mixed breed cats. Our results on the effects of sex, 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 an influence of host genetics on mutation of the feline enteric coronavirus or on susceptibility to FIP. Cheetahs, whose genome has become more homozygous with minimal allelic diversity due to an evolutionary bottleneck, have a very high prevalence of FIP (O Brien et al 1985). Similarly, the increased prevalence we found in some purebreed varieties could be due to a concentration of Prevalence of FIP ( ) 25 20 15 10 5 0 0.35 Mixed Breed 3.0 Abyssinian 12.5 Bengal 22.2 Birman 1.1 Himalayan 15.4 Ragdoll 11.8 Fig 2. Prevalence of feline infectious peritonitis (FIP) in mixed breed cats and in breeds with FIP prevalence significantly different (P! 0.05) from mixed breed cats. Rex

4 LD Pesteanu-Somogyi et al inherited factors through in-breeding or small founder populations. Given a common environment and viral strain, Foley and Pedersen (1995) calculated that slightly greater than 50% of FIP susceptibility in purebreed cats from six catteries could be attributed to inherited differences between individuals. Interestingly, in this study one of the catteries with numerous closely related FIP-affected cats was a Birman cattery (Foley and Pedersen 1995). Birmans were by far the most commonly affected in the study reported here, and therefore we may not be the first to provide evidence of an increase in susceptibility to FIP in this breed. Other investigators have questioned whether the increased prevalence of FIP in purebreed cats may actually be due to confounding factors. Purebreed cats are more likely to be raised in catteries, which may be inherently more stressful because of the multi-cat environment, regular introduction of new cats, and frequent breeding (Kass and Dent 1995, Pedersen 1995). Additionally, cattery cats presumptively have greater exposure to feline enteric coronavirus (a requirement for development of FIP) due to increased population density (Foley et al 1997a, 1997b, McReynolds and Macy 1997). Finally, the possible increased willingness of owners of expensive purebreed cats to pursue advanced diagnostics and supportive treatment at a referral veterinary facility such as the NCSU-VTH may skew the apparent prevalence of disease. However, these factors would be expected to falsely increase the prevalence of FIP in all purebreed cats and not just those breeds we report to be at increased risk of disease development. In this report we chose to include cases based on final diagnosis entered into our computerized medical database rather than by review of records and histopathology reports. As a result, we must acknowledge that future investigations that are limited to cases with confirmed diagnoses could yield different results. However, because the ante-mortem diagnosis of FIP at our tertiary care treatment hospital is expected to be similar to diagnostic algorithms proposed by other authors, we feel that our results, particularly in breeds with larger numbers or particularly strong associations with disease, are unlikely to conflict with future studies (Sparkes et al 1991, Rohrer et al 1993, Addie and Jarrett 1998). Multivariate analysis of the variables studied here would further define specific breed susceptibility to FIP. For example, it is unknown if the breeds with an increased prevalence of FIP actually had larger numbers of intact cats evaluated, thus influencing our calculations. Furthermore some breeds had very few individuals examined, and the large CI reflect the lack of precision in determining risk. We doubt that the absence of cats diagnosed with FIP in 23 breeds indicates an absolute resistance to disease, although it is possible that some of these breeds (such as Maine Coon cats, which were seen at the NCSU-VTH in relatively larger numbers) possess unrecognized protective factors that influence susceptibility. Unfortunately, because of the low prevalence of FIP in all cats a much larger population would need to be examined to determine if lack of disease in these breeds is statistically significant. The predisposition of certain breeds to the development of FIP demonstrated here warrants further research. Our results suggest that the index of suspicion for FIP should possibly be increased in some ill purebreed cats. A multicenter study that includes cases from primary as well as referral facilities with multivariate analysis is likely necessary to definitively answer the question of individual breed susceptibilities to FIP. Acknowledgements The authors thank Cavell Brownie, PhD (Department of Statistics, North Carolina State University) for performing the statistical analyses and Malcolm Roberts, BVSc, PhD, MPH, FRCVS, FACVSc (Department of Clinical Sciences, North Carolina State University) for manuscript review. References Addie DD, Jarrett O (1998) Feline coronavirus infection. In: Greene CE (ed), Infectious Diseases of the Dog and Cat (2nd edn). Philadelphia: WB Saunders, pp. 58e68. Foley JE, Pedersen NC (1995) The inheritance of susceptibility to feline infectious peritonitis in purebred catteries. Feline Practice 24, 14e22. Foley JE, Poland A, Carlson J, Pedersen NC (1997a) Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus. Journal of the American Veterinary Medical Association 210, 1313e1318. Foley JE, Poland A, Carlson J, Pedersen NC (1997b) Patterns of feline coronavirus infection and fecal shedding from cats in multiple-cat environments. Journal of the American Veterinary Medical Association 210, 1307e1312.

Prevalence of FIP 5 Hartmann K (2005) Feline infectious peritonitis. Veterinary Clinics of North America, Small Animal Practice 35, 39e79. Horzinek MC, Osterhaus ADME (1979) Feline infectious peritonitis: a worldwide serosurvey. American Journal of Veterinary Research 40, 1487e1492. Kass PH, Dent TH (1995) The epidemiology of feline infectious peritonitis in catteries. Feline Practice 23, 27e32. McReynolds C, Macy DM (1997) Feline infectious peritonitis. Part I. Etiology and diagnosis. Compendium of Continuing Education for the Practicing Veterinarian 19, 1007e1016. O Brien SJ, Roelke ME, Marker L, Newman A, Winkler CA, Meltzer D, Colly L, Evermann JF, Bush M, Wildt DE (1985) Genetic basis for species vulnerability in the cheetah. Science 227, 1428e1434. Pedersen N (1995) An overview of feline enteric coronavirus and infectious peritonitis virus infections. Feline Practice 23, 7e20. Robison RL, Holzworth J, Gilmore CE (1971) Naturally occurring feline infectious peritonitis: signs and clinical diagnosis. Journal of the American Veterinary Medical Association 158, 981e986. Rohrbach BW, Legendre AM, Baldwin CA, Lein DH, Reed WM, Wilson RB (2001) Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals. Journal of the American Veterinary Medical Association 218, 1111e1115. Rohrer C, Suter PF, Lutz H (1993) The diagnosis of feline infectious peritonitis (FIP): a retrospective and prospective study. Kleintierpraxis 38, 379e389. Scott FW (1991) Feline infectious peritonitis: transmission and epidemiology. In: Proceedings of the Symposium: New Perspectives On Prevention Of Feline Infectious Peritonitis, pp. 8e13. Sparkes AH, Gruffydd-Jones TJ, Harbour DA (1991) Feline infectious peritonitis: a review of clinicopathological changes in 65 cases, and a critical assessment of their diagnostic value. Veterinary Record 129, 209e212.