Академический Документы
Профессиональный Документы
Культура Документы
CREDITS CE Article
F
Affiliated Veterinary Specialists eline infectious peritonitis (FIP) is entering an animal shelter.6 Half of the
Maitland, Florida
caused by a mutated coronavirus cats that were originally FECV negative
and frequently results in death in were shedding FECV within 1 week of
cats. The difficulty of establishing the entering the shelter.6
diagnosis and the lack of effective treat-
ment options have frustrated veterinar- Pathogenesis
ians since FIP was identified more than FECV, which is highly contagious, is
At a Glance 40 years ago.1 Research is clarifying transmitted primarily via the fecal–oral
the complex pathogenesis of FIP. This route, although it may also be transmitted
Causative Agents review addresses the pathogenesis and by inhalation.1 It replicates in the epithe-
Page E1
clinical signs of FIP, as well as the cur- lial cells of the intestinal tract. Fecal shed-
Pathogenesis rent diagnostic tests and management ding begins within 2 days of infection,
Page E1
recommendations. and seroconversion occurs within 18 to 21
Signalment days after exposure to the virus.1 FECV
Page E2 Causative Agents replicates only in enterocytes. It can exist
Clinical Signs Feline coronavirus is a large, enveloped in the systemic circulation but cannot sus-
Page E2 RNA virus that exists in two forms: feline tain viral production there, so progression
Diagnostic Tests enteric coronavirus (FECV) and feline to FIP does not occur.7 However, if a cru-
Page E3 infectious peritonitis virus (FIPV). FECV cial deletion mutation (typically of the 3C
is virtually nonpathogenic, whereas FIPV or 7B gene) occurs, the virus can be taken
Treatment
Page E5
is almost invariably fatal.1 All FECV car- up by macrophages and gain access to the
riers have the potential to develop either systemic circulation, where it transforms
Prognosis enteritis or peritonitis, although only into the highly pathogenic FIPV.8 FIPV
Page E6
about 5% of infections develop into FIP.1 infection is sustained in monocytes and
Prevention Currently available diagnostic tests cannot macrophages, where the virus undergoes
Page E6
differentiate FECV from FIPV with 100% replication and spreads systemically.7
accuracy. Traditionally, FIP has been divided into
Multicat households have a much two distinct clinical forms: effusive (wet)
higher prevalence of FECV (75% to 100%) and noneffusive (dry). Approximately three
than single-cat households (25%).2–4 times as many cats present with the wet
Animal shelters and catteries facilitate the form as with the dry form.9 However,
transmission of FECV because of high these divisions are not absolute, as a com-
environmental stress and sharing of con- bination of both forms is often present in
taminated litterboxes.4,5 Increases of up to cats with FIP.10 The macrophage is the key
a millionfold in fecal shedding of FECV inflammatory cell in both forms of FIP.11
were seen in FECV-positive cats after Cats that are infected with FECV but do
a DNA copy (cDNA) is created in RT-PCR by ity (86%). However, false negatives and inad-
reverse-transcribing the mRNA. The cDNA is equate samples are common, yielding a very
then amplified using primers specific for the low diagnostic sensitivity (11% to 38%).52
highly conserved M gene so that large quanti- In many cases, lesions are observed only
ties of cDNA are available for identification of at necropsy. The classic lesions are pyogranu-
the virus.46 Of cats with confirmed FIP, 93% lomatous inflammation that has caused vascu-
tested positive with RT-PCR, and no false posi- litis, necrosis, and fibrosis.12 The wet form of
tives occurred in the study group.46 FIP affects a large number of blood vessels,
However, RT-PCR results may be incorrect. causing the typical effusion, and small plaques
False negatives can occur because of degra- form on the surfaces of abdominal and thoracic
dation by RNases, ubiquitous enzymes that organs. In the dry form, larger pyogranulomas
can easily contaminate a sample. Laboratory affect the kidneys, liver, eyes, and CNS.19,50
contamination and cross-reaction with other Solitary mural FIP lesions of the colon or ileo-
coronaviruses (e.g., canine coronavirus, trans- cecocolic junction may be grossly mistaken
missible gastroenteritis virus) can produce for neoplasia.26 Meningitis, ependymitis, and
false-positive results.1 hydrocephalus are seen in the neurologic form
Auburn University’s College of Veterinary of FIP.25,50 Lymphoid depletion is commonly
Medicine Molecular Diagnostics Laboratory observed in the spleen and lymph nodes of
is the only laboratory to offer the FIP mRNA
Multi Test. Samples of whole blood, effusion
cats that succumb to FIP.32 Lymphoid tissue is
hyperplastic in cats that survive infection.32
QuickNotes
fluid, and tissue/aspirate of an affected organ Immunofluorescent staining identifies the The macrophage
are submitted for RT-PCR testing. The PPV and coronavirus within macrophages in effusion is the key inflam-
NPV of this combined test are both reportedly fluid or tissue. This test is 100% specific but matory cell in the
close to 100%.47,a only 50% sensitive for FIP when performed
development of FIP.
on effusion samples.3,10 In other words, FECV
Cerebrospinal Fluid Analysis and Central should not be found in macrophages in effu-
Nervous System Imaging sion samples, so a positive result indicates that
Neurologic abnormalities are present in ap- the cat has FIP. Low numbers of macrophages
proximately 35% of cats with FIP.25,48 CSF with insufficient virus to create fluorescence
analysis may reveal an elevated protein con- can lead to a false-negative result.10 RT-PCR
tent or pleocytosis (lymphocytes and neutro- can also be performed on tissue that has not
phils).10,49,50 FIP should be strongly suspected been preserved in formalin.47
in a cat with inflammatory CNS disease and
hydrocephalus identified on magnetic reso- Treatment
nance imaging or computed tomography.25,48,51 No curative treatment exists for FIP. Therapy
is directed at suppressing the formation of
Histopathology immune complexes and thus trying to control
Histopathology is the gold standard for the the vasculitis that characterizes the disease.
diagnosis of FIP.3,12 Without histopathology, Supplemental therapies to increase the over-
any diagnosis of FIP is considered presump- all well-being of the cat, including fluids and
tive. However, cats with FIP are extremely nutritional support, should be provided.
debilitated, making exploratory surgery for If an owner or breeder chooses to test
biopsies risky and impractical. Fine-needle healthy cats, cats identified as FECV seroposi-
aspiration and Tru-Cut biopsy of the liver tive should not be subjected to stress because
and kidneys have been evaluated as diagnos- the onset of clinical signs is frequently seen
tic tests for FIP. Lesions consistent with FIP after events such as elective surgery or intro-
can be identified using these techniques, and duction to a new home.1 Avoiding stress in
combining fine-needle aspiration and Tru-Cut group-housing situations is especially impor-
biopsy of the liver has the highest sensitiv- tant. Cats with diarrhea suspected to be due
aMore
to FECV should be managed with supportive
information about this test, including pric-
care to maintain hydration, weight, and intes-
ing and shipping methods, may be obtained at the
Auburn University College of Veterinary Medicine tinal bacterial balance.1
Web site (www.vetmed.auburn.edu). Because the immune system of cats with FIP
starting at 16 weeks of age. The American ease, which should eventually lead to more
Association of Feline Practitioners lists the FIP effective methods of prevention and cure.
vaccine as “not generally recommended.”63 The recent development of RT-PCR testing QuickNotes
is providing encouraging results for possible
Conclusion antemortem diagnosis of FIP, although the Minimizing expo-
FIP is a devastating disseminated vasculitis laboratory providing this test has not pub- sure is the best
in cats that results from a complex interac- lished any information regarding its validation method for preven-
tion between a mutated FECV and the feline methods. Current treatments are crude at best tion of infection.
immune system. The virus is highly con- and involve supportive care and, sometimes,
tagious, so the disease is more common in blanket suppression of the host’s humoral and
multicat households and in purebred cats in cell-mediated immune responses. Minimizing
catteries. Researchers are continuing to eluci- exposure is the best method for prevention of
date the complex pathophysiology of the dis- infection.
References
1. Addie DD, Jarrett O. Feline coronavirus infections. In: Green CE, 19. Gunn-Moore DA, Caney SMA, Gruffydd-Jones TJ. Antibody and
ed. Infectious Diseases of the Dog and Cat. 3rd ed. St. Louis: Saun- cytokine responses in kittens during the development of FIP. Vet
ders Elsevier; 2006:88-102. Immunol Immunopathol 1998;65:221-242.
2. Barr MC. FIV, FeLV, and FIPV. Interpretation and misinterpreta- 20. Munson L, Marker L, Dubovi E, et al. Serosurvey of viral infections
tion of serological test results. Semin Vet Med Surg (Small Anim) in free-ranging Namibian cheetahs. J Wildl Dis 2004;40(1):23-31.
1996;11(3):144-153. 21. Pesteanu-Somogyi LD, Radzai C, Pressler BM. Prevalence of
3. Hartmann K, Binder C, Hirschberger J, et al. Comparison of dif- feline infectious peritonitis in specific cat breeds. J Feline Med Surg
ferent tests to diagnose FIP. J Vet Intern Med 2003;17:781-790. 2006;8:1-5.
4. Addie DD. Clustering of feline coronaviruses in multicat house- 22. Holst BS, Englund L, Palacios S, et al. Prevalence of antibodies
holds. Vet J 2000;159:8-9. against feline coronavirus and Chlamydophila felis in Swedish cats.
5. Addie DD, Dennis JM, Toth S, et al. Long-term impact on a J Feline Med Surg 2006;8:207-211.
closed household of pet cats of natural infection with feline corona- 23. Foley JE, Pedersen NC. The inheritance of susceptibility to
virus, feline leukemia virus, and feline immunodeficiency virus. Vet feline infectious peritonitis in purebred catteries. Feline Pract
Rec 2000;146:419-424. 1996;24(1):14-22.
6. Pedersen NC, Sato R, Foley JE, et al. Common virus infections 24. Colitz CMH. Feline uveitis: diagnosis and treatment. Clin Tech
in cats, before and after being placed in shelters, with emphasis on Small Anim Pract 2005;20(2):117-120.
FECV. J Feline Med Surg 2004;6:83-88. 25. Foley JE, Lapointe JM, Koblik P, et al. Diagnostic features of
7. Dewerchin HL, Cornelissen E, Nauwynck HJ. Replication of clinical neurologic FIP. J Vet Intern Med 1998;12:415-423.
feline coronaviruses in peripheral blood monocytes. Arch Virol 26. Harvey CJ, Lopez JW, Hendrick MJ. An uncommon intestinal
2005;150:2483-2500. manifestation of FIP. JAVMA 1996;209(6):1117-1120.
8. Vennema H, Poland A, Foley J, et al. Feline infectious peritonitis 27. Kipar A, Koehler K, Bellmann S, et al. FIP presenting as a tu-
viruses arise by mutation from endemic feline enteric coronavirus- mour in the abdominal cavity. Vet Rec 1999;144:118-122.
es. Virology 1998;243:150-157. 28. Siguroardottir OG, Kolbjornsen O, Lutz H. Orchitis in a cat asso-
9. Rohrbach BW, Legendre AM, Baldwin CA, et al. Epidemiology ciated with coronavirus infection. J Comp Path 2001;124:219-222.
of feline infectious peritonitis among cats examined at veterinary 29. Cannon MJ, Silkstone MA, Kipar AM. Cutaneous lesions associ-
medical teaching hospitals. JAVMA 2001;218(7):1111-1115. ated with coronavirus-induced vasculitis in a cat with FIP and con-
10. Hartmann K. Feline infectious peritonitis. Vet Clin North Am current FIV infection. J Feline Med Surg 2005;7:233-236.
Small Anim Pract 2005;35:39-79. 30. Macdonald ES, Norris CR, Berghaus RB, et al. Clinicopathologic
11. Berg AL, Ekman K, Belak S, et al. Cellular composition and and radiographic features and etiologic agents in cats with histolog-
interferon-γ expression of the local inflammatory response in FIP. ically confirmed infectious pneumonia. JAVMA 2003;223(8):1142-
Vet Microbiol 2005;111:15-23. 1150.
12. McReynolds C, Macy D. Feline infectious peritonitis. Part I. Eti- 31. Kipar A, Bellmann S, Gunn-Moore DA, et al. Histopathological
ology and diagnosis. Compend Contin Educ Pract Vet 1987;19(9): alterations of lymphatic tissues in cats without FIP after long-term
1007-1016. exposure to FIP virus. Vet Microbiol 1999;69:131-137.
13. Dewerchin HL, Cornelissen E, Nauwynck HJ. FIPV-infected 32. Kipar A, Kohler K, Leukert W, et al. A comparison of lymphatic
monocytes internalize viral membrane-bound proteins upon anti- tissues from cats with spontaneous FIP, cats with FIPV infections
body addition. J Gen Virol 2006;87:1685-1690. but no FIP, and cats with no infection. J Comp Pathol 2001;125:182-
14. Cornelissen E, Dewerchin HL, Van Hamme E, et al. Absence of 191.
surface expression of FIPV antigens on infected cells isolated from 33. Kohn B, Linden T, Leibold W. Platelet-bound antibodies detect-
cats with FIP. Vet Microbiol 2007;121:131-137. ed by a flow cytometric assay in cats with thrombocytopenia. J
15. Kiss I, Poland AM, Pedersen NC. Disease outcome and cytokine Feline Med Surg 2006;8:254-260.
responses in cats immunized with an avirulent FIPV and challenge- 34. Paltrinieri S, Cammarata MP, Cammarata G, et al. Some aspects
exposed with virulent FIPV. J Feline Med Surg 2004;6:89-97. of humoral and cellular immunity in naturally occurring FIP. Vet Im-
16. Gelain ME, Meli M, Paltrinieri S. Whole blood cytokine profiles munol Immunopathol 1998;65:205-220.
in cats infected by FCoV and healthy non-FCoV infected SPF cats. J 35. Paltrinieri S, Grieco V, Comazzi S, et al. Laboratory profiles in
Feline Med Surg 2006;8:389-399. cats with different pathological and immunohistochemical findings
17. Takano T, Hohdatsu T, Hashida Y, et al. A “possible” involve- due to FIP. J Feline Med Surg 2001;3:149-159.
ment of TNFα in apoptosis induction in peripheral blood lympho- 36. Peterson JL, Couto CG, Wellman ML. Hemostatic disorders in
cytes of cats with FIP. Vet Microbiol 2007;119:121-131. cats: a retrospective study and review of the literature. J Vet Intern
18. Dean GA, Olivry T, Stanton C, et al. In vivo cytokine response to Med 1995;9(5):298-303.
experimental FIPV infection. Vet Microbiol 2003;97:1-12. 37. Bence LM, Addie DD, Eckersall PD. An immunoturbidimet-
3 CE
CREDITS This article qualifies for 3 contact hours of continuing education credit from the Auburn University College of Veterinary Medicine. Subscrib-
ers may take individual CE tests online and get real-time scores at CompendiumVet.com. Those who wish to apply this credit to fulfill
state relicensure requirements should consult their respective state authorities regarding the applicability of this program.
1. Which is the key inflammatory cell in b. mass lesion in the cerebral cortex c. They may be falsely negative in cats
the development of FIP? c. no visible abnormalities with effusive FIP.
a. T cell d. cerebral edema d. all of the above
b. neutrophil
c. macrophage 5. What A:G ratio in effusion fluid is sug- 8. Why are indoor cats more at risk for
d. eosinophil gestive of FIP? developing FIP than outdoor cats?
a. <0.5 a. population density
2. Which breed of cat has a genetic sus- b. 0.6 to 0.8 b. environmental stress
ceptibility for the development of FIP? c. 0.8 to 1.0 c. shared litterboxes
a. Persian d. >1.0 d. all of the above
b. Manx
c. Siamese 6. What histologic lesion is not suggestive 9. What nondomestic feline is most sus-
d. Ragdoll of FIP? ceptible to FIP?
a. perivascular inflammation a. lion
3. What percentage of cats exposed to b. hepatic nodular regeneration b. tiger
FECV develop clinical FIP? c. tissue necrosis c. cheetah
a. <10% d. lymphoid depletion d. cougar
b. 20% to 30%
c. 50% to 60% 7. Why should anticoronavirus titers not be 10. What type of immune response pro-
d. 90% to 100% used to definitively diagnose FIP? duces dry FIP?
a. They cannot distinguish between FIPV a. strong humoral response
4. What finding on brain magnetic reso- and FECV. b. strong cell-mediated response
nance imaging is suggestive of FIP? b. Laboratory reporting of titers is c. partial cell-mediated response
a. hydrocephalus inconsistent. d. INF-γ