FIP Webinar
FIP Webinar
Why?
Fecal- al T a i i f FC V
Fecal-oral Transmission of FCoV
How?
(a) Beberapa kucing yang terinfeksi akan
menjadi long-term persistent atau
intermittent shedders ketika sel epitel
kolumnar di colon mengandung infeksi
FCoV yang persisten
How?
macrophages and scattered neutrophils and lymphocytes edersen, cause abdominal swelling Sometimes uveitis and neurological
How?
• Host immune response terhadap infeksi
FCoV adalah salah satu penentu
keparahan penyakit FIP yang
ditimbulkan
• Kucing yang terinfeksi low-virulent
FCoV dengan strong cell-mediated
immunity (CMI) response: tidak
berkembang menjadi FIP-associated
FCoV.
• Kucing dengan poor CMI response:
develop FIP-associated FCoV dengan
efusi
• Kucing dengan partial CMI response:
develop FIP-associated FCoV tanpa
efusi
• Namun, seiring perkembangan
penyakit, efusi dapat terjadi pada
kucing dengan primary FIP-associated
FCoV tanpa efusi dan sebaliknya.
Clinical sign & lesions
01 02 03
Infeksi FCoV biasanya Pada kucing dengan FCoV Efusi:
bersifat subklinis, yang baru mulai • Ascites
• efusi thorax
walaupun ada beberapa berkembang menjadi FIP • efusi pericardium
kucing (terutama kitten) biasanya akan muncul • Sebagian kecil pasien
yang menunjukan gejala fluctuating fever, weight mix ascites dengan
diare (usually self limiting) loss, anoreksia, & lethargy efusi thorax
04 05 06
Lesi granulomatous di Ocular: uveitis and/or Lesi di Central Nervous
organ abdomen maupun chorioretinitis terlihat sebagai System yang disebabkan
granulomatous “mutton-fat” encephalitis and/or myelitis,
thorax: biasanya multifocal & slow
• Renomegaly keratic precipitates, fibrin di progress: ataxia,
• Chronic diarrhea anterior chamber, aqueous flare hyperaesthesia, nystagmus,
• Lymph node enlargement tebal, retinal perivascular cuffing seizure, paralysis dll
The many faces of FIP
Non-specific manifestations
faces of
unthriftiness is a frequent complaint
in a kitten or young cat with FIP.
This kitten eventually developed
seizures from neurological FIP.
Courtesy of Julie Jacobs
FIP:
Neurological manifestations
Neurological manifestations
Many
faces of
FIP: Figure 6 Cortical blindness in a male Bengal
manifesting as bilateral dilated pupils. Courtesy of
Glenn Olah
Figure 7 Five-
year-old male
castrated
domestic
shorthair cat with
non-effusive FIP
presenting as
a progressive
weight loss,
anemia and
Figure 5 (a) Female spayed Persian development of
showing depression, weakness and blindness. The
tremors (see supplemental video 10, cat was PCR
which shows this patient’s neurological positive on FNAs
signs). (b) Same cat with progression of kidney, liver,
of neurological signs to decreased spleen and MLNs.
consciousness, weakness and focal b Courtesy of
seizures. Images courtesy of Tammy Evans Matthew Kornya
Many
faces of Figure 8 Oriental a b
Shorthair with anterior
uveitis, and corneal Figure 10 (a,b) Two cats demonstrating subtle differences in the clinical
Many
8-year-old male
neutered domestic
shorthair cat with
significant dermal
vasculitis and
faces of
neutrophilic splenitis
a b that later developed
effusion and was
Figure 8 Oriental diagnosed with FIP. Cats
Figure
Shorthair with10 (a,b) Two cats demonstrating subtle differences in the clinical
anterior
with skin changes can
uveitis, and corneal of anterior uveitis caused by FIP: iris color changes, haziness
presentation
FIP:
edemaindue be difficult-to-diagnose
thetoanterior chamber (hypopyon or hyphema) and lesion(s) (keratic FIP cases. These images
development of
precipitates) in the cornea. The young cat in (b) has additional evidence of show the initial (a) and
glaucoma. Courtesy
of Lisairregular
Callaway pupils, which can occur with anterior uveitis caused by FIP. Repeated later (b) presentation of
ophthalmoscopic examinations are indicated in difficult-to-diagnose FIP cases. the vasculitis. Courtesy
a
Images courtesy of Marybeth Rymer (a) and Haley Batemen (b) of Matthew Kornya
Figure 12 (a,b) Cat
with abdominal a
a effusion (ascites)
b
presenting with
abdominal distension,
weight loss and
decreased muscle
mass. This patient
Figure 9 Weight loss is shown in
and progression of supplemental video
neurological signs 11. Images courtesy of
accompaniedathe Stephanie Newton Figure 11 (a) Uveitis
presence of and leakage of fibrin
anisocoria in this into the anterior
12-year-old male chamber of the eye.
neutered domestic (b) Rubeosis iridis
shorthair cat.
b and a clump of fibrin.
Courtesy of Glenn Olah
Images courtesy of b
Jessica Meekins
Dermatological manifestations
Diagnosing
FIP
What is the challenge?
Laboratory work up Spesifik
Clinical Diagnostic Testing
presentation • Walaupun ada beberapa • Deteksi antigen virus pada
• Pasien dengan efusi hasil laboratorium yang khas makrofag yang terdapat di
dan dengan untuk pasien FIP (seperti jaringan yg terifeksi dengan
signalement yang ratio a/g, hyperbilirubinemia, metode IHC
tipical FIP anemia non regenerative) (immunohistochemistry)
mempermudah namun tidak pathognomonic menjadi gold standard
peneguhan diagnosa. hanya untuk kasus FIP. diagnosis
• Namun jika pasien • Beberapa kasus disertai • Deteksi RNA virus dengan
tanpa efusi peneguhan dengan penyakit lain yang metode Real Time RT-PCR
diagnosa akan lebih membuat hasil darah menjadi (RT-qPCR) memiliki nilai
sulit mengingat gejala bias. diagnostic yang baik.
klinis FIP bervariasi dan • Keduanya belum available
non spesifik di Indonesia
Da cW - FIP ‘B c b B c ’
k - u p
t ic Wor
n o s
ia g r F IP ’
D fo ric k
b y B
c k
‘Bri
History &
Risk factor Examples/comments
n-fold in some
elter.36 Origin < From environment with high FCoV load
nce of FCoV in Background < FIP diagnosed in the same litter/family lineage9
ority is to pre- < Immunosuppressive therapy9
Signalement:
s the potential < Adoption or acquisition from a cattery, shelter, rescue
nerable kittens or rehoming center62,63
< Recent stressful event:17,26,54,55,62,64,65
by identifying – Surgery (spay, neuter or other)
To detect FCoV – Vaccination
ach cat should – Gastrointestinal disease
hree fecal RT- – Upper respiratory tract disease ” Susceptibility to FIP in a cat involves the
– Travel, boarding, attending cat shows
ls of 1 week to – New household member (eg, new baby or pet), moving house interplay between virus virulence factors,
Signalment < Age at exposure to FCoV (less-virulent biotype): <2 years
host factors (eg, genetic characteristics,
th less-virulent
do not require old66–69 age), concurrent diseases and/or other
< Sex: intact (male) cats3,4,5,70,71
gastrointestinal < Breed: certain purebred cats (eg, Bengals, Birmans;3,68 stressors at the time of FCoV infection ”
or diarrhea).46,49 see supplemental file 7)
lly self-limiting Health status < Coinfection (eg, FIV, FeLV) or concurrent disease9,23,72
ever, in a small < Immunosuppression9
st for weeks to
Housing < Multi-cat household45,48
ooking at feline conditions < Frequent introductions and reintroductions to new cats73–75
ter cats found < Variable lengths of stay in multi-cat environments76
ut of 12 enteric < Mingling of different age groups77
< Overcrowding (>5 cats)63
s significantly
iarrhea than in
ectively).51
Given that FIP different cats with FIP in the same household
show mostly unique genetic characteristics,
Physical Examination
• Given that the clinical presentation of FIP is so highly variable, a comprehensive physical examination is
essential.
• Demam menjadi gejala non specific yang paling awal terdeteksi pada kasus FIP. Pemeriksaan suhu badan
pasien saat visit rutin dilakukan “cat friendly manner”: contohnya dengan menggunakan ear thermometer
(termometer rectal digunakan untuk konfimasi jika ada demam)
Table 3 Potential differential diagnoses for FIP85,120
FIP sangat luas dan Toxoplasmosis Less commonly seen than FIP in cats. Can involve multiple organs and cause signs such as gastrointestinal
(diarrhea), ocular, pancreatic, liver and neurological disease. Diagnosis is obtained by finding tachyzoites in
bervariasi, RU diagnosa samples, or by demonstration of antibodies with high immunoglobulin (Ig)M or rising IgG titers
Pancreatitis Cats with pancreatitis can exhibit anorexia, jaundice, fever and weight loss. Abdominal effusion can be present
banding menjadi bagian as a non-septic exudate, often with a high cell count of non-degenerate neutrophils. Abdominal ultrasound
and/or measurement of feline pancreatic lipase immunoreactivity can detect pancreatitis
penting dalam proses
Lymphocytic cholangitis Generally this is more chronic in nature than FIP. Liver enzymes (such as alkaline phosphatase [ALP] and alanine
mendiagnosa. aminotransferase [ALT]) are more likely elevated. Jaundice/hyperbilirubinemia can be present. Lymphocytic
cholangitis can be associated with inflammatory bowel disease and/or pancreatitis. Aspirates of bile or liver
and/or histopathology of liver tissue samples can be diagnostic
Saat FIP menjadi diagnosa Congestive heart failure Can lead to effusion, most commonly a modified transudate. Cats with congestive heart failure do not typically
have a fever. Heart murmur and/or gallop rhythm can be present. Cytology shows a very low cell count.
banding dari suatu kasus, Echocardiography can confirm the diagnosis
beberapa pemeriksaan Mycobacteriosis Fever, lymphadenopathy, respiratory signs, abdominal masses and uveitis can occur with Mycobacteria species
infections. Mycobacterial cases do not usually present with severe hyperglobulinemia or a reduced A:G ratio, as
rutin yang bisa dilakukan: seen with FIP. Cytology can demonstrate (acid-fast) bacteria in tissue samples. PCR and culture can be diagnostic
hematologi, serum Trauma Effusions caused by trauma are usually hemorrhagic and can be differentiated from FIP effusions by cytological analysis
biochemistry, urinalysis
914
dan test FIV/FeLV
Differential
JFMS CLINICAL PRACTICE
diagnoses
ed as supplemental file 12; the veterinarian nosed with FIP.
was concerned about FIP, until cytology
confirmed Mycobacteria species.
Diagnostic
A good understanding of each
various diagnostic tests for FIP121,122
diagnostic test’s sensitivity, speci-
ficity, predictive value, likelihood Sensitivity Test’s ability to recognize cats with FIP
ratio (LR) and diagnostic accuracy
Testing
is important when diagnosing FIP;
these are common statistical terms Specificity Test’s ability to recognize cats without FIP
used to describe how accurately a
diagnostic test can determine
Likelihood ratio (With FIP)/(Do not have FIP)
whether a cat has FIP (see box). (LR) or expected test Not influenced by disease prevalence
Sensitivity, specificity and LRs are result in cats Good diagnostic tests have LR+ >10 or LR– <0.1
not influenced by the prevalence of
disease in the test
Pemahaman terhadap diagnostic studied population,
yang akan (True positives + True negatives)/
while positive (PPVs) and negative Overall test accuracy
Total number of test results
dilakukan (meliputi sensitity, specivity,
predictive predictive
values (NPVs) are influ-
121
enced
value, likehood ratio (LR) dan byakurasi)
prevalence.sangat
PPVs will Positive predictive Probability cat with positive test result has FIP
be higher when the prevalence of value (PPV) based on disease prevalence in population examined
penting dalam mendiagnosadisease FIP.
is high and lower when
prevalence is low,123 and predictive Negative predictive Probability cat with negative test result does not have FIP
values should not be applied to dif- value (NPV) based on disease prevalence in population examined
In highly fatal disease such as FIP, the specifity
ferent populations of cats unless it
of the diagnostic test is more important than the
test sensitivity since it will help prevent
Table 3
euthanasia of cats misdiagnosed Potential
with FIP.differential diagnoses for FIP85,120
tein tH e l p f u l t i p s
e if
ou- How to perform the Rivalta’s test*
ion
atio < Mix 8 ml of distilled water at room temperature and 20 µl (1 drop)
the of 100% acetic acid in a plastic test tube (volume 10 ml).
550 < Carefully layer 20 µl (1 drop) of the effusion on the surface of this solution.
y of < Observe the behavior of this drop:
on- – A positive test is indicated by the drop precipitating and either staying
Effusion analysis
olo- attached to the surface of the solution, retaining its shape with a
cell connection to the surface, or floating slowly to the bottom of the tube
vity, as a drop or jellyfish-like.
lse- – A negative test is indicated by the drop dissipating (disappearing)
cus- and the solution remaining clear.
F g e 1: F e f e AFAST f d c g e a ca e a ge ga .A
e a e ega e f f ee f d a b f- e ab a e .T e de
a a d be g f 1 g 4. T e e a - e a 5 b e a d e f c ed ee
e ae . T e ca e e a eda ed a d a ed f a a e ec a d
g a ed f d dac c e ; eda a d a gae ef ed a e .
CC, C -C c; DH, D a ag a c -He a c; HRU, He a -Re a U b ca ; SR, S e -
Re a .
Diagnostic Imaging
How to Perform TFAST - Its 5 Acoustic Windows
In cases where there is not obvious
respiratory distress, but fluid is still
suspected, thoracic-focused
assessment with sonography for trauma,
triage, and tracking (TFAST) should be
performed, since like with
abdominal effusions, ultrasound is more
likely to be able to detect small amounts
of fluid
Histopathology
later studies also been positive in cats without FIP.
indicate the
Different types of FCoV RT-PCR tests are available, based on test design
< RT-PCR – conventional and semiquantitative. presence
< Real-time RT-PCR (also referred to as RT-qPCR) – quantitative and diagnostically more accurate than A positive
of FCoV, and
RT-PCR.*† RT-qPCR
< RT nPCR – two-step PCR reaction that first amplifies larger segment in cDNA; product is purified and not specifically
then smaller segment is amplified. This assay is used only if there is an issue with sensitivity/specificity
result
with the RT-qPCR, and it is not very useful diagnostically if the first-round cDNA needs to be purified.
the mutated
with high viral
< 7b-RT-qPCR – this RT-qPCR was developed to quantify the level of FIPV through specific targeting virusload
that moves
leads
of the 7b accessory gene. Typically, it is run first to verify FCoV presence and then followed by another
RT-qPCR to detect mutations. to FIP
FIP up. the list
< Real-time RT-PCR for M gene.† of differential
< Real-time RT-PCR detecting S gene mutations using specific hydrolysis probes.†
< Real-time RT-PCR followed by sanger sequencing for S gene mutations – more specific for detection
diagnoses.
of S gene mutations than special real-time RT-PCR detecting S gene mutations using specific primers.
• RT-PCR & Realtime RT-PCR yang tersedia saat ini belum bisa membedakan antara mutated
and after
sequencing non mutated form FCoV
real-time RT-PCR. 60,79,153
For < FCoV RT-qPCR–/spike mutant RT-qPCR+
the •mutation-specific
Di IndonesiaRT-qPCRs,
baru tersedia RT-PCR
these typical- A positive (eg, something is wrong with the assay).
ly will be combined into one assay, referred to In a recent study, FCoV containing S gene
as multiplexed, for interpretation of results. RT-qPCR result mutations was found in at least one body
The assay will involve one PCR amplicon set fluid or tissue in all cats with FIP, but the
targeting a conserved region that will detect
all FCoV species, and a second set where one
Detection of Viral Nucleic Acid
with high viral
load moves
distribution varied from cat to cat, hence a
recommendation that multiple samples be
of the primers (forward or reverse) is specific analyzed to increase sensitivity.58 The speci-
at the 3 end for the mutation being looked for, FIP up the list ficity of detection of S gene mutations for FIP
• Antigen FCoV dapat dideteksi dengan pewarnaan antigen dalam sel targetnya, cairan atau makrofag
jaringan, menggunakan metode pewarnaan untuk mewarnai antigen.
• Pengikatan antibodi dengan antigen host cell-associated FCoV kemudian divisualisasikan (oleh IHC, ICC
atau imunofluoresensi [IF]), menghasilkan warna perubahan atau fluoresensi.
Modified from: Barker E & Tasker S. (2020). Advances in Molecular Diagnostics and Treatment of Feline Infectious Peritonitis. Advances
ABCD TOOL Clinical examination NOTE: - slightly less likely + slightly more likely History
Fever (typically <40 C) +++
o
The + & - symbols indicate how likely or unlikely -- moderately less likely ++ moderately more likely Weight loss/failure to thrive /stunted growth +++
Mucous membranes: --- far less likely +++ far more likely Swollen abdomen ++++
Icterus/jaundice ++
factors listed are to make a diagnosis of FIP ---- extremely unlikely ++++ extremely likely Persistent/fluctuating fever non-responsive to antibiotics +++
Pallor + Lethargy/dullness ++
Abdominal palpation: Signalment Inappetence ++
Fluid thrill due to ascites ++++
Irregular organomegaly (e.g. kidneys, lymph nodes) +++
Signalment & history <2 years ++++
>5 years –
Dyspnoea ++
Vision or ocular abnormalities incl. iris colour change &/or
Masses (e.g. abdominal lymph nodes, intestinal) ++ nystagmus ++
Male +
Auscultation: Pedigree + (breeds vary geographically) Jaundiced mucous membranes ++
Absence or dullness of heart sounds ++ Dietary history compatible with thiamine Ataxia/paresis (para- or tetra-), hyperaesthesia, seizures ++
Heart murmur / arrhythmia – deficiency – Sibling (or in-contact) with FIP ++
Absence of lung sounds ++ Multi-cat household +++
Increased lung sounds with crackles – Serum biochemistry Pale mucous membranes +
Percussion of chest dull ventrally ++
Tachypnoea or dyspnoea ++
Clinical examination Hyperbilirubinaemia +++
Diarrhoea, vomiting &/or constipation +
Recent stress (e.g. vaccination, rehoming, neutering) ++
including looking for any evidence of an effusion Hyperglobulinaemia +++
Otoscopic examination : Outdoor only/feral cat – –
Hyperproteinaemia (or total solids) ++ History of fighting –
Evidence of ear disease (e.g. polyps, otitis externa /media) –
Hypoalbuminaemia +
Ocular examination (unilateral or bilateral changes):
Albumin to globulin [A:G] ratio
Change in iris colour ++++
Dyscoria/anisocoria +++
A:G ratio < 0.4 + Analyse any effusion
A:G ratio > 0.6 – Typically, high protein low cell count effusions in
Hyphaema ++
Alpha1-acid glycoprotein, if available: abdomen ± thorax ± pericardium
Aqueous or vitreous flare ++
Other signs of uveitis ++ Y
Serum biochemistry >1. 5 g/L ++
>3.0 g/L +++
Biochemistry:
Perivascular cuffing of retinal vessels ++ High protein (or total solids) >35 g/L ++++
<1. 5 g/L – Low protein (or total solids) < 25 g/L – –
Nystagmus ++
Serum protein electrophoresis, if performed: A:G ratio < 0.4 ++
Retinal detachment +
Polyclonal gammopathy + A:G ratio > 0.8 –
Neurological examination:
Marked elevation in ALT & ALP – Yellow ++++ Effusion cytology &
Ataxia +++
Only mild or moderate elevation in ALT & Rivalta’s test positive ++ biochemistry
Seizures +++
ALP with hyperbilirubinaemia + Rivalta’s test negative – – – consistent with FIP?
Mental state or behaviour changes +++
FCoV antibody test with high titre + Cell count: Go to diagram
Head tilt ++
Priapism ++
Scrotal enlargement ++
Locate & analyse effusion FCoV antibody test negative – Low cell count <5 x10 /L ++++
9
Adapted from: Felten S & Hartmann K. (2019). Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature. Viruses 11(11)
consistent with FIP nonspecific clinical signs: perform diagnostic imaging*
Findings that could be consistent with FIP:
Ultrasonography: abnormalities e.g. in lymph nodes (abdominal lymphadenopathy), liver, spleen (variable echogenicity), kidney (variable
Effusion sample analysis: echogenicity, medullary rim sign)
FCoV RT-PCR &/or immunocytochemistry for FCoV antigen Radiography: abnormalities e.g. lymphadenopathy, alveolar pattern consistent with pneumonia
*
Histopathology Histopathology not positive immunocytochemistry Histopathology
Note for IIa & IIb: consistent with FIP & consistent with FIP & In absence of any obvious for FCoV antigen with cytology consistent with FIP &
If you are submitting fluid or cytology immunohistochemistry negative localising signs or consistent for FIP immunohistochemistry
samples for FCoV antigen positive for FCoV immunohistochemistry abnormalities that allow positive for FCoV
immunostaining, it is wise to contact the antigen sampling, ultrasonography
laboratory first to ask for preferred indicated to evaluate antigen
samples &/or preparation methods. abdominal & thoracic organs
for any abnormalities & to
Confirms FIP FIP very unlikely direct sampling of tissue. FIP very likely2 Confirms FIP
1.Some authors regard a positive immunocytochemistry test for FCoV antigen on an 2.Some authors regard a positive immunocytochemistry test for FCoV antigen on an FNA sample
effusion (with biochemistry & cytology consistent with FIP) adequate to confirm FIP (with cytology consistent with FIP) adequate to confirm a diagnosis of FIP
FIP: diagnostic approach IIb
Looking for evidence that confirms FIP as a diagnosis following a high suspicion:
ABCD TOOL 3 4
Adapted from: Felten S & Hartmann K. (2019). Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature. Viruses 11(11)
Neurological findings consistent with FIP* Aqueous humor cytology consistent with FIP*
MRI: Obstructive hydrocephalus, syringomyelia, foramen magnum herniation, marked contrast enhancement of the meninges, (neutrophilic or pyogranulomatous)
third ventricle, mesencephalic aqueduct & brainstem reported with FIP
CT: hydrocephalus &/or syringohydromyelia
CSF: high protein (>0.3 g/L cisternal samples, >0.46 g/L lumbar samples), Aqueous humor sample analysis:
high cell count (>0.008 x 109/L cisternal or lumbar samples),
cytology predominantly neutrophilic, mononuclear, mixed or pyogranulomatous FCoV RT-PCR &/or immunocytochemistry for FCoV antigen
either positive negative
CSF sample analysis: FCoV RT-PCR &/or immunocytochemistry for FCoV antigen
Positive FCoV RT-PCR FIP unlikely
either positive negative with high FCoV RNA loads
&/or
Positive FCoV RT-PCR FIP unlikely positive If still suspicious of FIP, continue monitoring for non-
with high FCoV RNA loads immunocytochemistry ocular changes as abnormalities can develop over
&/or for FCoV antigen time, which can then be sampled for diagnosis by either
positive If still suspicious of FIP, continue monitoring for non- FNA, trucut or full biopsy
immunocytochemistry neurological changes as abnormalities can develop (cytology, immunocytochemistry for FCoV antigen, RT-PCR, histopathology,
immunohistopathology for FCoV antigen).
for FCoV antigen over time, which can then be sampled for diagnosis by If enucleation is performed due to severe
either FNA, trucut or full biopsy uveitis/glaucoma, eye can be submitted for
(cytology, immunocytochemistry for FCoV antigen, RT-PCR, histopathology,
immunohistochemistry for FCoV antigen) histopathology & immunohistochemistry
not consistent, FIP very likely2 not consistent,
negative negative
FIP very likely1 Positive FCoV RT-PCR Positive FCoV RT-PCR
with high FCoV RNA loads FIP very unlikely
* with high FCoV RNA loads FIP very unlikely
*
&/or In absence of any non- &/or
In absence of any non-neurological positive ophthalmological signs or positive
abnormalities that allow immunocytochemistry
signs or abnormalities that allow immunocytochemistry Histopathology sampling of alternative Histopathology
sampling of alternative sites, advanced for FCoV antigen with consistent with FIP & for FCoV antigen with
sites, collection of an consistent with FIP &
imaging via CT, or preferably MRI, is cytology consistent for FIP immunohistochemistry aqueous humour sample cytology consistent for FIP immunohistochemistry
indicated. Imaging allows for evaluation for
neurological system abnormalities & to positive for FCoV may be indicated. positive for FCoV
assess for any potential risk of herniation if antigen Referral may be indicated for this antigen
subsequent CSF collection is planned. procedure if veterinarian is
unfamiliar with ophthalmological
Referral may be needed for these procedures if
investigations.
vet is unfamiliar with neurological investigations. FIP very likely1 Confirms FIP FIP very likely2 Confirms FIP
1.Some authors regard a positive immunocytochemistry test for FCoV antigen on a CSF sample 2.Some authors regard a positive immunocytochemistry test for FCoV antigen on an aqueous
(with biochemistry & cytology consistent with FIP) adequate to confirm a diagnosis of FIP humor sample (with cytology consistent with FIP) adequate to confirm a diagnosis of FIP
FIP Differential diagnoses
ABCD TOOL 5
FIP: differential diagnoses to be considered
Modified from: Barker E & Tasker S. (2020). Advances in Molecular Diagnostics and Treatment of Feline Infectious Peritonitis.
geography/lifestyle dependent
Lymphocytic cholangitis or cholangiohepatitis: young, especially pedigree cats, jaundice ± abdominal
effusion, on biochemistry elevated ALP & GGT; histopathology
Pyothorax: outdoor cats, history of fighting, fever, leucocytosis with neutrophilia (± left shift) on
haematology, pleural effusion with high cell count & degenerative neutrophils (septic)
Toxoplasmosis: hunters &/or those fed raw meat diet, neurological/muscular/pulmonary/ocular signs all
possible, effusions, jaundice; serology (antibody); PCR; cytology or histopathology, responds to
clindamycin
Neoplasia: lymphoma in young cats with lymphadenopathy &/or organomegaly, carcinoma/other in older
cats, range of signs depending on type of neoplasia, can have bicavity effusions; cytology, histopathology
Septic peritonitis: fever, leucocytosis with neutrophilia (± left shift) on haematology, abdominal effusion
with high cell count & degenerative neutrophils (septic)
Pancreatitis: mainly middle-aged to older cats, reduced appetite, jaundice, weight loss, abdominal
effusion all possible, fever not prominent; ultrasonography & feline pancreatic lipase immunoreactivity
Mycobacterial infection: hunters &/or those fed raw meat diet: skin, abdominal, thoracic signs all
possible with lymphadenopathy, fever not prominent; Ziehl-Neelsen stain, interferon-gamma release blood
test assay, PCR (tissue samples), culture
Haemoplasmosis: cats with outdoor access, pallor, lethargy, fever, regenerative anaemia; PCR Effusion consistent
with FIP?
Congestive heart failure: pleural effusion more common but bicavity effusion possible, rare to see
If you found this ABCD information valuable, please tell a colleague. To download the ABCD tools, fact sheets, or the full disease guidelines, please visit our website: www.abcdcatsvets.org
The ABCD Europe is an association with an independent panel of experts in feline health. This tool was supported by Boehringer Ingelheim (founding sponsor) and Virbac. December 2021.
FIP: diagnostic approach I
Evidence contributing to being highly suspicious of a diagnosis of feline infectious peritonitis
Modified from: Barker E & Tasker S. (2020). Advances in Molecular Diagnostics and Treatment of Feline Infectious Peritonitis. Advances
OL Clinical examination NOTE: - slightly less likely + slightly more likely History
-- moderately less likely Weight loss/failure to thrive /stunted growth +++
Fever (typically <40oC) +++
Mucous membranes:
The + & - symbols indicate how likely or unlikely
factors listed are to make a diagnosis of FIP
--- far less likely
---- extremely unlikely
++ moderately more likely
+++ far more likely
++++ extremely likely
Swollen abdomen ++++
Persistent/fluctuating fever non-responsive to antibiotics +++
Jika tidak khas
Icterus/jaundice ++
Pallor +
Abdominal palpation: Signalment
Lethargy/dullness ++
Inappetence ++
terutama non
Fluid thrill due to ascites ++++
Irregular organomegaly (e.g. kidneys, lymph nodes) +++
Signalment & history <2 years ++++
>5 years –
Dyspnoea ++
Vision or ocular abnormalities incl. iris colour change &/or effusion suspect FIP
Masses (e.g. abdominal lymph nodes, intestinal) ++ nystagmus ++
Male +
Auscultation: Pedigree + (breeds vary geographically) Jaundiced mucous membranes ++
Absence or dullness of heart sounds ++ Dietary history compatible with thiamine Ataxia/paresis (para- or tetra-), hyperaesthesia, seizures ++
Heart murmur / arrhythmia – deficiency – Sibling (or in-contact) with FIP ++
Absence of lung sounds ++ Multi-cat household +++
Increased lung sounds with crackles – Serum biochemistry Pale mucous membranes +
Percussion of chest dull ventrally ++
Tachypnoea or dyspnoea ++
Clinical examination Hyperbilirubinaemia +++
Diarrhoea, vomiting &/or constipation +
Recent stress (e.g. vaccination, rehoming, neutering) ++
including looking for any evidence of an effusion Hyperglobulinaemia +++
Otoscopic examination : Outdoor only/feral cat – –
Hyperproteinaemia (or total solids) ++ History of fighting –
Evidence of ear disease (e.g. polyps, otitis externa /media) –
Hypoalbuminaemia +
Ocular examination (unilateral or bilateral changes):
Albumin to globulin [A:G] ratio
Change in iris colour ++++
Dyscoria/anisocoria +++
A:G ratio < 0.4 + Analyse any effusion
A:G ratio > 0.6 – Typically, high protein low cell count effusions in
Hyphaema ++
Aqueous or vitreous flare ++
Y
Alpha1-acid glycoprotein, if available: abdomen ± thorax ± pericardium
Rule Out DDx yang memiliki
Other signs of uveitis ++ Serum biochemistry >1. 5 g/L ++
>3.0 g/L +++
Biochemistry:
High protein (or total solids) >35 g/L ++++
Perivascular cuffing of retinal vessels ++
Nystagmus ++
Retinal detachment +
<1. 5 g/L –
Serum protein electrophoresis, if performed:
Low protein (or total solids) < 25 g/L – –
A:G ratio < 0.4 ++
gambaran klinis dan hasil
Polyclonal gammopathy +
Neurological examination:
Ataxia +++
Marked elevation in ALT & ALP –
Only mild or moderate elevation in ALT &
A:G ratio > 0.8 –
Yellow ++++ Effusion cytology &
biochemistry
laboratorium mirip.
Seizures +++ Rivalta’s test positive ++
ALP with hyperbilirubinaemia + Rivalta’s test negative – – – consistent with FIP?
Mental state or behaviour changes +++
FCoV antibody test with high titre + Cell count: Go to diagram
Head tilt ++
Priapism ++
Scrotal enlargement ++
Locate & analyse effusion FCoV antibody test negative – Low cell count <5 x109/L ++++
Moderate cell count ≤20 x109/L ++
1
Locate any effusion
if present* High cell count > 20 x109/L –
STUDI KASUS
• Without new, potentially curative, anti-coronaviral drugs (e.g. GC376, GS-441524 - not yet licensed),
FIP has a very poor prognosis.
• Veterinarians in many countries are not allowed to obtain or prescribe these unlicensed drugs but
many clients are sourcing the drugs themselves online.
• In some countries vets are supplying diagnostic and treatment monitoring support, without providing or
prescribing the drugs, to help support cat welfare.
• An accurate diagnosis is important to prevent unnecessary use of these drugs.
• Successful treatment indicators include improvement of clinical signs (e.g. reduced effusion, weight
increase) and laboratory parameters (e.g. decreasing globulin, bilirubin and AGP levels).
• Supportive treatment can include appetite stimulants for anorexia, effusion drainage (e.g.
thoracocentesis if dyspnoeic), anti-pyretic drugs.
Antiviral Drugs :
• GS 441524: not yet licensed
• Remdesivir (GS-5734): sudah ada produk legal di UK & Australia (injeksi dan oral). Di
Indonesia masih menggunakan human licensed injection
• Molnupiravir (EIDD-2801): belum ada scientific proved
• Mefloquine: anti malaria drugs Treatment
Severe disease (anorexic, dehydrated, cat
Less severe disease (normal hydration, eating)
usually will be hospitalised)
Oral only treatment protocol:
An oral GS-441524 treatment only protocol is
1. Initial treatment with once daily intravenous
recommended if injectable not tolerated/
remdesivir (Table 1) for 3-4 days i.e. on days 1, 2, 3
possible financially:
± 4. This
dosageprovides a loading
needed) dailydose
oral of the drug. On
GS-441524 (Table 1) on 1. Once (or twice if very high neurological dosage
s each day, dilute the remdesivir dose required to a needed) daily oral GS-441524 (Table 1) until at
total volume of 10ml with saline and administer least day 84.
of slowly over 20-30 minutes manually or with a
NOTE ON WEIGHING CATS: It is very important to
syringe driver. Options for cost limited clients – please note
2. Follow with once daily subcutaneous remdesivir at that, ideally, therapy should be given using the
the same dosage (Table 1) up to day 7-14 recommended formulations and dosages for as long
3. Change to once (or twice) daily oral GS-441524 as possible (up to 84 days) to increase likelihood of
cure. Only take the options below if absolutely
(Table 1) on day 8-15, and continue until at least
necessary, as relapse may occur, which then requires
day 84. longer treatment, increasing costs;
tions for remdesivir and GS-441524
• Give oral GS-441524 treatment only for 84 days, as
Less severe disease (normal hydration, eating) outlined above;
1. Initial treatment with once daily subcutaneous • Give injectable remdesivir or oral GS-441524 for as
remdesivir (Table 1) up to day 7-14 many days as the owner can afford before switching
2. Change to once (or twice if very high neurological to oral mefloquine 62.5mg 2-3 times weekly (large
dosage needed) daily oral GS-441524 (Table 1) on cat, give 3 times a week) or 20-25mg orally once daily
day 8-15, and continue until at least day 84. (if reformulation of tablets is possible e.g. PCCA Ltd)
for completion of an 84-day treatment protocol;
mefloquine is cheaper than remdesivir and
GS-441524 but more research is needed to judge its
effectiveness in this situation;
• If an increase in remdesivir dosage is required (e.g.
Treatment Protocol
What should I expect during treatment? What do I need to monitor during treatment?
• In the first 2-5 days you should see an improvement • Ideally, serum biochemistry and haematology after 2
in demeanour, appetite, resolution of pyrexia and weeks and then monthly;
reduction in abdominal (Figure 3) or pleural fluid if • For cost limited clients, monitor
an effusion is present (note that in some cases weight/demeanour/effusions (e.g. by in-house
pleural fluid can transiently worsen in the first scanning)/neurological signs/key biochemical
couple of days– if the cat is at home, advise owner abnormalities only (e.g. measuring just globulin,
to measure resting respiratory rate, plus respiratory bilirubin or spinning microhaematocrit tube for
effort) – effusion typically resolves by 2 weeks; PCV/TP/colour of plasma);
• If an effusion is still present at 2 weeks, consider • NB. ALT enzyme activity may increase – it is not
increasing dosage to one that is greater than that clear if this is due to FIP pathology vs. drug reaction,
being used e.g increasing the dosage from that and it is not usually a reason to stop therapy. It is not
used for cats with effusions only; known if the addition of hepatoprotective therapy
• Serum albumin increases and globulin decreases (e.g.SAMe) is helpful in these cases;
(i.e. they normalise) over 1-3 weeks, but note that • Point-of-care ultrasonography (POCUS) to monitor
for effusion resolution and/or lymph node size.
globulins can initially increase when a large volume
effusion is absorbed;
• Lymphopenia and anaemia may take longer to If I am seeing a positive response to treatment,
resolve, up to 10 weeks; when do I stop treatment?
• Not before 84 days (12 weeks);
• Mild peripheral eosinophilia is a common finding
and may be a favourable marker for disease • Confirm resolution of previous abnormalities
resolution, as it is in COVID patients; (clinically, POCUS, serum biochemistry, and
haematology);
• Lymph node size reduces over a few weeks;
• Only stop treatment once cat has been normal
• If progress is not as expected, consider reviewing (clinically and on serum biochemistry and
the diagnosis (see below) and/or increasing dosage. haematology) for at least 2 weeks (ideally 4 weeks).
1 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University,
1 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University,
Columbus, OH 43210, USA OH 43210, USA
Columbus,
2 Independent Researcher,
2 San Jose, CA 95123, USACA 95123, USA
Independent Researcher, San Jose,
3 3 Departments of Orthopaedic Surgery and Public HealthSchool
Sciences,
Departments of Orthopaedic Surgery and Public Health Sciences, ofSchool of Medicine,
Medicine, University
University of Virginia,
of Virginia,
Charlottesville, VA 22903, USA
Charlottesville, VA 22903, USA
* Correspondence: [email protected]
* Correspondence: [email protected]
Abstract: Feline infectious peritonitis (FIP) is a complex and historically fatal disease, though recent
Abstract: Feline infectious
advancesperitonitis (FIP) ishave
in antiviral therapy a complex
uncovered and historically
potential fatal Adisease,
treatments. though recent
newer therapeutic option,
• NO scientific research yet advances in antiviral unlicensed
therapy molnupiravir, is being used
have uncovered as a first-line
potential therapy forAsuspect
treatments. newerFIPtherapeutic
and as a rescue therapy
option,
to treat cats who have persistent or relapsed clinical signs of FIP after GS-441524 and/or GC376
• Dosage range 10-15mg/kg BID PO unlicensed molnupiravir,
to treat cats who have
is being used as a first-line therapy for suspect FIP and as a rescue therapy
therapy. Using owner-reported data, treatment protocols for 30 cats were documented. The 26 cats
persistent or relapsed clinical signs of FIP after GS-441524 and/or GC376
treated with unlicensed molnupiravir as a rescue therapy were treated with an average starting
• 12 weeks treatment therapy. Using owner-reported data, treatment
dosage of 12.8 mg/kg and an averageprotocols
ending for 30 cats
dosage of 14.7were documented.
mg/kg The
twice daily for 26 catsof
a median
Prevention
! FCoV-infected cats should be kept in a low-stress environment.
! An intranasal FIP vaccine is available in some countries for cats over
16 weeks. However its efficacy is doubtful and it is ineffective in cats
previously infected by FCoV. ! Fluid accumulation in a Sphinx cat with FIP.