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WHAT DO YOU NEED TO KNOW
ABOUT FELINE INFECTIOUS
DISEASES?
FANAN SUKSAWAT
DVM, MS, PH.D
FELINE INFECTIOUS DISEASES
Causative agents
FVR FCV P C FeLV FIP FIV
Chlamydophila
Coronavirus
Parvovirus
Cat
flu
Calicivirus
Herpesvirus
Feline
leukemia
virus
Feline
immunodeficiency
virus
FELINE INFECTIOUS DISEASES
Causative agents
Chlamydophila spp.
Bartonella spp.
Toxoplasma gondii
Cryptococcus spp.
Scope of this talk
Characteristics of each
disease
Diagnosis
Vaccination
Potential interferon
application
FELINE PARVOVIRAL INFECTION
FELINE PANLEUKOPENIA
Syn: feline distemper, feline infectious enteritis,
cat fever and cat typhoid
FELINE PARVOVIRUS, PANLEUKOPENIA
characteristics
diarrhea
DIC
Cerebellar hypoplasia
feline ataxia syndrome
Less prevalent nowadays
• Widely vaccinated
• Virus adjust to cats
• CPV to cats..Ab crossprotect to FPV
FELINE PANLEUKOPENIA
diagnosis
• clinical signs, and the presence of leukopenia
• Leukopenia (severe: 50-3000 at D4-D6, mild:
3000-7000 cells/ul)
• Thrombocytopenia
CPV Kit
• confirmed by
necropsy examination
virus isolation
identification of the virus infected tissues
Serology (Ag, serum, feces, 24-48 hrs after
infection)
serological tests do not differentiate between
infection- and vaccination-induced ab.
Vaccination
Age
>2m
<2 m.
Adult
Booster
3 m and yearly
3-4 wks after till
3 m. and yearly
1 time and
yearly
pregnanted cat
* MLV in <2 m of age
Type of vaccine
MLV
killed*
MLV, killed
no MLV and
killed vac
FELINE CORONAVIRUS INFECTION
Feline Infectious Peritonitis, FIP
More prevalent
• farm raised
• indoor raised
• inbred
FIP
characteristics
• effusion
• systemic serositis
• fibrin on internal organ’s surface
• granuloma
• peritonitis
http://www.vetmed.wsu.edu/courses_vm546/Co
ntent_Links/DfDx/Cat%20Case%204/systemic_d
iseases.htm
Wet FIP
Dry FIP
Wet
acute 4-8 wks, C’ fixation
increases permeability
Dry
chronic, months to
years, CMI
FIP
diagnosis
Good clinical skills- signs
history
environment
Serology IS NOT THE BEST!
Biopsy Immunohistochemical
immunofluorescent staining of gut
biopsy
RT-PCR good but negative doesn’t
mean FIP ruled out
WHY SEROLOGY IS NOT THE
BEST IN FIP?
• Either healthy and sick cats with disease other
than FIP have FCoV antibodies
• Effusive FIP cats have low titers or negative..
Ab bind to lots of viral Ag in effusion not many
left to bind with Ag in the test
• The presence of FCoV antibodies alone is NOT
diagnostic of FIP, if the other parameters of the
profile do not indicate a diagnosis of FIP
Rivalta’s test
1. Mix 8 ml of distilled water
with one drop of 98% acetic
acid
2. Carefully place one drop of
the pleural or abdominal fluid
on the surface
+
if the drop adheres to the
surface and hangs like a
jellyfish...85% positive
predictive value for FIP
-
If the drop mixes with the
solution and falls to the
bottom…nearly 100%
negative predictive value
Lab results
• A:G of < 0.4 indicates FIP is quite likely
• A:G of >0.8 rules out FIP
• A:G of between 0.4-0.8 is inconclusive
consider other parameters
Lab results
modified transudate.. total
protein> 35 g/l ..<5000
nucleated cells
effusion color: clear straw
viscous froth when shaken
may clot when refrigerated
Cytology
effusive FIP
generally < 3 x 109 nucleated
cells/L in the effusion
Neutrophils
macrophages predominate
Cytology of pleural effusions is
useful for differentiation of
thymic lymphosarcomas
GP level
• alpha one acid glycoprotein (AGP) is
an acute phase protein which has
been shown to be very useful in
distinguishing FIP from other clinically
similar conditions
• In FIP, AGP levels are usually > 1500
µg/ml) (normal range 500 µg/ml) )
Conclusions
wet FIP
•
•
•
•
•
FCoV seropositive
total protein of the effusion >35g/l
A:G < 0.4 (or at least less than 0.8)
AGP >1500 µg/ml)
cytology should reveal few nucleated cells which
are mainly neutrophils and macrophages
• Rivalta test should be positive
• Diagnosis can be confirmed by detecting FCoV
in the macrophages in the effusion
Conclusions
Dry FIP
• high FCoV antibody titre
• be hyperglobulinaemic and have a reduced
albumin:globulin ratio
• high AGP, lymphopenia, PCV < 30%, nonregenerative anemia and possibly a neutrophilia
• lost weight and ocular signs such as iritis, retinal
vessel cuffing, keratic precipitates, aqueous or
vitreous flare
Vaccination
•
•
•
•
Non-core
Primucell® -type 2 attenuated virus
intranasal
> 4 m old..booster 3-4 wks later and
annually
• can be used in FeLV cat
• safe in pregnanted cats
• Primucell doesn’t cause ADE
FELINE LEUKEMIA VIRUS (FeLV)
characteristics
leukemia
non-regenerative anemia
fadding kitten syndrome
infection after birth-thymus
atrophy-immunosuppression
anorexia
FeLV
diagnosis
•Serology
detect FeLV core protein p27 Ag
ELISA
immunochromatographic assays
(ICGAs)
direct FA test
recheck 90 days after
exposure/previous test
Free soluble
Ag in serum
and plasma,
tear saliva?
Ag in cytoplasm
In some insituations Ab can’t be detected
• Abortive infection
• FeLV induced malignant cell clone but not
permanently in genome and destroyed earlier
• FeLV infected cells that the body can’t detected
• Ab cannot be detected in B cell lymphoma but T
cell lymphoma
• 70-94% of cats with mesenteric lymphoma can
not detected Ab
• Therefore, use Ag testing forFeLV
• FeLV status of all cats should be known
• Testing and identifying positive cats is the
mainstay of managing this disease
• All new kittens and adult cats should be tested
before introduction into any house
• Kittens can be tested at any age
• FeLV vaccine does not interfere with the FeLV
test
• ELISA test is the preferred screening test
• Viral isolation
• PCR..strain specific when retrovirus
mutation but good to detect latent
infection
Vaccination
• all cats at a potential risk of exposure
should be vaccinated at the age of 8 or 9
weeks and repeat at 12 weeks
• Annually booster
• >older than 3-4 yrs, booster 2-3 years
interval
• Use killed vaccine because MLV can
cause disease
Vaccination of
immunocompromised cats
• The vaccination of FeLV-positive cats against
FeLV is of no benefit whatsoever
• FIV infection should be vaccinated against FeLV
infection, but only if they are at risk
• As the immune response in
immunocompromised cats is decreased, more
frequent boosters may be considered (in
asymptomatic cats)
FELINE IMMUNODEFICIENCY VIRUS, FIV
characteristics
• Immunodeficiency
• Stomatitis
• Tumor
Signs at terminal stage
AC stage
ARC stage
ARC stage
FIV
AID stage
Dermatological
Chronic
abscesses
Chronic gingivitis
Chronic stomatitis
Periodontitis
Pustular dermatitis
http://www.whitecourtvet.com/material/FIVcats.htm
Gastrointestinal
Chronic diarrhea
Weight loss
Immunological
Anemia
Leukopenia
Lymph node hypoplasia
Lymph adenopathy
Lymphosarcoma
Neurological
Behavioral changes
Dementia (mental deterioration)
Facial twitching
Peripheral neuropathies
Psychomotor abnormalities
Seizures
Ocular
Cataracts
Conjunctivitis
Glaucoma
Keratitis
Reproductive
Spontaneous abortions and stillbirths
Upper Respiratory
Chronic rhinitis
FIV
diagnosis
Serology is Mainstay
Ab: ELISA, Rapid immunomigration-type assay
best confirm with westernblot
Using serum better than whole blood
*Ab from vaccine interfere when vaccinated with
different subtype
* false
positive.._early stage of the disease- Ab from
mother-recheck 6-8 weeks after
* false
negative.. late stage of disease
FIV
interpretation of serology results
• After vaccination, 2-3 weeks, Ab. detected and
last for 4 years
• After infection, 8, 10 weeks to 6 months to have
Ab.
• Mistake: Cats vaccinated with one type of virus,
get infected with the other but interpreted as
false positive
maternal immunity
• Be aware of interpretation serology results in
cats younger than 6 months old,, detect at age
of >6 month
FIV
diagnosis
• FIV Antibody test
• Viral isolation
• PCR, false negative from strain specific
• AAFP recommends testing all cats being
introduced into a household to prevent
exposing any existing cats to the virus
Misdiagnosis of FIV in uninfected
cats may lead to the inappropriate
euthanasia of vaccinated cats or
kittens from vaccinated mother
Vaccination
• Fel-O-Vax vaccine, killed vaccine
• 5 clades of FIV virus
• The virus in the vaccine is not the virus
that is commonly causing FIV
• Fibrosarcoma risk
• For FIV cat, used killed vaccine for other
disease protection
http://www.newvaccinationprotocols.com/Cat%20Recommendations.htm
CAT FLU
•
•
•
•
•
•
•
Herpesvirus
Calicivirus
Reovirus
Cowpox
Bordetella bronchiseptica
Chlamydophila felis
Mycoplasma
CAT FLU
characteristics
Ulcer in oral cavity
Sneezing
conjunctivitis
PREDISPOSING FACTOR
• Crowded environment
Lethargy
Sneezing
Conjunctivitis
Hypersalivation
Ocular discharge
Nasal discharge
Oral ulceration
Keratitis
Coughing
Pneumonia
Lameness
FHV-1
+++
+++
++
++
+++
+++
(+)
+
(+)
(+)
-
FCVa
+
+
+
-c
+
+
+++
(+)
+
Bb
+
++
(+)
++
++
+
-
ChF
+
+
+++b
+++
+
+/-
FHV-1, feline herpesvirus; FCV, feline calicivirus; Bb, Bordetella bronchiseptica;
chF, Chlamydophila felis; +++,
; ++,
; +,
; (+),
; +/-,
-,
; a,
; b,
, c,
: Greene, CE, 2006.
FELINE HERPESVIRUS (FHV-1, FVR)
FELINE HERPESVIRUS
Characteristics: conjunctivitis
FELINE HERPESVIRUS
diagnosis
• Herpesvirus infection is
suspected anytime a cat
has an eye problem that
does not respond to
antibiotics, drooling
• PCR
Feline Calicivirus
FCV
characteristics
Oral ulcer
FELINE
HERPESVIRUS&CALICIVIRUS
Diagnosis
• Clinical signs
oral ulceration: FCV
hypersalivation, marked sneezing, severe
respiratory&conjunctival sign: FHV
• Viral isolation in feline cell culture
• Serology
ELISA, no good because Ab from vaccine
interfere interpretation
Immunofluorescence staining
• PCR
• all kittens should be vaccinated
against FCV
CHLAMYDOPHILA FELIS
characteristics
marked persistent conjunctivitis
CHLAMYDOPHILA FELIS
diagnosis
• Cultivation is definitive diagnostic test from
conjunctival&nasal swabs (rectal&vaginal
swabs) using cotton swabs not Dacron swabs
then placed immediately in Chlamydia transport
medium such as 2SP (0.2 M sucrose, 0.02 M
phosphate)
• Do not use viral transport medium containing
antibiotics (will inactivated the organisms if not
cultured within 24 hrs, keep at 4 C)
CHLAMYDOPHILA FELIS
diagnosis
• Cytology: Giemsa staining can detect in early
infection, melanin granules in cytoplasm of
conjunctival epith. can yield false positive
• Serology
direct FA test using MABs or ELISA
cross-reaction with the same genus
ELISA - lower specificity and sensitivity
• PCR
CHLAMYDOPHILA FELIS
Vaccination
• Both killed and MLV based on whole
Chlamydia organism are available as part of
multivalent vaccine preparations
• Vaccines are effective in protecting against
disease but not against infection
• Vaccination should be considered for cats at
risk of exposure to infection, particularly in
multicat environments, and if there has been
a previous history of Chl infection
• Vaccination of kittens generally begins at 810 weeks of age with a second injection 3-4
weeks later
BORDETTELLA BRONCHISEPTICA
diagnosis
B.bronchiseptica isolation
from oropharyngeal&nasal swabs or
from tracheal wash, placed into
charcoal Amies transport medium
before plating to selective medium
BORDETTELLA BRONCHISEPTICA
vaccination
live vaccine is licensed for use as a single
vaccination with annual boosters
MYCOPLASMA spp.
characteristics
Hemolytic anemia
Icterous
MYCOPLASMA spp.
diagnosis
• Clinical signs
• Blood smear
• films must be performed before therapy
Blood smears must be performed as soon as possible
after collected: detach from RBC so soon in EDTA
Do not use new methylene blue wet preparation
• PCR
Cytologic inaccuracies for detection of
hemotrophic Mycoplasmas in cats
Reasons
Remedy
False positive
Stain precipitate
Use fresh-filtered stains
Drying artifacts
Make thin smears, dry
rapidly
Howell-Jolly
bodies
Siderotic
inclusions
False negative
Transient
parasitemia
Excess amount or
exposure time to
EDTA
None
Positive with Prussian blue
stain
PCR
New bl. specimen, fresh
smears, heparin or no
anticoagulants
BARTONELLOSIS
characteristics
• not specific
• lymphadenopathy
• endocarditis
• rhinitis
• more studies are needed
BARTONELLOSIS
diagnosis
•
•
•
•
Clinical signs
Isolation*
IFA EIA WesternBlot
PCR
Isolation
• Blood in plastic EDTA tube or lysis
centrifugation blood culture
• Sheep or rabbit blood agar
• Due to often false negative, not
recommended for screening
Bartonella IFA IgG Slide
IFA test for the detection and semi-quantitation
of human serum IgG antibodies to
Bartonella henselae and Bartonella quintana
CRYPTOCOCCOSIS
characteristics
• sneezing
• epistaxis
• granulomatous
rhinitis
CRYPTOCOCCOSIS
diagnosis
• Cytology (60% positive of infected cats)
from deep nasal swabs, needle aspiration pleural
fluid, bronchoalveolar larvage specimens and CSF,
crushed preparation of biopsy samples
Romanovsky stains (DiffQuik Giemsa Wright) new
methylene blue, Gram stain
Viewed at X10
India ink (not recommended, lymphocyte and fat
droplet cause confusion)
CSF specimens best done by being cytocentrifuged
then stained with DiffQuik
CRYPTOCOCCOSIS
diagnosis
• Serology
(Commercial kits 90-100%
sensitivity, 97-100%
specificity)
• Tissue biopsy (impression
smear, KOH preparation)
• PCR
• Mycology
CONCLUSION
FPV: Serology (Ag, serum, feces, 24-48 hrs after
infection)
FIP:
Either healthy and sick cats with disease other than
FIP can get seropositive result, Effusive FIP cats
have low titers or negative.. Ab bind to lots of viral
Ag in effusion not many left to bind with Ag in the
test
FeLV: FeLV vaccine does not interfere with the FeLV test
The ELISA (Enzyme linked immunosorbant assay)
test is the preferred screening test
FIV: *Ab from vaccine interfere
false positive.._early stage of the disease- Ab from
mother-recheck 6-8 weeks after
false negative.. late stage of disease
FCV: oral ulceration
FHV: marked sneezing, severe respiratory&conjunctival
sign, hypersalivation
TOXOPLASMOSIS
characteristics
• pneumonia
• encephalitis
• stillbirths
TOXOPLASMOSIS
diagnosis
• Serology
Sabin-Felman dye test (human)
IFA
Agglutination tests
Indirect hemagglutination
Latex agglutination
Modified Agglutination tests
ELISA
TOXOPLASMOSIS
diagnosis
• Commercial kits are available
• However, the sensitivity and specificity of
these kits may vary widely from one
commercial brand to another
• This is of concern because serology
results can influence decisions on
continuation or termination of
pregnancies
Test serum for presence of Toxoplasma-specific IgG •
antibodies
TOXOPLASMOSIS
Diagnosis
• Cytology
tissues, body fluids (peritoneal&thoracic fluids)
during acute illness
Rarely found in blood, CSF fine-needle
aspirates, transtracheal or bronchoalveolar
washings
TOXOPLASMOSIS
• Fecal examination
Oocytes found so low (1%) cat shed
oocyte 1-2 weeks after exposure
•PCR
Interferon application in Vet. Med.
• Interferons (IFNs): proteins made and released
by lymphocytes in response to the presence of
pathogens—such as viruses, bacteria, or
parasites—or tumor cells
• allow communication between cells to trigger the
protective defenses of the immune system that
eradicate pathogens or tumors
• IFNs belong to the large class of glycoproteins
known as cytokines
• activate immune cells, such as natural killer cells
and macrophages
• increase recognition of infection or tumor cells by
up-regulating antigen presentation to T
lymphocytes
• increase the ability of uninfected host cells to
resist new infection by virus
Types of interferon
• Based on the type of receptor through
which they signal, human interferons have
been classified into three major types, I II
III
Interferon application in Vet. Med.
• Human IFN-α
viral replication in some infected
cats
not licensed for use in cats, but some
clinical studies found increased
activity, increased appetite,
improvement of blood abnormalities,
increased clearance of virus and
prolonged survival
• Feline IFN-
In Cats
low-dose interferon protocol as immunomodulator
has not been associated with side effects
possibly unpleasant salty taste
high dose protocol as antivirus
may be associated with fever, joint pain, and “flulike” symptoms
Human IFN-α
Low dose protocol
• Viral Upper Respiratory Infections
• Feline plasma cell stomatitis
• Feline eosinophilic granulomas
• FIP
•
• FIV
Human IFN-α
High dose protocol 10,000 unit
• FIP
• canine viral papillomas
Human IFN-α
• as foreign proteins, they stimulate the pet’s
immune system to react against them
Hypersensitivity
• After 3-7 weeks on the high dose protocols,
antibodies against interferon may make it
ineffective
Feline IFN-
• FeLV
• FIV
• FIP good for 1/3 of FIP cats
• non-effusive FIP orally given 30 i.u. / day
• effusive FIP >30 i.u. IM / day
• Cat flu
topically in the feline eye for herpes conjunctivitis
• Gingivitis&stomatitis
• Tumor
FIP
FIV
FeLV
Human IFN-α
Feline IFN-
Contradicated
May be
Ineffective
May be
Improved (antiviral
or 2nd infection?
5d 3t
Inhibit viral rep
FCV
FHV
yes
yes
Side effects of interferon
• Death, suicide
• Psychiatric
• Cardiovascular
myocardial infarction, septal, age undetermined, cardiomyopathy,
severe depression of left ventricular systolic function
• Renal
nephrotic syndrome, interstitial nephritis
• Hematologic
autoimmune thrombocytopenia, epistaxis
Side effects of interferon
• Neuroloqic
left-sided facial paralysis associated with
neutropenia and thrombocytopenia, oculomotor
nerve paralysis, diplopia, hearing loss
• Dermatologic
psoriasis aggravated, generalized urticaria
• Autoimmune
SLE-like syndrome
Side effects of interferon
• Ophthalmic
retinal ischemia, decreased visual acuity,
cotton wool spots, retinal vein thrombosis,
vision disorder
• Endocrine
autoimmune thyroiditis, myalgia,asthenia