what do you need to know about feline infectious diseases? fanan suksawat dvm, ms, ph.d
TRANSCRIPT
WHAT DO YOU NEED TO KNOW ABOUT FELINE INFECTIOUS DISEA
SES?
FANAN SUKSAWAT DVM, MS, PH.D
FVR FCV P C FeLV FIP FIV
Herpesvirus
Calicivirus
Parvovirus
Chlamydophila
Feline leukemia virus
CoronavirusFeline immuno-deficiency virus
FELINE INFECTIOUS DISEASES
Cat flu
Causative agents
Chlamydophila spp.
Bartonella spp.
Toxoplasma gondii Cryptococcus spp.
FELINE INFECTIOUS DISEASESCausative agents
Scope of this talk
Characteristics of each disease
Diagnosis
Vaccination
Potential interferon application
Syn: feline distemper, feline infectious enteritis, cat fever and cat typhoid
FELINE PARVOVIRAL INFECTIONFELINE PANLEUKOPENIA
FELINE PARVOVIRUS, PANLEUKOPENIA characteristics
Cerebellar hypoplasia
diarrhea
DIC
feline ataxia syndrome
Less prevalent nowadays
• Widely vaccinated
• Virus adjust to cats
• CPV to cats..Ab crossprotect to FPV
diagnosis
• clinical signs, and the presence of leukopenia
• Leukopenia (severe: 50-3000 at D4-D6, mild: 3000-7000 cells/ul)
• Thrombocytopenia
• 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.
FELINE PANLEUKOPENIA
CPV Kit
Vaccination
* MLV in <2 m of age
Age Booster Type of vaccine
> 2 m
<2 m.
Adult
pregnanted cat
3 m and yearly
3-4 wks after till 3 m. and yearly
1 time and yearly
MLV
killed*
MLV, killed
no MLV and killed vac
FELINE CORONAVIRUS INFECTIONFeline Infectious Peritonitis, FIP
More prevalent
• farm raised
• indoor raised
• inbred
FIPcharacteristics
• effusion
• systemic serositis
• fibrin on internal organ’s surface
• granuloma
• peritonitis
Wet FIP Dry FIP
http://www.vetmed.wsu.edu/courses_vm546/Content_Links/DfDx/Cat%20Case%204/systemic_diseases.htm
Wet acute 4-8 wks, C’ fixation increases permeability
Dry chronic, months to
years, CMI
FIPdiagnosis
Good c linical skills- sssss sssssrs
environmentSerology 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 test1. Mix 8 ml of distilled water with one drop of 98% acetic acid2. 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.. 3totalprotein>5 / .. sssssss< 5 0 0 0ss sssss
ssssssss sssss: clear straw viscous froth when shaken may clot when refrigerated
Cytology
effusive FIPgenerally < 3 x 109 nucleated cells/L in the effusion
Neutrophilsmacrophages 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
• 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
wet FIP
Dry FIP
• high FCoV antibody titre• be hyperglobulinaemic and have a reduced
albumin:globulin ratio• high AGP, lymphopenia, PCV < 30%, non-
regenerative anemia and possibly a neutrophilia• lost weight and ocular signs such as iritis, retinal
vessel cuffing, keratic precipitates, aqueous or vitreous flare
Conclusions
• 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
Vaccination
FELINE LEUKEMIA VIRUS (FeLV)characteristics
leukemia
non-regenerative anemia
fadding kitten syndrome infection after birth-thymus atrophy-immunosuppression anorexia
i
FeLVdiagnosis
detect FeLV core protein p27 Ag
ELISA
immunochromatographic assays (ICGAs)
direct FA test
ssss sssss sss9 0 osure/previous test
Free soluble Ag in serum and plasma, tear saliva?
Ag in cytoplasm
•Serology
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 mains
tay of managing this disease • All new kittens and adult cats should be tested b
efore introduction into any house • Kittens can be tested at any age • FeLV vaccine does not interfere with the FeLV te
st• 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, FIVcharacteristics
• Immunodeficiency
• Stomatitis
• Tumor
Signs at terminal stage
AC stage
ARC stage
ARC stage AID stageFIV
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
FIVdiagnosis
Ab - : ELISA, Rapid immunomigration type assay
best confirm with westernblot
Using s erum better than whole blood
* Ab from vaccine interfere when vaccinated wit h different subtype
* sssss ssssssssssssssss sssss ss sss sssssss- Ab from mother- - recheck 6 8 weeks after
* false negative .. late stage of disease
Serology is Mainstay
FIVinterpretation 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
FIVdiagnosis
• 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
• 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
Vaccination
CAT FLU
• Herpesvirus • Calicivirus• Reovirus• Cowpox• Bordetella bronchiseptica• Chlamydophila felis• Mycoplasma
CAT FLUcharacteristics
Ulcer in oral cavitySneezingconjunctivitis
PREDISPOSING FACTOR• Crowded environment
зњѥєѝѤєёѤьыҙі ѣўњҕѥкѠѥдѥі ъѥкзј ѧьѧддѤэѯнѪѸѠлѫј нѨёеѠкі ѣээъѥкѯчѧьўѥѕѲлѲьѰєњ
Ѡѥдѥі FHV-1 FCVa Bb ChF Lethargy Sneezing Conjunctivitis Hypersalivation Ocular discharge Nasal discharge Oral ulceration Keratitis Coughing Pneumonia Lameness
+++ +++ ++ ++
+++ +++ (+) +
(+) (+) -
+ + + -c + +
+++ - -
(+) +
+ ++ - -
(+) ++ - -
++ + -
+ +
+++b -
+++ + - - -
+/- -
FHV-1, feline herpesvirus; FCV, feline calicivirus; Bb, Bordetella bronchiseptica; chF, Chlamydophila felis; +++, єѥд; ++, юѥьдј ѥк; +, ѠѕҕѥкѠҕѠь; (+), ѳєҕёээҕѠѕ; +/-, ѳєҕѰѝчкѠѥдѥі -, ѳєҕёэ; a, єѨзњѥєѰшдшҕѥкіѣўњҕѥкѝѯшіь; b, ёэѳчҖшј Ѡчѯњј ѥ, c, ўѥдєѨѰяј ўј ѫєѲьюѥдъѼѥѲўҖіѠэюѥдєѨдѥіѯюҍѕдѰмѣ ъѨѷєѥ: 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
FCV
Feline Calicivirus
characteristicsOral ulcer
FELINE HERPESVIRUS&CALICIVIRUS
• Clinical signsoral ulceration: FCVhypersalivation, marked sneezing, severe respiratory&conjunctival sign: FHV
• Viral isolation in feline cell culture• Serology
ELISA, no good because Ab from vaccine interfere interpretationImmunofluorescence staining
• PCR
Diagnosis
• 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
• Serologydirect 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 8-10 weeks of age with a second injection 3-4 weeks later
BORDETTELLA BRONCHISEPTICAdiagnosis
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 anemiaIcterous
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
False positive
Stain precipitate
Drying artifacts
Howell-Jolly bodies
Siderotic inclusions
False negative Transient parasitemia
Excess amount or exposure time to EDTA
Remedy
Use fresh-filtered stains
Make thin smears, dry rapidly
None
Positive with Prussian blue stain
PCR
New bl. specimen, fresh smears, heparin or no anticoagulants
BARTONELLOSIScharacteristics
• not specific• lymphadenopathy• endocarditis• rhinitis• more studies are needed
BARTONELLOSISdiagnosis
• 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
CRYPTOCOCCOSIScharacteristics
• sneezing
• epistaxis
• granulomatous rhinitis
CRYPTOCOCCOSISdiagnosis
• 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
CONCLUSIONFPV: 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 interferefalse positive.._early stage of the disease- Ab from mother-recheck
6-8 weeks afterfalse negative.. late stage of disease
FCV: oral ulceration FHV: marked sneezing, severe respiratory&conjunctival sign,
hypersalivationChlamydophila felis: Marked conjunctivitis
TOXOPLASMOSIScharacteristics
• pneumonia
• encephalitis
• stillbirths
TOXOPLASMOSISdiagnosis
• Serology
Sabin-Felman dye test (human)
IFA
Agglutination tests
Indirect hemagglutination
Latex agglutination
Modified Agglutination tests
ELISA
TOXOPLASMOSISdiagnosis
• 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
• Cytology
tissues, body fluids (peritoneal&thoracic fluids) during acute illness
Rarely found in blood, CSF fine-needle aspirates, transtracheal or bronchoalveolar washings
Diagnosis
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 catsnot 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 “flu-like” 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
• 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
• Gingivitis&stomatitis
• Tumor
topically in the feline eye for herpes conjunctivitis
Feline IFN-
Human IFN-α Feline IFN-
FIP
FIV
FeLV
FCV
FHV
Contradicated
May be
yes
Ineffective
May be
Improved (antiviral or 2nd infection? 5d 3t
Inhibit viral rep
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
• 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
Side effects of interferon