Feline Infectious Dz 1 (Garden) Flashcards
Family of FeLV ?
- Retroviridae (family)
- Oncovirinae (subfam)
- Gammaretrovirus (genus)
Where does FeLV replicate and what are its effets?
- replicates in many tissues
- non-cytopathic
Describe the type of retrovirus FeLV is. What does it contain?
- labile, enveloped, ssRNA (~100nm)
- reverse transcriptase: ssRNA to dsDNA (provirus) integrated into host DNA
What are the 3 possible ‘fates’ of a FeLV infected cell?
- destruction infected cell by immune response
- infection +- virus production
- transformation to neoplastic cell
What 3 major protein groups are in FeLV?
- gag
- pol
- env
What is the basis of most diagnostic tests?
- core protein p27 gag protein
- produced within infected cells
- circulates in plasma/excreted tears and saliva
> ELISA/immunochromatographic testing - anti-p27 Ab not effective viral neutralisation
- envelope masks presence of core protein in intact virion
What envelope proteins are present on FeLV virus? What do they do?
> p15E (spike) -> immunosuppression
gp70 9knob) -> defines viral subgroup and induces antiVNAbs
- Ab subgroup specific (immunity to reinfection)
- target for vax production
Prevalence of FeLV in UK?
- 1-2% in healthy cats
- 20% symptomatic cats
> decreasing since mid-1980s (testing and vax)
Outline pathogenesis of FeLV
see lecture for flow diagram
- oral/nasal exposure
- replicaition in oropharyngeal lymphoid tissue
> effective immune response
- virus cleared, p27 negative, latent virus in BM, lymphoid tissue (integrated non-replicating)
- haematopoetic malignancy and myelosuppression
- p27 negative
> ineffective immune response
- viraemia (lymph and monocytes)
- replication: marrow, lymphoid cells
- transient viraemia/persistent viraemia
- p27 positive
-> healthy carrier/immunosuppression/myelosuppression/malignancy/stress, immunosuppression GCs
> can interchange between transient viraemia and latent virus and persistnet viraemia
What are the 4 forms of disease pathogenesis with FeLV?
- abortive (virus cleared)
- regressive (transient viraemia -> latent virus in BM/lymphoid tissue)
- progressive (replication -> persistent viraemia)
- focal/atypical (persistent viraemia -> malignancy/myelosuppression/immunosuppression/stress GCs)
How is FeLV shed? SOurce of infection?
> source of infection: PI cats > virus shed in - saliva - nasal secretion - feaces - urine - milk > short survival outside body (fews hrs)
How is FeLV transmitted?
> intimate prolonged contact - sharing food/water, mutual grooming > beonates - in utero/nursing > blood transfusion
Risk factors for transmission of FeLV?
HOME STUDY
Result of infection with FeLV?
- persistnet viraemia
- transient viraemia
- latent infection
- localised infection
Clinical signs of FeLV?
- many asymptomatic
- varied and non-specific clinical signs
- depends on organ system +- 2* dz
eg. inappetence, weigh loss, wasting - pooor coat
- lymphadenopathy
- persistent fever
- pale mm
- ocular dz, gingivitis, stomatitis
- infections (skin, bladder, URT)
- persisnt D+
= seizures, behavioural change, neuro - queens: abortion
Pathophysiology of 2* dz associated with FeLV?
> immunosuppression (most common manifestation of virus)
depletion/interference w/ function of lymphocytes +- neutrophils
susceptible to co-infection
- common for FeLV+ cats to have concurrent infection (opportunistic pathogens)
Pathophsiology of haematological disorders associated with FeLV?
> BM suppression d/t vira linfection of haematopoeitic stem cells and stromal cells
- anaemia (non-regenerative in pure red cell aplasia/ aplastic anaemia pancytopenia/ regenerative ~10% inIMHA/mycoplasma spp.)
- thrombocytopenia
- granulocytopaenia
Myelodysplasia -> myelodysplastic syndrome
Leukaemia (all cell lines affected)
How is lymphoma related to FeLV?
- FeLV+ cats 60x ^ Risk lymphoma
- expect to develop in 25% FeLV cats within 2y dx
- some cats with lymphoma test FeLV - but have virus in the tumours
What lymphoma is most commonly seen with FeLV?
- medastinal (thymic)
- multicentric
What is FOCMA?
- Feline oncornavirus cell membrane antigen
- present on membrane of maligant cells, absent on all other cells even if infected with FeLV
- anti FOCMA abs + complement lyse tumour cells -> immune surveillance against tumour developnenet - protective
How is FeLV associated with immune-mediated dz?
- Overactive/dysregulated response to virus
- eg. IMHA, glomerulonephritis, uveitis (immune complex deposition in iris and ciliary body), polyarthritis
How is FelV associated with reproductive dz?
- Infertility: fetal death and resorption in middle trimester
- abortion less common
- transmission FeLV transplacentally +- colostrum, both viraemic and latently infected queens may give birth to PI infected kittens
- > FADING KITTEN SYNDROM
How is FelV associated with skeletal abnormalities?
> Osteochondromatosis
- benign proliferatie dz of bone: multiple cartilagenous exostoses of flat bones
chronic progressive PA
- young cats: fibrous ankylosing arthritits and periostitis
- older cats: progressive lymphoplasmacytic synovitis, joint instability and deformity
How is FelV associated with neurological dz?
- Neuropathies infrequent and need to r/o CNS lymphoma
- clinical signs: anisocoria, urinary incontinence, vague pain, spinal hyperaesthesia, posterior paresis
- acute demyelinating myelopathies also seen in infected cats
IS dx of FeLV / FIV basis for PTS?
No!
+ test only confirms retroviral infection not clinical dz
Dxx tests to detect FeLV?
> Immunoassay - ELISA/immunochromatic lateral flow devices -p27 ag screening tests > IFA - p27 in lecocytes and platelets after marrow infection - not widely available > PCR - detects nucleic acid sequences - qPCR supersede IFA > viral culture - gold standard - rarely done > Ab tests - not for dx but VNA canbe sueful
What does a + test for FeLV indicate?
> Antigen test - transient/persistnet viraemia - d/t low prevalence of FeLV consider repeating (ideally using different test) > IFA - BM infection or persistent viraemia - not seen with transient viraemia
What does a - test for FeLV indicate?
- unexposed
- eliminated infection
- early infection (retest @9-12w)
- latent/localised infection
- false negative rare, test relable
See lecture for table on location of FeLV and p26 detectino in various tests?
serum ELISA
* IFA
* Tears/saliva
> oropharynx - - -
> 1 viraemia + - -
> lymphoid tissue + - -
> BM + -/+ -
> marriow virameia + + -
> epithelial tissue + + +
What does + Ag test but - IFA/viral isolation indicate? How should this be dealt with clinically?
(discordant results)
- early infection (virus not replicating)
- recovery
- false + (v prevalence)
- detection of incomplete virus
- localised infection w/ ag released but not virus
- ^ sensitivity Ag test
> isolate from other cats, repeat bloods in 4w
- if neg for ag and virus, likely free (repeat 8w to check)
- if still discordant, recheck 8w too
What should a + screening test be followed up with?
- confirmatory test (IFA, qPCR, viral isolation)
Tx FeLV in cats?
> systemically well - preventative healthcare - nutiriton and control of 2* infections (GI parasites, fleas, vx) - neuter - confine indoors > sicks - supportive care - tx 2* dz - confine indoors
What shoudl theoretically be checked before vax for FeLV?
> test FeLV status - not point vax if already + > assess risk of exposure - outdoor/lives w/ cats of unknown FeLV status > risks - efficacy? - ISS
What type of virus is FIV? How many subtypes are there?
- family retroviridae, genus Lentivirus
- RNA virus (reverse transcriptase)
- 5 subtrypes
What dz is FIV similar to in humans? Is it transmissable to humans?
HIV not transmissable to humans
Prevalence of FIV?
- varies country UK ~5% US ~2%
- sick cats ~17%
- most common free-roaming aggressive males
- infection least common indoor cats
How is FIV transmitted?
- bite wounds (virus in saliva)
- less commonly:
- vertical (transplacental/mmilk)
- sexual (rare)
- sharing food bowl (v low risk)
5 phases of FIV infection?
- acute
- asymptomatic carrier
- persistent generalised ymphadenopathy
- terminal (AIDs-related complex/AIDS)
Outline the acute phase of FIV
- dd-ww
- transient mild illness (signs ^ in ounger cats but still may not be noticed)
- lethargy, D+, lymphadenopathy can persist for months, +- fever
- early replication in lymphoid tissue (eg. thymus) and salivary glands
- then spread to mononuclear cells non-lymphoid (lung, GIT, kidney)
- +- neutropenia, lymphopenia
How long can a cat be an asymptomatic carrier on FIV?
up to 10y
How do asymptomatic carriers appear?
- immune compromised but appear healthy
- low level circulating virus after host immune response (seroconversion)
- CBC normal
- CD4:CD8 T cell ration decreased (inverted)
How many FIV cats will reach the “AIDS” stage?
10%
Survival time for AIDS cats?
- ww/mm
What is seen in AIDS stage of FIV?
- opportunistic infection (herpes virus, calicivirus, toxoplasma, crytpsporidium , candida, mycobacterium, demodex)
- neuro dz
- neoplasia
- CBC: leucopenia, anaemia, CD4: CD8 ratio inverted
Most common clinical syndomes assoc w/ FIV?
- stomatits
- neoplasia (risk 5x cf. FIV- for lymphoma and SCC)
- ocular inflam (uveitis and chorioretinitis)
- anaemia and leucopenia
- opportunistic infection
- renal insufficiency
How can FIV be dx?
> CBC - neutropenia and anaemia - thrombocytopenia - co-infection w/mycoplasla haemofelis -> HA > biochem - NAD +- polyclonal gammopathy > FIV specific tests (See later)
What FIV speecific tests are there?
- AB tests
- core/envelope proteins
- most cats develop abs within 60d
- interference= vax, MDA
> IFA - FIV infected cells fixed to slide, test sample applied, fluoro 2nd Ab applid
> western blot - confiromatoy test for + ELISA
> PCR - commercially available
> viral isolation - only research
What does a positive FIV test indicate?
- PI
- FIV infected queens: test kittens >6mo (MDA) if tested
What does a negative FIV test indicate?
- not infected
- infected but Abs not detected
- test error (retest if suspicious)
- no ab respone mounted (immunosuppression)
- warly infection (8-12w post infect no Ab made yet, retest q60d if needed )
What action should be taken if contact with a knwon FIV+ cat has been had?
- cats tests -ve, retest min 120d after initial exposure to confirm
- retest if result doesnt match suspicion
- PCR helpful if suspect
> interfecrence: MDA, immunosuppression, detection before ab production (1-3w v 2-4mo)
Tx FIV?
> supportive
- Abx for anaerobes
- cautious use of steroids w/ Abx (stomatitis, gingivitis)
- lactoferrin poss in stomatitis
antiviral tx
- zidovudine (AZT)
- nucleoside analogue, blocks RT of retroviruses
- inhibits new infection but not replicatio nin already infected cells
- v plasma viral load, improves CD4+ T cell count and stomatitis
- generally well tolerated, monitor for Heniz body HA (propylene glycol) and non-regen anaemia (myelotox)
- AZT-resistant mutants can develop within6mo
- lipid-zidovudin conjugate (fozivudine tidoxil) encouraging?
How can FIV infection be prevented?
- prevent exposure
- virus killed by disinfectants or within hrs in environment
- low risk transmission by social contact
- DO NOT BREED FIV+ QUEENS (or hand rear kittnes)
- vax in USA
What are the subgroups of FeLV
A - present in almost all FeLV infected cats - only group transmitted between cats - basis for production other subgroups - least pathogenic B - recombination of A with endogenous FeLV proviral sequences C - arises from mutation of subgroup A - non-regenerative anaemia
Risk factos for FeLV?
- male
- young
What does persistent viraemia with FeLV result in?
- persistnet viramia -> FelV assoc dz within 3-5y
- no VNA
- neoplasia and non-neoplasia dz
How long can a transient viraemia last? What is seen concurrently with a transient viraemia ? FeLV
- 3 months
- usually high titres VNA
What is latent FeLV infection? What proprotionof FeLV Infected cats will become latent carriers?
- persists in some tissues but no replication so undetected
- hard to dx (needs BM culture/PCR)
- 30%
How can latent FeLV infection progress?
- remain latently infected
- develop persistnet viraemia (stress/illness/steroids)
- some eliminate virus within 30m exposure
Is localised FeLV infection common? What tissues can it localise to? How may this be seen?
- uncomon
- mammary glands, bladder, eyes
- may give discordant test results (positive ag test, negative other)
What 2* infections are commonly seen with FeLV?
- chronic bacteria
- calicivirus
- cryptococus neoformans
- dermatophytosis
- FIP
- mycoplasma haemofelis
- toxoplasma gondii
What does the outcome of FeLV infection depend on
- age
- viral factor
- immune status (concurent dz, vax, GCs)
What may cause false negatives and positives of FeLV IFA test?
> false - - neutropenia - thrombocytopenia > false + - smears too thick - inexperienced personnel
Most sesnsitive test for FeLV?
PCR
Why are Ab tests not usefeul for dx FeLV?
- ^ rate exposure to FeLV in environment
- vax
- MDA in colostrum
What can be tested for to indicate a ‘protected’ cat?
- VNAs
- indicates exposed to and eliminated virus
- useful to decide if test - cat can live with test+
When are antivirals helpful for FeLV? eg?
- zidovudine (AZT reverse transcriptsse inhibitor)
- no use once infected
Is there much data to support use of immunotherapies for FelV? egs?
No - acemannan - proprionibacterium acnes - PIND-ORF - recombinant human interferon > all ineffective - staph protein A poss effective - lactoferrin poss effective stomatitis - feine recomb IFN *Only vet lic product* improves survival
How can FeLV spread be minimised in practice?
- standard hygeine
- blood transfusions be careful
What FeLV vax are available?
> 5 types lic UK - whole inactivated virus - inactivated gp70 and FOCMAs - recominant envelope protein - live canrypox recomb vax with gag, env and protease proteins > all excpet canarypox contain adjuvant
How many FIV cats present at lymphadenopathy stage? How long can this last? What is seen?
1/3
+ vague clinical signs (anorexia, weight loss, PUO)
- 6mo - several years
- CBC: +- leucopenia, anaemia, CD4+:CD8+ T cell ratio inverted
What is the comerically available test for FIV?
- Ab against core/env proteins
How many FIV+ cats present at AIDS-related complex stge? How long can this last? What is seen?
1/2
- 2* bacterial infections (oral cavity, GIT, URI, skin)
- neuro signs/neoplasia less common
- 6m-2y
- CBC: anaemia, leucopenia/lecuocytosis, CD4:CD8 T cell ratio inverted
Tx FIV
- Immunomodulators?
- restore imune fucntion
- IL2 some effectivity
- evening primrose oil
- recombinant human/feline IFN no evidence
- poss contraindications of non-spec stimulants (in peoplecan activate latent HIV in infected lymphocytes and macrophages)
Challenges with vax for FIV?
- error prone RT enzymes ^ mutation rate so ^ escape from immune surveillance
- viruses take advantage of Ab production: paradoxical enhancement of viral replication and disease expression
Is FIV vax available?
- only in US
- inactivated virus with adjuvant -> strong cellular and humoral immunity but ? efficacy in field
- ^ susceptibility to infection post-vac so separate FIV- and + for several weeks post-infection
Perventative healthcare for FIV+ cats?
> keep indoors - minmise contact with other dz carrying cats (eg. FeLV) - prevent spread > routine health mesasures (cf. FeLV) - vax use killed vax - flea control - prevent hunting and eating raw meat
