LHS Infectious disease : FIV and FeLV Flashcards
Where does FeLV replicate?
many tissues
Is FeLV cytopathic?
No
Describe the type of virus that FeLV is
- retrovirus
- labile, enveloped
- ssRNA
- reverse transcriptase: ssRNA to dsDNA (provirus), integration into host DNA
- 3 possible fates: destruction infection cell by IR, infection +/- virus production, transformation to neoplastic cell
- 3 major proteins: gag, pol, env
What is core protein p27?
- FeLV
- a gag protein: basis for most diagnostic tests
- produced within infected cells
- may circulate free in plasma or excreted in tears, saliva
- anti-p27 AB not effective in viral neutralisation
- envelope masks presence of core protein in intact virion
What are the FeLV envelope proteins?
- p15E (spike) –> immunosuppression
- gp70 (knob): defines viral subgroup (A, B, C) and important for inducing anti-viral neutralising Abs. Abs subgroup specific (immunity to re-infection), target for vaccine production
Outline FeLV epidemiology
- prevalence in 1-2% in healthy cats in UK
- prevalence in symptomatic cats 20%
- some geographic variance, although similar rate worldwide
- decreasing since mid-1980s (testing programmes, vaccination)
In what cells does FeLV infect for viraemia?
- lymphocytes and monocytes
Where does FeLV replicate?
marrow, lymphoid cells
What does persistent FeLV viraemia cause?
- stress, immunosuppression, GCs
- malignancy
- myelossuppression
- immunosuppression
How is FeLV shed?
- saliva
- nasal secretions
- faeces
- urine
- milk
How long does FeLV survive outside body?
short survival (few hours)
Transmission - FeLV?
- intimate prolonged contact: sharing food and water, mutual grooming
- neonates (in utero and nursing)
- blood transfusions
4 results of FeLV infection?
- persistent viraemia
- transient viraemia
- latent infection
- localised infection
CS - FeLV
- many cats asymtomatis
- varied and non-specific
- depend on organ system +/- secondary dz
- inappetance
- wt loss, wasting
- poor coat
- lymphadenopathy
- persistent fever
- pale MM
- ocular dz
- gingivitis
- stomatitis
- infection: skin, urinary bladder, upper respiratory tract
- persistent diarrhoea
- seizures, behavioural changes, other neuro disorders
- queens - abortion etc
Why do you get secondary infections with FeLV?
- immunosuppression: common
- depletion of itnerference with function of lymphocytes +/- neutrophils
- susceptible to co-infection: common, opportunistic pathogens
Outline haematological disorders of FeLV
- BM suppression: viral infection of haemopoietic stem cells and stromal cells: anaemia (non-regen - pure RBC aplasia, aplastic anaemia - pancytopaenia, regenerative - 10% with IMHA/ Mycoplasma), thrombocytopaenia, granulocytopaenia
- myelodysplsaia –> myelodysplastic syndrome
- leukaemia (all cell lines)
What is the relationship b/w FeLV and lymphoma?
- FeLV + cats have >60% increased risk of developing lymphoma
- expect to develop in 25% of FeLV+ cats within 2 years of diagnosis
- usually mediastinal (thymic) and multicentric)
- some cats with lymphoma test FeLV- but have virus in tumours
Prognosis - FeLV cats
- cats infected with FeLv or FIV may live for several years
- euthanasia decision shouldn’t be made on basis of infection
- confirmed positive test only indication of RV ifxn, not clinical dz
Dx- FeLV
- IMMUNOASSAY: elisa or immunochromati lateral flow devices, look for p27 Ag, screening test
- IFA: detects p27 in leukocytes and PLTs (after marrow infection), confirmatory, no longer widely available
- PCR: detects viral nucleic aicd, confirmatory is qPCR which ha slargely superseded IFA
- VIRAL CULTURE: gold standard to confirm, rare in practice
- AB test: not for dx (but viral neutralising Ab can be useful)
Interpret a positive test result for Ag test for FeLV
- transient or persistent viraemia
- owing to low prevelance of FeLV, consider repeating (ideally using different test)
- IFA: BM infection, persistent viraemia (rarely transient viraemia)
Interpret a positive test result for IFA test for FeLV
BM infection, persistent viraemia (rarely transient viraemia)
Interpret a negative test result for FeLV
- unexposed
- elimination of previous infection
- early infection (retest in 9-12 wks)
- latent infection
- localised infection
- false negative (usually test reliable)
What are the different stages of FeLV infection?
1 oropharynx 2 primary viraemia 3 lymphoid tissue 4 BM 5 marrow viraemia 6 epithelial tissue
How to interpret positive antigen, negative IFA or viral isolation for FeLV (i.e. discordant results)?
- early infxn (virus not yet replicating)
- in recovery
- false positive (low prevalence)
- detection of incomplete virus
- localised infection, Ag released but not virus
- greater sensitivity of Ag test
What should you do if you have a positive screening test for FeLV?
run confirmatory test (IFA, qPCR (viral isolation))
What should you do with a cat with discordant results (e.g. positive Ag and negative IFA or viral isolation) for FeLV?
Isolate from other cats, repeat blood sample in 4 wks
- if negative for Ag and virus, likely to be virus free, confirm by repeating in 8 wks
- if still discordant, re-check in 8 wks
Tx - FeLV that is systemically well
- general preventative healthcare (nutrition, prevent 2 infection, neuter if entire, confine indoors)
Tx - FeLV that is sick
- supportive care
- tx secondary illness
- confine indoors
Outline vaccination for FeLV
- test before vaccinating, no benefit if already FeLV positive
- assess risk of exposure: outdoors, resides with cats of unknown or FeLV+ satatus
- Risks: quesiton of efficacy? development of ISS
What type of virus is FIV?
- Retroviridae, Lentivirus
- RNA virus (uses RT)
- 5 subtypes
- similar to HIV
- no risk of transmission to people
Epidemiology - FIV
- varies by country (HEALTHY: 3-6% UK cats, 1.5-3% USA, SICK: 15-19%)
- usually free-roaming, aggressive male cats
- infection least common in indoor cats
Transmission - FIV
- primarily bite wounds, large amount of virus in saliva
- less commonly: vertical (transplacental, milk), sexual (minor), sharing food bowls (minor)
Pathogenesis - FIV
5 PHASES:
- acute
- asymptomatic carrier
- persistent generalised lymphadenopathy
- terminal (AIDS-related complex and AIDS)
Describe the acute phase of FIV
- several days to wks
- transient mild illness (young cats usually slow –> severe signs, +/- fever, lethargy, diarrhoea, lymphadenopathy)
- early replication in LT (thymus) and salivary glands
- later spread to mononuclear cells in non-lymphoid organ (lung, GIT, kidney)
+/- neutropaenia, lymphopaenia
Describe FIV asymptomatic carrier
- up to 10 yrs
- healthy appearance, but defects of immune system
- low level of circulating virus after host I.R. (seroconversion)
- CBC usually normal
- CD4+: CD8+ ratio decresed
What is the AIDS stage of FIV
- only 10% FIV cats reach this stage
- survival: wks- months
- opportunistic infections (herpes, calicivirus, toxoplasma, cryptosporidium, candida, mycobacterium, demodex)
- neuro dz (5%) and neoplaisia
- CBC: leukopaenia, anaemia, CD4:CD8 decreased/ inverted
Commonest clinical syndromes of FIV
- stomatitis
- neoplasia (5times increased for lymphoma, SCC)
- ocular inflammation (uveitis, chorioretinitis)
- anaemia and leukopaenia
- opportunistic infections
- renal insufficiency
Dx - FIV
- CBC: neutropaenia, anaemia, thrombocytopaenia, co-infection with M.haemofelis –> haemolytic anaemia
- BIOCHEM: usually NAD, +/- polyclonal gammopathy
- FIV test
What are the FIV tests?
- AB test: for core protein p24 or envelope protein gp41, most cats develop Ab within 60d, interference with vaccination and MAb
- IFA: detects Ab, FIV-infected cells fixed to slide, test sample applied, fluorescent secondary Ab applied
- WESTERN BLOT: detects Ab, confirmatory test for positive ELISA
- PCR: commercially available
- VIRAL ISOLATION: research centres
Interpret - positive test result for FIV
- PI
- FIV-infected queens: test kittens > 6 months old (MAb)
- false positive result (low prevalence)
- weak positive result –> repeat
- if kitten
Interpret - negative test result for FIV
- not infected
- infected by Ab not detected by test
- test error (re-test is highly suspicious)
- no Ab response mounted by cat (immunosuppression)
- early infection 8-12wks post-infection, before detectable Ab, re-test every 60d if needed
Recommendations - if cat is in contact with known/ potential FIV+ cat
cat tests negative: re-test at least 120d after initial exposure to confirm negative
Recommendations for possible FIV cat where test result doesn’t fit clinical suspicion
re-test
When is PCR helpful for FIV?
IF YOU SUSPECT:
- interference: MAb
- immunosuppressed
- detection prior to Ab production: 1-3wks vs 2-4 mo
Tx - FIV
- SUPPORTIVE: AB (anaerobes), care if using corticosteroids with ABs (gingivitis, stomatitis), lactoferrin (for stomatitis)
- ANTIVIRAL: Zidovudine (little/no help once infected)
What is Zidovudine?
- antiviral tx for FIV
- little/no use once infected
- nucleoside analogue
- blocks RT of retroviruses
- inhibits new infection, but not replcation in pre-infected cells
- reduces plasma viral load, improves CD4+ count and stomatitis
- generally well tolerated but monitor for HB HA and non-regenerative anaemia
- AZT- resistant FIV mutants can develp as soon as 6m
Prevention of FIV infection
- prevent virus exposure (keep cat indoors or confined when outside)
- virus readily killed by disinfectants, dies within a few hours in environment
- low risk transmission by social contact
- don’t breed from FIV+ queens
- if FIV+ queen, hand-rear kittens
- vaccine (USA only)
- introduce only infection-free cats into household
Describe FeLV subgroup A
- present in almost all FeLV-infected cats
- only group transmitted cat-cat
- basis for production of other subgroups
- least pathogenic of 3
Describe FeLV subgroup B
- recombination of subgroup A with endogenous FeLV proviral sequences
- oncogenic
Describe FeLV subgroup C
- arises from mutation of subgroup A
- non-regenerative anaemia
Risk factors - FeLV
- Male > female
- young cat (1-6 yo)
- multi-cat household
- outdoor> indoor
- susceptibility to infection highest in young kittens
- kittens
Describe persistent viraemia with FeLV
- majority of persistently viraemic cats develop FeLV-associated dz within 3-5 years after infection
- don’t develop VNAb
- neoplastic and non-neoplastic dz
Describe transient viraemia with FeLV
- virus completely eliminated
- may take up to 3 months
- usually high titres of VNAb
Describe latent infection - FeLV
- virus persists in some tissues but no viral replication, so undetected
- difficult to diagnose, only BM culture or PCR
- 30% cats with FeLV
- OPTIONS; either latently infected, develop persistent viraemia (stress, ill, steroids), some eliminate virus within 30 months exposure
Describe localised infection with FeLV
- uncommon
- viral infection sequestered in certain tissues (mammary glands, bladder, eyes)
- may give discordant test results (positive Ag, negative other)
Describe secondary infections with FeLV
- OPPORTUNISTS: bacteria, viruses, fungi, protozoa
- chronic bacterial infxn
- calicivirus
- Cryptococcus neoformans
- dermatophytosis
- FIP
- Mycoplasma haemofelis
- Toxoplasma gondii
FeLV - outcome depends on …
- age
- viral factors
- immune status (other ifxn, vaccination, GCs)
Defien FOCMA
Feline Oncornavirus Cell Membrane Antigen
What is FOCMA?
= Feline Oncornavirus Cell Membrane Antigen
- present on membrane of malignant cells
- absent on all other cells of body, even those infected with FeLV
- anti-FOCMA Ab + complement lyse tumour cells –> immune surveillance against tumour development, protective
What I-M dz may result from FeLV?
- IMHA
- glomerulonephritis
- uveitis (immune complex deposition in iris and CB)
- PA
What repro problems may arise from FeLV?
- INFERTILITY: fetal death and resorption in middle trimester
- ABORTION: less common
- TRANSMISSION: transplacental +/- colostrum, both viraemic and latently infected queens may give birth to PI kittnes
- ‘fading kitten syndrome’ may ensue
What skeletal abnormalities may result from FeLV?
- OSTEOCHONDROMATOSIS: benign proliferative dz of bone, multiple cartilaginous exostoses of flat bones
- CHRONIC PROGRESSIVE PA: young cats - fibrous ankylosing arthritis and periostitis, older cats - progressive lymphoplasmacytic synovitis, joint instability and deformity
What neuro dz may result from FeLV?
- NEUROPATHIES: infrequent, need to be distinguished from CNS lymphoma
- CS: anisocaria, urinary incontinence, vague pain or spinal hyperaesthesia, posterior paresis
- ACUTE DEMYELINATING MYELOPATHIES also seen
Describe the immunoassay for FeLV
- ELISA or immunochromatic lateral flow device (Recognised screening test)
- detection of viral p27 Ag
- serum preferred (fewer false+ and false- than plasma, blood, tears and saliva)
- various kits
Describe IFA test for FeLV
- detects p27 Ag after BM infection and incorporation of p27 Ag into leukocytes and PLTs
- confirmatory test
- special processing and fluorescent microscopy - qualified ref lab
- blood or BM smears (unfixed)
When might you get a false negative IFA test result?
neutropaenia or thrombocytopaenia
Why might you get a false positive IDA test result?
- smear too thick
- inexperienced personnel
Describe PCR detection of FeLV
- detect viral nucleic acid (RNA or DNA)
- may be most sensitive test
- may be useful confirmatory test
- specialised labs
- blood, solid tissues, tissue cultures, fixed specimens
Describe viral culture in detection of FeLV
- langford or glasgow
- blood in heparin or EDTA
- gold standard to confirm
- not all cats with FeLV yield positive culture
Describe Ab test in detection of FeLV
- not to diagnose ifxn
- high rate of exposure to FeLV in environment
- FeLV vaccination induces FeLV Abs
- MAbs in colostrum
- Ab tests not to detect infxn, so vaccination and MAbs don’t interfere with current test method
Describe FeLV virus neutralising Abs (VNAbs)
- produced by cats that have been exposed to and eliminated virus
- indicator of protected cat
- useful when deciding if test negative cat can continue to live with FeLV+ cat
- serum or plasma
Prevention - FeLV infection in vet practice
- routine hygiene, cleaning, susceptible to regular disinfectants and detergents: patient area, wash hands b/w patients, fluid line, multi dose meds vials and food etc not to be shared, dental and sx instruments etc
- blood transfusions
Vaccination - FeLV
5 types licensed in UK:
- whole inactivated virions
- inactivated gp70 and FOCMAs from tissue culture cells
- recombinant envelope protein p45
- live canarypox recombinant vaccine that expresses gag, env and protease proteins
- all except canarypox vaccine contain adjuvant
1/3 cats with FIV present in which stage?
lymhadenopathy
What are CS of lymphadenopathy with FIV?
- anorexia
- wt loss
- FUO
- lymphadenopathy - persistent, generalised
Duration - lymphadenopathy stage of FIV
6mo- several years
CBC - FIV cat in lymphadenopathy stage
+/- leucopaenia
- anaemia
- CD4:CD8 ratio inverted
What is the AIDS related complex with FIV?
- approx 1/2 infected cats present in this stage
- secondary bacterial infections: URI, GIT, skin
- neuro signs and neoplasia less common
- duration: 6mo - 1-2years
- CBC: anaemia, leucopaenia or leucocytosis, CD4:CD8 ration inverted
What are the Ab tests against FIV?
- Ab against core protein p24 or envelope protein gp41
- most cats develop Ab within 60d
- serum or plasma
- various kits
- immunochromatic test preferred: confirm positive with IFA, WB, qPCR
- commercial labs (ELISA, IFA)
- INTERFERENCE: vaccination, MAbs
Describe IFA test for FIV
- detects Abs
- FIV-infected cells fixed to slide (Ag source), AB from test sample allowed to bind
- bound Ab detected with fluorescent secondary Ab against feline IgG
Describe WB test for FIV
- detects Abs
- more specific than ELISA
- laborious, expensive
- confirmatory test for a positive ELISA
Other tests for FIV
- VIRAL AG: not possible as circulating levels too low for detection
- VIRAL ISOLATION: only in research centres
- qPCR: commercially available, variability in viral genome
Outline use of immunomodulators in tx of FIV
- restore immune function?
- IL2 (some promise)
- evenign primrose oil
- recombinant feline or human IFN
- no firm evidence of efficacy
- possible CI f non-specific stimulants
What are the challenges of FIV vaccination?
- error-prone RT enzymes
- viruses take advantage of Ab production: paradoxical enhancement of viral replication and dz expression
- large genetic diversity
Describe the FIV vaccine
- USA only
- inactivated subtypes A and D with adjuvant
- strong cellular and humoral immunity but unknown field efficacy
- portection against frequent subtype B in USA and Europe?
- increased susceptibility to infection post-vaccination so separate FIV negative cats from positive for several weeks post-vaccination
Preventative healthcare if FIV+
- KEEP INDOORS: minimise contact with other dz-carrying cats
- prevent spread
- ROUTINE HEALTH MEASURES: routine vaccination, use killed vaccines, flea control, prevent hunting, eating raw meat
