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Lymphoreticular and haematopoeitic > LHS Infectious disease : FIV and FeLV > Flashcards

LHS Infectious disease : FIV and FeLV Flashcards

1
Q

Where does FeLV replicate?

A

many tissues

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2
Q

Is FeLV cytopathic?

A

No

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3
Q

Describe the type of virus that FeLV is

A
  • 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
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4
Q

What is core protein p27?

A
  • 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
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5
Q

What are the FeLV envelope proteins?

A
  • 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
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6
Q

Outline FeLV epidemiology

A
  • 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)
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7
Q

In what cells does FeLV infect for viraemia?

A
  • lymphocytes and monocytes
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8
Q

Where does FeLV replicate?

A

marrow, lymphoid cells

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9
Q

What does persistent FeLV viraemia cause?

A
  • stress, immunosuppression, GCs
  • malignancy
  • myelossuppression
  • immunosuppression
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10
Q

How is FeLV shed?

A
  • saliva
  • nasal secretions
  • faeces
  • urine
  • milk
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11
Q

How long does FeLV survive outside body?

A

short survival (few hours)

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12
Q

Transmission - FeLV?

A
  • intimate prolonged contact: sharing food and water, mutual grooming
  • neonates (in utero and nursing)
  • blood transfusions
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13
Q

4 results of FeLV infection?

A
  • persistent viraemia
  • transient viraemia
  • latent infection
  • localised infection
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14
Q

CS - FeLV

A
  • 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
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15
Q

Why do you get secondary infections with FeLV?

A
  • immunosuppression: common
  • depletion of itnerference with function of lymphocytes +/- neutrophils
  • susceptible to co-infection: common, opportunistic pathogens
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16
Q

Outline haematological disorders of FeLV

A
  • 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)
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17
Q

What is the relationship b/w FeLV and lymphoma?

A
  • 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
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18
Q

Prognosis - FeLV cats

A
  • 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
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19
Q

Dx- FeLV

A
  • 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)
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20
Q

Interpret a positive test result for Ag test for FeLV

A
  • transient or persistent viraemia
  • owing to low prevelance of FeLV, consider repeating (ideally using different test)
  • IFA: BM infection, persistent viraemia (rarely transient viraemia)
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21
Q

Interpret a positive test result for IFA test for FeLV

A

BM infection, persistent viraemia (rarely transient viraemia)

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22
Q

Interpret a negative test result for FeLV

A
  • unexposed
  • elimination of previous infection
  • early infection (retest in 9-12 wks)
  • latent infection
  • localised infection
  • false negative (usually test reliable)
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23
Q

What are the different stages of FeLV infection?

A 
1 oropharynx
2 primary viraemia
3 lymphoid tissue
4 BM
5 marrow viraemia
6 epithelial tissue
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24
Q

How to interpret positive antigen, negative IFA or viral isolation for FeLV (i.e. discordant results)?

A
  • 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
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25
Q

What should you do if you have a positive screening test for FeLV?

A

run confirmatory test (IFA, qPCR (viral isolation))

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26
Q

What should you do with a cat with discordant results (e.g. positive Ag and negative IFA or viral isolation) for FeLV?

A

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
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27
Q

Tx - FeLV that is systemically well

A
  • general preventative healthcare (nutrition, prevent 2 infection, neuter if entire, confine indoors)
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28
Q

Tx - FeLV that is sick

A
  • supportive care
  • tx secondary illness
  • confine indoors
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29
Q

Outline vaccination for FeLV

A
  • 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
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30
Q

What type of virus is FIV?

A
  • Retroviridae, Lentivirus
  • RNA virus (uses RT)
  • 5 subtypes
  • similar to HIV
  • no risk of transmission to people
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31
Q

Epidemiology - FIV

A
  • 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
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32
Q

Transmission - FIV

A
  • primarily bite wounds, large amount of virus in saliva

- less commonly: vertical (transplacental, milk), sexual (minor), sharing food bowls (minor)

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33
Q

Pathogenesis - FIV

A

5 PHASES:

  • acute
  • asymptomatic carrier
  • persistent generalised lymphadenopathy
  • terminal (AIDS-related complex and AIDS)
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34
Q

Describe the acute phase of FIV

A
  • 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
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35
Q

Describe FIV asymptomatic carrier

A
  • 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
36
Q

What is the AIDS stage of FIV

A
  • 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
37
Q

Commonest clinical syndromes of FIV

A
  • stomatitis
  • neoplasia (5times increased for lymphoma, SCC)
  • ocular inflammation (uveitis, chorioretinitis)
  • anaemia and leukopaenia
  • opportunistic infections
  • renal insufficiency
38
Q

Dx - FIV

A
  • CBC: neutropaenia, anaemia, thrombocytopaenia, co-infection with M.haemofelis –> haemolytic anaemia
  • BIOCHEM: usually NAD, +/- polyclonal gammopathy
  • FIV test
39
Q

What are the FIV tests?

A
  • 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
40
Q

Interpret - positive test result for FIV

A
  • PI
  • FIV-infected queens: test kittens > 6 months old (MAb)
  • false positive result (low prevalence)
  • weak positive result –> repeat
  • if kitten
41
Q

Interpret - negative test result for FIV

A
  • 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
42
Q

Recommendations - if cat is in contact with known/ potential FIV+ cat

A

cat tests negative: re-test at least 120d after initial exposure to confirm negative

43
Q

Recommendations for possible FIV cat where test result doesn’t fit clinical suspicion

A

re-test

44
Q

When is PCR helpful for FIV?

A

IF YOU SUSPECT:

  • interference: MAb
  • immunosuppressed
  • detection prior to Ab production: 1-3wks vs 2-4 mo
45
Q

Tx - FIV

A
  • SUPPORTIVE: AB (anaerobes), care if using corticosteroids with ABs (gingivitis, stomatitis), lactoferrin (for stomatitis)
  • ANTIVIRAL: Zidovudine (little/no help once infected)
46
Q

What is Zidovudine?

A
  • 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
47
Q

Prevention of FIV infection

A
  • 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
48
Q

Describe FeLV subgroup A

A
  • present in almost all FeLV-infected cats
  • only group transmitted cat-cat
  • basis for production of other subgroups
  • least pathogenic of 3
49
Q

Describe FeLV subgroup B

A
  • recombination of subgroup A with endogenous FeLV proviral sequences
  • oncogenic
50
Q

Describe FeLV subgroup C

A
  • arises from mutation of subgroup A

- non-regenerative anaemia

51
Q

Risk factors - FeLV

A
  • Male > female
  • young cat (1-6 yo)
  • multi-cat household
  • outdoor> indoor
  • susceptibility to infection highest in young kittens
  • kittens
52
Q

Describe persistent viraemia with FeLV

A
  • majority of persistently viraemic cats develop FeLV-associated dz within 3-5 years after infection
  • don’t develop VNAb
  • neoplastic and non-neoplastic dz
53
Q

Describe transient viraemia with FeLV

A
  • virus completely eliminated
  • may take up to 3 months
  • usually high titres of VNAb
54
Q

Describe latent infection - FeLV

A
  • 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
55
Q

Describe localised infection with FeLV

A
  • uncommon
  • viral infection sequestered in certain tissues (mammary glands, bladder, eyes)
  • may give discordant test results (positive Ag, negative other)
56
Q

Describe secondary infections with FeLV

A
  • OPPORTUNISTS: bacteria, viruses, fungi, protozoa
  • chronic bacterial infxn
  • calicivirus
  • Cryptococcus neoformans
  • dermatophytosis
  • FIP
  • Mycoplasma haemofelis
  • Toxoplasma gondii
57
Q

FeLV - outcome depends on …

A
  • age
  • viral factors
  • immune status (other ifxn, vaccination, GCs)
58
Q

Defien FOCMA

A

Feline Oncornavirus Cell Membrane Antigen

59
Q

What is FOCMA?

A

= 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
60
Q

What I-M dz may result from FeLV?

A
  • IMHA
  • glomerulonephritis
  • uveitis (immune complex deposition in iris and CB)
  • PA
61
Q

What repro problems may arise from FeLV?

A
  • 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
62
Q

What skeletal abnormalities may result from FeLV?

A
  • 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
63
Q

What neuro dz may result from FeLV?

A
  • 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
64
Q

Describe the immunoassay for FeLV

A
  • 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
65
Q

Describe IFA test for FeLV

A
  • 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)
66
Q

When might you get a false negative IFA test result?

A

neutropaenia or thrombocytopaenia

67
Q

Why might you get a false positive IDA test result?

A
  • smear too thick

- inexperienced personnel

68
Q

Describe PCR detection of FeLV

A
  • 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
69
Q

Describe viral culture in detection of FeLV

A
  • langford or glasgow
  • blood in heparin or EDTA
  • gold standard to confirm
  • not all cats with FeLV yield positive culture
70
Q

Describe Ab test in detection of FeLV

A
  • 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
71
Q

Describe FeLV virus neutralising Abs (VNAbs)

A
  • 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
72
Q

Prevention - FeLV infection in vet practice

A
  • 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
73
Q

Vaccination - FeLV

A

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
74
Q

1/3 cats with FIV present in which stage?

A

lymhadenopathy

75
Q

What are CS of lymphadenopathy with FIV?

A
  • anorexia
  • wt loss
  • FUO
  • lymphadenopathy - persistent, generalised
76
Q

Duration - lymphadenopathy stage of FIV

A

6mo- several years

77
Q

CBC - FIV cat in lymphadenopathy stage

A

+/- leucopaenia

  • anaemia
  • CD4:CD8 ratio inverted
78
Q

What is the AIDS related complex with FIV?

A
  • 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
79
Q

What are the Ab tests against FIV?

A
  • 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
80
Q

Describe IFA test for FIV

A
  • 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
81
Q

Describe WB test for FIV

A
  • detects Abs
  • more specific than ELISA
  • laborious, expensive
  • confirmatory test for a positive ELISA
82
Q

Other tests for FIV

A
  • VIRAL AG: not possible as circulating levels too low for detection
  • VIRAL ISOLATION: only in research centres
  • qPCR: commercially available, variability in viral genome
83
Q

Outline use of immunomodulators in tx of FIV

A
  • 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
84
Q

What are the challenges of FIV vaccination?

A
  • error-prone RT enzymes
  • viruses take advantage of Ab production: paradoxical enhancement of viral replication and dz expression
  • large genetic diversity
85
Q

Describe the FIV vaccine

A
  • 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
86
Q

Preventative healthcare if FIV+

A
  • 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

Lymphoreticular and haematopoeitic (21 decks)

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