Feline Viral Diseases Flashcards
FIV subclades in Aust and NZ
A and B in Aust, A and C in NZ
Fel-O-vax is A only
FIV Diseases phases/Pathophysiology
Primary/Acute Phase: infection via bite, virus enters macrophages, transported to LNs where it replicates in immune cells and causes acute viraemia
Preferential replication in CD4 T cells and their activation results in high levels of IFNy and IL12 which causes eventual anergy of TH2 cells. Hyperactivation of B cells results in polyclonal response and eventual tolerance
(mild symptoms, most likely to be PCR positive)
Subclinical Phase apoptosis and anaergy of infected T cells and upregulation of T reg cells results in progressive immune dysfunction and declining lymphocyte numbers. Usually low viral load in blood.
May see BM suppression due to MDS manifesting as neutropenia or non-regenerative anaemia.
Terminal/Clinical Phase - functional immunodeficiency with risk of opportunistic infection.
See gingivostomatitis and 6 fold increase in risk of leukaemia/lymphoma. Mostly large B cell, likely due to interaction with Th2 cells and impaired CMI.
Sens and Spec of different FIV tests
2017 JVIM comparative paper and JFMS AAFP review:
Witness and Anigen brand have 95% sensitivity adn 99% specificity
Idexx and vetscan 91% sensitivity and 99% specificity. Because affected by prior vaccination status
Tests may be able to be performed on saliva - AVJ 2022
CD4:CD8 ratio may be useful in documenting transition to terminal phase though more evidence is needed.
Flow cytometry is also being investigated for this purpose.
FIV Tx and reported efficacy
Zidovudine - nucleoside analogue reverse transcriptase inhibitor.
In trials reported to decrease viral load and improve CD4:CD8 ratio as well as QoiL assessment
However - difficult to determine if extend life expectancyt
May cause BM suppression manifesting as nonregenerative anaemia
IFN-omega - did not affect viral load in one study but did improve QoL so may just help with 2ry infections
Good husbandry and low stress env resulted in normal life expectancy in cats with FIV compared to those with FIV living in multicat houses and high stress env,
Reported Fel-O-Vax protective efficacy in Aust
case control field study - 56%
Another study found lack of broadly neutralising Abs so cats may not be protected.
FeLV infetion outcomes
Horizontal or vertical transmission, outcome dependent on host immune status and environmental factors inducing stress/altering viral dose
Abortive = strong immune response and no ongoing infection
Focal - virus sequesters in glandular tissue, unclear why this occurs, seems to be more common experimentally
Regressive - transient viraemia followed by partial or strong immune response in 3-216 weeks. Viral infection of BM cells can develop in this time and proviral DNA incorporates into genome., strong Ab response keeps virus from causing viraemia though can relapse with immune suppression
Progressive - minimal or no host immune response to virus, it replicats in variaous lymphoid and glandular tissues, is shed in saliva and other secretions. These are the main source of infections in new cats.
Carry a high risk of FeLV associated disease
Reported FeLV associated disease
- Immune suppression due to reduce lymphoid proliferation or anergy.
- Immune mediated disease due to loss of Treg cells or other suppressing signals which can result in type III hypersensitivities.
- Oncogenesis - 60 fold high risk of T cell lymphoma (B cell in FIV), a result of viral genome insertion near oncogenes resulting in activating mutations or downregulating mutation near tuimour suppressor genes. Most likely to occur in progressive infections where there is active viral replication.
Also see generation of feline sarcoma virus and FOCMA which are recombinant version so fELV) - BM infection can result in PRCA or thrombocytopaenia (possible type II mediated disease) along with myelodysplastic syndromes which may progress to leukaemia.
FeLV associated enteritis is also reported along with neurological symptoms from LP inflammation and ocular changes.
Diagnostic Tests for FeLV
Antigen - IFA or ELISA to detect p27
Sens 85-100; Spec 85-100%
PPVv 80%, lower in low disease prevalence areas
Recent JFMS study reported discordant ELISA and proviral PCR results - PPV 72% based on prevalence of 3% in population. This was performed in anaemic cats with other dises that had clinical features of FeLV.
Saliva viral RNA - good detection of shedders, can pool samples in screening
Antibody detection - rarely used as sens 77%; Spec 85% and does not differentiate abortive from regressive infections
Proviral DNA/Plasmid RNA PCR - most sensitive for detection of infection as RNA positive at 1 week, DNA at 2 weeks.
Can be run on BM aspirates to detect regressive infection in cats with anaemia or MDS.
Negative results are quite reliable except in instance of focal infection.
Ideal for screening donors if wasn’t expensive.
FeLV prevention
AAFP recommend screening all cats with p27 antigen detection at time of acquisition and if positive perform further testing to confirm (as false positive may occur in low prevalence population). Negative results generally reliable especially in healthy cats
PCR also has limits in differentiation of progressive vs regressive infection
Discordant results may occur due to changes in viraemia and Ab status with time
Segregation of carrier cats prevents transmission. Virus does not persist in environment.
Vaccine - significantly reduces infection risk but does not induce a sterilising immunity. Protection is not absolute and vaccination is not a replacement for testing.
Canarypox vectored live vaccine stimulates humoral and CM immunity
proviral DNA PCR recommended for screening blood donors in case of regressive infections.
Instrument sterilisation
To screen breeding colony all cats would need to be tested for proviral DNA in blood on 2 occasions 60d apart
(p27 or saliva viral RNA would only indicate no shedding cats)
Reasons why FeLV vaccine efficacy has been difficult to assess
- only small trials published, using experimentally infected cats
- performed by manufacturers
- reported low prevalence of dz in Australia (2%) so not considered a core vaccine
- occurrence of natural resistance in some cats complicates evaluation
- Studies looking at high risk multicat transmission may not be representative of standard exposure in rest of population
- Most studies looked at virus isolation and antigen detection, but when used PCR proviral DNA was found thus may just prevent progressive disease/prolong survival
- neutralising Ab titres do not develop in all vaccinated cats, but some of those without Ab are still protected (presumed CMI)
Treatments for FeLV and FeLV associated disease
Clinically well cats don’t need treatment. Presence of FeLV is not a reason to not investigate disease.
Still give preventative parasite Tx and vaccines.
Confine and good healthcare
High stress env increases the prevalence of progressive infections.
Avoid immunosuppression in regressive infected cats (if known)
Avoid myelosuppressive medications
Worsens prognosis if concurrent neoplasia. Leukaemias have very poor RR to chemo. Also have severe disease with involvement of very early precursors. Consider BM stimulation or transfusions to palliate. Some have IM component
Haematological disorders are mostly irreversible. Check for Mycoplasma and treat if detected.
A few long term controlled studies in naturally infected cats have shown benefit of zudovudine (AZT) and feline interferon omega.
Former can cause non-regenerative anaemia, latter may just be inhibiting secondary infections. But both seem to improve QoL
FIP symptoms by body system
Non-specific - fever, lethargy, weight loss, jaundice, non-regenerative anaemia
GI - fluid wave, intestinal masses, Lymphadenomegaly; D+
Renal - ICGN and proteinuria
Resp - dyspnoea, pleural effusion
Cardiac - pericardial effusion and tamponade
Neuo - seizures, multifocal deficits, central vestibular disease, tetra/paraparesis, hyperaesthesia, CN deficits, obstructive hydrocephalus (increasing ICP)
Ocular - chorioretinitis, uveitis, blindness, hyphaema, hypopyon and retinal detachment, iris colour change,
Derm - vasculitidies due to type III dzx; toxic epidermal necrolysis
Tests for FIP - Sens and Spec
Baseline: non-regen anaemia, increased globulins, hyperbilirubinemia, hypoialbuminemia,
A:G <0.4 Sensitive but not specific (A:G >0.8 has high NPV)
Acute phase proteins - SAA and AGP seem most sensitive (not specific) and can monitor trends
Effusion - TP >35 and TNCC <5000 with mostly neuts and macs is strongly supportive
+ revolta test has PPV of 86% and NPV 97%
Antigen detection (ICC, IFA, IHC) - need to demonstrate virus INSIDE macs, IHC on tissue considered gold standard (98% sens, 100% spec), ICC on tissue aspirates has lower sens (17-90%) but good specificity (91-98%) - recent JFMS study in cases with strong index of suspicion had high sens and spec for LN aspirates. Lowest ICC sens/spec seen with renal aspirates.
RT PCR - dependent on primer used and site. In effusion has high sens and spec (70-90 and 80-100) but in CSF sensitivity is lower (17-86%) though specificity higher (100%)
Not as useful on blood as can give false positives (any FCoV infection)
antibody detection considered not useful due to + from incidental FCoV infection and ability for Ab to be present in CSF and effusions. Can also get false negative due to Ab binding to viral antigens and not reacting in test.
Abdo u/s findings of FIP in recent JFMS study
80% liver abnormalities (varied)
LN enlargement common up to 80%
Variable GI and splenic changes but <50%
Renal changes <30%
What causes FCoV to result in FIP
Mutation of virus (most often in cats with high viral load) gaining function to infect and replicate within macrophages and evade CM immune defences
Spike protein, 7b nonsrtuctural protein and membrane gene protein mutations have all been attributed. No single mutation causes all FIP cases as demonstrated by recent IHC studies and studies looking at FIP virus genome in multiple samples from same FIP infected cat.
Macrophage activation releases IL1,6,TNFa which down regulate NK response and CMI, as well as cause polyclonal B cell expansion through Th2 activation generating a non-protective Ab response.
Subneutralising antibodies may contribute to pathogenesis by enhancing internalisation of FIP virus by macrophages.
