Feline leukemia virus disease in Cats (Felis) | Vetlexicon
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Feline leukemia virus disease

ISSN 2398-2950

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Synonym(s): leukaemia

Introduction

  • Cause: feline leukemia virus (FeLV) Feline leukemia virus.
  • Signs: relate to specific malignancies, eg:
    • Weight loss.
    • Diarrhea.
    • Vomiting.
  • Immunosuppression, eg:
    • Chronic or repeated infections.
    • Anemia.
    • Reproductive disorders and glomerulonephritis.
  • Diagnosis: ELISA, RIM, immunofluorescence, PCR or virus isolation.
  • Treatment: cannot stop viral excretion; specific treatments for lymphomas and infections; supportive, eg transfusion.
  • Prognosis: good if transient viremia, poor if persistently viremic.
    Print off the Owner factsheet on FeLV Feline Leukaemia Virus (FeLV) to give to your client.

Presenting signs

  • Depends on disease resulting from infection - see clinical signs.

Geographic incidence

  • Occurs worldwide.
  • There are significant geographical differences in the prevalence of FeLV infection, eg in Sydney (Australia) there has always been a very low prevalence. General prevalence in most European countries is low (around or below 1%), although in some regions it can exceed 20%.
  • More common in sick cats, multi-cat households and outdoor cats.

Age predisposition

  • High rates of disease and death in cats that are persistently viremic.
  • <5 months - more susceptible to development of persistent viremia, but most cats are diagnosed aged 1-6 years.
  • With age, cats become increasingly resistant to FeLV; however they can still become infected with persistent or high challenge doses.

Pathogenesis

Etiology

Predisposing factors

General

  • Age (resistance develops with age).

Specific

  • Multi-cat households.
  • Outdoor access (contact with infected cats).
  • High local prevalence of infection.
  • Sick cats.

Pathophysiology

  • FeLV oronasal infection   →   replication in local lymphoid tissue   →    FeLV spreads via mononuclear cells = transient viremia and production of free p27 antigen   →    after ~3 weeks infection of bone marrow occurs   →    infected granulocytes and platelets occur which are positive for cell-associated p27 antigen   →    the longer the bone marrow is infected, the more likely persistent viremia is to occur.
  • The cat can mount an immune response to FeLV at different times following infection:
    • Abortive recovery occurs if the effective immune response occurs before a transient viremia develops.
    • Recovery is still possible after transient viremia, either before or shortly after bone marrow infection has occurred. Transient viremias typically last about 3 weeks but can be a maximum of 16 weeks.
    • If bone marrow infection occurs before recovery, cats can become latently infected after resolution of the transient viremia.
    • Not all, but the majority of cats that undergo bone marrow infection will become persistently viremic.
  • Latent infections can theoretically be reactivated by stress or corticosteroids (immunosuppression)   →   persistent viremia but this is believed to be rare.
  • Focal (localized) infections can result in a small percentage of infected cats. Here FeLV is sequestered in certain tissues (eg gastrointestinal tract, lymph nodes, spleen, bone marrow) where viral replication occurs.
  • Persistent viremia   →   various pathogenic variants of FeLV, eg immunosuppressive, anemogenic or tumorogenic.
  • There are three subgroups of FeLV:
    • FeLV-A - inter-host transmission; all infected cats.
    • FeLV-B - may be associated with increased risk of neoplastic disease; 50% infected cats.
    • FeLV-C - associated with the development of non-regenerative anemia via direct effect on erythroid precursors in bone marrow; <2% infected cats.
  • FeLV-B and FeLV-C are variants that are derived from FeLV-A which have differing vitro cell tropisms from the parent wild type (FeLV-A).

Timecourse

  • 85% persistently infected cats die within 3 years (cf 20% non-viremic controls).

Epidemiology

  • Free range, single cats: 50% exposed to FeLV, 1% develop active infection   →   low risk of disease.
  • Multi-cat household: 100% exposed to FeLV, 40% develop active infection   →   high risk of disease.
  • Latent/localized infection - virus can sometimes be transmitted in milk.

Diagnosis

Presenting problems

Client history

  • Varies with presenting disease.

Clinical signs

Immunosuppression
  • Septicemia.
  • Repeated infections, sometimes with unusual or opportunistic infections.
  • Infections unresponsive to conventional therapy.
  • 'Poor-doers'.

Lymphoma

  • See lymphoma Lymphoma.
  • Anterior mediastinal (thymic) lymphomas   →   esophageal compression   →   vomiting, regurgitation. Loss of anterior 'rib spring' (manual compression of the anterior thorax) is useful aid in clinical examination.
  • Alimentary   →   weight loss, diarrhea +/- vomiting.
  • Extranodal/miscellaneous lymphomas involving CNS, kidneys, nose, ocular (uveitis seen) etc.
  • Leukemias Acute lymphoblastic leukemia and multicentric lymphoma   →   inappetence, weight loss, plus dyspnea (due to pleural effusion), often anemia as well.
  • Note that in recent years (with the advent of widely available vaccination and testing protocols) there has been a shift in the nature of FeLV-associated lymphoma in the cat.  There is now a greater prevalence of alimentary lymphoma (than anterior mediastinal or multicentric), which occurs in an older cohort of cats, and may not necessarily be FeLV associated.

Anemia

  • Pale mucous membranes.
  • Rapid weak pulse.
  • Lethargy.

Reproductive disorders

Neurological disease

  • Hyperaesthesia.
  • Abnormal vocalization.
  • Paresis.
  • Anisocoria.

Glomerulonephritis

  • Protein losing nephropathy.
  • Polyuria/polydipsia.

Polyarthritis

Hemorrhagic enteritis

Diagnostic investigation

Tests for free p27 antigen: ELISAs Enzyme linked immunosorbent assay (ELISA) and immunochromatography (Rapid Immunomigration) methods

  • Performed on serum or plasma and in-house test kits available.
  • Positive results indicate presence of free FeLV p27 in the cat's blood indicating the presence of viremia at that stage. However the cat may be able to overcome the FeLV infection so that the viremia is only transient. Transient viremia can last up to 16 weeks (although usually <3 weeks) so repeat testing is recommended to confirm persistent viremia. Alternatively another test method can be used to evaluate the cat's FeLV status, eg immunofluoresence or PCR PCR (Polymerase chain reaction). Interpretation will be influenced by the health status of the cat being treated.

Test for cell-associated p27 antigen: immunofluorescence Indirect immunofluorescence 

  • Performed in commercial laboratories only and detects p27 antigen within neutrophils and platelets on blood or bone marrow aspirate smears.
  • Positive smears indicate presence of cell-associated FeLV p27, indicating bone marrow infection. Since bone marrow infection occurs after a few weeks of FeLV infection, most cats that are IFA positive will be persistently viremic. However transient viremia is still possible so repeat testing may be indicated to confirm the cat's FeLV status. Interpretation will be influenced by the health status of the cat being tested.

PCR

  • Detect viral RNA or DNA (provirus) in blood; those commercially available usually detect proviral DNA. A positive proviral PCR result indicates presence of FeLV provirus in the sample, which occurs with viremia (transient or persistent) and some abortive infections. With latter, and those cats that had a transient viremia only, ELISA and IFA tests will be negative once cat has recovered. Large amounts of provirus (measured by quantitative PCR) usually equate with persistent viremia whilst lower amounts of provirus equate with abortive and recovered infections. The significance of a positive PCR result, concurrent with negative ELISA and IFA tests, is unknown. Although there is a theoretical possibililty that provirus could cause disease or lead to reactivation of infection, preliminary studies suggest this is unlikely.

Virus isolation (VI) - detects whole living virus

  • This involves culture of FeLV from blood at specialist laboratory but now performed less as time-consuming. Indicates presence of whole FeLV in the blood, which occurs with bone marrow infection. Interpretation similar to IFA testing.

Confirmation of diagnosis

Discriminatory diagnostic features

  • Signs.

Definitive diagnostic features

  • IFA, PCR or VI.

Differential diagnosis

  • Depends on presenting disease.

Treatment

Standard treatment

  • No treatment will stop viral excretion.
    Check for other FeLV diseases before treating.

Interferon

  • Experimentally, cats with FeLV infection have been treated with recombinant human interferon alpha in combination with the antiviral drug AZT.
  • Recombinant interferon has been administered orally or systemically.
  • Prolonged systemic treatment with human interferon alpha leads to the induction of neutralizing antibodies.
  • Recent studies with subcutaneous recombinant feline interferon omega Interferon (Virbagen Omega") have also been performed in FeLV infected cats and showed that treated cats lived longer than non-treated cats but the mechanism of action is not known since no virological parameters were measured.
  • The outcome of these studies has been variable in terms of clinical efficacy. 

Lymphoma

  • Most are chemosensitive.

Anemia

Immunosuppression

  • Symptomatic.

General management

Prevention

Prophylaxis

  • Vaccination against FeLV is recommended for cats at risk:
    • Inactivated virus vaccine.
    • Recombinant vaccine with FeLV gene in canarypox vector.
    • Recombinant subunit (FeLV subgroup A) vaccine made using bacterial expression system.
    • Subunit vaccine (FeLV subgroups A, B and C) made of purified glycoprotein from infected cat cells.
    • Others available in US.
  • All cats which test negative should be vaccinated. However, positive results obtained with in-house test kits should be interpreted with caution. Since the prevalence of FeLV in healthy cats is very low, the chance of a positive result being truely positive is low; you must therefore rule out a false positive.  The ABCD (European Advisory Board on Cat diseases www.abcd-vets.org) recommends that an unexpected positive result in a healthy cat should always be confirmed, eg with PCR or VI  by a reliable laboratory.
  • Test all cats prior to vaccination:
    • Asymptomatic cats are major source of infection and owners may regard an untested but vaccinated cat as 'safe'.
    • Allows correct management of positive cases and avoids pointless vaccination.
  • Vaccinate young, ie at 8 weeks of age, before routine vaccination.
  • ABCD recommends that kittens receive initial vaccinations at 9 and 12 weeks of age, followed by annual boosters. It is recommended that boosters be given not more often than very 2-3 years to cats of 3 years or older - and only if they are at risk.
    No commercially available vaccine reliably induces FeLV neutralizing antibodies, but the products may still be protective.
  • Latent infections are hard to diagnose, but vaccination will do no harm (cats are immune anyway).
  • No known benefit to vaccinating persistently viremic cats.

Group eradication

  • Test all cats in household   →   :
    • Quarantine positive cats.
    • Restrict movement of negative cats.
  • Retest all cats after 12-16 weeks   →   :
    • 'FeLV free' - test annually if in breeding colony.
    • If negative on second test   →   test annually.
    • If two positive tests   →   remove cat.
    • If negative on first, positive on second test   →   quarantine and retest in 12-16 weeks.
  • Virus is extremely labile in environment and spread by direct cat to cat contact - unaffected cats are therefore not at risk if introduced in environment previously inhabited by affected cat.
  • Do not breed from FeLV infected queens.

Outcomes

Prognosis

  • Poor: 85% of persistently infected cats die within 3 years.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Little S, Levy J, Hartmann K, Hofmann-Lehmann R, Hosie M, Olah G, Denis K S (2020) 2020 AAFP Feline Retrovirus Testing and Management Guidelines. J Feline Med Surg 1, 5-30 (Full Article).
  • Cattori V, Tandon R, Riond B et al (2009) The kinetics of feline leukaemia virus shedding in experimentally infected cats are associated with infection outcome. Vet Microbiol 133 (3), 292-296 PubMed.
  • Lutz H, Addie D, Belák S et al (2009) Feline leukaemia. ABCD guidelines on prevention and management. J Fel Med Surg 11 (7), 565-574 PubMed.
  • Dunham S P & Graham E (2008) Retroviral infections of small animals. Vet Clinics North Am Sm Anim Pract 38 (4), 879-901 PubMed.
  • Goldkamp C E, Levy J K, Edinboro C H et al (2008) Seroprevalences of feline leukemia virus and feline immunodeficiency virus in cats with abscesses or bite wounds and rate of veterinarian compliance with current guidelines for retrovirus testing. JAVMA 232 (8), 1152-1158 PubMed.
  • Hofmann-Lehmann R, Cattori V, Tandon R et al (2008) How molecular methods change our views of FeLV infection and vaccination. Vet Immunol Immunopathol 123 (1-2), 119-123 PubMed.
  • Levy J, Crawford C, Hartmann K et al (2008) 2008 American Association of Feline Practitioners' feline retrovirus management guidelines. J Fel Med Surg 10 (3), 300-316 PubMed.
  • Hartmann K, Griessmayr P, Schulz B et al (2007) Quality of different in-clinic test systems for feline immunodeficiency virus and feline leukaemia virus infection. J Feline Med Surg (6), 439-445 PubMed.
  • Hofmann-Lehmann R, Cattori V, Tandon R et al (2007) Vaccination against the feline leukaemia virus: outcome and response categories and long-term follow-up. Vaccine 25 (30), 5531-5539 PubMed.
  • Pinches M D, Helps C R, Gruffydd-Jones T J et al (2007) Diagnosis of feline leukaemia virus infection by semi-quantitative real-time polymerase chain reaction. J Fel Med Surg (1), 8-13 PubMed.
  • de Mari K, Maynard L, Sanquer A et al (2004) Therapeutic effects of recombinant feline interferon-omega on feline leukemia virus (FeLV)-infected and FeLV/feline immunodeficiency virus (FIV)-coinfected symptomatic cats. JVIM 18 (4), 477-482 PubMed.
  • Lappin M R (2000) Feline infectious uveitis. J Feline Med Surg​ (3), 159-163 PubMed.
  • Malik R, Kendall K, Cridland J et al (1997) Prevalences of feline leukaemia virus and feline immunodeficiency virus infections in cats in Sydney. Aust Vet J 75 (5), 323-327 PubMed.

Other sources of information