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Viral Disease - Feline Leukemia Virus

Definition:

FeLV causes a chronic infection that may induce neoplasia, immune deficiency, or bone marrow suppression.

Etiology

FeLV is an SS-RNA virus of the family Retroviridae, subfamily Oncornavirinae.

Epidemiological findings

Horizontal and vertical transmission occur.

Close contact is required, and fomites are minimally involved.

FeLV, though shed in all bodily secretions, is transmitted primarily via saliva (usually during grooming); bite wounds; and shared use of food bowls, water bowls, and litter boxes.

Rarely, transmission occurs transplacentally via the milk during nursing and through blood transfusions, needles, or surgical instruments.

Viral particles are shed from both ill and healthy infected cats.

Kittens are far more susceptible to infection than adult cats.

Pathogenesis

Many outcomes are possible after exposure, including recovery, latent infection, or persistent viremia.

The outcome depends on the subgroup of FeLV, age of the cat, immune response, and other variables.

If the initial immune response is ineffective, viremia occurs with replication in lymphoid tissue and bone marrow.

With an effective immune response, viremia ceases, but virus may remain integrated in bone marrow cells.

  • » Latently infected cats are not viremic and not a source of exposure for other cats.
  • » Infections can remain latent for life or may reactivate during stress or immunosuppression.

Many viremic cats remain persistently viremic, with viral particles in bone marrow, epithelial tissues, and salivary glands.

  • » Persistently viremic cats may be healthy for a period of time or develop one of several clinical diseases.
  • » Malignancy is thought to result from insertional mutagenesis during viral replication.
  • » Antibodies to feline oncornavirus cell-associated membrane antigen protect the cat from malignancy, but not from other disease manifestations.
  • » Direct viral invasion of stem cell precursors or stromal damage causes myelosuppression.
  • » Immunosuppression may arise from lymphopenia and alterations in lymphocyte function.
  • » Decreased T suppressor cells and antigen-Ab complexes contribute to immune-mediated disease.

Clinical Signs

Acute infection has a variety of manifestations.

  • » Often subclinical
  • » Fever, depression, diarrhea, lymphadenopathy, leukopenia
  • » Possible apparent recovery with no signs for months to years

Cats with latent infection may be asymptomatic.

Immunosuppression with secondary infections is the major cause of morbidity and mortality.

Myelosuppression causes non regenerative anemia, leukopenia, and thrombocytopenia.

Malignancy has several forms.

  • » Lymphoma is the most common neoplasia associated with FeLV infection.
  • » Clinical signs of lymphoma reflect the site involved, and include dyspnea (mediastinal); uremia (renal); and ataxia, paralysis, or seizures (CNS).
  • » Less commonly, hematopoietic malignancies (leukemias) develop and can involve any cell line, with clinical signs reflecting a reduction in normal hematopoietic cell numbers.

Other signs include evidence of immune-mediated hemolytic anemia (IMHA), glomerulonephritis, infertility, abortion, and osteo chondromatosis.

Diagnosis

Hematological findings

A. Non regenerative anemia, macrocytic anemia, nucleated red blood cells

B. Possibly circulating blast cells, cytopenia, or leukemia

Serum biochemistries and urinalysis: nonspecific changes reflecting secondary conditions

Lymph node, bone marrow, or mass aspirates: confirm neoplasia or secondary infection

Radiography and ultrasonography: useful to identify neoplasia

FeLV-specific diagnostic testing

  • » A very sensitive and specific ELISA test detects circulating FeLV p27 core antigen.

    • » No false positives occur with maternal Abs.
    • » In-hospital kits can be used on serum, plasma, whole blood, saliva, or tears; saliva and tears are less reliable than serum.
    • » ELISA tests are positive earlier in infection than FA tests.
    • » Test results may revert from positive to negative with latent or cleared infection, so confirm a positive ELISA result by FA testing or a second ELISA test in 1 to 3 months.

  • » FA tests are confirmatory.

    • » FA detects p27 core antigen in leukocytes and platelets from blood or bone marrow.
    • » Because a positive FA test means the virus has replicated in precursor cells in the bone marrow, positive cats are unlikely to revert to a negative status.

  • » Culture or FA of bone marrow samples can be done to diagnose latent FeLV infection.
  • » PCR has no advantage over ELISA on blood samples and is useful only to identify FeLV in preserved neoplastic tissues.
  • » Identification of FeLV does not confirm a particular illness is secondary to FeLV.

    Differential Diagnosis

    Acute illness: feline panleukopenia, FCoV, bacterial infections, FIP

    Anemia: hemorrhage, hemotrophic Mycoplasma spp. chronic disease, renal failure, IMHA, histoplasmosis, atypical tuberculosis, myelophthisis, toxin exposure, etc.

    Neoplasia: non-viral-related leukemia and lymphoma, non-neoplastic causes of lymphadenopathy, pleural effusion, renomegaly, etc.

    Treatment

    No specific treatment is necessary in asymptomatic cats.

    FeLV-induced neoplasia is treated similarly to non-FeLV neoplasia.

    Myelosuppression is addressed as follows:

    Anemia

    Blood transfusion may be life saving.

    Although erythropoietin levels in anemic FeLV positive cats are elevated, short-term use of exogenous erythropoietin is potentially beneficial at 100 U/kg SC 3 times per week

    Address other causes of anemia, such as hemotrophic Mycoplasma spp. infection and IMHA.

    Neutropenia

    The use of human recombinant G-CSF (5 mg/kg/day SC for ≤2 weeks) in severe neutropenia is controversial because at higher doses or for longer periods it may cause production of antibodies to feline colony stimulating factors.

    Consider prophylactic antibiotics.

    Secondary bacterial infections require prompt therapy with appropriate antibiotics.

    Immune modulator and antiviral therapy may be tried, but evidence of efficacy is slim

    • » Staphylococcus aureus protein A 10 mg/kg IP twice weekly
    • » Human recombinant interferon-a 30 U PO SID on alternating weeks
    • » Feline recombinant interferon omega 1 μ 106 U/kg/day SC for 5 consecutive days in 3 series, beginning on days 0, 14, and 60

    Monitoring and Prevention

    Isolate cats with FeLV from noninfected cats; keep infected cats indoors, vaccinate them for other infectious diseases, and do not breed them.

    Vaccination involves the following .

    • » Test before FeLV vaccination, because vaccination of positive cats provides no benefits.
    • » Vaccination is not indicated for low-risk cats (e.g. Indoor cats, single-cat households, or households in which all cats test negative).
    • » Killed and subunit vaccines are equally efficacious.
    • » Vaccine efficacy is <100%, and estimates of true efficacy vary
    • » Initially give two vaccines 3 to 4 weeks apart, with annual booster vaccinations.
    • » Use of FeLV vaccine has been associated with injection site sarcomas in cats.


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