Feline Leukemia Virus Infection Update on Diagnosis and Prognosis
World Small Animal Veterinary Association World Congress Proceedings, 2003
Craig E. Greene
University of Georgia
Athens, GA, USA

Etiology and Epidemiology

FeLV is a retrovirus that can be acquired any time in a cat's life: prenatal, neonatal or older. Younger cats are more susceptible to infection. Infection is transmitted via oronasal secretions and cats in high feline population densities have the highest prevalence of infection. Testing and removal and vaccination programs have decreased the prevalence of infection in recent years.

Clinical Signs

FeLV exposure results in a number of possible outcomes including solid immunity, transient viremia with latency and clearance and overwhelming persistent viremia. The outcome as for other infections is determined by virulence of the infecting strain, host immune responses and environmental exposure. Highly inbred cats, young kittens, and crowded cats are predisposed to develop persistent viremia. While transient viremia and latent infections are associated with recovery, persistently viremic cats usually die of secondary diseases caused by immunosuppression, within 3 years of infection. Approximately 25% of persistently viremic cats develop lymphogenous neoplasia, usually by 4 years of age. In addition to immunosuppression and secondary infection, cats that are persistently infected can develop a number of different viral-induced bone marrow disturbances including myeloproliferative diseases, and myelosuppression.

Diagnosis

There are two main types of tests for FeLV. The first is the enzyme linked immunosorbent assay (ELISA). The other main type of test for FeLV is the immunofluorescent (IFA) assay. Most veterinarians in practice or the commercial laboratories, to which they send samples for analysis, are screening for FeLV by ELISA testing. The FeLV test, whether done by ELISA or IFA, detects circulating blood antigen. The FeLV-ELISA test on blood detects small quantities of soluble antigen in serum; the IFA tests for antigen in leukocytes. The ELISA is more sensitive and can detect antigen in the early viremic and incubation periods when only lymphocytes are infected. Cats that cannot eliminate the virus get infection of their marrow and the IFA becomes positive since circulating leukocytes become virus-positive.

Never exposed or recovered cats are similar in their test results by being negative on all tests except the level of neutralizing antibodies. Some cats successfully eliminate the virus from the circulation, the virus goes into hiding in their genetic material; this is called latent infection. These cats are ELISA and IFA negative. The only way to determine the FeLV-positive status of these cats is by culturing their bone marrow in vitro. Direct FA on their marrow without culture is negative. Cultivation of marrow is impractical in veterinary practice. Nevertheless this research tool tells us that some FeLV-negative cats can still have virus in their body.

Presently PCR can give us the same information as bone marrow cultivation. It does so in an easier and more rapid manner. There is no standardization of this procedure and the results may vary according to which tissues are examined.

Cats that can suppress the virus from entering the bone marrow are called immune carriers. They are ELISA positive (usually weak) but IFA negative. With time many immune carriers eliminate virus from the blood, become latently infected, then subsequently eliminate the virus from their genome, becoming recovered cats. Those cats that can't eliminate the infection develop infection of all lymphoid and myeloid cells and become persistently viremic.

On the basis of ELISA alone, it is hard to tell the difference between the immune carrier cat and the persistently viremic cat. Unfortunately there is a big difference in prognosis between these two categories. In 2 to 3 years most persistently viremic cats develop lymphosarcoma or a secondary infection which necessitates their being euthanized. In contrast about 50 % of immune carriers will clear the virus from their blood, about 50 % will stay the same status and only a small percentage will become persistently viremic. Therefore any cat that is positive by ELISA should be separated from other cats since they do shed the virus. All cats in the immediate environment of this cat should be similarly tested and segregated if positive. These cats should be tested by ELISA 4 to 8 weeks later and, if still positive, should have an IFA done to determine if they are persistently viremic, which will help to give a long-term prognosis.

Tests for FeLV neutralizing antibody are rarely done in practice and offer vague information as to the prognosis or diagnosis of FeLV. Detecting neutralizing antibody titers against envelope antigens indicates exposure to the virus at a given point in time and high levels of antibody can indicate a cat's immune status with regard to protection from viremia.

PCR Revelations

In the past, at the time that FeLV testing became universal, it was estimated that somewhere between 50% and 70% of cats with lymphoid neoplasia were viremic. This percentage has been getting lower in the last decade. Cats with lymphoid neoplasia that test negative by ELISA on peripheral blood are generally older than 7 years and have visceral involvement. Studies using PCR on tumor tissue rather than peripheral blood have shown a higher prevalence of FeLV-associated neoplasia than previously appreciated. In tissues from cats with lymphoma, most had FeLV detected by PCR while approximately 50% tested positive by immunohistochemistry. Of these same cats, 10% had ELISA and histochemical tests that were negative. Multicentric and mediastinal lymphomas were more likely positive for FeLV as compared to alimentary forms. In another study, few cats from with lymphoid neoplasia had FeLV positive test results on serum ELISA. Despite this low level of viremia detected by ELISA, Twenty-five percent of the tumors contained FeLV viral nucleic acid as determined by PCR. There is still limited information as to the outcome or prognosis of treated cats with lymphoma that are infected with FeLV as compared to uninfected cats. Further evaluation of latently infected cats during treatment will be needed to see if chemotherapy causes reversion to viremia. In checking suspected cats by PCR, bone marrow testing appears to be more sensitive than peripheral blood.

Vaccination

There are many products now available for FeLV and it has become a competitive market. In general, testing cats for FeLV is recommended prior to vaccination. The cost and delay of testing may outweigh the convenience of vaccinating. False-negative results may occur very early due to maternal antibodies but the delay in testing after the owners become attached to a new kitten makes the results less important. Although the ELISA cannot distinguish between transient and persistent infections, it is a good predictor as to whether or not cats can respond to vaccination. Even latently infected cats can respond. In contrast any cat that tests positive on ELISA (immune carrier or persistently positive cat) does not respond to the vaccine.

Efficacy of currently available FeLV vaccines varies between 0 to 100 %. This efficacy varies according to the method of challenge, vaccine regimen, and means of determining infection. None of these variables have been consistent between products. Therefore, as a general recommendation, even vaccinated cats should be separated from FeLV test positive cats.

Immunotherapy

Oral interferon orally has been used to treat viremic, clinically ill cats. The precise mechanism of action is unknown. It is the only such drug with controlled efficacy studies. Doses vary between 1 to 30 units/cat per day PO. Staphylococcal Protein A has also been used in controlled studies but it must be given IP over an extended period.

Speaker Information
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Craig E. Greene
University of Georgia
Athens, GA, USA


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