Chapter 4: Feline Leukemia and Feline Immunodeficiency Virus 2 CE Hours

By: Catherine Barnette, DVM

Learning objectives ŠŠ Compare and contrast the epidemiology of feline leukemia virus ŠŠ Describe strategies used to manage cats infected with feline and feline immunodeficiency virus. leukemia virus or feline immunodeficiency virus. ŠŠ Develop a rational testing strategy for feline leukemia virus and ŠŠ Educate veterinary clients on vaccination strategies for feline feline immunodeficiency virus. leukemia virus and feline immunodeficiency virus. Introduction Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) contact between cats, whereas FIV is most frequently spread through are both retroviral infections of cats. These viruses have a number of bite wounds. Additionally, the two viruses differ significantly in key similarities: both viruses have the potential to induce tumor formation aspects of diagnosis because of variations in test methodology and as well as suppressing the immune system. Additionally, both viruses in feline response to the two viruses. Finally, there are significant are unstable in the environment and require transmission through differences in vaccination strategies for FeLV and FIV virus. FeLV bodily fluids, either vertically or horizontally. vaccination is recommended for all at-risk cats; FIV vaccination is far There are also significant differences between the two viruses, more controversial. however. Feline leukemia virus is often spread through close friendly

Feline leukemia virus Feline leukemia virus (FeLV) is a single-stranded RNA virus with vary significantly among cats. Therefore, it is impossible to predict the worldwide distribution. Feline leukemia is classified as a retrovirus, likelihood of infection or an infectious dose of FeLV for any particular a term used to describe an RNA virus that inserts a DNA copy of cat. All cats with possible exposure should be considered at risk of its genome into the host cell to allow replication. Other examples contracting the disease (American Association of Feline Practioners, of retroviruses include feline immunodeficiency virus and human 2013). immunodeficiency virus. Feline leukemia is an oncogenic (tumor- Feline leukemia, like other retroviruses, is an enveloped RNA virus. producing) virus capable of replication in a variety of feline The virus contains an enzyme that reverse-transcribes the viral genome tissues, including the bone marrow, salivary glands, and respiratory into a DNA form referred to as the FeLV provirus. This DNA provirus epithelium. is then integrated into the host cat’s genome, allowing it to replicate In the United States, an overall FeLV prevalence of 2.3% was reported within the host cells (Hofmann-Lehmann, 2016). in a 2006 study of healthy cats (Levy, 2006). Prevalence is higher in Feline leukemia virus can be divided into four major subgroups sick cats, as well as in some particular geographic areas. based on the virus envelope and properties that this envelope confers Feline leukemia can be transmitted horizontally, from cat to cat, (Hofmann-Lehmann, 2016): through close contact. Feline leukemia is often described as a disease ●● FeLV-A: This subgroup is the form of FeLV that is involved in of “friendly” cats, passed through mutual grooming. Infected cats horizontal transmission between cats. The FeLV-A subgroup is shed feline leukemia virus primarily in the saliva, although urine, found in all infected cats. The pathogenicity of FeLV-A is low, but feces, and milk also contain the virus (Hofmann-Lehmann, 2016). The it is highly infectious. transmission of FeLV is typically associated with close contact because ●● FeLV-B: This subgroup is less prevalent than FeLV-A. The the virus is unstable in the environment and dies within minutes; FeLV-B virus forms within the individual cat when FeLV-A virus therefore, FeLV cannot be readily transmitted via fomites. Sharing recombines with endogenous FeLV-related sequences. Lymphoid food bowls and litter boxes may potentially allow transmission, but malignances are often associated with FeLV-B. this is typically regarded as uncommon (Litster, 2015). ●● FeLV-C: This subgroup is also less prevalent than FeLV-A. Feline leukemia virus can also be spread vertically, from mother to Like FeLV-B, FeLV-C arises in the individual cat; however, its offspring. Infected pregnant queens frequently suffer reproductive formation is caused by mutations or deletions in the FeLV-A losses and do not carry their kittens to term. Kittens that do survive to surface glycoprotein gene. Aplastic anemia is typically associated term, however, are frequently born viremic. These kittens often fade with FeLV-C. quickly, experiencing death early in life, although as many as 20% ●● FeLV-T: Like FeLV-C, FeLV-T also arises in the individual cat of kittens born with FeLV may survive to adulthood with persistent caused by mutations or deletions in FeLV-A surface glycoproteins. infection (American Association of Feline Practioners, 2013). If the Immunodeficiency is typically associated with FeLV-T because it kittens of an infected queen are not infected in utero, they may also is a T-cell tropic cytopathic virus and causes lymphoid depletion. be infected through the queen’s milk while nursing or saliva during At this time, FeLV is not regarded as a zoonotic disease. Some studies grooming (American Association of Feline Practioners, 2013). have suggested that human infection with FeLV could be a possibility; The highest susceptibility to FeLV virus is observed in kittens up to however, there are no reports of transmission and no documented cases 4 months of age. Adult cats typically demonstrate some degree of of FeLV-associated human leukemia (Litster, 2015). resistance to infection. It is important to note, however, that biological behavior differs between FeLV strains, and immune responses can

Page 35 veterinarians.elitecme.com Pathophysiology destruction or secondary Mycoplasma hemofelis infection. In other In exposed cats, FeLV infection typically begins in the oropharynx. cases, liver disease may be the cause of icterus. This liver disease may Viral replication occurs in the tonsils and adjacent lymphoid tissues, be attributed to lymphoma, Toxoplasma gondii infection, or hepatic and the virus is then spread throughout the body in the lymphatic lipidosis (Fenimore, 2014). system. At this time, any one of four possible courses of disease may Many cats with feline leukemia will experience reproductive be observed (Hofmann-Lehmann, 2016; Litster, 2015): difficulties, with kittens dying before, or shortly after, birth. ●● Abortive infection: These cats are able to mount an effective Additionally, evidence of neurologic disease may also be observed immune response. Abortive infections are often associated with (Lutz, 2012). Neurologic signs associated with FeLV include ataxia, exposure to low doses of FeLV. These cats will not test positive weakness, anisocoria, para- or tetraparesis, behavioral changes, and for FeLV at any time. In the past, these cats were referred to as urinary incontinence. These signs may be attributed to polyneuropathy regressor cats. or lymphoma (Fenimore, 2014). ●● Regressive infection: Most adult cats exposed to FeLV fall into this category. After infection, the FeLV virus does reach the bone Additionally, there have been reports of immune-complex deposition marrow in these cats and triggers a transient infection. These leading to polyarthritis and glomerulonephritis in FeLV-positive cats will temporarily test FeLV-positive, and they may shed virus cats (Litster, 2015). When a cat with FeLV develops kidney disease, during this time. Within 3 to 16 weeks of infection, these cats will however, it is also important to consider the possibility that renal mount an immune response that suppresses the virus. At this time, failure may also be caused by renal lymphoma (Fenimore, 2014). ELISA testing will be negative though PCR tests may remain Diagnosis positive. The risk of clinical infection in these cats is low though Because of the varying manifestations of FeLV infection, it is viral replication may be reactivated in the future. These cats important that all sick cats be tested for FeLV. Especially strong were previously described as transient viremic followed by latent indicators for FeLV testing include complete blood cell count infection. abnormalities (anemia, leukopenia, leukocytosis, thrombocytopenia, ●● Progressive infection: Persistent viremia, with positive tests thrombocytosis, pancytopenia, leukemia), chronic oral infections repeated weeks or months apart. These cats shed high numbers of (gingivitis, stomatitis), uveitis, immune-complex deposition virus and are most capable of infecting other cats. Progressively (evidence of polyarthritis or glomerulonephritis), other signs of infected cats are at a high risk of death within the next several immunodeficiency, reproductive problems, or neurologic disease. months to years, although some may go on to live long lives. In studies of unvaccinated, exposed cats, approximately 30% to 40% Additionally, cats that have been exposed, or potentially exposed, developed progressive infection (Lutz, 2012). to FeLV should be tested. This includes newly adopted cats and cats ●● Focal or atypical infection: Although rare in naturally infected who have been in contact with a known FeLV-positive cat. It can take cats, viral replication can be confined to one anatomical region 6 weeks or longer for FeLV to be detected in peripheral blood on an of the body. These cats may test weakly, intermittently ELISA in-house ELISA test after infection, so in-house FeLV testing should positive. This is unlikely to be of clinical significance. occur approximately 2 months following suspected exposure. High- risk cats (outdoor cats, cats living with a FeLV-positive housemate, or In cats with progressive or reactivated regressive FeLV infection, cats living in homes with frequent changes in housemates) should also malignancy can occur. This most frequently manifests as be tested on an annual basis if not vaccinated. hematopoietic neoplasia, such as leukemia or lymphoma. Rarely, myeloproliferative disorders occur (Litster, 2015). Most commonly, Among healthy cats, it is also important to test for FeLV before cats with FeLV experience immunodeficiency. Infected cats often FeLV vaccination. The FeLV vaccine does not cause a false positive develop anemia and opportunistic infections, which eventually prove on diagnostic testing, but FeLV status should be determined before fatal (Litster, 2015). vaccination to allow an educated decision regarding the expected benefits of vaccination. Additionally, testing before vaccination will be Clinical signs beneficial in the case that there is ever a suspected vaccine failure. The clinical signs of FeLV are variable, depending on which organ system is affected by the disease. Commonly observed signs of FeLV In the veterinary clinic, the p27 ELISA antigen test is often used as include neoplasia; recurrent infections caused by immunosuppression; an in-house test to assess for the presence of FeLV antigen in the or evidence of hepatic, reproductive, or neurologic disease. blood of infected cats. The p27 antigen is the major core component of FeLV, and its presence indicates viremia (Lutz, 2012). This test is Many FeLV-infected cats present with signs of leukemia or lymphoma highly sensitive and specific; however, it is important to remember caused by the oncogenic properties of FeLV. Dysphagia or dyspnea that the predictive value of a positive test is inversely related to the may be observed in cats with mediastinal lymphoma (Fenimore, prevalence of a disease. Therefore, false positives may be common 2014). Owners may also notice such signs as weight loss, anorexia, in low-prevalence areas (Litster, 2015). Confirmatory testing of or lethargy. If the virus is replicating in the bone marrow, blood count positive ELISA tests should be performed; two tests are used for abnormalities—such as anemia, leukopenia, and thrombocytopenia— confirmation. The currently recommended test for confirmation of may be observed on screening laboratory tests. FeLV-positive ELISA tests is PCR for feline provirus (Litster, 2015). Because of immunosuppression, FeLV-infected cats may also present Immunofluorescent antibody testing can also be used; however, false with recurrent or resistant infections involving any part of the body. negatives may occur with this test in cases of abortive or regressive Infected cats may present with recurrent upper respiratory infections, infection, or in cats with low circulating leukocyte counts (Litster, either viral or bacterial. Many FeLV-positive cats develop chronic 2015). Cats who test positive on an ELISA test should be considered stomatitis associated with bacterial infections or chronic calicivirus positive and quarantined appropriately until the results of confirmatory that cannot be cleared because of immunosuppression (Fenimore, testing are available. 2014). Chronic enteritis may also develop, leading to vomiting If a cat tests positive on both an ELISA and a confirmatory test, and diarrhea. This enteritis typically resembles that seen with an ELISA should be repeated in 1 to 3 months. This will allow panleukopenia and is often caused by bacterial overgrowth (Fenimore, determination of whether the cat is regressively or progressively 2014). infected (Hofmann-Lehmann, 2016). Not all cats that are positive, Clinical icterus may be seen in FeLV-infected cats. This icterus even on both an ELISA and confirmatory test, will go on to develop may be prehepatic and caused by immune-mediated red blood cell progressive infection. Cats that test positive for FeLV may go on veterinarians.elitecme.com Page 36 to live for many years. For this reason, it is never appropriate to living in multicat homes are expected to die within 3 years (Litster, euthanize a cat solely based on positive FeLV testing (American 2015). Association of Feline Practitioners, 2009). Prevention Management The AAFP currently recommends vaccination of all kittens for Feline leukemia cannot be cured; however, there are a number of FeLV virus because cats under 4 months of age are more susceptible strategies used in the management of this condition. Recommended to FeLV than adult cats are. Additionally, many owners may not management strategies depend on the specific manifestations of FeLV determine whether their cat will live indoors or outdoors until it infection within a particular patient, as each of these manifestations is reaches adulthood, leaving cats potentially vulnerable to infection if managed differently. the owners do not contact their veterinarian to discuss the change in Lymphoma is the most commonly reported tumor in FeLV- housing status and needed vaccines (American Association of Feline infected cats, and the presence of FeLV infection does not affect Practitioners, 2013). the management strategies for feline lymphoma or its response to Feline leukemia vaccines can be given to cats as young as 8 weeks of therapy. A number of chemotherapy protocols have been utilized for age. The vaccine should then be boostered 3 to 4 weeks later. After the the treatment of feline lymphoma. Prednisone alone may provide initial vaccination series, the decision to continue vaccination should some relief of clinical signs. Chemotherapeutic protocols—including be made based on lifestyle and risk assessment after discussion with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) the owner. and cyclophosphamide, vincristine, and prednisone (COP)—are In adult cats, the decision of whether to initiate or continue FeLV frequently utilized if owners are interested in pursuing more aggressive vaccination should be based on lifestyle. Cats that go outdoors should treatment. Cats that achieve complete remission after induction be vaccinated for FeLV, as should housemates of cats that go outdoors. of chemotherapy often go on to have long disease-free intervals, Additionally, cats living in households with frequent new feline providing substantial benefits in mean survival time and overall quality additions to the home (such as in the case of owners who foster cats, of life. Cats with mediastinal and multicentric lymphoma, in particular, where FeLV could easily be introduced to the household) and cats with frequently achieve complete remission with chemotherapy (up to an FeLV-infected housemate should also receive FeLV vaccines even 90% of cats), and 1-year survival rates of up to approximately 55% if all of the cats in the home are indoor-only cats. Cats that live indoors have been reported. Cats with aggressive GI lymphoma have a more only in a stable household group do not require vaccination as adults. guarded prognosis; approximately 50% of cats will achieve a complete remission with chemotherapy, and 1-year survival rates of 20% to 40% If an adult cat with no prior history of FeLV vaccination is determined are typically observed in this group (Litster, 2015). to be at risk of infection, an initial series of two vaccines should be given 3 to 4 weeks apart. The FeLV vaccine should then be boostered Myelosuppression is the most severe effect of FeLV, and it carries 1 year later (American Association of Feline Practitioners, 2013). a poor prognosis. Whole blood may be beneficial for the short-term treatment of anemia, but this often becomes impractical because of For previously vaccinated adult cats, most FeLV vaccines are associated costs and the immune consequences of repeated blood labeled for a 1-year duration of immunity. Yearly vaccine boosters transfusions. Recombinant human erythropoietin (rHuEPO) can be are recommended in the case of cats at high risk of FeLV infection also used in cats with clinical signs associated with anemia, usually to maintain high immunity. Cats that are at low, but not zero, risk of when hematocrit (HCT) is less than 20%. This drug is typically FeLV may benefit from vaccines given every 2 to 3 years, allowing administered every 48 hours (100 U/kg SQ) for 3 to 4 weeks of the adverse effects of vaccines to be minimized while still providing treatment before seeing an effect and is continued long-term if it is a moderate level of protection against FeLV infection (American beneficial for the patient. Successful treatment should elevate the HCT Association of Feline Practitioners, 2013). to 30% or higher. Unfortunately, approximately 20% to 30% of treated A number of commercially available vaccines are available for cats will develop anti-erythropoietin antibodies that will adversely the prevention of FeLV infection, including killed whole virus affect the therapy’s efficacy. These antibodies typically develop 6 to 12 (adjuvanted) vaccines, killed subunit (adjuvanted) vaccines, and months into treatment, rendering further therapy ineffective (Litster, recombinant (adjuvant-free) vaccines. These vaccines do not induce 2015). In cats with neutropenia, recombinant human granulocyte sterilizing immunity. Vaccines do, however, inhibit viral replication, colony-stimulating factor (rHuG-CSF, filgrastim) may be used to viral persistence, and FeLV-associated disease (American Association stimulate neutrophil production. Like rHeEPO, however, antibody of Feline Practioners, 2013). development often occurs and limits the benefits of this product (Litster, 2015). None of the commercially available FeLV vaccines interferes with obtaining accurate results on a later FeLV test; vaccinated cats will Cats with FeLV are more susceptible to infection than not test positive for FeLV. Despite this fact, however, it is important immunocompetent cats. It is important that any infections that to test cats before vaccination. This pre-vaccine test will allow the do develop in FeLV-infected cats be treated promptly, as these veterinarian to document the cat’s disease status in the unlikely event infections can become severe and life-threatening more readily that of a future vaccine failure while allowing a determination of whether in immunocompetent cats. Good nursing care is also essential to vaccination is necessary/beneficial for that particular cat (Litster, maintaining quality of life in these cats, keeping them clean in order to 2015). decrease infection risk and ensuring an adequate diet. Adverse events associated with FeLV vaccines include localized Asymptomatic cats with FeLV should be housed indoors to prevent swelling or pain, transient lethargy or fever, and granuloma formation transmission and decrease exposure to pathogens that may result in (American Association of Feline Practioners, 2013). Feline vaccine- opportunistic infections. These cats should also receive a physical associated sarcoma (VAS) has been associated with FeLV vaccination exam every 6 months to detect any sequelae of FeLV infection and in the past, as well as with a number of other injections in cats. There to remain up-to-date on all core vaccines. Additionally, infected is no evidence that FeLV vaccine is associated with a higher risk cats should receive fecal examinations twice yearly to assess for the of VAS than other vaccines; however, the administration of FeLV presence of intestinal parasites and remain on year-round broad- vaccination should be based on individual patient risk and lifestyle spectrum parasite prevention. A small percentage of FeLV-infected factors (Litster, 2015). cats may remain healthy for a number of years, but most infected cats

Page 37 veterinarians.elitecme.com Feline immunodeficiency virus Feline immunodeficiency virus (FIV) is another retroviral disease of changes—including anemia, lymphopenia, and neutropenia—may cats with worldwide distribution. Feline immunodeficiency virus is a occur (Litster, 2015; Little, 2013). Elevated globulin levels may also lentivirus causing progressive impairment of the immune system and be observed during the asymptomatic phase. This elevation occurs as eventual AIDS-like immunodeficiency in affected cats (Little, 2013). cell-mediated immunity is reduced, stimulating antibody-mediated Worldwide prevalence of FIV varies from 1% to 31% in healthy cats, immunity (Litster, 2015). but prevalence in generally higher when sick cats are studied (Litster, With progression, cats may develop an AIDS-related complex or 2015). A 2006 study noted a prevalence of 2.5% in the United States terminal stage of FIV infection. This phase typically takes years to (Levy, 2006), but marked regional variation occurs and locally higher develop and is often observed in older cats. In this stage, cats become numbers are observed in some areas. Feline immunodeficiency virus more susceptible to secondary infection and begin showing clinical infection is most common in intact male cats with outdoor access signs that can suggest an underlying immunodeficiency (Litster, 2015). (American Association of Feline Practitioners, 2009). Clinical signs Feline immunodeficiency virus, like FeLV, is divided into subgroups. Clinical signs during the acute stage of infection are missed by many There are five unique subgroups, or clades, of FIV, characterized based owners. They include fever, lymphadenopathy, lethargy, anorexia, on their envelope glycoprotein, gp120. Prevalence of the different and weight loss (Fenimore, 2014). These stages are caused by viral clades varies geographically, and there are genotypic and phenotypic replication and the resulting immune response. Following this acute variations within each clade. Subtypes A and B are the predominant phase, however, there is a prolonged period (years) in which most cats subtypes within the United States, and there are large differences are entirely asymptomatic. within and between subtypes (Little, 2013). Feline immunodeficiency Clinical signs in the later stages of FIV are most commonly related virus has been observed to have a high mutation rate because of to secondary infections that develop as a result of immunodeficiency. characteristics of its reverse-transcriptase enzyme, and these mutations These secondary infections may be bacterial, viral, fungal, or protozoal can affect antigenicity and virulence (American Association of Feline and can affect a variety of organs and organ systems. Affected cats Practitioners, 2013). may develop chronic respiratory issues, gastrointestinal disease caused Feline immunodeficiency virus is transmitted in the saliva, most by bacterial overgrowth, or other infections. commonly via bite wounds. Infection is most common in free-roaming Cats with FIV are at a higher risk of developing a number of male cats because of their tendency to fight with other cats (American different malignancies. These include lymphoma and other lymphoid Association of Feline Practitioners, 2013). Feline immunodeficiency neoplasias, myeloproliferative diseases, and several types of sarcomas virus appears to affect both adults and kittens with equal frequency, and carcinomas (Fenimore, 2014). In some cats, the first sign of FIV unlike FeLV (American Association of Feline Practitioners, 2013). may be clinical signs associated with the secondary neoplasia. Like FeLV, however, FIV may also be transmitted via sustained close contact among household contacts (Addie DD D. J., 2000), though Other viral effects can include slow, progressive weight loss, with this is not common. In one study examining cohabiting rescue cats of or without chronic small-intestinal diarrhea. Infected cats may both FIV-positive and FIV-negative cats, FIV transmission was not develop ocular inflammation, including anterior uveitis or pars observed despite years of exposure (Litser, 2014). In the environment, planitis (inflammation in the anterior vitreous humor). Chronic oral the virus is very unstable and dies within minutes, so fomite inflammation is frequently observed, and these cats may initially transmission and casual contact are not significant causes for concern. present to the veterinarian for evaluation of gingivostomatitis. Neurologic disease—including seizures, ataxia, nystagmus, and Feline immunodeficiency virus can be transmitted vertically, from other abnormalities—is another common manifestation of FIV. mother to kittens, both transplacentally and via the milk (American Renal disease may also be observed, including glomerulonephritis. Association of Feline Practitioners, 2013). It is important to note, (American Association of Feline Practitioners, 2013; Fenimore, 2014; however, that not all kittens of an infected mother will be infected with Litster, 2015). the virus (Little, 2013). Diagnosis Furthermore, blood transfusions have also been documented as a All sick cats should be tested for FIV. Additionally, newly adopted source of FeLV transmission and mucosal transmission via the vaginal, cats or kittens and all cats that are to be group housed should be tested; rectal, or oral route can occur under laboratory conditions but requires these individuals should be retested 2 months later if negative to such large numbers of virus particles to be clinically insignificant ensure that the test was not given during the disease’s prepatent period. (Litster, 2015). All cats with exposure to an FIV-infected cat or with a bite wound Feline immunodeficiency is not a zoonotic disease. Studies of from a cat of unknown status should also be tested 2 months after veterinarians and their staff have shown no evidence of FIV infection exposure. High-risk cats, including cats living outdoors and cats living (Butera ST, 2000). with an FIV-positive cat, should be tested annually. Additionally, all Pathophysiology cats should be tested before vaccination. Finally, all blood donor cats The initial stages of acute FIV infection may be associated with should be tested to ensure that they are FIV negative (Litster, 2015). transient fever and lymphadenopathy. In many cases, however, this The most common test for FIV involves screening for FIV antibodies acute stage of FIV infection goes undetected by pet owners. During (capsid protein p24 or transmembrane envelope protein gp40) using an this phase, large amounts of virus circulate in the bloodstream. The in-house ELISA test. These tests detect antibodies, not viral antigen, immune system develops antibodies against the virus; however, the because circulating levels of the virus are very low following infection infection is not typically eliminated. The immune system effects may (Little, 2013). Because FIV results in a persistent, life-long infection, be sufficient to cause a decrease in viral load during the later stages of detection of antibodies in an unvaccinated cat is sufficient to meet the the acute phase (Litster, 2015). criteria for diagnosis of FIV. After this initial acute phase, infected cats then enter a long The most common cause of a false-negative FIV test is testing too asymptomatic phase. During this asymptomatic phase, CD4+ early in infection. Because the FIV test is an antibody test, testing T-lymphocytes begin to decline in number. In some cases, a reduction before seroconversion will result in a false-negative test. False in the CD4:CD8 lymphocyte ratio occurs that may be observed with negatives can also be seen in cats that are in the late terminal stages specialized testing. During this phase, complete blood cell count of the disease. In these patients, FIV-induced immunodeficiency may veterinarians.elitecme.com Page 38 result in decreased antibody production that is not detected by the test. If FIV-positive cats develop significant anemia or neutropenia, fresh Less commonly, false-negative tests may be attributed to exceptionally whole blood transfusions may be beneficial. Unfortunately, repeated high viral loads. In these patients, all of the FIV antibodies may be blood transfusions can cause anaphylaxis; therefore, this treatment is bound to circulating virus and therefore not available for detection by of limited utility. Plasma transfusion carries similar risks and benefits. the test (Little, 2013). Recombinant human erythropoietin (rHuEPO) can be also used in Commercially available ELISA SNAP tests have high sensitivity cats with FIV that have clinical signs associated with anemia, usually and specificity in unvaccinated cats. False-positive tests can occur, when hematocrit (HCT) is less than 20%. This drug is used in FIV however, especially in low-risk populations. Therefore, all positive as it is used in FeLV, every 48 hours (100 U/kg SQ) for 3 to 4 weeks results on FIV ELISA tests should be confirmed using an alternative of treatment before seeing an effect, and is continued long-term if test. The most accurate test for confirmation is virus culture; however, it is beneficial for the patient. Successful treatment should elevate this test is not readily available. Currently, a western blot is the the HCT to 30% or higher. Approximately 20% to 30% of treated recommended confirmatory test for unvaccinated cats that test positive cats will develop anti-erythropoietin antibodies that will adversely for FIV on an ELISA test (Little, 2013). affect the therapy’s efficacy, decreasing the long-term benefits of this treatment. These antibodies typically develop 6 to 12 months into Polymerase chain reaction (PCR) testing has been promoted as a treatment, rendering further therapy ineffective (Litster, 2015). In cats test that may help distinguish vaccinated cats from infected cats. with neutropenia, recombinant human granulocyte colony-stimulating These tests work by detecting FIV, RNA, or DNA (provirus) genetic factor (rHuG-CSF, filgrastim) may be used to stimulate neutrophil sequences. Unfortunately, studies have indicated that currently production. Like rHeEPO, however, antibody development often available PCR tests at commercial laboratories are unreliable; occurs and limits the benefits of this product (Litster, 2015). therefore, their use is not recommended at this time (Little, 2013). There are few published reports examining treatments for the When performing FIV testing in kittens, it is important to remember immunodeficiency that develops in FIV-infected cats. Recombinant that not all kittens born to an infected queen will be infected. feline interferon therapy has been attempted in other countries; Therefore, when a pregnant queen or a litter of kittens is found however, it is unavailable in the United States. Human interferon or relinquished, each individual kitten should be tested. It is not has shown some promising results, as have azathioprine and appropriate to test only the mother, to test only one of the kittens, or to 9-(2-phosphonylmethoxyethyl) adenine (PMEA), but none of these test a pooled blood sample containing a small amount of blood from products is widely used at this time (Litster, 2015). Interestingly, each of the kittens (Little, 2013). multiple studies have shown that FIV infection does not significantly Kittens also present an additional complication in regards to FIV impact life expectancy in infected cats despite the increased testing. Because the FIV test is an antibody test, kittens may test susceptibility to infections seen in these cats (Addie, 2000; Ravi, positive despite not being infected with the virus. Kittens born to 2010). infected or vaccinated queens may ingest anti-FIV antibodies in the In cases of FIV-associated stomatitis, removal of all of the teeth is colostrum or milk despite not actually being infected with the virus. often the most effective way to restore quality of life (Fenimore, Therefore, it is recommended that any kittens who test positive for 2014). Antibiotics, including clindamycin, may offer some benefits; FIV be retested after 4 months of age to confirm their infection status. however, these benefits are often short-lived, and full-mouth Kittens who test negative before 4 months of age can be regarded as extractions are typically more effective. truly negative (Little, 2013). Prevention Cats who test positive for FIV may go on to live long, healthy lives for There is a commercially available FIV vaccine. This vaccine contains many years. For this reason, it is never appropriate to euthanize a cat inactivated whole virus isolates from clades A and D combined with solely based on positive FIV testing (American Association of Feline infected cells and an adjuvant. The FIV vaccine induces both antibody Practitioners, 2009). formation and cell-mediated immunity, which are effective when Management vaccinated cats are exposed to many, but not all, subtypes of clades The management of FIV-infected cats relies largely upon managing the A and B (American Association of Feline Practitioners, 2013). This cat’s environment in an effort to decrease infectious disease risks and vaccine is thought to offer some protection to at-risk cats, but it does decrease stress. Infected cats should be kept indoors, both to prevent not reliably prevent infection. Therefore, its use remains controversial FIV transmission and to decrease exposure to infectious agents. and it is not regarded as a core vaccine in cats (American Association These cats should be maintained on a high-quality commercial diet to of Feline Practitioners, 2013). Cats who may benefit from FIV vaccine decrease the risk of foodborne illness and should receive year-round include outdoor cats that are frequently involved in fights and cats parasite prevention to protect against vector-borne parasites, such as living with an FIV-positive housemate. Mycoplasma hemofelis (Gunn-Moore, 2014). Another controversy involving FIV vaccination in cats is the fact Infected cats should receive regular veterinary care. Routine physical that FIV vaccination will interfere with later test results. Vaccination exams will allow ongoing monitoring of overall health and early against FIV produces antibodies that will be detected in commercially detection of secondary infections so that these infections can be treated available FIV antibody tests, creating a number of difficulties in early with a better prognosis. If bacterial infections are detected, vaccinated cats. First, because we know that the vaccine is not fully bactericidal antibiotics may be more effective than bacteriostatic effective, being unable to test for infection is a significant drawback. antibiotics because of the cat’s immunodeficiency. Additionally, Second, vaccinated cats who end up in shelters or rehomed may antibiotic choices should be guided by culture and sensitivity when be wrongly suspected of having FIV infection when, in fact, they possible to decrease the likelihood of resistant infections, which may are merely vaccinated. Feline immunodeficiency virus antibodies be more difficult to control than in immunocompetent cats. Infected develop within weeks of vaccination and may persist for up to 4 years cats should also be kept current on routine vaccinations to decrease (American Association of Feline Practitioners, 2013), leading cats the risks associated with infectious diseases. Cats infected with FIV to test positive for a prolonged period. It is important that clients be should also receive fecal examinations twice yearly to assess for the notified of this fact—vaccination should not be performed without presence of intestinal parasites, and remain on year-round broad- thorough discussion and consideration. Vaccinated cats should be spectrum parasite prevention. permanently identified with a tattoo or microchip to prevent euthanasia should they ever arrive in a shelter setting and be tested upon intake.

Page 39 veterinarians.elitecme.com All cats should be tested for FIV before vaccination. Although Adverse reactions to FIV vaccination include localized swelling or vaccination is not contraindicated in an infected cat, knowing the cat’s pain; transient lethargy or fever; and gastrointestinal signs, including status is important to establish a baseline and inform owner decisions. anorexia, vomiting, and diarrhea (American Association of Feline The initial vaccination should be given as a three-dose series, Practitioners, 2013). beginning as early as 8 weeks of age, with yearly revaccination if risk persists (American Association of Feline Practitioners, 2013).

Conclusion Feline leukemia virus and feline immunodeficiency virus can both all cats that become infected with the virus will eventually develop have significant impacts on the health of feline patients. Although there evidence of infection. Although FeLV and FIV are both initially are many similarities between the two viruses, including their impacts diagnosed using a combined ELISA SNAP test, a positive result for on the immune system and ability to produce neoplasia, it is important either test should be confirmed through further testing. Because of for veterinary practitioners to remain mindful of the differences the possibility of regressive infection, even confirmed positive FeLV between the viruses. When thinking of epidemiology, it may be helpful cases should be retested after several months; this is in contrast to to remember that FeLV is typically a disease of “friendly” cats that FIV, where a confirmed positive does not need to be retested, as an are in close social contact, whereas FIV is a greater concern in cats infected cat will remain infected for the rest of its life. Although that fight and receive bite wounds. When cats do become infected the management of FeLV and FIV is essentially the same, there are with one of these retroviruses, practitioners should remain mindful key differences in prevention strategies related to the limitations of of the fact that many cats exposed to FeLV will successfully suppress currently available vaccines and diagnostic tests. These differences the infection; less than half of infected cats will actually develop should be taken into consideration when developing feline vaccination progressive FeLV infection. This is in direct contrast to FIV, where programs.

References ŠŠ Addie, D. D., Dennis, J. M., Toth, S., Callanan, J. J., Reid, S., & Jarrett, O. (2000). Long-term ŠŠ Levy, J. K., Scott, H. M., Lachtara, J. L., & Crawford, P.C. (2006). Seroprevalence of feline impact on a closed household of pet cats of natural infection with feline coronavirus, feline leukemia virus and feline immunodeficiency virus infection among cats in NorthAmerica and risk leukaemia virus and feline immunodeficiency virus. Veterinary Record, 146, 419–424. factors for seropositivity. Journal of the American Veterianary Association, 228, 371–376. ŠŠ American Association of Feline Practioners. (2013). Disease information fact sheet: Feline leukemia ŠŠ Litser, A. (2014). Transmission of feline immunodeficiency virus (FIV) among cohabiting cats in virus. Journal of Feline Medicine and Surgery, 15, Supplementary File. two cat rescue shelters. Veterinary Journal, 201(2), 184–188. ŠŠ American Association of Feline Practitioners. (2009). Feline retrovirus management guidelines. ŠŠ Litster, A. (2015). Feline immunodeficiency virus: An update. Atlantic Coast Veterinary Conference. Retrieved from http://www.catvets.com/public/PDFs/PracticeGuidelines/RetrovirusGLS-Summary. Atlantic City, NJ, pdf ŠŠ Litster, A. (2015). FeLV: How new classifications help us understand pathogenesis, diagnosis and ŠŠ American Association of Feline Practitioners. (2013). 2013 AAFP feline vaccination advisory panel prognosis. Atlantic Coast Veterinary Conference. Atlantic City, NJ. report. Journal of Feline Medicine and Surgery, 15, 785–808. ŠŠ Little, S. (2013). Update on FIV: Prevalence, clinical disease, and diagnostic testing. Atlantic Coast ŠŠ American Association of Feline Practitioners. (2013). Disease information fact sheet: Feline Veterinary Conference. Atlantic City, NJ. immunodeficiency virus. Journal of Feline Medicine and Surgery, 15, Supplementary File. ŠŠ Lutz, H. (2012). State of the art: Feline leukaemia virus: Looking over the horizon. International ŠŠ Butera, S. T., Brown, J., Callahan, M. E., Owen, S. M., Matthews, A. L., Weigner, D. D., Chapman, Society of Feline Medicine Feline Symposium. L. E., & Sandstrom, P. A. (2000). Survey of veterinary conference attendees for evidence of zoonotic ŠŠ Ravi, M., Wobeser, G. A., Taylor, S. M., & Jackson, M. L. (2010). Naturally acquired feline infection by feline retroviruses. Journal of the American Veterianary Association, 217, 1475–1479. immunodeficiency virus (FIV) infection in cats from western Canada: Prevalence, disease ŠŠ Fenimore, A. (2014). Update on feline retrovirus infections. Atlantic Coast Veterinary Conference. associations, and survival analysis. Canadian Veteernaity Journal, 51(3), 271–276. Atlantic City, NJ. ŠŠ Gunn-Moore, D. (2014). FIV. British Small Animal Veterinary Congress. Birmingham, UK. ŠŠ Hofmann-Lehmann, R. (2016). Feline leukemia virus infection: New advances in diagnosis. Fourth International Society for Companion Animal Infectious Diseases Symposium. Bristol, UK.

veterinarians.elitecme.com Page 40 Feline leukemia virus and Feline immunodeficiency Virus Final Examination Questions Choose the best answer for each question and mark your answers on the Final Examination Sheet found on Page 68 or take your test online at Veterinarians.elitecme.com.

31. Feline leukemia virus is typically transmitted via mutual 36. Feline immunodeficiency virus is most commonly transmitted via grooming. bite wounds. ¨¨ True ¨¨ True ¨¨ False ¨¨ False

32. Feline leukemia vaccination may cause false positives on later 37. All kittens born to a FIV-infected queen will be infected with FIV. FeLV tests. ¨¨ True ¨ ¨ True ¨¨ False ¨¨ False 38. Cats with FIV are at a higher risk of developing cancer than 33. Kittens who test positive for FeLV should be euthanized uninfected cats are. immediately. ¨¨ True ¨ ¨ True ¨¨ False ¨¨ False 39. Kittens who test positive for FIV are always infected with FIV. 34. All kittens under 4 months of age should be vaccinated for FeLV. ¨¨ True ¨ ¨ True ¨¨ False ¨¨ False 40. Cats with FIV-associated stomatitis may benefit from full-mouth 35. The prevalence of FIV in the United States is < 5%. dental extractions. ¨¨ True ¨¨ True ¨¨ False ¨¨ False

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