Danielle Gunn-Moore, BSc, BVM&S, PhD, FHEA, MACVSc, MRCVS, RCVS Specialist in Feline Medicine
Royal (Dick) School of Veterinary Studies Hospital for Small Animals, University of Edinburgh
Scotland
Introduction
The management of retrovirus-infected cats may be divided into general management, management of immunosuppression, treatment of anaemia, and chemotherapy for lymphosarcoma (and other neoplasia). This lecture will concentrate on the general management, and treatment options for immunosuppression and anaemia. It will only briefly consider retrovirus-infected cats with neoplasia.
Management
The successful long term management of cats with FeLV or FIV infection depends on a number of factors including the type of environment in which the cat has to live, and the willingness of the owner to care for their cat. The long-term care of an immunocompromised animal is not to be undertaken lightly. An affected cat should be exposed to as few infectious organisms as possible. Ideally, it should be isolated, or at least kept in a small stable group. If access outside is permitted (which is not recommended), instigate a 'night curfew' (most fighting occurs at night). Avoid overcrowding. It should be fed separately, and on a high quality diet. Exposure to parasites should be prevented. This is particularly so for fleas because they are believed to transmit Mycoplasma haemofelis (previously called Haemobartonella felis). Since stress will accentuate immune dysfunction, exposure to stressful situations should be minimised.
Care must be taken when vaccinating immunosuppressed cats. Clinically unwell animals should not be vaccinated. Since live attenuated vaccines can induce clinical disease in immunocompromised patients they should not be used. Where exposure to infectious disease cannot be avoided, killed vaccines and regular boosters are generally recommended. While it has been suggested that any vaccination can result in exacerbation of FIV infection (through activation of T cells) the clinical significance of this is not yet known. To prevent exposure to live attenuated viruses, in-contact animals should also be vaccinated with killed vaccines.
Therapy
When disease occurs, appropriate therapy should be instigated at the earliest possible opportunity. Retrovirus-infected cats should therefore have regular health checks. At each examination the cat should be carefully and thoroughly evaluated, and weighed. When a secondary infection is noted the causal pathogen should be identified. Appropriate treatment should begin early and be aggressive. This is particularly true of infectious disease, where aggressive anti-microbial therapy is essential. Therapeutics should be chosen with care. Bactericidal antibiotics should be used wherever possible, with the choice being made according to culture and sensitivity. Retrovirus-infected cats may respond rather slowly, even when given appropriate therapy. However, the presence of these infections does not necessarily preclude against a successful outcome, at least in the short term. Prolonged or intermittent courses of treatment may be required. Retrovirus-infected cats may also respond atypically to certain drugs, e.g., griseofulvin in FIV positive cats can cause life-threatening neutropenia.
Unfortunately, there are no treatments that will reverse these diseases once clinical signs have developed. Therapy is therefore symptomatic. While a number of authors claim to have found suitable treatment products and regimens, caution should always be applied when interpreting these reports. The most commonly-considered treatments are immuno-suppressive drugs, particularly prednisolone, with or without more potent agents. A number of immunomodulating or antiviral agents have also been considered, including AZT, PMEA, ribavirin, human recombinant alpha interferon (rHuIFNα), feline IFNβ, Propionibacterium acnes, and Promodulin, generally with equivocal or poor results (Table 1).
When considering the use of immunotherapy in retrovirus-infected cats, independent of which compounds are going to be used, it is important that the client has realistic expectations. Treatment is not going to cure the cat; at best it will reduce the clinical signs and improve the cat's quality of life. The potential benefits of any therapy must therefore be balanced with potential toxic side effects and possible costs. Also, it is recommended that for immunotherapy to be effective the cat must live to receive at least the first three-to-four weeks of treatment. These compounds are therefore best reserved for use in non-critical patients.
Antiviral Drugs
A number of specific antiviral drugs are available. Treatment with azidodideoxythymidine (AZT), phosphonylmethoxyethyladenine (PMEA), diethylcarbamazine (DEC), or ddC have been associated with improvement of both clinical signs and immune status. However, these drugs are usually expensive, and may cause severe side effects, particularly anaemia.
Immunomodulating Drugs
A number of immunomodulating drugs may be of use in the management of FeLV and/or FIV infection. Those that may give beneficial results, and are currently fairly readily available, include human recombinant interferon-α (IFNα) and feline recombinant interferon-ω (IFNω), and possibly acemannan, Propioniacterium acnes, and Staphylococcus protein A (SPA). They may be most beneficial when used in combination with antiviral agents (e.g., IFNω with AZT). Corticosteroids may appear to be contraindicated, but their use in FeLV-infected cats may result in clinical improvement, possibly due to their anti-inflammatory action. A number of food supplements are claimed to have immune-enhancing effects, but their beneficial effects have yet been proven in retrovirus-infected cats.
Chemotherapeutic options for retrovirus-infected cats with neoplastic diseases can be considered. However, while retrovirus-infected cats with lymphoma may undergo clinical remission (when treated with appropriate chemotherapy), their remission tends to be shorter than non-infected cats. Also, giving immunosuppressive drugs to retrovirus-infected cats increases their immunosuppression and may also increase the risk of them spreading their retrovirus to other cats with which they live.
Table 1. Antiviral and immunomodulating drugs.
|
Drug |
Route |
Cost/month |
Monitoring |
|
AZT |
PO, SQ, IV q12h |
~ £30 |
√ |
|
hrIFNα |
PO, SQ q24h |
~ £8 |
|
|
frIFNω |
PO,SQ, IV q24h |
~ £8-150 |
|
|
G-CSF |
SQ q12-24h <3wk |
~ £250 |
√ |
|
Human Ig |
IV over 6-12h |
~ £90 |
√ |
|
EPO |
SQ q24h |
~ £100 |
√ |
Management of Cats with FeLV and/or FIV
Consider each case individually
Isolate (where possible)--avoid risk of transmission of infections between cats
Reduce exposure to pathogens & prevent parasites
Reduce stress
Feed separately & feed a high quality diet
Make a full diagnosis & monitor closely
Regular health and weight checks
Careful and thorough physical evaluation
Early and aggressive treatment of secondary disease
Careful choice of therapeutics
Vaccinate regularly? (killed vaccines)
Remember: no cure, only improved quality of life
Therapeutic Options for Cats with FeLV or FIV Infection (Excluding Chemotherapeutics) (Table 2)
Table 2. Therapeutic options for cats with FeLV or FIV infection (excluding chemotherapeutics).
|
Therapy: |
Uses and comments: |
|
Bone marrow transplantation or lymphocyte adoptive transfer |
Expensive, not readily available. |
|
Fresh whole blood transfusion (contains erythrocytes, leukocytes, immunoglobulins and compliment) |
Used to treat anaemia, neutropenia, or overwhelming infections. Effect is transient. Risk of anaphylactic reaction with repeated transfusions. |
|
Plasma transfusions |
Effect is transient. Risk of anaphylactic reaction with repeated transfusions. |
|
Erythropoietin (100 IU/kg, SC, q48h, until desired PCV is reached, ~2 weeks) Adjust to keep PCV ~30% |
Useful in some forms of non-regenerative anaemia. Prolonged use may induce antibodies and result in severe anaemia. |
|
Granulocyte colony-stimulating factor (G-CSF) (5-20 μg/kg, SC, q12-24h, for 1-2 weeks) |
Expensive. Treatment for > 3 weeks results in induction of antibodies and resultant neutropenia. |
|
Human immunoglobulin (dogs) (0.5-1.5 g/kg, IV over 6-12h) |
Effect is transient. Risk of anaphylactic reaction. Only anecdotal cases of its use in cats have been documented. |
|
Antiviral agents: |
|
Azidodideoxythymidine / zidovudine (AZT) (Retrovir, Burroughs Wellcome) (5-10 mg/kg, PO, SC, or IV q12h)a Stop if PCV <20% |
May be useful in the management of immunosuppression. Monitor for anaemia and other signs of toxicity (neutropenia, anorexia, weight loss, vomiting). |
|
Phosphonylmethoxyethyladenine (PMEA) (2.5 mg/kg, IM, q12h) Can use loading dose 20mg/kg q8h for 7 days then reduce. |
PMEA is more effective than AZT and more toxic. |
|
Immune stimulators: |
|
Human recombinant interferon alpha (hrIFNα) e.g., Roferon-A, Hoffman LaRoche (1-30 IU, PO, q24h, treat continuously or alternate weeks b. Some authors use much higher dose parentally, e.g., M IU SQ q24h) |
Particularly useful for immunosuppression. Given parenterally at high doses will cause toxicity and induce production of anti-IFNα antibody. Lower doses tend to be immunostimulating while higher doses tend to be immunosuppressive. |
|
Feline recombinant interferon omega (frIFNω) e.g., Virbagen Omega, Virbac (Doses suggested range from these shown for hrIFNα up to 1 M IU/kg SQ q24h, for 5 days) |
In 1 study: 1 M IU SQ q24h for 5 days as 1 or 2 courses may result in subtle improvements in survival times and clinical parameters. In another study, FIV infected cats were given 104 IU/cat q24h PO for 6 weeks or 106 IU/kg q24h SC for 5 days and failed to show any biochemical improvements. |
|
Acemannan (derived from Aloe vera) (Carrisyn, Carrington Labs.) (2 mg/kg IP q7 days for 6 weeks, can also be given IV, PO or topically) |
Side effects include pain on injection, hyperactivity, lethargy, fever, and hypotension. |
|
Propionibacterium acnes (Immunoregulin, Immuno Vet) (0.5 ml IV twice weekly for 2 weeks, then q7 days for 20 weeks) |
Licensed in USA, but no controlled studies. |
|
Staphylococcus protein A (SPA, Pharmacia) (10 μg/kg of diluted SPA IP twice weekly for 10 weeks, then treat monthly)c |
Perhaps most useful when treating anaemia. |
|
Bovine lactoferrin (40mg/kg, topically PO, q24h, as needed) |
Useful in the treatment of FeLV associated gingivitis / stomatitis? |
|
Paramunity inducer PIND-ORF (Baypamun, Bayer) |
Placebo-controlled studies show complete lack of efficacy. |
|
Herbal and homeopathic remedies |
Most lack proof of efficacy or safety. |
|
Lithium carbonate--Toxic in cats (11mg/kg, PO, q12h--dogs) |
Induces neutrophilia via release of colony-stimulating factors. Risk of nephrotoxicosis. |
IV, give intravenously. SC, give subcutaneously. PO, give per os. IP, give intraperitoneally. PCV, packed cell volume.
a. For PO administration use customised gelatin capsules, for SC dilute lyophylate in 5ml of saline.
b. Obtained as 3M IU--dilute in one litre of saline, aliquot into 1ml volumes, freeze for over a year. Defrost as required, dilute to required concentration, keep refrigerated for up to a week.
c. Dissolve a 5 mg lyophylised vial in 500 ml sterile water to give 10 μg/ml. Freeze in 5 ml aliquots which are stable for years. Do not re-use after thawing.