Various protocols have been used in the treatment of Feline leukaemia virus (FeLV) infections. The use of “immune modulators” has often been proposed to restore the function of the immune system of FeLV-infected subjects, to help patients to maintain the viraemia under control and to reduce the incidence of correlated diseases. Antiretroviral drugs should play a role in controlling the infection.
IMMUNOMODULATION
The immune modulators include:
- Acemannan. This is a complex polymerised carbohydrate (mannan) derived from a plant, aloe vera. Acemannan stimulates the release of interleukin-1, interleukin-6, tumour necrosis factor-alpha, interferon-alpha and nitric oxide from macrophages, inducing tumour apoptosis and necrosis. In addition, it increases the phagocytic capacity and the cytotoxicity of macrophages. Its potential direct antiviral activity seems to be associated with an alteration of glycosylation in both the viruses and in infected cells, thus decreasing the infectiveness and reproductive capacity of the viruses. In some cats the administration of a bolus of acemannan i.v. has been associated with episodes of acute collapse (2 mg/kg i.p. every week for 6 weeks).
- Propionibacterium acnes. This is an inactivated product of bacterial origin. The dose is 0.25-0.5 ml i.v. twice a week, then every other week for 16 weeks.
- Human interferon-alpha (hIFN-a)is given at low doses (50 units/cat per os per day via the oral mucosa, for 7 days, then every other week for 6 months, followed by a 2-month pause and then another 6 months of treatment). Interferons are antiviral substances, produced by virtually all cells of the body and not only by specialised cells. They have a non-specific activity against any virus and they represent the first response of the body against a viral infection. They consequently play a fundamental role in the defence against viruses when specific antibodies are still not present. Indeed, in the presence of viral infections the alpha-interferons are produced during the first hours, reaching a peak within 48 hours. IFNa-2 is one of the many interferons which have shown a dual effect, depending on the dose: at a high dose it is a direct antiviral agent, while at a low dose it has an immunomodulatory effect. Unfortunately antibodies develop within 5-6 weeks if it is administered at high doses via injection.
- Staphylococcus A(SPA). This is another purified product of bacterial origin, obtained from cells infected with Staphylococcus aureus (20 μg/2.75 kg i.p. twice a week, for 8 weeks).
- PIND-ORF. This product is derived from an inactivated Parapox ovis virus . The dose is 1.0 ml s.c. twice a day, for 1 week, then weekly for 6 weeks).
There are still many doubts about the efficacy of these therapies, mainly because of the lack of placebo-controlled trials.
ANTIVIRAL THERAPY
The efficacy of antiviral agents is still under investigation; many studies have suggested that some of these drugs are effective, but others have highlighted the various doubts that still exist.
In fact only a few controlled studies show some positive effects. The drugs which can be used are:
- Azidovudine/zidovudine (5-15 mg/kg s.c. twice a day)
- High doses of hIFN-a(10,000-1,000,000 U/kg s.c. every day)
- High doses of recombinant feline interferon (fIFN) omega (1,000,000 U/kg s.c. per day, for 5 days, starting on days 0, 14 and 60).
Azidovudine (AZT)is one of the most studied drugs for both FeLV and Feline immunodeficiency virus (FIV); some recent publications have confirmed the beneficial effects of this drug, although no one has yet shown that the virus can be eliminated in natural conditions. AZT is a selective inhibitor of viral reverse transcriptase; it may temporarily reduce viral excretion, but it is not capable of eliminating the infection.
In experimental studies AZT has been shown to reduce viral excretion, to boost the immune system, to improve clinical conditions and health status and to prolong the life expectancy of some FeLV-infected cats. It has also been shown to be capable of preventing infections and of eliminating the virus from the organism, but only if the treatment is started within 96 hours of contagion. FIV and FeLV-positive cats, in particular those with virus-induced neurological diseases or stomatitis, may gain clinical benefit from treatment with AZT.
In various trials FIV and/or FeLV-infected cats, all with pathologies correlated to the infection (chronic oral inflammation – stomatitis), were treated with AZT, or with a placebo, for 3 weeks, without other concomitant treatments. In these trials, FIV-infected cats treated with AZT had an improvement, compared to the placebo group, in terms of overall clinical status, in the grade of stomatitis and in the count of T-helper cells. FeLV-infected cats also had an improvement in signs and a decrease in antigenemia. However, although zidovudine is capable of reducing the viral load and improving signs in infected cats, it is not able to modify the natural evolution of the disease to a relevant degree.
AZT is used in the collateral therapy of FeLV and FIV in cats at the dose of 5-10 mg/kg per os every 12 hours, for 2-3 months.
Regular complete blood counts are necessary during treatment because non-regenerative anaemia is a common side effect of this drug, especially when it is used at the higher dose. During the first month a complete blood count must be carried out every week; if values are stable then one test per month is sufficient. Cats with myelosuppression should not be treated with AZT, in view of the risk of developing an extremely severe, life-threatening anaemia. In cats with concomitant chronic renal failure the dose must be reduced, in order to avoid toxicity resulting from drug accumulation. Studies in which cats were treated with AZT for 2 years have shown that the drug is well tolerated in most FIV-infected cats. During the first 3 weeks of therapy some cats may suffer a slight decrease in the haematocrit, which resolves even without suspending treatment. If the haematocrit falls below 20% the drug should be suspended; the anaemia usually resolves in a few days.
Unfortunately, as for human immunodeficiency virus (HIV), AZT-resistant mutant forms of FIV may develop even after as few as 6 months of treatment (Hartmann, 2005).
Feline interferon omega(IFN-ω) is a type III IFN-awith a marked antiviral effect. It has shown considerable efficacy against feline and canine cells, with its effect being greater than that of human interferon. The animal origin of IFN-ω makes high-dose parenteral use possible, without the inconvenience of antibody development.
Feline interferon was used in a multicentre, placebo-controlled, double-blind field trial (De Mari et al., 2004) in FeLV-infected and in FeLV and FIV co-infected cats; one group received feline interferon at the dose of 106 U/kg s.c. once a day for 5 consecutive days, repeated three times starting in weeks 0, 2 and 8. Both groups received supportive care specific for the clinical signs (e.g. rehydration, antibiotics). The efficacy of the treatment was assessed over a 4-month period. Clinical signs improved considerably in the interferon-treated group, compared to the control group, although no difference was observed in terms of survival.
The use of interferon at antiviral dosages is based on the assumption that if an effective level of circulating interferon is maintained beyond the first 2 days of infection this should inhibit the viral load, allowing T cells to mount an effective and specific response against the infection. It should be noted that the interferon produced by one species may also be active against viruses of another species. Interferon has also proven efficacious against Parvovirus of the dog and, in experimental trials, against distemper [6]. In the cat, it is effective at preventing Feline herpesvirus (FHV-1) infections from becoming chronic and in the treatment of Calicivirus and FHV-1 infections, reducing the severity and duration of clinical manifestations.
If used in subjects which are clinically sick, the dose is as follows: recombinant fIFN 1,000,000 U/kg s.c. on days 0, 1, 2, 3 and 4, and then on days 14, 15, 16, 17 and 18 and on days 60, 61, 62, 63 and 64 (3 series of 5 inoculations s.c.).
Highly active antiretroviral therapy(HAART): Drug cocktails are now the most effective therapy in HIV-infected humans. This type of antiviral treatment has also been studied in cats, although the number of drugs available in veterinary medicine is more limited and the treatment tends to be more toxic than in humans (Hartmann 2006).