viernes, 17 de junio de 2011

INTERFERON THERAPY IN DOGS AND CATS

Interferon Therapy in Dogs and Cats

Atención de Carolina Rossana Sepúlveda Fernández

The license for use of the first feline omega interferon especially developed for
veterinary medicine applies exclusively to the reduction in mortality and clinical
signs of the enteric form of canine Parvovirus infection.
Additionally, it is also successfully used in feline Parvovirus infection, cat flu, FIV and FeLV, chronic stomatitis, distemper and kennel cough infections. Further
possible areas of use include the prophylaxis against viral infections and the
treatment of certain canine and feline tumours.
The exact mechanism of action of interferon is not yet understood, although it plays
a role in increasing the body’s non-specific defences and hinders internal synthetic
mechanisms in infected cells.
Interferon treatment is better tolerated in dogs and cats than in humans, who may
show flu-like symptoms and other serious side effects. Contraindications include
vaccination during or after interferon therapy, until recovery is complete.

Treatment of canine Parvovirus with interferon
Canine Parvovirus (CPV type 2) causes an infectious enteritis. Despite vaccination,
Parvovirus infection is a commonly occurring, highly contagious viral infection with a characteristic high mortality rate. Puppies and young animals are especially at risk, as are older animals kept in large numbers in a confined space. The main clinical signs are those of haemorrhagic enteritis, vomiting, loss of appetite, dehydration sudden collapse and death. Parvovirus infection is characterised by the sudden appearance of dramatic clinical signs and its aggravation linked to immunocompromisation of the patient.
The virus is excreted in the faeces and is extremely resistant to disinfectants and heat, which aids its endemic spread, for example in animal shelters. Parvovirus is a singlestranded DNA virus, of which there are two currently known antigenic types (CPV 2a and CPV 2b). Parvoviruses affect many species, especially domestic and wild carnivores.
Parvovirus infections also occur in humans.
Puppies are mainly protected by maternal antibodies. As soon as the concentration of
maternal antibodies declines, they are particularly susceptible to infection. The greatest stresses occur at time of weaning and when changing to new surroundings. The situation becomes more critical when the bitch herself produces insufficient antibodies. There is at present no known primary antiviral therapy. Treatment is symptomatic and consists mainly of supportive measures, such as replacing fluid losses by infusions, use of anti-emetics, H2 receptor antagonists and analgesic spasmolytics. Secondary bacterial infections are countered with broad-spectrum antibiotics.
Administering homologous immunoglobulins recovered from super-immunised dogs can
provide diseased animals with a good antibody titre; these antibodies are naturally quickly broken down and the technique is therefore only suitable as a supplementary therapy.
Immune sera (Stagloban P®) is only effective during the viraemic phase, which appears 2- 3 days after the start of the incubation period.

start of disease 1st inj 2nd inj 3rd inj
2.5MU/kg 2.5MU/kg 2.5MU/kg
d0 d2 d4 d7
max. clinical clinical clinical clinical
4 days evaluation evaluation evaluation evaluation
1st & 2nd evaluation
of efficacy
Fig. 1: Treatment of canine Parvovirus infection with omega interferon

Indications for the use of immunoglobulins in Parvovirus infection: support in the initial phase in order to prevent further spread of infection; in later stages
their use is less successful prophylaxis in puppies in problem groups and to close the "immunity gap" Type 1 interferons have antiviral, antiproliferative and immune modulating properties.
Human as well as veterinary interferons have been investigated with respect to their
possible veterinary clinical application. The recently available feline recombinant interferon (rFelFN-Ω) has been shown to have in vitro anti-viral properties, dependent on the dose, the virus type and the host cell type. Interestingly the rFelFN-Ω possesses an inter-species efficacy, and can be used in dogs suffering from enteritis caused by Parvovirus.

Experimental infection with canine Parvovirus (CPV 2b) Specific pathogen free Beagle puppies were infected by oronasal route with a virulent strain of CPV 2b virus. The animals were treated after they had shown clinical signs for one day; signs included
enteritis, vomiting, lethargy and excretion of virus in the faeces. The infected dogs were divided into two groups:
Group one
The treatment (figure 1) comprised the intravenous administration of feline interferon (rFelFN-Ω) at a dose of 2.5MU/kg body weight on three consecutive days as well as symptomatic supportive therapy. Survivors of the acute phase were given an easilydigestible diet.
Group two
The second group of diseased dogs received a placebo instead of interferon.
Results
On the first treatment day there was no significant difference in clinical signs between the two groups. Shortly afterwards the placebo group animals developed a severe enteritis and a dramatic worsening of their overall clinical condition. In contrast to this the IFN treated animals showed a fundamentally different clinical picture: their general condition improved, and diarrhoea, vomiting, anorexia and lethargy all subsided. On the third day after starting the treatment, the enteritis was brought under control. In the interferon group four out of five dogs survived the experimental infection. In contrast to this all five dogs in the control group died despite general supportive therapeutic measures. They had shown a leucocytosis on the fourth day following infection, followed within two days by a leucopoenia which persisted until death. The interferon group, however, showed a moderate leucocytosis which later normalised. The results of this experimental model have been largely confirmed in many studies under field conditions. Feline omega interferon at a
dose of 2.5MU/kg body weight greatly reduced the clinical signs and significantly improved the survival rate, without observable side effects. An accompanying symptomatic
Reports and Analyses

Indications
Parvovirus infection in the dog:
2.5MU/kg i/v for 3 days
Calicivirus infection in the cat:
2.5MU/kg i/v or s/c for 3 days
FeLV in the cat:
1MU/kg s/c for 5 days
FeLV + FIV:
1MU/kg s/c for 5 days
FIV
1MU/kg 3x5 injections (d0 + d15 + d60)
fig. 2 Indications and dosages for feline omega interferon
Indications
prophylaxis:
dog + cat 0.5 - 1MU/kg
1 injection - 1 day before exposure
metaphylaxis:
dog + cat 0.5 - 1MU/kg
as early as possible 2 injections
24 - 48 hours apart
convalescence:
dog + cat 0.5MU/kg
3 injections - d0 + d2 + d9
fig. 3 Further indications and dosages for feline omega interferon in the reinforcement of the body’s own defences treatment for animals with Parvovirus infection is necessary and useful in all cases. The
These therapeutic measures were effective in the early stages of disease, but lost their efficacy as the infection progressed. Since the late eighties research has been directed at substances with direct anti-retroviral activity. AZT and PMEA are the two medicines authorised for the treatment of HIV infection in humans. They also have effects in
Reports and Analyses

Use of interferon omega 4 years after its launch on the Japanese market cat flu feline and canine prophylaxis feline and canine Parvovirus infection FIV & FeLV
chronic stomatitis feline and canine tumours distemper & kennel cough
other

fig. 5 Statistics for the commonest uses of omega interferon in practice persistently infected cats by decreasing antigen load and reducing signs of concurrent disease.

These antiviral treatments do not, however, eliminate the virus from the body.
They do increase patients’ survival time and quality of life. On the other hand the therapy has marked toxicity resulting in a non-regenerative anaemia, diarrhoea, anorexia and weight loss. As soon as cats become anaemic the treatment must be
discontinued. The antiviral,immunomodulatory and antiproliferative effects of the interferons have also proved helpful in feline retroviral infections. The high dose therapy with human interferon resulted initially in a complete suppression of circulating antigen - however cats developed specific neutralising antibodies to the
human interferon within a few weeks, making further treatment impossible. In
some treatment protocols a combination of interferon and AZT was used. However the
limitation of many of the treatments so far described is that they never developed beyond the experimental stage, whether because of their doubtful efficacy, possible side-effects or because of resistance due to the cats’ antibody production. They are therefore of hardly any use in veterinary practice.

Treatment of feline Retrovirus infections with feline omega interferon (rFelFN-Ω) Many experimental results, however, indicate that omega interferon of feline origin could be of great interest in the treatment of FeLV and FIV. In persistently infected cats the large viral load, and thus the advance of disease, can be reduced.
The dose is 1MU/kg s.c over a period of 5 days. The results of one field trial show that omega interferon improves the survival rate and the general condition of cats naturally infected with FeLV or FIV, by reducing the signs of concurrent disease. Every so often, cats with clinical signs of retroviral infection present with phases of secondary infections.
The periods of illnesses can be separated by quiescence of clinical signs. The further the disease progresses, the less it can be influenced by symptomatic treatment. The administration of rFeIFN-Ω in the form of an interval therapy during the evolution of the disease aims to avoid relapses and to improve the efficacy of symptomatic treatment. The quality of life and life expectancy of the diseased cats are improved. These results are based on a limited number of animals. Therefore more extensive studies are currently being conducted in Europe to further support the indications of a positive effect of feline omega interferon.

Conclusion

There are currently over 100 scientific publications, articles and reports on the efficacy of feline omega interferon (figure 5). At present the generally accepted indications for the use of interferons in dogs and cats are infections with Parvovirus, Calicivirus, FeLV and FIV and prophylactic immune stimulation. In addition, the antitumour efficacy of interferon makes it a useful palliative aid in the management of certain types of tumours.

Vaccination during or after interferon treatment is contraindicated until complete recovery of the patient.
compiled and edited
Dr. Dieter Müller, specialist in small animal medicine, ophthalmology, Kempener Str. 59, D-52525 Heinsberg

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