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Evaluating alternative treatments of chronic upper respiratory tract infections in shelter cats

Fenimore A, Carter K, Fankhauser J, Hawley JR, Lappin MR. Evaluation of intranasal vaccine administration and high-dose interferon- α2b therapy for treatment of chronic upper respiratory tract infections in shelter cats. J Feline Med Surg. 2016 Aug;18(8):603-11. 

Upper respiratory traction infections (URTIs) are a major cause of disease in cats all around the world, however cats in high density housing situations are particularly affected. Cats in shelters particularly are often in less than ideal health, unvaccinated, and affected by concurrent diseases. They are also subject to many stresses and are regularly mixed with other cats. These factors make the development of upper respiratory tract infections extremely common. These infections are most often caused by either feline herpesvirus 1 (FHV1) or feline calicivirus (FCV), with mycoplasma, chlamydia, Bordetella, and pasturella playing lesser roles.

Antibiotic (and to a lesser extent, antiviral) therapies have classically been the mainstay of upper respiratory tract infection treatment. While these are valid methods for the control of secondary and tertiary infection, there are many concerns with the use of these drugs, including antibiotic resistance, failure to address the underlying cause, cost, and side effects of medications. As the underlying cause of these conditions is generally viral, antibiotics are often not the most appropriate choice. While antivirals for FHV1 exist, they have limited efficacy, and anti calici-virals are not available.

While disease often resolves with supportive care and stress relief, persistent, chronic infections are possible. In these cases, antibiotic therapy is rarely effective, and antiviral therapy (lysine and famciclovir) has had mixed success. Multiple therapies have been proposed to treat these chronically infected cats. Intranasal vaccination is a potential method of control disease, through modulating local immune response and stimulating local antibody production. As vaccines against the most common respiratory pathogens are readily available, this provides an attractive route of therapy.

Another potential option is the administration of Type 1 interferons (specifically human IFNg and feline IFNw). These chemicals have powerful immunomodulatory and antiviral properties, and have been tested in topical, oral and injectable forms at a wide range of doses.

The study was designed as a prospective, randomized, non-blinded clinical trial comparing two treatment groups with no control. While there are obvious downsides to this style of study, it allowed for some good preliminary information in a clinical setting to be collected.

Over 700 cats were screen to identify a population of 47 who had clinical signs or URTI refractory to therapy with multiple antibiotics and antivirals for  greater than 3 weeks. All cats were between 16w and 3y of age. Several cats were disqualified due to resolution of clinical signs. A total of 13 cats were entered into Group A and 12 into Group B.

Inflammatory cytokines in peripheral blood were determined in each group before and after therapy. PCR of pharyngeal swabs was used to determine the infectious agents present in each animal.

Group A cats were administered human IFN-a2b at 10000 U/kg SQ every 24h for 14 days. They were also administered sterile saline into each nostril once to simulate intranasal vaccination. Group B cats were administered one dose of commercially available intranasal FHV1/Calici vaccine.  They were also given 1 mL sterile saline SQ every 24h to mimic IFN administration.

A clinical score was determined on all cats each morning based on degree of conjunctivitis, blepharospasm, ocular discharge, attitude, appetite, temperature, and sneezing. All cats started with scores greater than 6.  A response was concerned a score of less than 3. Cats with scores >3 on day 13 were entered into the opposite treatment group.

All cats administered the combination vaccine intranasal responded with 14 days. Median response time was 8 days. 61.5% of cats administered IFN responded by day 14, with a median response time of 8 days. 4 of 5 cats who changed from IFN to vaccines responded. One cat failed both therapies, as well as famciclovir rescue therapy, and was euthanized. Post mortem found a severe, chronic rhinitis.

The method of action of the intranasal vaccines is unsure. It may include replacement of pathologic viruses with vaccine strains, immunomodulation, or induction of local immunity.

Molecular diagnostics preformed during this study failed to detect viruses in 65-70% of cases. This may be due in part to sampling methods, strain variations, and low viral loads. The cytokine panel likewise failed to provide significant information in the majority of causes, likely due to small sample sizes.

Further work is needed to determine the exact roles of topical immunotherapy and IFN in the management of feline chronic URTI. Combinations of multiple therapies should also be investigated to determine if this may be more successful than monotherapy. However, the current data suggests that either parenteral IFN or topical immunotherapy may be effective at managing the clinical signs of chronic URTI in cats. (MRK)

See also:
Lappin MR, Sebring RW, Porter M, et al. Effects of a single dose of an intranasal feline herpesvirus 1, calicivirus, and panleukopenia vaccine on clinical signs and virus shedding after challenge with virulent feline herpesvirus 1. J Feline Med Surg 2006; 8: 158–163.

Haid C, Kaps S, Gonczi E, et al. Pretreatment with feline interferon omega and the course of subsequent infection with feline herpesvirus in cats. Vet Ophthalmol 2007; 10: 278–284.