Agents Responsible for Feline URTD (Cat 'Flu')

Several infectious agents contribute to URTD: feline herpes virus (FHV) and feline calicivirus (FCV) are most commonly involved, whilst Chlamydophila felis, Mycoplasma spp., and Bordetella bronchiseptica can also play a part. Secondary bacterial infections are also common, e.g., Staph, Strep, Pasteurella. Acute and chronic URTD is seen in cats; acute being ≤ 10 days in duration, whereas chronic URTD lasts > 10 days.

Clinical Signs

FHV and FCV

Typical signs of cat 'flu' are pyrexia, sneezing, conjunctivitis (hyperaemia, chemosis), oculonasal discharges (initially serous then mucopurulent crusting of external nares and eyelids), depression, inappetence, dehydration, salivation with drooling (FHV > FCV), oral ulcers (FCV > FHV) and ulcerative keratitis (dendritic ulcers, when seen, pathognomonic for FHV). Occasionally see ulcerated/erosive facial skin lesions with FHV. FHV can cause more severe URTD, especially in young kittens,¹ whilst FCV-associated disease is often mild and varies with strain involved.²

Additional atypical syndromes reported with FCV:

 Transient limping syndrome
Pyrexia and acute transient lameness seen ± URTD signs; the lameness can be severe and may shift quickly from one limb to another. Full recovery usually occurs within 24–48 hours without treatment, but NSAIDs may be useful.

 Acute severe virulent systemic disease (VSD)
A syndrome reported in the USA and Europe, typically affecting multiple cats in a group,³ but individual cats too.⁴ Associated with high mortality (30–50%), interestingly especially in adult cats. Clinical signs include facial and paw cutaneous oedema and ulceration, bruising, pyrexia, icterus and cat 'flu' signs.

Chlamydophila felis

C. felis is a common cause of conjunctivitis, especially in young (< 1 year of age) cats.⁵ Conjunctivitis, ocular discharge (initially serous and unilateral, then mucopurulent and bilateral) and chemosis are seen, but corneal ulceration is not a feature. Occasionally may see sneezing and a nasal discharge too.

Mycoplasma spp. and Bordetella bronchiseptica

Both Mycoplasma spp. and B. bronchiseptica can be found in normal cats, but have also been associated with disease. Mycoplasma spp. can cause conjunctivitis, and an association with URTD has been reported,⁶ whilst B. bronchiseptica can cause ocular and nasal discharge, sneezing, pyrexia ± coughing.⁷

Carrier Cats

All FHV-infected cats probably become lifelong carriers; FHV exists in a latent form in nervous tissue and is shed intermittently following activation, e.g., stress due to boarding, travel, immunosuppressive treatment; such reactivation may or may not be accompanied by clinical signs. If clinical signs occur, they are often less severe than with primary infection and are usually unilateral and ocular in nature. Most cats shed FCV following infection (continuously; no latency), but the number shedding virus progressively decreases over time such that lifelong carrier status occurs in only a minority of cats. Asymptomatic carriers also exist for B. bronchiseptica and C. felis.

Transmission of Infection

Multicat households have more URTD. Organisms are shed in ocular, nasal, and oral secretions to transmit infection via direct contact between cats, including asymptomatic carrier cats. Fomite transmission is less important (C. felis is very labile), but indirect transmission can occur with FHV, FCV and B. bronchiseptica if a high load is present.

Diagnosis

In an individual cat, identification of the aetiological agent(s) responsible for URTD, especially in acute disease, may not be required. If several ill cats are being dealt with, the household is a breeding cattery or shelter, or chronic or severe disease is present, identification of agent(s) may become more important to direct specific management.

FHV and FCV

Virus Isolation (VI) can be performed on oropharyngeal or conjunctival swabs collected into viral/chlamydophila transport medium; results take 48 hours to 7 days. VI, however, is now largely superceded by PCR on swabs; results much faster (24–48 hours). Quantification of FHV or FCV copy number on quantitative PCR assays can help interpretation of results, as high viral loads in clinical specimens suggest active viral replication and involvement in the disease process, whereas lower loads may be more consistent with asymptomatic carrier status. Cats recently vaccinated with modified live vaccines may also be PCR positive. Serology cannot differentiate vaccinated and naturally infected cats and so is of limited use in diagnosis.

Other Agents

C. felis is now most commonly detected via PCR on conjunctival swabs, but serology exists for antibody detection. Mycoplasma spp. infection is usually diagnosed via PCR (culture is more difficult) on conjunctival or oropharyngeal swabs. B. bronchiseptica can be detected via PCR or culture (on selective media) of oropharyngeal swabs. Bronchoalveolar lavage fluid samples can also be used for PCR detection of B. bronchiseptica and Mycoplasma spp. when pneumonia is suspected alongside URTD.

Treatment

Antibiotics

Although the majority of URTD cases will be due to viral infections, 2° bacterial infections are important to control. An empirical choice is usually made with culture and sensitivity only performed if a poor response is seen or in chronic cases. Doxycycline (10 mg/kg/day) has recently been recommended by the ISCAID (www.iscaid.org) Antimicrobial Guidelines Working Group as first-line treatment for URTD in cats; it is effective against many of the common agents that cause 2° bacterial infections but also has efficacy against Bordetella, Mycoplasma spp. and C. felis, and is antiinflammatory! The ISCAID guidelines recommend a fluoroquinolone (effective against Bordetella and Mycoplasma spp.) as a second-line antibiotic for URTD in cats. A 10- to 14-day course may be adequate for acute infections, although 4 weeks of treatment is recommended to eliminate C. felis infection, and 6 weeks of treatment has been recommended for elimination of Mycoplasma spp. infection (for both C. felis and Mycoplasma spp. infections, concurrent treatment of in-contacts is recommended). Amoxicillin-clavulanate (can be effective for C. felis too) is an alternative agent. Topical ocular antibiotics may be required if severe ocular signs are present. Liquid oral antibiotics or injectables, or palatable formulations, may be easier to administer if the cat has a sore mouth.

Chronic rhinosinusitis cases need 6–8 weeks of antibiotic treatment (e.g., clindamycin, doxycycline, amoxicillin-clavulanate, cephalexin), ideally based on culture and sensitivity results from nasal flushes or biopsies. Occasionally pulse antibiotic therapy is used.

Supportive Care

The importance of aggressive supportive care cannot be understated for both acute and chronic cases.

Diligent supportive nursing is important; cleaning away discharges, grooming, TLC, regular application of treatments, e.g., nebulisation (see below).

Fluid therapy to correct dehydration (debilitating and worsens congestion).

Steam therapy can be provided by owners in the home by sitting with the cat in a bathroom with hot running water (BID or several times a day if possible), or cheap small nebulisers can be purchased for use in the clinic or home for regular nebulisation therapy. These techniques rehydrate the upper respiratory tract, loosen secretions, and increase comfort.

Nutritional support is important as inappetance is common; tempting the cat to eat by hand-feeding warm, smelly, blended foods may be sufficient in mild cases, but appetite stimulants (e.g., mirtazapine, 1.88 mg/cat PO, SID, or EOD) and/or enteral tube feeding may be required. Commonly used options for tube feeding include nasooesophageal (good as no sedation required for placement, although cats may resent tube around nose if URTD - sometimes intermittent placing for each feed can work better than leaving one in place) and oesophagostomy (rapidly placed under a short GA, and good to keep the tube away from the face; www.kittykollar.com) tubes.

NSAID therapy, e.g., meloxicam, may be helpful as an antiinflammatory, antipyretic, and analgesic agent, although ensure the cat is rehydrated before use, does not have kidney disease, and give with food.

Nasal decongestants, e.g., phenylephrine, and mucolytics, e.g., bromhexine used by some.

Antivirals

The use of antivirals is limited due to cost, side effects and practicalities of application. Topical ocular antiviral treatment is not usually indicated in acute URTD unless corneal ulceration is present or the ocular disease is particularly severe, but may be useful in chronic FHV-associated ocular problems. Cidofovir (0.5% ophthalmic drops) is practical as it only requires twice-daily administration (1–2 drops into eyes BID for 2–3 weeks).⁸ 1% trifluorothymidine (Viroptic) is said to be most effective, but is an irritant and requires five times-daily application. Famciclovir, an oral antiviral, is being increasingly used for FHV-associated disease (especially ocular disease but URTD too) and is well tolerated. Studies have documented improvements in systemic and ocular signs of experimental FHV infection at a dose of 90 mg/kg PO TID for 3 weeks,⁹ but lower doses and shorter courses have also been beneficial (125 mg PO BID in adult cats, or 30–50 mg/kg PO BID in kittens, for 2–3 weeks) in naturally infected cats.¹⁰ Concurrent use of an antibiotic (oral doxycycline) and lubricant (hyaluronic acid or Lacri-Lube) with famciclovir is recommended to optimise treatment in cats with URTD.

Oral lysine (500 mg/cat SID/BID) competes with arginine which is essential for FHV replication. Although lysine has been shown to have FHV replication inhibiting properties in vitro and in vivo, evidence of efficacy in clinical trials¹¹ has been less convincing, but it is used and valued by some, so remains an option.

Feline interferon-omega therapy has also been reported for both FHV and FCV-associated disease; can be given systemically or topically, although clinical trials confirming efficacy are limited. Doses reported for use are 1 MU/kg SC q 24–48 hours or 50,000–100,000 U PO SID, or drops applied to eyes 3–5 times/day [30–50 U/ml in artificial tears]).

Chronic Rhinosinusitis/'Snufflers'

This can occur after severe FHV and/or FCV-induced damage to the nasal mucosa and turbinates resulting in the development of chronic 2° bacterial infections with associated sneezing and nasal discharge. Usually diagnosed after exclusion of other causes of URTD (e.g., neoplasia, fungal infection, foreign body, dental disease) using nasal imaging, flushes, histopathology and culture. Treatment is palliative and recurrences are common. Use supportive treatments as described above; severe cases may also benefit from intermittent nasal flushing (e.g., repeated flushing of 10-ml saline aliquots via the nostril whilst throat is well packed, with cat's head pointing downwards over the end of the table) to dislodge inspissated discharge (submit samples for culture and cytology if necessary too). Longer term antibiotic (6–8 weeks) treatment required, and intermittent pulse antibiotics may be required thereafter (e.g., one week every four, attempting to taper out).

References

1.  Thiry E, Addie D, Belak S, et al. Feline herpesvirus infection. ABCD guidelines on prevention and management. Journal of Feline Medicine and Surgery. 2009;11:547–555.

2.  Radford AD, Addie D, Belak S, et al. Feline calicivirus infection. ABCD guidelines on prevention and management. Journal of Feline Medicine and Surgery. 2009;11:556–564.

3.  Reynolds BS, Poulet H, Pingret JL, et al. A nosocomial outbreak of feline calicivirus associated virulent systemic disease in France. Journal of Feline Medicine and Surgery. 2009;11:633–644.

4.  Meyer A, Kershaw O, Klopfleisch R. Feline calicivirus-associated virulent systemic disease: not necessarily a local epizootic problem. Veterinary Record. 2011;168:589.

5.  Gruffydd-Jones T, Addie D, Belak S, et al. Chlamydophila felis infection. ABCD guidelines on prevention and management. Journal of Feline Medicine and Surgery. 2009;11:605–609.

6.  Holst BS, Hanas S, Berndtsson LT, et al. Infectious causes for feline upper respiratory tract disease - a case-control study. Journal of Feline Medicine and Surgery. 2010;12:783–789.

7.  Egberink H, Addie D, Belak S, et al. Bordetella bronchiseptica infection in cats. ABCD guidelines on prevention and management. Journal of Feline Medicine and Surgery. 2009;11:610–614.

8.  Fontenelle JP, Powell CC, Veir JK, Radecki SV, Lappin MR. Effect of topical ophthalmic application of cidofovir on experimentally induced primary ocular feline herpesvirus-1 infection in cats. American Journal of Veterinary Research. 2008;69:289–293.

9.  Thomasy SM, Lim CC, Reilly CM, Kass PH, Lappin MR, Maggs DJ. Evaluation of orally administered famciclovir in cats experimentally infected with feline herpesvirus type-1. American Journal of Veterinary Research. 2011;72:85–95.

10. Malik R, Lessels NS, Webb S, et al. Treatment of feline herpesvirus-1 associated disease in cats with famciclovir and related drugs. Journal of Feline Medicine and Surgery. 2009;11:40–48.

11. Rees TM, Lubinski JL. Oral supplementation with L-lysine did not prevent upper respiratory infection in a shelter population of cats. Journal of Feline Medicine and Surgery. 2008;10:510–513.