Feline Upper Respiratory Infection: Diagnosis & Treatment. Chumkee Aziz, DVM Resident, UC-Davis

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Feline Upper Respiratory Infection: Diagnosis & Treatment Chumkee Aziz, DVM Resident, UC-Davis

Etiology

What causes it? Pathogens: Feline herpes virus type 1 (FHV-1) Feline calicivirus (FCV) Chlamydia felis Mycoplasma felis Bordetella bronchiseptica What causes URI in a shelter?

What causes it in the shelter w/ high URI rate?

What causes it in a shelter w/ low URI rate?

What causes it in the shelter? Herpesvirus = majority of endemic shelter URI Calicivirus & Bordetella What does = sporadic this mean? Chlamydia Implications = rare but problematic for URI management Mycoplasma = common but mostly a secondary player

Stress Inadequate housing Crowding Poor air quality Poor sanitation Host health Length of stay Risk Factors

Why It s Challenging Multifactorial disease Presence of pathogens in clinical & nonclinical cats Pathogens Host factors Environmental factors Cats enter with viruses How to prevent transmission? Overlapping, non-specific clinical signs How to diagnose? Costly & impractical to do diagnostics on every cat When are diagnostics needed? How to manage it? Different treatment options Shelter policies? Vaccine does not induce sterile immunity How to prevent?

Characteristics

Transmission STRESS reactivates herpesvirus Fomites Direct contact Droplet transmission up to 5 ft Aerosolization not as important Should the public be allowed to touch the cats?

Disease Course - Herpesvirus First timer Incubation = 2-6 d Shedding period = 14-21 d Reactivated Lag phase = 4-11 d Shedding period = 1-13 d (avg 7d)

Disease Course - Calicivirus Incubation period: 2-6 d Shedding period: typically < 30 d Carrier state can be lifelong shedder In shelter setting, ~25% of cats can be shedding at any one time

Recognition & Identification

Diagnosis Overlapping clinical signs makes diagnosis of a specific pathogen difficult Pathogens are found in healthy cats presence of pathogens does not prove disease causation Disease severity & course are variable based on host, environmental, and pathogen factors

Clinical Signs Limping Calici Oral Ulcers Keratitis/Dendritic Corneal Ulcers Conjunctivitis w/o nasal signs Dermatitis/Dermal Ulcers Calici Herpes Herpes Chlamydia Mycoplasma VS-Calici Herpes

Lingual Ulceration Calicivirus Quat toxicity Herpesvirus

Clinical Features - Bacterial Pathogens Chlamydia felis Conjunctivitis Responds to treatment but signs recur Bordetella bronchiseptica Coughing may be more common Transmission between dogs & cats possible Mycoplasma spp. Commensal in URT Unclear role

Common Diagnostics Primary PCR Necropsy Secondary Bacterial culture + sensitivity Virus isolation

Challenges of PCR Chronic infections low level shedding false negatives Subclinial shedding makes positives hard to interpret Avoid topical anesthetics + fluorescein reduces sensitivity Recent MLV vax false positives

When to do diagnostics Persistent disease > 7-10 days Unusual, severe, increased frequency of signs Lower respiratory disease present Changing infectious disease protocols

Who to test Acutely affected (< 4 days of signs) & exposed cats Prior to treatment Sample most affected site Enough to reflect larger population 10 30% of the population, min of 5 cats

Necropsy Can directly identify presence & role of pathogens Fresh, unfixed tissue submitted for PCR & culture/isolation Obtain first before contamination Refrigerate for bacteria, freeze for viruses URT & lung samples Histopathology samples Formalin (10:1, formalin:tissue) Nasal sinus, trachea, lung, heart, hilar or thoracic inlet LNs GI, liver, kidney, spleen if systemic disease Chapter 7, Infectious Disease Management in Animal Shelters, Miller and Hurley

Virulent Systemic Calicivirus Rare, sporadic outbreaks of different strains Typical signs precede severe signs Challenging to diagnose (VS-Calici is not genetically distinguishable Calici) Must immunohistochemically link presence of virus in viscera w/ lesions

How Virulent Is It? - Most Many scenarios strains turn of different out not to pathogenicity be VS-Calici varying degrees of clinical signs - Rule out other causes of severe disease/acute death: Eg. Staff member s pet is affected It is much more common to diagnose panleukopenia with calicivirus or another respiratory pathogen compared to VS-Calici Mild during signs a URI in young outbreak cats w/ low high risk mortality Panleukopenia Quaternary ammounium toxicity Streptococcal infections Gauge how the population is affected Mutlifactorial etiology (host, environment, & pathogen factors) Severe signs in healthy, vaccinated adults higher risk - Contact for help.

Treatment of Acute URI

Treatment Isolation Supportive Care Nursing Care Hydration Promote appetite Analgesia NSAIDs Lysine Minimize Stress Antibiotics Antivirals Ophthalmic Treatment

Isolation Importance of prompt recognition Ideally, separate ward In-cage isolation is ok if fomite transmission is considered at all times & cat is not on antibiotics Do not house kittens in same room Place signage Partial cage cover Spot clean Handle last

Minimize Stress Hide box Fresh air Conservative disinfectant use spot clean Minimize noise Separate from dogs

Nursing Care Keep them comfortable, clean, nourished, & warm Clear discharge Hand feed Provide soft bedding Low stress Familiar routine Familiar caregiver

Hydration - Makes secretions less viscous - Helps mucociliary apparatus function - Reduces invasion of secondary pathogens - Low stress - Warm fluids - Do not have to move the cat

Promote Appetite Wet foods Hand-feed Warm, smelly, soft foods Baby foods without onion/garlic powder Add in chicken broth or tuna juice Remove if cat is averse Place away from litter box Appetite stimulant Mirtazapine 1.87mg PO q 48h (smaller, more freq dose) Do not give Cyproheptadine with Mirtazapine

Minimize Discomfort Analgesia If oral or corneal ulcers are present IV, IM, or OTM buprenorphine NSAIDs Meloxicam dose once In euhydrated patients

Lysine Competitive inhibitor of arginine theoretically decreases replication of herpesvirus Ineffective as preventative in shelter trials Likely needs to be BID bolus (not ad lib w/ food) which is likely stressful to cats Can try in client-owned or foster cats

Antibiotic Therapy Considerations Antibiotic use is shelter & animal dependent Downsides to treatment adverse effects, stress, cost, antibiotic resistance Conservative treatment is best If all cats progress to signs of bacterial infection, then start antibiotic tx early BUT reassess: Stress control Air quality Crowding

Treating Bacterial Infections Doxycycline 10mg/kg PO SID x 7-10 d most commonly used first line Effective against Chlamydia, Bordetella, & Mycoplasma Good airway + ocular penetration Safe in kittens Follow w/ fluid bolus if tablets used

Second Line Antibiotic Therapy If no response by ~ 5-7 d, consider Switching for broader coverage against pathogens Shelter URI is viral-driven in which secondary pathogens & Mycoplasma play a more frequent role than Bordetella or Chlamydia Alternatives to consider switching to or adding on: fluoroquinolones, beta lactams

Antibiotics Ophthalmic Therapy For mild disease Doxycycline (effective ocular penetration) For severe disease Add in topical Broad spectrum that s also effective against Chlamydia (tetracycline or erythromycin) Avoid triple AB in cats Can be irritating, monitor closely Topical mucinomimmetic for depleted goblet cells Antivirals Reserve for refractory herpes cases Topical 0.5% Cidofovir BID Systemic Famciclovir 40mg/kg PO TID

Treatmentmonitoring Record daily signs Attitude Appetite Clinical signs Elimination Ensure initializing!

Treatment Course Discontinue treatment once signs resolve Consistent monitoring imperative Move back to adoptions once signs resolve Significantly reduced shedding

Treatment of Chronic URI

If signs are not resolving, consider: Population problem: Flow issues Ventilation Treatment noncompliance Different pathogen Individual problem: Chlamydia infection Nasopharyngeal polyps Dental disease Fungal infection Neoplasia Foreign body

Chronic URI Response Initiate after two treatment failures: Careful physical exam Test for retroviral disease Diagnostics Treatment trial Foster or adopt w/ disclosures do not keep in isolation limbo!

Chlamydia Treatment Signs Conjunctivitis/chemosis +/- resp signs Ocular discharge (serous/unilateral mucopurulent/bilateral) Corneal ulceration uncommon Responds to treatment within 7 d but recurs in 14-30 d PCR if relapse occurs Treat w/ doxycycline for 28 d or 14 d past clinical resolution Foster to adopt candidate Reassess environmental factors

Chronic URI Therapy Antibiotics: If initially responds, tx for 6-8 weeks & don t switch antibiotics Clindamycin, Clavamox, Chloramphenicol, Azithromycin* Systemic antivirals for severe & persistent herpes signs Famciclovir 40mg/kg PO TID for 2-3 weeks Intermittent nasal flushing Prednisone (if evidence of lymphocytic-plasmacytic diesease) Intranasal vaccine (FVRC) Nasal decongestant drops Anti-inflammatories

Fostering Okay for: Run-of-the-mill URI cases Herpesvirus low risk to pet cats who are vax & aren t stressed Not for suspect severe calicivirus Keep pet cats safe: Revaccinate w/ intranasal FVRC +/- bivalent calicivax

Antiviral Use in Shelters - Single dose of famciclovir in shelter at intake* did not limit development of URI signs or reduce herpes shedding - Further studies needed to look at timing, dosage, duration - Antiviral drug-resistant strains of herpes have been described restrict use

References Bradley A, Kinyon J, Frana T, et al. Efficacy of intranasal administration of a modified live feline herpesvirus 1 and feline calicivirus vaccine against disease caused by Bordetella bronchiseptica after experimental challenge. J Vet Intern Med 2012;26:1121 5. Cohn, L. A. (2011). "Feline respiratory disease complex." Vet Clin North Am Small Anim Pract 41(6): 1273-1289.Gaskell R, Dawson S, Radford A, et al. Feline herpesvirus. Vet Res. 2007;38:337-354. Litster, A. L., et al. Clinical and antiviral effect of a single oral dose of famciclovir administered to cats at intake to a shelter. Veterinary Journal, 2014. Epub McManus C.M., et al., Prevalence of upper respiratory pathogens in four management models for unowned cats in the southeast United States. The Veterinary Journal, 2014. 201(20):p. 196-201 Pesavento PA & BG Murphy. Common and Emerging Infectious Disease in the Animal Shelter. Vet Path. 2014:51:478-491.

References Pesavento, P. A., et al. (2004). "Pathologic, immunohistochemical, and electron microscopic findings in naturally occurring virulent systemic feline calicivirus infection in cats." Vet Pathol 41(3): 257-263. Scherk, M. (2010). "Snots and snuffles: rational approach to chronic feline upper respiratory syndromes." J Feline Med Surg 12(7): 548-557. Sparkes, A. H., et al. (1999). "The clinical efficacy of topical and systemic therapy for the treatment of feline ocular chlamydiosis." J Feline Med Surg 1(1): 31-35. Stiles, J. Ocular manifestations of feline viral diseases. Vet J, 2014. 201(2): p. 166-173.

Questions?! Thank you! mcaziz@ucdavis.edu