Acute feline upper respiratory infection (Proceedings)

Upper respiratory infections (URI) are quite common in cats. Mortality due to common URI is very rare. However, these infections are not trivial. In group settings, and especially when young or unvaccinated cats congregate, URI can spread easily and affect large proportions of the population. In animal shelters especially, these infections can result in tremendously increased costs and decreased ability to place animals in homes. Although a causal link remains unproven, it is entirely possible that acute URI can predispose to later development of chronic rhinosinusitis, a problem in cats which is difficult to manage and usually impossible to cure. Additionally, more virulent strains of the common calicivirus infection can and does result in significant mortality as well as morbidity.

Causation

Feline URI is multifactorial. Multiple risk factors are involved, as are multiple pathogens. Pathogens may cause infection in isolation, or in combination. Particularly, secondary bacterial infection may follow primary viral URI. Evidently, viral pathogens are the most common cause of URI in cats. Feline calicivirus (FCV) is perhaps more prevalent, but feline herpesvirus-1 (FHV-1; a.k.a., feline rhinotracheitis) often causes a more severe clinical disease (with virulent calicivirus infection proving the exception to the rule). Primary bacterial pathogens involved in feline URI include Bordetella bronchiseptica and Chlamydophila felis. Secondary bacterial infection with a variety of pathogens can complicate either viral or primary bacterial URI. Each of the primary causes of feline URI will be addressed briefly.

FCV: Typical (FCV) and virulent systemic strains (VS-FCV): Typical FCV infection is a very common cause of URI in cats throughout the world. There are numerous strains of FCV resulting in variable disease manifestations and varied antigenicity. Depending on strain and host factors, infected cats may remain healthy or may develop fever, oral ulcerations, nasal discharge and sneezing, and sometimes lameness. The typical oral/respiratory disease is most severe in unvaccinated kittens after maternal antibody has waned (~10-14 weeks). The virus is shed via oral, nasal, and ocular secretions, and although more stable in the environment than other causes of feline URI, probably remains infectious for only a week. The greatest viral shedding occurs in the weeks during and after clinical infection, but apparently recovered cats may shed virus persistently for months to years. These recovered carriers may be wide-spread in localized populations of cats making it nearly impossible to eliminate exposure altogether in large group settings.

VS-FCV results from hypervirulent viral mutants. Unlike typical FCV, these virulent strains seem to cause more severe disease in adult (and often in FCV vaccinated) cats than kittens. VS-FCV results in a disease presentation quite distinct from that of typical FCV infection. Infected cats develop high fevers; swelling (edema) of the face and limbs; alopecia, crusting, and ulceration of the skin (especially the face, ears, and feet); and death. Mortality rates approach 50% even with supportive care. The virus is shed through feces and sloughed skin/hair as well as nasal, oral, and ocular secretions. Mildly affected cats (often kittens) can pass a virulent and potentially fatal form of VS-FCV, so all exposed cats must be considered potentially contagious. The virus itself is readily spread by fomites, and may be carried by veterinary personnel to other cats in the facility or even to their own pets at home. Facilities with documented cases of VS-FCV may need to temporarily shut down feline admissions to stop the spread of infection. Fortunately, this disease is rare.

FHV-1: Most cats are likely exposed to the single serotype of FHV-1 at some point in their lives. Exposure in susceptible cats can result in moderate to severe respiratory and ocular infection, although vaccinated or older cats may be infected but display minimal clinical signs. The most severe infections typically occur in kittens shortly after maternal antibody wanes (~ 9 weeks) and young, unvaccinated cats. Viral shedding in nasal, oropharyngeal, and ocular discharges is responsible for cat-to-cat and fomite-transmission; aerosol transmission is uncommon and the virus itself does not persist long in the envrionment. Two to six days after initial exposure, fever, anorexia, nasal discharge and sneezing, and ocular discharge develop. Many cats hypersalivate. Ulcerative and interstitial keratitis, corneal sequestrum formation, and anterior uveitis may be seen. Rarely, viral pneumonia and dermatologic symptoms are seen. Mortality rates are low, with most affected cats improving spontaneously in 10 to 20 days. As with all herpesviral infections, although clinical signs may resolve on their own, the immune system does not eliminate the infection. Instead, viral latency develops. Reactivation of virus can occur at any point later in life, generally in association with stress or immune suppression.

B. bronchiseptica: This Gram negative coccobacillus is an important cause of respiratory infection in dogs, but only recently it has been given attention as a primary respiratory pathogen of cats. Kittens are no more likely to be infected than adult cats, but may show more severe clinical signs. Clinical signs following experimental infection of cats included sneezing, oculonasal discharges, submandibular lymphadenopathy, and cough. The organism has also been isolated from naturally infected cats with a range of respiratory signs, including pneumonia. Spread of infection may be through cat-to-cat contact or via infectious discharges, and shedding can occur for weeks after infection from recovered cats. The organism is also found in healthy cats; it is more likely to cause disease in conditions of stress or overcrowding. The same bacterium can be transmitted between dogs and cats, and can also infect immunocompromised humans.

Chlamydophila felis: This bacterial species is predominantly an ocular pathogen. The organism is labile in the environment and is spread primarily through cat-to-cat contact. From 5-10 days after exposure, serous ocular discharge may be seen from one or both eyes. This progresses to bilateral mucopurulent discharge and chemosis, sometimes with sneezing and nasal discharge. Although not a commonly recognized problem, there is evidence that the infection may be transmitted from cats to people resulting in human conjunctivitis. Infected cats may continue to shed organisms for months after recovery.

Mycoplasma: The true role of these fastidious organisms in URI of cats is unknown. Mycoplasma species may be found in the upper airways and oropharynx of both healthy dogs and cats, and can be detected during lower and upper respiratory infections. They may be simply secondary pathogens, or may have a more important but yet undefined primary role in disease. Because they lack a cell wall, they are not cultured with routine methods nor are they killed with beta lactam type antibiotics.

Diagnosis

Clinical findings associated with URI due to any pathogen are similar (sneezing, nasal/ocular discharge, hyporexia), but particular manifestations are more likely with one type of infection than another. For example, Chlamydophila is more likely to cause severe conjunctivitis with milder nasal signs, B. bronchiseptica is more likely to cause cough, FCV is likely to result in oral ulcerations, and cats with FHV-1 infection are often more severely lethargic and demonstrate marked nasal signs and possible keratitis. In many situations (especially kittens or cats recently adopted into single cat households), specific etiologic diagnosis is unnecessary. However, confirmation of a specific diagnosis can sometimes be helpful in settings such as catteries or animal shelters. Sometimes, a simple test such as microscopic evaluation of a conjunctival scraping may identify inclusions suggestive of Chlamydophila, or characteristic ocular lesion such has dendritic ulcers may strongly suggest FHV-1 infection.

Often, confirmation of disease diagnosis is complicated. For example, although the best way to confirm infection with B. bronchiseptica via positive culture, it can be isolated from the upper airways of healthy cats. Serologic evidence of exposure to the pathogens associated with URI may be associated with infection, simple past exposure, or even vaccination. For organism with latency or carrier states, detection of nucleic acids via PCR methods may not imply active infection. Confirmation of VS-FCV depends on isolation of identical viral strains (usually from oropharyngeal swabs or necropsy specimens) from more than one affected cat. No test can differentiate VS-FCV from typical FCV in a single cat.

When bacterial infections are suspected culture can be used to identify pathogens. For any of the primary pathogens (Bordetella, Chlamydophila, or Mycoplasma) the laboratory should be notified of the clinical suspicion so that appropriate culture media and procedures can be used. Oropharyngeal, tracheal, or deep nasal culture swab samples should be collected into charcoal Amies transport medium when B. bronchiseptica is suspected. Chlamydophila can be cultured after vigorous conjunctival sampling; swabs should be placed in special media and kept refrigerated prior to timely laboratory submission.

Recently, panels of real-time PCR assays have been offered to detect common causes of URI. Feline URD panels offered by at least one commercial and another university laboratory include assays for Feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), Chlamydophila felis, Mycoplasma felis and Bordetella bronchiseptica. Such panels offer advantages in real-life situations such as animal shelters where multiple different pathogens may be present. However, as mentioned previously, detection of nucleic acid sequences from a given pathogen cannot be assumed to prove disease causation.

Therapy

In most cases, cats with URI will recover without specific treatment. Basic nursing care is usually best provided in a home situation, rather than in hospital, both to minimize exposure of other cats to a contagious infection and to minimize stress and likelihood of secondary infection in the affected cat. Hyporexia/anorexia is common, but can sometimes be overcome with simple measures such as feeding foods with strong odors such as fish-based cat food or by warming the food. Rarely, forced feeding is required (eg, via nasoesophageal tube). Adequate systemic hydration should be maintained (subcutaneous or intravenous fluids are seldom required), and humidification of the environment can help keep respiratory secretions moist.

Although ineffective against the most common causes of URI (viral infection), antibiotics are often employed empirically. Amoxicillian-clavulanic acid is a good broad spectrum empiric choice for control or prophylaxis of secondary infection. For treatment of specific bacterial infections, other antibiotics may be indicated. Doxycycline has good efficacy against Bordetella, Chlamydophila, and Mycoplasma but may be associated with discoloration of teeth in kittens (including developing feti) and with esophagitis. Other reasonable choices include trimethoprim-sufamethoxazole, fluoroquinolones, and erythromycin-type compounds such as azithromycin and clarithromycin. In cats with C. felis conjunctivitis, ophthalmic chloramphenicol or tetracycline ointments should also be applied. These same ophthalmic ointments may be useful in cats with corneal ulcers due to FHV.

Anti-viral drugs are not generally used to treat URI. Acyclovir, used to treat herpes infections in humans, does not seem to have good efficacy against FHV-1. Other antiviral drugs are potentially toxic in cats. The one antiviral medication in common usage is L-lysine. Available as a nutricutical, L-lysine (500 mg/PO BID) is believed to interfere with herpes viral replication. In cats with corneal ulcers resulting form FHV, topical antiviral drugs such as trifluridine, idoxuridine, or adenine arabinoside are also used.

Prevention

Prevention of feline URI is dependant on both management practices to minimize exposure and vaccination. Minimization of crowding and stress, cleanliness, and routine disinfection are all crucial when cats are housed in groups, such as in catteries or shelters. A thorough discussion of shelter design and management is beyond the scope of this talk. A valuable resource with more detail on this topic can be found at the University of California – Davis Koret Shelter Medicine Program website (http://www.sheltermedicine.com/portal/is_cleaning.shtml#top3). As an undeveloped virus, FCV is resistant to many routine disinfectants but is susceptible to a 5% bleach solution diluted 1:32 (1/2 cup per gallon) or potassium peroxymonosulfate. It should be noted that there are no disinfectants which work in the presence of organic debris, so basic cleaning must precede disinfection.

Vaccinations are available for FCV, virulent FCV, FHV-1, Chlamydophila, and B. bronchiseptica in cats. For individual pet cats, recommendations from the 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel suggest that vaccination against both FCV and FHV-1 should be considered core vaccines. However, it is important to understand that vaccination does not prevent infection or development of a carrier state, but rather minimizes disease severity. Additionally, there may well be resistant strains of typical (and of course, virulent) FCV. Both FCV and FHV-1 vaccines can be found as modified live (MLV) and killed vaccine for parenteral injection, or as a MLV for intranasal (IN) administration. Occasionally, respiratory signs follow IN vaccination. Killed vaccines may be preferred for pregnant queens and cats with concurrent retroviral infection, but otherwise use of MLV is standard. After initial vaccination and booster vaccination at one year, duration of immunity is likely at least 3 years so revaccination need not be carried out more frequently. Both Chlamydophila and Bordetella vaccines are considered "non-core" and are generally not suggested for use in pet cats.

Vaccination in shelters has a different set of consideration than individual pet vaccination. Unless records are available to prove otherwise, cats are assumed to be unvaccinated and vaccinated immediately upon shelter entry. Because IN vaccination can induce mild clinical signs, this can serve as a source of confusion in shelters deciding which cats should be isolated, or even culled. However, even injectable MLV vaccine occasionally induce clinical signs, IN vaccines may offer more rapid protection than injectable vaccines, and at least one paper suggest that IN vaccination in addition to injectable vaccination for FCV/FHV-1 offers increased protection. (Edinboro, 99) Vaccination against Chlamydophila is reserved for shelters with a demonstrated problem with the infection. Even then, vaccination does not prevent infection or shedding. Because there is some risk of zoonotic transmission, some shelters prefer to cull infected cats. The importance of Bordetella in causing URI in sheltered cats is unclear, but the infection can be transmitted between species (dogs and cats). In shelters with a demonstrable problem with Bordetella infection, IN vaccination of cats may be warranted.

Recently, a vaccination for virulent systemic FCV has become available (CaliciVax®, Fort Dodge Animal Health). This killed virus vaccine incorporates one of several strains of FCV known to cause severe systemic disease. Generally, hypervirulent strains of FCV have arisen from new genetic mutations in each group of cats infected. Although the new vaccine demonstrated protection from challenge with the same virulent strain used in its development, to our knowledge challenge has not be attempted (and therefore protection has not been demonstrated) with any other virulent strain.

Selected References

1. Bannasch MJ, Foley JE. Epidemiologic evaluation of multiple respiratory pathogens in cats in animal shelters. J Feline Med Surg. 2005;7:109-19.

2. Helps CR, Lait P, Damhuis A, et al. Factors associated with upper respiratory tract disease caused by feline herpesvirus, feline calicivirus, Chlamydophila felis and Bordetella bronchiseptica in cats: experience from 218 European catteries.Vet Rec. 2005;156:669-73.

3. Hurley KE, Pesavento PA, Pedersen NC, et al. An outbreak of virulent systemic feline calicivirus disease J Am Vet Med Assoc. 2004;224:241-9.

4. Pedersen NC, Sato R, Foley JE, et al. Common virus infections in cats, before and after being placed in shelters, with emphasis on feline enteric coronavirus. J Feline Med Surg. 2004;6:83-8.

5. Stiles J, Townsend WM, Rogers QR, et al. Effect of oral administration of L-lysine on conjunctivitis caused by feline herpesvirus in cats. Am J Vet Res. 2002;63:99-103.

6. The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel Report. http://www.aafponline.org/resources/guidelines/2006_Vaccination_Guidelines_JAVMA.pdf