Feline infectious respiratory disease (Proceedings)

Feline upper respiratory infection (URI) is perhaps the most frustrating illness facing shelter veterinarians, managers and staff. Many cats enter shelters already silently carrying the viruses that lead to illness; vaccines are partially effective at best; and specific treatments are limited. Factors such as overcrowding, poor air quality, poor sanitation, stress, concurrent illness, parasitism, poor nutrition, and other causes of immunosuppression predispose to disease.

In spite of these challenges, recent research has shown that some shelters have dramatically greater success than others in controlling this seemingly ubiquitous disease. We now know that having fewer than 5% of cats develop URI in shelter care is an achievable goal. Because of its close association with herpesviral activation and stress, URI is also a bellwether for overall shelter cat health and wellbeing. We can not sincerely expect to provide a humane, safe sheltering experience for cats if a substantial fraction develop illness in our care. Conversely, the measures necessary to control URI can have a widespread impact on overall cat comfort, well being and even likelihood for adoption.

Etiologic agents

Any of the agents listed below can be a primary cause of URI. In general, approximately 80-90% of cases are thought to be caused by one of the two viruses listed. In shelter cats, herpesvirus appears to be more closely linked to endemic shelter URI. Calicivirus, while undoubtedly the cause of periodic outbreaks, has not been consistently associated with an increased risk of URI in shelter populations nor does it appear to spread as readily as herpesvirus or even coronavirus. Contrary to popular belief, aerosol transmission is not a significant means of spreading URI. FADDIN EN.CITE. Feline URI is much more readily spread via fomites and droplet transmission (over distances of 5 feet or less), or, importantly, via reactivation of latent herpesvirus due to stress.

      1. Feline Herpesvirus-1 (FHV-1 - probably the most common)

      2. Feline Calicivirus (FCV - perhaps not as common as herpes, but potentially more severe)

      3. Chlamydophila felis

      4. Mycoplasma spp.

      5. Bordetella bronchiseptica

Diagnosis

Most often, a causative agent is not identified in individual cases of URI. Sometimes a best guess can be made based on clinical signs: FCV is relatively likely to be associated with oral ulceration or limping, FHV-1 is more likely to cause keratitis or corneal ulceration, Chlamydophila and Mycoplasma more often seen with conjunctivitis without other signs. However, all can cause overlapping clinical signs. In some cases additional testing to identify specific pathogen(s) is indicated, e.g.:

     • Unusual signs, severity or frequency of disease in a population of cats

     • Planned husbandry changes (e.g. before investing in vaccination for a particular pathogen such as Bordetella.)

     • Legal issues (e.g. hoarding investigation, liability concerns)

     • Detect carriers (e.g. low turnover shelter that has recurrent severe disease)

Diagnostic testing has become more widely available in recent years with the advent of RT-PCR testing and panels specific for feline URI. A negative test result in a correctly handled specimen is a reasonably sure way of ruling out acute infection, though intermittent shedding can occur with several of the URI pathogens. Interpretation of positive test results in an individual cat, however, is complicated by the fact that any of these pathogens can be isolated from clinically normal cats. A positive PCR test result on an oro-nasal sample from an individual cat has little meaning. Ideally at least 5-10 typically-affected cats should be sampled and evaluated in light of the expected frequency of carriage in shelter populations. Samples should be obtained from the most prominently affected location (e.g. eyes, oral cavity, nasal swabs), or as per laboratory guidelines. In a serious outbreak when cats are dying or being euthanized as a result of severe URI, necropsy and histopathology should be performed. This can often rapidly identify a cause and permit effective intervention.

Management, length of stay, and URI

Crowding and the attendant stress is undoubtedly the single greatest risk factor for respiratory (and other) disease in shelters. Increased population density leads to a greater risk of disease introduction, higher contact rate between animals, reduced air quality, and often, compromises in housing and husbandry. Unfortunately, crowding of shelter cats is not uncommon, especially during kitten season. In some cases this is due to insufficient facilities to humanely house stray cats for a required holding period or make a reasonable number available for adoption. Even when facilities are adequate to house stray and an optimal number of a adoptable cats, many shelters have not identified a humane capacity beyond which they are not able to keep cats healthy or maximize live release. Given the abundance of cats in need of homes in most communities, crowding will inevitably occur unless capacity is established and some policy is in place to balance the number of cats admitted with the number released alive on an ongoing basis (e.g. limiting/scheduling intake only as space becomes available, placing adult cats in long term foster care during the height of kitten season, or performing euthanasia based on criteria other than shelter-acquired illness).

The fear is often raised that housing fewer cats at any one time will result in an increase in euthanasia, but this is not the case. The number of feline lives saved in a community depends on the number of adoptions and/or reduction of intake by preventing unwanted births or keeping cats in homes. Neither of these numbers will be positively affected by an overcrowded shelter. On the contrary, a shelter full of healthy cats will expend less on medical care, very probably see an increase in adopter interest, and have more resources for prevention that otherwise might have gone into medical care of animals with shelter-acquired illness. Adoption promotions can be planned around predictable surges in intake (such as kitten season) or around special events, rather than implemented only in response to crowding.

Reducing length of stay

An underappreciated strategy for reduction of crowding and respiratory disease prevention is to simply reduce the amount of time each cat spends in the shelter environment. Length of stay in a shelter is a significant risk factor for development of feline URI[1]. Illness further increases the length of stay. Conversely, reducing the length of stay on average for each cat will result in fewer cats housed in the shelter each day. This in turn results in less crowding and better care for each cat, further reducing the risk of illness. Reducing length of stay does not equate to "time limits" nor should this be achieved by euthanizing more cats. Rather, each cat should be provided the necessary care and attention to move it seamlessly through the shelter to its outcome without delay. Staffing must be adequate at all critical control points. Management practices that increase length of stay for shelter cats should be carefully assessed to ensure the benefit of these practices outweighs the cost. This could include routine quarantine of apparently healthy animals, delays created by backlogs in behavior assessment or surgery, or failure to move cats to public-viewing areas of the shelter as soon as they are available for adoption.

A sufficient number of cats and kittens should be available for adoption to ensure that potential adopters always have a variety to choose from. Beyond this, however, the number awaiting adoption should be based on the optimum rather than the maximum that can possibly fit in the available space. Fewer cats in the shelter awaiting adoption will mean a shorter wait for each one – if 30 cats are available for adoption and on average one cats is adopted each day, the wait will be 30 days for each cat. If only 15 at a time await adoption, the average time to adoption will be 15 days. Adopters may also have an easier time choosing if they are confronted with fewer choices; an increasing body of research shows that people are more likely to make choices, and to feel good about their choice, when they have relatively fewer options from which to select. A good general rule is to have no more than 7-14 times more cats moving actively through the shelter towards adoption than the average daily number of adoptions for that month. (Don't include cats in active rehabilitation that are not ready for adoption in this calculation.) This does not equate to time limits: the average length of stay will naturally fall if fewer cats are made available at any one time. Some cats may still stay considerably longer than 7-14 days, while others may be adopted within a few days of shelter entry. As noted above, initially reducing the number of cats available for adoption does not entail additional euthanasia. Rather it can be achieved simply by decreasing the time to adoption for each one by eliminating delays; through special adoption promotion events; or by controlling intake until adoptions have caught up with ongoing admissions. For more information on "adoption driven capacity", see www.sheltermedicine.com.

Stress reduction

Because clinical signs and shedding of FHV-1 are specifically activated by stress, reduction is crucial to feline URI control. Efforts to reduce stress must be continuous from the moment a cat enters the shelter's care. Even moving cats from cage to cage is enough to induce reactivation in some cats[7, 8]. "Spot cleaning" where possible and providing housing that does not require extensive movement or handling for care is key to control of URI. Regrouping of cats in group housing has also been associated with reactivation of URI[9]. If group housing it utilized, more smaller groups are preferable to a few large ones to minimize the need for frequent addition and removal of cats. Even partitioning separate areas within a large room can be helpful. Providing hiding places, decreasing noise exposure (especially exposure to dogs barking), maintaining light/dark cycles and comfortable temperatures, and providing toys and scratching surfaces are also important to relieve feline stress. Unnecessary handling for treatment should be minimized – the theoretical benefit of interventions that involve aversive handling or forceful medication must be weighed against the certain stress these procedures cause.

Feline socialization programs can be helpful in relieving stress but must be implemented and monitored with care. Being removed from a cage, cuddled by a stranger and carried to an unfamiliar room to play may provide welcome relief from boredom for some cats, but may be highly stressful for others, as well as serving to efficiently spread disease. Train volunteers to assess the cat's response to interaction and offer options such as grooming or petting the cat within its cage, or letting the cat exercise or sit in their lap in a clean, quiet area out of the cage (for healthy, vaccinated cats). If possible, provide each cat a carrier within its housing unit, or if space within the unit is insufficient assign each cat a carrier stored elsewhere that is used throughout its shelter stay. Use the carrier to transport cats to socialization areas and allow the cat to choose when to exit, explore and interact. If this is not possible, at least bring the cat's own towel or bed from its cage. Ensure that all volunteers and staff assess both the cat and the kennel for signs of URI or other illness prior to interaction. Healthy cats should not be handled after handling a sick cat without a change of top and thorough hand sanitation.

Disinfection

Most URI pathogens survive in the environment no more than a few hours (FHV-1) to a few weeks (Bordetella) and are inactivated by routinely used disinfectants. While a tidy and sanitary shelter is always a desirable goal, feline URI is not likely to be vanquished simply by ramping up disinfection practices without attending to stress reduction and feline comfort. Feline calicivirus is an exception – although not as durable as the notorious parvoviruses, it can survive for up to a month or even longer in dried discharge. Rigorous attention to disinfection is required when an FCV outbreak is suspected. Calicivirus is inactivated by household bleach (5% sodium hypochlorite) diluted at 1:32 (½ cup per gallon), applied to a clean surface. Products in the same family as bleach that have also been found effective against un-enveloped viruses include calcium hypochlorite (e.g. Wysiwash®) and sodium dichloroisocyanurate (e.g. Bruclean®). Like bleach, these have no detergent properties and must be applied to a pre-cleaned surface. Other proven products include potassium peroxymonosulfate (e.g. Trifectant®) and accelerated hydrogen peroxide (e.g. Virox®, Accel®), which both reportedly have greater detergent properties and better activity in the face of organic matter compared to bleach and related products. Independent studies have repeatedly shown that quaternary ammonium disinfectants (e.g. Triple Two®, Rocal®) do not reliably kill un-enveloped viruses, in spite of repeated reformulation and label claims of efficacy. Calicivirus is not reliably inactivated by alcohols, and hand sanitizers commonly used in shelters may not be completely effective (though they should still be available in all animal housing areas to protect public health). Sanitizers containing 60-90% ethanol and propanol are more effective than other alcohols. As noted above, the stress and fomite transmission associated with cleaning a typical box style single cat cage may outweigh the benefit of thorough disinfection. If possible, cages should be spot-cleaned while cats are in residence, and thoroughly cleaned, disinfected and dried between residents.

Air Quality

Although aerosol transmission per se is of minimal significance, air quality is undoubtedly important to respiratory health and URI control. The relevant air quality is at the level of the cat's nose, not the room at large. Cages or condos that are open on at least two sides provide better passive ventilation than those that are open on only one. Housing cats in fully enclosed cages (all four sides, top and bottom) results in poor air quality and should be avoided unless each cage is individually actively ventilated. Although fresh air exchange is often emphasized, reduction of airborne contaminants is equally or more effective (e.g. through reducing population density, frequent litter box cleaning, low dust litter, use of disinfectants at correct dilution). Air filtration (i.e. HEPA filter) may be tried, although it is less effective than fresh air exchange or contaminant reduction. Filters need to be replaced frequently to prevent them from becoming a source of infection in themselves. Ozone based air filters should be avoided, as ozone itself may be a respiratory irritant.

Housing

Housing, stress reduction and safe, effective cleaning go hand in hand when it comes to feline care in a shelter. Good quality housing directly impacts feline well being, greatly facilitates both cleaning and stress relief, and is likely the most important single factor in URI frequency in shelters. For instance, in one recent study, only 60 out of 1,434 cats admitted to shelters in the United Kingdom developed URI during their shelter stay (2). Cats in the study shelters were typically held in large, comfortable indoor/outdoor runs separated by guillotine doors. This housing provided for ample hiding spaces, separation of litter and food, complete isolation from dog noise, and care of the cats without disruption. For more details on recommended cat housing, please see specific notes on feline housing elsewhere in these conference proceedings (Hurley, Feline Housing, Shelter Medicine Track).

Vaccination

Vaccination does not prevent infection or development of a carrier state for any URI pathogen, and many strains of feline calicivirus are vaccine resistant. At best, vaccination reduces severity and duration of disease. Modified live (MLV) parenteral vaccines are available containing feline herpesvirus, feline calicivirus and feline panleukopenia (FVRCP). Even with an MLV product, two vaccinations 2-3 weeks apart are required for full protection against the respiratory viruses. If owners or finders are amenable to keeping cats for a short period prior to surrender, administer the two-vaccine series prior to shelter entry. At minimum, vaccine all cats 6 weeks of age and older at the time of admission. Revaccinate kittens every two weeks throughout their stay in a high risk environment (e.g. shelter, high volume foster home), until 18-20 weeks of age. If possible, revaccinate adult cats two weeks after the first vaccine.

Intranasal (IN) MLV two-way (FVRC) or three-way (FVRCP) vaccines are also available. Modified live vaccines are generally preferred over inactivated products for the more rapid protection induced (at least 5-7 days parenteral, 3-5 days intranasal). Because URI and panleukopenia vaccines are generally delivered in combination, this is a consideration in vaccine selection. Panleukopenia is recognized with increasing frequency throughout the US, and the superior protection provided by the MLV parenteral vaccine against this disease makes it the best choice in most situations. In one study the 2-way intranasal FVRC vaccine given in addition to an inactivated parenteral FVRCP vaccine provided modestly improved protection against URI[. On the other hand, a recent study showed no difference between shelter cats that received an intranasal MLV FVRC vaccine in addition to a parenteral MLV FVRCP vaccine, versus only the parental MLV vaccine [. Anecdotal reports from shelters are extremely varied regarding the efficacy of this strategy (from those that report a significant apparent decrease to those that report no change or even increased URI). If a modified live intranasal vaccine is used in addition to a subcutaneous 3 way FVRCP vaccine, an effort should be made to track the impact on URI within an individual shelter (see data collection section below). Under no circumstances should use of a modified live subcutaneous vaccine against panleukopenia be discontinued, as this vaccine is necessary for rapid protection of shelter cats against this common and deadly infection.

A two-way inactivated calicivirus vaccine is now available in the United States, containing a strain of calicivirus isolated from a single outbreak of virulent systemic FCV. No cross protection between virulent systemic strains has been documented, and as an inactivated vaccine this product has limited application in shelters. A MLV Bordetella vaccine for cats is available, but is not generally recommended for shelters except when repeated problems are demonstrated by laboratory diagnostics. Killed and modified live vaccines are available for C. felis (often given in combination with FVRCP). This vaccine is not generally recommended, as it has a short duration of effect, is only partially effective, and may have a relatively high frequency of adverse reactions. Frequent recognition of clinical Bordetella or Chlamydophila in cats is often an indicator of overall husbandry problems, and prevention should focus on improvement of environmental management, rather than control of these agents specifically. The need for this vaccine, if used, should be periodically revisited. No Mycoplasma vaccine is available for cats. For more information on vaccination for feline URI, see the American Association of Feline Practitioners Vaccine Guidelines, available online. This document includes specific recommendations for shelter cats.

Isolation

Many cats shed URI pathogens without showing clinical signs, hence the need for careful hygienic precautions even when handling apparently healthy cats. Cats with active signs of infection are likely to be shedding much greater amounts. Isolation of these cats from the general population is a requirement for even a minimal disease control program. In-cage isolation is acceptable if housing is such that the cat can be genuinely separated from other cats and cared for in such a way that fomite transmission is fully avoided. Most shelter housing requires that cats be moved to a separate room to achieve meaningful isolation. This is also beneficial to provide more efficient treatment and avoids the perception that the shelter is just "full of sick cats". Many cats are still shedding increased amounts for a few weeks following recovery. Ideally these cats would not be mixed directly back into the general population, or at least not with vulnerable populations such as kittens or recent arrivals. However the risk of transmission is greatly reduced once clinical signs have fully resolved, and re-introduction of these cats into the general healthy population usually poses no great problems. If a chronic cycle of URI occurs following reintroduction of recovered cats, re-evaluate stress management and crowding. Consider additional diagnostics if the problem persists even in the face of good husbandry and stress control.

Treatment

Prevention must be the cornerstone of population URI management. Once cats become ill, more than half the battle is lost. Even at shelters able to provide treatment, sick cats will suffer through a spell in isolation, crowding and costs will increase as cats are held for treatment, public trust may decrease, and staff time is diverted from preventive efforts and adoptions. Some cats suffer chronic and even fatal complications from URI.

That said, treatment is an important component of URI management, for the population as well as the individual cat. Staff morale and community support often improves when sick cats can be treated. A discussion of specific treatment strategies based on clinical presentation can be found at: http://www.sheltermedicine.com/portal/is_feline_upper_res.shtml#treatment. (Or email the author if you have trouble locating this information sheet.)

While we want to do all we can to speed recovery, it's important to recognize that treatment itself is associated with risks and costs, especially in a shelter. Over-use of antibiotics compromises normal gastrointestinal flora, leaving cats vulnerable to the many GI pathogens lurking in shelters. Antibiotics also cause undesirable side effects, and the risk of selecting for antibiotic resistant organisms is a constant concern. Never use blanket antibiotic treatment as a substitute for good husbandry: not only is it not safe, it just doesn't work to manage this largely viral disease. Antibiotic treatment should ideally be reserved for cats with signs suggestive of bacterial infection. However, in some shelters almost all cats progress to these signs within a few days. If this is the case, revisit air quality, stress control and crowding in the treatment area, but in the meantime consider starting antibiotics immediately for cats placed in the treatment area. There is no benefit in treating mild cases of URI for a specific time period; antibiotics can be discontinued once clinical signs resolve (if monitoring is spotty, it may be best to continue 2-3 days past the last observed sign of URI, in case a few last sneezes were missed). Chronic URI or suspected Chlamydia infection is a different matter. In these cases treatment for 6-8 weeks may be required to fully resolve infection.

With any treatment that involves handling and manipulation of cats, the risk of spreading disease is increased, and treatment itself can be quite stressful for cats and caretakers alike. Overtreatment should therefore be avoided. While it can be tempting to try a variety of anecdotal treatments or give antibiotics just to be doing something about this frustrating disease, treatment should ideally be limited to therapies for which there is a reasonably strong clinical justification.

Most cases of URI will resolve within 7-10 days. A few cats may take longer or may never recover in the shelter, but if a longer time to recovery is the rule rather than the exception, again re-evaluate stress control, crowding and care of cats in treatment. Evaluate shelter cats with chronic URI for contributing problems such as nasal polyps, foreign bodies, and immunosuppressive disease, just as you would approach any other individual patient. If these other causes are ruled out, long term antibiotics with good tissue penetration may alleviate symptoms. These cats should not remain in the shelter long term just waiting for symptoms to resolve, as this may never occur. For some cats, symptoms will resolve in the home setting of foster care. Even if symptoms don't resolve in foster care, it is ideal for these cats to be placed via a foster home/internet-based adoption/off site adoption events where the condition can be explained to potential adopters versus lingering, sneezing, in the shelter.

References:

1. Dinnage, J.D., J.M. Scarlett, and J.R. Richards, Descriptive epidemiology of feline upper respiratory tract disease in an animal shelter. J Feline Med Surg, 2009.

2. Edwards, D.S., et al., Risk factors for time to diagnosis of feline upper respiratory tract disease in UK animal adoption shelters. Prev Vet Med, 2008. 87(3-4): p. 327-39.

3. Bannasch, M.J. and J.E. Foley, Epidemiologic evaluation of multiple respiratory pathogens in cats in animal shelters. J Feline Med Surg, 2005. 7(2): p. 109-19.

4. Pedersen, N.C., 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(2): p. 83-8.

5. Gaskell, R.M. and R.C. Povey, Transmission of feline viral rhinotracheitis. Vet Rec, 1982. 111(16): p. 359-62.

6. Wardley, R.C. and R.C. Povey, Aerosol transmission of feline caliciviruses. An assessment of its epidemiological importance. Br Vet J, 1977. 133(5): p. 504-8.

7. Gaskell, R.M. and R.C. Povey, Experimental induction of feline viral rhinotracheitis virus re- excretion in FVR-recovered cats. Vet Rec, 1977. 100(7): p. 128-33.

8. Maggs, D.J., M.P. Nasisse, and P.H. Kass, Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus. Am J Vet Res, 2003. 64(1): p. 37-42.

9. Hickman, M.A., et al., An epizootic of feline herpesvirus, type 1 in a large specific pathogen-free cat colony and attempts to eradicate the infection by identification and culling of carriers. Lab Anim, 1994. 28(4): p. 320-9.

10. Dvorak, G. and C. Petersen, Sanitation and Disinfection, in Infectious Disease Management in Animal Shelters, L. Miller and K.F. Hurley, Editors. 2009, Wiley-Blackwell: Ames, Iowa. p. 49-60.

11. Edinboro, C.H., et al., A clinical trial of intranasal and subcutaneous vaccines to prevent upper respiratory infection in cats at an animal shelter. Feline Practice, 1999. 27(6): p. 7-13.

12. Newbury, S.P., et al. A placebo controlled field trial of an intranasal vaccine for feline calici virus and feine herpes virus to prevent clinical signs of feline infectious respiratory disease complex in an animal shelter. in Conference of Research Workers in Animal Diseases, Proceedings of the 88th Annual Meeting, . 2007. Chicago.