Canine infectious respiratory disease complex: management and prevention in canine populations (Proceedings)

Canine respiratory disease complex arises out of an interaction between an assortment of viral and bacterial pathogens; the animal's immune response; and a host of environmental factors. No single strategy will be sufficient for prevention, treatment or control. The good news is we do have many options to reduce the level of environmental contamination and support animals' ability to ward off infection. When armed with the right tools and information, the impact of this disease can be considerably lessened. Effective preventive strategies mean fewer dogs become ill, and those few can be more readily isolated and treated appropriately without putting others at risk.

What causes CIRDC?

It is common to use the term "kennel cough", "infectious tracheobronchitis" and variations on "canine infectious respiratory disease complex" interchangeably. However, this is an overly simplistic view of a complicated syndrome. Disease is not limited to the trachea, nor does it always manifest as coughing. Clinical syndromes of CIRDC may include sneezing, nasal and ocular discharge, and sometimes lower respiratory and/or systemic disease.

Bacterial pathogens implicated in CIRDC include Bordetella bronchiseptica and Mycoplasma spp. Recently, outbreaks of severe infectious respiratory disease associated with Streptococcus zooepidemicus have also been reported. It is likely that secondary bacterial invaders of many species play a significant role in causing more severe disease in some dogs. Viral pathogens associated with upper respiratory disease in dogs include parainfluenza, adenovirus, canine respiratory coronavirus (this is distinct from canine enteric coronavirus), and canine herpesvirus. Canine distemper and canine influenza may also be associated with upper respiratory signs, as well as potentially causing more severe systemic disease in a proportion of infected dogs. We are still unraveling the complicated etiology of CIRDC, as evidenced by the fact that several of the pathogens listed above have only been recognized in recent years.

Environmental factors and the animal's immune response play an equally important role in facilitating development of CIRDC. There's a reason it's called "kennel cough" – several of the pathogens listed above are insufficient in themselves to cause disease without the additional stress, high contact rate, and other factors associated with kenneling.

Diagnostic options for CIRDC outbreaks

Virtually all pathogens listed above cause a similar overall clinical presentation of coughing and/or nasal discharge. While Bordetella-induced kennel cough is classically thought of as causing only relatively mild disease, more severe disease may be seen, especially in a crowded shelter or boarding facility where stress and a high load of secondary pathogens provide a synergistic effect. Therefore, the cause of CIRDC cannot be diagnosed based on clinical signs in a single dog. However, the pattern of affected animals can at least provide some clue as to the likely pathogens. For example, canine distemper is unlikely to affect vaccinated dogs over four months of age. Canine influenza, on the other hand, is likely to affect a high percentage of exposed dogs, regardless of age or vaccine status. Therefore this rule-out would be unlikely in an outbreak limited to puppies or unvaccinated animals. If some animals show distinctive clinical signs, such as neurological signs characteristic of distemper, it is possible that other dogs showing milder disease are also infected with the same pathogen. Conversely a distemper outbreak is unlikely if many dogs are affected and none show characteristic neurological signs.

Additional diagnostics are warranted if CIRDC is occurring in a population with unusual frequency or severity, or if there is the slightest suspicion of zoonotic infection. Acutely affected animals should be sampled – ideally 10-30% of the affected population, with a minimum of 5-10 dogs. The cause of an outbreak can not be identified based on a specimen from a single dog. The ideal sample depends on the localization of clinical signs: if signs are predominantly upper respiratory, deep nasal swabs should be obtained. If lower respiratory disease is suspected, tracheal wash is the preferred specimen. Samples should be submitted for bacterial culture and sensitivity for Bordetella, Mycoplasma, Streptococcus and others such as e.coli, Klebsiella, Pasteurella, enterobacter etc. PCR is the most practical option for viral detection; panels are available which include most common viral pathogens. PCR testing is available at a discounted rate for shelters through Idexx laboratories. See http://www.sheltermedicine.com/services/pcr.shtml for more information about this program. Keep in mind that false negatives may be caused by problems with sample handling or timing. For instance, canine influenza is shed only very early in the course of disease, and may be missed by the time clinical signs are recognized. False positives can occur following vaccination, especially with a very sensitive method such as PCR; this has been documented as long as three weeks after vaccination for canine distemper, for example.

Merely documenting the presence of a pathogen does not necessarily indicate causation, of course. Most of the pathogens associated with CIRDC can be isolated with some frequency even from clinically normal dogs, especially in a densely housed canine population. If the same pathogen is found in several dogs, this raises the index of suspicion that a causative relationship exists, but still does not rule out other contributing, or even primary, agents. For definitive diagnosis, necropsy is the most powerful tool available, and should be utilized if possible whenever dogs die or are euthanized with suspected severe infectious respiratory disease. If you are uncertain whether a single death represents an isolated incident or the beginning of an outbreak, it is prudent (and virtually free) to obtain lung specimens and oropharyngeal swabs and hold for future analysis if indicated. Formalin fixed, frozen and refrigerated specimens should be obtained, for histopathology, viral isolation, and bacterial culture respectively.

Prevention of CIRDC

Strategies for prevention of CIRDC rely on supporting the animal's ability to ward off disease and reducing the level of environmental contamination. Important strategies to accomplish the first goal include vaccination, stress reduction, and prevention of airway irritation (e.g. by minimizing barking). The latter goal is accomplished through reduction of crowding, effective sanitation, and maintenance of good air quality.

Reduction of crowding and stress

Crowding and the attendant stress is undoubtedly the single greatest risk factor for severe respiratory (and other) disease outbreaks in populations. Increased population density leads to a greater risk of disease introduction, higher contact rate, reduced air quality, and often, compromises in housing and husbandry. Housing dogs in each side of a double-sided cage intended for a single dog; housing multiple unrelated dogs per cage (particularly if not done in "all in/all out" fashion"); failure to isolate symptomatic animals; and delays in moving animals through the facility are frequent precursors of serious outbreaks in over-crowded shelters. Even in a boarding facility or vet clinic, it is important to anticipate times of peak population, recognize that these will be periods of increased risk for respiratory disease outbreaks, and plan sufficient additional staff that husbandry is not compromised.

An underappreciated strategy for CIRDC prevention is to simply reduce the amount of time dogs spend in densely housed environments. One study showed that each day in a shelter increased the risk if CIRDC by 3%[2]. Reducing length of stay may not be possible (or desirable) in a boarding facility or vet hospital, but management practices that increase length of stay for shelter dogs should be carefully assessed to ensure the benefit of these practices outweighs the risk of disease they may create. This could include routine quarantine of apparently healthy animals, delays while dogs await behavior assessment or surgery, or failure to move dogs to public-viewing areas of the shelter as soon as they are available for adoption. Increased time for each dog in the shelter also contributes to increased crowding with all the associated risks.

Vaccination

Canine infectious respiratory disease complex, almost by definition, is not a vaccine preventable condition. There are no vaccines available for some contributory or primary pathogens, some vaccines only provide partial protection at best, and it is not always possible to vaccinate animals prior to exposure in a shelter environment. In spite of these limitations, vaccination plays an important supporting role in controlling CIRDC. In some cases disease can be almost entirely prevented (e.g. canine distemper), while in other cases frequency and severity can be mitigated. In one study, vaccination for Bordetella and parainfluenza (with or without adenovirus) of even a fraction of dogs on intake to a shelter resulted in a significant reduction in the risk of coughing [.

For protection against canine distemper, all dogs should receive a modified live (MLV) or recombinant subcutaneous distemper vaccine (usually as part of a DHPP/DA2PP combination product) between three years and one week prior to admission to a boarding kennel environment, and immediately upon intake to a shelter. Puppies should be vaccinated starting at 4 – 8 weeks of age, and revaccinated every 2-4 weeks until 16-18 weeks of age. The younger end of the age range and shorter revaccination interval should be used in high risk environments such as many animal shelters. Adenovirus and parainfluenza virus vaccines can be given in combination with MLV distemper/parvo vaccination or in combination with Bordetella via intranasal vaccination (see below).

Both intranasal MLV and subcutaneous antigen extract vaccines are available for vaccination against Bordetella. In general, intranasal vaccination is recommended due to the demonstrated rapid onset of immunity (3-5 days) and the potential benefits of local IgA derived protection. Additionally, this vaccine can be used in puppies as young as 2-3 weeks of age, and may provide local immunity even in the face of maternal antibody. Vaccines should be given within one year and at least one week prior to admission to a boarding facility, and immediately upon intake to a shelter.

Previous studies suggested that a killed whole bacterin SC vaccine provided superior IgG levels, and vaccination with both the IN and this killed bacterin vaccine in succession provided superior protection against clinical signs. However, this vaccine is no longer available. Little information is available about the efficacy of the antigen extract vaccine; one recent study found no difference in clinical signs between dogs receiving this vaccine and a placebo[. However, if staff are unable to administer the intranasal vaccine, there may be some benefit in giving the subcutaneous antigen extract vaccine; keep in mind this vaccine must be boostered for full effect, and therefore a series should be completed at least 2 weeks prior to admission to a boarding facility.

A subcutaneous killed vaccine is available for canine influenza (Intervet/Schering-Plough). This vaccine is labeled to reduce the severity of clinical signs and decrease the duration of viral shedding, though like many respiratory vaccines it may not completely prevent infection. The vaccine is labeled for use in puppies 6 weeks of age and older, and should be given as two injections, 2-4 weeks apart. The requirement for a booster limits the usefulness of this vaccine in some shelters, but it should be considered for pet dogs that stay in boarding kennels, attend doggy day care centers, frequent dog parks, or otherwise congregate with other dogs, especially in areas known to be endemic for canine influenza. The series of two vaccines should be completed at least two weeks before boarding to allow for optimal immune response. This vaccine may also be useful for shelters in endemic areas if dogs frequently stay for a prolonged period, or for shelters transferring dogs from non-endemic to endemic areas.

Environmental decontamination/removal of infected animals

Most CIRDC pathogens survive in the environment no more than a few hours (canine distemper) to a few weeks (Bordetella) and are inactivated by virtually all routinely used disinfectants. Adenovirus is an exception; like other un-enveloped viruses, it is reliably inactivated by a limited number of disinfectants, including household bleach (5% sodium hypochlorite) diluted at 1:32 (½ cup per gallon), calcium hypochlorite (e.g. Wysiwash®) and sodium dichloroisocyanurate (e.g. Bruclean®), potassium peroxymonosulfate (e.g. Trifectant®) and accelerated hydrogen peroxide (e.g. Virox®, Accel®). [ Survival of primary and secondary pathogens may be greatly enhanced by persistent moisture in the environment; therefore surfaces should be in good repair to prevent pooling of water, and cleaning should be followed by thorough drying on a daily basis.

The cleaning process itself may serve to spread, rather than prevent, disease if not carefully thought out. Ideally dogs should be held in doubled sided runs separated by a guillotine door, such that the dog can be held on one side while the other side is cleaned. For facilities with a good dog walking program such that runs are not soiled with urine or feces, complete cleaning and disinfection need only occur at the conclusion of a dogs' stay, with daily spot cleaning sufficient to kept the run tidy. If dogs must be removed from their run for cleaning, they should not be left in a common holding kennel nor tied in aiselways while contaminated water and disinfectant is sprayed nearby. Disinfectant should be applied via a sprayer or other application system rather than a mop and bucket which will quickly become contaminated. For more information on cleaning and disinfection methods, see http://www.sheltermedicine.com/portal/is_cleaning.shtml#top3.

Remember that mildly infected dogs may play a substantial role in maintaining CIRDC in a given population, especially for the less environmentally durable pathogens such as canine distemper. A common – and dangerous - misapprehension is that a mildly infected dog is shedding only a mild pathogen. In fact, the severity of clinical signs is dictated as much by the dog's immune system as by the inherent virulence of the pathogen. A perky dog with a midly snotty nose may very well be shedding a pathogen such as canine distemper or influenza which could be fatal for another animal. Prompt removal of all symptomatic animals, no matter how mild the signs, has been critical in resolving many outbreaks. Staff should be trained to carefully scan for sneeze marks on kennel walls as well as observing dogs for clinical signs before walking, cleaning or otherwise interacting. Because airborne transmission of CIRDC is a possibility, ideally isolation areas should have separate air flow. However, if this can not be achieved, don't despair. Facilities have managed to maintain effective isolation by providing at least 20 feet of physical distance between sick and healthy dogs and paying careful attention to fomite control.

Treatment

There is no single "drug of choice" for treatment of CIRDC. For dogs in a pet home with mild illness, antibiotic treatment may be un-necessary. For dogs in the more challenging environment of a shelter or boarding kennel, however, antibiotic treatment is often indicated. Doxycycline and potentiated sulfas are relatively good empirical choices when Bordetella infection is suspected, although resistance is possible even to these. Bordetella is always resistant to Cephalexin. For secondary infections subsequent to canine influenza or other viral infections, on the other hand, cephalexin, fluoroquinolones, clavamox or other broad spectrum antibiotics have been found more effective. Orally administered prednisone had been recommended to reduce the severity of symptoms; while this may be beneficial if constant coughing is a problem for dog or owner, it has not been found to shorten the course of illness[6]. For dogs unresponsive to oral or parenteral antibiotics, nebulization with aerosol/non-absorbable antibiotics (e.g. gentamycin, polymyxin) may be beneficial. Other supportive care should include minimizing barking and walking on harness or gentle leader to avoid pressure on the trachea.

There is no evidence that antitussive or expectorants are beneficial to reduce symptoms of CIRDC in dogs; there is minimal evidence that dextromethorphan based cough suppressants are helpful even in humansNarcotic antitussives are specifically not recommended because they can decrease respiratory function. These drugs are not without side effects, and administration to numerous dogs in an outbreak can be time consuming and facilitate fomite spread of disease; therefore treatments with questionable benefit should be avoided in a population setting.

References

1. Pesavento, P.A., et al., A clonal outbreak of acute fatal hemorrhagic pneumonia in intensively housed (shelter) dogs caused by Streptococcus equi subsp. zooepidemicus. Vet Pathol, 2008. 45(1): p. 51-3.

2. Edinboro, C.H., M.P. Ward, and L.T. Glickman, A placebo-controlled trial of two intranasal vaccines to prevent tracheobronchitis (kennel cough) in dogs entering a humane shelter. Preventive Veterinary Medicine, 2004. 62(2): p. 89-99.

3. Davis, R., et al., Comparison of the mucosal immune response in dogs vaccinated with either an intranasal avirulent live culture or a subcutaneous antigen extract vaccine of Bordetella Bronchiseptica. Veterinary Therapeutics, 2007. 8(1).

4. Scott, F.W., Virucidal disinfectants and feline viruses. Am J Vet Res, 1980. 41(3): p. 410-4.

5. Eleraky, N.Z., L.N. Potgieter, and M.A. Kennedy, Virucidal efficacy of four new disinfectants. J Am Anim Hosp Assoc, 2002. 38(3): p. 231-4.

6. Ford, R.B., Canine infectious tracheobronchitis, in Infectious diseases of the dog and cat, C. Greene, Editor. 2005, W. B. Saunders Company: Philadelphia. p. 54-63.

7. Paul, I.M., et al., Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. Pediatrics, 2004. 114(1): p. e85-90.