Canine infectious disease update (Proceedings)

October 1, 2008

Richard B. Ford, DVM, MS, DACVIM, DACVPM (Honorary)

Article

Closely related to Bordetella pertussis, the cause of "whooping cough" in humans, Bordetella bronchiseptica is a gram negative, Aerobic coccobacillus particularly well adapted to colonize the ciliated respiratory epithelium of dogs and cats.

Bordetella Bronchiseptica Infection and Prevention

Closely related to Bordetella pertussis, the cause of "whooping cough" in humans, Bordetella bronchiseptica is a gram negative, aerobic coccobacillus particularly well adapted to colonize the ciliated respiratory epithelium of dogs and cats. Today, this organism is regarded as the principle etiologic agent of canine infectious tracheobronchitis (ITB). In the clinical setting, however, B. bronchiseptica infection should not be regarded as synonymous with ITB. Dogs infected with canine parainfluenza virus (CPiV) or canine adenovirus-2 (CAV-2) are expected to experience more severe respiratory disease when co-infected with B. bronchiseptica than with any these agents alone. Canine bordetellosis, i.e. B. bronchiseptica infection in the absence of either CPiV or CAV-2, is known to occur and can be associated with acute, fatal pneumonia in young dogs. B. bronchiseptica is transmitted through aerosolization of respiratory secretions. Bacteria can also be transmitted directly by contaminated dishware, human hands, and other fomites. Because B. bronchiseptica possesses several intrinsic mechanisms for evading host defenses, it is recognized for its role as a significant complicating factor in dogs with multiple-agent respiratory infections. The fact that outbreaks of canine ITB are common, despite widespread use of topical and parenteral vaccines in dogs for over 20 years, highlights the fact that current vaccines are not highly effective in preventing infection. On the other hand, our understanding of the role that B. bronchiseptica has in feline respiratory disease is only beginning to undergo scientific scrutiny.

Pathogenesis of Infection

Most of what is known about the pathogenesis of B. bronchiseptica is based on information derived from studies in dogs. In addition to dogs, infections have been documented in cats, pigs, various laboratory species, and humans. B. bronchiseptica rarely infects tissues outside the respiratory tract, a fact that supports the ease of transmissibility among dogs, particularly when housed in close quarters. Contributing to the ability of B. bronchiseptica to colonize respiratory epithelium is the fact that the bacterium possesses both fimbrial and non-fimbrial adhesins, that facilitate the attachment to host cells. Two non-fimbrial adhesins, filamentous hemagglutinin (FHA) and pertactin (Prn), are essential for the attachment of B. bronchiseptica to respiratory epithelial cells. Understanding the role of such proteins in the pathogenesis of B. bronchiseptica infection has been fundamental in investigations that may lead to the first acellular whooping cough vaccine. It is not unreasonable that such research may ultimately lead to improved vaccines for dogs and cats. Fimbriae, hair-like appendages extending from the cell membrane of B. bronchiseptica, recognize specific receptors within the respiratory tract. This allows B. bronchiseptica to colonize specific tissues where it then releases various exotoxins (such as adenylate cyclase-hemolysin and dermonecrotic toxin) and endotoxins that impair function of the respiratory epithelium (ciliastasis) and compromise the ability of the infected host to eliminate the infection. These potent toxins not only disrupt the protective action of the mucociliary apparatus, but also are believed to compromise phagocytosis and suppress both cellular and humoral immune responses. Additionally, B. bronchiseptica is regarded as an extracellular pathogen that has the unique ability to invade host cells. Once contained within the intracellular environment, bacteria are able to avoid immunologic defense mechanisms and establish a persistent infection (months) or carrier state.

Clinical Presentation

Clinical signs of canine infectious tracheobronchitis (ITB) include paroxysmal coughing episodes, frequently associated with retching and expectoration, in an otherwise healthy, active dog. Swelling of the vocal folds, associated with laryngitis, can result in a loud, high-pitched cough often described as a "goose honk" or "seal honk." Expectoration of mucus following an episode of retching or hacking behavior may be misinterpreted by the owner as vomiting. Anorexia, fever, and lethargy may be observed among infected dogs during an outbreak. The onset of clinical signs typically ranges from 3 to 10 days following exposure. In most clinical cases, the onset of clinical signs can be associated with recent exposure to other dogs or general anesthesia and endotracheal intubation. The ability to elicit a cough on manipulation of the trachea is an inconsistent clinical finding that should not be used exclusively to rule canine ITB in or out.

A second, more severe respiratory syndrome has been observed in dogs residing within kennel environments during an outbreak of ITB. Although cough may be present, the predominant clinical sign is associated with mucoid to mucopurulent nasal and ocular discharge. Pneumonia is likely to be a complicating factor and, in some cases, may become life threatening, particularly in puppies. In these cases, B. bronchiseptica has been isolated from the pharynx and trachea as a pure culture. Affected dogs are characteristically febrile, lethargic, anorexic, and may show some degree of respiratory distress or even dyspnea. Such cases are difficult to distinguish from those with bacterial pneumonia as well as non-bacterial causes of pneumonia. We have observed outbreaks to occur at any time of the year and may affect more than 50 percent of the dogs in a densely populated environment. Puppies are more severely affected and are at significant risk of dying if not treated.

The recent introduction of a topical (intranasal) vaccine against feline B. bronchiseptica has prompted concerns over the actual prevalence of feline respiratory infections caused by or associated with B. bronchiseptica and the indications for vaccinating. Unfortunately, there are few published reports that describe the clinical features and pathogenesis of B. bronchiseptica infection in cats. Among cats with confirmed infections, cough is the predominant presenting complaint. Unlike the dog, the character of the cough is neither unique-sounding nor inordinately loud. Age and housing may be important risk factors for infection. Most reports of severe respiratory infections associated with B. bronchiseptica involve multiple kittens (< 6 months of age) housed together. While the occurrence of B. bronchiseptica infection is likely to be greater among cats maintained in multiple cat households with a history of "respiratory disease", the overall prevalence of infection within the cat population is not known. Serological surveys have shown rate of seropositivity range from 30% to as high as 85% in multiple cat households. Over 130 isolates of B. bronchiseptica examined by pulse field gel electrophoresis have been recovered from cats. Cats housed together were found to carry similar or identical strains and subtypes. The fact there was no reported difference in the electrophoresis patterns in isolates from carrier cats and those with clinical infections implies that active infections are likely to be opportunistic. Furthermore, the likelihood of a particular isolate to produce disease may be related to host or environmental factors such as concurrent respiratory virus infection, crowding, and stress.

It is important to note, however, that the presence of B. bronchiseptica antibody in an individual cat is not indicative of active infection. Furthermore, B. bronchiseptica may be one of many resident bacteria in the oral cavity of healthy cats. Until additional information can be made available, specific recommendations for vaccination of cats against B. bronchiseptica will be difficult to make.

Diagnosis

A clinical diagnosis of infectious tracheobronchitis is based on historical or physical examination findings that meet clinical criteria described above. In addition, a history of exposure to other dogs (whether or not they have signs of coughing) is helpful in establishing the diagnosis. A favorable and rapid response to empiric antibacterial and antitussive treatment supports the diagnosis of uncomplicated ITB. Routine thoracic radiography, hematology, and biochemistry profiles are neither diagnostic nor prognostic in uncomplicated cases. An inflammatory leukogram with significant leukocytosis or left shift may develop in dogs with a complicated infection associated with pneumonia. It should be noted that because of the large number of indigenous microflora in the canine respiratory tract, bacterial isolates from the nasal and oral cavities will not distinguish a primary infection from a secondary or opportunistic infection. In dogs with uncomplicated ITB, thoracic radiographs are typically unremarkable. Dogs with respiratory complications associated with ITB may have radiographic signs of pulmonary hyperinflation, interstitial pneumonia, and segmental atelectasis.

Treatment Recommendations

Treatment of B. bronchiseptica is centered around oral administration of an appropriately sensitive antimicrobial. However, it may be in the patient's best interest to administer cough suppressants in the form of anti-inflammatory and/or antitussive drugs, particularly on a short-term basis.

Antimicrobials

Most cases of uncomplicated ITB can be regarded as self-limiting and do not necessarily require antimicrobial therapy. However, conventional practice standards include empiric, short-term administration of an antimicrobial to prevent opportunistic infections. Whether or not dogs with clinical signs of ITB are at significant risk of developing bacterial pneumonia has not been definitively established. On the other hand, evidence of a mucoid to mucopurulent nasal and/or ocular discharge justifies administration of an antimicrobial. Doxycycline, administered orally at 5.0 to 10.0 mg/kg, once daily, for a minimum of 2 weeks is the first choice of antibiotic due to its efficacy against B. bronchiseptica. However, the ability of B. bronchiseptica to persist in the respiratory tract of infected dogs for as long as 3 months justifies a treatment duration of up to 30 days, particularly when attempting to manage simultaneous infections in multiple dogs living in the same environment.

Glucocorticoids

Short-term administration of glucocorticosteroids, administered concurrently with an antimicrobial, is safe and effective in attenuating severe cough in dogs having an uncomplicated infection. Prednisolone can be administered at anti-inflammatory doses, 0.25-0.5 mg/kg, orally, once or twice daily, for up to 5 days as needed to control cough. Since some of the antimicrobials recommended in the treatment of canine ITB are bacteriostatic, concurrent use of glucocorticoids should not be extended beyond 5 days. It is recommended that antimicrobial therapy be continued for at least 5 to 7 days beyond the day that the corticosteroid is discontinued.

Antitussives

Antitussives alone and in combination with bronchodilators, have been recommended in the treatment of canine ITB. Either hydrocodone or butorphanol are recommended antitussives. In cases of ITB that are complicated by bacterial pneumonia, administration of narcotic antitussives is not recommended.

Bronchodilators

The benefits of bronchodilator therapy in dogs and cats with B. bronchiseptica infection remain unclear. At issue is whether or not the airway response to bacteria and viruses increases airway hyperactivity and baseline resistance to airflow. Two categories of bronchodilators are used in veterinary medicine: the methylxanthine derivatives and beta2-agonists. The beta2-agonists, terbutaline and albuterol, have been shown to be of benefit when administered to dogs with chronic bronchitis and are preferred when managing severe B. bronchiseptica infections. These drugs have the advantage of reducing cough as well as reducing pulmonary infiltrates associated with uncomplicated bronchitis. Excitability or tremors may be encountered during the first few days of treatment. The role of bronchodilators in treating cats with B. bronchiseptica infection has not been described and is currently not recommended.

Aerosol Therapy

In contrast to humidification therapy, aerosol therapy, also called nebulization, refers to the production of a liquid particulate suspension within a carrier gas, usually oxygen. Dogs and cats with ITB that derive the most benefit from aerosol therapy are those with excessive accumulations of bronchial and tracheal secretions and those with bacterial bronchial or pulmonary infections. Small, disposable, hand-held jet nebulizers are inexpensive and readily available through hospital supply retailers. Experience has shown that patients do benefit from aerosol therapy when from 6 to 10 ml of sterile saline is nebulized over 15 to 20 minutes, 1 to 4 times daily. Oxygen must be delivered at flow rates of 3 to 5 liters per minute to effectively nebulize saline. Aerosol therapy must be administered in the hospital and is generally administered over 1 to 4 days as needed to control respiratory signs. There is no value in nebulizing mucolytic agents. They can be irritating and induce bronchospasm. Nebulization of glucocorticoid solutions, such as methylprednisolone sodium succinate, have not been critically studied in veterinary medicine. Dogs unresponsive to oral or parenteral administration of antibiotics may respond to nebulized antibiotics.

Vaccination

Several commercially licensed canine vaccines for protection against B. bronchiseptica, CAV-2, and CPiV are available. At this time, there is only one vaccine licensed for protection against feline B. bronchiseptica infection. Canine vaccines are available for topical (intranasal) as well as parenteral administration while the feline B. bronchiseptica vaccine is approved for topical (intranasal) administration only. The efficacy of vaccination administered by either the topical or the intranasal route is well documented. Regardless of the route of administration, vaccinated dogs experience substantially less coughing when compared to control dogs following challenge. Vaccination is not expected to completely eliminate the risk of infection and development of subclinical to mild infection following exposure. At issue, however, is whether or not sequential vaccination (i.e., administering a topical B. bronchiseptica vaccine and a parenteral vaccine during the same appointment) provides superior protection compared to either vaccine given alone. From the studies available at this time, it is suggested that sequential vaccination may, in fact, provide a superior protective response in seronegative puppies than either the intranasal or parenteral product alone. On the other hand, administration of an intranasal vaccine may not effectively booster young adult, seropositive dogs whereas subcutaneously administered vaccine do. There appears to be no benefit to administering both parenteral and topical vaccine to adult, seropositive dogs. Duration of immunity studies on parenterally vs. topically administered vaccines have not been compared. With regard to the onset of immunity, it is recommended that dogs be vaccinated at least 5 days prior to a known (or potential) exposure to ITB, e.g. being housed in a boarding kennel. Despite the assumption that topically administered vaccine provides the most rapid onset of immunity, it is not known if intranasally administered vaccine will immunize a susceptible dog in less than 5 days.

Recommendations outlined by the American Association of Feline Practitioners indicate that B. bronchiseptica vaccination in not required in all cats. Use of the vaccine is generally limited to cluster households and shelters where B. bronchiseptica is known to be associated with lower respiratory infection in cats. As occurs in dogs, transient post-vaccinal sneezing or cough is expected in some cats within 24-hours post-vaccination.

Public Health Considerations

Human infection with B. bronchiseptica is most likely to occur in children and immunocompromised adults. Although infections are uncommon, at greatest risk are individuals whose immunosuppression is related to alcoholic malnutrition, hematologic malignancy, long-term glucocorticoid therapy, concurrent HIV infection, splenectomy, and pregnancy.