Infectious Diseases of the Dog and Cat, 3rd Edition

CHAPTER 6 Canine Infectious Tracheobronchitis

Richard B. Ford
ETIOLOGY
Infectious tracheobronchitis ([ITB] synonyms: kennel cough, canine cough, canine croup) describes an acute,
highly contagious respiratory infection of dogs characterized by sudden-onset, paroxysmal cough with variable
expectoration and nasoocular discharge. The cough is typically described as hoarse or a loud honking sound.
Clinical signs are attributed to infection by one or a combination of bacterial or viral agents (or both) that colonize
the epithelium of the nasal cavity, larynx, and trachea, as well as bronchi, bronchioles, and the pulmonary
interstitium (Table 6-1).
55
Vaccines are available for most of the organisms known to be associated with canine
ITB, and immunoprophylaxis of puppies and adult dogs is recommended for those considered to be at risk of
exposure. Although uncommon, Bordetella bronchiseptica infections have been reported in people as a zoonosis
(see Public Health Considerations in this chapter).
Respiratory signs of ITB in dogs known to have single-agent infections are generally mild and frequently
self-limiting. The prognosis for recovery from uncomplicated infections is excellent, although the duration of
postinfection immunity may be short-lived (months). In the clinical setting, the high prevalence of multiple-agent
infections complicates the clinical presentation. Canine parainfluenza virus (CPiV) and B. bronchiseptica are the
most common organisms isolated from dogs with signs of ITB. However, several other viruses and bacteria are
known to influence the clinical course and outcome of infection. Compared with adults, puppies appear more
vulnerable to life-threatening B. bronchiseptica pneumonia.
Viruses
For several years, CPiV-2 has been reported as the most common virus isolated from the respiratory tract of dogs
with ITB. Distribution is apparently worldwide. CPiV-2 is a single-stranded RNA virus belonging to the family
Paramyxoviridae and is closely related to simian virus 5.
5
Infection generally results in self-limiting, short-lived
cough, with minimal systemic effects. Although natural infection may result in detectable serum antibody for
periods of up to 3 years, antibody titer to CPiV-2 does not correlate well with protection from clinical disease.
43
Canine adenovirus type 2 ([CAV-2]; cause of infectious laryngotracheitis) and, to a lesser extent, CAV type 1
([CAV-1]; infectious canine hepatitis virus) are reported to cause mild, self-limiting acute upper respiratory
disease, characterized by cough, in dogs. These viruses are antigenically related DNA viruses of the family
Adenoviridae (see Chapter 4).
4
Depending on virus strain, canine distemper virus (CDV) can cause acute to subacute systemic infections
associated with a high mortality rate among infected dogs. Infections are known to occur in dogs worldwide.
CDV is also known to cause lower respiratory tract disease in dogs independent of other systemic signs.
Although CDV does act synergistically with CPiV-2 and B. bronchiseptica, it is not regarded as a primary
pathogen in the cause of ITB (also see Chapter 3).
Other viruses, such as canine herpesvirus (CHV; see Chapter 5) and reovirus-1, -2, and -3, have occasionally
been isolated from coughing dogs. However, none of these viruses is regarded as being primarily responsible for
the clinical syndrome described as ITB.
6
54
6
6.1
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Bacteria and Mycoplasmas
B. bronchiseptica is a gram-negative bacterium and a principal etiologic agent of ITB in dogs.
*
Hundreds of
isolates of B. bronchiseptica, with variable virulence patterns and pathogenicity, have been recovered from dogs.
Several other domestic and wild animal species may become infected with B. bronchiseptica, and it may play an
important role in kittens with acute herpesvirus-1 or calicivirus infection (see Chapter 16).
27
Of the hundreds of
isolates, considerable variation exists among individual clones with respect to host distribution and virulence
potential.
30,38,42
Other bacteria recovered from the respiratory tract of dogs with ITB include Streptococcus sp., Pasteurella sp.,
Pseudomonas, and various coliforms.
49
Although these bacteria are regarded as opportunistic invaders, secondary
bacterial infections are the cause of serious, life-threatening complications (pneumonia and sepsis) in the patient
with ITB. Streptococcus equi subsp. zooepidemicus has been associated with increased severity of ITB in
kenneled dogs with endemic respiratory disease
10
; it is also considered a cause of pneumonia in dogs as a
primary pathogen (see Streptococcal Infections, Chapter 35).
Mycoplasmas are fastidious, prokaryotic microbes that are distinguished from bacteria by the fact that they are
enclosed in a cytoplasmic membrane but lack a distinct cell wall.
7,32,41
Nonetheless, unclassified groups of
mycoplasmas, acholeplasmas, and ureaplasmas are commonly recovered in specimens collected from the
nasopharyngeal and laryngeal mucosa of healthy dogs and cats. The presence of Mycoplasma in specimens
collected from the lower respiratory tract of dogs (especially M. cynos) and cats (M. felis) is usually associated
with pneumonia (see Chapters 32 and 88).
7,41,44
* References 7, 20, 21, 38, 56.
EPIDEMIOLOGY
Canine ITB is considered to be among the most prevalent infectious respiratory diseases of dogs. Outbreaks of
canine ITB are relatively common. Clinical infections can reach epizootic proportions when dogs are housed in
high-density population environments such as pet shops, boarding facilities, commercial kennels,
6,7
and veterinary
hospitals.
15,23
Despite their apparent synergism in producing disease, B. bronchiseptica and CPiV2 the two
pathogens appear to spread independently in the dog population.
17
The host range of B. bronchiseptica includes
wildlife, rodents, and cats; however, most outbreaks are the result of direct dog-to-dog or airborne contact with
infectious respiratory secretions. Theories suggest that B. bronchiseptica can be transmitted from dogs to cats. B.
bronchiseptica has been shown to survive in unsupplemented lake water for up to 24 weeks and replicate in natural
waters for at least 3 weeks at 37 C.
39
Both CPiV-2 and B. bronchiseptica are spread from mixing older carrier
animals with younger or otherwise naive dogs, allowing for outbreaks of clinical disease and more rapid spread of
infection.
The common viral agents of ITB are transmitted for up to 2 weeks postinfection. For Mycoplasma sp. and B.
bronchiseptica, however, shedding may occur for 3 months or longer.
5,6
Although infections are transmitted rapidly
and efficiently in high-density populations with high morbidity, death associated with complicated respiratory
infection is uncommon, particularly in adult dogs.
54
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6.1.2
6.2
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PATHOGENESIS
Viruses
Because CPiV does not replicate in macrophages, infections with CPiV are typically restricted to the upper
respiratory tract in dogs. CPiV infection of the larynx can cause edema of the vocal folds resulting in the
high-pitched, honking cough commonly associated with canine ITB. Damage to the tracheal epithelium allows
for secondary infection by other pathogens (Figs. 6-1, A, and 6-1, B). Animals 2 weeks of age and older are
susceptible.
6
Transmission occurs predominantly by aerosolized microdroplets. After a 3- to 10-day incubation
period, viral shedding can occur for 6 to 8 days postinfection.
5
In single-agent infections, signs are limited to a
dry, hacking cough and serous nasal discharge. After recovery, a CPiV carrier state does not appear to exist. Cats
are capable of becoming subclinically infected and shedding the virus. Whether this is a significant source of
infection for dogs is unknown.
Table 6-1 Agents Associated with Infectious Tracheobronchitis in Dogs
Viruses Canine parainfluenza virus
Canine adenovirus-2
Canine distemper virus
Canine herpesvirus
Bacteria Mycoplasma
Bordetella bronchiseptica
Streptococcus spp.
Fig 6-1 A, Electron microscopic (EM) scan of normal canine tracheal epithelium.
B, EM scan shows mucous hypersecretion and the tracheal epithelium
completely denuded of cilia only 72 hours after experimental infection
with CPiV. (Courtesy Pfizer Laboratories, New York, N.Y.)
Infection with CAV-2 occurs after oronasal contact. The virus replicates in the epithelium of the nasal mucosa,
pharynx, tonsillar crypts, trachea, and bronchi and in nonciliated bronchiolar epithelium. Replication peaks by
day 3 to 6 after inoculation corresponding to a peak in serum antibody titer.
4
In immunocompetent dogs,
6.3
6.3.1
CHAPTER 6 Canine Infectious
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Infectious Diseases of the Dog and Cat, 3rd Edition
infection is typically short-lived; virus usually cannot be isolated beyond day 9 of infection. Infection of type-2
alveolar cells has been associated with interstitial pneumonia.
4
Single-agent infections may be associated with
tonsillitis or lung consolidation, or both.
6
In other dogs, overt clinical signs may not be apparent.
Bacteria and Mycoplasmas
B. bronchiseptica has been associated with respiratory infections in dogs and cats (see Chapter 16).
29
B.
bronchiseptica is a gram-negative, aerobic coccobacillus regarded as one of the principal causative agents of
canine ITB. Although either CPiV or CAV-2 may cause mild clinical infections, clinical disease is expected to
be more severe in dogs co-infected with B. bronchiseptica than with any these agents alone. Transmission most
likely occurs after direct contact with infected dogs or contact with aerosolized microdroplets either from
infected dogs or through contaminated dishware, human hands, and other fomites.
During an incubation period of approximately 6 days, B. bronchiseptica preferentially attaches to, and replicates
on, the cilia of respiratory epithelium. Bordetella attach to the surface of ciliated respiratory mucosae by means
of adhesin molecules (Fig. 6-2). Once they colonize the respiratory tract, Bordetella produce a variety of potent
toxins that impair phagocytic function and induce ciliostasis. B. bronchiseptica is uniquely capable of facilitating
co-colonization of the respiratory tract by other opportunistic organisms. B. bronchiseptica possesses several
intrinsic mechanisms for evading host defenses.
4,15,40,60
It is well recognized for its role as a significant
complicating factor in dogs with multiple-agent respiratory infections. For example, fimbriae (hairlike
appendages extending from the cell membrane of B. bronchiseptica) recognize specific receptors within the
respiratory tract.
8
This allows B. bronchiseptica to colonize specific tissues where it then releases various
exotoxins and endotoxins that impair the function and integrity of the respiratory epithelium and compromise the
ability of the infected host to eliminate the infection.
15,23
Additionally, although B. bronchiseptica has been
regarded as an extracellular pathogen, it 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 or carrier state. The pathogenesis of B. bronchiseptica has recently been reviewed.
*
Fig 6-2 Transmission EM scan of tracheal mucosa showing ciliated epithelial cells
with adherent B. bronchiseptica (arrow). (Courtesy EM Laboratory,
College of Veterinary Medicine, University of Georgia, Athens, Ga.)
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Despite the fact that infection elicits production of local antibody, the organisms are not completely cleared from
the respiratory tract for an average of 3 months. Although by itself B. bronchiseptica can cause rhinitis, mucous
nasal discharge, and cough, the most naturally occurring illness is associated with viruses or other bacteria. The
organism has been isolated primarily from the upper respiratory tract of clinical healthy dogs. In combined
infections with CPiV, tracheal mucosal injury is associated with clinically apparent pneumonia.
In addition to B. bronchiseptica, several species of Mycoplasma and Ureaplasma have been associated with
pneumonia in dogs.
7,32,41,44
Although endogenous to the nasopharynx of dogs and cats, mycoplasmas are not
typically found in the lower respiratory tract. Unlike B. bronchiseptica, mycoplasmas colonize both ciliated and
nonciliated epithelia. Both natural and experimental infections are characterized by purulent bronchitis and
bronchiolitis. Epithelial and lymphoid hyperplasia and interstitial pneumonia may develop. Systemic infection is
rare. Once bacteria colonize the lower respiratory epithelium, chronic bacterial shedding of several months'
duration is likely.
7
* References 4, 20, 21, 38, 56.
CLINICAL FINDINGS
B. bronchiseptica and CPiV are among the most common agents isolated from dogs affected with ITB. Because
multiple agents cause most natural infections of ITB, associating a distinct set of clinical signs with a particular
bacterium or virus is difficult.
7,49
Acute-onset, paroxysmal coughing episodes, typically associated with retching, in an otherwise healthy, active dog
characterizes the clinical presentation. Swollen vocal folds, associated with laryngitis, restrict airflow through the
glottis during a cough. This results in a loud, high-pitched cough described as a honking sound. Cough is likely to
be productive. However, expelled secretions are not consistently observed because of the small volume and the
tendency for dogs to swallow expectorated secretions. Although dogs are affected most commonly during summer
and fall, the high density of dogs living in shelters or kennels can be expected to result in infections at any time of
year. Dogs that have received prior vaccination against CDV and CAV-2 may still develop signs.
4,6,43,49
The time
between exposure and onset of signs of canine ITB ranges from 3 to 10 days, regardless of the agents involved in
the primary infection.
4-6,38
A history of exposure to other dogs, particularly in kennel or shelter settings, although
common, not a prerequisite. Expectoration of mucus, described as retching or hacking, may occur after a coughing
episode and is commonly misinterpreted by owners as vomiting. Physical examination is usually unremarkable,
although cough may be easily elicited on manipulation of the trachea, particularly at the thoracic inlet. 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. Although secondary bacterial pneumonia can develop in affected dogs,
most infections are self-limiting and may resolve without treatment.
A second more severe syndrome is described in dogs with no prior natural or vaccine exposure to the various agents
that cause ITB or complicating bacterial infection.
6
Affected dogs are more likely to have a history of recent stays
in a pet shop, boarding facility, kennel, or shelter. ITB may be associated with or without rhinitis and
accompanying mucoid to mucopurulent nasal and ocular discharges. Complications associated with
bronchopneumonia may become life threatening, particularly in puppies. On physical examination, affected dogs
are usually febrile and may be lethargic, anorexic, or dyspneic. Affected dogs are difficult to distinguish from those
with CDV infections or other pneumonias. Outbreaks of ITB may affect more than 50% of dogs in a densely
populated environment.
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Infectious Diseases of the Dog and Cat, 3rd Edition
DIAGNOSIS
Clinical diagnosis is based on a history of recent exposure to other dogs, signs, and response to empiric therapy. An
uncertain vaccination history can be helpful in determining susceptibility. However, a history of recent vaccination
(within 6 months) in a dog with characteristic respiratory signs does not exclude a diagnosis of ITB. Routine
hematology and biochemistry profiles are not diagnostic but do serve to establish and monitor the health status of
affected dogs. A stress leukogram characterized by mature neutrophilia, lymphopenia, and eosinopenia may be
evident. An inflammatory leukogram with significant leukocytosis or left shift may be present in dogs with
complicating bacterial pneumonia. Fluid obtained from transtracheal aspirates may provide evidence of a
neutrophilic exudate. Neutrophils are often degenerate in the presence of numerous extracellular and intracellular
bacteria. Bacterial culture of aspirated fluid may be particularly helpful in confirming bacterial pneumonia and
prescribing appropriate therapy.
26
Because of indigenous microflora, bacterial isolates obtained from swabs of the nasal and oral cavities, oropharynx,
and nasopharynx do not necessarily represent primary or secondary pathogens. However, bacteria cultured from
transtracheal aspiration fluid, endotracheal or bronchoalveolar lavage, or sterile swabs of tracheal epithelium are
more likely to represent disease-causing organisms. In collecting specimens for Bordetella isolation,
nasopharyngeal swab collections yield fewer bacteria than does aspiration of lavage fluids because these bacteria
adhere to fiber-tipped swabs made of Dacron, alginate, or cotton.
25
The best results are improved if a transport
medium intended for Bordetella is used.
Thoracic radiographic findings are typically unremarkable in animals with uncomplicated ITB. Dogs with
complications associated with ITB may have radiographic signs of pulmonary hyperinflation and segmental
atelectasis. Dogs with combined B. bronchiseptica and CPiV infections may develop lobar consolidation evident on
thoracic radiographs.
Although uncommonly performed on clinical patients, viral isolation of CPiV or CAV-2 can be accomplished on
swabs taken from the nasal, pharyngeal, or tracheal epithelium. The ability to inhibit virus growth, cytopathic
effect, or hemadsorption with a standardized antiserum confirms the diagnosis.
6
Acute and convalescent serum
neutralizing or hemagglutination inhibition antibody titers can be used to establish exposure to any of the viral
agents involved in canine ITB. The ability to demonstrate a rising titer, however, has little clinical application
because of the relatively short duration of viral infection. Antibody titers to lipopolysaccharide (LPS) antigens of B.
bronchiseptica had no predictive value in determining which animals will contract respiratory disease, how severe
the disease will be, or which dogs have colonization of their lungs.
11
56
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Table 6-2 Treatment Options for Canine Infectious Tracheobronchitis
DRUG
DOSE
a
(mg/kg)
ROUTE INTERVAL (HOURS) DURATION (DAYS)
Antimicrobials
Amoxicillin-clavulanate 12.525.0 PO 12 1014 (minimum)
Azithromycin 5.0 PO 24 57
Trimethoprim-sulfonamide
b
15 PO 12 1014 (minimum)
Doxycycline
c
2.55.0 PO 12 10 (minimum)
Enrofloxacin
d
5.0 PO 24 10
Chloramphenicol
e
1525 PO 12 10
Antitussives
Hydrocodone 0.22 PO 812 prn
Butorphanol 0.55 PO, SC 812 prn
Glucocorticoids
Prednisolone 0.250.50 PO 12 35 days
Bronchodilators
Aminophylline 10 PO 812 prn
Terbutaline 2.5 PO, SC 812 prn
PO, By mouth; SC, subcutaneous; prn, as needed.
a Dose per administration at specified interval. For additional information on antimicrobials, see
formulary, Appendix 8.
b In vitro susceptibility is higher than clinical efficacy since resistance develops rapidly.
c Dental staining is possible in young (under 16 weeks) animals, although this is less likely than with
tetracycline.
d Adverse effects on cartilage of young growing animals; susceptibility of Bordetella isolates (40%60%)
is not as high as with others gram-negative bacteria.
e High susceptibility of isolates; however causes idiosyncratic aplastic anemia in people and reversible
myelosuppression in dogs.
Nested polymerase chain reaction has been shown to be most sensitive in detecting B. pertussis in human patients.
25
THERAPY
Antimicrobials
In uncomplicated cases of ITB, the value of antimicrobial therapy appears limited. However, in at least one
study,
50
administration of an oral or a parenteral antibacterial agent reduced the duration of coughing in affected
dogs. Drugs found to be particularly effective were trimethoprim-sulfonamide and amoxicillin. Because dogs
with clinical signs of ITB may be at increased risk for bacterial bronchopneumonia, administration of empiric
antimicrobial therapy is justified even when infections are not complicated by overt bacterial pneumonia.
54
Systemic antimicrobial therapy is indicated if deeper respiratory or systemic bacterial infection develops,
particularly bacterial bronchopneumonia or interstitial pneumonia. Although the antimicrobial prescribed should
be ideally based on results of bacterial culture and susceptibility results, in the clinical setting empiric
antimicrobial therapy may be most appropriate.
21,54
Table 6-2 lists appropriate antimicrobials in the empiric
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6.6.1
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treatment of dogs with signs consistent with ITB. With increasing antimicrobial use, more recent isolates of B.
bronchiseptica from cats in California and Liverpool have been resistant to a large number of antibiotics,
including some cephalosporins, fluoroquinolones, and sulfonamides.
18,45
Isolates from dogs in Liverpool and
California were sensitive to doxycycline, amoxicillin-clavulanate, and enrofloxacin.
3,46
Glucocorticoids
Antiinflammatory doses (see Table 6-2) of orally administered glucocorticoids are effective in ameliorating the
cough associated with uncomplicated cases of ITB. Orally administered prednisolone can be used as needed to
suppress coughing for periods of up to 5 to 7 days. However, glucocorticoids do not significantly shorten the
clinical course.
50
In contrast to previous claims,
52
no controlled studies substantiating the value of intratracheal
administration of glucocorticoids over oral administration have been conducted.
Antitussives
Antitussives, alone and in combination with bronchodilators, have been recommended in the treatment of canine
ITB. Objectively, these drugs are intended to interrupt the cough cycle; however, certain limitations to
antitussive therapy should be noted. Over-the-counter cough suppressant drugs appear to offer little or no relief
from the cough associated with ITB. Narcotic cough suppressants, such as hydrocodone, are generally effective
in suppressing cough frequency and intensity. However, excessive or prolonged use of these drugs can lead to
compromised ventilation and reduced expectoration, with subsequent retention of respiratory secretions and
diminished clearance of bacteria.
6,49,50
In cases of ITB that are complicated by bacterial pneumonia,
administration of narcotic antitussives is not recommended.
Bronchodilators
The methylxanthine bronchodilators, theophylline and aminophylline (theophylline-ethylenediamine), prevent
bronchospasm and may therefore be effective cough suppressants in selected conditions, such as occurs in human
asthma. However, dogs with signs of ITB are not expected to derive significant benefit from bronchodilator
therapy alone.
Aerosol Therapy
Aerosol therapy (or nebulization) refers to the production of a liquid particulate suspension within a carrier gas,
usually oxygen. Patients with ITB that derive the most benefit from aerosol therapy are those with excessive
accumulations of bronchial and tracheal secretions and those with secondary bronchial or pulmonary infections,
particularly with B. bronchiseptica. Small, disposable, hand-held jet nebulizers are inexpensive and available
through hospital supply retailers. From 6 to 10 ml of sterile saline can be nebulized over 15 to 20 minutes one to
four times daily. Oxygen is delivered at flow rates of 3 to 5 L/min to nebulize the solution. Aerosol therapy must
be administered in the hospital. Most patients tolerate aerosol therapy well and generally do not require physical
restraint after the first treatment.
There is no value in nebulizing mucolytic agents, for example, acetylcysteine, which can be irritating and induce
bronchospasm. Furthermore, liquefying tenacious respiratory secretions may not be an effective means of
facilitating airway clearance. Nebulization of glucocorticoid solutions, such as methylprednisolone sodium
57
58
6.6.2
6.6.3
6.6.4
6.6.5
CHAPTER 6 Canine Infectious
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succinate, has not been critically studied in veterinary medicine. However, in acute paroxysms of cough that may
lead to or predispose the animal to airway obstruction, such therapy may provide short-term benefits.
Dogs that are unresponsive to oral or parenteral administration of antibiotics may respond to nebulized
antibiotics. Aerosolized nonabsorbable antibiotics, such as kanamycin, gentamicin, and polymyxin B, have been
shown to be effective in reducing the population of B. bronchiseptica in the trachea and bronchi of infected dogs
for up to 3 days after discontinuation of treatment.
7
Although clinical signs are not eliminated, the severity of
signs may be significantly reduced.
Supportive Care
Supportive treatment of the individual dog with ITB is directed at maintaining adequate caloric and fluid intake
during the acute infection; preventing secondary or opportunistic bacterial infections, especially pneumonia;
suppressing the cough; and reducing exposure to other dogs. When practical, this treatment is better
accomplished in the owner's home rather than in a kennel or veterinary hospital. This approach can reduce the
potential spread of infection by separating affected dogs from susceptible ones.
TREATMENTS NOT RECOMMENDED
Considering the fact that canine ITB represents a significant percentage of the total cases of infectious upper
respiratory disease in dogs, it is not unusual that creative therapeutic modalities have been administered in an
attempt to shorten the course of disease and minimize the clinical signs. The treatments listed in this chapter are
largely anecdotal, have not been subjected to scientific scrutiny, and at this time are not recommended in the
treatment of canine ITB.
Antiviral Therapy
Given that at least three agents associated with canine ITB are viruses (CPiV, CAV-2, and CDV), the
administration of various antiviral drugs approved for use in humans has been suggested for use in dogs with
ITB. However, antiviral therapy is highly specific and is generally targeted at specific viruses. In veterinary
medicine, antiviral therapies for use against viruses associated with canine ITB are not available. At this time, no
human antiviral therapy is recommended for use in either the dog or the cat.
Intranasal Vaccination
Unpublished and anecdotal reports from veterinarians have suggested that some dogs with ITB may derive
therapeutic benefit from administration of a single dose of an intranasal (IN) B. bronchiseptica vaccine.
Experience with this treatment modality in outbreaks of canine ITB within a shelter environment have not been
shown to diminish the intensity of clinical signs or to shorten the course of disease. Also suggested is that dogs
experiencing chronic or persistent cough beyond the expected recovery time for acute ITB may benefit from
therapeutic vaccination. To date, no controlled studies have been done to support this recommendation. Because
attenuated B. bronchiseptica vaccines in themselves produce mild respiratory signs, vaccination of already ill
animals may cause more severe respiratory illness.
6.6.6
6.7
6.7.1
6.7.2
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Expectorants
A variety of over-the-counter expectorants have been used in canine ITB to facilitate the clearance of mucous
secretions within the trachea and bronchi. Saline expectorants, guaifenesin, and volatile oils that can be inhaled
as a vapor are intended to stimulate secretion of the less viscous bronchial mucus and, thereby, enhance
clearance of viscous respiratory secretions. However, the value of expectorant therapy in dogs with ITB has not
been established and is not currently recommended. Numerous over-the-counter cough suppressant medications
are available and are occasionally administered to coughing dogs. The author's experience with these products
suggests that they offer little to no physical benefit in ameliorating the clinical signs associated with ITB.
PREVENTION
Maternal Immunity
Maternal immunity to the viruses known to cause canine ITB provides variable degrees of protection. Maternally
derived CPiV antibody does not appear to interfere with parenteral vaccination of puppies that are 6 weeks of age
and older.
5
In contrast, maternal antibody interference to parenteral CAV-2 vaccination can persist for as long as
12 to 16 weeks, but it does not protect against infection.
4
Natural Immunity
The duration of immunity after recovery from CPiV and CAV-2 infection has not been studied, although one
unpublished study documented CPiV neutralizing antibody 2 years after infection in dogs that were not
reexposed to virus.
6
However, enzyme-linked immunosorbent assaybased antibody titers to LPS did not
correlate to the degree of protection in infected dogs in one outbreak.
11
Dogs that have recovered from B.
bronchiseptica infection are highly resistant to reinfection for at least 6 months.
7
However, the level of
protection derived from infection should be expected to vary, depending on the age and health status of the
individual animal, the viruses and bacteria involved, and the opportunity for reexposure.
Vaccination
Both viral and bacterial vaccines are available against most of the agents having a known pathogenic role in
canine ITB. Various B. bronchiseptica, CAV-2, and CPiV vaccines are licensed for parenteral administration or
for IN administration to dogs. Intranasal vaccines are attenuated and those for parenteral use are inactive whole
cell or cellular antigenic extracts (Table 6-3). Vaccines must be administered only by the route indicated on the
package label (vaccine insert). Currently, no vaccine has been approved for administration by both routes. CDV,
CAV-2, and CPiV vaccines are commonly incorporated into routine vaccine protocols recommended for all dogs
(see Table 6-3). B. bronchiseptica bacterins are in widespread use throughout the United States; no commercial
vaccine is currently in use for protecting dogs against Mycoplasma sp. For a listing of some currently available
vaccines, see Table 6-4 and Appendix 3. For further recommendations on vaccination for ITB, see Chapter 100
and Appendix 1.
58
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6.7.3
6.8
6.8.1
6.8.2
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Table 6-3 Types of Licensed Vaccine for Protection of Dogs Against Bordetella
bronchiseptica, Canine Parainfluenza Virus, and Canine Adenovirus-2
VACCINE
VOLUME/ROUTE
a
MINIMUM AGE AT FIRST
DOSE
INITIAL SERIES
B. bronchiseptica
(killed-extracted cellular
antigens)
1 ml parenteral (SC only) 8 weeks 2 doses, 24 weeks apart
B. bronchiseptica (a virulent
live culture) plus MLV CPiV,
CAV-2, CDV
1 ml parenteral SC or IM Not stipulated (8 weeks
recommended)
2 doses, 24 weeks apart.
Dogs vaccinated before the
age of 4 months should
receive a single dose on
reaching 4 months of age.
B. bronchiseptica (avirulent
live culture) plus MLV CPiV
0.4 or 1.0 ml, depending on
manufacturer
IN
2 or 3 weeks, depending on
manufacturer
1 dose (NOTE: some
manufacturers stipulate a
second dose at 6 weeks of
age in puppies that receive
the first dose between 3 and
6 weeks of age.)
B. bronchiseptica (avirulent
live culture) plus MLV CPiV,
CAV-2
0.4 or 1.0 ml, depending on
manufacturer
IN
3 or 8 weeks, depending on
manufacturer
1 dose
CPiV, Canine parainfluenza virus, CAV-2, canine adenovirus-2; CDV, canine distemper virus; IM, intramuscular; SC,
subcutaneous; IN, intranasal.
a When the vaccine manufacturer stipulates the route of administration for a particular vaccine, optional
routes are not indicated.
Despite the numerous monovalent and combined canine vaccines on the market today, only B. bronchiseptica
vaccination has been recently evaluated for efficacy against a defined challenge.
12,15,16
Studies support the fact
that B. bronchiseptica vaccines, whether administered by the parenteral or IN route, are effective in providing
substantial reduction in clinical signs associated with ITB in puppies challenged under laboratory conditions.
Vaccinating seronegative puppies by both routes sequentially appears to provide a greater degree of protection
compared with puppies vaccinated by either the parenteral or IN route alone (compare Figs. 6-3 and 6-4).
15

When the disease prevalence is high in an environment, current protocols should be modified to use at least two
parenteral and one intranasal vaccine during the primary vaccination series. For adult dogs, annual vaccination
with parenterally administered products can be used in addition to intranasal vaccination before anticipated
exposure.
On the other hand, administering B. bronchiseptica vaccine sequentially by the parenteral and IN routes to adult,
seropositive (previously vaccinated ) dogs does not appear to effectively boost systemic antibody titers. In fact,
administration of IN vaccines to adult, seropositive dogs may not be effective as a booster inoculation.
16

Parenterally administered (subcutaneous) B. bronchiseptica vaccine, on the other hand, has been shown to boost
antibody levels in previously vaccinated or exposed dogs.
16
These findings are in contrast to previous reports
suggesting that vaccine administered by the IN route induce both local and systemic immunity and protect
against challenge more rapidly than parenterally administered vaccines.
7,26,48
Depending on the vaccine, puppies
inoculated by the IN route can be immunized as early as 2 to 3 weeks of age.
59
60
CHAPTER 6 Canine Infectious
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Table 6-4 Vaccines Available for Canine Infectious Tracheobronchitis
a
VACCINE NAME MANUFACTURER TYPE ANTIGENS ROUTE
Bronchi-Shield III Fort Dodge Attenuated Bb, CAV-2, CPiV IN
Intra-Trac-II ADT Schering Plough Attenuated Bb, CPiV IN
Intra-Trac-II Schering Plough Attenuated Bb, CPiV IN
Naramune-2 Bio-Ceutic Attenuated Bb, CPiV IN
Progard-KC Intervet Attenuated Bb, CPiV IN
Nasaguard-B Pfizer Attenuated Bb IN
Cough Guard B Pfizer Whole cell Bb SC
Vanguard-5B Pfizer Whole cell Bb, CPiV and others SC
Bronchicine Bayer Antigen extract Bb SC
Camune B Bayer Antigen extract Bb SC
Performer Borde-Vac Agri Labs Antigen extract Bb SC
Bb, Bordatella bronchiseptica; CAV-2, canine adenovirus-2; CPiV, canine parainfluenza virus; IN, intranasal; SC, subcutaneous.
a See Appendix 3 for further information on these products and manufacturers.
Fig 6-3 Photomicrograph of a section of trachea from a pup that was vaccinated
IN with modified-live, and intramuscularly with inactivated B.
bronchiseptica and was euthanatized 10 days after challenge exposure.
The absence of bacterial colonies is noted on the epithelium. Bar, 100
m. (From Ellis JA, Haines DM, West KH, et al. 2001. Effect of vaccination
on experimental infection Bordetella bronchiseptica in dogs, J Am Vet
Med Assoc 218:367-375, with permission.)
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Fig 6-4 Photomicrograph of a section of trachea from an unvaccinated control
pup that was euthanatized 10 days after challenge exposure with B.
bronchiseptica. Numerous brown-stained bacterial colonies are noted on
the epithelium. Immunohistochemical stain; Bar, 100 m. (From Ellis JA,
Haines DM, West LK et al. 2001. Effect of vaccination on experimental
infection Bordetella bronchiseptica in dogs, J Am Vet Med Assoc
218:367-375, with permission.)
Many parallels can be drawn between B. bronchiseptica vaccination for kennel cough for dogs and B. pertussis
vaccination for whooping cough in people. Vaccines for B. bronchiseptica were originally developed based on
the genetic homogeneity of the bacteriocin. As for B. pertussis, antigenic divergence of strains is one reason for
outbreaks that have occurred following vaccination.
37
Similarly, in a genetic study of more recent B.
bronchiseptica isolates from dogs, the genotypic polymorphism of encoding for outer membrane proteins were
much more heterogeneous than the original licensed vaccine strains.
28
Another problem in people is that primary
vaccination has been restricted to children, and waning immunity has occurred beginning in adolescence and an
increasing exposure.
31
The problem of immune senescence may be overcome by broadening recommendations
to use boosters in adults at risk with newly developed parenteral acellular products that are less reactogenic. In
animals, vaccine development shifted to the use of IN-attenuated products. In the future, purified acellular
60
61
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vaccines may solve the dilemma of being highly immunogenic for extended immunity with little risk of
postvaccinal illness.
Annual revaccination is recommended for dogs considered at risk for exposure. Before known or potential
exposure to other dogs (e.g., boarding), a single booster vaccination, administered IN, is recommended at least 5
days before exposure in dogs that have not been vaccinated within the preceding 6 months.
7,16
Vaccination has
not been proven to provide any therapeutic effect in dogs with active infection.
The occurrence of adverse reactions after administration of parenteral vaccine for canine ITB is rare and
typically is limited to local irritation at the injection site. In contrast, IN vaccines can be associated with
development of a cough or nasal discharge (or both) 2 to 5 days after inoculation, sometimes longer.
Postvaccinal signs will rarely be sufficiently severe or persistent that administration of an antimicrobial will be
indicated. Occurrence of postvaccinal cough in dogs inoculated by the IN route can have significant implications
in animal shelters because it may be difficult to distinguish vaccinates from clinically affected dogs. Inadvertent
subcutaneous inoculation of an attenuated IN CPiV-2 and B. bronchiseptica vaccine resulted in local
inflammation and acute nonseptic hepatocellular degeneration and necrosis.
51
An experimental IN vaccine against B. bronchiseptica has been developed by selective inactivation of the aroA
gene a known virulence gene in Bordetella that enables colonization of the respiratory tract.
47
The vaccine
induced higher antibody titers and resulted in lower bacterial counts in the respiratory tract of experimentally
challenged mice. Clinical signs were avoided in vaccinates in this rationally attenuated vaccine.
Management of Outbreaks
Environments in which transient dogs are housed in adjoining kennels are conducive to efficient and rapid
transmission of the agents capable of causing canine ITB. Although impor-tant in preventing infections,
vaccination may not guarantee protection against development of signs, particularly in high-density populations.
Because airborne transmission is common, dogs suspected of having contagious respiratory disease should be
isolated when signs first develop in an effort to limit exposure to susceptible dogs. Thorough, routine cleaning of
housing facilities, preferably using fresh sodium hypochlorite, chlorhexidine, or benzalkonium solution, is
necessary to control the spread of ITB. Disinfection of sur-faces is important to remove pathogenic viruses and
bacteria; however, airborne spread from respiratory discharges of infected animals poses the greatest risk for
exposure. Adequate ventilation, from 12 to 20 air exchanges per hour,
6,26
is recommended in kennel or shelter
facilities. To further limit exposure, relative humidity should be maintained between 50% and 65%, with ambient
temperature between 21 C and 23.8 C. No evidence exists that IN vaccination, administered when clinical
signs are exhibited, will alter the course of an outbreak.
Once an outbreak has developed, isolating or depopulating the entire facility for up to 2 weeks may be the only
reasonable and most efficacious method of containing infections. This measure is necessary because clinically
healthy previously infected dogs can be shedding organisms in low numbers. In addition to extensive cleaning,
individual dogs are treated as necessary to manage clinical signs.
Animal facilities that maintain a large number of dogs, especially transient populations, are at considerable risk
for canine ITB outbreaks. A reduction in the incidence of ITB has been observed in dogs whose vaccinations for
all infections were current. However, attempts to prevent outbreaks through routine, widespread IN vaccines may
be ineffective if vaccination and exposure are likely to occur within the same day. Furthermore, postvaccinal
coughing or nasal discharge may preclude adoption of otherwise healthy dogs from impoundment facilities. In
addition to vaccination, adequate housing, proper cleaning, and adequate ventilation are critical factors in
6.8.4
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preventing outbreaks of ITB whenever dogs are housed within crowded environments. For further information,
see Chapter 98.
PUBLIC HEALTH CONSIDERATIONS
The zoonotic potential of canine B. bronchiseptica infection has been reviewed.
16,19,58,59
Over the last several
years, reports of human respiratory infections caused by B. bronchiseptica continue to appear in the human
literature. At greatest risk are individuals who are immunosuppressed resulting from conditions related to alcoholic
malnutrition, hematologic malignancy, long-term glucocorticoid therapy, concurrent human immunodeficiency
virus infection, splenectomy, and pregnancy. As expected, individuals subjected to tracheostomy or endotracheal
tube intubation are also at risk for infection. Humans with preexisting respiratory disease, such as chronic
bronchitis, bronchiectasis, and pneumonia, are particularly susceptible. Although human bordetellosis has been
associated with a variety of domestic and wildlife animal species, transmission of disease from pets to humans is
largely circumstantial. In one instance, infection associated with exposure to rabbits was found to persist in a person
with bronchopneumonia for at least 2.5 years.
24
Estimates suggest that up to 40% of immunocompromised adults living in the United States today have pets.
2
A
logical assumption therefore is that, as pet owners, these individuals may be at increased risk of acquiring
opportunistic zoonotic infections.
*
The risk of a child or immunocompromised adult becoming infected with
pet-associated B. bronchiseptica infection must be considered small, particularly when exposure to a large number
of dogs in kennels and animal shelters can be avoided. For further discussion concerning immunocompromised
people and pets, see Chapter 99.
* References 1, 14, 33, 35, 36.
Suggested Readings

See the CD-ROM for a complete list of references.

15. Ellis, JA, Haines, DM, West, KH, et al.: Effect of vaccination on experimental infection with Bordetella
bronchiseptica in dogs. J Am Vet Med Assoc. 218, 2001, 367375.
16. Ellis, JA, Krakowka, SG, Dayton, AD, et al.: Comparative efficacy of an injectable vaccine and an
intranasal vaccine in stimulating Bordetella bronchiseptica-reactive antibody responses in seropositive dogs.
J Am Vet Med Assoc. 220, 2002, 4348.
6.9
6.10
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