Bordetellosis (Bordetella bronchiseptica)

Bordetellosis is a contagious bacterial respiratory disease of rabbits and other small mammals caused by the Gram-negative coccobacillus Bordetella bronchiseptica. In rabbits, the bacterium colonizes the ciliated epithelium of the upper respiratory tract, often asymptomatically, but can cause rhinitis, sinusitis, bronchopneumonia, and otitis media, especially in immunocompromised or stressed animals. The disease is zoonotic in reverse (rabbits can be infected by dogs, cats, and pigs), and co-infections with Pasteurella multocida are common. In rabbits, the clinical presentation ranges from subclinical carrier state to severe respiratory distress, with mucopurulent nasal discharge, sneezing, and dyspnea. The bacterium produces toxins (e.g., tracheal cytotoxin, adenylate cyclase toxin) that impair mucociliary clearance, facilitating secondary bacterial invasion. Diagnosis relies on culture, PCR, and serology, and treatment involves supportive care and appropriate antimicrobial therapy, though elimination of the carrier state is challenging.

The primary causative agent is Bordetella bronchiseptica, a small, aerobic, Gram-negative coccobacillus. It possesses fimbriae and adhesins that bind to ciliated respiratory epithelium. Key virulence factors include: filamentous hemagglutinin (FHA), pertactin, adenylate cyclase toxin (ACT), dermonecrotic toxin (DNT), and tracheal cytotoxin (TCT). These factors cause ciliostasis, epithelial damage, and impaired local immunity. In rabbits, B. bronchiseptica is often a primary pathogen but can also act synergistically with Pasteurella multocida, leading to more severe disease. Environmental stressors such as poor ventilation, high ammonia levels, overcrowding, and temperature fluctuations can trigger clinical disease in carriers. The bacterium is transmitted via aerosol, direct contact, and fomites. It can survive in the environment for weeks, especially in moist organic material. Other Bordetella species (e.g., B. avium in birds) are not typically associated with rabbits, but cross-species transmission from dogs, cats, and pigs is documented.

Bordetellosis is prevalent in rabbitries and laboratory rabbit colonies, with seroprevalence rates ranging from 20% to 90% in some populations. It affects domestic rabbits (Oryctolagus cuniculus) of all breeds and ages, but young rabbits (weanlings) and geriatric rabbits are more susceptible to clinical disease. There is no sex predilection. The bacterium is endemic in many conventional rabbitries, and carrier animals serve as reservoirs. Wild rabbits (Sylvilagus spp.) can also carry the organism. In pet rabbits, the prevalence is lower but still significant, especially in multi-rabbit households or those with exposure to dogs, cats, or pigs. The disease is more common in facilities with poor biosecurity, high stocking density, and inadequate ventilation. Concurrent infections with Pasteurella multocida, Staphylococcus aureus, or Mycoplasma spp. increase morbidity and mortality. Stress factors such as transport, weaning, parturition, and concurrent illness precipitate clinical outbreaks.

Bordetella bronchiseptica colonizes the ciliated epithelium of the nasal cavity, trachea, and bronchi. The bacteria adhere via fimbriae and FHA to cilia and mucus. The release of TCT and ACT causes ciliostasis, loss of cilia, and epithelial cell damage, leading to impaired mucociliary clearance. This allows the bacterium to persist and proliferate, and facilitates secondary bacterial invasion. The inflammatory response involves neutrophil infiltration, release of pro-inflammatory cytokines, and production of mucopurulent exudate. In severe cases, the infection spreads to the lower respiratory tract, causing bronchopneumonia, and to the middle ear via the Eustachian tube, resulting in otitis media. The dermonecrotic toxin can cause local tissue necrosis. Systemic signs are rare but can occur in immunocompromised animals. In rabbits, the infection is often limited to the upper respiratory tract, but stress or concurrent disease can lead to pneumonia and septicemia. The bacterium can also be shed in urine and feces, but respiratory transmission is primary.

Intrinsic factors include the anatomical structure of the rabbit respiratory tract: relatively narrow nasal passages, a small oropharynx, and a large tongue that makes intubation difficult. Rabbits are obligate nasal breathers, so any nasal obstruction can cause severe respiratory distress. Age is a factor: young rabbits have immature immune systems, and geriatric rabbits may have decreased immunity. Stress from poor husbandry, such as inadequate ventilation, high ammonia levels, overcrowding, and temperature extremes, predisposes to clinical disease. Concurrent infections, especially with Pasteurella multocida, are significant. Nutritional deficiencies, particularly vitamin A and C (though rabbits synthesize vitamin C), can impair mucosal immunity. Immunosuppression from corticosteroid therapy or concurrent diseases (e.g., Encephalitozoon cuniculi) increases susceptibility. Poor biosecurity, introduction of new animals without quarantine, and exposure to dogs, cats, or pigs that carry B. bronchiseptica are extrinsic risk factors.

Clinical signs vary from subclinical to severe. In subclinical carriers, there are no apparent signs. In mild cases, rabbits may show serous to mucoid nasal discharge, sneezing, and occasional coughing. As the disease progresses, the discharge becomes mucopurulent and may be accompanied by dyspnea, tachypnea, and open-mouth breathing (since rabbits are obligate nasal breathers). Rabbits may exhibit pawing at the nose, head shaking, and ocular discharge due to obstruction of the nasolacrimal duct. With otitis media, torticollis (head tilt), nystagmus, and ataxia may occur. Severe pneumonia leads to lethargy, anorexia, fever, and cyanosis. In chronic cases, rabbits may develop chronic rhinitis with persistent nasal discharge and weight loss. On auscultation, crackles and wheezes may be heard. In some cases, subcutaneous abscesses may form. Sudden death can occur in peracute cases, especially in young rabbits.

Differential diagnoses include: 1) Pasteurellosis (Pasteurella multocida) - very similar clinical signs, but often causes abscesses and more severe pneumonia; culture and PCR differentiate. 2) Staphylococcus aureus infection - can cause rhinitis and pneumonia, but also skin abscesses; culture. 3) Mycoplasmosis (Mycoplasma spp.) - chronic respiratory disease, but less common; PCR. 4) Encephalitozoon cuniculi - causes neurological signs like torticollis, but also renal disease; serology and PCR. 5) Rhinitis due to foreign bodies or dental disease (e.g., tooth root abscess) - imaging and oral exam. 6) Allergic rhinitis - history and response to environmental changes. 7) Neoplasia (e.g., nasal adenocarcinoma) - imaging and biopsy. 8) Aspiration pneumonia - history of improper feeding. 9) Viral infections (e.g., rabbit hemorrhagic disease) - acute death and hemorrhagic signs. 10) Fungal rhinitis (e.g., Aspergillus) - rare, culture and histopathology.

The diagnostic approach begins with a thorough history and physical examination, including assessment of respiratory effort and nasal discharge. 1) Triage: stabilize dyspneic rabbits with oxygen supplementation. 2) Physical exam: auscultation, palpation of trachea, and examination of nasal passages with an otoscope. 3) Sample collection: deep nasal swabs or tracheal wash for culture and PCR. In rabbits, sedation may be required; use midazolam (0.2-0.5 mg/kg IM) and butorphanol (0.1-0.5 mg/kg IM). 4) Blood work: CBC and serum biochemistry to assess systemic health. 5) Imaging: lateral and dorsoventral radiographs of the thorax and skull to evaluate for pneumonia and otitis. 6) Advanced imaging: CT or MRI if otitis media/interna is suspected. 7) Endoscopy: rhinoscopy and bronchoscopy to visualize lesions and collect samples. 8) Serology: ELISA for B. bronchiseptica antibodies, but not definitive. 9) PCR: confirmatory and species-specific. 10) Post-mortem: culture and histopathology if fatal.

Hematology: In acute infection, there may be leukocytosis with heterophilia (neutrophilia in mammals) and a left shift. In chronic cases, mild anemia may be present. Serum biochemistry: Usually within normal limits unless systemic disease; may show elevated globulins due to chronic infection. Fecal analysis: Not directly relevant, but may be performed to rule out gastrointestinal disease. PCR: Detection of B. bronchiseptica DNA from nasal swabs or tracheal wash is highly sensitive and specific. Serology: ELISA can detect antibodies, but does not distinguish between past and current infection. Culture: Isolation of B. bronchiseptica on MacConkey or Bordet-Gengou agar; colonies are small, smooth, and hemolytic. Urinalysis: Not typically helpful, but may be done to rule out renal disease. In rabbits, normal WBC is 5-12 x10^9/L, heterophils 20-75%, lymphocytes 30-80%.

Radiography: Thoracic radiographs (lateral and dorsoventral views) may show bronchial or alveolar patterns in cases of pneumonia. Skull radiographs (lateral, dorsoventral, and oblique views) can reveal increased opacity in the nasal cavity or tympanic bullae thickening in otitis media. Ultrasonography: Not commonly used for respiratory disease, but can evaluate lung consolidation or abscesses. CT: Provides detailed imaging of the nasal passages, tympanic bullae, and lungs; is the modality of choice for otitis media/interna and chronic rhinitis. MRI: Superior for soft tissue contrast, useful for evaluating brain involvement in otitis interna. Endoscopy: Rhinoscopy allows direct visualization of the nasal mucosa, and bronchoscopy can assess the trachea and bronchi; samples can be collected for culture and cytology.

Cytology: Nasal swabs or tracheal wash samples can be stained with Diff-Quik or Gram stain. Findings include neutrophils, macrophages, and extracellular and intracellular Gram-negative coccobacilli. Histopathology: In affected tissues, there is mucopurulent rhinitis, tracheitis, bronchitis, or bronchopneumonia. The epithelium shows loss of cilia, goblet cell hyperplasia, and infiltration of neutrophils and mononuclear cells. In chronic cases, there may be fibrosis and lymphoid hyperplasia. In otitis media, the tympanic bulla contains purulent exudate with inflammatory cells. Special stains (e.g., Giemsa) can highlight the bacteria. Immunohistochemistry can confirm the presence of B. bronchiseptica antigens.

Treatment involves supportive care and antimicrobial therapy. 1) Emergency stabilization: Provide oxygen supplementation (40-60%) via oxygen cage or mask. 2) Fluid therapy: Administer isotonic crystalloids (e.g., Lactated Ringer's solution) at 50-75 ml/kg/day SC or IV. 3) Assisted nutrition: If anorexic, syringe feed a critical care formula (e.g., Oxbow Critical Care) at 10-15 ml/kg q6h. 4) Antimicrobial therapy: Based on culture and sensitivity, but common choices include: enrofloxacin (10 mg/kg PO q12h), trimethoprim-sulfamethoxazole (30 mg/kg PO q12h), doxycycline (5 mg/kg PO q12h), or azithromycin (15 mg/kg PO q24h). Treatment duration is 2-4 weeks. 5) Nebulization: With saline or antibiotics (e.g., gentamicin 10 mg/ml) can help. 6) Anti-inflammatory: NSAIDs like meloxicam (0.3-1.0 mg/kg PO q24h) may reduce inflammation. 7) Nasal flushing: With warm saline to clear discharge. 8) Surgery: For abscesses or severe otitis media, surgical drainage or bulla osteotomy may be needed. 9) Husbandry: Improve ventilation, reduce ammonia, and minimize stress.

The prognosis for subclinical carriers is good, as they may never develop clinical disease. For mild upper respiratory infections, the prognosis is good with appropriate treatment, but recurrence is common. For severe pneumonia or otitis media, the prognosis is guarded to poor, especially if there is systemic involvement or concurrent pasteurellosis. Chronic rhinitis can be managed but not cured. Negative prognostic indicators include: severe dyspnea, cyanosis, anorexia, weight loss, and neurological signs. Response to treatment within 48-72 hours is a positive sign. Long-term management may be required for chronic cases.

Recheck examinations should be performed at 2 weeks, 4 weeks, and 8 weeks after initiation of treatment. At each visit, assess clinical signs, body weight, and respiratory rate. Repeat nasal swabs for culture or PCR at 4 weeks to evaluate clearance. If the rabbit is on long-term antibiotics, monitor for gastrointestinal stasis and perform fecal examinations. For chronic cases, monthly rechecks may be needed. Radiographs or CT should be repeated if clinical signs persist. Husbandry audits should be conducted to ensure optimal ventilation, temperature, and hygiene. In multi-rabbit households, treat all rabbits if one is infected, and quarantine new arrivals.

Pearls: 1) Rabbits are obligate nasal breathers, so any nasal discharge can cause severe respiratory distress; provide oxygen early. 2) Use a deep nasal swab (not just the nares) for culture to increase yield. 3) Nebulization with saline can help loosen secretions. 4) Enrofloxacin is effective but may cause cartilage damage in young rabbits; use with caution. 5) Always check for concurrent Pasteurella multocida infection. 6) Use a rabbit-safe sedative protocol for diagnostic procedures. Pitfalls: 1) Do not use corticosteroids in rabbits, as they can cause immunosuppression and exacerbate disease. 2) Avoid using amoxicillin or other penicillins in rabbits, as they can cause fatal enterotoxemia. 3) Do not rely solely on clinical signs; confirm with culture/PCR. 4) Do not stop antibiotics prematurely; treat for at least 2 weeks. 5) Do not forget to address environmental stressors, as they are key triggers.

Based on Carpenter's Exotic Animal Formulary (6th edition): 1) Enrofloxacin: 10 mg/kg PO q12h or 5-10 mg/kg IM q12h (but IM can cause tissue necrosis). 2) Trimethoprim-sulfamethoxazole: 30 mg/kg PO q12h. 3) Doxycycline: 5 mg/kg PO q12h. 4) Azithromycin: 15 mg/kg PO q24h. 5) Gentamicin: 2-4 mg/kg SC q24h (but nephrotoxic; use with caution). 6) Nebulization: Gentamicin 10 mg/ml in saline for 15-20 minutes q12h. 7) Meloxicam: 0.3-1.0 mg/kg PO q24h. 8) Fluid therapy: Lactated Ringer's solution at 50-75 ml/kg/day SC or IV. 9) Oxygen: 40-60% via mask or cage. 10) For otitis media, systemic antibiotics may not penetrate well; consider intratympanic injection or surgery.

Studies have shown that B. bronchiseptica is a common cause of respiratory disease in rabbits, often co-infecting with P. multocida. A study by Deeb et al. (1990) found that 60% of rabbits with rhinitis were positive for B. bronchiseptica. Treatment with enrofloxacin has been shown to be effective in reducing clinical signs, but does not eliminate the carrier state. A study by Rougier et al. (2006) demonstrated that a combination of enrofloxacin and doxycycline was more effective than either alone. Nebulization with gentamicin has been shown to improve clinical signs in chronic cases. The use of vaccines is not recommended in rabbits. The ABVP and ECZM guidelines recommend culture and sensitivity testing before antimicrobial therapy. Overall, the literature emphasizes the importance of husbandry and stress reduction in preventing clinical disease.