JPC SYSTEMIC PATHOLOGY
Signalment (JPC #4081936-02): domestic brown (fancy) rat
HISTORY: This 13-month-old female domestic brown (fancy) pet rat presented for acute weight loss, lethargy, behavioral change, and hair loss. At clinical presentation, the rat was dull but responsive and tachycardic.
HISTOPATHOLOGIC DESCRIPTION: Lung (2 sections): Affecting 40-50% of the two lung sections, bronchioles are markedly ectatic (bronchiectasis), compressing adjacent parenchyma. Bronchiolar lumens are variably occluded by an exudate composed of basophilic to eosinophilic cellular and karryorhectic necrotic debris, mineral, and inflammatory cells composed of viable and degenerate neutrophils, fewer large foamy macrophages, multinucleate giant cells (foreign body and Langhans type), lymphocytes, plasma cells, and mucin. This exudate often extends thorough the bronchiolar wall, infiltrating the peribronchiolar connective tissue and filling adjacent alveoli. Multifocally, bronchioles exhibit one or more of the following changes: discontinuous walls with loss or sloughing of the bronchiolar epithelium; attenuation with loss of cilia; or hyperplasia, piling up to 5 cell layers deep with goblet cell hyperplasia, and rare mitoses (regeneration). Multifocally, bronchiolar cilia are colonized by numerous lightly basophilic filamentous (0.5 x 8 um) bacilli. There are peribronchiolar and perivascular infiltrates of lymphocytes, plasma cells (mild BALT hyperplasia), and fewer foamy macrophages that often contain brown globular to granular pigment (hemosiderin). Multifocally within adjacent, less affected alveoli, there is a pale eosinophilic homogenous fluid (edema) admixed with increased numbers of foamy alveolar macrophages. Multifocally, alveolar septa are mildly expanded by edema and few macrophages. There is multifocal alveolar emphysema.
Warthin-Starry stain: There is heavy colonization of the ciliary borders of bronchiolar epithelial cells by slender, filamentous, argyrophilic bacteria that are 0.5 X 8 microns and are usually arranged parallel to the cilia.
MORPHOLOGIC DIAGNOSIS: Lung: Bronchopneumonia, necrosuppurative and lymphohistiocytic, chronic-active, multifocal to coalescing, moderate, with bronchiectasis, mineral, bronchiolar associated lymphoid hyperplasia, and many filamentous argyrophilic cilia-associated respiratory bacilli, domestic brown (fancy) rat, rodent.
ETIOLOGIC DIAGNOSIS: Cilia‑associated respiratory (CAR) bacillary bronchopneumonia
CAUSE: CAR bacillus
- Gram-negative, argyrophilic, filamentous, gliding bacteria
- Sequence analysis of the 16S rRNA gene demonstrates that rat isolates are related most closely to members of Flavobacterium and Flexibacter genera
- Colonize the ciliated epithelium of the respiratory tract of rats, mice, rabbits, goats, pigs, cattle, and wild deer
- Different bacteria, possibly of different genera may represent CAR bacilli in different mammalian hosts
- CAR bacillus can produce significant chronic respiratory disease, particularly in rats, but most rats with clinical disease are co-infected with one or more agents: Mycoplasma pulmonis, Sendai virus, coronavirus, Streptococcus pneumoniae, Corynebacterium kutscheri, Bordetella bronchiseptica, Klebsiella pneumoniae or Pasteurella pneumotropica
- Retrospective staining suggests that CAR bacillus may have been associated with outbreaks of respiratory disease for decades
- Direct contact
- Dam to offspring
- Colonization of the upper respiratory tract and airways
- CAR bacillus interdigitate between ciliaàinduce lymphocytic bronchitis and bronchiolitis, bronchietasis and abscesses
TYPICAL CLINICAL FINDINGS:
- Often inapparent or non-specific related to chronic respiratory disease (wheezing, dyspnea, hunched posture, weight loss, cyanosis)
TYPICAL GROSS FINDINGS:
- Noncollapsing lungs; cranioventral lung lobe consolidation
- Slightly elevated opaque yellow to gray foci tracking airways may be visible on the pleural surface
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Chronic suppurative bronchitis and bronchiolitis
- Bronchial and bronchiolar epithelial hyperplasia and hypertrophy, mucosal and peribronchial lymphoplasmacytic infiltrates, and neutrophilic exudation
- Mucopurulent alveolitis
- Can be subclinical with minimal or no lesions
- Slender filamentous bacteria present within the ciliated borders of bronchiolar epithelial cells, lying parallel to and among the cilia
- Gram-negative, argyrophilic (Warthin-Starry) filamentous bacilli
- Increased epithelial cell height, decreased Clara cells, increased goblet cells
- Decreased numbers of cilia on ciliated cells
- Bacilli among and parallel to cilia with one end of the organism on or near the cell membrane
- 15 - 0.35 um in diameter, 3.5 - 9.0 um long, fusiform, with a taper and rounded slightly knobbed ends
ADDITIONAL DIAGNOSTIC TESTS:
- IFA, ELISA, PCR
- Can be grown in cell culture, cell culture medium and embryonated hen’s eggs
- Mycoplasma pulmonis is the most important differential diagnosis for CAR bacillus; lesions may be identical, except for the lack of organisms visible among the cilia. Ulcerative bronchiolitis and mucopurulent alveolitis are not typically seen with Mycoplasma pulmonis
- Corynebacterium kutscheri – large Gram-positive colonies; multifocal suppurative pneumonia (abscesses) without bronchiectasis
- Streptococcus pneumoniae – large Gram-positive colonies; fibrinopurulent bronchopneumonia, pleuritis, pericarditis, meningitis
- Sendai virus (parainfluenza 1) – Usually subclinical; bronchitis, bronchiolitis, and alveolitis
- Rat coronavirus (sialodacryoadenitis virus and Parker's rat coronavirus): Produce lacrimal, salivary, and pulmonary lesions in young rats.
- Pneumonia virus of mice/pneumovirus (paramyxovirus) – Acute multifocal, non-suppurative vasculitis and interstitial alveolitis with necrosis
- Pneumocystis carinii – Diffuse interstitial pneumonia with alveolar flooding by an eosinophilic foamy or “honeycomb” exudate (edema + organisms) with fungal cysts containing fungal bodies
- There are distinct antigenic differences between CAR bacillus in different species
- Rabbit isolates have been shown to be related most closely to members of Helicobacter
- Wild urban rats (Rattus norvegicus and Rattus rattus) – significantly associated with rhinitis, submucosal and periglandular lymphoplasmacytic tracheitis
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents & Rabbits, 4th ed. Ames, IA: Blackwell Publishing Ltd; 2016:61, 63, 125, 133-134, 201, 272-273.
- Bergottini R, Mattiello S, Crippa L, Scanziani E. Cilia-associated respiratory (CAR) bacillus infection in adult red deer, chamois, and roe deer. J Wildl Dis 2005;41:459-462.
- Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier; 2015:547.
- Fox JG, Anderson LC, Otto GM, Pritchett-Corning KR, Whary MT. Laboratory Animal Medicine. 3rd ed. San Diego, CA: Academic Press; 2015:102-104, 173-74.
- Rothenburger JL, Himsworth CG, Clifford CB, Ellis J, Treuting PM, Leighton FA. Respiratory pathology and pathogens in wild urban rats (Rattus norvegicus and Rattus rattus). Vet Pathol. 2015;52(6):1210-1219.
- Schoeb TR, Lindsay JR. Cilia associated respiratory bacillus infection, rat, mouse, and rabbit. In: Jones T, Dungworth D, Mohr U, eds. Respiratory System: Monographs on Pathology of Laboratory Animals. 2nd ed. Berlin, Germany: Springer-Verlag; 1996:117-126.