JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

August 2023

P-B13

Signalment (JPC #2288032): 5-year-old male Rhesus monkey

HISTORY: This single-housed, SRV and SIV negative Rhesus monkey was depressed for 3 days after anesthesia. On the 4th day, the animal was found down in his cage, dehydrated, and in shock. All lung lobes appeared firm and consolidated, and there were multiple purulent and hemorrhagic foci on the pleural surfaces.

HISTOPATHOLOGIC DESCRIPTION: Lung: Alveolar and bronchiolar lumina are diffusely filled with viable and degenerate neutrophils, macrophages, eosinophilic beaded to fibrillar material (fibrin), and eosinophilic cellular and karyorrhectic debris (necrosis). Within alveolar lumina and surrounding blood vessels, there are abundant extracellular and intrahistiocytic 1 x 3 µm regularly spaced bacilli surrounded by a 1 µm clear halo (capsule). Alveolar septa are often discontinuous and replaced with fibrin and cellular debris (septal necrosis). Bronchiolar epithelial cells are frequently swollen with vacuolated cytoplasm (degeneration), attenuated, sloughed into the lumen, or lost, and the bronchiolar wall is thin and frequently contains previously described inflammatory cells. Vessel walls are diffusely expanded by abundant clear space (edema), fibrin, and few of the previously described inflammatory cells, and there is often marked perivascular hemorrhage. Less frequently, vessel walls contain abundant fibrin and inflammatory cells (fibrinoid vascular necrosis) and frequent fibrin thrombi that occlude the lumens. Multifocally, the pleura is moderately expanded by similar inflammatory cells, hemorrhage, fibrin, and edema.

MORPHOLOGIC DIAGNOSIS: Lung: Bronchopneumonia, fibrinosuppurative, necrotizing, acute, diffuse, severe, with vasculitis, fibrinous pleuritis, and numerous intrahistiocytic and extracellular encapsulated bacilli, Rhesus monkey (Macaca mulata), nonhuman primate.

ETIOLOGIC DIAGNOSIS: Pneumonic klebsiellosis

CAUSE: Klebsiella pneumoniae

GENERAL DISCUSSION:

A Gram-negative, non-motile, facultative anaerobic, heavily encapsulated, non- spore forming, non-flagellated, 0.3-1.0 x 0.6-6.0µm bacillus of the Enterobacteriaceae family that occurs singly, in pairs, and in short chains
Component of normal fecal and oral flora in Old and New World Monkey species, humans, and other animals; also live freely in soil and water
Important cause of severe pneumonia, meningitis, peritonitis, cystitis, septicemia, and air sacculitis
Significant cause of morbidity and mortality in owl monkey and chimpanzee colonies
Highly virulent hypermucoviscosity (HMV) phenotype can cause localized or disseminated infections in healthy hosts; predominantly associated with African green monkeys; rhesus macaques can be unaffected carriers
Multidrug resistant strains have contributed to increased prevalence of infection (Cole, JVDI 2022)

PATHOGENESIS:

Transmission: Oral or respiratory route
Most strains are opportunistic pathogens and disease is associated with shipping, quarantine, and overcrowding or otherwise debilitated by stress or concurrent disease, especially in the infants and juveniles
Colonization by Klebsiella is prevented by normal flora; any disruption (i.e. antibiotic therapy) can result in overgrowth or colonization
Many pathogenic strains possess fimbriae (pili) that act as adhesins, permitting colonization of mucosal surfaces and inhibiting phagocytosis and intracellular killing
The thick polysaccharide capsule (K antigen) creates a barrier that prevents opsonization and phagocytosis
The HMV phenotype virulence due to capsular serotypes (K1 and K2) that carry genes MagA (mucoviscosity-associated gene/K1 specific capsular polymerase gene) and rmpA (regulator of mucoid phenotype) which make the bacteria more invasive and highly resistant to phagocytosis
Klebsiella pneumoniae strains can produce carbapenemase (KPC) conferring antibiotic resistance; KPC can be isolated from other Enterobacterales, which has been reported in people and dogs (Cole, JVDI 2022)

TYPICAL CLINICAL FINDINGS:

Pneumonia, enteritis, and septicemia with non-specific signs and varying severity
Early signs: Coughing, sneezing, facial edema, serous to mucopurulent nasal discharge
Severely affected animals are febrile, depressed, anorectic, and markedly dyspneic
In septicemia, the clinical course is rapid, and animals may die suddenly
High case fatality (90%) in untreated patients

TYPICAL GROSS FINDINGS:

Often diffuse bronchopneumonia +/- abscessation, consolidation, and pleuritis
Fibrinopurulent exudates on pleura, meninges, and peritoneum
Liver may be enlarged, firm, and mottled tan or purple
HMV phenotype in African green monkeys causes multisystemic abscessation (including in abdomen), peritonitis, mesenteric adhesions

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Suppurative bronchopneumonia of variable severity, focal or diffuse, +/- necrosis, abscessation; exudate fills alveoli and plugs smaller bronchioles
Bacteria that are evenly-spaced with a thick, clear capsule
Multifocal atelectasis, congestion, alveolar hemorrhage, and edema
Suppurative meningitis in some septicemic animals

ULTRASTRUCTURAL FINDINGS:

    Capsule has a fibrous appearance on EM with slender thread-like capsular fibrils at regular intervals

ADDITIONAL DIAGNOSTIC TESTS:

    Bacterial culture/isolation: colonies appear mucoid; HMV phenotype has a positive string test (an inoculation loop pulled through the bacterial colony forms a long mucoid string of more than 5 mm) 

DIFFERENTIAL DIAGNOSIS:

Bacterial pneumonia in NHPs:

Mixed infections are common (especially with Pasteurella multocida)
Escherichia coli, Streptococcus pneumoniae, Bordetella bronchiseptica, Pasteurella multocida, and Hemophilus influenzae (differentiate by culture)

COMPARATIVE PATHOLOGY:

All species: Urinary tract infection
Horses: Second most commonly isolated cause of bronchopneumonia in recent study of non-racing horses in California; most common cause was Streptococcus equi ssp. zooepidemicus. (Rahman, JVDI 2022)
Apes and owl monkeys: Air sacculitis
Cattle and swine: Mastitis; can progress to fatal endotoxic shock in cows
Horses: Metritis, infertility, and abortion; neonatal septicemia in foals with failure of passive transfer
Neonatal swine: Rare cause of villous atrophy and diarrhea; septicemia
Lab animals:
1. Rabbits: K. oxytoca and K pneumonia have been isolated in outbreaks of severe hemorrhagic enterotyphlitis in kits
2. Guinea pigs: K. pneumoniae epizootics occur rarely; cause septicemia and/or acute necrotizing bronchopneumonia; K. oxytoca also isolated occasionally
3. Mice: Normal flora; K. oxytoca and K pneumoniae can cause a wide range of opportunistic infections
4. Rats: Normal flora; can cause abscesses in lymph nodes and kidneys and suppurative rhinitis
California sea lions: HMV phenotype reported to cause severe purulent bronchopneumonia and fibrinonecrotic pleuritis with pyothorax; New Zealand sea lion pups also develop bacteremia, meningitis, synovitis, abscesses
K. pneumoniae has been reported to cause fin rot in rainbow trout

REFERENCES:

Cole SD, Rankin SC. Characterization of 2 Klebsiella pneumoniae carbapenemase-producing Enterobacterales isolated from canine rectal swabs. J Vet Diagn Invest. 2022; 34(2): 306-309.
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Fahey MA, Westmoreland SV. Nervous system disorders of nonhuman primates and research models. In: Abee CR, Mansfield K, Tardiff S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases. Vol 2. 2^nd ed. San Diego, CA: Academic Press; 2012:744.
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