JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

August 2023

P-B07

 

Signalment (JPC# 1361378): A Mangabey (Cercocebus sp.)

 

HISTORY: This monkey died shortly after arrival from the supplier.

 

HISTOPATHOLOGICAL DESCRIPTION: Lung: Diffusely, alveolar and bronchiolar lumina are filled by abundant hemorrhage, variably organized fibrin, edema, moderate numbers of viable and degenerate neutrophils, lymphocytes, and plasma cells, and scant karyorrhectic debris (necrosis). Multifocally, similar inflammatory infiltrates efface bronchial/bronchiolar walls and alveolar septa. Rarely, alveolar septa display a loss of differential staining with retention of cellular architecture (coagulative necrosis) or are lost (alveolar septal necrosis). Bronchiolar epithelial cells are cuboidal to attenuated with absence of cilia or are lost. Multifocally, peribronchiolar and perivascular connective tissue is expanded up to 5x normal by hemorrhage, fibrin, and edema. Pulmonary vessels frequently have discontinuous endothelium, and the tunica intima and tunica media are often expanded by variably organized fibrin, edema, low numbers of nondegenerate and degenerate neutrophils, and necrotic debris (necrotizing vasculitis) associated with abundant perivascular hemorrhage, fibrin, and edema. 

 

MORPHOLOGIC DIAGNOSIS: Lung: Bronchopneumonia, fibrinohemorrhagic and necrosuppurative, acute, diffuse, severe, Mangabey (Cercocebus sp.), nonhuman primate.

 

ETIOLOGIC DIAGNOSIS: Streptococcal pneumonia

 

CAUSE: Streptococcus pneumoniae

 

ETIOLOGY SYNONYMS: Diplococcus pneumoniae, Pneumococcus pneumoniae

 

GENERAL DISCUSSION:

• Gram-positive, 1 µm diameter, encapsulated, lancet-shaped, coccoid bacteria occurring in pairs and short chains, α-hemolytic
• Most common cause of bacterial meningitis in nonhuman primates, and a major cause of pneumonia
• Most common cause of community-acquired acute pneumonia in humans
• Zoonotic and reverse zoonotic (anthropozoonotic): Human reservoir carriers, normal flora in oropharynx. Some documented NHP carriers, but it is not normal flora of NHP’s

 

PATHOGENESIS:

• Stress-related factors, viral infections (respiratory syncytial virus, parainfluenza 3, human metapneumovirus, influenza virus) and immunosuppression predispose all ages of nonhuman primates to infection and disease
• Transmitted by aerosolization of bacteria into the upper respiratory tract and middle ear or mouth; bacterial and viral co-infections common
• Respiratory virus or stress as predisposing factor(s) > aerosolization or activation of resident oral/nasal organisms > secondary upper respiratory bacterial infection > fluid exudate facilitates spread of organisms and also interferes with phagocytosis > pneumococci adhere to a target receptor on epithelial cells > invasion > either/or:
  • Pneumococcal bacteremia via lymphatics > tracheobronchial and mediastinal lymph nodes > systemic circulation via thoracic duct (if not phagocytized in the nodes)  
  • Paranasal sinus infection > subarachnoid space > cerebral venous sinuses via the arachnoid villi

• Splenic macrophages important in bacterial phagocytosis
• Virulence factors:
  • Polysaccharide capsule: Most important virulence factor, mediates resistance to phagocytosis by neutrophils; more than 95 capsular polysaccharide types
  • Pneumolysin: Cytosolic bacterial protein, inserts into target cell membranes resulting in cell lysis
  • Quorum sensing used to turn on genetic transformation
  • Numerous serotypes allow immune evasion
  • Cell wall adhesin proteins facilitate mucosal membrane attachment to fibronectin and invasion.
  • Alteration of antibiotic binding site “penicillin-binding proteins” enables antibiotic resistance

 

TYPICAL CLINICAL FINDINGS:

• Illness characterized by low morbidity and high mortality with rapid progression to death, often without prodromal clinical signs
• Disease syndromes include meningitis, fibrinopurulent bronchopneumonia; bacteremia; fibrinopurulent polyserositis; suppurative inflammation of the middle or inner ear, joints, peritoneum, lungs, air sacs, heart, kidneys, and panophthalmitis
• Pneumonia: Dyspnea, cough, cyanosis, nasal discharge
• Meningitis: Ataxia, pyrexia, flaccid paralysis of legs, circling, clonic seizures, convulsions, pupillary constriction, nystagmus, head pressing, nuchal rigidity, blindness, coma, rapid mortality
• Clinical Pathology:
  • Neutrophilic leukocytosis with left shift
  • Spinal fluid: Elevated WBC count and elevated protein levels, free or phagocytosed diplococci in CSF

 

TYPICAL GROSS FINDINGS:

• Lungs: Lobular to lobar suppurative and fibrinous bronchopneumonia that may progress to lobar consolidation; dark red to gray hepatization of affected lobes (usually ventral) and variable amounts of fibrin on the pleura, pulmonary edema; congestion; secondary pleuritis and epicarditis possible
• CNS: Marked cerebral and cerebellar meningeal congestion; dull, thickened and opaque leptomeninges; white, yellow or gray-yellow purulent exudate filling cerebral subarachnoid space, sulci and/or ventricles; meningeal petechiation; in severe cases lesions may extend to spinal cord

• Other sites: Suppurative peritonitis, suppurative arthritis, polyserositis, panophthalmitis, purulent otitis interna, sinusitis, tonsilitis, pleuritis and epicarditis

• Arterial thrombosis secondary to vasculitis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lungs: Varies from serous inflammation with congestion to exudative bronchopneumonia; perivascular neutrophilic, histiocytic, and lymphocytic infiltrates; edema; ectatic lymphatics, occasional pulmonary arterial thrombosis
• CNS: Fibrinopurulent meningoencephalitis; necrotizing vasculitis, possibly with thrombosis; encephalitis with encephalomalacia and hemorrhage; perivascular cuffing; neuronal necrosis and mineralization; astrocytosis

• Other sites: Multifocal purulent inflammation in the heart or kidney; septicemia

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

Pneumonia:

Meningitis in nonhuman primates:

 

COMPARATIVE PATHOLOGY:

Streptococcus pneumoniae infections in other species:

• Rats: Fibrinopurulent bronchopneumonia and pleuritis; rhinitis; sinusitis; conjunctivitis; pericarditis; peritonitis; meningitis; otitis; periorchitis; and embolic suppurative hepatic, splenic and renal lesions
• Guinea pig: Bronchopneumonia; fibrinopurulent pleuritis, pericarditis, peritonitis
• Hamsters: Bronchopneumonia, respiratory disease, otitis
• Calves: Acute splenitis, polyarthritis, meningitis

 

References:

1. Abee CR, Mansfeld K, Tardiff S, Morris T.  Nonhuman Primates in Biomedical Research, Volume 2: Diseases. San Diego, CA: Academic Press; 2012:107-109,447, 452-453, 742.
2. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents & Rabbits. 4th ed. Ames, IA: Blackwell Publishing Ltd; 2016:144-145,186,230.
3. Cantile C, Youssef S. Nervous System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:354. 
4. Davis KL, Gonzalez O, Kumar S, Dick EJ Jr. Pathology Associated With Streptococcus spp. Infection in Baboons (Papio spp.). Vet Pathol. 2020;57(5):714-722.
5. Durham AC, Boes KM. Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:853.
6. Frank KM, McAdam AJ. Infectious diseases. In: Kumar V, Abbas AK, Aster JC. eds. Robbins and Cotran Pathologic Basis of Disease. 10th ed. Philadelphia, PA: Elsevier Saunders; 2021:360-361.
7. Lopez A, Martinson SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:585.
8. Lowenstine LJ, McManamon R, Terio KA. Apes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:387, 392.
9. Matz-Rensing K, Lowenstine LJ. New World and Old World Monkeys. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:363-364.
10. Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:199. 

 

 

Click the slide to view.

---