Adult male African green monkey (Cercopithecus aethiops)This single-housed nonhuman primate was on a research protocol but had not been exposed to an agent. The monkey had not been eating well for several days. One morning, caretakers noted the monkey had dark tarry feces and respiratory difficulty. Moist rales were auscultated bilaterally. Radiographs were taken and showed a gasfilled stomach and intestines and a cloudy hemithorax. Rule outs were gastric dilatation and intestinal intussusception. The monkey was treated by passing an orogastric tube to relieve the gas and giving IV fluids, furosemide, and enrofloxacin. Barium was also administered via the orogastric tube for further radiographs. The animal was found dead in the cage a couple of hours after treatment began.

Gross Description:  

The monkey was in thin body condition (body condition score of 2/5) with small amounts of subcutaneous and abdominal fat and severe dehydration. There was a self-bite wound on the left lateral aspect of the cranial tongue. The nasal passages were mildly edematous and there was a small amount of clear mucus present. There was focally extensive subcutaneous and muscular bruising over the right cranial skull and mild subcutaneous edema of the ventral neck. The lungs were non-collapsed and consolidated with extensive multifocal to coalescing dark red to pale firm areas and multifocal pleural adhesions to the thoracic wall and the diaphragm. The pericardium was moderately thickened. The liver was diffusely dark and congested with multifocal pitting over all lobes. The gallbladder was markedly distended by clotted blood, fibrin, and bile. The stomach was moderately distended by white fluid (barium) and gas. The upper half of the small intestine contained a moderate amount of barium-stained digesta and the lower half contained a moderate amount of dark green fluid digesta. The cecum contained abundant dark green soft material. The colon was empty except for a small amount of gas. There were no significant gross findings in any of the other organs observed.

Histopathologic Description:

Diffusely affecting the section of lung, bronchi, bronchioles, and alveoli are filled by an exudate composed of abundant fibrin, neutrophils that are often degenerate, hemorrhage, and eosinophilic proteinaceous edema fluid and fewer macrophages. Normal tissue architecture is disrupted and displace by distinct multifocal to coalescing abscesses composed of abundant necrotic debris, degenerate neutrophils, fibrin, and hemorrhage. Multifocally the bronchial and bronchiolar epithelium is hyperplastic. There is multifocal mild to moderate perivascular edema, fibrin, and hemorrhage with occasional neutrophils. The pleura is expanded multifocally by fibrin, hemorrhage, and hyperplastic mesothelial cells. Numerous cilia-associated gram-negative coccobacilli are noted with the Brown-Hopps stain.

Morphologic Diagnosis:  

Lung: Bronchopneumonia, fibrinosuppurative and necrohemorrhagic, diffuse, severe, with fibrinous pleuritis and gram-negative cilia-associated coccobacilli.

Lab Results:  

Bordetella bronchiseptica was cultured from the lung.


Bordetella bronchiseptica

Contributor Comment:  

Other notable histopathologic findings in this animal included a severe hemorrhagic and fibrinosuppurative cholecystitis, a diffuse moderate subacute periportal hepatitis with bile stasis, a mild acute tracheitis, and numerous cecocolic oxyurids (pinworms) with minimal granulomatous typhlitis and colitis.

Bordetella bronchiseptica is a small gram-negative coccobacillus of the respiratory tract in numerous animal species. Along with other factors, it is the cause of nonprogressive atrophic rhinitis in pigs as well as bronchopneumonia and is considered the primary cause of infectious tracheobronchitis in dogs.(1) It is also considered a major cause of respiratory disease in guinea pigs.(2) Bordetella bronchiseptica is an occasional opportunistic respiratory pathogen causing suppurative bronchopneumonias in several other species including rabbits, rats, foals, cats, and sea otters.(1-3) In nonhuman primates, Bordetella bronchiseptica has been documented as a cause of pneumonia and upper respiratory infections in prosimians (bushbabies), new world primates (marmosets and squirrel monkeys), and old world primates (African green monkeys and rhesus macaques).(4-5) Nonhuman primates can be naturally infected with Bordetella pertussis and develop whooping cough-like disease also.(5) Bordetella is transmitted by aerosolization or fomites and the bacteria adhere to the ciliated epithelium of the upper respiratory tract. Interspecies transmission can occur. The bacteria evade the immune defenses via several virulence factors (hemolysin, lipooligosaccharide, and tracheal cytotoxin) and replicate among the cilia. Ciliostasis with decreased mucociliary clearance and host cell death occurs.(1) Bronchopneumonia typically occurs in animals with weakened pulmonary defenses due to age, stress, viruses or other infectious agents, or other predisposing factors.(5) Once the defenses are breached, the bacteria can enter the lung and the inflammatory process begins centered on the bronchioles, then spreads upward into the bronchi and downward into the alveoli. The inflammatory exudate collects in the airways and tends to spread centrifugally and exudate can be coughed up and aspirated into other lobules, continuing the process. The cytokines released from pulmonary injury cause rapid recruitment of neutrophils and alveolar macrophages and cause increased vascular permeability resulting in leakage of edema fluid, fibrin, and sometimes hemorrhage.(6)

Other ruleouts considered at necropsy for the bronchopneumonia in this case included Streptococcus pneumoniae or other Streptococcus spp, Klebsiella pneumoniae, Mycoplasma spp, Pasteurella spp, and viruses such as influenza, measles, and cytomegalovirus. An interesting finding in this animal was the hemorrhagic and fibrinosuppurative cholecystitis, which is typically associated with gram-negative agents like Salmonella or E. coli. It is possible the cholecystitis was caused by the Bordetella infection but since cultures were not taken of the gallbladder, this cannot be definitively proven.

JPC Diagnosis:  

Lung: Pneumonia, bronchointerstitial, fibrinosuppurative and necrotizing, diffuse, severe, with hemorrhage and numerous cilia-associated coccobacilli.

Conference Comment:  

The typical gross appearance of pulmonary bordetellosis in primates is a purulent bronchopneumonia with severe pulmonary consolidation and fibrinopurulent pleuritis and pericarditis. Other reported gross findings include mucopurulent exudate within the nares, nasal passages, trachea and often tympanic bullae; middle ear infection; and meningitis(5).

As mentioned by the contributor, Bordetella spp. have several important virulence factors. Adenylate cyclase toxin, known as hemolysin, is a member of the RTX (repeats in toxin) family of toxins and is secreted by the bacteria. The RTX domain forms ion-permeable pores in host cell membranes and allow the transfer of the adenylate cyclase domain. Increased cAMP production occurs after entry of the toxin into leukocytes, which greatly inhibits phagocytosis and the oxidative burst. Tracheal cytotoxin is secreted by the bacteria and stimulates host cells to secrete nitric oxide which induces ciliostasis and apoptosis of ciliated epithelial cells. Dermonecrotic toxin (DNT) is an intracellular toxin that is vasoconstrictive and cytotoxic and is released upon bacterial lysis; it shares structural and functional homology with cytotoxic necrotizing factor 1 (CNF1) of E. coli.

Filamentous Hemagglutinin (FHA), pertactin and fimbriae are adhesive proteins that allow attachment of the bacteria to ciliated epithelial cells. Lipooligosaccharide is a lipopolysaccharide with endotoxin activity found in the bacterial cell wall. The Bordetella virulence gene (Bvg) operon regulates the expression of most of these virulence factors(1,6).

Although Bordetella is usually a co-pathogen in pigs, cattle, dogs and cats, it is the primary agent in several important veterinary diseases. Bordetella bronchiseptica, as a primary agent, can cause severe pneumonia in guinea pigs(2). B. avium is the primary agent of turkey coryza. B. avium can also infect several species of fowl, psittacines, ratites, finches and domestic songbirds, and in cockatiels, it has been associated with lockjaw syndrome, which is a respiratory disease with temporomandibular rigidity(8). B. hinzii, a commensal organism in the upper respiratory tract of poultry and an opportunistic pathogen in immunocompromised humans, has been identified as the causative agent of rhinitis, tracheitis, and bronchopneumonia in a rabbit and a B6 mouse(7).


1. Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmers Pathology of Domestic Animals. 5th ed., Vol. 2. New York, NY: Elsevier; 2007:589-590, 632, 638-639, 650.

2. Percy DH, Barthold SW. Pathology of Laboratory Rodents and Rabbits. 3rd ed. Ames, IA: Blackwell Publishing; 2007:141-142, 226-228, 267-268.

3. Staveley CM, Register KB, Miller MA, et al. Molecular and antigenic characterization of Bordetella bronchiseptica isolated from a wild southern sea otter (Enhydra lutris nereis) with severe suppurative bronchopneumonia. J Vet Diagn Invest. 2003;15:570-574.

4. Gibson SV. Bacterial and mycotic diseases. In: Bennett BT, Abee CR, Henrickson R, ed. Nonhuman Primates in Biomedical Research Diseases. San Diego, CA: Academic Press; 1998:75-76.

5. Osborn KG, Lowenstine LJ. Respiratory diseases. In: Bennett BT, Abee CR, Henrickson R, ed. Nonhuman Primates in Biomedical Research Diseases. San Diego, CA: Academic Press; 1998:294-295.

6. L³pez A. Respiratory system, mediastinum, and pleurae. In: McGavin MD, Zachary JF, ed. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Elsevier; 2012:458-9, 472-3, 480, 499, 520-1, 524-5.

7. Hayashimoto N, Yasuda M, Goto K, Takakura A, Itoh T. Study of a Bordetella hinzii isolate from a laboratory mouse. Comp Med. 2008 Oct;58(5):440-6.

8. Charlton BR, et al. Avian Disease Manual. 6th edition. American Association of Avian Pathologists. 2006:71-3.

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