Two-month-old male African green monkey (Chlorocebus aethiops sabaeus).This animal was found dead in the enclosure on the morning of the day of necropsy.

Gross Description:  

Approximately 75% of the left and 50% of the right lung lobes were replaced by randomly scattered, multifocal to coalescing, umbilicated, 3x3x3 mm to 1.5x3x2cm, firm, off-white to tan nodules, surrounded by 1-5 mm wide dark red zones. The remainder of the left lung was dark red, heavy and wet, and the lateral aspect was adhered to the adjacent costal pleura. Neither side collapsed upon opening the thoracic cavity, and the left lung sank in formalin.

Histopathologic Description:

Most of the architecture is effaced and replaced by fragmented eosinophilic cellular and karyorrhectic to streaming nuclear debris (necrosis), innumerable neutrophils, many degenerate, and large foamy macrophages. Colonies of small bacterial rods are prominent in areas of necrosis. The wall of the left bronchus is transmurally effaced by similar necrotic inflammatory exudate which extends into the lumen and also lies within adjacent bronchioles. The remaining alveolar spaces are filled with homogeneous proteinaceous material (edema fluid), frequent neutrophils and foamy alveolar macrophages. Connective tissue fibers surrounding the pulmonary vasculature are separated by clear space (edema).

Morphologic Diagnosis:  

Pneumonia, multifocal, chronic, severe, necrotizing with bacilli (consistent with Yersinia enterocolitica).

Lab Results:  

Aerobic bacterial culture positive for Yersinia enterocolitica.


Necrotizing pneumonia/Yersinia enterocolitica

Contributor Comment:  

Yersinia enterocolitica is a short gram-negative bacillus within the family Entero-bacteriaceae. It is an important food-borne pathogen that is commonly found in the gastrointestinal tract of humans and other species.  Pigs and rodents are sources of human infection, and transmission occurs through contaminated food and water. This pathogen most often produces necrotizing gastrointestinal lesions with large colonies of bacteria in humans and animals, but can also affect the urinary, respiratory, musculo-skeletal, integumentary and cardiovascular systems in humans.1,7.

Yersinia enterocolitica is classified into 6 biotypes and 57O group strains. Among the 6 biotypes, all except the 1A biotype (1B and 2-5) are pathogenic. 1B/O:8, 2/O:5, 2/O:9, 3/O:3 and 4/O:3 are most commonly isolated from humans. 1B/O:8 is considered the “new world” strain and is highly pathogenic to humans and predominantly present in the United States, while 4/O:3 and 2/O:9 are found in the Europe and Asia. Strain 4/O:3 has frequently been isolated from pigs and 1B/O:8 has been isolated from rodents.1,3,7

Pathogenic strains of Y. enterocolitica contain the virulence plasmid pYV/pCD which encodes Yersinia adhesin A (yadA), Ysc-Yop type III secretion system (TTSS), chromosomally encoded virulence genes ail, myfA, ystA, ysa, and the high pathogenicity island (HPI-) that aids in iron acquisition. The expression of virulence genes depends on temperature and calcium availability in-vivo. Virulence proteins produced by PYV plasmid resist phagocytic killing and complement mediated lysis of the bacteria by the host.

Successful infection begins with colonization of the distal small intestinal mucosa. Attachment and entry into the intestinal epithelial cells are facilitated by yadA and INV, respectively. Upon entering the epithelial cells the bacteria preferentially enter M cells in the Peyer’s patches where macrophages internalize them and transport them to the mesenteric lymph nodes (MLN). Yersinia bacteria multiply within the macrophages and also extracellularly in the lymphoid organs leading to abscess formation, often bacteremia and frequently, hepatitis. 1,3,7

This case was the first in an outbreak involving more than 20 Y. enterocolitica fatalities in 2015 – 2016, and was unique in that the pneumonia occurred in the absence of intestinal and MLN lesions. The finding of necrotizing tracheitis and large airway orientation in the lung suggests a respiratory route of infection. Some reports in humans have also suggested primary infection by inhalation, without gastrointestinal involvement.2,9

JPC Diagnosis:  

Lung: Pneumonia, necrosuppurative, multifocal to coalescing, subacute, severe, with fibrin thrombi, hemorrhage, edema, and numerous colonies of coccobacilli, African green monkey, Chlorocebus aethiops sabaeus.

Conference Comment:  

The contributor provides a rare case of pneumonia caused by Yersinia enterocolitica in an African green monkey, as well as an excellent discussion of the virulence factors and pathogenesis of the bacterium. Despite the highly usual presentation, this case illustrates the characteristic appearance of the gram-negative coccobacilli forming multifocal to coalescing bacterial microcolonies surrounded by intense infiltrates of viable and degenerate neutrophils and necrotic cellular debris filling and replacing pulmonary architecture.  Yersinia sp. Micro-colonies are readily distinguishable from other large colony-forming bacteria such as Actinomyces, Actinobacillus, Coryne- bacterium, Staphylococcus and Streptococcus spp. Other species of Yersinia (pseudotuberculosis and pestis) have the same histologic appearance in tissue section as is present in this case. Speciation of the bacteria requires culture or bacterial isolation.1,9

Yersinia enterocolitica has a worldwide distribution and affects a many different animal species and humans.1,2,7,9 As mentioned by the contributor, the most common mode of transmission is caused by foodborne outbreaks in humans. In nonhuman primates, infections are typically acquired by the fecal-oral route.8,9 The organism can be shed in the feces by asymptomatic animals in the collection, as well as by rodents and birds in the environment where it can survive and grow at low temperatures. Disease is often secondary to stress, poor nutrition, environmental flooding, and cold weather.9 The contributor suggests that the route of infection for this animal is via inhalation of the organism, perhaps via aerosolized feces, causing the development of necrotizing tracheitis and pneumonia without gastrointes-tinal lesions.

Many conference participants noted the presence of numerous large fibrin thrombi within peribronchial veins and lymphatic vessels. Gram-negative bacteria, such as Yersinia spp, commonly cause sepsis and its associated coagulopathy. During gram-negative septic shock, lipo-polysaccharide (LPS, endotoxin) induces increased tissue factor (TF) and factor XII expression.4,5,6 TF (factor III) then forms a complex with plasma factor VII as part of the extrinsic coagulation pathway. This complex activates factor X of the common pathway and factor IX of the intrinsic pathway, leading to the formation of thrombin (factor II) which generates fibrin from fibrinogen (factor I). Fibrin is cross-linked and polymerized via factor XIII and deposited as a fibrin clot. During sepsis, procoagulant activity predominates over anticoagulation and fibrinolysis due to inhibition of tissue factor pathway inhibitor (TFPI), thrombomodulin, and protein C as well as activation of plasminogen activator inhibitor (PAI-1), and previously mentioned TF.5,6 This leads to disseminated intravascular coagulation (DIC) and exuberant fibrin deposition. DIC eventually consumes critical blood-clotting factors leading to hemorrhage and shock.5,6 However, a recent study in mice has shown that fibrin can also perform critical protective functions during infection with Yersinia enterocolitica. These studies suggest that fibrin may be an attempt by the host to physically trap bacteria limiting dissemination, in addition to facilitating the recruitment and activation of neutrophils and macrophages within infected tissues via interleukin 6 (IL-6) and monocyte chemotactic protein-1 (MCP-1).5 In fact, mice treated with the anticoagulant warfarin prior to inoculation with Yersinia enterocolitica had a markedly higher systemic bacterial burden and shortened survival time compared to untreated mice.5


1. Galindo CL, Rosenzweig JA, Kirtley ML, Chopra AK. Pathogenesis of Y. enterocolitica and Y. pseudo-tuberculosis in human yersiniosis. J Pathog 2011; 2011:182051.

2. Hosaka S, Uchiyama M, Ishikawa M, Akahoshi T, Kondo H, Shimauchi C, et al. Yersinia entero-colitica serotype O:8 septicemia in an otherwise healthy adult: analysis of chromosome DNA pattern by pulsed-field gel electrophoresis. J Clin Microbiol 1997; 35(12):3346-3347.
3. Kay BA, Wachsmuth K, Gemski P, Feeley JC, Quan TJ, Brenner DJ. Virulence and phenotypic characterization of Yersinia enterocolitica isolated from humans in the United States. J Clin Microbiol 1983; 17(1):128-138.
4. Kumar V, Abbas AK, Fausto N. Hemodynamic Disorders, Thromboembolic Disease, and Shock. In: Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA:Elsevier Saunders; 2015:117-134.
5. Luo D, Szaba FM, Kummer LW, et al. Protective roles for fibrin, tissue factor, plasminogen activator inhibitor-1, and thrombin activatable fibrinolysis inhibitor, but not factor XI, during defense against the gram-negative bacterium Yersinia enterocolitica. J Immunol. 2011; 187(4):1866-1876.
6. Mosier DA. Vascular disorders and thrombosis. In: McGavin, MD, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO:Elsevier; 2017:51-72.
7. Sabina Y, Rahman A, Ray RC, Montet D: Yersinia enterocolitica: Mode of transmission, molecular insights of virulence, and pathogenesis of infection. J Pathol. 2011; 2011:429069.
8. Simmons J, Gibson S. Bacterial and mycotic disease of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, Morris T eds. Nonhuman Primates in Biomedical Research: Diseases. Vol 2. 2nd ed. Philadelphia, PA: Elsevier; 2012:138-140.
9. Wong KK, Fistek M, Watkins RR. Community-acquired pneumonia caused by Yersinia enterocolitica in an immunocompetent patient. J Med Microbiol 2013; 62(4):650-651.
10. Uzal FA, Plattner BL, Hostetter JM. Alimentary system In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed.  Philadelphia, PA: Elsevier; 2016:176-177.

Click the slide to view.

4-1. Lung, African green monkey.

4-2. Lung, African green monkey.

4-3. Lung, African green monkey.

4-4. Lung, African green monkey.

4-5. Lung, African green monkey.

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