Signalment:  

1-year-old male quarter horse (Equus caballus).The body of a 1-year-old quarter horse colt was submitted for postmortem examination. The animal had been observed the day before and was reported to be healthy. The next day the colt was found dead with no evidence of a struggle. No other animals on the premises were sick.

Gross Description:  

Received the body of a 1-year-old, bay, quarter horse colt for postmortem examination. The body was in good nutritional condition and there was evidence of dehydration. Mild autolysis was noted. Over the left side and dorsal aspect of the thorax, there were locally extensive areas of subcutaneous hemorrhage and edema. Within the thoracic cavity, there were multifocal to coalescing ecchymoses located immediately below the costal pleura. The trachea contained a moderate amount of stable white froth consistent with pulmonary edema. The lungs had failed to completely collapse and multifocal areas of hemorrhage were noted on the pleural surface and within the pulmonary parenchyma. Foci of pulmonary hemorrhage measured up to 0.8 cm in diameter. Within the pericardial sac approximately 10 ml of serosanguinous fluid was noted. On the epicardial surface of the heart, there were innumerable petechiae. On the endocardial surface, extensive ecchymotic hemorrhage was noted in both the right and left ventricles. On the capsular surface of the spleen, numerous petechiae were noted. The liver was diffusely congested. Bilaterally the renal medulla was dark red and congested. Multifocally and randomly distributed within the renal cortices there were numerous, 1-3 mm, white foci. 

Histopathologic Description:

Kidney: Randomly scattered within the cortex and occasionally extending into the medulla, there is a severe inflammatory process characterized by the presence of numerous microabscesses. The inflammation frequently centers on and effaces the glomeruli and is seen to extend into the adjacent tubules and interstitium. Glomeruli, which remain intact, are characterized by congestion, and numerous bacterial emboli and fibrin microthrombi within the glomerular capillaries. This is further accompanied by necrosis, hemorrhage and marked neutrophilic inflammation resulting in the formation of abscesses. In some areas the bacterial colonies and neutrophilic inflammation extend into the adjacent proximal tubules and there is degeneration and necrosis of the tubular epithelium. Focally suppurative inflammation extends into the renal capsule (not present in every slide). The bacterial colonies are large and are characterized by a myriad of 1X2 μm coccobacilli. While bacterial emboli are most prominent within glomerular capillaries they are also observed within intertubular capillaries. Marked medullary congestion is a feature. Gram stain reveals the presence of innumerable gram-negative coccobacilli.

Similar bacterial emboli were noted in many other organs including the liver, lung, spleen, lymph nodes, brain and spinal cord consistent with septicemia (not shown in this slide).

Morphologic Diagnosis:  

Nephritis, suppurative, embolic, acute, severe with intralesional coccobacilli.

Lab Results:  

4+ Actinobacillus equuli isolated from the kidney.

Condition:  

Actinobacillus equuli

Contributor Comment:  

Actinobacillosis, also known as sleepy foal disease, is an acute and highly fatal septicemia of newborn foals caused by Actinobacillus equuli. In many countries it is the most important cause of equine neonatal deaths.(6,9) A. equuli is a small, nonmotile, gram-negative, pleomorphic rod. This is a diverse species with at least 28 different antigenic groups.(2) Certain strains of A. equuli form part of the normal flora of the gastrointestinal and respiratory tracts of horses.(3,4) There is a high degree of strain variability within horse populations and within individual horses over time. It is currently unknown whether there are specific strains of A. equuli with greater virulence for foals and/or adult horses or whether such strains are common inhabitants of the equine gastrointestinal and respiratory tracts.(4)

Typically actinobacillosis is a disease of newborn foals and the pathogenesis of the infection remains speculative. It is postulated that one of the main sources of infection is from the gastrointestinal or respiratory tracts of the mare, although some foals may be infected in utero via placental transmission of the organism resulting in abortion. The majority of foals are likely infected at or during parturition through inhalation, ingestion, or via the umbilicus.(3) Colostrum deprivation is often implicated in cases of actinobacillosis in the early neonatal period; therefore, components of the colostrum from the mare are thought to be passively protective to the foal.(3,8)

Foals may either die of acute fulminating septicemia in the early neonatal period or survive for several days allowing the organism to localize to multiple organ systems. Aborted foals and those with fulminating septicemia generally do not have distinctive gross lesions at postmortem. Animals that survive 2-4 days post-infection often develop miliary microabscesses and fibrinopurulent arthritis. Microabscesses, which are of embolic origin, are most easily observed in the renal cortices and are characterized by the presence of numerous, 1-3 mm, white foci.(6,9) In fact, A. equuli is the most common cause of embolic suppurative nephritis in horses. Typical histopathologic features in the kidney include the presence of numerous bacterial colonies within the glomerular and intertubular capillaries admixed with hemorrhage, necrotic debris and intense suppurative inflammation. The inflammation frequently obliterates the glomerulus.(9)

While the lesions in the current case are classical for infection with A. equuli, the unusual feature in this case is the older age of the horse. As previously mentioned, actinobacillosis is primarily a disease of neonatal foals and the organism is seldom of significance in older horses.(6,9) Although infections in adult horses are uncommon, cases of arthritis, endocarditis, orchitis, periorchitis, pleuropneumonia and enteritis have been reported.(4) In addition, both acute and chronic forms of A. equuli peritonitis have been described in adult horses. In acute infections, horses present with abdominal pain, ileus, lethargy and inappetance. In chronic cases, weight loss is the most common clinical signs. The source of infection has not been identified, but some have postulated that migrating strongyle larvae from the intestinal tract may play a role. Although A. equuli peritonitis is a rare disease in horses, clinicians and pathologists need to be aware of this condition as it is potentially treatable.(4,6)

While A. equuli is typically recognized as an opportunistic pathogen of horses, historically A. equuli has also been recognized as a rare opportunistic pathogen of pigs. The infection in pigs has been typically associated with abortion, septicemia and polyarthritis.(8) Interestingly, there have been two recent reports of A. equuli associated disease in pigs in North America and one outbreak was associated with a high level of morbidity and mortality in sows as the result of septicemia.(7,10) While in foals the primary source of infection is believed to be the mare, there is conflicting evidence concerning the role of the adult horse as a source of infection in pigs.(10) Furthermore, it has been suggested that the rarity of A. equuli infections in North American pigs may be the result of the separation of pigs and horses in modern farming systems.(5) A single report of A. equuli septicemia has been reported in the human medical literature.(1)

JPC Diagnosis:  

Kidney: Nephritis, embolic and suppurative, multifocal, severe, with numerous large colonies of bacilli. 

Conference Comment:  

Actinobacillus species are within the family Pasteurellaceae. Most of the bacteria in this family are commensal, often colonizing the mucosal tissues of both humans and animals; however, there are several species of Actinobacillus that are of importance in veterinary medicine, including the following pathogens:(5)

Actinobacillus species	Associated species: disease
A. lignieresii	Cattle: Lesions in the tongue, lymph nodes, rumen, and skin Sheep: Lesions in the skin Pigs: Granulomatous mastitis
A. pleuropneumoniae	Pigs: Pleuropneumonia
A. suis	Piglets, foals: Septicemia, pneumonia Pigs, horses: Pneumonia
A. equuli	Foals: Septicemia Piglets: Septicemia Pigs: Arthritis, enteritis Calves: Enteritis Mares: Abortion
A. seminis	Rams: Epididymitis Lambs: Polyarthritis

Two subspecies of Actinobacillus equuli have been identified, A. equuli subsp. equuli, and A. equuli subsp. haemolyticus.(2) The former appears to be pathogenic, while the latters pathogenicity appears to be associated with its expression of a repeats-in-structural toxin (RTX) called Aqx, which is cytotoxic for equine leukocytes. RTX toxins, which are expressed by many species in the family Pasteurellaceae, are pore-forming proteins that, when present in high concentrations, bind to β2-integrins and cause cell lysis and necrosis or, when present in low concentrations, lead to apoptosis by inducing apoptotic signaling cascades. Ultimately, the cellular destruction results in inflammation and disease. RTX toxins bind to specific β2-integrins, such as CD18, and therefore play an important role in the host and host cell specificity of pathogenic Pasteurellaceae.(2)

References:

1. Ashhurst-Smith C, Norton R, Thoreau W, et al. Actinobacillus equuli septicemia: an unusual zoonotic infection. J Clin Microbiol. 1998; 36:2789-2790.
2. Frey J. The role of RTX toxins in host specificity of animal pathogenic Pasteurellaceae. Veterianry Microbiology. 2011;153:51-58. 
3. Matthews S, Dart AJ, Dowling BA, et al. Peritonitis associated with Actinobacillus equuli in horses: 51 cases. Aus Vet J. 2001;79:536-539.
4. Patterson-Kane JC, Donahue JM, Harrison LR. Septicemia and peritonitis due to Actinobacillus equuli infection in an adult horse. Vet Pathol. 2001;38:230-232.
5. Quinn PJ, et al. Actinobacillus. In: Veterinary Microbology and Microbial Disease. 2nd ed. Ames, Iowa: Wiley Blackwell; 2011, Kindle edition, location 10980 of 35051.
6. Radostits OM, Gay CC, Blood DC, Hinchcliff KW. Veterinary Medicine: A Textbook of the Diseases of Cattle, Sheep, Pigs, Goats and Horses. Edinburgh, UK: WB Saunders Company Ltd; 2000.
7. Ramos-Vara JA, Wu CC, Mitsui I, et al. Metritis, valvular endocarditis, and septicemia by Actinobacillus equuli in a gilt in the United Sates. Vet Pathol. 2008;45:495-499.
8. Rycroft AN, Garside LH. Actinobacillus species and their role in animal disease. Vet J. 2000;159: 18-36.
9. Schlafer DH, Miller RB. Female genital system. In: Maxie MG, ed. Jubb, Kennedy and Palmers Pathology of Domestic Animals. 5th ed. Edinburgh, UK: Saunders Elsevier; 2007:431-563.
10. Thompson AB, Postey RC, Snider T, et al. Actinobacillus equuli as a primary pathogen in breeding sows and piglets. Can Vet J. 2010;51:1223-1225.

Click the slide to view.

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3-1 Lung

3-2 Kidney

3-3 Kidney

3-4 Kidney

3-5 Kidney

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