Pathobiology and diagnosis of clostridial hepatitis in animals

Abstract

Clostridia can cause hepatic damage in domestic livestock, and wild and laboratory animals. Clostridium novyi type B causes infectious necrotic hepatitis (INH) in sheep and less frequently in other species. Spores of C. novyi type B can be present in soil; after ingestion, they reach the liver via portal circulation where they persist in phagocytic cells. Following liver damage, frequently caused by migrating parasites, local anaerobic conditions allow germination of the clostridial spores and production of toxins. C. novyi type B alpha toxin causes necrotizing hepatitis and extensive edema, congestion, and hemorrhage in multiple organs. Clostridium haemolyticum causes bacillary hemoglobinuria (BH) in cattle, sheep, and rarely, horses. Beta toxin is the main virulence factor of C. haemolyticum, causing hepatic necrosis and hemolysis. Clostridium piliforme, the causal agent of Tyzzer disease (TD), is the only gram-negative and obligate intracellular pathogenic clostridia. TD occurs in multiple species, but it is more frequent in foals, lagomorphs, and laboratory animals. The mode of transmission is fecal–oral, with ingestion of spores from a fecal-contaminated environment. In affected animals, C. piliforme proliferates in the intestinal mucosa, resulting in necrosis, and then disseminates to the liver and other organs. Virulence factors for this microorganism have not been identified, to date. Given the peracute or acute nature of clostridial hepatitis in animals, treatment is rarely effective. However, INH and BH can be prevented, and should be controlled by vaccination and control of liver flukes. To date, no vaccine is available to prevent TD.

Clostridial Diseases of Horses: A Review

“…The term clostridial hepatitis refers to those diseases produced by species of Clostridium in which the liver is the main affected organ [69]. In horses, Tyzzer disease (TD) is the most relevant condition that fulfills this description.…”

“…In horses, Tyzzer disease (TD) is the most relevant condition that fulfills this description. Other clostridial hepatitis that can affect horses less frequently include bacillary hemoglobinuria (BH) and infectious necrotic hepatitis (INH) [69]. The following section describes the main features of these three diseases in horses.…”

“…This is supported by experimental reproduction of the disease in foals following oral administration of feces from infected horses [72]. The spores would then colonize, multiply, and cause direct damage to the enterocytes of the ileum, cecum, and colon, from where they are absorbed into the blood, reaching first the liver by portal circulation, and then other organs [69,70].…”

“…For most animal species affected by TD (particularly laboratory animals), a triad of lesions involving the heart, liver, and the intestinal tract is considered characteristic of the disease [69,70,75]. However, this is not always a prominent feature of TD in foals, which frequently exhibit hepatic lesions only [71].…”

Study design synopsis: Bias can cast a dark shadow over studies

“…The foals of visiting mares had a four times higher odds (OR = 4) of being diagnosed with Tyzzer's disease compared to foals born to resident mares based on the crude unadjusted statistical analysis. However, susceptibility for Tyzzer's disease varies by age 51 and this is a potential confounder of the measured association (Figure 4). Within the study population, the average age of foals when visiting mares arrived at the breeding farm was 13 days (range, 0‐77 days) compared to a mean of 0 days (range, 0‐13) for mares that were resident on the farm.…”