Infectious necrotic hepatitis is an acute toxemia primarily of sheep, with sporadic cases described in cattle and horses. It is caused by Clostridium novyi type B. Death is sudden, often without clinical signs, and typically in animals infected with liver flukes. Other causes of liver damage have also been suggested as predisposing factors. The most characteristic gross lesions are grayish-yellow, necrotic foci in hepatic tissue, caused by young, migrating flukes. Control is via disruption of the liver fluke's life cycle (by decreasing the population size of the intermediate snail host) and via vaccination with C novyi toxoid.
Infectious necrotic hepatitis (INH) is a highly lethal, acute toxemia of sheep that can also affect cattle and, rarely, horses.
Etiology and Pathogenesis of Infectious Necrotic Hepatitis
The pathogenesis of infectious necrotic hepatitis is similar to that of bacillary hemoglobinuria. The etiological agent, Clostridium novyi type B, is soilborne and part of the intestinal microbiota and liver of healthy ruminants and, possibly, horses. It can be present on skin surfaces and dormant in muscles and is a potential source of wound infections.
Fecal contamination of pasture by carrier animals is the most important source of infection. C novyi type B multiplies in areas of liver necrosis typically caused by the migration of liver flukes (Fasciola hepatica, Fascioloides magna, and Dicrocoelium dendriticum); however, sometimes the inciting event cannot be determined. A powerful necrotizing toxin (alpha) and, to a lesser extent, edema-inducing toxin (beta) are produced. INH is worldwide, occurring most commonly in regions where liver flukes are endemic.
C novyi has been suspected but not yet confirmed as a cause of sudden death in cattle and pigs that were fed high-concentration grain diets but had no detectable preexisting liver lesions. The lethal and necrotizing toxins damage hepatic parenchyma, thereby permitting the bacteria to multiply and produce a lethal amount of toxin.
Clinical Findings of Infectious Necrotic Hepatitis
Typically, death in cases of infectious necrotic hepatitis is sudden, without clear clinical signs. Affected animals often are well nourished and> 4 months old. They tend to lag behind the flock, assume sternal recumbency, and die within a few hours. Unlike sheep with bacillary hemoglobinuria, sheep with INH do not tend to develop icterus or hemoglobinuria.
Pearls & Pitfalls
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Cattle with INH develop signs similar to those in sheep; they can also show constipation or hematochezia. Horses with INH might show icterus, hematuria, and even neurological signs (ataxia, head tilt).
Most INH cases occur in the summer and early autumn, when liver fluke infection is highest. Differentiation of INH from acute fascioliasis might be difficult; however, peracute deaths of animals with typical lesions found on necropsy should arouse suspicion of INH.
Lesions of Infectious Necrotic Hepatitis
The subcutis of sheep with infectious necrotic hepatitis often appears quite dark ("black disease") because of the characteristic congestion of subcutaneous blood vessels and hemorrhages (see ). In addition, there might be subcutaneous edema over the sternum and ventral abdomen, plus serosanguineous pericardial and peritoneal fluid.
Necropsy photograph of the liver from a ewe that was noted to be thin and slightly lethargic for a few days before death. Note the black areas of ischemic necrosis and hemorrhage secondary to the migration of Fascioloides magna, creating an ideal environment for the germination of Clostridium novyi spores.
Courtesy of Dr. Carolyn Pierce.
The most characteristic gross lesions of INH are grayish-yellow, necrotic hepatic foci with a hyperemic rim, sometimes accompanied by fibrinous adhesions. Infestation and migration of immature flukes (see ) might be evident with necrotic and hemorrhagic tracts in the liver capsule and parenchyma. In one affected horse, only a single necrotic focus was reported (1).
This immature Fascioloides magna fluke, resting on a US penny for scale, was removed from the liver of a ewe infected with Clostridium novyi.
Courtesy of Animal Health Diagnostic Center, Parasitology Unit.
Histologically, liver lesions of INH and bacillary hemoglobinuria include focal or multifocal areas of coagulative necrosis with a mostly neutrophilic rim throughout the liver. Large gram-positive rods with subterminal spores often occur within the inner margin of this inflammatory rim.
Horses with INH might have fibrin thrombi and hemorrhage in organs like the liver, lungs, and adrenal glands. Protein-rich edema can occur in the brain, and horses can also develop renal tubular protein casts (containing hemoglobin).
Diagnosis of Infectious Necrotic Hepatitis
Clinical signs
Necropsy findings
Identification of C novyi type B via culture, fluorescent antibody testing, or PCR assay of the liver
Identification of INH toxins by PCR assay or immunohistochemistry
Diagnosis of infectious necrotic hepatitis is based on history, clinical signs, and lesions found at necropsy, using criteria similar to those used for the diagnosis of bacillary hemoglobinuria. The diagnosis can be confirmed by identification of C novyi type B via culture, fluorescent antibody testing, or PCR assay of the liver.
Alternatively, INH toxins can be identified by PCR assay, or, via immunohistochemistry, the organism can be detected in association with the characteristic lesions. However, immunohistochemistry might not discriminate between the different types of C novyi.
Treatment and Control of Infectious Necrotic Hepatitis
Treatment typically not effective
Prevention of fluke infestation
Vaccination
Antimicrobial treatment of infectious necrotic hepatitis is typically not effective, because of the acute onset of disease and the abundant toxin production characteristic of the disease-causing pathogen.
The main control strategies for preventing INH are aimed at decreasing fluke infestation by minimizing exposure to the snail intermediate host. Effective measures include fencing off animals from wetland areas and administering strategic flukicide treatments.
Importantly, vaccination with commercial multivalent vaccines that contain toxoids and/or bacterins against C novyi type B and other pathogenic clostridia is generally highly effective. Vaccination should be initiated at the age of 6 months, followed by a booster 3–4 weeks later and then biannual boosters thereafter, because immunity is short-lived.
INH contamination of pastures can be minimized by proper disposal of affected carcasses (via burning).
Key Points
Infectious necrotic hepatitis is a rapidly fatal disease that affects primarily sheep and is often associated with liver fluke infestation.
Necrotic foci in the liver are the characteristic lesions found on postmortem examination.
Disease is best controlled with two strategies in combination: vaccinating susceptible animals using a multivalent vaccine composed of bacterins and toxoids against C novyi and other pathogenic clostridia, and instituting measures aimed at decreasing fluke infestations in the flock.
For More Information
Uzal FA, McClane BA, Gohari IM, Navarro MA, Popoff MR, eds. Clostridial Diseases of Animals. 2nd ed. John Wiley & Sons; 2026.
Navarro MA, Uzal FA. Pathobiology and diagnosis of clostridial hepatitis in animals. J Vet Diagn Invest. 2020;32(2):192-202.
References
Nyaoke AC, Navarro MA, Beingesser J, Uzal FA. Infectious necrotic hepatitis caused by Clostridium novyi type B in a horse: case report and review of the literature. J Vet Diagn Invest. 2018;30(2):294-299. doi:10.1177/1040638717737125
