Black Disease
Geoffrey W. Smith
■ Etiology Infectious necrotic hepatitis (black disease) is a peracute, highly fatal disease occurring worldwide. The disease most commonly affects sheep, particularly adults in good body condition, but cattle, horses, goats, and occasionally pigs may also be affected.1,2 There has even been recent speculation that black disease is the cause of epidemic catarrh of sheep, a significant cause of mortality in Australian sheep dating back to the mid-1800s.3 Black disease is caused by toxins produced by the bacterium Clostridium novyi type B, spores of which are commonly found in the soil and can also be present in the digestive tracts and livers of animals grazing affected pastures.
Clostridial organisms require an anaerobic environment for growth, so black disease occurs only when there has been enough damage to the liver to provide the anaerobic environment required for growth of the organism and subsequent toxin production. In practice, the liver insult is almost always caused by larval migration of the common liver fluke, Fasciola hepatica. Therefore this is a seasonal disease related to the liver fluke cycle and occurring in animals typically infested by F. hepatica. Other liver parasites, such as Fascioloides magna or Dicrocoelium dendriticum (especially in France), are occasionally implicated, as is damage to the liver by biopsy or trauma severe enough to result in anaerobic conditions in the liver. Such a scenario should be considered when sudden deaths occur at times when flukes are not usually migrating or in families like Equidae that are not normal hosts for F. hepatica. Black disease occurs worldwide wherever liver flukes are present.■ Pathophysiology The C. novyi strains that cause black disease produce at least two potent exotoxins: alpha toxin and beta toxin. The alpha toxin enters cells by receptor-mediated endocytosis and inhibits ras and rho guanosine triphosphatases by glycosylation.4 The beta toxin is a necrotizing and hemolytic phospholipase C (lecithinase).
Other toxins may contribute to the pathophysiology as well.C. novyi type B is widely distributed in soils, and its spores are continuously ingested and shed in feces of grazing animals. Some of these organisms cross the intestinal mucosa and become disseminated throughout the animal's macrophage system, including the Kupffer cells of the liver. When localized anaerobic conditions occur in the liver, as with migration of liver fluke larvae, these resident spores may germinate and enter a vegetative state. As they proliferate, they release their toxins and create enlarging zones of coagulative necrosis in the liver. The exotoxins produced will enter the circulation, where they cause damage to neurons, vascular endothelium, and other tissues, eventually causing sudden death of the animal.
■ Clinical Signs Peracute death is the most common clinical presentation associated with black disease. When affected animals are recognized prior to death, clinical signs are relatively nonspecific. The animal will often be isolated from the herd and will appear depressed, anorexic, and possibly in respiratory distress. Temperature is elevated initially (40° to 41° C [104° to 106° F]) but declines before death. Sheep become sternally recumbent and generally die after a clinical course of only a few hours. Venous congestion darkens the skin, giving the disease its common name, black disease.2 Unlike closely related bacillary hemoglobinuria, or “redwater” (see later discussion), affected animals do not show red urine or bleeding from the nose or rectum. Clinical signs in cattle are similar, but the disease course occurs over 1 to 2 days.
■ Diagnosis Necropsy is often difficult because autolysis of the tissues after death is usually rapid. Fluid is often found in the pericardial sac and pleural and peritoneal cavities. Endocardial and epicardial hemorrhage is also a consistent finding. Urine is grossly normal. Tissues, especially solid organs like liver and kidney, appear to be in a much more advanced state of autolysis than time of death would suggest.
The liver is usually swollen and congested with small pale areas of coagulative necrosis, particularly along its diaphragmatic surface. The primary lesions of black disease are single or multiple areas (2 to 3 cm in diameter) of hepatic necrosis that appear yellow to white in color and are surrounded by a broad zone of hyperemia.4Diagnosis of black disease is generally made by a combination of history, clinical presentation, necropsy findings, and isolation of C. novyi type B from the liver. A history of sudden death, particularly in endemic fluke areas, is highly suggestive of black disease, especially during warmer weather when fluke transmission is active. Flock or herd vaccination will be either overdue or absent. Time of death should be ascertained as closely as possible. The animal is usually presented in lateral recumbency without signs of struggle. It will be severely bloated even if death has occurred quite recently, giving the impression of a carcass in a more advanced state of decomposition than timing would suggest. Acute liver fluke infection in sheep can have a high mortality by itself, and postmortem findings may be similar to black disease. Other causes of sudden death (e.g., enterotoxemia, blackleg, anthrax) should also be ruled out.2
If necropsy does not confirm a diagnosis of black disease, or if additional documentation is necessary, a simple Gram stain of an impression smear taken from the margin of the liver lesion will typically reveal numerous gram-positive rods. Because clostridial organisms proliferate rapidly after death, such findings must always be interpreted carefully, with consideration of time elapsed between death and necropsy. Further diagnostic measures include anaerobic culture and isolation of C. novyi type B, identification of the specific toxins, and fluorescent antibody identification of the organism. Characteristic histopathologic changes may also be seen in fixed sections of liver associated with necrotic lesions.
Impression smears obtained from the liver lesions are ideal for fluorescent antibody identification of C. novyi type B.■ Treatment and Control Treatment of black disease is rarely undertaken because of its peracute presentation; animals are usually found dead. Although C. novyi is highly sensitive to penicillin and the tetracyclines, toxin production is usually too far advanced for antibiotics to be of value. If used, they should be administered at high doses, intravenously if possible for most rapid onset (20,000 to 40,000 IU/kg sodium or potassium penicillin or 10 mg/kg oxytetracycline q12h), followed by intramuscular (IM) or IV doses at appropriate intervals. Supportive fluid therapy should be initiated to correct dehydration. Even with aggressive therapy the prognosis is poor and the chances for survival slim. In the event of an outbreak, vaccination should be initiated immediately, along with possible metaphylactic administration of penicillin or oxytetracycline.
A good prevention program involves both proper fluke control and the use of clostridial bacterins. Efforts to clear soils of the offending organism are unrewarding. However, it is recommended that carcasses of animals dying from black disease be burned, buried deeply, or removed from the premises. Commercial bacterin-toxoids against C. novyi are available in combination with other clostridial organisms. These products are generally safe and highly effective. Duration of protection is short, however, and should not be relied on for more than 5 to 6 months. Animals vaccinated when younger than 3 to 4 months old require revaccination at weaning. Local reactions at the site of subcutaneous vaccination are common but primarily of cosmetic concern. Intramuscular vaccination should be avoided because it frequently results in permanent damage to muscle tissue, with a negative impact on meat marketing. Timing of vaccination must be determined by the local climate and liver fluke season. In more severe climates where the fluke season is relatively short, a single annual injection before fluke transmission season may be sufficient. In more moderate climates with longer periods of fluke exposure, two vaccinations per year may be required.
Control of liver fluke infestation is also closely linked to prevention of black disease. Control measures include pasture or range management; control of water sources; strategic treatment of animals with appropriate anthelmintics; and limiting access to streams, canals, ponds, and marshes. This is a complex subject, and the reader should refer to the Liver Flukes in Ruminants section for more detail.