Bacillary Hemoglobinuria ("Redwater")
Geoffrey W. Smith
■ Etiology Bacillary hemoglobinuria (redwater, icteric hemoglobinuria) is a disease causing sudden death in cattle, small ruminants, and occasionally horses.
The disease was first reported in California in 1916 and is caused by the toxins of Clostridium haemolyticum (formerly C. novyi type D). Bacillary hemoglobinuria is quite similar to black disease, where clostridial infections of the liver occur under anaerobic conditions, presumably from liver fluke migration. However, in a recent study involving 20 cattle with naturally occurring bacillary hemoglobinuria, none had gross or histologic lesions indicative of liver flukes, suggesting that some other predisposing factor might be involved.1 The major toxin in C. haemolyticum infection is the beta toxin, which is a phospholipase C that causes hepatocyte necrosis, hemolysis, and damage to capillary endothelium.1,2 This results in hemoglobinuria and loss of fluids into tissues and cavities. The primary action of beta toxin is to induce localized hepatic necrosis and intravascular hemolysis. Like C. novyi type B, C. haemolyticum is also found in the soil. Spores are routinely present in the liver and can be passed in feces and urine of healthy animals grazing affected pastures. Disease occurs only when there is sufficient insult to the liver to provide the anaerobic conditions required for bacterial growth and toxin production. In many cases the liver insult is caused by migration of F. hepatica (common liver fluke) larvae.3-5 As in black disease, F. magna, D. dendriticum (the lancet liver fluke), and Cysticercus cellulosae have also been occasionally implicated in the disease, as has liver biopsy or trauma severe enough to result in liver bruising.6 Bacillary hemoglobinuria is, for the most part, a seasonal disease occurring at the time of larval fluke migration. In the United States, most cases are seen during summer and early fall. However, the disease is sometimes diagnosed in cattle in animals without liver flukes.1,5Bacillary hemoglobinuria is a regionalized disease. It has been reported that C. haemolyticum is limited to alkaline soils, but the disease is also endemic in regions with acid soils. Outbreaks often follow flooding, which can bring spores into previously uninfected areas. The factors affecting distribution of the disease are not well understood. Even in areas where it is common, distribution is erratic, with some farms severely affected while others nearby are disease free.
■ Pathophysiology Spores of C. haemolyticum are ingested by susceptible animals, cross the intestinal mucosa, and are transported to the liver and other organs, probably within the phagosomes of cells of the mononuclear macrophage series. The spores can persist in the liver within Kupffer cells for long periods. Any localized anaerobic area of the liver will allow these spores to germinate. Release of toxins from the bacteria further exacerbates the anaerobic environment, favoring accelerated bacterial proliferation, toxin production, and hepatic necrosis. Beta toxin leads to hepatocyte, erythrocyte, and endothelial cell disruption and thrombus formation. The progression of this lesion is likely responsible for the large necrotic foci observed in virtually all cases of the disease.1 Absorption of toxins into the circulatory system rapidly leads to intravascular hemolysis, icterus, hemoglobinuria, and death.
■ Clinical Signs Bacillary hemoglobinuria is most common in animals older than 1 year of age. Like black disease, sudden death without obvious clinical signs is common in animals that have peracute disease. In those rare cases where disease is recognized antemortem, signs include depression, anorexia, and fever of 40° to 41° C (104° to 106° F), declining as death approaches. Breathing may be rapid and shallow, and blood or blood-tinged froth may be present in the nostrils.
Rectal bleeding or bloody feces may also be observed. Severe hemoglobinuria or passage of dark red, port wine-colored urine is often reported. Blood is thin and watery and coagulates slowly. Mucous membranes are pale and icteric. Severity of signs increases as the disease progresses. Postmortem, the animal is usually in lateral recumbency, severely bloated, and without signs of struggle. Blood is often present in the nostrils, mouth, rectum, or vagina. The carcass appears to be in an advanced state of decomposition even when it is actually quite fresh. A tentative diagnosis can be made on the basis of history and observation of the carcass.At necropsy the mucous membranes and tissues can appear icteric. Skinning the animal reveals numerous subcutaneous petechial and ecchymotic hemorrhages, edema, and sometimes emphysema. There will be significant amounts of red-tinged abdominal and thoracic fluid. Hemorrhages are present on all serosal surfaces. Dark red urine is present in the bladder. Lymph nodes are congested and usually hemorrhagic. There may be hemorrhage into the bowel lumen. The spleen is enlarged. The lungs are usually filled with blood-tinged froth or foam. Pericardial fluid is blood tinged, and hemorrhages are present on both the epicardium and the endocardium. Solid organs such as liver and kidney appear to be in advanced stages of autolysis, even in fresh carcasses. The pathognomonic lesion is the so-called ischemic hepatic infarct, which has a zone of hyperemia at its interface with viable liver tissue. This area of coagulative necrosis, sometimes partially liquefied at its center, can reach up to a 30-cm diameter and have a very irregular outline.4 Unlike a classic infarct, the lesion in bacillary hemoglobinuria results from progressive enlargement of the focus of coagulative necrosis caused by the bacterial toxins. Any thrombosis seen in the lesion is secondary, with the vasculature being included in the necrotic process, along with other hepatic tissue.6
■ Diagnosis Antemortem animals with bacillary hemoglobinuria will be anemic and have elevated hepatic enzymes such as AST and GGT.7,9 Total bilirubin concentrations are also dramatically elevated.7,9 If a urine sample can be collected, hemoglobinuria will be obvious.
Postmortem, a Gram-stained impression smear from the liver will reveal numerous typical clostridial organisms. Smears may also be made from spleen, blood, or abdominal fluid, with the same outcome. Postmortem presence of clostridial organisms must be interpreted with caution because they are always present and proliferate rapidly after death. It is important to have an accurate estimate of time of death to determine the significance of these findings. Laboratory confirmation depends on identification of both the causative bacteria and the toxin. Fresh (refrigerated) and formalin-fixed liver lesions should be submitted. Fluorescent antibody tests on impression smears taken from a liver “infarct” will be positive for C. haemolyticum antigens. Extensive biochemical and toxin identification tests are confirmatory but seldom used if lesions and fluorescent antibody tests are compatible. A PCR assay that can detect C. haemolyticum in the blood of affected cattle has also been reported,7 as have PCR assays to detect the beta toxin.1■ Treatment and Prevention Although successful treatment of cattle with bacillary hemoglobinuria has been described,7,10 it is seldom undertaken because of the acute nature of the disease. If there is opportunity for treatment, penicillin at high dosages (at least 20,000 to 40,000 IU/kg IV or IM twice daily) is the antibiotic of choice, although tetracyclines (10 mg/kg IV twice daily) are acceptable. Fluids are given intravenously or intraruminally to correct dehydration. Because of severe hemolytic anemia, blood transfusion is recommended and should be repeated as necessary. In animals that recover, there will be a noticeable reduction in the severity of hemoglobinuria daily.7
An effective prevention program requires consideration of both the pathophysiology and immunology of the disease and the natural history of the liver fluke (F. hepatica) that is so intimately involved in expression of bacillary hemoglobinuria.
Efforts to clear soils of the offending organism are unrewarding, but carcasses of animals dying from bacillary hemoglobinuria should be burned, buried deeply, or removed from the premises.Commercial bacterin-toxoids against C. haemolyticum are available both in monovalent form and in combination with other clostridial vaccines. These products are generally safe and highly efficacious. Duration of protection is short, however, and should not be relied on for more than 5 to 6 months. Animals vaccinated when less 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 beef 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 measures include pasture or range management, control of water sources, strategic treatment of animals with products effective against flukes, 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.