Hemorrhagic bowel syndrome: an update (Proceedings)

Following the initial report of jejunal hemorrhage syndrome (JHS) in 1992 by Ruggles et al, the disease has subsequently been reported in dairy cows in the US, dairy and beef cows in Canada, dairy cows in Europe and dairy cows in the Middle East. It has emerged as an economically important disease, particularly within the higher density dairy areas of the United States. The published literature on JHS has concentrated on retrospective case series from a number of countries and investigations into potential risk factors for the disease in dairy cattle in the United States.

JHS is more common in mature dairy cows than in first calf heifers and bulls according to the published literature, but herd investigations at our institution have involved dairies that also report problems in cattle of all ages and stages of lactation. The largest retrospective published to date reported that JHS showed a predilection for older cattle 100-110 days in milk2 but we have seen the disease at any stage of lactation, in dry cows and even in mature breeding bulls at stud. Most cattle appear to be in good health immediately prior to the development of JHS. There does not appear to be a consistently increased level of other production related diseases such as subclinical milk fever (hypocalcemia), mastitis or ketosis on dairies that experience JHS but there is undoubtedly much about this condition that we do not yet understand.

The typical cow with JHS becomes depressed, goes acutely off feed, and frequently has cold ears and extremities. Mild, ventral abdominal distension may develop, manure production is scant or absent and pain may be demonstrated by teeth grinding, kicking at the abdomen, or getting up and down frequently. The condition usually advances quite rapidly from initial onset. Affected cattle usually have no fever but heart and respiratory rates are high commensurate with the degree of pain and dehydration. Upon rectal examination, the veterinarian usually finds scant manure that contains fresh blood, blood clots and digested blood. Palpable, distended small intestine is not a common feature per rectum but transabdominal ultrasound examination typically reveals numerous distended loops of small intestine in the right ventral, mid and caudal abdomen. JHS can be difficult to distinguish from other causes of small intestinal obstruction particularly when the animal is presented peracutely, prior to the presence of blood clots in the rectum. Many cows with JHS die within the first 6-36 hours of showing clinical signs. Some progress more slowly over a couple of days and others appear to improve over the first 24 hours only to dwindle and do poorly over the following days. We have seen affected cattle that survive for up to 10 days from the initial episode of pain and abnormal manure without surgical intervention. These individuals may survive longer because the intestine is not completely blocked but death results due to intestines that gradually lose their integrity and leak resulting in peritonitis.

Because JHS cannot be experimentally reproduced in cattle, the definitive cause is as yet unknown, although considerable attention etiologically has been given to potential roles for the bacterium, Clostridium perfringens type A, and the mold, Aspergillus fumigatus. While both theories about cause have strong supporters, it is difficult to discern what truly initiates the syndrome from what happens as a result of the disease. Clostridium perfringens bacteria are normal inhabitants of the intestinal tract of healthy cattle and are commonly found in the environment. C. perfringens type A, the type incriminated as playing a role in JHS, can also be found in haylage under some storage conditions. While the organism is ubiquitous and generally considered to be innocuous, it can become problematic with dietary stress, injury, changes in management, parasitism or other unusual circumstances that set up a favorable growth environment that allows the bacteria to proliferate and produce potent toxins. Clostridium perfringens type A has been associated with conditions similar to JHS of cattle in poultry (necrotic enteritis of fowl) and in people (pigbel), making further investigation of its role either as a cause or a consequence of JHS important. As a group, these bacteria can proliferate after death and invade tissues of the cow's body other than the intestine, creating problems in interpretation of a positive culture from post mortem specimens where there has been a delay between the time of death and sample collection and/or submission. In our veterinary hospital, we have obtained pure cultures of specific toxin producing Clostridium perfringens type A bacteria from fresh, appropriately handled post mortem specimens and from intestinal contents from JHS-affected cattle undergoing surgery to remove the blood clot or the abnormal portion of intestine. While the presence of toxins (alpha and beta-2) can help distinguish the potentially normal bacteria from disease producing strains, it is impossible in an affected cow to determine whether the toxins are a primary or secondary factor. Management practices may also play a role in the condition via their impact on the microflora of the small intestine, creating an environment that could enhance the growth of toxin producing Clostridium perfringens to disease producing levels. The mold, Aspergillus fumigatus, has also been associated with JHS. This organism, commonly found in soil, can be detected in feeds and forages and has been found in the blood and tissues of JHS-affected cattle. Although a causal relationship has not been established, some researchers believe that a primary insult like rumen acidosis, abnormal GI motility, metabolic disease, stress or an immune suppression, creates an environment for Aspergillus to gain entrance into the blood in high numbers. Alternatively, a heavy load of Aspergillus fumigatus may gain entrance into the blood through an injured intestinal or abomasal lining. Further, more recent evidence for a potential role of mycotoxins in the aetiopathogenesis of the condition has been provided by Baines et al and their work linking the consumption of feedstuffs containing multiple mycotoxins with the development of JHS clinically. These authors were able to demonstrate concurrent colonization of damaged intestinal tissue with specific toxin producing O157:H7 E. coli strains heretofore unassociated with clinical disease in adult cattle.

Management and nutritional factors have also been implicated and recent publications by Godden et al9 and Berghaus et al have suggested that high milk production and the consumption of high energy diets may be risk factors associated with the condition. Although Clostridium perfringens type A appears to be frequently isolated from feces or intestinal contents of affected cattle. and both alpha toxin producing and alpha and beta-2 toxin producing strains are more likely to be obtained from cattle with JHS than abomasal displacements, it has not proven possible to reproduce the disease with a beta-2 toxin producing isolate from a field case experimentally, further supporting earlier doubts that this organism on its own is not capable of causing the disease.

Because the exact cause and/or contributing factors that lead to JHS are currently uncertain, consistently effective preventive strategies are yet to be determined. The interventions that have seemed to decrease the prevalence of the disease on problem dairies include vaccination, feed additives and nutritional management. There has been considerable interest amongst some herd owners and veterinarians in the development of autogenous vaccines (bacterin-toxoids) to Clostridium perfringens type A isolated from affected herds. To be effective, products made under fermentation processes maximized for bacterial growth and toxin production using a genotypically appropriate Clostridium perfringens type A are necessary. At this point, testimonials are the best evidence we have for the efficacy of autogenous vaccines. Other herds have used Clostridium perfringens type C and D toxoid or 7- and 8-way Clostridium bacterin-toxoids. Some herds report a reduction in prevalence by vaccinating 2 to 3 times per year with these products. With the recent availability of a USDA licensed Clostridium perfringens type A, toxoid (Novartis Animal Health, Greensboro, NC) there is now a specific product available commercially, designed to protect against diseases associated with the alpha toxin. Again, only testimonial reports currently exist for the beneficial effect of this product in protecting against JHS. Much of the preventative effort has been directed towards nutritional management on problem dairies. Control of subacute rumen acidosis, metabolic disease, diseases like Salmonellosis that affect gastrointestinal motility, and consistency of feed components, mixing, and delivery are logical targets when trouble-shooting a problem herd. Clostridial bacteria as a group tend to multiply rapidly in response to specific opportunities such as carbohydrate overload, an overly acidic environment (either in the abomasum or rumen), high concentration protein or sugar overspill from the rumen into the small intestine or motility disturbances. Insuring a healthy rumen microflora, limiting oral medications and maintaining appropriate fiber length with high quality storage and fermentation of total mixed rations are also important. Inappropriately stored forages can be a source of pathogenic Clostridia and may also pose an added risk for contaminating molds like Aspergillus fumigatus. Feed additives have been used in problem herds. Omni-Gen AF™ (Prince-Agri Products Inc, Quincy, Ill) claims to tie up Aspergillus fumigatus in moldy feed, while mannan oligosaccharides, fragments of yeast cell walls, are included in hopes of reducing toxin load, binding harmful bacteria like Salmonella and Clostridia perhaps stimulating some immunity. The recent study by Baines et al8 also demonstrated a beneficial effect in vitro for the feed additive Celmanax™, although to what extent this compound's ability to act as an anti-adhesive for Shiga toxin producing E.coli and a mycotoxin binder in vitro would be communicated to a beneficial effect in vivo is uncertain at this time.

Treatment of cattle with JHS is challenging. High mortality rates (between 77%2 and 100%) have been documented for JHS in the retrospective case studies published to date. There are anecdotal reports of successful medical treatment that has alleviated the need for surgery but we consider the condition to indicate surgery at our institution. Medical treatment may include oral or ruminal fluids, catharctics, pain-killers or anti-inflammatory drugs, antibiotics and Clostridium perfringens C and D antitoxin. Unfortunately, there is no specific antitoxin for Clostridium perfringens type A, but there may be limited cross protection from the antitoxin of Clostridium perfringens type C and D. Surgical relief of the jejunal obstruction may involve aborad massage of occlusive blood clots or their removal at enterotomy. In situations where bowel compromise is deemed significant, a resection and anastomosis may prove necessary. Post-surgical management commonly involves many of the same medical therapies indicated previously. There is an observed risk of reformation of blood clots with subsequent re-obstruction that can be evident clinically immediately intra-operatively or in the hours to days following surgery.

Retrospective study

In 2008 we performed a retrospective study designed to report on the signalment, operative findings, short, medium and long term outcome of cattle undergoing celiotomy for JHS, as well as recurrence rate and an analysis of potential risk factors influencing survival and reoccurrence. The study used case material from the in-patient population in the large animal clinic at the University Of Wisconsin's Veterinary Medical Teaching Hospital. Cattle were determined to have JHS at surgery by virtue of intra-luminal blood clots that occupied the jejunum. Follow-up telephone interviews with the owners of cattle that were discharged from the hospital as short term survivors provided longer term survival data.

Sixty one percent of cattle identified with JHS survived to initial discharge, with 52% and 41% surviving to 6 and 12 months post-admission to the hospital respectively. A relatively high rate of recurrence (33%) was documented in short term survivors that were discharged from the hospital. A significant proportion of affected cattle were of the Brown Swiss breed. Manual massage aborad alone was associated with higher survival rates compared to cattle that underwent either enterotomy or enterectomy. The survival rates that we documented were higher than previously reported. Prompt surgical exploration and resolution of intraluminal clots by manual massage was associated with higher survival rates.

References

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