JOHNE'S DISEASE - William P. Shulaw DVM, Extension Veterinarian, The Ohio State University, College of Veterinary Medicine, 1900 Coffey Rd, Columbus, Ohio 43210
Johne's disease, or paratuberculosis, is a chronic infectious disease of ruminants that has worldwide distribution. In the United States it is probably most common in cattle, however, all ruminants are considered susceptible, and some monogastrics can be infected experimentally. A recent study conducted by the National Animal Health Monitoring System (NAHMS) studied samples from 32,622 cows on 1,004 dairy farms representing about 80% of the dairy operations in the United States. In this study 22% of herds and about 3% of cows were considered infected. A similar study is currently being conducted for beef cattle and results should be available soon. A nationwide study of cull beef cattle conducted in 1987 in processing plants across the country suggested that about 0.5% of cull beef cows were infected. No estimates of the disease prevalence for sheep and goats are available. The economic impact of the disease on the dairy and beef cattle industry because of premature culling, loss of productivity, and reproductive failure is difficult to assess, but loss on individual farms can be very substantial.
CAUSE AND DISEASE SIGNS
The causative agent of the disease is Mycobacterium paratuberculosis, a hardy bacterium related to those that cause tuberculosis and leprosy. In cattle, the clinical disease is characterized by an uncontrollable and profuse diarrhea accompanied by progressive weight loss and eventual death. In sheep and goats, diarrhea is not a common sign, but extreme weight loss is the primary finding in infected animals. The disease has often been confused with other diseases that cause diarrhea and weight loss such as internal parasitism. Mycobacterium paratuberculosis may survive in the environment in soil, manure, or water, for a year or more which is a characteristic of crucial importance in the spread of the disease.
TRANSMISSION
Fecal material (manure) from infected animals may contain tens of billions of bacteria per teaspoonful. It is believed that most animals become infected by ingesting bacteria from a contaminated environment, such as when nursing from contaminated udders. Additionally, most animals are infected early in life, and a relative resistance to infection develops with age. Animals less than 6 months-of-age seem to be at most risk with those less than 30 days-of-age at perhaps the highest risk. Contaminated maternity pens and housing for young stock expose these animals at an early age and provide the mechanism for perpetuating the disease.
The time lapse from the beginning of the infection until the onset of clinical signs may range from 1 to 13 years. The typical clinical case is about 4 years old (cattle and sheep), although in herds where exposure is high, onset of signs may frequently be as early as 2 years of age. Disease can develop in animals as young as a year-of-age, but rarely. There is no treatment, and the animal becomes progressively emaciated and eventually dies if it is not salvaged. On an infected premise where clinical cases have been observed, as many as 70% of the animals may be in various stages of infection and disease progression. Infected cows may shed bacteria for a considerable time, perhaps years, before they develop signs of disease. Realizing that the animal that develops clinical disease usually represents the completion of a lifelong infection, and that these animals are only the tip of the infection iceberg, is important.
Recently, studies at Ohio State and the University of Pennsylvania have suggested that transmission to the unborn fetus in the uterus may be of more importance in the spread of the infection than previously thought. In one study, as many as 25% of infected cows carried infected fetuses. It is not known how the disease progresses in animals so infected.
Milk and colostrum from infected cows have also been shown to be sources of the bacteria for the calf. Results from one recent OSU study done on an infected dairy farm showed that 22% of subclinically infected cows (no signs of disease) were shedding the organism in their colostrum, and 8% harbored it in their milk. In other experimental work, it has been shown that antibodies (as might be present in colostrum or milk) may promote the uptake of the bacteria by macrophages in the intestinal wall. In other words, the first food a calf gets may be the source of infection for it. More work needs to be done on the significance of colostrum and milk in the spread of this disease.
After ingestion, Mycobacterium paratuberculosis enters the intestine in the specialized areas called Peyer's patches. Tissue macrophages, or bacterial killer cells of the immune system, engulf the bacteria but are not effective in killing them. The reasons for this ineffective killing are not completely understood. Progressive bacterial multiplication results in rupture of the cell and bacteria are carried to deeper layers of the gut and finally to lymph nodes and other parts of the body. The bacteria make no toxin but cause intense tissue reactions that produce the diarrhea and the changes in the intestinal wall that are observed in cases of Johne's disease. These changes may interfere with nutrient absorption and gut wall metabolism.
OTHER CONCERNS
The changes observed in the intestine of animals with Johne's disease are very similar to the changes observed in a disease of humans called Crohn's disease, a chronic, debilitating, and incurable disease of the intestinal tract. This has been noted and studied for about 80 years, but no direct links between the two were found until 1984. In that year a report from a Rhode Island hospital revealed that M. paratuberculosis could be isolated from some patients with Crohn's disease. Subsequently, other reports from around the world have confirmed these findings and considerable interest from the medical community is now focused upon this organism. In fact, the DNA probe that is now available and licensed for diagnostic use cattle is a direct result of the work in humans, not animals. In some countries, the incidence of Crohn's disease appears to be rising significantly.
Although the medical community is divided, some researchers now believe that at least some cases of Crohn's disease are caused by M. paratuberculosis, and that animals may be the reservoir of the bacteria for humans. Two European groups have investigated pasteurized milk as a source of these bacteria, and some researchers believe that this organism may be more resistant to heat than we once thought. This is a subject of active research currently. The fact that the medical community is paying attention to this organism is now widely known among non-veterinary and non-agriculture audiences. This is especially so since the announcement last year from a Florida research group that they had found Mycobacterium paratuberculosis in the breast milk of two women with Crohn's disease. However, not all medical researchers believe that this bacterium is involved in Crohn's disease, and many questions still need to be answered about a potential role for M. paratuberculosis in Crohn's disease and whether animals are a part of the whole picture.
IMPORTANCE TO THE CATTLE INDUSTRY
Although the NAHMS studies reveal that many dairy and beef producers have never heard of this disease, the incidence in cattle appears to be increasing, and some veterinarians report that a significant number of their dairy clients have the disease. The 1996 NAHMS study of Johne's disease indicated that about 22% of the nation's dairy herds are infected. Nationally, the prevalence of the disease in beef cattle also appears to be rising, or possibly it is just being diagnosed more commonly. The 2001 NAHMS study report indicated that about 7% of beef herds are infected, however, the study design would not have been expected to detect low prevalence herds, and some question the usefulness of the detection method (ELISA) in beef cattle herds with different management than dairy. The disease is being increasingly diagnosed in sheep and goats, and the American Sheep Industry Association has developed an update to inform shepherds about the disease. In 2001 and 2002 the NAHMS group will attempt to address prevalence of the disease in sheep.
Some cattle producers have lost significant numbers of animals to the disease, as many as 10% yearly, and research is revealing greater milk production and reproduction losses in dairy animals than was once believed. The 1996 NAHMS Dairy study reported in 1997 that in infected herds where 10% or more of the culled cows had signs compatible with Johne's disease, the yearly loss was as much as $227 per cow in the herd. The United States Animal Health Association has commissioned the National Johne's Working Group to study control of this disease in the United States and to develop guidelines for testing cattle herds to provide prospective buyers with reasonable assurances that they are buying disease free animals. Several states already have programs in place to certify the test negative status of cattle herds.
Because the disease has such a long incubation period before signs develop and because our available diagnostic tests cannot identify all infected animals, especially in the early stages of infection, introducing the disease into a herd is easy. Once infection is established, it is very difficult to eradicate from the herd. With appropriate management changes, producers can limit the effects of the disease in their herd, however, this may increase the cost of production and may reduce the sale value of animals from the herd.
DIAGNOSIS
A diagnosis of Johne's disease in animals with the typical signs is relatively easy. These animals usually shed large numbers of the bacteria in the manure, are usually positive on blood tests, and examination of tissues after death by culture or microscopic examination usually reveals the typical lesions, or changes, and the bacteria. Detecting the inapparently infected animals, before they develop clinical signs and before they can significantly contaminate the environment, has become one of our greatest challenges.
Numerous test methods have been developed and used over the years, and all have shortcomings. Currently, the tests most often employed in diagnosis are culture of the feces for the organism, and blood tests such as enzyme-linked immunoassay (ELISA) and the agar gel immunodiffusion (AGID) test. Recently, a DNA probe used to detect M. paratuberculosis in bovine feces has been marketed, and is available in a few laboratories. It can be done in about 48 hours, but is not readily available and is usually expensive.
Besides the DNA probe, fecal culture is the only test that positively identifies the bacteria - the shedding animal. It is, however, time consuming and expensive to perform in the laboratory and takes 8-16 weeks for results. It is still the most sensitive test we have, however, animals must be shedding bacteria to be detected (this true for the DNA probe as well). Furthermore, only a very small proportion of the infected young stock may be shedding and thus detectable. Fecal culture can be used to confirm a diagnosis of Johne's disease in an individual animal and is a good screening test for a herd if waiting for the results is not a concern. Most cattle with clinical signs of disease will be culture positive, and about half of the subclinically infected animals in the herd above 2 years-of-age will test positive. Repeated cultures over time will eventually detect those animals shedding organisms in their feces. Because a positive test shows that M. paratuberculosis is in the feces, it is considered a confirmation of infection and is the official test in many states.
The ELISA is done on blood serum and may be completed in a few hours, however, in the past it has suffered from a lack of sensitivity and some false positive results. Improvements have been made, and the USDA-licensed ELISA now available is thought to give relatively few false positive results. It will give positive results in most animals showing clinical signs. It does not detect low shedders very well with estimates as low as 15% sensitivity (compared with fecal culture) in these animals. Sensitivity estimates (compared with fecal culture) of 45-65% have been reported for animals shedding moderate to large numbers of bacteria in their feces. Most research groups and laboratories recommend that positive ELISA results be confirmed by fecal culture (or DNA probe) before culling animals, especially in low prevalence herd situations.
ELISA is a good test to monitor the disease prevalence in a herd and may be useful in testing animals prior to purchase. It can provide information as to the effectiveness of control programs and to assign risk in herds being monitored or offered for sale. It is a good test for estimating herd status in certification programs.
The AGID test is less sensitive than ELISA and fecal culture. However, it appears that a positive AGID test correlates well with the presence of large numbers of organisms in the feces and with clinical disease. Therefore, it is useful to quickly support a diagnosis of M. paratuberculosis infection in a sick animal and can be used to screen a herd to remove animals that are shedding the most bacteria. It can be performed in 24-48 hours, and a commercial kit is available that can be used in a veterinary practitioner's office. It gives very few false positive results but fails to identify many infected animals that are not showing signs of the disease.
CONTROL
If Johne's disease is diagnosed in a herd, the producer and his veterinarian should assess the potential extent of infection in the remainder of the animals in the herd. For example, if an infected animal was purchased as a replacement female or as a sire and the farm's young stock have not been exposed, it is possible that spread to other animals has not occurred. If the infected animal was a natural addition to the herd, then it is likely that there are additional infected animals in the herd. Depending upon the circumstances, your veterinarian may, or may not, recommend additional herd testing at the time of the initial diagnosis.
Total eradication of Johne's disease, given currently available diagnostic tests and knowledge, may not be economically feasible, or desirable, in some commercial herds. Periodic screening with selective culling and preventive management strategies may be sufficient to keep losses at a low level. However, a more intensive intervention program may be warranted in herds that sell breeding stock. Herds merchandising breeding stock for export may find that negative herd status is necessary for export to some countries. As newer diagnostic tests are developed that are better able to identify all infected animals in a herd, control and eradication will become easier. The potential for this disease to cause serious losses under some management conditions, and for some producers, is considerable and warrants attention to some control and prevention strategies.
The control and ultimate eradication of Johne's disease is dependent upon three fundamental steps: 1) the accurate diagnosis of the disease to determine herd or flock infection, 2) the subsequent identification of infected animals, and 3) the institution of appropriate management changes designed to limit exposure of susceptible animals. Although the disease occurs in dairy cattle, beef cattle, sheep, goats in Ohio, it is most appropriate to discuss dairy, beef, and sheep separately. Let us assume that a correct diagnosis of Johne's disease has been made in a farm-raised animal and that a decision has been made to identify infected animals and to institute control measures.
MANAGEMENT RECOMMENDATIONS FOR CONTROL of JOHNE'S DISEASE IN BEEF CATTLE
1. In infected herds, reduce environmental contamination by identifying infected animals and culling them from the herd. Fecal culture identifies animals that are shedding the causative bacteria. The AGID test is less sensitive, but more rapid, and because it correlates well with heavy shedding of M. paratuberculosis it has sometimes been recommended as an initial herd test when calving time is near in order to remove heavy bacterial shedders which pose the greatest risk for newborn calves.
2. Provide clean, well-drained areas for calving. Dilution of the bacteria in the environment is essential to reducing spread. Calving areas for many beef herds in eastern USA often become wet, muddy, and otherwise contaminated with fecal material. Cow udders commonly become soiled with environmental contamination as well as manure of the dam. Dirty udders and cows are sources of Mycobacterium paratuberculosis for the young calves at the time they are most susceptible. Remove cow and calf pairs from the calving area as soon as possible after calving and place them on uncontaminated pasture. This recommendation is useful to prevent other calfhood diseases as well.
If calving pens are used, clean pens between animals and sanitize with phenolic-based disinfectants such as One Stroke EnvironT, AmphylT, OsylT, WexcideT. The use of lower stocking rates has been recommended to reduce concentration of bacteria on the pastures.
3. When possible, raise heifers separate from adults. Adult cattle represent potential carriers of infective bacteria. Do not spread manure on heifer pastures. Fence off ponds that may have become contaminated by barnyard drainage.
4. Isolate unthrifty animals or animals with diarrhea until a diagnosis is made or until the animal is culled. Work closely with your veterinarian to obtain an accurate diagnosis of all diseases. Some severe problems with Johne's disease have been created when a well-meaning producer has penned thin infected cows with his young heifers in order to "give them a little more to eat."
5. Consider culling the most recent progeny of infected animals. Contamination of the udder of the cow with her feces increases the risk of infection of her calf. In addition, it is now known that some fetuses that are infected in the uterus may survive to young adulthood and may harbor the organisms.
6. A vaccine is available for Johne's disease. However, in addition to creating persistent injection site inflammation, and frequently, a persistent positive skin test for tuberculosis, the vaccine does not prevent all animals from becoming infected or from shedding the bacteria. It may help in reducing the number of clinical cases of the disease and may be helpful in badly infected herds. In Ohio and many other states, the vaccine must be administered by an accredited veterinarian, and permission and guidelines for its use must be obtained from the office of the state veterinarian.
7. If you do not already have Johne's disease, DON'T BUY IT. Ask about the status of a seller's herd before purchasing if possible. Purchasing animals from tested herds and finding out how long they have been testing is less risky than buying from herds with unknown status. If you purchase replacement heifers and bulls and their status is unknown or questionable, you can test them with ELISA before purchase. However, the sensitivity of ELISA in subclinical animals may not be high enough to give sufficient confidence that test-negative animals are truly uninfected. Alternatively, a simple preventive strategy is to culture the feces of all replacement animals, including bulls, on a yearly (or twice yearly) basis in an attempt to identify infected animals as soon as they begin shedding M. paratuberculosis and before extensive exposure of your young stock occurs.