JOHNE'S DISEASE

Johne's disease (pronounced yo-NEES) is a condition of cattle and other ruminants that causes chronic diarrhea, weight loss, infertility, and eventual death in animals that were infected years earlier. The causative agent of Johne's disease is Mycobacterium paratuberculosis, a slow growing bacterium that can live in the environment for a year or more. Johne's disease in cattle has economic, regulatory, legal and human health significance that we will review.

The first key to understanding Johne's disease is to review how the organism causes infection and how it is transmitted from animal to animal. The organism, M. paratuberculosis, usually gains access to the host via oral ingestion, although other routes of infection are possible. The M. paratuberculosis bacterium initially infects the last segment of the small intestine, the ileum. The growth of the organism organism and spread of infection in the ileum is slow and usually takes several years before any disease is detectable in the individual animal. As the amount of small bowel inhabited by the bacterium increases, the number of organisms shed in the feces increases. These M. paratuberculosis organisms in the feces of cattle are the primary way Johne's is spread from animal to animal. With time, the infection in the intestinal tract becomes more widespread, and the lymph nodes near the bowel (the mesenteric lymph nodes) become infected with M. paratuberculosis. Later, the organism can become disseminated outside the intestinal tract and infect the uterus, mammary lymph nodes, udder, and sexual organs of bulls. Therefore, the agent can be shed in the milk and semen in addition to the feces. By the time the agent has spread outside the intestinal tract, the feces contain large numbers of M. paratuberculosis, which can serve as a source of infection for many animals in the herd.

Transmission can occur in several ways. The first to consider is prenatal or in utero transmission of the agent. In this instance, the agent passes from the infected cow to the calf before birth, and the calf is born infected. Infected cows that are showing clinical signs of Johne's disease (weight loss, diarrhea) transmit the agent to the unborn calf 20 to 40% of the time. For infected cows that are not showing signs of Johne's disease (asymptomatic), in utero transmission occurs about 8% of the time. Clearly, heavily infected, pregnant cows that are showing signs of weight loss or diarrhea should not be kept in the herd to "get just one more calf." These cows will have too high a chance of infecting their calf prenatally and will also shed high numbers of the organism in the environment. If these cows do not transmit the agent to their calf in utero, it is probable they will infect their calf (and perhaps many others) soon after birth.

The most common time of infection of calves occurs soon after birth. The young calves are most susceptible to the disease. The organism can be in the feces of the cow and can also be in the colostrum or milk. Also, there is usually some manure on the udder of cows, even in the best of circumstances. Therefore, the act of suckling can expose the calf to M. paratuberculosis in feces on the udder, in the milk (or colostrum), or to fecal contamination in the environment. Two factors determine susceptibility to infection by the Johne's agent; (1) age, and (2) dose of the organism. The younger the animal, the greater its susceptibility. As an animal reaches one year of age, the resistance rises to that of adult levels. Also, the higher the dose, i.e., the more Johne's organisms encountered, the more likely an infection will result. So very young cattle ingesting a high dose of organisms are most likely to become infected and conversely, adult animals ingesting a low dose of organism are least likely to become infected. On beef operations, occasionally, twin calves or orphan calves do not have access to colostrum from their dams and colostrum from dairy cattle is given to these beef calves. Because the incidence of Johne's disease is much higher in dairies, there is some risk that the M. paratuberculosis organism could be introduced into a clean beef herd in this manner. This could be a potential for herd to herd transmission.

Other means of transmission exist. This agent can also infect sheep, goats, and wildlife ruminants such as deer. Johne's disease can affect all these species in a similar way to which it affects cattle. Therefore, transmission can theoretically occur between these ruminant species. Because deer, sheep, and goats have pelleted feces the chance of widespread fecal contamination is less than with cattle. Fecal contamination of clothes, boots, and equipment could also move the agent from one premise to another or from animal to animal. Therefore, human activity can be a significant means of transmission of Johne's disease.

One of the more important means of transmission on beef operations is via infected bulls. The M. paratuberculosis organism can be found in the semen and accessory sex organs of infected bulls. Inoculation of the uterus with the Johne's organism can result in infection of the cow. Additionally, bulls are with the cow herd when the calves are young and if the bull is infected and shedding the organism in his feces (even when he has no signs of disease) he is exposing all the calves at a time when they are most susceptible. The practice of sharing or leasing breeding bulls (particularly older bulls who could be shedding the organism in their feces at high levels) can result in significant spread of Johne's disease in beef herds.

How important is this disease? In the dairy industry it is a significant source of economic loss.In Wisconsin alone, the losses are estimated to be $54 million per year. In a national survey of cull cows the prevalence in dairy cattle was found to be 2.9% and the prevalence in beef cattle was 0.8%. The disease affects beef cattle through decreased productivity, infertility, increased culling, and increased susceptibility to other diseases. It is a disease that can be devastating to a herd over time and can be particularly important in purebred herds.

The bacterial agent that causes this disease, Mycobacterium paratuberculosis, is most commonly transmitted via ingestion of feces by young cattle; however, it can also be transmitted in the semen of bulls, in the milk (or colostrum), and across the placenta to the newborn calf (in utero transmission). The agent survives in nature partly because there is a prolonged carrier state when the infected animal shows no illness and sheds large numbers of the M. paratuberculosis organisms into the environment where other cattle can become infected.

Diagnosis of cattle with clinical signs of Johne's disease is relatively easy. These animals exhibit weight loss and diarrhea as the primary signs. However, many diseases show signs of diarrhea and weight loss, including: (1) parasites (roundworms, liver flukes, coccidiosis), (2) BVD (bovine virus diarrhea), (3) copper deficiency, (4) liver failure, (5) grain overload (founder), (6) selenium deficiency, and (7) Salmonellosis, to list just a few. Cattle with advanced Johne’s disease have "bottle jaw" (fluid accumulation under the jaw).

A serum sample submitted by your veterinarian to the California Veterinary Diagnostic Laboratory can confirm a diagnosis of Johne's disease for these animals exhibiting diarrhea and weight loss. The serum sample is tested for antibodies to the Johne's agent. If the sample is positive, the animal has Johne's disease. If an animal dies or is euthanized, the post mortem examination can also easily diagnose the condition. Also, for clinical cases, the feces can be cultured for the presence of M. paratuberculosis. When testing serum from cattle that have not yet developed clinical signs of diarrhea or weight loss, this laboratory test is often negative, despite the fact that these carrier animals will eventually develop clinical disease and be positive on the serum tests. The laboratory culture of this organism takes about 12-16 weeks, as it is a very slow-growing bacterium. The problem with Johne's disease diagnosis is in identifying the carrier animal that is not yet showing signs of weight loss or diarrhea and is shedding M. paratuberculosis. At present the best tool for identifying these infected cattle that are not yet losing weight is the culture of feces for the organism. As stated, this takes about 12-16 weeks and there are many false negative test results, i.e., no growth of the organism from animals that will eventually have the disease and are presently shedding the organism in small numbers - too small to be detected on the test. Your veterinarian, working with the laboratory, can easily and quickly diagnose cattle with clinical signs of Johne's disease. Also, your veterinarian can help you make the more difficult decisions about diagnosis of the carriers that are not yet showing clinical signs of diarrhea and weight loss.

Animals of exceptional genetic value are sometimes candidates for treatment. It is important to remember that M. paratuberculosis has been isolated from semen and genital organs of infected bulls. Also, M. paratuberculosis has been shown to survive freezing and semen processing, although antibiotics used in semen preparation may diminish the viability of the organism in the semen. While the risk of causing infection in the cow with contaminated semen is low, it is within the realm of possibility and may influence the decision to treat an infected bull. Because transplacental transmission can occur in a pregnant cow, possible infection of the fetus can be a limiting factor when considering the economic value of a cow with Johne's disease. The goal of treatment is the prolongation of life; the drugs used do not cure the disease, but only prolong the animal's life so semen or embryos can be collected. No drugs are approved for treatment of Johne's disease; so all effective drugs must be used in an extralabel manner.

Your veterinarian must prescribe the appropriate drugs and monitor the progress of the animal being treated. Drugs used to treat Johne's disease patients include isoniazid, rifampin, clofazimine and dapsone. The cost of therapy ranges from a few dollars per day to more than $200 per day, depending on the drug(s) selected. Drug therapy will not prolong life indefinitely as Johne's disease is invariably fatal. Prolongation of life for six to 12 months is a possibility with effective treatment.

Johne's disease is one of the diseases reportable to the animal health authorities, i. e., the California Department of Food and Agriculture's Animal Health Branch. This is because of the infectious nature of the disease and the consequences when spread from one herd to another. Because of the insidious nature of this disease, it can be potentially devastating to purebred herds. Infected herds that sell bulls or replacement heifers could lose their market. Knowingly selling cattle from an infected herd could cause the seller to become liable for future losses by the buyer due to Johne's disease.

Control of Johne's disease is essential for a healthy herd. One very important point of control is preventing the introduction of known infected cattle into a herd. The problem with controlling the spread of Johne's disease is that we can't efficiently identify the carrier animals before they show signs of weight loss or diarrhea. Therefore, you must avoid introducing animals into your herd from unknown sources, such as leasing bulls, purchasing dairy cattle (which have a higher incidence of Johne's disease than beef cattle) for nurse cows, fertilizing pastures with manure from other herds (particularly dairy herds), or other practices that would expose calves to manure from potential Johne's carrier cattle. Preventing Johne's disease introduction is particularly important because elimination of the disease from a herd can be very difficult.

Eliminating Johne's disease from a herd is complicated by two major factors: (1) the difficulties involved with identification of carrier cattle not showing clinical signs of diarrhea or weight loss, and (2) the fact that M. paratuberculosis can survive in the environment (manure, soil, pasture, stream water) for up to one year. Methods to control or eliminate Johne's disease from an infected herd must be ranch-specific and account for such things as the prevalence of Johne's in the herd, sources of replacement heifers, and other risks specific to the herd. The basics of control involve (1) hygiene---reducing fecal contamination in the environment of calves, and (2) testing and culling of infected cattle and their offspring. In some states, vaccination can be used to assist in control of Johne's disease and you may read about the use of a Johne's vaccine.

The vaccine must be given to very young calves (35 days of age) and does not prevent infection, but can reduce the shedding later in life. The vaccine is usually only of benefit in herds with large numbers of infected cattle. Vaccination interferes with Johne's disease testing and with tuberculosis testing. The Johne's vaccine cannot be used in California because of these reasons.

Recently, there has been quite a lot written about the possible link between Johne’s disease in ruminants and a disease in humans called Crohn's disease. Crohn's disease is an inflammatory disease of the intestine (ileum and colon) that usually affects patients during the prime of life (teens to early twenties). Most Crohn's disease patients require surgery and intensive medical therapy and suffer chronic pain throughout their lives. Most Crohn's disease patients describe their quality of life as poor. Whether M. paratuberculosis is the cause of Crohn's disease is not known at present. Some of the evidence that argues for a link between M. paratuberculosis and Crohn's disease is (1) the tissue abnormalities is similar between Johne's disease and Crohn's disease, (2) M. paratuberculosis can be isolated from the feces of some Crohn's patients (10-20%), and (3) these isolates can cause disease in experimental animals.

Evidence that argues against a causative link between Johne's disease and Crohn's disease is (1) there are no M. paratuberculosis organisms in the diseased intestinal tissues of patients with Crohn's disease, and (2) M. paratuberculosis can be found in the feces of patients with ulcerative colitis (another intestinal disease) and in control patients (no disease). The association may be that patients with severe bowel disease have more chance of opportunistic colonization of their disrupted intestinal mucosa by these types of bacterial agents. To date, there is no evidence that the agent of Johne's disease causes Crohn's disease in humans. Research in this area will continue, however.