Host range

In cattle, Johne's disease is an infectious bacterial disease primarily affecting the intestinal tract.Johne�s disease should be considered a herd problem besides an individual animal problem.Domestic ruminants are most commonly affected, however, the disease has been reported in several species of wild ruminants, both captive and free ranging, i.e., deer, elk and antelope.In addition, a few isolated cases have been reported in nonruminants including, pigs, horses, chickens, llamas and nonhuman primates, but these species are not believed to be sources for Johne�s disease in cattle.

There are some recent reports of culturing the microbe or detecting its genetic components in humans with Crohn�s disease.However, the significance of these findings in humans as they relate to any human disease has yet to be determined.

The causal agent

Johne�s disease is caused by a mycobacterium named Mycobacterium avium subspecies paratuberculosis (MAP).It is a distant relative of the bacteria Mycobacterium bovis, tuberculosis and leprae that cause TB in humans and animals and leprosy in humans. M. paratuberculosis does not cause TB or leprosy.MAP is very similar to another mycobacterium called Mycobacterium avium. 

A genetic feature that separates MAP from M. avium is a short DNA element named IS900.Genetic probe detection of IS900 is also used to identify MAP infections. 

MAP microbes are engulfed by the macrophages in Peyer�s patches in the ileum. Once there, the microbe multiplies very slowly eventually killing the macrophage and escaping to infect other cells.How this organism neutralizes the macrophage�s immune response is unknown.Billions of microbes are excreted in the feces, to contaminate soil surfaces and water sources. 

Outside the animal, the organism does not multiply, but it can survive over a year in the environment because of its resistance to heat, cold and drying.So, the primary source of infection is directly from infected animals. 

Signalment of disease

It must be emphasized that, because of the slowly progressive nature of the infection, signs of Johne�s disease may not be seen until years after initial infection. Cattle may be infected for years before they show any signs of disease. 

When they finally do occur, the signs of Johne�s disease are intermittent bouts with diarrhea eventually becoming chronic diarrhea and weight loss despite a good appetite. 

Affected cattle do not generally have a fever.Some infected animals appear unthrifty and often weak while others just have chronic diarrhea.The signs of this disease can easily be confused with several other diseases.In the infected cow or heifer, noticeable signs commonly start within a few weeks after a stressful event like calving.

In the subclinical stages cattle are more susceptible to other infectious diseases.These animals also may suffer from inefficient utilization of nutrients and drop off in performance especially milk production.

Causes of clinical signs

Mycobacteria are taken up by specialized cells (M cells) in the ileum.M cells present the microbe to macrophages and lymphocytes in Peyer�s patches. The immune system reacts to the invasion by recruiting more macrophages and lymphocytes to the site of infection. Lymphocytes release a variety of cytokines, in an attempt to increase the bacterial killing power of the macrophages. Macrophages fuse forming large cells in an apparent attempt to kill the mycobacteria. Infiltration of infected tissues with millions of lymphocytes and macrophages leads to visible thickening of the intestine. Late in the infection, antibody production by the animal occurs, but this does not affect control of mycobacterium�s multiplication.

Figure 1. A graph showing hypothetical concentrations of mycobacteria and antibodies through stages of infection. Horizontal line suggests test detection level.

As the body tries to rid itself of these bacteria, the immune response causes a thickening of the intestinal lining, preventing it from functioning normally. This leads to poor absorption of nutrients and eventual diarrhea.As a result, although animals may be feeling and eating well, they begin to lose weight gradually.

When to suspect a herd is infected

The obvious answer is a herd is exhibiting cows with chronic diarrhea and/or weight loss in the face of good appetites.However, some animals may be infected, appear normal and be culled before they show any clinical signs. So, some owners may never realize their herd is infected.A hinting complaint in these herds, could be that herd production is going down or is not as high as it should be, especially in three to six-year-old cows.

In attempting to find the cause of low herd production, tests for Johne�s disease on several poor?doing animals would be advised. In other herds, owners may see one or more cows with diarrhea or weight loss and suspect Johne�s disease as a possible cause.In chronically infected herds, for each animal with clinical signs of disease there may be from five to 15 other animals infected but not showing signs of Johne�s disease.See figure 2.

Explaining asymptomatic infected cattle 

Any infectious disease, including Johne�s disease, typically passes through four stages.Stage I is the initial infection: the animal is infected, not showing signs of disease and may be shedding small numbers of microbes into the environment that are not detectable by diagnostic tests.In Stage II, the infection is progressing and the animal still does not show any clinical signs.Nevertheless, the organism is being excreted in very high numbers, probably enough to infect others nearby or in contact. Infection is detectable by fecal culture techniques but not often by blood tests (Figure 1).In Stage III, the animal is showing the early signs of disease and many diagnostic tests can also detect the infection.Stage IV is the obvious clinical disease and readily recognized by the trained observer and detected by diagnostic tests.

In some herds with Johne�s disease, animals in all four stages of disease exist. For each animal showing obvious signs of Johne�s disease (Stage IV), five to 15 other animals at various stages of infection are not showing signs.

Figure 2. Stages of Johne�s disease progression. For each animal in Stage IV, the hypothetical animals in other Stages are in parentheses.

Common sources of infection

1.The most common source of infection is feces or manure. Except under unusual circumstances infection begins in the first few months of life. Animals become more resistant with age, though resistance is never complete. If given a sufficiently large dose of the bacteria adults can become infected. Nevertheless, under normal animal husbandry conditions, exposure to such large doses probably rarely occurs. This means, for example, that an infected adult dairy cow in a stanchion or tie-stall barn is not going to infect the cow standing next to her. Infected cows are primarily just a source of infection for calves.

The vast majority of infections in young animals are acquired by ingestion of the bacteria. This happens accidentally when they consume manure containing the bacterium. Sucking on manure contaminated teats, licking contaminated bars in the stall where they are born, or being housed in a location where they have access to manure from the adult herd are ways young animals have opportunities to ingest this microbe.

Johne�s disease typically enters a herd when infected, but healthy?looking, animals come in.As the disease progresses in that animal, the frequency and number of bacteria being excreted increase.Every day, billions of Johne�s microbes may be excreted from an animal in Stage III or IV of the disease.The infection spreads to calves and herd mates without the owner's knowledge.Eventually the owner may recognize signs of the disease in one or more animals. 

2. Another source of infection is milk from infected dams. The likelihood of Johne�s bacteria being excreted in milk of infected females increases as the disease progresses.Studies suggest that 36% of Stage III and IV cows could have Johne�s microbes in their colostrum and milk.In beef herds, where calves remain with their mothers and nurse daily, the chance for transmission of the infection through colostrum and milk is high. These bacteria may be excreted directly through the mother's milk or, it might be present on the outside the teats in contaminated feces.

3. In-utero exposure may be a source of infection for calves. For a fetus to become infected in-utero is possible, if its mother is in the late stages of disease. Studies have shown that, in disease Stages III and IV in the dam, 8% to 40% of the fetuses were infected from their mothers in-utero.Infected fetuses can abort, or they could be born live and grow to become infected adults. How in-utero infections affect diagnostic tests on those animals that survive to adulthood is not known.Risk for infection of the fetus is low from mothers in disease Stages II and I.

4. Standing water. Pond water contaminated with infected feces is another potential source of infection.Other possible, but less likely infection sources, are pastures contaminated with infected feces. Mycobacterium avium is commonly found in these areas.

The zoonotic debate

This is a very controversial subject.A human illness, Crohn's Disease, which resembles Johne�s disease, is the subject of much debate.Crohn's disease most commonly affects people 15 to 35 years old and is a chronic intestinal disease that has no established cause or cure. 

Regarding the association between Johne�s disease in cattle and Crohn�s Disease in humans, to date the evidence for a causal relationship between MAP and Crohn�s disease is not conclusive.Main discussion points follow.

Some researchers have reported finding a significant difference in the percent of Crohn's patient groups that tested positive for the genetic components (DNA) of MAP versus the percent of positive tests in non-Crohn�s patients. Other researchers have found no significant difference between groups. 

Researchers have reported finding a high percentage Crohn's patient groups that tested positive for RNA genetic components of MAP, showing live microbes, versus no RNA components of MAP in non-Crohn�s patients.

Some investigators have cultured MAP from Crohn's patient specimens while others could not. When inoculated into goats, the microbe isolated from Crohn's patient specimens caused Johne�s/Crohn�s-like abnormalities in some of those animals.

Further, both DNA and RNA components of MAP were detected in a child who later developed Crohn�s Disease. This was the first reported case of the microbe being found in a person before they developed Crohn�s disease.

Finally, some patients have had their symptoms stay in remission up to four years after being treated with antibiotics.Typical remission of Crohn�s disease symptoms is two years.If the treatments result in cures, it could show that some microbe is at least partially responsible for the symptoms of Crohn�s Disease 

Members of the medical community are not in agreement as to the meaning of the associations found between MAP and Crohn�s disease. 

So far, no epidemiological studies have been published that examine any connection between direct contact with Johne�s diseased animals and humans who develop Crohn's Disease.Although, one researcher has proposed that an overlaying geographic relationship may exist between CD patients and dense dairy cattle populations in North America.

No studies have been done to examine any association between milk consumption and Crohn�s Disease.Based on review of data, the FDA has stated that commercial high-temperature, short-time (HTST) pasteurization in the U.S. eliminates the hazard from raw milk products.However, some experts and other countries still question the % killing efficacy of HTST pasteurization on MAP.

Note: the National Johne�s Working Group, a subcommittee of the Johne�s Committee of the U. S. Animal Health Association, has reviewed Information for this article.Some of this material has been adapted with the kind permission of Michael Collins, Univ. of Wisconsin, at the Johne's Information Center, also found at web site http://www.vetmed.wisc.edu/pbs/johnes/