Johne's disease
Encyclopedia
Paratuberculosis or Johne's disease (icon) is a contagious, chronic and sometimes fatal infection
that primarily affects the small intestine
of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis
. Infections normally affect ruminant
s (mammal
s that have four compartments of their stomachs, of which the rumen
is one), but have also been seen in a variety of nonruminant species, including rabbits, foxes and birds. Horses, dogs and nonhuman primates have been infected experimentally. Paratuberculosis is found worldwide, with Norway
, Sweden
and some states in Australia
as the only areas proven to be free of the disease.
Some sources define "paratuberculosis" by the lack of Mycobacterium tuberculosis
, rather than the presence of any specific infectious agent, leaving ambiguous the appropriateness of the term to describe Buruli ulcer
or Lady Windermere syndrome
.
, an acid-fast bacillus
, often abbreviated MAP. MAP is akin to, but distinct from, Mycobacterium tuberculosis
, the main cause of tuberculosis
in humans, and Mycobacterium bovis
, the main cause of tuberculosis in cattle and occasionally also in humans. MAP is 99 percent genetically related to Mycobacterium avium, but has different phenotypic
characteristics such as:
Also, the environmental distribution of MAP is markedly different from that of M. avium, which can produce mycobactin, and therefore can grow and multiply outside the body.
and wasting
. Most cases are seen in 2 to 6 year old animals. The initial signs can be subtle, and may be limited to weight loss, decreased milk production, or roughening of the hair coat. The diarrhea is usually thick, without blood, mucus, or epithelial debris, and may be intermittent. Several weeks after the onset of diarrhea, a soft swelling may occur under the jaw. Known as "bottle jaw" or intermandibular edema
, this symptom is due to protein
loss from the bloodstream into the digestive tract. Paratuberculosis is progressive; affected animals become increasingly emaciated and usually die as the result of dehydration
and severe cachexia
.
Signs are rarely evident until two or more years after the initial infection, which usually occurs shortly after birth. Animals are most susceptible to the infection in the first year of life. Newborns most often become infected by swallowing small amounts of infected manure
from the birthing environment or udder
of the mother. In addition, newborns may become infected while in the uterus
or by swallowing bacteria passed in milk
and colostrum
. Animals exposed at an older age, or exposed to a very small dose of bacteria at a young age, are not likely to develop clinical disease until they are much older than two years.
The clinical signs are similar in other ruminants. In sheep and goats, the wool or hair is often damaged and easily shed, and diarrhea is uncommon. In deer, paratuberculosis can progress rapidly. Intestinal disease has also been reported in rabbits and nonhuman primates.
. The wall of the ileum contains a large number of pockets of lymphoid tissue known as Peyer's patches that lie just beneath the interior surface of the intestine. Peyer's patches are clusters of macrophage
s and lymphocyte
s that are organized much like lymph node
s. Covering Peyer's patches are a layer of cells called M cells. These cells function to sample the content of the lumen of the intestines and pass antigens (bacteria) through to the underlying cells of the Peyer's patch to "show" these antigens to the macrophages and lymphocytes. This is a means of "educating" the cells in a young animal about its environment, and is a protective mechanism designed to help the animal become immune to pathogens in its environment.
Unfortunately, when M cells bring M. paratuberculosis to the Peyer's patch, the bacteria find an ideal place for growth. Macrophages in Peyer's patches engulf M. paratuberculosis for the purpose of destroying the foreign invader, but for reasons that are unclear, these macrophages fail to do this. Inside a macrophage, M. paratuberculosis multiplies until it eventually kills the cell, spreads and infects other nearby cells. In time, other parts of the ileum and other regions of the body are teaming with millions of the mycobacteria. How M. paratuberculosis neutralizes or evades the normally efficient bacterial killing mechanisms of the macrophages is unknown, although the unusually resistant cell wall of mycobacteria likely plays an important role.
The animal's immune system reacts to the M. paratuberculosis invasion by recruiting more macrophages and lymphocytes to the site of the infection. The lymphocytes release a variety of chemicals signals, called cytokine
s, in an attempt to increase the bacterial killing power of the macrophages. Macrophages fuse together, forming large cells, called multinucleated giant 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 intestines. This prevents nutrient absorption, and diarrhea results. Late in the infection, antibody production by the animal occurs to M. paratuberculosis in serum of animals, and is an indicator that clinical signs of disease and death from the infection will soon follow.
For goats infected with this disease, the most apparent sign of having it is their body wasting away, even with a sufficient diet. If a goat develops Johne's and it has diarrhea, it is most likely going to die. When it has diarrhea, the goat is at the last stages of the disease. Herds should be tested once or twice a year to maintain the health and keep out the disease.
carriers. The mortality rate
is approximately 1%, but up to 50% of the animals in the herd can be asymptomatically infected, resulting in losses in production. Once the symptoms appear, paratuberculosis is progressive and affected animals eventually die. The percentage of asymptomatic carrier
s that develops overt disease is unknown.
in humans, and because of this, some researchers contend that the organism is a cause of Crohn's disease
., however, the organism is found more often in asymptomatic people than in those with Crohn's disease.
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
that primarily affects the small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis
Mycobacterium avium subspecies paratuberculosis
Mycobacterium avium subspecies paratuberculosis is an obligate pathogenic bacterium in the genus Mycobacterium. It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and also perhaps...
. Infections normally affect ruminant
Ruminant
A ruminant is a mammal of the order Artiodactyla that digests plant-based food by initially softening it within the animal's first compartment of the stomach, principally through bacterial actions, then regurgitating the semi-digested mass, now known as cud, and chewing it again...
s (mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s that have four compartments of their stomachs, of which the rumen
Rumen
The rumen, also known as a paunch, forms the larger part of the reticulorumen, which is the first chamber in the alimentary canal of ruminant animals. It serves as the primary site for microbial fermentation of ingested feed...
is one), but have also been seen in a variety of nonruminant species, including rabbits, foxes and birds. Horses, dogs and nonhuman primates have been infected experimentally. Paratuberculosis is found worldwide, with Norway
Norway
Norway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...
, Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
and some states in Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
as the only areas proven to be free of the disease.
Some sources define "paratuberculosis" by the lack of Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
, rather than the presence of any specific infectious agent, leaving ambiguous the appropriateness of the term to describe Buruli ulcer
Buruli ulcer
The Buruli ulcer is an infectious disease caused by Mycobacterium ulcerans. The genus also includes the causative agents of tuberculosis and leprosy...
or Lady Windermere syndrome
Lady Windermere Syndrome
Mycobacterium avium-intracellulare is an atypical mycobacterial infection which can occur in the later stages of AIDS. It can also affect people who do not have AIDS and usually first presents as a persistent cough. Additionally, cases in elderly men have increased recently...
.
Bacterium
The disease, discovered by Heinrich A. Johne, a German bacteriologist and veterinarian, in 1905, is caused by a bacterium named Mycobacterium avium subspecies paratuberculosisMycobacterium avium subspecies paratuberculosis
Mycobacterium avium subspecies paratuberculosis is an obligate pathogenic bacterium in the genus Mycobacterium. It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and also perhaps...
, an acid-fast bacillus
Bacillus
Bacillus is a genus of Gram-positive, rod-shaped bacteria and a member of the division Firmicutes. Bacillus species can be obligate aerobes or facultative anaerobes, and test positive for the enzyme catalase. Ubiquitous in nature, Bacillus includes both free-living and pathogenic species...
, often abbreviated MAP. MAP is akin to, but distinct from, Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
, the main cause of tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
in humans, and Mycobacterium bovis
Mycobacterium bovis
Mycobacterium bovis is a slow-growing , aerobic bacterium and the causative agent of tuberculosis in cattle...
, the main cause of tuberculosis in cattle and occasionally also in humans. MAP is 99 percent genetically related to Mycobacterium avium, but has different phenotypic
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
characteristics such as:
- slower growth,
- requires the addition of an iron transport chemical known as mycobactin when grown in vitro (outside the body)
- forms a rough colony when grown on a solid agarAgarAgar or agar-agar is a gelatinous substance derived from a polysaccharide that accumulates in the cell walls of agarophyte red algae. Throughout history into modern times, agar has been chiefly used as an ingredient in desserts throughout Asia and also as a solid substrate to contain culture medium...
medium, and - infects mammalMammalMammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s instead of birdBirdBirds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s.
Also, the environmental distribution of MAP is markedly different from that of M. avium, which can produce mycobactin, and therefore can grow and multiply outside the body.
Signs
In cattle, the main signs of paratuberculosis are diarrheaDiarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
and wasting
Wasting
In medicine, wasting refers to the process by which a debilitating disease causes muscle and fat tissue to "waste" away. Wasting is sometimes referred to as "acute malnutrition" because it is believed that episodes of wasting have a short duration, in contrast to stunting, which is regarded as...
. Most cases are seen in 2 to 6 year old animals. The initial signs can be subtle, and may be limited to weight loss, decreased milk production, or roughening of the hair coat. The diarrhea is usually thick, without blood, mucus, or epithelial debris, and may be intermittent. Several weeks after the onset of diarrhea, a soft swelling may occur under the jaw. Known as "bottle jaw" or intermandibular edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
, this symptom is due to protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
loss from the bloodstream into the digestive tract. Paratuberculosis is progressive; affected animals become increasingly emaciated and usually die as the result of dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
and severe cachexia
Cachexia
Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
.
Signs are rarely evident until two or more years after the initial infection, which usually occurs shortly after birth. Animals are most susceptible to the infection in the first year of life. Newborns most often become infected by swallowing small amounts of infected manure
Manure
Manure is organic matter used as organic fertilizer in agriculture. Manures contribute to the fertility of the soil by adding organic matter and nutrients, such as nitrogen, that are trapped by bacteria in the soil...
from the birthing environment or udder
Udder
An udder is an organ formed of the mammary glands of female quadruped mammals, especially ruminants such as cattle, goats, sheep and deer. The udder is a single mass hanging beneath the animal, consisting of pairs of mammary glands...
of the mother. In addition, newborns may become infected while in the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
or by swallowing bacteria passed in milk
Milk
Milk is a white liquid produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals before they are able to digest other types of food. Early-lactation milk contains colostrum, which carries the mother's antibodies to the baby and can reduce the risk of many...
and colostrum
Colostrum
Colostrum is a form of milk produced by the mammary glands of mammals in late pregnancy. Most species will generate colostrum just prior to giving birth...
. Animals exposed at an older age, or exposed to a very small dose of bacteria at a young age, are not likely to develop clinical disease until they are much older than two years.
The clinical signs are similar in other ruminants. In sheep and goats, the wool or hair is often damaged and easily shed, and diarrhea is uncommon. In deer, paratuberculosis can progress rapidly. Intestinal disease has also been reported in rabbits and nonhuman primates.
Clinical characteristics
The primary site targeted by Johne's disease is the lower part of the intestine known as the ileumIleum
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
. The wall of the ileum contains a large number of pockets of lymphoid tissue known as Peyer's patches that lie just beneath the interior surface of the intestine. Peyer's patches are clusters of macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s and lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s that are organized much like lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s. Covering Peyer's patches are a layer of cells called M cells. These cells function to sample the content of the lumen of the intestines and pass antigens (bacteria) through to the underlying cells of the Peyer's patch to "show" these antigens to the macrophages and lymphocytes. This is a means of "educating" the cells in a young animal about its environment, and is a protective mechanism designed to help the animal become immune to pathogens in its environment.
Unfortunately, when M cells bring M. paratuberculosis to the Peyer's patch, the bacteria find an ideal place for growth. Macrophages in Peyer's patches engulf M. paratuberculosis for the purpose of destroying the foreign invader, but for reasons that are unclear, these macrophages fail to do this. Inside a macrophage, M. paratuberculosis multiplies until it eventually kills the cell, spreads and infects other nearby cells. In time, other parts of the ileum and other regions of the body are teaming with millions of the mycobacteria. How M. paratuberculosis neutralizes or evades the normally efficient bacterial killing mechanisms of the macrophages is unknown, although the unusually resistant cell wall of mycobacteria likely plays an important role.
The animal's immune system reacts to the M. paratuberculosis invasion by recruiting more macrophages and lymphocytes to the site of the infection. The lymphocytes release a variety of chemicals signals, called cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s, in an attempt to increase the bacterial killing power of the macrophages. Macrophages fuse together, forming large cells, called multinucleated giant 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 intestines. This prevents nutrient absorption, and diarrhea results. Late in the infection, antibody production by the animal occurs to M. paratuberculosis in serum of animals, and is an indicator that clinical signs of disease and death from the infection will soon follow.
For goats infected with this disease, the most apparent sign of having it is their body wasting away, even with a sufficient diet. If a goat develops Johne's and it has diarrhea, it is most likely going to die. When it has diarrhea, the goat is at the last stages of the disease. Herds should be tested once or twice a year to maintain the health and keep out the disease.
Morbidity and mortality
In an endemic herd, only a minority of the animals develops clinical signs; most animals either eliminate the infection or become asymptomaticAsymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...
carriers. The mortality rate
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
is approximately 1%, but up to 50% of the animals in the herd can be asymptomatically infected, resulting in losses in production. Once the symptoms appear, paratuberculosis is progressive and affected animals eventually die. The percentage of asymptomatic carrier
Asymptomatic carrier
An asymptomatic carrier is a person or other organism that has contracted an infectious disease, but who displays no symptoms. Although unaffected by the disease themselves, carriers can transmit it to others...
s that develops overt disease is unknown.
Human risks
There are clinical similarities between Johne's disease in ruminants and inflammatory bowel diseaseInflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
in humans, and because of this, some researchers contend that the organism is a cause of Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
., however, the organism is found more often in asymptomatic people than in those with Crohn's disease.