Paratuberculosis (Johne’s Disease)

Paratuberculosis is a chronic, contagious granulomatous enteritis characterized in cattle by

persistent diarrhea, progressive weight loss, debilitation, and eventually death. It is considered a listed
disease by the OIE, meaning it is a priority disease for international trade (Aiello, 2016).
I. ETIOLOGY
The causative agent of paratuberculosis in ruminants is Mycobacterium paratuberculosis, also
known as Mycobacterium avium subspecies paratuberculosis (MAP), a slow growing acid-fast aerobic
microorganism. MAP has been subdivided into two main lineages designated as the slow growing type I
(or S for sheep) and the faster growing type II (or C for cattle) according to the species from which these
lineages were first isolated. Type I strains indeed appear to have a strong host preference for sheep and
are more virulent for this species, whereas type II strains are more commonly isolated from cattle and a
broad range of other species (Constable, Hinchcliff, Done, & Grunberg, 2017).
MAP is an obligate pathogen and parasite of animals and in theory can be eradicated by removal
of all infected animals. However, the organism is resistant to environmental factors and can survive for
long periods in the environment, enabling it to persist and spread in the grassland environment and to
withstand a periodic lack of suitable hosts (Constable, Hinchcliff, Done, & Grunberg, 2017).

II. EPIDEMIOLOGY
The disease occurs worldwide most commonly in cattle and to a lesser extent in sheep and goats.
M paratuberculosis is excreted in large numbers in feces of infected animals and in lower numbers in their
colostrum and milk (Aiello, 2016). Infected cows and other species excrete MAP directly into the milk
during at least the late disseminated stage of the infection (Constable, Hinchcliff, Done, & Grunberg,
2017).
Approximately 20% of cows with Johne’s disease will pass MAP across their placenta to the
developing fetus. The risk of this happening increases dramatically in cows with clinical signs of Johne’s
disease (Chase, Lutz, Mckenzie, & Tibary, 2017).
MAP was isolated from dust and bioaerosols collected in barns housing MAP-infected cows,
suggesting that inhalation or ingestion of these bioaerosols has the potential to function as an alternative
route of infection (Constable, Hinchcliff, Done, & Grunberg, 2017).
III. PATHOGENESIS
The primary source of infection is feces that contain MAP. Infected animals can produce large
amounts of the bacteria and shed this organism in their feces. Another important source of transmission
is milk and colostrum. About one third of cows infected with MAP, whether they are showing clinical signs
or not, will shed the bacteria in their colostrum or milk. (Chase, Lutz, Mckenzie, & Tibary, 2017). Infection
is acquired by ingestion of the organism when nursing on contaminated teats; consumption of milk, solid
feed, or water contaminated by the organism; or licking and grooming behavior in a contaminated
environment (Aiello, 2016)
Following oral ingestion, the organism localizes in the mucosa of the small intestine, its associated
lymph nodes, and, to a lesser extent, in the tonsils and suprapharyngeal lymph nodes. The primary portal
of entry is the terminal part of the small intestine and the large intestine (Constable, Hinchcliff, Done, &
Grunberg, 2017).
 The presence of MAP within the intestinal submucosa and mesenteric lymph nodes triggers an
inflammatory response as well as the attraction of more macrophages and lymphocytes to the area. The
result is a granuloma formation with multinucleated giant and immune cells infiltrating the intestinal
submucosa, which results in decreased absorption, chronic diarrhea, and ensuing malabsorption. There is
a reduction in protein absorption and leakage of protein into the lumen of the jejunum, termed protein
losing enteropathy. The loss of protein results in muscle wasting, hypoproteinemia, and edema
(Constable, Hinchcliff, Done, & Grunberg, 2017).

IV. CLINICAL FINDINGS

Four stages of paratuberculosis in cattle have been described.
Stage One (Silent Infection)
Calves, heifers, and young cattle up to 2 years of age are affected. There are no clinical signs and
no effects on body weight gain or body condition, but these animals may shed the organism.
Clinicopathologic tests cannot detect the infection, but culture of the feces or demonstration of the
organism in tissues may be possible (Constable, Hinchcliff, Done, & Grunberg, 2017).
Stage Two (Subclinical Disease)
Carrier adults show no specific clinical signs but may be affected by other abnormalities such as
mastitis or infertility. Most of these animals will be negative on fecal culture but 15% to 25% may be
positive on fecal culture. These are also negative to most serologic tests (Constable, Hinchcliff, Done, &
Grunberg, 2017).
Stage Three (Clinical Disease)
Clinical signs in most cases do not appear before 2 years of age and are most common in the 2- to
6-year-old age group. Cases occur only sporadically because of the slow rate of spread of the disease. A
hallmark of the clinical stage is gradual loss of body weight despite a normal appetite. During a period of
several weeks, concurrent with the weight loss, diarrhea develops. Milk production declines but the
temperature, heart rate, and respirations are within normal limits. The fall in milk yield is often apparent
in the lactation before diarrhea commences. The feces are soft and thin, homogeneous, and without
offensive odor. There is marked absence of blood, epithelial debris, and mucus. Diarrhea may be
continuous or intermittent with a marked tendency to improve in late pregnancy only to reappear in a
severe form soon after parturition. A temporary improvement may also occur when animals are taken off
pasture and placed on dry feed (Constable, Hinchcliff, Done, & Grunberg, 2017).
Stage Four (Advanced Clinical Disease)
As the disease worsens, emaciation is the most obvious abnormality and is usually accompanied
by intermandibular edema, which has a tendency to disappear as diarrhea develops. The diarrhea is
characterized by a fluid “waterhose” or “pipestream” passage of feces. The course of the disease varies
from weeks to months but always terminates in severe dehydration, emaciation, and weakness with an
ultimately fatal outcome. (Constable, Hinchcliff, Done, & Grunberg, 2017)
In infected herds, the mortality rate may be low for a number of years, but as many as 50% of
animals may be infected subclinically with associated production losses. (Aiello, 2016)
 V. GROSS LESIONS
A diverse array of pathology may be seen in infected animals, ranging from a complete lack of
gross lesions to a thickened and corrugated intestine with enlarged and edematous neighboring lymph
nodes. Carcasses may be emaciated, with loss of pericardial and perirenal fat in more advanced, cachectic
cases (Aiello, 2016). Intestinal lesions can be mild, but typically the distal small-intestinal wall is diffusely
thickened with a nonulcerated mucosa thrown into prominent transverse folds. Lesions may extend
proximally and distally to the jejunum and colon (Aiello, 2016). Serosal lymphangitis and enlargement of
mesenteric and other regional lymph nodes are usually apparent. The ileocecal valve is always involved,
with the lesion varying from reddening of the lips of the valve in the early stages to edema with gross
thickening and corrugation later. A high incidence of arteriosclerosis has been observed in advanced cases
of Johne’s disease, with a distinct correlation between the vascular lesions and macroscopic changes in
the intestine. (Constable, Hinchcliff, Done, & Grunberg, 2017)
VI. MICROSCOPIC LESIONS
Histologically, there is a diffuse granulomatous enteritis characterized by the progressive
accumulation of epithelioid macrophages and giant cells in the mucosa and submucosa of the gut. Sparse
to myriad acid-fast organisms may be seen within the macrophages (Aiello, 2016).
VII. DIAGNOSIS
To diagnose paratuberculosis in an individual animal, several testing methods are available.
Although in clinical cases the clinical presentation can be highly suggestive of paratuberculosis,
confirmation of the diagnosis will require either directly identifying MAP in feces or tissue or identifying a
humoral or cell-mediated immune response of the affected animal (Constable, Hinchcliff, Done, &
Grunberg, 2017).
Direct identification of MAP in feces or tissue can be achieved by microscopy, culture, or the use
of specific DNA probes in combination with PCR (Chase, Lutz, Mckenzie, & Tibary, 2017).
M paratuberculosis has been isolated from a wide variety of tissue sites, but the mesenteric and
ileocecal lymph nodes, ileum, and liver are most frequently recommended for diagnostic sampling (Aiello,
2016).
Serologic tests for paratuberculosis in cattle identifying the presence of specific antibodies
include the absorbed ELISA, complement fixation (CF), and agar gel immunodiffusion (AGID). The choice
of the appropriate test must be based on the intended purpose of testing. (Constable, Hinchcliff, Done, &
Grunberg, 2017).
Use of different tests in combination can increase diagnostic sensitivity. Given the biology of the
infection and the need to manage it on a herd basis, diagnostic information should be gathered for a group
of animals rather than for an individual case. An animal showing signs of disease is more likely to provide
diagnostic evidence of the infection (shedding, antibody production) than an animal at the preclinical
stage of infection (Aiello, 2016).
VIII. PREVENTION
Stopping the transmission of MAP from infected cattle that are shedding the bacteria (generally
adult animals) to susceptible animals (generally young animals) is key to controlling the disease (Chase,
Lutz, Mckenzie, & Tibary, 2017). Specific recommendations include making sure newborns are born into
and housed in a clean environment, reducing the chance of spread through colostrum and milk by not
sharing colostrum and milk between multiple young stock or feeding only pasteurized sources of milk or
milk replacers, making sure that weaned young stock are separated from adult animals. Feed and water
sources for young stock should be protected from contamination with adult cow feces. Infected animals
should be identified and either culled or managed so as to reduce the chances that they spread MAP to
susceptible animals, primarily young stock. Calves born to known MAP-infected cattle should be
considered at high risk for being infected with MAP, and managed accordingly (Chase, Lutz, Mckenzie, &
Tibary, 2017)
The formulation of M paratuberculosis vaccines varies by manufacturer. In many countries, their
use is subject to approval by regulatory agencies and may be restricted to heavily infected herds.
Vaccination of calves <1 mo old can reduce disease incidence but does not prevent shedding or new cases
of infection in the herd. Vaccination thus does not eliminate the need for good management and
sanitation (Aiello, 2016).
IX. TREATMENT

Currently there are no definitive cures for paratuberculosis and no therapeutic agents registered
for the treatment of MAP infection. Because of this lack of efficacy and the failure of any of the
antimicrobials to provide a bacteriologic cure, treatment is not recommended. If initiated, treatment that
typically must be maintained for life is aimed at reducing clinical signs and possibly the degree of fecal
MAP shedding. (Constable, Hinchcliff, Done, & Grunberg, 2017)
X. ZOONOTIC RISK
There are conflicting data on the involvement of the causative organism in Crohn disease, a
chronic granulomatous enteritis of unknown cause in people. However, M paratuberculosis is consistently
detected by PCR in people with Crohn disease. This fact, coupled with its broad host range, including
nonhuman primates, indicates that paratuberculosis should be considered a zoonotic risk until the
situation is clarified. (Aiello, 2016)

References
Aiello, S. E. (2016). The Merck Veterinary Manual (11th ed.). Kenilworth, New Jersey, USA: Merck & Co.,
Inc.

Chase, C. C., Lutz, K. A., Mckenzie, E. C., & Tibary, A. (2017). Blackwell's Five-Minute Veterinary Consult:
Ruminant (2nd ed.). NJ, USA: John Wiley & Sons, Inc.

Constable, P. D., Hinchcliff, K. W., Done, S. H., & Grunberg, W. (2017). Veterinary Medicine: A Textbook of
the Diseases of Cattle, Horses, Sheep, Pigs, and Goats (11th ed.). Missouri: Elsevier.