Paratuberculosis is a chronic, contagious granulomatous enteritis in cattle and other ruminants that is caused by Mycobacterium avium paratuberculosis. The disease is characterized by progressive weight loss, debilitation, and eventually death. Diagnosis is primarily made by PCR assay or serological evaluation. There is no satisfactory treatment. Control requires good sanitation and management to avoid exposure among young animals, as well as culling of infected animals.
Paratuberculosis is a listed disease by the World Organisation for Animal Health, meaning it is a priority disease for international trade. The infection has also been recognized in captive and free-ranging wild ruminants, as well as in omnivores and carnivores such as wild rabbits, foxes, weasels, pigs, and nonhuman primates.
Distribution of paratuberculosis in ruminants is worldwide. Many countries have national control programs. The highest published prevalence is in dairy cattle: approximately 20–90% of herds in most major dairy-producing countries are infected (1).
The disease is of economic importance for the goat industry in Spain and the sheep industry in Australia.
Etiology and Pathogenesis of Paratuberculosis in Ruminants
Paratuberculosis in ruminants is caused by Mycobacterium avium paratuberculosis (MAP). MAP is excreted primarily in feces of infected animals and to a lesser extent through the mammary gland. Intrauterine transmission from dam to fetus also occurs. The pathogen has a high tenacity in the environment and can survive on pasture for > 1 year; survival in water is longer than in soil.
MAP transmission is primarily by the fecal-oral route; however, inhalation of contaminated aerosol can also occur. The dose needed to infect an animal is not known. Herds or flocks become MAP-infected by introduction of subclinically infected carriers.
Infection occurs early in life; however, clinical signs rarely develop until after the animal reaches sexual maturity. Progression to clinical disease occurs slowly. Resistance to infection is thought to increase with age but is never complete. Young ruminants become infected by ingesting MAP while nursing on contaminated teats; consuming milk, solid feed, or MAP-contaminated water; or licking and grooming in a contaminated environment.
After ingestion and uptake of the organism in the Peyer’s patches of the lower small intestine, this facultative intracellular pathogen infects macrophages in the GI tract and associated lymph nodes. In most cases, the organisms multiply and eventually provoke a chronic granulomatous enteritis that interferes with nutrient uptake, leading to the cachexia typical of advanced infections.
Clinical disease progresses over a period of months to years and is accompanied by a progressive decline in cell-mediated immunity, a rise in serum antibody, and bacteremia with dissemination of the infection beyond the GI tract. Fecal shedding begins before clinical signs are apparent, and animals in this “silent” stage of infection are important sources of transmission.
Clinical Findings of Paratuberculosis in Ruminants
Clinical paratuberculosis in cattle is characterized by weight loss and diarrhea in the late phases of infection; however, infected cattle can appear healthy for months to years. Diarrhea in cattle might be constant or intermittent, whereas in sheep, goats, and other ruminants, diarrhea might not occur.
Feces of affected cattle do not contain blood, mucus, or epithelial debris and are passed without tenesmus. Over weeks or months, diarrhea becomes more severe, further weight loss occurs, and brisket and submandibular edema (see ) can develop as a result of hypoproteinemia, which is due to the protein-losing enteropathy.
Holstein cow with clinical paratuberculosis showing “bottle jaw” (submandibular edema).
Courtesy of Dr. Michael T. Collins.
In dairy cattle and goats, milk yield can drop or fail to reach expected levels. Animals remain alert, and temperature and appetite are usually normal; however, thirst might be increased.
Paratuberculosis in cattle is progressive and ultimately ends in emaciation and death. As the within-herd MAP infection prevalence rises, so too does the herd cull rate, while dairy herd milk production declines.
The disease in sheep and goats is similar; however, as previously noted, diarrhea is not a common feature, and advanced cases might shed wool easily. In cervids (deer and elk), the course of the disease might be more rapid.
Lesions of Paratuberculosis in Ruminants
A diverse array of pathological findings are observed in ruminants with paratuberculosis. Findings can range from a complete lack of gross lesions to a thickened and corrugated intestine (see ) with enlarged and edematous neighboring lymph nodes (see ). Often, there is no correlation between clinical signs and the severity of lesions. Carcasses might be emaciated, and a loss of pericardial and perirenal fat might be evident in more advanced, cachectic cases. Intestinal lesions can be mild; however, typically, the distal wall of the small intestine is diffusely thickened with a nonulcerated mucosa thrown into prominent transverse folds. Lesions can extend proximally and distally to the jejunum and colon. Serosal lymphangitis and enlargement of mesenteric and other regional lymph nodes are usually apparent.
Thickened and corrugated ileum from a cow with clinical paratuberculosis. On the left side of the image, the serosal surface is visible. On the right side of the image, the intestine has been incised longitudinally to reveal the corrugated mucosal surface.
Courtesy of Dr. Michael Collins.
Enlarged mesenteric lymph nodes from an Angus cow with clinical paratuberculosis.
Courtesy of Dr. Michael Collins.
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 might be observed within the macrophages. Sheep, goats, and deer sometimes develop foci of caseation with calcification in the intestinal wall and lymph nodes.
Diagnosis of Paratuberculosis in Ruminants
PCR assay
ELISA: antibody detection in milk or serum
Necropsy
Many commercially available tests are available for paratuberculosis, each with their own advantages, disadvantages, and appropriate application. The assays focus on detecting MAP in feces or tissue (culture, PCR assay) or on detecting antibody against MAP antigens in blood or milk (ELISA). 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, herd-based testing is as important, if not more important, than testing of individual animals. Many control programs are based on repeated testing of the whole herd at regular intervals (usually 6 months to 2 years), depending on the suspected infection prevalence of the herd.
A patient showing clinical signs of paratuberculosis is more likely to provide diagnostic evidence of the infection (shedding, antibody production) than a patient at the preclinical stage of infection. Necropsy with culture and histological evaluation of multiple tissues is the gold standard for definitive diagnosis.Ziehl-Neelsen stains of tissue samples for acid-fast bacteria usually reveal abundant mycobacteria in lesions; however, in some cases, a careful search still might not reveal their presence. Acid-fast staining of an impression smear made from the ileum of a cow (see ) with typical pathology is a quick, low-cost method for arriving at a preliminary diagnosis.
Pearls & Pitfalls
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Acid-fast stain of an ileocecal lymph node from a Holstein cow with paratuberculosis. Blue cells are mononuclear inflammatory response (macrophages and lymphocytes), and red-stained bacteria are Mycobacterium avium paratuberculosis. Original magnification 100X.
Courtesy of Dr. Michael Collins.
Biopsy of full-thickness sections of ileum and regional lymph nodes for culture or PCR assay and histological evaluation might provide a definitive diagnosis; however, this approach is usually restricted to particularly valuable animals. MAP has been isolated from a wide variety of tissue sites, but the mesenteric and ileocecal lymph nodes, ileum, and liver are most often recommended for diagnostic sampling.
Serological tests for blood and milk are rapid, low-cost methods for antemortem confirmation of a clinical diagnosis; sensitivity is > 85% in clinically affected patients. These tests can also help detect infection in clinically normal cattle in the later stages of infection that are shedding large numbers of MAP; sensitivity is approximately 45% in these cases (2).
Of the serological tests, those based on ELISA technology offer the highest sensitivity and specificity and are best used to determine the infection prevalence in a herd. Quantitative use of ELISA to identify animals for selective culling or isolation in herds can be a cost-effective strategy for disease control; higher ELISA values are associated with higher probabilities of infection and higher rates of fecal shedding. Serological testing of milk can be done on pooled milk samples of several animals or on a bulk tank samples. In case of a positive result, testing of samples from individual animals included in the pool is required.
PCR assay is more sensitive and more specific than serological testing. PCR assay has replaced culture for MAP detection, because the organism grows very slowly (over 2–4 months) and culture is more costly. PCR testing of pooled fecal samples (eg, five samples per pool) or feces from farm sites where cattle commingle (environmental sampling) can establish a herd’s infection status at a lower cost, despite some decrease in test sensitivity. Use of a laboratory that has passed a proficiency test for the specific assay being used is recommended. Most MAP strains infecting sheep will not grow on solid media but may be isolated using liquid culture media systems. Commercial PCR assay kits are as sensitive and specific as fecal culture and much more rapid and less expensive.
Tests of cell-mediated immunity, such as the intradermal Johnin test, lymphocyte transformation test, and interferon-gamma assay, are used in research. The genome of MAP has been described and might provide the basis for new diagnostic approaches.
Tests for paratuberculosis that have fallen out of favor because of reports of low sensitivity and/or specificity are the microscopic examination of Ziehl-Neelsen–stained fecal samples and the IV Johnin test; the complement fixation test (CFT) also reportedly is less accurate than other serological tests (3). The CFT is still required by many countries for importation of animals; however, many of the reagents used in the CFT are made to different specifications in different countries, resulting in a lack of standardization.
Control of Paratuberculosis in Ruminants
Limiting pathogen exposure in young animals
Identification and culling or segregation of infected adult animals
No satisfactory treatment for paratuberculosis in ruminants is known, and attempts to treat clinically affected ruminants are discouraged. Such attempts only prolong the period of environmental contamination by the affected animal (which presumably sheds large amounts of bacteria), and the likelihood for cure is near nil.
Control of paratuberculosis requires good sanitation and management practices aimed at limiting the exposure of young ruminants to MAP and culling of infected animals. Calves, kids, or lambs should be birthed in areas free of feces, removed from the dam immediately after birth in the case of dairy cattle, bottle-fed colostrum that has been pasteurized or obtained from dams that test negative, and then reared apart from adults and their feces as much as possible. Use of milk replacer instead of waste milk is recommended, unless the waste milk has been pasteurized.
Paratuberculosis control programs are usually based on repeated testing of all adult animals in the herd at regular intervals. Low-cost tests (eg, ELISA) on either blood or milk have the greatest cost benefit for commercial dairy herds in which infection has been confirmed by culture or PCR assay. Animals testing positive, particularly heavy MAP shedders or those that have strong-positive ELISA results, should be culled as soon as possible. Testing intervals are chosen on the basis of the suspected infection prevalence of the herd: 6 months for herds with high infection prevalence, and 2 years for herds with a presumed infection prevalence < 5% (4). Because intrauterine infection can occur, more aggressive control programs include culling of calves from dams that have or develop clinical signs of the disease.
Herd replacements should be obtained from herds assumed to be free of paratuberculosis on the basis of a history of regular herd testing with negative results. The replacements should be tested before introduction to the new herd.
More general procedures to minimize fecal contamination on the farm can also help. These include elevating food and water troughs, providing piped water rather than ponds, and harrowing the pasture frequently to disperse feces. Herd owners should be advised that paratuberculosis control is a long-lasting endeavor.
The formulation of MAP vaccines varies by manufacturer. In many countries, their use is either forbidden or subject to approval by regulatory agencies and might be restricted to heavily infected herds. Vaccination of calves < 1 month old can decrease disease incidence but does not prevent bacterial shedding or new cases of infection in the herd. Vaccination, thus, does not eliminate the need for good management and sanitation.
In the goat industry in Spain and Australia, vaccination has increased productive herd life.
Cattle inoculated with an inactivated whole-cell, mineral-oil vaccine develop granulomas, 1 to several inches in diameter, at the site of inoculation (the brisket) and might react positively on subsequent tuberculin tests (5). Accidental self-inoculation can result in severe acute reactions with sloughing and chronic synovitis and tendinitis.
Zoonotic Risk of Paratuberculosis in Ruminants
MAP may play a role in Crohn disease, a chronic granulomatous enteritis of unknown cause in humans. Although MAP is sometimes detected by PCR assay in humans with Crohn disease, causation has not been proven. Nonetheless, there is a potential zoonotic risk of MAP that, thus far, has been neither confirmed nor refuted.
Key Points
Paratuberculosis is prevalent in many food-producing animals.
There is no proven treatment for paratuberculosis.
Paratuberculosis can be controlled; however, it takes years of concerted effort, using both animal husbandry and diagnostic testing.
The cause of paratuberculosis, Mycobacterium avium paratuberculosis, is found in foods of animal origin.
For More Information
Johne's Information Center. University of Wisconsin–Madison, School of Veterinary Medicine.
Johne's Disease. Animal and Plant Health Inspection Service, USDA.
Johne's Control. Animal Health Ireland.
Listed Disease: Paratuberculosis. World Organisation for Animal Health.
Learn more about Crohn disease in humans in the MSD Manual for medical professionals.
References
Fecteau ME. Paratuberculosis in cattle. Vet Clin North Am Food Anim Pract. 2018;34(1):209-222. doi:10.1016/j.cvfa.2017.10.011
Sweeney RW, Whitlock RH, Buckley CL, Spencer PA. Evaluation of a commercial enzyme-linked immunosorbent assay for the diagnosis of paratuberculosis in dairy cattle. J Vet Diagn Invest. 1995;7(4):488-493. doi:10.1177/104063879500700411
Mortier RA, Barkema HW, De Buck J. Susceptibility to and diagnosis of Mycobacterium avium subspecies paratuberculosis infection in dairy calves: a review. Prev Vet Med. 2015;121(3-4):189-198. doi:10.1016/j.prevetmed.2015.08.011
Weber MF, Kelton D, Eisenberg SWF, Donat K. Progress in paratuberculosis control programmes for dairy herds. Animals (Basel). 2024;14(7):1127. doi:10.3390/ani14071127
Lei L, Plattner BL, Hostetter JM. Live Mycobacterium avium subsp. paratuberculosis and a killed-bacterium vaccine induce distinct subcutaneous granulomas, with unique cellular and cytokine profiles.Clin Vaccine Immunol. 2008;15(5):783-793. doi:10.1128/CVI.00480-07
