Paratuberculosis (Johne's disease)

What it is

Paratuberculosis or Johne's disease is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), a very slow-growing acid-fast mycobacterium that survives for months in the environment. Animals are almost always infected in their first months of life, when they are most susceptible, by the faecal-oral route: by suckling teats soiled with faeces, by ingesting colostrum or milk from infected cows or from the contaminated environment of the calving pen and calf housing. Intrauterine transmission also occurs.

The bacterium enters through the Peyer's patches of the ileum and persists inside macrophages. A very long subclinical phase follows, lasting years, during which the animal can start shedding bacteria in its faeces without showing signs and infect the herd. Only some infected animals reach the clinical phase, usually between 2 and 5 years of age. The granulomatous enteritis prevents nutrient absorption and causes a protein-losing enteropathy.

The link between MAP and human Crohn's disease has been studied for decades: the bacterium is detected more often in people with Crohn's disease, but it has not been shown to cause it and the question remains debated (see Key studies).

Who it affects

Cattle, especially dairy cattle, as well as sheep, goats, deer and other ruminants. It is present in most countries with intensive livestock farming. Infection is acquired as a calf, but signs appear in young adults, often after calving or at peak lactation. The disease usually enters a herd with purchased infected animals.

Anatomy involved

• Small intestine: the typical lesion is in the ileum and the ileocaecal valve. The mucosa thickens and forms transverse folds that do not disappear when the wall is stretched, giving a "corrugated" appearance. The mesenteric and ileocaecal lymph nodes are enlarged and oedematous, and the lymphatic vessels of the serosa and mesentery appear thickened and prominent (lymphangitis). Microscopically, the mucosa is infiltrated by epithelioid macrophages and giant cells laden with acid-fast bacilli.
• Large intestine: in advanced cases the granulomatous enteritis extends to the caecum and colon. Loss of the water-absorbing capacity of the large intestine contributes to the watery diarrhoea.

Clinical signs

• Chronic diarrhoea, watery or pasty, intermittent at first and then persistent, without blood or mucus.
• Progressive weight loss with a preserved appetite and no fever.
• Reduced milk yield and fertility.
• In the advanced phase, hypoproteinaemia with submandibular oedema ("bottle jaw"), cachexia and death.
• Clinical disease is irreversible. Most infected animals in a herd are in the subclinical phase and show no signs.

Diagnosis

• Antibody ELISA on serum or milk: cheap and widely used to screen herds and animals, but antibodies appear late and its sensitivity is low in subclinical animals.
• Faecal culture and faecal PCR: detect animals shedding the bacterium; culture takes weeks. Culture or PCR of environmental samples (manure from alleys and pits) is used to classify herds.
• Necropsy and histopathology of the ileum, ileocaecal valve and mesenteric lymph nodes, with Ziehl-Neelsen staining: confirms the diagnosis.
• A negative result does not rule out infection; tests are interpreted at herd level and repeated over time. Infection can cause cross-reactions in the tuberculin test.

Treatment and control

There is no practical or effective treatment; clinical animals are removed from the herd. In some countries it is notifiable or subject to official or voluntary control programmes. Control is long term and combines:

• Calf-rearing hygiene: a clean, dry calving pen, early separation of the calf from the dam, colostrum from negative cows or heat-treated, pasteurised milk or milk replacer, and avoiding calf contact with adult faeces.
• Test and cull of positive animals, starting with heavy shedders and clinical cases.
• Biosecurity: buying animals from low-risk herds.
• Vaccination: inactivated vaccines reduce clinical cases and bacterial shedding but do not prevent infection; they interfere with the tuberculin test and with ELISA, cause injection-site nodules, and accidental self-injection is dangerous for people, so in many countries their use is restricted.

Key studies

• Doré et al. (2012), systematic review of 23 articles from 11 countries on risk factors for MAP transmission to calves in dairy herds. Contact of calves with adult cow faeces was the most important risk factor, linked to the calving environment, colostrum, milk and housing. Most studies were cross-sectional (16), with highly variable case definitions and serum ELISA as the main test.
• Nielsen and Toft (2008), systematic critical review of the accuracy of ELISA, interferon-gamma and faecal culture for three conditions: infected animal, animal shedding the bacterium and diseased animal. Shedding and diseased animals can often be detected, but sensitivity for detecting infected animals is generally low. The authors conclude that the quality of design and reporting of test evaluation studies is generally poor.
• Liu et al. (2026), systematic review and meta-analysis of 101 studies from 75 articles (1983–2024) on ELISA in cattle, against culture or PCR as the reference. Pooled specificity was 0.93 (95% credible interval 0.91–0.94) and sensitivity only 0.56 (0.50–0.62), with an area under the curve of 0.75. Heterogeneity was considerable, and the reference tests themselves miss infected animals.
• McAloon et al. (2016), systematic review and meta-analysis of 20 estimates from 15 studies on the effect on milk yield. A pooled effect could only be calculated for studies that defined cases by detection of the bacterium: cows positive on faecal culture or PCR produced 1.87 kg less milk per day, 5.9% of their yield. Studies based on serology were very heterogeneous.
• Feller et al. (2007), systematic review and meta-analysis of 28 case-control studies on MAP and Crohn's disease. Compared with people without inflammatory bowel disease, the pooled OR was 7.01 (95% CI 3.95–12.4) in studies using PCR on tissue and 1.72 (1.02–2.90) in those using serum ELISA, with similar values compared with ulcerative colitis patients. The association appears specific, but its role in causing Crohn's disease remains undefined: studies of this kind cannot tell whether the bacterium causes the disease or colonises an already diseased gut.