PARATUBERCULOSIS

Paratuberculosis, also known as Johne’s disease, is a chronic regional enteritis that affects ruminants and is caused by the paratuberculosis subspecies of the Mycobacterium avium (MAP) bacteria. It is endemic all over the world and affects both the meat and dairy industries. This disease is normally silent, with a long incubation period and subclinical stage with no visible symptoms.

Species affected
Cattle

Sheep

Goats

Although this disease mainly affects ruminants, including wild species like deer and bison, cases have also been detected in wild rabbits and their predators. These, along with wild ruminants, may act as reservoirs, helping spread the pathogen in the environment.

Risk factors

Ruminants under 6 months run a greater risk of paratuberculosis infection, although animals may be infected at any age in the right circumstances.

Replacement animals

Replacement animals shouldn’t be introduced without proper health verifications.

Environmental contamination

Certain conditions like soil type, shaded areas, cold, damp grazing lands with standing water and acidic soil or soil without phosphorus and calcium help MAP survive in the environment.

Hygiene and crowding

Overcrowding and incorrect equipment and facility hygiene promote the spread of these pathogens.

Animal age

Young animals are very susceptible to contamination, which can come from their environment, their mother’s dirty udders, colostrum or directly in utero.

Poor nutrition

Often associated with growing feed in poor soils, which has a negative impact on animal immunity.

Genetic susceptibility

Certain breeds of ruminants are much more susceptible to infection than others.

Spreads of paratuberculosis

Causative agent

Paratuberculosis is caused by Mycobacterium avium subsp. paratuberculosis, a highly resistant bacteria. It prefers cold, shady environments and can survive many months in damp grazing lands, ponds and feces.

 

It is less resistant in soils high in calcium or alkaline soils, it is sensitive to UV rays, dryness and heat.

MAP infection

The main characteristic of this disease is its long incubation period. Animals are normally exposed at a young age, but the first symptoms can take up to two years to appear after infection, generally after the first calving in reproductive females.

 

Fecal matter is the main source of exposure, and animals can start shedding the bacteria up to 18 months before they show symptoms, or even in animals that never show any symptoms. The disease can spread to other animals in the subclinical phase, even though there are no perceivable symptoms.

  • Oral transmission: Spread through feed, soil, water, milk and colostrum carrying the bacteria.
  • Transplacental transmission: Between 20% and 40% of mothers with the clinical disease will infect their fetus in utero.

Exposure most commonly takes place in indoor areas, followed by in utero transmission. The second most common exposure site in the first four years is the local environment. Contrary to common belief, colostrum and milk are less common transmission routes.

Prevalence of paratuberculosis in the world

Johne’s disease is present around the world. Studies have been done in various countries to see how widespread it is and they estimate more than 20% of herds and flocks are infected. Prevalence could even be over 40% in countries with a highly developed cattle industry.

 

In dairy herds, MAP prevalence of over 50% has been seen in countries with intensive breeding systems. In the United States, more than half of all dairy herds may be infected.

 

Prevalence is often under-reported and underestimated, and the true incidence of paratuberculosis isn’t known for many countries.

Clinical signs and symptoms of paratuberculosis

Whether an animal develops symptoms depends largely on a series of factors, like their age when exposed and degree of infection, where the animal is and their breeding and feeding conditions. Subclinical cases are more common and are mostly found in well-managed farms with good feed.

    • Diarrhea
  •  
    • Progressive weight loss
  •  
    • General weakness
    • Decreased milk yield.
    • Greater susceptibility to other infectious diseases, like mastitis or metritis.
    • Reproductive issues like abortions and infertility.
Financial losses FROM PARATUBERCULOSIS

There are both direct and indirect losses, affecting both traditional farmers and breeders. In general, lost yield is estimated to have a financial impact of €100 ($107) per animal per year, although this figure varies widely from country to country.

Direct
  • Death of infected animals and cost of replacing them: This can be due to the disease itself or the need to cull infected animals. The culling value of infected cattle can be 20% to 30% less than non-infected animals, and in many countries animals with paratuberculosis are not allowed to be taken to the slaughterhouse. At the same time, as more animals have to be culled, more replacement animals are needed, which drives up costs.
  • Decreased milk yield: Studies show that paratuberculosis can decrease milk production between 500 and 1,400 kg per cow per lactation.
  • Decreased meat yield: Seropositive animals can weigh between 21 kg and 58 kg less than animals without the disease.
  • Increased diagnosis costs: If an animal is found to have paratuberculosis, the other animals in the herd must be tested periodically, which drives up costs.
  • Decreased productive life: Normal productive life expectancy is 50% shorter in infected animals with clinical signs.
  • Decreased fertility: Paratuberculosis can cause reproductive issues that increase the time between calving.
Indirect
  • Prone to other diseases: From the time clinical signs appear, the animals’ physical condition deteriorates, making them more susceptible to other diseases that can increase veterinary costs per animal.
  • Commercial restrictions: Some countries require any animals or animal products sold to be from healthy animals, which doesn’t include those that are MAP positive.
  • Potential public health implications: Although there is no proven link between MAP and the disease in humans, the perception of risk can lead to decreased demand for milk.
Cost of paratuberculosis in the world
  • United States: The total lost yield due to MAP infection is estimated to cause annual losses of €187 million ($200 million). The cost for seropositive herds has been estimated at €93 per head ($100) and up to €187 ($200) for clinical cases.
  • United Kingdom: In 2004, the average cost of paratuberculosis per animal per year was €30 ($32) for a dairy livestock and €20 ($21) for meat livestock.
  • Ireland: In 2006, a study showed that paratuberculosis incidence in cattle decreased the profit margin between €168 and €253 per head (approximately $210 to $316).
  • Other countries: Total annual losses per cow in infected herds are estimated at €28 – €54 ($30 – $58) in Australia, €32 ($34) in Canada and up to €234 ($250) in France.
Stages of paratuberculosis

The clinical course of paratuberculosis can be broken into three phases:

 

Initial phase

This happens at the end of the long incubation period. Animals become unthrifty and show progressive weight loss. They have mild or no diarrhea and still have a healthy appetite. This phase can include remission periods varying in length. In this phase, which can last several months, bacteria shedding is already very high.

 

Phase two

Most commonly in females after calving. The animal suffers intense, ongoing diarrhea, with a hard abdomen and fast muscle loss. This phase can last from two to six months.

 

Terminal phase

The constant diarrhea in the previous phase causes extreme malnutrition. The animals suffer anemia and edemas due to caquexia, which lead to death.

For each animal with clinical signs there can be up

to 25 animals infected.

How to control and prevent paratuberculosis?

Prevention:the best solution

Controlling paratuberculosis is a significant challenge for farmers and veterinarians. It is essential to combine proper diagnostic methods and biosafety and vaccination measures to control and eventually eradicate the disease from the herds. The difficulty lies in the long incubation period and constant shedding of bacteria in feces, even in asymptomatic animals.

 

Treatment is not advisable because, although it decreases the symptoms, the animals continue shedding bacteria in their feces, which helps them spread and contaminate the environment.

Control

Although tuberculosis, a more well-known mycobacterial infection, has been successfully controlled in animals in numerous countries, paratuberculosis remains an unresolved issue. Educating farmers and establishing health guidelines for purchasing animals are key parts of a control program, as well as being low cost measures.

Monitoring health status of replacement animals: The microbiology and serological results for all new animals must be taken into account, as well as the paratuberculosis history of their previous herd, before introducing them into the farm.
Avoid contact between young animals and infected adults: Newborn animals must be kept away from sources of fecal contamination, given colostrum from non-infected mothers and given a milk substitute or milk from healthy cows. Young animals should be kept separate from adults, only sharing grazing lands and facilities after they are one year old.
Ensure good hygiene and biosafety conditions: It is essential to deep clean all the equipment, drinking and feeding troughs, and ground with a high-pressure washer and detergent, and use the right disinfectants. The calving area should be cleaned and disinfected periodically.
Genetic selection of animals resistant to infection: Johne’s disease has an important genetic component. Breeding more resistant animals can help stop it from spreading.
Controlling manure: Manure storage and disposal must be carefully controlled and not spread in areas with cattle under one year old.
Proper nutrition: The animals need a balanced diet that strengthens their immune system.

Diagnosis

As the disease is subclinical in most animals, it is difficult to diagnose from signs and symptoms. In the incubation or subclinical phase, PCR and/or ELISA tests should be used. For animals with clinical paratuberculosis, bacterial cultures of fecal samples can be taken, which also allow for classification of the degree of infection.

Bacterioscopy or fecal culture: Shows MAP in feces with staining. Given its relatively low sensitivity and specificity, it should be used in combination with serological and PCR testing. It should never be used to examine asymptomatic animals.

PCR: Detects the presence of MAP-specific DNA in feces. It is affordable, sensitive, fast and able to detect animals in the early stage of infection, before they develop clinical signs. However, it has a large margin of error.

ELISA: Detects MAP antibodies. It is simple, fast, affordable, specific (97% – 99% precision) and can be automated, perfect for controlling paratuberculosis. Not recommend for animals under 18 months as the antibodies take time to appear. It is used to complement bacterioscopy and PCR in clinical cases.

 

These tests are helpful for detecting infected animals but ineffective when not used in conjunction with other control measures. These diagnostic measures are normally implemented along with culling infected animals, as there is no cure for this disease and the animal continues shedding bacteria into its environment, which can spread the disease to the rest of the livestock.

Vaccination

So far, controlling infection with preventive measures like improving hygiene and handling, testing and culling positive animals, despite reducing the spread of paratuberculosis, hasn’t yielded the anticipated results.

 

Vaccination has a good benefit-cost ratio, as it isn’t very expensive for the results it produces. Paratuberculosis vaccination reduces the risk of microbial contamination and prevents clinical signs, decreasing the resulting financial losses. Vaccination strategies have been widely applied in sheep in various countries with great success. Vaccination is recommended in young animals (under 1 month).

The main drawback to vaccination is that it can interfere with serological diagnosis of paratuberculosis and tuberculosis infections. However, using the comparative intradermal tuberculin test instead of the single intradermal tuberculin test could resolve the issue in the vast majority of cases.

 

This test consists in a simultaneous intradermal injection in two different spots with Mycobacterium bovis and Mycobacterium avium tuberculins. Greater reaction to the avian tuberculin indicates infection or vaccination with avian mycobacteria and rules out tuberculosis infection in mammals.

Bibliography
  • Bastida, F. y Juste, R.A. (2011) Paratuberculosis control: a review with a focus on vaccination. Journal of Immune Based Therapies and Vaccines, 9:8. doi: 10.1186/1476-8518-9-8.
  • Biemans, F., Ben Romdhane, R., Gontier, P., Fourichon, C., Ramsbottom, G., More, S.J. & Ezanno, P. (2021) Modelling transmission and control of Mycobacterium avium subspecies paratuberculosis within Irish dairy herds with compact spring calving. Preventive Veterinary Medicine, Vol 186, 105228. doi: 10.1016/j.prevetmed.2020.105228.
  • Donat, K., Schmidt, M., Köhler, H. & Sauter-Louis, C. (2016) Management of the calving pen is a crucial factor for paratuberculosis control in large dairy herds. Journal of Dairy Science. May;99(5):3744-3752. doi: 10.3168/jds.2015-10625.
  • Ezanno, P., Arnoux, S., Joly, A. & Vermesse, R. (2021) Rewiring cattle trade movements helps to control bovine paratuberculosis at a regional scale. Preventive Veterinary Medicine, Vol 198. doi: 10.1016/j.prevetmed.2021.10552.
  • Garcia, A.B. & Shalloo, L. (2015) Invited review: The economic impact and control of paratuberculosis in cattle. Journal of Dairy Science. 98(8):5019-39. doi: 10.3168/jds.2014-9241.
  • Garcia, A.B. & Shalloo, L. (2015) Invited review: The economic impact and control of paratuberculosis in cattle, Journal of Dairy Science Vol 98, 8; 5019-5039. doi: 10.3168/jds.2014-9241.
  • Garvey, M. (2020) Mycobacterium Avium Paratuberculosis: A Disease Burden on the Dairy Industry. Animals (Basel). 1;10(10):1773. doi: 10.3390/ani10101773.
  • GDS France (2021) Dossier paratuberculose bovine. Recuperado de: https://www.gdscreuse.fr/wp-content/uploads/2021/09/Paratuberculose-dossier-2021-08.pdf
  • GDS France (2021) Vers lamaitrise de la paratuberculose dans les élevages français grâce à la sélection génomique. Recuperado de: https://www.gdsfrance.org/wp-content/uploads/Fiche_Paratuberculose.pdf
  • Kirkeby, C., Græsbøll, K., Nielsen, S.S., Christiansen, L.E., Toft, N., Rattenborg, E. & Halasa, T. (2016) Simulating the Epidemiological and Economic Impact of Paratuberculosis Control Actions in Dairy Cattle. Frontiers in Veterinary Science. 3:90. doi: 10.3389/fvets.2016.00090.
  • Whittington, R., Donat, K., Weber, M.F. et al. (2019) Control of paratuberculosis: who, why and how. A review of 48 countries. BMC Veterinary Research. 15, 198. Doi: 10.1186/s12917-019-1943-4

DR. RAMON A. JUSTE

Researcher at NEIKER Research Institute

Dr. Ramón A. Juste got his B.S. in Veterinary Medicine from the University of Zaragoza in 1979, and a PhD from the same university in 1990. After a period in clinical practice, he started his research career at the Basque research institute NEIKER (then SIMA), where he has been SERIDA Managing Director since 2015.

 

He participated in the first descriptions of several diseases not yet formally reported in Spain, such as bovine paratuberculosis, besnoitiosis, hereditary parakeratosis in calves, oslerus rostratus in cats, and others. He also helped set up a veterinary diagnostic service that later became the model for others in Spain. He has published over 200 scientific papers and has an h-index of 40 according to the WOS.

 

We talk to him to learn more about paratuberculosis and how we can prevent and control its occurrence.

Vacuna Gudair
GUDAIR

Vaccine to immunize sheep and goats against Mycobacterium avium spp. paratuberculosis.

vacuna silirum

SILIRUM

Inactivated vaccine for cattle against Mycobacterium avium spp. paratuberculosis.

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