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Institute of Molecular Pathogenesis (IMP)

National Reference Laboratory for Paratuberculosis

Paratuberculosis, also called „Johne´s disease“, is a chronic inflammatory intestinal disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (Map).

After a latency period of several years clinical symptoms (diarrhea, weight loss and fatigue) are only visible in the final stage of the disease. Chronic diarrhea is observed in cattle and increasingly also in goats, while sheep are mainly characterized by weight loss and fatigue. However, Map is shed in high amounts via faeces also before clinical symptoms occur. Young animals are most susceptible for infection. Paratuberculosis is spread via trade with clinically healthy, latently infected animals.

The disease, which is reportable in Germany, has been reported from all regions of the country. Up to now it was detected in cattle, sheep, goats, red deer, roe deer und in a donkey. It causes considerable direct and indirect economic losses which are most severe in dairy herds (reduced milk yield, diminished slaughter value because of weight loss, increased susceptibility to other diseases, direct animal losses).

The zoonotic potential of the disease is controversial. Ongoing discussion and research addresses the role of Map in Morbus Crohn, a chronic inflammatory bowel disease of man.

Diagnosis of paratuberculosis is based on the detection of the causative agent in faeces and tissues (jejunum, ileum, ileocaecal valve, gut-associated lymph nodes) or on detection of antibodies in blood serum or milk. Detection of the causative agent is done by bacterioscopy (Ziehl-Neelsen staining) or by bacteriological culture followed by identification of the Map genome by PCR. Target regions for PCR can be IS900, f57 and others (Möbius et al., Vet. Microbiol. 126: 324-333, 2008.). Meanwhile, molecular detection of MAP in faecal samples using quantitative real-time PCR is an established diagnostic method. By January 2020, six real-time PCR-systems for the direct detection of MAP genome in DNA preparations from different specimen have been approved in Germany.

At present (01/2020), four ELISA assays for the detection of antibodies against Map in serum and milk samples of cattle and in part also of small ruminants are licensed in Germany.

Because of the chronic course of the disease detection of infected animals is delayed for a long time. Especially in young animals (cattle up to about 2 years) a negative test result does not exclude infection. Even in older animals repeated testing is necessary to increase the detection rate. Prevalence estimation is difficult with the established diagnostic methods.

Cultural and/or molecular biological examination of environmental faecal samples or boot swabs proved a cost-efficient approach for the detection of the paratuberculosis herd status even in low prevalence herds. Antibody detection in serum or milk samples of individual animals is also useful for the classification of the infection status of the herd. Antibody detection in pooled milk samples or bulk milk samples allows the identification of herds with high numbers of MAP shedders.

  • Reduction of paratuberculosis incidence in dairy goats by vaccination (ParaVac). EAFRD, European Innovation Partnership for Agriculture, 2020-2023. 
    https://www.thtsk.de/new/firstparavac/
  • Volatile organic compounds (VOC) of causative agent and host as biomarker for bacterial infections. (DFG, 2012-2015, Collaboration with WG Pathology and Pathophysiology of the IMP)
  • Identification of host-derived biomarkers of latent infections with Mycobacterium avium ssp. paratuberculosis (MAP). (Part of the EMIDA-ERA-Net consortium „Mycobactdiagnosis“, 2012-2015)
  • Differentiation of Mycobacterium avium subsp. paratuberculosis isolates – Relation between genotype and phenotype. (Partner VI: BMBF-Consortium „ZooMAP“, 2010-2013)
  • Development of improved test systems for the diagnosis, development and testing of vaccines for paratuberculosis. (FLI, Animal Health Insurance (AHI) of Baden-Wuerttemberg, AHI of Hesse, AHI of Mecklenburg-West Pomerania, AHI of Lower Saxony, AHI of Rheinland-Palatine, Thuringian AHI, 2009-2012)
  • Veterinary Network of Laboratories Researching into Improved Diagnosis and Epidemiology of Mycobacterial Diseases. (Co-ordination Action SSPE-CT-2004-501903, VENoMYC, EU, 2004-2010)
  • Differentiation of Mycobacterium avium subsp. paratuberculosis isolates of different origin with a standardized typing protocol. (Partner VI: BMBF Consortium „ZooMAP“, 2007-2010)
  • Evaluation of the efficiency of vaccination for controlling paratuberculosis in cattle. (FLI, 2007-2009).
  • Cultural isolation of Map and other mycobacteria from faeces and tissue
  • Cultural examination of mycobactin-dependence of Map
  • Direct detection of Map in faeces, tissue and environmental samples using real-time PCR
  • Molecular typing of Map using PCR, PCR-REA, RFLP, MIRU-VNTR and MLSSR
  • Detection of antibodies against Map in serum and milk using ELISA
  • Consultant for federal and state authorities regarding diagnosis and control of paratuberculosis
  • Clarification of ambiguous test results
  • Molecular typing of Mycobacterium avium subsp. paratuberculosis isolates
  • Supply of reference material (serum, milk samples)
  • Experimental evaluation of diagnostic kits for licensing
  • Organization of national proficiency tests
  • Panels of serum and milk samples from proved paratuberculosis positive or negative cattle
  • Reportable animal disease act of 20 December 2005 (BGBl. IS. 3517)
  • Recommendations of hygiene requirements for ruminant husbandry. III. Hygienic measures for particular diseases, 1. Measures for the protection against paratuberculosis in bovine holdings (Banz AT 01.08.2014 B1)