Lecture Notes on Paratuberculosis in Animals

Lecture notes on Paratuberculosis

1. Lecture Notes on Paratuberculosis Dr Vidya Singh Senior Scientist Division of Pathology, ICAR-Indian Veterinary Research Institute Izatnagar, Bareilly, UP, India- 243122

2. Paratuberculosis Synonym : Johne’s disease A chronic, progressive, and incurable granulomatous enteropathy of ruminants, caused by Mycobacterium avium subspecies paratuberculosis (MAP). It is a wasting disease that results in: Malabsorption, Protein-losing enteropathy , cachexia and death Etiology Mycobacterium avium subspecies paratuberculosis (MAP) Characteristics of MAP Morphology Acid-fast, Gram-positive, rod-shaped Growth Extremely slow-growing ; takes 8–16 weeks Culture requirement Requires Mycobactin J (iron- chelator ) for growth Resistance Highly resistant to heat, cold, drying, many disinfectants Intracellular survival Lives in macrophages by inhibiting phagosome -lysosome fusion Unique genomic feature contains IS900 insertion sequence (used in PCR) Type Host Preference Characteristics Type I & III Sheep/Goats Slow growth, more difficult to culture Type II Cattle Faster growth , more studied Type B Bison More virulent in wild ruminants

3. Epidemiology and Transmission Global Distribution: Worldwide in dairy cattle, sheep, goats, buffalo, wild ruminants . Endemic in India , especially in Rajasthan, Gujarat, Punjab, and southern states. Transmission : Fecal-oral: Ingestion of fecal-contaminated feed/water Milk/colostrum: Infected dams In utero: Rare but documented Semen: Possible but insignificant Risk Factors : Intensive farming , poor hygiene, mixed age group housing Exposure of neonates Environmental persistence (MAP survives >1 year ) Host Range : Species Clinical Susceptibility Cattle High Sheep & Goats High Buffalo High (India-specific) Deer, Antelope High Pigs, Horses Rare, subclinical Rabbits, Birds Experimental infections possible

4. Pathogenesis Oral ingestion of MAP (most commonly by neonates) Entry via Peyer’s patches in terminal ileum Phagocytosed by intestinal macrophages Inhibition of phagolysosome fusion → MAP survives & replicates Chronic granulomatous response in mucosa & lymph nodes Progressive villous atrophy , malabsorption, protein loss Systemic emaciation, hypoproteinemia , diarrhea Immunopathology: Early Th1 response : IFN-γ, macrophage activation (cellular immunity) Later Th2 switch : Humoral response dominates → ineffective Immunosuppressio n may occur in end-stage disease Clinical Signs Cattle Chronic watery diarrhea , emaciation, decreased milk, bottle jaw Sheep/Goats Emaciation, poor coat, rarely diarrhea, gradual wasting Buffalo Intermittent diarrhea , infertility, progressive weight loss Deer Rapid wasting , soft feces, sudden death

5. Gross Pathology Thickened, corrugated intestines (especially ileum, cecum, colon) Intestinal mucosa → rough, folded (" cerebriform ") Mesenteric lymphadenopathy Edematous mesentery Bottle jaw ( intermandibular edema due to hypoproteinemia ) In advanced cases: fatty liver, serous atrophy of fat Histopathology Tissue Lesions Intestine Granulomatous enteritis , macrophages with abundant cytoplasm, acid-fast bacilli, Langhans-type giant cells Lymph Nodes Enlarged, infiltrated with granulomas Ziehl-Neelsen stain Clumps of AFB in macrophages (" lepromatous " form) Special form “ Multibacillary ” (many bacilli) vs “ paucibacillary ” (few bacilli in goats)

6. Diagnosis Presumptive Diagnosis: Age >2 years, chronic wasting, unresponsive diarrhea, poor response to dewormers / antibiotics B. Laboratory Diagnosis: Test Principle Remarks Ziehl-Neelsen stain Acid-fast staining of feces Low sensitivity Fecal Culture (HEYM) Culture on mycobactin J media Gold standard; slow (8–16 wks ) PCR (IS900) Molecular detection of MAP DNA Rapid, highly specific ELISA Detects anti-MAP antibodies Good for herd screening Histopathology Tissue biopsy (ileum/LN) + AFB staining Confirmatory IFN- γ assay Cell-mediated immune response Early detection Johnin test Intradermal hypersensitivity Not widely used now

7. Differential Diagnosis Disease Differentiating Feature BVD-MD Oral erosions, mucosal disease, immunosuppression Coccidiosis Younger age group, blood/mucus in stool Salmonellosis Febrile enteritis, rapid progression Helminthiasis Anemia , eosinophilia Malnutrition History, low protein diet, no AFB Treatment No effective curative treatment exists Antimicrobials like Rifampicin + Clarithromycin or Clofazimine + Ethambutol have been tried but are costly and resistance-prone Supportive therapy: Electrolytes Digestive tonics Multivitamins Culling is economically preferred strategy

8. Control & Prevention A. Farm Biosecurity: Separate young calves from infected dams Use of pasteurized colostrum/milk Proper disposal of faeces and periodic disinfection of pens and floors B. Test and Culling: Periodic ELISA and PCR surveillance Culling or segregation of positives C. Vaccination: Killed whole-cell vaccines (e.g., Gudair ) used in sheep in Europe India: Indigenous vaccines from CIRG , IVRI in limited programs Not DIVA compatible (interferes with TB testing) ZOONOTIC POTENTIAL Strongly suspected link with Crohn’s disease in humans MAP DNA and cultures recovered from Crohn’s lesions MAP detected in raw milk, pasteurized milk, cheese Still under debate; WHO and FAO advise caution CURRENT RESEARCH Development of live attenuated vaccines Identification of MAP-specific antigens for DIVA-compatible ELISAs Use of bacteriophages , phage-therapy trials Nanoparticle-based diagnostics and LAMP assays Studies on genetic resistance in indigenous breeds