Concluding Remarks

Ovine paratuberculosis is a worldwide issue that is overlooked in many countries. There are sev­eral reasons for this. One is the lower value of individual sheep compared with cattle, and the second is a greater focus on other mycobacterial infections (particularly Mycobacterium bovis) in other species.

The spread of the paratuberculosis in sheep has been helped by the slow development of clin­ical signs, the slow rate of transmission between animals and the low sensitivity of diagnostic tests, especially in the earlier stages of infection and disease. Overall there has been an increase in understanding of the issues surrounding MAP infection in sheep. For instance, while previous research predominately focused on diseased animals in comparison with uninfected sheep, the examination of sheep that have overcome a challenge with MAP may provide a better un­derstanding of the immune processes implicated in resistance to the disease. Improvements in the focus of current and future research may lead to increased understanding of the disease process and over time may result in improved diagnosis and better control measures.

References

Alzuherri, H.M., Woodall, C.J. and Clarke, C.J. (1996) Increased intestinal TNF-α, IL-1β and IL-6 expres­sion in ovine paratuberculosis. Veterinary Immunology and Immunopathology 49(4), 331-345. DOI: 10.1016/0165-2427(95)05477-4.

Alzuherri, H.M., Little, D. and Clarke, C.J. (1997) Altered intestinal macrophage phenotype in ovine para­tuberculosis.

Arsenault, J., Singh Sohal, J., Leboeuf, A., Helie, P., Fecteau, G. etal. (2019) Validation of an in-house real­time PCR fecal assay and comparison with two commercial assays for the antemortem detection of Mycobacterium avium subsp. paratuberculosis infection in culled sheep. Journal of Veterinary Diagnostic Investigation 31(1), 58-68. DOI: 10.1177/1040638718810744.

Bakker, D., Willemsen, P.T.J. and van Zijderveld, F.G. (2000) Paratuberculosis recognized as a problem at last: a review. Veterinary Quarterly 22(4), 200-204. DOI: 10.1080/01652176.2000.9695058.

Bannantine, J.P. and Stabel, J.R. (2002) Killing of Mycobacterium avium subspecies paratuberculosis within macrophages. BMC Microbiology 2(1), 2. DOI: 10.1186/1471-2180-2-2.

Bauman, C.A., Jones-Bitton, A., Jansen, J., Kelton, D. and Menzies, P. (2016a) Evaluation of fecal culture and fecal RT-PCR to detect Mycobacterium avium ssp. paratuberculosis fecal shedding in dairy goats and dairy sheep using latent class Bayesian modeling. BMC Veterinary Research 12(1), 212. DOI: 10.1186∕s12917-016-0814-5.

Bauman, C.A., Jones-Bitton, A., Menzies, P., Toft, N., Jansen, J. et al. (2016b) Prevalence of paratuber­culosis in the dairy goat and dairy sheep industries in Ontario, Canada. The Canadian Veterinary Journal 57, 169-175.

Beard, P.M., Rhind, S.M., Sinclair, M.C., Wildblood, L.A., Stevenson, K. et al. (2000) Modulation of γδ T cells and CD1 in Mycobacterium avium subsp. paratuberculosis infection. Veterinary Immunology and Immunopathology 77(3-4), 311-319. DOI: 10.1016∕S0165-2427(00)00238-5.

Begg, D.J. and Whittington, R.J. (2008) Experimental animal infection models for Johne's disease, an infectious enteropathy caused by Mycobacterium avium subsp. paratuberculosis. The Veterinary Journal 176(2), 129-145. DOI: 10.1016∕j.tvjl.2007.02.022.

Begg, D.J., O'Brien, R., Mackintosh, C.G. and Griffin, J.F.T.

Begg, D.J., de Silva, K., Carter, N., Plain, K.M., Purdie, A. et al. (2011) Does a Th1 over Th2 dominancy really exist in the early stages of Mycobacterium avium subspecies paratuberculosis infections? Immunobiology 216(7), 840-846. DOI: 10.1016/j.imbio.2010.12.004.

Begg, D.J., de Silva, K., Plain, K.M., Purdie, A.C., Dhand, N. et al. (2015) Specific faecal antibody re­sponses in sheep infected with Mycobacterium avium subspecies paratuberculosis. Veterinary Immunology and Immunopathology 166(3-4), 125-131. DOI: 10.1016/j.vetimm.2015.06.011.

Begg, D.J., Purdie, A.C., de Silva, K., Dhand, N.K., Plain, K.M. etal. (2017) Variation in susceptibility of dif­ferent breeds of sheep to Mycobacterium avium subspecies paratuberculosis following experimental inoculation. Veterinary Research 48(1), 36. DOI: 10.1186/s13567-017-0440-7.

Begg, D.J. and Griffin, J.F.T. (2005) Vaccination of sheep against M. paratuberculosis: immune parameters and protective efficacy. Vaccine 23(42), 4999-5008. DOI: 10.1016/j.vaccine.2005.05.031.

Berger, S.T. and Griffin, F.T. (2006) A comparison of ovine monocyte-derived macrophage function follow­ing infection with Mycobacterium avium ssp. avium and Mycobacterium avium ssp. paratuberculo­sis. Immunology and Cell Biology 84(4), 349-356. DOI: 10.1111/j.1440-1711.2006.01431.x.

Burrells, C., Clarke, C.J., Colston, A., Kay, J.M., Porter, J. et al. (1998) A study of immunological respons­es of sheep clinically-affected with paratuberculosis (Johne's disease): the relationship of blood, mesenteric lymph node and intestinal lymphocyte responses to gross and microscopic pathology. Veterinary Immunology and Immunopathology 66, 3-4.

Burrells, C., Clarke, C.J., Colston, A., Kay, J.M., Porter, J. etal. (1999) Interferon-gamma and interleukin-2 release by lymphocytes derived from the blood, mesenteric lymph nodes and intestines of nor­mal sheep and those affected with paratuberculosis (Johne's disease).

Bush, R.D., Windsor, P.A. and Toribio, J.A. (2006) Losses of adult sheep due to ovine Johne's dis­ease in 12 infected flocks over a 3-year period. Australian Veterinary Journal 84(7), 246-253. DOI: 10.1111/j.1751-0813.2006.00001.x.

Carrigan, M.J. and Seaman, J.T. (1990) The pathology of Johne's disease in sheep. Australian Veterinary Journal 67(2), 47-50. DOI: 10.1111/j.1751-0813.1990.tb07693.x.

Chiodini, R.J. (1996) Immunology: resistance to paratuberculosis. Veterinary Clinics of North America: Food Animal Practice 12, 313-343.

Clarke, C.J. (1997) The pathology and pathogenesis of paratuberculosis in ruminants and other species. Journal of Comparative Pathology 116(3), 217-261. DOI: 10.1016/S0021-9975(97)80001-1.

Clarke, C.J. and Little, D. (1996) The pathology of ovine paratuberculosis: gross and histological changes in the intestine and other tissues. Journal of Comparative Pathology 114(4), 419-437. DOI: 10.1016/ S0021-9975(96)80017-X.

Clarke, C.J., Colston, A., Little, D., Kay, J., Alzuherri, H.M. et al. (1996) The immune response in para­tuberculosis infection of small ruminants. Veterinary Immunology and Immunopathology 54(1-4), 321-324. DOI: 10.1016∕S0165-2427(96)05666-8.

de Juan, L., Mateos, A., Dominguez, L., Sharp, J.M. and Stevenson, K. (2005) Genetic diversity of Mycobacterium avium subspecies paratuberculosis isolates from goats detected by pulsed-field gel electrophoresis. Veterinary Microbiology 106(3-4), 249-257. DOI: 10.1016∕j.vetmic.2004.12.013.

de Silva, K., Begg, D.J., Plain, K.M., Purdie, A.C., Kawaji, S. et al. (2013) Can early host responses to my­cobacterial infection predict eventual disease outcomes? Preventive Veterinary Medicine 112(3-4), 203-212. DOI: 10.1016∕j.prevetmed.2013.08.006.

de Silva, K., Plain, K., Purdie, A., Begg, D. and Whittington, R. (2018) Defining resilience to mycobac­terial disease: characteristics of survivors of ovine paratuberculosis.

Delgado, L., Marin, J.F.G., Munoz, M., Benavides, J., Juste, R.A. etal. (2013) Pathological findings in young and adult sheep following experimental infection with 2 different doses of Mycobacterium avium sub­species paratuberculosis. Veterinary Pathology 50(5), 857-866. DOI: 10.1177/0300985813476066.

Dennis, M.M., Reddacliff, L.A. and Whittington, R.J. (2011) Longitudinal study of clinicopathological fea­tures of Johne's disease in sheep naturally exposed to Mycobacterium avium subspecies paratuber­culosis. Veterinary Pathology 48(3), 565-575. DOI: 10.1177/0300985810375049.

Dhand, N.K., Eppleston, J., Whittington, R.J. and Toribio, J.-A.L.M.L. (2007) Risk factors for ovine Johne's disease in infected sheep flocks in Australia. Preventive Veterinary Medicine 82(1-2), 51-71. DOI: 10.1016∕j.prevetmed.2007.05.007.

Ferguson,A.(1990)Mucosalimmunology. Immunology Today 11,1-3.DOI:10.1016/0167-5699(90)90002-Q. Fernandez, M., Benavides, J., Sevilla, I.A., Fuertes, M., Castano, P. et al. (2014) Experimental infection of lambs with C and S-type strains of Mycobacterium avium subspecies paratuberculosis: immunologi­cal and pathological findings. Veterinary Research 45(1), 5. DOI: 10.1186/1297-9716-45-5.

Florou, M., Leontides, L., Kostoulas, P., Billinis, C. and Sofia, M. (2009) Strain-specific sensitivity estimates of Mycobacterium avium subsp. paratuberculosis culture in Greek sheep and goats. Zoonoses and Public Health 56(1), 49-52. DOI: 10.1111/j.1863-2378.2008.01179.x.

Fridriksdottir, V., Gunnarsson, E., Sigurdarson, S. and Gudmundsdottir, K.B. (2000) Paratuberculosis in Iceland: epidemiology and control measures, past and present. Veterinary Microbiology 77(3-4), 263-267. DOI: 10.1016/S0378-1135(00)00311-4.

Gardner, I.A., Nielsen, S.S., Whittington, R.J., Collins, M.T., Bakker, D. et al. (2011) Consensus-based re­porting standards for diagnostic test accuracy studies for paratuberculosis in ruminants.

Gossner, A., Watkins, C., Chianini, F. and Hopkins, J. (2017) Pathways and genes associated with immune dysfunction in sheep paratuberculosis. Scientific Reports 7(1), 46695. DOI: 10.1038/srep46695.

Gumber, S., Eamens, G. and Whittington, R. (2006) Evaluation of a Pourquier ELISA kit in relation to agar gel immunodiffusion (AGID) test for assessment of the humoral immune response in sheep and goats with and without Mycobacterium paratuberculosis infection. Veterinary Microbiology 115(1-3), 91-101. DOI: 10.1016/j.vetmic.2006.01.003.

Gurung, R.B., Begg, D.J. and Whittington, R.J. (2018) A national serosurvey to determine the prevalence of paratuberculosis in cattle in Bhutan following detection of clinical cases. Veterinary Medicine and Science 4(4), 288-295. DOI: 10.1002/vms3.114.

Hein, W.R. and Griebel, P.J. (2003) A road less travelled: large animal models in immunological research. Nature Reviews Immunology 3(1), 79-84. DOI: 10.1038/nri977.

Hemalatha, S., Roy, P., Purushothaman, V. and Iyue, M. (2013) Paratuberculosis in different breeds of sheep: a retrospective study of cases. International Journal of Mycobacteriology 2(3), 166-170. DOI: 10.1016/j.ijmyco.2013.07.002.

Jones, D.G. and Kay, J.M. (1996) Serum biochemistry and the diagnosis of Johne's disease (paratubercu­losis) in sheep. Veterinary Record 139(20), 498-499. DOI: 10.1136/vr.139.20.498.

Kawaji, S., Taylor, D.L., Mori, Y. and Whittington, R.J. (2007) Detection of Mycobacterium avium subsp. paratuberculosis in ovine faeces by direct quantitative PCR has similar or greater sensitivity compared to radiometric culture. Veterinary Microbiology 125(1-2), 36-48. DOI: 10.1016/j.vetmic.2007.05.002.

Koets, A., Rutten, V., Hoek, A., van Mil, F., Muller, K. et al. (2002) Progressive bovine paratuberculo­sis is associated with local loss of CD4+ T cells, increased frequency of gamma delta T cells, and related changes in T-cell function. Infection and Immunity 70(7), 3856-3864. DOI: 10.1128/ IAI.70.7.3856-3864.2002.

Kumthekar, S., Manning, E.J.B., Ghosh, P., Tiwari, K., Sharma, R.N. et al. (2013) Mycobacterium avi­um subspecies paratuberculosis confirmed following serological surveillance of small ruminants in Grenada, West Indies. Journal of Veterinary Diagnostic Investigation 25(4), 527-530. DOI: 10.1177/1040638713490688.

Kurade, N.P. and Tripathi, B.N. (2008) Lymphoproliferative response and its relationship with histological lesions in experimental ovine paratuberculosis and its diagnostic implications. Veterinary Research Communications 32(1), 107-119. DOI: 10.1007∕s11259-007-9008-8.

Kurade, N.P., Tripathi, B.N., Rajukumar, K. and Parihar, N.S. (2004) Sequential development of histologic lesions and their relationship with bacterial isolation, fecal shedding, and immune responses during progressive stages of experimental infection of lambs with Mycobacterium avium subsp. paratuber­culosis. Veterinary Pathology 41(4), 378-387. DOI: 10.1354∕vp.41-4-378.

Lambeth, C., Reddacliff, L.A., Windsor, P., Abbott, K.A., Mcgregor, H. et al. (2004) Intrauterine and transmammary transmission of Mycobacterium avium subsp paratuberculosis in sheep. Australian Veterinary Journal 82(8), 504-508. DOI: 10.1111∕j.1751-0813.2004.tb11171.x.

Landsverk, T., Halleraker, M., Aleksandersen, M., McClure, S., Hein, W. et al. (1991) The intesti­nal habitat for organized lymphoid tissues in ruminants; comparative aspects of structure, function and development. Veterinary Immunology and Immunopathology 28(1), 1-16. DOI: 10.1016∕0165-2427(91)90038-E.

Liapi, M., Leontides, L., Kostoulas, P., Botsaris, G., Iacovou, Y. et al. (2011) Bayesian estimation of the true prevalence of Mycobacterium avium subsp. paratuberculosis infection in Cypriot dairy sheep and goat flocks. Small Ruminant Research 95(2-3), 174-178. DOI: 10.1016∕j. smallrumres.2010.09.010.

Little, D., Alzuherri, H.M. and Clarke, C.J. (1996) Phenotypic characterisation of intestinal lymphocytes in ovine paratuberculosis by immunohistochemistry. Veterinary Immunology and Immunopathology 55(1-3), 175-187. DOI: 10.1016∕S0165-2427(96)05716-9.

Ma, J.-G., Tian, A.-L., Zheng, W.-B., Zou, Y., Zhang, Y.-T. et al. (2019) First report of bovine viral diarrhea virus and Mycobacterium avium subspecies paratuberculosis infection in Tibetan sheep (Ovis aries) in Tibetan Plateau, China. Tropical Animal Health and Production 51(3), 719-722. DOI: 10.1007∕ s11250-018-1718-0.

Mackay, C.R., Beya, M.-F. and Matzinger, P. (1989) γ∕δ T cells express a unique surface molecule ap­pearing late during thymic development. European Journal of Immunology 19(8), 1477-1483. DOI: 10.1002∕eji.1830190820.

Mackintosh, C.G., Labes, R.E., Clark, R.G., de Lisle, G.W. and Griffin, J.F.T. (2007) Experimental infections in young red deer (Cervus elaphus) with a bovine and an ovine strain of Mycobacterium avium subsp paratuberculosis. New Zealand Veterinary Journal 55(1), 23-29. DOI: 10.1080∕00480169.2007.36731.

McGregor, H., Dhand, N.K., Dhungyel, O.P. and Whittington, R.J. (2012) Transmission of Mycobacterium avium subsp. paratuberculosis: dose-response and age-based susceptibility in a sheep model. Preventive Veterinary Medicine 107(1-2), 76-84. DOI: 10.1016∕j.prevetmed.2012.05.014.

Merkal, R.S., Kluge, J.P., Monlux, W.S., Larsen, A.B., Kopecky, K.E. et al. (1968) Experimental paratu­berculosis in sheep after oral, intratracheal, or intravenous inoculation: histochemical localization of hydrolase activities. American Journal of Veterinary Research 29, 985-994.

Moloney, B.J. and Whittington, R.J. (2008) Cross species transmission of ovine Johne's disease from sheep to cattle: an estimate of prevalence in exposed susceptible cattle. Australian Veterinary Journal 86(4), 117-123. DOI: 10.1111∕j.1751-0813.2008.00272.x.

Momotani, E., Whipple, D.L., Thiermann, A.B. and Cheville, N.F. (1988) Role of M cells and macrophages in the entrance of Mycobacterium paratuberculosis into domes of ileal Peyer's patches in calves. Veterinary Pathology 25(2), 131-137. DOI: 10.1177∕030098588802500205.

Munoz, M., Delgado, L., Verna, A., Benavides, J., Garcfa-Pariente, C. et al. (2009) Expression of trans­forming growth factor-beta 1 (TGF-β1) in different types of granulomatous lesions in bovine and ovine paratuberculosis. Comparative Immunology, Microbiology and Infectious Diseases 32(3), 239­252. DOI: 10.1016∕j.cimid.2007.11.009.

Mutwiri, G., Watts, T., Lew, L., Beskorwayne, T., Papp, Z. et al. (1999) Ileal and jejunal Peyer's patches play distinct roles in mucosal immunity of sheep. Immunology 97(3), 455-461. DOI: 10.1046∕j.1365-2567.1999.00791.x.

Nalubamba, K., Smeed, J., Gossner, A., Watkins, C., Dalziel, R. et al. (2008) Differential expression of pat­tern recognition receptors in the three pathological forms of sheep paratuberculosis. Microbes and Infection 10(6), 598-604. DOI: 10.1016∕j.micinf.2008.02.005.

Navarro, J.A., Ramis, G., Seva, J., Pallares, F.J. and Sanchez, J. (1998) Changes in lymphocyte subsets in the intestine and mesenteric lymph nodes in caprine paratuberculosis. Journal of Comparative Pathology 118(2), 109-121. DOI: 10.1016∕S0021-9975(98)80003-0.

Nicol, L., Wilkie, H., Gossner, A., Watkins, C., Dalziel, R. et al. (2016) Variations in T cell transcription fac­tor gene structure and expression associated with the two disease forms of sheep paratuberculosis. Veterinary Research 47(1), 83. DOI: 10.1186∕s13567-016-0368-3.

Nielsen, S.S. and Toft, N. (2009) A review of prevalences of paratuberculosis in farmed animals in Europe. Preventive Veterinary Medicine 88(1), 1-14. DOI: 10.1016∕j.prevetmed.2008.07.003.

O'Brien, R., Mackintosh, C.G., Bakker, D., Kopecna, M., Pavlik, I. etal. (2006) Immunological and molecu­lar characterization of susceptibility in relationship to bacterial strain differences in Mycobacterium avium subsp. paratuberculosis infection in the red deer (Cervus elaphus). Infection and Immunity 74(6), 3530-3537. DOI: 10.1128∕IAI.01688-05.

Perez, V., Marin, J.F.G. and Badiola, J.J. (1996) Description and classification of different types of le­sion associated with natural paratuberculosis infection in sheep. Journal of Comparative Pathology 114(2), 107-122. DOI: 10.1016∕S0021-9975(96)80001-6.

Plain, K.M., Purdie, A.C., Begg, D.J., de Silva, K. and Whittington, R.J. (2010) Toll-like receptor (TLR)6 and TLR1 differentiation in gene expression studies of Johne's disease. Veterinary Immunology and Immunopathology 137(1-2), 142-148. DOI: 10.1016∕j.vetimm.2010.04.002.

Plain, K.M., Marsh, I.B., Waldron, A.M., Galea, F., Whittington, A.-M. et al. (2014) High-throughput direct fecal PCR assay for detection of Mycobacterium avium subsp. paratuberculosis in sheep and cattle. Journal of Clinical Microbiology 52(3), 745-757. DOI: 10.1128∕JCM.03233-13.

Ponnusamy, D., Periasamy, S., Tripathi, B.N. and Pal, A. (2013) Mycobacterium avium subsp. paratuber­culosis invades through M cells and enterocytes across ileal and jejunal mucosa of lambs. Research in Veterinary Science 94(2), 306-312. DOI: 10.1016∕j.rvsc.2012.09.023.

Rast, L. and Whittington, R.J. (2005) Longitudinal study of the spread of ovine Johne's disease in a sheep flock in southeastern New South Wales. Australian Veterinary Journal 83(4), 227-232. DOI: 10.1111∕j.1751-0813.2005.tb11658.x.

Reddacliff, L.A. and Whittington, R.J. (2003) Experimental infection of weaner sheep with S strain Mycobacterium avium subsp. paratuberculosis. Veterinary Microbiology 96(3), 247-258. DOI: 10.1016∕j.vetmic.2003.07.004.

Reddacliff, L.A., McClure, S.J. and Whittington, R.J. (2004) Immunoperoxidase studies of cell medi­ated immune effector cell populations in early Mycobacterium avium subsp. paratuberculosis in­fection in sheep. Veterinary Immunology and Immunopathology 97(3-4), 149-162. DOI: 10.1016∕j. vetimm.2003.09.001.

Reddacliff, L., Eppleston, J., Windsor, P., Whittington, R. and Jones, S. (2006) Efficacy of a killed vac­cine for the control of paratuberculosis in Australian sheep flocks. Veterinary Microbiology 115(1-3), 77-90. DOI: 10.1016∕j.vetmic.2005.12.021.

Reynolds, J.D. and Morris, B. (1983) The evolution and involution of Peyer's patches in fetal and postnatal sheep. European Journal of Immunology 13(8), 627-635. DOI: 10.1002∕eji.1830130805.

Robbe-Austerman, S., Gardner, I.A., Thomsen, B.V., Morrical, D.G., Martin, B.M. et al. (2006a) Sensitivity and specificity of the agar-gel-immunodiffusion test, ELISA and the skin test for detection of para­tuberculosis in United States Midwest sheep populations. Veterinary Research 37(4), 553-564. DOI: 10.105Vvetres:2006018.

Robbe-Austerman, S., Stabel, J.R. and Palmer, M.V. (2006b) Evaluation of the gamma interferon ELISA in sheep subclinically infected with Mycobacterium avium subspecies Paratuberculosis using a whole­cell sonicate or a Johnin purified-protein derivative. Journal of Veterinary Diagnostic Investigation 18(2), 189-194. DOI: 10.1177∕104063870601800208.

Rossi, G., Nigro, G., Tattoli, I., Vincenzetti, S., Mariani, P. et al. (2009) Adhesion molecules and cytokine profile in ileal tissue of sheep infected with Mycobacterium avium subsp. paratuberculosis. Microbes and Infection 11(6-7), 698-706. DOI: 10.1016∕j.micinf.2009.04.006.

Seaman, J.T., Gardner, I.A. and Dent, C.H.R. (1981) Johne's disease in sheep. Australian Veterinary Journal 57(2), 102-103. DOI: 10.1111∕j.1751-0813.1981.tb00465.x.

Sergeant, E.S.G. (2001) Ovine Johne's disease in Australia - the first 20 years. Australian Veterinary Journal 79(7), 484-491. DOI: 10.1111∕j.1751-0813.2001.tb13021.x.

Sergeant, E.S.G. and Baldock, F.C. (2002) The estimated prevalence of Johne's disease infected sheep flocks in Australia. Australian Veterinary Journal 80(12), 762-768. DOI: 10.1111∕j.1751-0813.2002. tb11348.x.

Sevilla, I., Aduriz, G., Garrido, J., Geijo, M. V. and Juste, R.A. (2002) A preliminary survey on the prevalance of paratuberculosis in dairy cattle in Spain by bulk milk PCR. In: Juste, R. A., Geijo, M. V. and Garrido, J. (eds) Seventh International Colloquium on Paratuberculosis. International Association for Paratuberculosis, Bilbao, Spain, pp. 332-336.

Sevilla, I., Singh, S. V., Garrido, J.M., Aduriz, G., Rodriguez, S. et al. (2005) Molecular typing of Mycobacterium avium subspecies paratuberculosis strains from different hosts and regions. Revue Scientifique et Technique 24, 1061-1066.

Sevilla, I., Li, L., Amonsin, A., Garrido, J.M., Geijo, M.V. etal. (2008) Comparative analysis of Mycobacterium avium subsp. paratuberculosis isolates from cattle, sheep and goats by short sequence repeat and pulsed-field gel electrophoresis typing. BMC Microbiology 8(1), 204. DOI: 10.1186/1471-2180-8-204.

SigurSardottir, O. G.., Press, C.M. and Evensen, O. (2001) Uptake of Mycobacterium avium subsp. para­tuberculosis through the distal small intestinal mucosa in goats: an ultrastructural study. Veterinary Pathology 38(2), 184-189. DOI: 10.1354∕vp.38-2-184.

Smeed, J.A., Watkins, C.A., Rhind, S.M. and Hopkins, J. (2007) Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis. BMC Veterinary Research 3(1), 18. DOI: 10.1186/1746-6148-3-18.

Sohal, J.S., Arsenault, J., Leboeuf, A., Helie, P., Buczinski, S. et al. (2019) Molecular characterization of Mycobacterium avium subspecies paratuberculosis C-type and S-type isolated from sheep and goats by using a combination of MIRU-VNTR loci. Canadian Journal of Veterinary Research 83, 160-167.

Sonawane, G.G. and Tripathi, B.N. (2016) Comparative evaluation of diagnostic tests for the detection of Mycobacterium avium subsp. paratuberculosis in the tissues of sheep affected with distinct pa­thology of paratuberculosis. International Journal of Mycobacteriology 5(Suppl 1), S88-S89. DOI: 10.1016∕j.ijmyco.2016.09.005.

Stabel, J. (2000) Transitions in immune responses to Mycobacterium paratuberculosis. Veterinary Microbiology 77(3-4), 465-473. DOI: 10.1016∕S0378-1135(00)00331-X.

Stabel, J.R. (2006) Host responses to Mycobacterium avium subsp. paratuberculosis : a complex arsenal. Animal Health Research Reviews 7(1-2), 61-70. DOI: 10.1017∕S1466252307001168.

Stewart, D.J., Stiles, P.L., Whittington, R.J., Lambeth, C., Windsor, P.A. et al. (2002) Validation of the interferon-g for diagnosis of ovine Johne's disease: sensitivity and specificity field trials. Seventh International Colloquium on Paratuberculosis 148-153.

Sunderman, F. (2004) Update on the OJD program in Western Australia. Ovine Johne’s Disease - an Update of Australian Research. Meat & Livestock Australia, Sydney.

Taylor, D.L., Zhong, L., Begg, D.J., de Silva, K. and Whittington, R.J. (2008) Toll-like receptor genes are differentially expressed at the sites of infection during the progression of Johne's disease in outbred sheep. Veterinary Immunology and Immunopathology 124(1-2), 132-151. DOI: 10.1016/j. vetimm.2008.02.021.

Verin, R., Perroni, M., Rossi, G., De Grossi, L., Botta, R. et al. (2016) Paratuberculosis in sheep: histo­chemical, immunohistochemical and in situ hybridization evidence of in utero and milk transmission. Research in Veterinary Science 106, 173-179. DOI: 10.1016∕j.rvsc.2016.04.006.

Verna, A.E., Garcia-Pariente, C., Munoz, M., Moreno, O., Garcia-Marin, J.F. et al. (2007) Variation in the immuno-pathological responses of lambs after experimental infection with different strains of Mycobacterium avium subsp. paratuberculosis. Zoonoses and Public Health 54(6-7), 243-252. DOI: 10.1111∕j.1863-2378.2007.01058.x.

Whittington, R.J., Marsh, I., Turner, M.J., McAllister, S., Choy, E. et al. (1998) Rapid detection of Mycobacterium paratuberculosis in clinical samples from ruminants and in spiked environmen­tal samples by modified BACTEC 12B radiometric culture and direct confirmation by IS900 PCR. Journal of Clinical Microbiology 36(3), 701-707. DOI: 10.1128∕JCM.36.3.701-707.1998.

Whittington, R.J., Marsh, I., McAllister, S., Turner, M.J., Marshall, D.J. et al. (1999) Evaluation of modi­fied BACTEC 12B radiometric medium and solid media for culture of Mycobacterium avium sub­sp. paratuberculosis from sheep. Journal of Clinical Microbiology 37(4), 1077-1083. DOI: 10.1128∕ JCM.37.4.1077-1083.1999.

Whittington, R.J., Fell, S., Walker, D., McAllister, S., Marsh, I. et al. (2000a) Use of pooled fecal cul­ture for sensitive and economic detection of Mycobacterium avium subsp. paratuberculosis in­fection in flocks of sheep. Journal of Clinical Microbiology 38(7), 2550-2556. DOI: 10.1128∕ JCM.38.7.2550-2556.2000.

Whittington, R.J., Reddacliff, L.A., Marsh, I., Mcallister, S. and Saunders, V. (2000b) Temporal patterns and quantification of excretion of Mycobacterium avium subsp paratuberculosis in sheep with Johne's disease. Australian Veterinary Journal 78(1), 34-37. DOI: 10.1111∕j.1751-0813.2000.tb10355.x.

Whittington, R.J., Taragel, C.A., Ottaway, S., Marsh, I., Seaman, J. et al. (2001) Molecular epidemiological confirmation and circumstances of occurrence of sheep (S) strains of Mycobacterium avium subsp. paratuberculosis in cases of paratuberculosis in cattle in Australia and sheep and cattle in Iceland. Veterinary Microbiology 79(4), 311-322. DOI: 10.1016∕S0378-1135(00)00364-3.

Whittington, R.J., Whittington, A.-M., Waldron, A., Begg, D.J., de Silva, K. et al. (2013) Development and validation of a liquid medium (M7H9C) for routine culture of Mycobacterium avium subsp. paratu­berculosis to replace modified BACTEC 12B medium. Journal of Clinical Microbiology 51(12), 3993­4000. DOI: 10.1128∕JCM.01373-13.

Whittington, R.J., Begg, D.J., de Silva, K., Purdie, A.C., Dhand, N.K. et al. (2017) Case definition termi­nology for paratuberculosis (Johne's disease). BMC Veterinary Research 13(1), 328. DOI: 10.1186/ s12917-017-1254-6.

Whittington, R., Donat, K., Weber, M.F., Kelton, D., Nielsen, S.S. etal. (2019) Control of paratuberculosis: who, why and how. A review of 48 countries. BMC Veterinary Research 15(1), 198. DOI: 10.1186∕ s12917-019-1943-4.

Williams, E.S., Demartini, J.C. and Snyder, S.P. (1985) Lymphocyte blastogenesis, complement fixation, and fecal culture as diagnostic tests for paratuberculosis in North American wild ruminants and do­mestic sheep. American Journal of Veterinary Research 46, 2317-2321.

13