Transmission of Mycobacterium avium subsp paratuberculosis: Dose-response and age-based susceptibility in a sheep model

Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden, 2570 NSW, Australia.
Preventive Veterinary Medicine (Impact Factor: 2.51). 07/2012; 107(1-2):76-84. DOI: 10.1016/j.prevetmed.2012.05.014
Source: PubMed

ABSTRACT Factors which influence the transmission of Mycobacterium avium subsp. paratuberculosis (MAP) between susceptible hosts are poorly defined, despite this organism causing economically significant disease in ruminants worldwide. A randomised longitudinal field trial was conducted using natural pasture-based exposure of 840 Merino sheep in a factorial design to test infection and disease outcomes in relation to age at first exposure and the level of exposure to MAP. Pasture contamination was initiated by MAP infected "donor" sheep which were present for 14.5 weeks of the 2.5 year study period. Sheep exposed to higher doses had 3.5 times greater odds to shed MAP in their faeces (assessed by faecal culture) compared to animals exposed to lower doses of infection. Similarly, sheep exposed to MAP as lambs had 7 times higher odds to shed MAP compared to sheep that were exposed for the first time as adults. However, animals of all ages and exposed at all doses were equally likely to be colonised by MAP (measured by culture of intestinal tissues) suggesting that some animals are inherently susceptible to infection. Age at first exposure was a significant determinant of histopathological lesion development, as lambs had about three times higher odds of developing severe lesions than adults after equivalent time (P=0.026). Mortalities due to paratuberculosis were strongly determined by the level of exposure; sheep exposed to high doses had 18 fold higher odds of death (P=0.007). Sheep exposed as lambs had 5 fold higher odds of dying due to paratuberculosis than adults (P=0.046). The results of this study provide sound experimental evidence for management recommendations in extensively grazed livestock to reduce the transmission of MAP by limiting exposure of young animals and reducing the levels of MAP pasture contamination.

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    • "This clinical phase is commonly manifested at a younger age in deer and wild ruminants (Mackintosh and Griffin, 2010). However, the length of the pre-clinical phase in sheep and goats is more difficult to assess without laboratory testing, due to a lack of definitive symptoms other than weight loss (which can be due to multiple other causes) (Robbe-Austerman, 2011) and has been reported to be as short as 1 month or as long as 5 years, possibly dependent on exposure dose (McGregor et al., 2012). "
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    ABSTRACT: Abstract This review addresses the survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP), the causative pathogen of Johne's disease (JD), once it has left its ruminant host. JD has significant economic impact on dairy, beef and sheep industries and is difficult to control due to the long-term sub-clinical nature of the infection, intermittent or persistent MAP shedding during and after this period, inadequate test effectiveness, and the potential for MAP to exist for extended periods outside the host. The role that environmental factors play in the persistence and spread of MAP and consequent disease is assessed. Published risk factor analysis, organism survival across various environmental media and conditions, presence and spread in ruminant and non-ruminant wildlife, and the general potential for survival and multiplication of MAP ex-host both on and off-farm are discussed and knowledge gaps highlighted. An inclusive approach to disease management that takes into account the persistence and transport of the causative organism in on-farm soils and waters, land use and management, dispersal by domestic and non-domestic host species, as well as general animal husbandry is required on those farms where more traditional approaches to disease management have failed to reduce disease prevalence.
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    ABSTRACT: Mycobacterium avium subsp paratuberculosis (Map) is assumed to infect young ruminants; however, little is known concerning the possibility of adult animals becoming infected. An experimental infection was conducted to establish the effect of age and doses of Map on susceptibility to paratuberculosis in sheep. Sixteen of twenty-four 1.5-month-old Churra lambs and 23 of 30 adult ewes (from 2-11 years old) were orally challenged with an ovine field strain of Map. Thirteen ewes and 8 lambs were infected with a high dose (HD) and 10 adult sheep and 8 lambs with a low dose (LD) of Map. The remaining animals were unchallenged controls. Animals were euthanized at 110 to 120 and 210 to 220 days postinfection. Histological, bacteriological, and nested polymerase chain reaction (PCR) studies were conducted in samples of intestine and related lymphoid tissue (Peyer patches, lymph nodes). Animals were classified according to their lesions. The number of granulomas was counted in 3 tissue sections from each sample. Only the HD groups showed lesions associated with paratuberculosis (92.3% of ewes and 100% of lambs). Adults had lesions characterized by few small demarcated focal granulomas restricted to the lymphoid tissue, whereas granulomas were more numerous and larger, appearing in the lamina propria unrelated to lymphoid tissue, in the lambs. Only HD-infected lambs were positive to culture, whereas nested PCR also detected positive HD ewes and some LD animals. These results suggest that adult sheep can become infected by Map, as seen by the development of lesions, but they are focal and restricted to the lymphoid tissue.
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    ABSTRACT: Diagnostic tests used for Johne's disease in sheep either have poor sensitivity and specificity or only detect disease in later stages of infection. Predicting which of the infected sheep are likely to become infectious later in life is currently not feasible and continues to be a major hindrance in disease control. We conducted this longitudinal study to investigate if a suite of diagnostic tests conducted in Mycobacterium avium subspecies paratuberculosis (MAP) exposed lambs at 4 months post infection can accurately predict their clinical status at 12 months post infection. We tracked cellular and humoral responses and quantity of MAP shedding for up to 12 months post challenge in 20 controls and 37 exposed sheep. Infection was defined at necropsy by tissue culture and disease spectrum by lesion type. Data were analysed using univariable and multivariable logistic regression models and a subset of variables from the earliest period post inoculation (4 months) was selected for predicting disease outcomes later on (12 months). Sensitivity and specificity of tests and their combinations in series and parallel were determined. Early elevation in faecal MAP DNA quantity and a lower interferon gamma (IFNγ) response were significantly associated with sheep becoming infectious as well as progressing to severe disease. Conversely, early low faecal MAP DNA and higher interleukin-10 responses were significantly associated with an exposed animal developing protective immunity. Combination of early elevated faecal MAP DNA or lower IFNγ response had the highest sensitivity (75%) and specificity (81%) for identifying sheep that would become infectious. Collectively, these results highlight the potential for combined test interpretation to aid in the early prediction of sheep susceptibility to MAP infection.
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