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

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.