Age and Dose Dependent Susceptibility to Mycobacterium avium subspecies paratuberculosis Infection in Dairy Calves.

摘要

Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease (JD), a chronic enteritis in ruminants. Control programs focus on prevention of infection of susceptible individuals: calves < 6 months of age. However, this age-cut-off for susceptibility is not well supported scientifically. Additionally, control programs struggle with low sensitivity of diagnostic tests in the early stages of JD.;The main objective of this thesis was to determine age-dependent susceptibility in dairy calves. Additionally, the course of immune responses as well as fecal shedding was assessed. Furthermore, gross lesions, histology and MAP-culture from tissues were used to confirm infection status of each calf, and to investigate age-dependent susceptibility.;Fifty calves were inoculated per os on 2 consecutive days at 2 weeks and 3, 6, 9, or 12 months. Within each age group calves received either a high (5 x 109 CFU) or low dose (5 x 107 CFU) of MAP. Six calves served as a negative control group. Serum, whole blood and fecal samples were collected regularly until necropsy at 17 months of age. Macroscopic and histological lesions were assessed and bacterial culture was performed on tissue samples.;Calves were successfully infected with MAP up to 1 year of age even with a low dose of MAP. Calves inoculated at 2 weeks, 3, or 6 months of age with a high dose of MAP had more severe necropsy lesions, were shedding MAP in feces more frequently, and had a stronger humoral and cellular immune response, than calves inoculated with a low dose. Shedding and humoral immune responses differed between individual calves and were detected in about half of the calves, which was more than anticipated. A dose-dependent cellular immune response was detected in each inoculated calf soon after inoculation using an interferon-gamma release assay and is therefore a good candidate test for early diagnosis. To conclude, calves are susceptible to MAP infection up to 1 year of age and could be infectious to other calves. Keeping the infection pressure low on-farm could reduce the severity of JD. Early diagnosis of MAP-infection is possible and this could improve the potential to control JD on-farm.