Abstract
The objective of this paper is to study shedding patterns of cows infected with Mycobacterium avium subsp. paratuberculosis (MAP). While multiple single farm studies of MAP dynamics were reported, there is not large scale meta-analysis of both natural and experimental infections. Large difference in shedding patterns between experimentally and naturally infected cows were observed. Experimental infections are thus probably driven by different pathological mechanisms. For further evaluations of shedding patterns only natural infections were used. Within such infections, the transition to high shedding was studied as a proxy to the development of a clinical disease. The majority of studied cows never developed high shedding levels. Those that do, typically never reduced their shedding level to low or no shedding. Cows that eventually became high shedders showed a pattern of continuous shedding. In contrast, cows with an intermittent shedding pattern had a low probability to ever become high shedders. In addition, cows that start shedding at a younger age (less than three years of age) have a lower hazard of becoming high shedders compared to cows starting to shed at an older age. These data suggest the presence of three categories of immune control. Cows that are intermittent shedders have the infection process under control (no progressive infection). Cows that start shedding persistently at a young age partially control the infection, but eventually will be high shedders (slow progressive infection), while cows that start shedding persistently at an older age cannot effectively control the infection and become high shedders rapidly.
Highlights
Incubation periods and sub-clinical periods of chronic infectious diseases are quite variable in duration, with some individuals becoming ill shortly after infection and some individuals surviving months or years without illness (e.g. Human Immuno-deficiency Virus (HIV) infections [1], Herpes virus infections [2,3,4], prion induced diseases [5], Mycobacterium bovis [6], Mycobacterium tuberculosis infections [7] and Bovine Leukemia virus (BLV) infections [8]
This is in stark contrast with experimental infections (Gray bars in Figure 1D), where almost all animals eventually become high shedders (85%) (Figure 1D)
This rate of becoming a high shedder is at least 10 times higher for experimental infections, with over 50% of cows becoming high shedders by the age of three and almost all cows becoming high shedders at some stage of their live
Summary
Incubation periods and sub-clinical periods of chronic infectious diseases are quite variable in duration, with some individuals becoming ill shortly after infection and some individuals surviving months or years without illness (e.g. Human Immuno-deficiency Virus (HIV) infections [1], Herpes virus infections [2,3,4], prion induced diseases [5], Mycobacterium bovis [6], Mycobacterium tuberculosis infections [7] and Bovine Leukemia virus (BLV) infections [8]. An important mycobacterial infection in farm animals is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Mitchell et al Veterinary Research (2015) 46:66 animals, eventually clinical disease will develop. A number of infected animals will show signs of clinical disease, many infected animals do not progress during their lifetime on the farm to a clinical state. These animals may be detected with diagnostic testing during their lifetime, or in post-mortem testing of tissues in the slaughterhouse. Note that even if these high shedders do not eventually develop clinical signs, they probably are the main source of infection, and their dynamics are important as such
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