Elucidating transmission patterns of endemic Mycobacterium avium subsp. paratuberculosis using molecular epidemiology
Mitchell, Rebecca M. ; Beaver, Annabelle ; Knupfer, Elena ; Pradhan, Abani K. ; Fyock, Terry ; Whitlock, Robert H. ; Schukken, Ynte H. - \ 2019
Veterinary Sciences 6 (2019)1. - ISSN 2306-7381
MLSSR typing - Mutation rate - Mycobacterial co-infections - Mycobacterium avium subsp. paratuberculosis (MAP) - Vertical transmission - Within-host evolution
Mycobacterial diseases are persistent and characterized by lengthy latent periods. Thus, epidemiological models require careful delineation of transmission routes. Understanding transmission routes will improve the quality and success of control programs. We aimed to study the infection dynamics of Mycobacterium avium subsp. paratuberculosis (MAP), the causal agent of ruminant Johne's disease, and to distinguish within-host mutation from individual transmission events in a longitudinally MAP-defined dairy herd in upstate New York. To this end, semi-annual fecal samples were obtained from a single dairy herd over the course of seven years, in addition to tissue samples from a selection of culled animals. All samples were cultured for MAP, and multi-locus short-sequence repeat (MLSSR) typing was used to determine MAP SSR types. We concluded from these precise MAP infection data that, when the tissue burden remains low, the majority of MAP infections are not detectable by routine fecal culture but will be identified when tissue culture is performed after slaughter. Additionally, we determined that in this herd vertical infection played only a minor role in MAP transmission. By means of extensive and precise longitudinal data from a single dairy herd, we have come to new insights regarding MAP co-infections and within-host evolution.
Impact of the shedding level on transmission of persistent infections in Mycobacterium avium subspecies paratuberculosis (MAP)
Slater, Noa ; Mitchell, Rebecca Mans ; Whitlock, Robert H. ; Fyock, Terry ; Pradhan, Abani Kumar ; Knupfer, Elena ; Schukken, Ynte Hein ; Louzoun, Yoram - \ 2016
Veterinary Research 47 (2016)1. - ISSN 0928-4249
Super-shedders are infectious individuals that contribute a disproportionate amount of infectious pathogen load to the environment. A super-shedder host may produce up to 10 000 times more pathogens than other infectious hosts. Super-shedders have been reported for multiple human and animal diseases. If their contribution to infection dynamics was linear to the pathogen load, they would dominate infection dynamics. We here focus on quantifying the effect of super-shedders on the spread of infection in natural environments to test if such an effect actually occurs in Mycobacterium avium subspecies paratuberculosis (MAP). We study a case where the infection dynamics and the bacterial load shed by each host at every point in time are known. Using a maximum likelihood approach, we estimate the parameters of a model with multiple transmission routes, including direct contact, indirect contact and a background infection risk. We use longitudinal data from persistent infections (MAP), where infectious individuals have a wide distribution of infectious loads, ranging upward of three orders of magnitude. We show based on these parameters that the effect of super-shedders for MAP is limited and that the effect of the individual bacterial load is limited and the relationship between bacterial load and the infectiousness is highly concave. A 1000-fold increase in the bacterial contribution is equivalent to up to a 2-3 fold increase in infectiousness.