title: Two state model for a constant disease hazard in paratuberculosis (and other bovine diseases).
abstract: Many diseases are characterized by a long and varying sub-clinical period. Two main mechanisms can explain such periods: a slow progress toward disease or a sudden transition from a healthy state to a disease state induced by internal or external events. We here survey epidemiological features of the amount of bacteria shed during Mycobacterium Avium Paratuberculosis (MAP) infection to test which of these two models, slow progression or sudden transition (or a combination of the two), better explains the transition from intermittent and low shedding to high shedding. Often, but not always, high shedding is associated with the occurrence of clinical signs. In the case of MAP, the clinical signs include diarrhea, low milk production, poor fertility and eventually emaciation and death. We propose a generic model containing bacterial growth, immune control and fluctuations. This proposed generic model can represent the two hypothesized types of transitions in different parameter regimes. The results show that the sudden transition model provides a simpler explanation of the data, but also suffers from some limitations. We discuss the different immunological mechanism that can explain and support the sudden transition model and the interpretation of each term in the studied model. These conclusions are applicable to a wide variety of diseases, and MAP serves as a good test case based on the large scale measurements of single cow longitudinal profiles in this disease.
authors.affiliation: Gonda Brain Research Center and Department of Mathematics, Bar-Ilan University, Ramat Gan, Israel. louzouy@math.biu.ac.il.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Louzoun
authors.affiliation: ASM Post Doctoral Fellow at Centers for Disease Control and Prevention, Atlanta, Georgia. rmm257@gmail.com.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mitchell
authors.affiliation: Gonda Brain Research Center and Department of Mathematics, Bar-Ilan University, Ramat Gan, Israel. hilla.behar2@gmail.com.
authors.forename: Hilla
authors.initials: H
authors.lastname: Behar
authors.affiliation: GD Animal Health, Deventer, the Netherlands. yschukken@cornell.edu.|Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY, USA. yschukken@cornell.edu.
authors.forename: Ynte
authors.initials: Y
authors.lastname: Schukken
mesh_terms: D000818:Animals; D057138:Bacterial Shedding; D002417:Cattle; D002418:Cattle Diseases / Q000453:epidemiology* / Q000382:microbiology; D003612:Dairying; D005260:Female; D008390:Markov Chains; D008962:Models, Theoretical; D016927:Mycobacterium avium subsp. paratuberculosis / Q000254:growth & development / Q000502:physiology*; D010283:Paratuberculosis / Q000453:epidemiology* / Q000382:microbiology; D013269:Stochastic Processes