Epidemiological Evidence Investigating Transmissible Infection

An extensive amount of recent research has supported the presence of MAP in several po­tential routes of human exposure. Both vi­able MAP and MAP DNA have been detected in milk (Boulais et al., 2011; Okura et al., 2012)

Table 3.2.

MAP, Mycobacterium avium subsp. paratuberculosis; PCR, polymerase chain reaction.

including in commercially available milk (Carvalho et al., 2012; Gerrard et al., 2018) re­vealing the ability of this pathogen to withstand pasteurization. MAP has also been detected in meat (Lorencova et al., 2019), cheese (Botsaris et al., 2010; Faria et al., 2014), infant formula (Botsaris et al., 2016; Acharya et al., 2017), water sources (Beumer et al., 2010; Rhodes et al., 2013; Espeschit et al., 2018) and aerosols (Rhodes et al., 2014). From these data, it can be agreed upon that there are numerous opportu­nities for humans to be exposed to MAP. Yet the ability to detect MAP in the environment does not provide direct evidence of transmission of bacteria into humans, nor does it demonstrate that the burden in these sources exceeds the un­known infectious dose for humans.

A 2009 report described three individuals who developed Crohn's disease that lived in close proximity to one another but otherwise had no recorded contact. The author hypothesized that exposure may have occurred due to a shared water system (Pierce, 2009). Another study published by the same author described seven unrelated children who developed Crohn's dis­ease after moving to Forest, Virginia, where the number of cases of IBD was 47 times more than expected. Of these seven individuals, five (71.4%) were positive for MAP-specific antibod­ies (anti-p35 and anti-p36) (Pierce et al., 2011).

An argument raised in regard to the epi­demiology of the disease is that there is no evi­dence of an increased risk to developing Crohn's disease associated with persons in contact with MAP-infected animals such as farmers or veteri­narians (Jones et al., 2006). Since the previous edition, there have been few published stud­ies that have addressed this argument. A 2010 cross-sectional survey of 1476 cattle farmers and veterinarians found no relationship between Crohn's disease and MAP exposure (Qual et al.,

2010), although there were only seven cases of Crohn's disease recorded in total. In contrast, a study conducted on 58 animal attendants with reported gastrointestinal problems cultured more MAP compared with controls (Singh et al., 2011a). These data suggest a role of additional confounding factors such as location or the type of livestock.

Additional research is required in order to gain a clearer picture of the epidemiology sur­rounding the link between MAP and Crohn's disease. But there are several circumstances concerning these types of studies that should be considered. First, research aimed at associat­ing exposure to MAP (today) with presentation of disease (later) is impeded by the unknown incubation period; in cattle bacteria typically persist undetected in a subclinical state for 2-5 years before disease manifests (United States Department of Agriculture, 2008). Therefore, studies starting with ascertained MAP exposure may fail to link cases, which present years later; conversely, studies starting with Crohn's disease cases are unable to do microbial analysis of the environment to which one was exposed in the preceding years. Second, the idea that contact with infected animals must lead to an increased risk in development of the disease is not found with other bacteria whose aetiological role is ac­cepted. For example, cattle are the known reser­voirs for E. coli O157:H7, however no increased risk was associated with disease development in those in direct contact with infected cattle (Rangel et al., 2005). Third, Crohn's disease development is thought to involve a combina­tion of factors including genetic susceptibility and immune dysregulation. If MAP only plays a pathogenic role in such susceptible hosts, the vast majority of those exposed would not devel­op disease. Future research aimed at rigorously evaluating this argument must be long-term and evaluate both bacteriological exposure and host predisposition.

3.4