Mycobacterium avium ssp. paratuberculosis is the etiologic agent of Johne’s disease in ruminants and is hypothesized to be an infectious cause of Crohn’s disease, as well as some other human diseases. Due to key knowledge gaps, the potential public health impact of M. paratuberculosis is unknown. This scoping review aims to identify and characterised the evidence on potential sources and vehicles of M. paratuberculosis exposure for humans to better understand how exposure is likely to occur. Evidence from 255 primary research papers is summarized; most examined the prevalence or concentration of M. paratuberculosis in animals (farmed domestic, pets and wildlife) (n=148), food for human consumption (62) (milk, dairy, meat, infant formula) or water (drinking and recreational) and the environment (farm, pasture and areas affected by runoff water) (20). The majority of this research has been published since 2000 (Figure- abstract). Nine case-control studies examining risk factors for Crohn’s disease highlighted significant associations with the consumption of processed meats and cheese, while direct contact with ruminants, high risk occupations (farmer, veterinarian), milk consumption and water source were factors not associated with the disease and/or M. paratuberculosis exposure status. Molecular epidemiology studies demonstrated strain-sharing between species. Produce and seafood were the only previously suggested sources of human exposure for which there was no supporting evidence identified in this scoping review. The results of this review indicate that ruminant populations from around the globe are infected with M. paratuberculosis and many non-ruminant species have also been found to carry or be infected with M. paratuberculosis. Several potential sources for human exposure to M. paratuberculosis were identified; however there remain important gaps in quantitative information on the prevalence and concentration of M. paratuberculosis in contaminated sources of exposure. This information is critical to understanding the risk of exposure, opportunities for risk mitigation interventions and modelling exposures to distill the importance of various sources of human exposure to M. paratuberculosis including direct contact with animals and the environment as well as consumption of contaminated foods and water. Results of this study may be used to prioritize future research and to support evidence-informed decision-making on the M. paratuberculosis issue.

The aim of this licentiate thesis is to assess by literature the potential exposure of humans to Mycobacterium avium subspecies paratuberculosis (MAP) through food and drinking water in Finland and Minnesota, USA and to represent the prevalence (the total number of cases of a disease at a specific time) of Johne's disease and the prevalence and incidence (the number of new cases of a disease during a certain period of time) Crohn's disease in the United States, Minnesota and Finland. Johne's disease (JD), also known as paratuberculosis, is a globally important chronic intestinal disease of cattle and other ruminants such as goats and sheep caused by MAP. Crohn's disease (CD) is a chronic intestinal disease of humans. The etiology of CD is unknown but in addition to genetic susceptibility, environmental factors have been found to have an impact on the onset of the disease. It has been suggested that MAP could be one of the etiologic agents of CD. In the United States, JD is more common in dairy cattle than in beef cattle. The apparent cow-level prevalence is 6% and apparent herd-level prevalence is 68 % in dairy cattle. In Minnesota the apparent prevalence of JD in dairy cattle at the cow-level is 3% and at the herd-level 46%. In beef cattle the prevalence at the cow-level is only 0.3 % in Minnesota. The prevalence of CD in the United States is 241/100,000 and the annual incidence 20/100,000. The prevalence of CD in Minnesota is 222/100,000 and the annual incidence 13/100,000. In Finland, JD has been diagnosed in five beef cattle herds since 1992. The disease has not been diagnosed in dairy cattle or sheep or goats in Finland. The prevalence of CD in Finland is 124/100,000 and the annual incidence 9/100,000. The prevalence of MAP in food and drinking water in Finland has not been studied. Despite this, it is unlikely that people are exposed to MAP through drinking water or by eating foods of Finnish origin because the prevalence of JD in Finland is very low. However, exposure to the bacterium is possible by eating imported beef and dairy products such as cheese and yogurt. The share of imported foods within these food groups is relatively large in Finland. Dairy products and beef are imported for example from Germany and Denmark where the prevalence of JD at the herd-level is about 50–80 %. In the United States the occurrence of MAP in foods and drinking water has been studied quite much. It appears that the bacterium is found in foods and drinking water of U.S. origin. Because JD is so common in the United States and Minnesota, it is likely that people are exposed to the bacterium in Minnesota even though not all the food eaten is produced in the state. It is likely that people in areas of high prevalence of JD are exposed more to MAP than people in areas of low prevalence of JD. Comparing subsets of CD patients with high exposure to MAP to healthy controls with and without exposure to MAP could reveal the possible role of MAP in the complex etiology of CD. Based on this literature review it can be assumed that in Finland CD is caused by some other environmental agent than MAP. This licentiate thesis sets up further research needs to estimate the true human exposure to MAP. | Tämän lisensiaatin tutkielman tarkoituksena on arvioida kirjallisuuden avulla ihmisten altistumista Suomessa ja Minnesotan osavaltiossa, Yhdysvalloissa Mycobacterium avium subspecies paratuberculosis (MAP) -bakteerille elintarvikkeiden ja juomaveden välityksellä sekä raportoida paratuberkuloosin prevalenssi eli vallitsevuus (sairaiden lukumäärä tietyllä hetkellä) ja Crohnin taudin prevalenssi ja insidenssi eli ilmaantuvuus (uusien sairastapauksien määrä tiettynä ajanjaksona) Yhdysvalloissa, Minnesotassa ja Suomessa. Paratuberkuloosi (englanninkielisessä kirjallisuudessa usein Johnen tauti) on maailmanlaajuisesti merkittävä nautojen ja muiden märehtijöiden kuten vuohien ja lampaiden krooninen suolistosairaus, jonka aiheuttaa MAP-bakteeri. Crohnin tauti puolestaan on ihmisten krooninen suolistosairaus. Crohnin taudin etiologia eli sairauden syy on epäselvä, mutta geneettisen alttiuden lisäksi myös ympäristötekijöillä on todettu olevan vaikutusta taudin puhkeamiseen. On ehdotettu, että MAP saattaisi olla yksi Crohnin taudin aiheuttajista. Yhdysvalloissa paratuberkuloosi on yleisempi lypsykarjoissa kuin lihakarjoissa. Lypsylehmillä prevalenssi on yksilötasolla 6 % ja tilatasolla 68 %. Minnesotassa lypsylehmillä paratuberkuloosin prevalenssi on yksilötasolla 3 % ja tilatasolla 46 %, kun taas osavaltion lihanaudoilla prevalenssi on ainoastaan 0,3 %. Crohnin taudin prevalenssi on Yhdysvalloissa 241/100.000 ja vuosittainen insidenssi 20/100.000. Minnesotassa Crohnin taudin prevalenssi on 222/100.000 ja vuosittainen insidenssi 13/100.000. Suomessa paratuberkuloosia on todettu viidellä eri lihakarjatilalla vuoden 1992 jälkeen. Tautia ei ole löydetty lypsykarjoista eikä myöskään vuohilla tai lampailla. Crohnin taudin prevalenssi on Suomessa 124/100.000 ja vuosittainen insidenssi 9/100.000. Suomessa MAP-bakteerin esiintyvyyttä elintarvikkeissa ja juomavedessä ei ole tutkittu. Siitä huolimatta on epätodennäköistä, että ihmiset altistuisivat bakteerille juomaveden kautta tai syödessään kotimaisia elintarvikkeita, koska paratuberkuloosin prevalenssi Suomessa on erittäin alhainen. Bakteerille altistuminen on kuitenkin mahdollista esimerkiksi ulkomaalaisten maitotuotteiden, kuten juuston ja jogurtin sekä naudanlihan välityksellä, joiden maahantuonti ja osuus kulutetuista elintarvikkeista Suomessa on kohtalaisen suurta. Maitotuotteita ja naudanlihaa tuodaan Suomeen paljon muun muassa Saksasta ja Tanskasta, missä paratuberkuloosin tilatason prevalenssi on noin 50–80 %. Yhdysvalloissa MAP-bakteerin esiintyvyyttä elintarvikkeissa ja juomavedessä on tutkittu kohtalaisesti. Vaikuttaa siltä, että bakteeria esiintyy Yhdysvalloissa juomavedessä sekä elintarvikkeissa. Koska paratuberkuloosi on niin yleinen Yhdysvalloissa ja Minnesotassa, on todennäköistä, että ihmiset Minnesotassa altistuvat bakteerille, vaikkei kaikki minnesotalaisten syömä ruoka olisikaan tuotettu tämän osavaltion alueella. On todennäköistä, että korkeilla paratuberkuloosin prevalenssialueilla asuvat ihmiset altistuvat MAP-bakteerille enemmän ruoan ja juomaveden välityksellä kuin ihmiset alhaisilla prevalenssialueilla. Vertailemalla Crohnin taudin potilaiden osajoukkoja terveisiin kontrolleihin, jotka sekä altistuvat, että eivät altistu MAP-bakteerille on mahdollista selvittää MAP-bakteerin mahdollista roolia Crohnin taudin monitahoisessa etiologiassa. Tämän kirjallisuuskatsauksen perusteella voidaan olettaa, että Suomessa Crohnin taudin aiheuttaa jokin muu ympäristötekijä kuin MAP. Tämä lisensiaatin tutkielma antaa pohjatietoa todellisen MAP-bakteerille altistumisen arvioinnille.