University of Wisconsin–Madison

MAP: A Zoonosis

Today’s news highlights the human health implications of MAP citing three different recently published articles. Shahzad and coauthors from Pakistan published a review article titled “Paratuberculosis; A Potential Zoonosis” in the journal Zoonosis (Open Access). Antonio and colleagues in Mexico describe detecting MAP in goat milk and various intermediate products in the production of cheese from goat milk (Journal of Veterinary Medicine and Animal Health, 2023 – Open Access) which is an example of how humans can be exposed to MAP even if they are not farmers.  The third article is a book chapter written by C.T. Dow titled “Mycobacterium avium ss. paratuberculosis and Human Disease: Bridging Infection and Autoimmunity”. This chapter focuses on the fact that an immune response to a microbial pathogen like MAP can trigger a variety of human diseases that are labeled as autoimmune diseases.

ABSTRACT

Paratuberculosis, commonly known as Johne’s disease (Yo’-nees), is primarily a disease of ruminants such as cattle, sheep and goats. It is a chronic infectious disease. The name of the disease is derived from the scientist’s name who  discovered it in 1985 named Johne’s along with his colleague Frothingham. The disease is associated with Mycobacterium avium subspecies paratuberculosis (abbreviated as MAP) is an obligate intracellular organism. This bacterium mainly damages the intestines. MAP is a member of Mycobacteriaceae family which also includes M. tuberculosis and M. leprae, causative agents of tuberculosis and leprosy, respectively. Paratuberculosis is also known as “Silent slayer” in USA. The prevalence of this disease is continuously increasing every year due to lack of proper disease control programmes. The reasons behind could be lack of awareness in public as well as the lack of concern shown by respective governmental disease control authorities. Paratuberculosis is chronic in nature due to which there is no accurate treatment for it. The transmission source for this disease is the infected animal. There is an ongoing uncertainty regarding its transmission to human as various researches have produced contradicting results. Its prevalence rate varies in different regions of the world however; it is found most commonly in the countries having intense livestock farming. Crohn’s disease (CD) is the term used for the disease in human where the clinical symptoms are similar to those seen in Johne’s disease in animals. MAP is considered the primary cause of CD along with other associated factors however it is yet not confirmed. Primarily, the consumption of dairy products, obtained from infected animals, is considered its mode of its transmission to human. Actual burden of CD is yet unknown as it goes unreported in most of the countries due to lack of awareness among the people & lack of sufficient funding for research purpose. Interdisciplinary research collaborations are necessary to cover the knowledge gaps regarding paratuberculosis, highlighting the significance of surveillance and preventive measures to reduce possible health hazards to people.

ABSTRACT

Mycobacterium avium subspecies paratuberculosis (MAP) is the etiological agent of paratuberculosis, which is one of the chronic diseases that cause financial losses in livestock production. MAP can be present in cheese and other dairy products, especially those made with unpasteurized milk. Contamination of the food supply chain exposes humans to the bacteria, making the disease an important zoonosis of public health significance and a one-health  emergency. The purpose of the study was to determine the presence of MAP in raw goat milk, natural rennet, and artisanal fresh cheese. A total of 18 milk samples were collected directly from the bulking tank, 23 from fresh cheese, and 10 from milk rennet from five municipalities in the State of San Luis Potosi, Mexico. Samples were analyzed through bacteriological culture and IS900 PCR-n. Statistical analysis was carried out in STATA® 7.0, analyzing frequencies and the Kappa test to determine the concordance index between bacteriological culture and IS900 PCR-n results. MAP was isolated from four milk samples  (n=4/18, 22%), one from cheese (n=1/23, 4.3%), while none were obtained from rennet samples. IS900 PCR-n detected 22 positive samples: 6/18 (33.3%) in milk, 8/10 (80%) in rennet and 8/23 (34.74%) in cheese. Concordance between IS900 PCR-n and bacteriological culture in milk samples was high (0.7273) but low in cheese samples (0.0707). MAP was detected in milk and artisanal cheese, although it is noteworthy that MAP genomic material was detected in 80% of rennet samples analyzed with PCR. Quality control of milk, rennet, and all the inputs used for making cheese is necessary.

Abstract

Common to many inflammatory/autoimmune diseases is the concept of an “environmental trigger.” Mycobacterium avium subspecies paratuberculosis (MAP) is the known infectious cause of Johne’s disease, an enteric inflammatory disease mostly studied in ruminant animals. For years, MAP has also been implicated in the very similar Crohn’s disease of humans and sarcoidosis, a systemic granulomatous disease. More recently, MAP has been associated with juvenile sarcoidosis (Blau syndrome), autoimmune diabetes, autoimmune thyroiditis, multiple sclerosis, rheumatoid arthritis, and Parkinson’s disease. While it may be intuitive to implicate MAP in granulomatous diseases where the microbe participates in the granuloma, it is more difficult to assign a role for MAP in diseases where autoantibodies are a primary feature. MAP may trigger autoimmune antibodies via its heat-shock proteins. Mycobacterial heat-shock protein 65 (HSP65) is an immunodominant protein that shares sequential and conformational elements with several human host proteins. This chapter proposes that MAP is a source of mycobacterial protein antigens and acts as a trigger to an array of inflammatory and autoimmune diseases.

COMMENTS

All major mycobacterial pathogens are zoonotic, and yet medical science seems resistant to assigning this designation to MAP. Moreover, diseases can be triggered both by the direct effects of infection or by a misguided immune response leading to immune-mediated (autoimmune) diseases. Well known human examples for this autoimmune mechanism are Strep throat, caused by Group A Streptococcus sp., leading to rheumatic fever (heart damage) and food poisoning due to Campylobacter jejuni leading to Guillain-Barré Syndrome (nerve paralysis).

Lacking the zoonotic pathogen designation, it is hard for researchers to secure funding to study MAP as a human health concern. It is a circular problem: when MAP is not considered zoonotic by human health agencies it results in no research funding which in turn results in no clarity about this problem of potentially enormous human impact, and so we continue with the status quo. Likewise, until MAP is officially declared a zoonotic pathogen the financial burden to control MAP in food-producing animals, and thereby limit public exposure to MAP, rests largely on the shoulders of animal owners. Control of zoonotic pathogens should be a societal responsibility.

For more on the link of MAP and Crohn’s disease, visit this page of our website which contains at the end a long list of refereed scientific publications supporting the link, or watch the short presentation titled MAP is a Zoonotic Pathogen on this page.