Causation of Crohn's disease by Mycobacterium avium subspecies paratuberculosis

Mycobacterium avium subspecies paratuberculosis (MAP) is a member of the M avium complex (MAC). It differs genetically from other MAC in having 14 to 18 copies of IS900 and a single cassette of DNA involved in the biosynthesi s of surface carbohydrate. Unlike other MAC, MAP is a specific cause of chr onic inflammation of the intestine in many animal species, including primat es. The disease ranges from pluribacillary to paucimicrobial, with chronic granulomatous inflammation like leprosy in humans. MAP infection can persis t for years without causing clinical disease. The herd prevalence of MAP in fection in Western Europe and North America is reported in the range 21% to 54%. These subclinically infected animals shed MAP in their milk and onto pastures. MAP is more robust than tuberculosis, and the risk that is convey ed to human populations in retail milk and in domestic water supplies is hi gh. MAP is harboured in the ileocolonic mucosa of a proportion of normal pe ople and can be detected in a high proportion of full thickness samples of inflamed Crohn's disease gut by improved culture systems and IS900 polymera se chain reaction if the correct methods are used. MAP in Crohn's disease i s present in a protease-resistant nonbacillary form, can evade immune recog nition and probably causes an immune dysregulation. As with other MAC, MAP is resistant to most standard antituberculous drugs. Treatment of Crohn's d isease with combinations of drugs more active against MAC such as rifabutin and clarithromycin can bring about a profound improvement and, in a few ca ses, apparent disease eradication. New drugs as well as effective MAP vacci nes for animals and humans are needed. The problems caused by MAP constitut e a public health issue of tragic proportions for which a range of remedial measures are urgently needed.