02296nas a2200241 4500000000100000008004100001260001300042653001200055653002600067653001100093653001800104653001100122653001200133653004800145653002100193653001700214100001800231245011100249300001100360490000600371520166300377022001402040 2003 d c2003 Aug10aAnimals10aAnti-Bacterial Agents10aCattle10aCrohn Disease10aHumans10aleprosy10aMycobacterium avium subsp. paratuberculosis10aParatuberculosis10aTuberculosis1 aGreenstein RJ00aIs Crohn's disease caused by a mycobacterium? Comparisons with leprosy, tuberculosis, and Johne's disease. a507-140 v33 a

Although Crohn's disease is considered to be autoimmune in origin, there is increasing evidence that it may have an infectious cause. The most plausible candidate is Mycobacterium avium subspecies paratuberculosis (MAP). Intriguingly, Koch's postulates may have been fulfilled for MAP and Crohn's disease, even though they still have not been met for Mycobacterium leprae and leprosy. In animals MAP causes Johne's disease, a chronic wasting intestinal diarrhoeal disease evocative of Crohn's disease. Johne's disease occurs in wild and domesticated animals, including dairy herds. Viable MAP is found in human and cow milk, and is not reliably killed by standard pasteurisation. MAP is ubiquitous in the environment including in potable water. Since cell-wall-deficient MAP usually cannot be identified by Ziehl-Neelsen staining, identification of MAP in human beings requires culture or detection of MAP DNA or RNA. If infectious in origin, Crohn's disease should be curable with appropriate antibiotics. Many studies that argue against a causative role for MAP in Crohn's disease have used antibiotics that are inactive against MAP. However, trials that include macrolide antibiotics indicate that a cure for Crohn's disease is possible. The necessary length of therapy remains to be determined. Mycobacterial diseases have protean clinical manifestations, as does Crohn's disease. The necessity of stratifying Crohn's disease into two clinical manifestations (perforating and non-perforating) when interpreting the results of antibiotic therapy is discussed. Rational studies to evaluate appropriate therapies to cure Crohn's disease are proposed.

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