Background: Although controversial, there is evidence that IBD may be caused by infection with MAP. Recently, three agents (5-ASA, methotrexate and 6-MP) used to treat IBD because of clinical efficacy, but without an accepted mechanism of action, have been shown to inhibit MAP growth in culture. The purpose of this study was to determine the prevalence of MAP DNA in the blood of healthy controls and patients with IBD, to determine the influence of chronic treatment with these anti-MAP antibiotics and to evaluate the associations between MAP DNA prevalence, disease activity and patterns of treatment by geographical location.

Methods: The blood of 100 healthy individuals and 246 patients with IBD was evaluated for MAP DNA using nested PCR. Statistical analysis was by the Fischer Exact Test or Pearson Correlation as necessary.

Results: MAP DNA was detected in 47% (47/100) of the healthy controls and in 16.3% (40/246) of all subjects with IBD (p<0.0001). MAP DNA was found in 15% (37/246) IBD patients, who were receiving any anti-MAP antibiotic therapy. The lowest MAP DNA frequency was observed with combined methotrexate, sulfasalazine, 6-Mercaptopurine or Ciprofloxacin therapy 3.1% (1/32) (p<0.02). The group receiving azathioprine (a precursor of 6-MP) combined with prednisolone was 42% (5/12) MAP DNA+, compared to the group with azathioprine without prednisolone that were 10.5% (4/38) MAP DNA+ (p<0.03). MAP DNA prevalence varied by geographical location and showed a correlation with disease activity and pattern of treatment (p<0.001).

Conclusions: Analogous to leprosy, our data show an unsuspectedly high incidence of MAP DNA in healthy human blood donors. Chronic use of anti-MAP antibiotics is associated with a significantly lower incidence of MAP DNA, possibly an indication of therapeutic efficacy. The use of prednisolone is associated with an increased prevalence of MAP DNA. This may indicate prednisolone immunosuppression, and/or reflect IBD disease activity. The geographical variation may reflect different IBD therapy by local physicians and may become a useful indicator of therapeutic efficacy. These data are compatible with an etiological role of MAP in IBD that could be comparable with leprosy where for every case of clinical leprosy, >100 asymptomatic individuals shed M. leprae DNA.