This is from my pathologist Dr J T Kuenstner. I am currently on the Anti-map protocol and doing great
Dear Sir:
I wish to comment on the recent article by Warwick Selby and others entitled, “Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazamine for Crohn’s disease.” In the conclusion of the abstract, the authors claim that the findings of their study do not support a significant role for Mycobacterium avium paratuberculosis (MAP). Had the authors identified which patients were infected with MAP, provided evidence of eradication of MAP infection, and shown that patients were still symptomatic, they could more convincingly claim that their study does not support a significant role for MAP in Crohn’s disease.
The results of the Selby trial are encouraging (significantly better short-term remission rate in the treatment arm than the control arm) and suggest modifications of the current trial for future studies, which may lead to better outcomes. A blood culture method is now available to detect MAP infection in Crohn’s patients1
and could be used to assess MAP eradication in a properly designed controlled trial with more appropriate doses of the same drugs. The treatment of other nontuberculous mycobacterial infections such as Mycobacterium avium complex typically requires higher doses of clarithromycin, rifabutin, and clofazamine than were used in this trial.2
Ciprofloxacin could be added to the current regimen as well.
The study design required an unrealistically high response rate for a positive outcome. Most of the current Crohn’s therapies including infliximab would probably fail to show a positive outcome by this measure.
The Selby et al study was not designed to exclude the possibility of MAP reinfection following or during the course of therapy. MAP is present in viable form in pasteurized milk3
and many of the study patients most likely encountered repeated challenges with the organism during and after therapy. Furthermore, the possibility that the MAP-infected patients in this trial developed antibiotic resistance cannot be excluded by this study.
The study may not have had sufficient statistical power to show a more substantial benefit to a subset of the Crohn’s patients who might have benefited from the therapy. Studies show that approximately 50% of Crohn’s patients are infected with MAP.1
The other 50% may not benefit from therapy targeting MAP. In this study, 102 patients were in the antibiotic arm and thus, of these patients, approximately 51 may have been MAP infected. It is doubtful that this group is large enough to show a significant difference with this treatment.
In summary, the authors’ conclusions are not supported by their work. The authors consider the absence of a highly effective therapy as evidence that MAP is not pathogenic, and the fallacy of this argument is obvious. Would the authors maintain that Johne’s disease is not caused by MAP because curative therapies with antimycobacterial drugs have never been described for this disease? Case reports have shown suppression of Johne’s disease activity but not cures.4
The results of this trial should emphasize the direction for future efforts to ameliorate Crohn’s disease. Public health measures should be taken to prevent further spread of this infection and better therapies targeting MAP should be developed.
