david.crichton
Joined: 02 May 2008
Posts: 83
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 Posted: Sat Aug 09, 2008 5:41 am Post subject: |
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The cons don't seem that compelling.
1. It depends on how MAP is transmitted. If it is by aerosol, then there is an observed occupational risk for those working near the pathogen (tuberculosis, brucellosis), or, similarly, by direct contact (cutaneous anthrax, hepatitis B). But there is not necessarily an observed increased occupational risk for farmers if the pathogen is spread by food. (campylobacter, e-coli O157) (Behr and Kapur 2007 Gastroenterology). Plus, and perhaps counterintuitive to the above, the risk of TB on farms was lower despite TB being a transmissible agent. And finally, what about all the acquired immunity considerations, and how one mycobacteria can confer protection against another?
2. There is dissimilarity between all species. That is, ParaTB infection differs depending on the host genetics; bovine paraTB different than sheep, but sheep closely resembles CD.
3. CD patients are usually tested later in disease after having been on immunesuppressants for years, of course there could be a failure to detect a strong immune response. Plus, immune response likely cellular and not humoral. Behr has demonstrated a cellular immune response in at least one patient, and Clancy et al. demonstrated significantly higher levels of TNF-alpha secretion in patients with CD and positive for MAP than for patients with UC or normal controls.
4. No evidence from clinical or experimental practice that anti-TNF biologics exacerbate MAP infections. It would be inappropriate to assume so based on the experience of TB. In fact, studies show a different role for TNF-alpha in TB infection than in infection with M. avium (Behr and Kapur 2007 Gastroenterology). Plus, anti-TNF biologics are almost certainly causing cell death of immune cells, and it is quite plausible that immune cells contain MAP. Whereas TB can survive extracellularly where the cell death of immune cells would not kill it, MAP must be intracellular, where cell death of immune cells would kill it. Steroids are sometimes used in mycobacterial infections - pulmonary tuberculosis is often treated with short term use of corticosteroids in order to reduce inflammation and improve oxygenation while the antibiotics kill off the infection. Steroids are also used in the treatment of leprosy (Chamberlin and Naser 2006 Medical Science Monitor). And while short term gain is sometimes achieved, without the antibiotics, the long term benefit from steroids would likely be negative, which is maybe the case with CD where most patients are given steroids at one point or another and most require at least one surgery and many others require two surgeries.
5. Might say more about the drugs than the theory. The doses were lower than what is recommended now. Patients were removed fairly early if they didn't meet higher response expectations. Treatment was not that long compared to other mycobacterial diseases. A reanalysis shows an absolute benefit that was significant at all timepoints (Behr June 2008 Lancet Vol 8)...
Plus, maybe factors inherent in mycobacteria or host factors that predisposed patients to the infection in the first place might make it difficult to eradicate the bacteria even if appropriate ABXs are used (Chamberlin and Naser 2006 Medical Science Monitor). Nonetheless, the response rate at 16 weeks was similar to that achieved by Remicade in its original studies (Ibid), SO WHY THE RELUCTANCE TO USE ABXs IN PATIENTS WHO HAVE FAILED EVERYTHING ELSE AND ARE FACING THE KNIFE??? |
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