LYME POLICY WONK: “The IDSA will not hesitate to change its guidelines”– True or False?
If you don't read medical journals or medical ethics journals, you may have missed a comment made by Dr. Ann Gershon in the Southern Medical Journal. She is responding to an article by Susan Ronn that was published together with an editorial by me and Dr. Stricker. It took me a couple of times reading this, but I think she made a promise based on a dare. She says: "If and when there is credible evidence of the existence of chronic Lyme disease and of the benefits of long-term antibiotic therapy to treat it, IDSA WILL NOT HESITATE TO CHANGE ITS GUIDELINES TO REFLECT THIS EVIDENCE."
If it is true that the IDSA will not hesitate to change it guidelines to reflect the evidence, we should be in good shape. Those who saw the video of the hearings were truly blown away by the weight of evidence in Dr. Phillips’ presentation on persistence. He presented not just one or two instances of persistence, but a remarkable number of studies demonstrating persistence of the organism notwithstanding treatment in animals and man as evidence by PCR, culture and other methods of direct detection. He backed these up with an 81 page submission to the panel that included 226 citations to peer-reviewed scientific research documenting the persistence of Lyme disease bacteria notwithstanding treatment. That sounds pretty convincing to me. How about you?
Oh, yeah. And then Dr. David Volkman said there was evidence of persistence and Dr. Ben Luft also said that. Well, this is now beginning to look like a rout on the issue of persistence.
The IDSA’s viewpoint seems to be that, well, if there is persistence, we should be able to demonstrate it in every patient. The problem is that direct detection methods are notoriously bad in Lyme. With antibody tests, we know that the tests themselves are bad (no better than a coin toss) in terms of detecting cases of Lyme by those who have it. But with direct detection tests, the issue is different. The tests are good enough, but the organism is not cooperative. The two direct detection methods for the Lyme bacteria are PCR and culture. It is extremely hard to culture Lyme bacteria and this is not commercially feasible. Lyme bacteria are what is known as “sparse” and “fastidious”. This means there aren’t many of them and they stick to themselves (for instance, don’t replicate often). In a culture Petri dish, this means they won’t replicate or grow enough to produce a positive result in a reasonable amount of time. The time it takes to grow a culture of Lyme is very long. Physicians do not use this method of detection of Lyme because it is not practical.
While PCR positive Lyme is very specific–meaning if you are PCR positive you have it–it is not very sensitive–meaning it misses a lot of patients. In fact, if you know that 100 patients have Lyme only 10-15 of these will test positive by PCR in blood. This is because the PCR blood test has “low yield.” The organism that causes Lyme disease is sparse–there are very few floating in the blood. They also tend to head for the hills–meaning tissues, brain, bladder, ligaments, eyes, etc. A PCR blood test has to capture an organism in the blood in order to test positive. This is why so few patients test positive by PCR blood tests. There is also the fact that while antibiotics may not kill all of the Lyme in the body, particularly if it is hiding out in places that the antibiotics may not reach, they do clear the blood of the infection. So a patient on antibiotics is expected to test negative by PCR and only 10-15% of those not on antibiotics will test positive. Dr. Stricker pointed out to me an interesting parallel with AIDS. When they first came out with the combination anti-virals to treat the infection, the tests for HIV turned negative and the researchers and physicians assumed the virus was “gone.” Not so, it just was no longer detectable by those tests and came back out from tissue hideouts and became detectable again when the anti-virals were stopped.
PCR culture is good in some tissue sites (like near the EM rash), but testing may require more samples to obtain a positive result in other areas of tissue. For instance, in the Straubinger dog studies, they euthanized the dogs and took 25 tissue samples. Clearly, this is too invasive for humans.
Well, what about the Klempner study that showed that 0 patients, ZERO, tested postive. How can that be? You would expect 10-15% to test positive, right? A rather obvious conclusion would be that the PCR test being used was faulty. Interestingly, this possibility is not raised in the study or its conclusions. How could this not have been considered? The PCR test used there was “home brewed”, new, and unvalidated. The issue of it not being accurate should have been front and center.
At the end of the day, the evidence for persistence is pretty overwhelming. Does this mean the guidelines hearing panel will take out that statement in the guidelines that says “there is no evidence of persistence”? Will they go further and call the science what it is and say “there is substantial evidence of persistence of Bb notwithstanding prior antibiotic treatment”? Your guess is as good as mine, but if they take Dr. Gershon’s advice, the “IDSA WILL NOT HESITATE TO CHANGE ITS GUIDELINES TO REFLECT THIS EVIDENCE.”
What do you think? Should the IDSA guidelines be changed on the issue of persistence?
- October 10, 2009 at 2:41 pm
yes. Yes. YES. YES! i think, with a disease that causes a human beings to have to stop participating in a beneficial way in their society, and also makes them want to die because the pain is so bad, and eventually kills them, long-term antibiotic treatment should be an option no matter how dangerous they think it is, which means, i think it should have been an option a LOOOOONG time ago. the IDSA has been irresponsible and immoral in their fight against treating Lyme disease. May every single one of them experience what it's like to have Lyme disease and not be able to get care for it.
- October 22, 2009 at 4:21 pm
Regarding the Klempner study, another important fact to consider to help explain 0% PCR positivity in the patients is that anybody that tested PCR positive for B. burgdorferi in either their plasma or CSF sample at baseline were EXCLUDED from the study.(Page 86 of NEJM article) The subsequent samples that were tested by PCR were done while the patients were on antibiotics, and I suspect that antibiotic therapy will also decrease the chance of a positive PCR finding in these fluids in people with active borreliosis. If anyone has first-hand knowledge of this study, I would be interested in knowing more details about other exclusion criteria, for example for which other coexisting conditions were applicants excluded from the study (Did this include CFS or FM, for example); also, why was active inflammatory arthrtitis an exclusion criteria, and on what basis was this determined (physical exam finding only, or were inflammatory markers used as well?)
Another concern with regards to your quote of Dr. Gershon's comment "If and when there is credible evidence of the existence of chronic Lyme disease and of the benefits of long-term antibiotic therapy to treat it, IDSA will not hesitiate to change its guidelines to reflect this evidence".
I apologise that I am unable to access the SMJ articles directly, but reading that quote here are some thoughts: That quote actually may embed several qualifiers:
1. Credible evidence for Bb persistence in tissues after IDSA-recommended treatment
2. Credible evidence that the persisting organisms are still alive
3. Credible evidence that, if still alive, they are capable of and indeed responsible for disease.
4. …if still alive and capable of causing disease that this is the case in humans, not necessarily animals
5. ….if still present, alive, and capable of causing disease in humans that there is proof of the benefit of long-term antibiotics in humans.
I truly don't mean to be tedious, but believe that I have seen this kind of progression through the years in the arguments of the naysayers.
If IDSA does not at this time change their guidelines, is it possible to ask them to clearly state in a statement that they will stand by (and that all will agree on), exactly what evidence they need to change the guidelines? And wouldn't it be appropriate for them to accurately reflect the information present in the literature with respect to persistence, while awaiting their decision whether or not to change their recommendations?
That's it for now. I'd appreciate the opportunity to talk more about this with others. Anyone who is interested in the discussion of direct detection, including anyone who may have knowledge of studies that have not been published in the literature, feel free to reply here if appropriate, or contact me at firstname.lastname@example.org.
PS which study do you cite for 10-15% PCR-positivity in active lyme?
- July 28, 2010 at 5:19 am
Valuable information! Looking forward to seeing your notes posted.
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