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184 Comments

1. chris powell February 22, 2012 at 10:13 pm Log in to Reply

   would it be possible for you to interview the authors and ask the reason for the delay?

   many thanks once again for your enlightening, thought provoking article.
   • lou February 23, 2012 at 9:51 am Log in to Reply

     Doubtful that the authors will want to answer this question. Embarrassing, leaves them open to retaliation. Means NIH will write them off, and put their institutions in the position of leaning on them to shut up. NIH is fully capable of refusing grant money to anyone who doesn’t follow the party line. They have been doing it for years. They have billions to bestow. Who is going to cross them if they ever want to get grant money or publish again?
   • Phillip J. Baker February 24, 2012 at 9:51 am Log in to Reply

     I completely agree. Mario Philipp should be asked to explain why it took him so long to publish this work.
2. Phillip J. Baker February 23, 2012 at 7:40 am Log in to Reply

   I resent your incorrect, if not frankly false, accusation that either I — or the NIH– had anything to do with “delaying” or “suppressing” publication of the work reported in Embers et al. Everyone knows that data collected on a NIH-funded research grant is the intellectual property of the principle investigator of the grant, not the NIH; consequently, investigators are free to publish the scientific results they obtained, whenever they believe that the work is complete and ready for publication. I challenge you to ask both Drs. Philipp and Barthold to publicly affirm and substantiate your account that either I or anyone else at the NIH attempted to suppress publication of their research results.
   • Rebecca February 23, 2012 at 4:02 pm Log in to Reply

     12 years? R e a l l y ? really?
   • Kris Newby February 23, 2012 at 8:54 pm Log in to Reply

     When I began interviewing Lyme experts for our documentary, I discovered that it was widely known among academic Lyme researchers that live, metabolizing Lyme bacteria were found in the autopsied brains of monkeys that were given the equivalent Klempner study antibiotic protocol for treating Lyme disease in humans. Yet this important evidence was not mentioned in Klempner’s NEJM article or in the IDSA Lyme guidelines for 12 years.

     Dr. Gary Wormser, a Klempner study participant and the lead author of the IDSA guidelines, told me that these live organisms were simply “zombie” organisms that were alive, but didn’t cause disease in humans. How could they possibly know this if they never autopsied the brains of the human subjects in their study?

     Truly open-minded scientists would’ve mentioned the mirror monkey study in the “Discussion” section of the NEJM article, as a question that needed to be addressed. As an avenue for further research. Not mentioning the primate results – which cannot be ignored because monkeys are our closest mammalian relatives – is a scientific sin of omission.

     So here is the central question: Did Phil Baker, the person who supervised the awarding and results of the $4.2M Klempner study, know about this evidence? Did he ignore it, suppress it, or simply not know about it?

     Either way, it’s an immeasurable tragedy.
3. Phillip J. Baker February 23, 2012 at 8:57 am Log in to Reply

   I should have added in my previous posting that investigators are not required by the NIH to submit copies of manuscripts for approval prior to submission for publication or for oral presentation at scientific meetings. It is ludicrous for any one to imagine that I or anyone else connected with the NIH could have suppressed or delayed the publication of any scientific findings, even if we wanted to do so.
4. Phyllis Mervine February 23, 2012 at 12:24 pm Log in to Reply

   Dr. Baker, when Carl Brenner and I were on the NIH Advisory Panel for the Klempner treatment trials, and you were the NIH Lyme Program Officer, we asked for longer treatment, but you said it would be too expensive. We were afraid the chosen protocol would prove not to be enough for such sick patients, but you assured us that Klempner would only prove that this particular treatment worked or didn’t work – and that it was just the first treatment trial of a series. We believed you.
   We were concerned that the study used only subjective methods to evaluate the patients, so we pushed for a parallel monkey trial to give us objective evidence to balance the scale. You funded Philipp’s study but we never saw the results – until now.
   After the results of Klempner’s aborted trial were published with such fanfare, the “Clinical Alert” on the NIH website blared, “Chronic Lyme Disease Symptoms Not Helped by Intensive Antibiotic Treatment.” NIH quotes Klempner as saying, “[W]e think it is unlikely that a longer course of treatment or different antibiotic combinations would result in greater improvement than what we found in these studies.”
   I asked NIH to change their headline to “90-Day Treatment Inadequate for Chronic Lyme Disease.” They – and you – ignored my request. And now you are asking us to believe that the NIH had nothing to do with the suppression of evidence of persistence for over a decade? What did you did to get these results out in the public? What did you do to control the damaging spin of the Klempner trials that has hurt patients enormously?
   • Phillip J. Baker February 23, 2012 at 1:49 pm Log in to Reply

     Phyllis

     For your information, I did not see the results of Philipp’s study as reported in Embers et al. until just a few days ago. So, How could I have been involved in suppressing/delaying its publication?

     You keep talking about the Klempner trial being ABORTED. Nothing of the kind happened. The protocol for both the seropositive and seronegative study, which you must have seen as a member of the panel since you and others approved it, called for an interim statistical analysis when 129 patients were enrolled. So, that’s exactly what was done, under the supervision of an independently appointed Data Safety Monitoring Board that included a biostatistician. It was THEIR decision to terminate the trial because the results obtained were conclusive and not likely to be different even if the study been continued until full enrollment was achieved.

     You forget, Phyllis that we were doing a placebo controlled study. For safety reasons, it could not have been longer due to the increased risk of sepsis — that could be life-threatening– in the placebo group. That is why we elected to do 30 days of IV ceftriaxone, followed by 60 days of oral doxycycline. If you look at the data for the Krupp and Fallon studies, that were of shorter duration than the Klempner study, you will see that the number of adverse events reported were more than Klempner found. This could have been due to better care provided by Klempner and the infusion company he hired to insert and manage the pic lines.
     • Phyllis Mervine February 24, 2012 at 11:48 am Log in to Reply

       Phil, I have not forgotten anything, especially my shock at seeing the NIH tout conclusions I knew were not supported by the design of the Klempner trials.

       But I am not going to argue with your facts, because the point is, we know that long-term antibiotics help some people and until there are better treatments for chronic Lyme, patients should have the right to choose.

       If you take antibiotics for your strep throat and then relapse, your doctor is not afraid to give you more. If you have tuberculosis or endocarditis your doctor may prescribe months of treatment, no problem. If you have cancer, your doctor lets you choose between chemotherapy, radiation, surgery – none of them risk-free options. If you have HIV and you die, no one blames your doctor. No, the medical community supports providers who take on the most challenging patients. Why should chronic Lyme be different?

       The IDSA-recommended treatment regimen has a 50% failure rate! Two-tier testing misses half the patients! WHO recently condemned a TB test that missed 50% as being unethical. Are you sure you want to stake your reputation on this miserable track record?

       The truth is, NIH, CDC, and IDSA have created an atmosphere of fear and intimidation where many doctors will not treat Lyme patients at all. Why risk collegial censure for patients who don’t conveniently recover with the officially recommended treatments, especially when those patients are complicated and so time-consuming? Why risk your license to practice medicine in an area where insurance refuses to reimburse most of what you feel is best for the patient? Our Lyme specialists are true heroes.

       As long as NIH continues to use its influence to prevent seriously ill patients from obtaining potentially life-giving treatment, while failing to offer effective alternatives, they are guilty of turning a treatable illness into a chronic one. This is both inhumane and very costly to both the individual and society.
5. Lorraine Johnson February 23, 2012 at 12:36 pm Log in to Reply

   Dr. Baker

   I actually say that you “deny” allegations of suppression, which you do. However, you were the person at the NIH who was responsible for overseeing this study, which was funded with taxpayer dollars. It was your job to make sure that the study was carried out and that the results were timely distributed to the public. You failed to do this. As a result, the real research that should have been done — how to best treat this persistent infection — has not been done because the issue wasn’t even on the agenda. I hope you understand what a staggering loss that is to patients debilitated with this disease and to the science of Lyme disease in general.
   • Phillip J. Baker February 23, 2012 at 2:14 pm Log in to Reply

     Actually, no one was more eager to learn of the results of Mario’s studies than I, and I contacted him repeatedly all during the time that his grant was active to find out what was happening. Initially, he told me that he was having technical problems with the strain of Borrelia that he had been using in all of his previous work. It appeared to have changed properties in that it was no longer as infective as it once was in previous studies. This necessitated re-deriving a new strain and then conducting a series of preliminary studies to standardize the dose to be used for infection in the planned definitive studies.Unfortunately, things like that sometimes happen and are a part of doing scientific research. Also, he told me that he was having difficulties getting adequate numbers of NHPs, mainly because of increased demands for such animals in research on HIV-AIDS. The long and short of the matter is that he had no conclusive results to report that closely resemble those reported in the Embers et al. paper before his grant expired.

     Furthermore, the significance of the results reported by Embers et al. with respect to human disease are far from clear and remain to be established. Sufficient information was not provided to indicate that the antibiotic regimen used was adequate to clear the disseminated infection, specially since ceftiofur — not ceftriaxone — was used. Since ceftiofur differs significantly from ceftriaxone in structure, one can not assume that it has the same PK/PD properties or even the same MID. Furthermore, ceftiofur has not been approved for use in human studies and its efficacy for the treatment of borreliosis — in humans and/or in animals– has not been established. More important, no evidence is provided to indicate that “persistors” — even those taken up by ticks in the xenodiagnosis experiments are infective and cause disease. On the basis of all these deficiencies, it is unclear why the work was accepted for publication by PlosOne in the first place.
6. lou February 23, 2012 at 1:45 pm Log in to Reply

   Does anyone doubt the ability of the NIH to influence the direction of research? They have made sure, for instance, that more than 3 decades after the discoveries in Lyme,CT and many thousands of patients treated, we are still being told by the federal health agencies that chronic lyme does not exist. The people who have been funded for lyme research are more often those that will support the party line.

   Here is more than a billion reasons for NIH to get what it wants Not likely that any institution will want to cross the people who provide this kind of funding.

   http://www.medcitynews.com/2011/03/top-nih-grant-funding-by-institutions-states-for-2010/
   • Phillip J. Baker February 23, 2012 at 3:27 pm Log in to Reply

     Lou

     Sounds to me like what you are really trying to say is that if a study does not provide you with the results that you want to get, then it is biased and no good. To date, the NIH has spent millions of dollars to fund 4 clinical trials, none of which indicate that extended antibiotic therapy is beneficial for the treatment of “chronic Lyme disease”. So why do you think longer treatment with more or different antibiotics will help? I have no doubt that these people are suffering from something other than antibiotics is needed to cure. It is time to examine other possibilities, if one truly wishes to help these people.
     • Kris Newby February 23, 2012 at 9:15 pm Log in to Reply

       Of the four double-blind placebo-controlled studies cited in this debate, the $4.2M “Klempner Study” is the **only** antibiotic trial that definitively concludes that antibiotics don’t help chronic Lyme patients. The Embers study certainly casts a shadow of doubt on this conclusion.

       The Klempner study was rife with controversy from the beginning. The awarding of this grant was so contentious, that a GAO investigation was initiated (B-274269). The study was terminated early, and the conclusions were rushed into publication without a rigorous peer review process. (For an excellent autopsy of the flaws in this study, read Pam Weintraub’s book, “Cure Unknown.”)
       • Phillip J. Baker February 24, 2012 at 5:41 am Log in to Reply

         As I said before, the Embers et al. study does not prove that the “persistors” are infectious and can cause disease, even those taken up by ticks in the xenodiagnosis experiment. More important, grave questions remain as to whether the treatment used was adequate to eliminate the massive disseminated infection induced. No PD/PK or an MIC were provided by the authors for ceftiofur, which was the antibiotic used in the study — not ceftriaxone. So, let;s be fair. The study did not in fact mimic the Klempner clinical trial in which ceftriaxone+ doxycycline was used.

         I remind you that the GAO decided in FAVOR of the government. If you want to know why, read the transcript of the hearing.

         As I related to Phyllis, the Kelmpner study was not terminated early or aborted. All clinical trials supported by the NIH MUST be conducted under the terms of a clinical protocol that MUST be approved by the FDA and the NIH clinical studies group BEFORE the trial can ever begin. The protocol for the Klempner trial stipulates that an interim statistical analysis, supervised by an independent Data Safety Monitoring Board, MUST be conducted when an enrollment of 129 is attained. That was done. That is what was done. The analysis showed no significant differences between patients who were treated with antibiotics vs those given placebo; it also indicated that the results would be no different if the study were continued to full enrollment. In other words, sufficient evidence was obtained at the time of the interim analysis to make to answer the question. Based on that information, the Data Safety Monitoring Board recommended that the study be closed and the results made public — which we did. The clinical protocol was observed to the letter throughout the clinical trial. Knowing the results of the interim analysis, it would have been UNETHICAL to continue to enroll and treat patients in the study.

         . . . .One other thing. I find it strange that in the Embers et al. paper, the term ceftriaxone is used dozens of times throughout the paper. Yet, it is only when one reads the first paragraph on page 9, that one learns that ceftriorfur — not ceftriaxone– was used. So, in truth, the Embers et al. study does NOT mimic the clinical trial conducted by Klempner, who used ceftriaxone + doxycycline. Since ceftriofur and ceftriaxone differ significantly in chemical structure, there is no assurance that they have the same PK and PD properties — which makes all the difference in the world with respect to their therapeutic efficacy– let alone the same MIC. To the best of my knowledge there are no published data on the efficacy of cetriofur for the treatment of borreliosis in animals. It has not been approved by the FDA for use in humans.

         . . . .I believe that I have responded to all that. Due to technical problems, Mario’s Philipp did not complete the NHP study before his grant expired (see other postings here). I saw the data published in the Embers et al. paper for the first time a few days ago when it appeared in print. It was not available — at least to me– before I retired from the government in 2007.
         • Phyllis Mervine February 24, 2012 at 11:53 am

           As you no doubt know, ceftriofur is the veterinary equivalent of ceftriaxone. The reviewers apparently thought it was close enough.
         • Betty Maloney February 24, 2012 at 12:29 pm

           Dr. Baker,

           Your points related to differences between the IV treatment agents in the Klempner and Embers studies are worth noting and whether or not these differences impact outcomes should be investigated. You are also correct to point out that the decision and duties of publishing belong to the authors.

           The factual nature of that statement becomes convoluted when it’s considered in the context of other real-world facts. Researchers are respected for their pursuit of scientific answers but, as you surely know, they also need to pursue funding – how many government-funded grants could a researcher expect to win if he/she decided to challenge the party line on a scientific topic with no apparent middle ground? With the publication of the Klempner trials in 2001, it quickly became was clear that those with influence within academia and those who controlled scientific funding had aligned against the theory of persistent infection.

           Lacking a test of cure, researchers are forced to use surrogate outcomes such as follow-up serologic or PCR testing, serial cognitive batteries and instruments measuring subjective symptoms, such as the SF-36 and the FSS-11. Even animal models can only take us so far because they, too, are surrogates. Given the scientific facts and political realities, the reluctance to climb out a very thin limb is understandable. Unless the authors choose to address questions about the delay, we are left with guessing.

           Guessing might make an interesting parlor game but let’s get back to understanding Lyme disease. In the 11 post-Klempner years, the outcry from patients with persistent symptoms has grown all the louder, physicians willing to consider all reasonable options for alleviating pain and suffering have reported positive outcomes from aggressive antibiotic regimens and research into the molecular aspects of B. burgdorferi , make it increasingly clear that persistence is possible via an array of adaptive mechanisms which allow the organism to escape killing by the immune system and antibiotics. Mouse models , have twice demonstrated persistence following standard courses of antibiotics when the infection is treated after the disease has entered the late stage and now we have the work by Embers et al. in non-human primates. What else needs to be done to turn the political scientific ship around?

           In their discussion, Klempner et al. over-generalized their findings in what could be interpreted as an attempt to stifle further research on the topic. Although the trials had significant design flaws, the authors concluded that because they couldn’t find a treatment benefit, it was unlikely that other regimens would yield different results. Given the heterogeneity of persistent symptoms and the long list of confounding variables which could be operating within an individual patient, it was a rash conclusion to draw.

           From my perspective, it seems that instead of tempering that conclusion, those with the power to shape scientific opinion had jumped on the Klempner bandwagon. Thankfully, studies by Krupp and Fallon were already funded or their contributions might have been lost.

           The Krupp et al. trial, published in 2003, had 3 primary endpoints but only the fatigue endpoint was well designed; it demonstrated a clinically significant benefit from retreatment, with P < 0.001, in a very specific patient subset. It was only by invoking an unsubstantiated theory about unmasking and overemphasizing the life-threatening adverse events seen in the placebo arm and the lack of effect on mental processing speed and clearance of OspA from the CSF that Krupp et al. were able to fall back in line, recommending against retreatment. That was quite a feat, given the authors opened the discussion by calling the fatigue finding “encouraging” and recommending additional research.

           Fallon et al., in 2008, provided additional information. In an under-enrolled but well analyzed trial within a strictly defined and homogeneous subset of patients with persistent symptoms, the authors found retreatment had demonstrable benefits. While it’s true that the cognitive improvements obtained with 10 weeks of ceftriaxone were unsustainable, patients with fatigue matching the criteria set forth in Krupp, benefited from retreatment.
           Like Krupp, Fallon et al. called for more studies.

           Klempner must be one exciting ride because instead of jumping off the bandwagon after 2 consecutive trials found retreatment to be beneficial, influential people and organizations, such as you, in this forum and the IDSA, in its guidelines seem even more determined to deny evidence demonstrating bacterial persistence and the possibility that it may be responsible for the ongoing symptoms experienced by some patients who failed to recover after receiving standard antibiotic treatments for Lyme disease.

           Please don’t take my arguments for bacterial persistence to mean that I deny the possibility of other mechanisms for persistent symptoms, because I don’t. Unrecognized co-infections, immune dysfunction, tissue injury (either permanent or slow to heal) and Lyme as a trigger of secondary conditions may all be in play. Until we have more direct markers of disease and sufficient evidence from well-designed trials across the spectrum of patient subsets, it is premature to declare any of these theories as non-viable.

           Expanded research on disease persistence will benefit many patients with Lyme disease and could inform the work of researchers looking at other diseases. Because there’s no financial incentive for the pharmaceutical industry to perform the needed investigations and patient groups lack sufficient monies to pay for it, this research must be government-funded. Those with influence over funding are free to ride the scientific vehicle of their choice but, if their duties include protecting the public health, they must be careful not to prematurely shutdown the creation of other useful vehicles through funding denials or implied threats of professional ostracism. Anything short of a full investigation of all potential mechanisms of persistent disease forces fellow citizens to walk the painful road of chronic illness. Given the continued rise in incidence, the heterogeneity of persistent symptoms,4-6,9 the significant impairments and costs associated with persistent disease,4,6, , and the evolving scientific discoveries in this field (including the Ember’s study which was the original focus of this conversation), efforts to limit research cannot be justified.

           Betty Maloney, MD
       • Phyllis Mervine February 24, 2012 at 11:56 am Log in to Reply

         And even in the Klempner trial, there was a subgroup that did better on treatment, minimal though it was.
         • Phillip J. Baker February 24, 2012 at 1:52 pm

           Believe what you will, Phyllis, but you are wrong. Ceftiofur and ceftriaxone are chemically different in structure. Embers et al. have provided no assurances in their work that they have similar PK and PD properties, let alone the same MIC. It is incumbent upon them to provide such data, as well as to show that therapeutic regimen used was adequate to clear the huge inoculum that was used to produce a disseminated infection. Obviously, their experimental design did not mimic the Klempner study, which is what Mario was initially funded to do. Why he chose to use ceftiofur is for him to explain, not me. As I said before, ceftiofur has not been approved by the FDA for use in humans and there are no published data showing that it is effective for treating borreliosis in animals, let alone humans. There is one report showing that it is not effective for treating borreliosis in ponies.
     • Rebecca February 24, 2012 at 6:06 am Log in to Reply

       Dr. Baker,

       Unless you have personally reviewed my, (and others,) medical records and seen the patients in person how dare you say, “…these people are suffering from other than antibiotics is needed to cure”.

       Are you a psychic? You couldn’t possibly know what’s wrong with me unless you have seen me. I have Lyme. If I was treated/tested for Lyme back when I was getting stress tests, and heart scans, maybe I wouldn’t have needed so many abx. The current guidelines do not adequately detect Lyme in a timely manner, then Dr’s like you say short-term abx is sufficient, and that’s if it is found at all.
       • Phillip J. Baker February 24, 2012 at 9:47 am Log in to Reply

         You’ve mis-understood my point. Please read the attached article and you will see what I have in mind.

         http://www.fasebj.org/content/26/1/11.long
         • Bob February 24, 2012 at 9:09 pm

           Phil – i read your article. One of your most important statements in it is patently false:

           “It is important also to note that if the therapy was truly beneficial, one would expect to see significant and lasting improvement in a large percentage (>90%) of all patients treated in the same manner; that is, benefit would be noted in a percentage well beyond the 38% attributable to a placebo effect.”

           A therapy isn’t successful if it works in 80% of people? Huh?

           The right answer is: of course it is. Even if the success rate was 50%, it still has value. And it then needs to be weighed against cost and risk.

           But your most important assumption in the entire article is untrue.
     • Mike N. February 24, 2012 at 8:51 am Log in to Reply

       Of course, none of these studies ever take into account the fact that borrelia is driven into cyst form when IV rocephin or doxycycline is introduced. Or, the fact that the vast majority of chronic lyme patients are cross infected with bartonella, babesiosis, etc., etc. Oral doxycycline and IV rocephin would have little effect on these patients symptomology.

       It’s common knowledge that the IDSA Lyme Guidelines panel is severely contradicted with financial interests. I would suspect this is all going to end up in a courtroom in the not too distant future and people affiliated with the IDSA, etc., will have ample opportunity to defend their positions under oath. I’m sure a jury would be quite interested to hear why a Vet can routinely prescribe 30-60 days of doxycycline for a pet yet, humans must pass a battery of inaccurate tests to be given the luxury of one pill of doxycycline or if they plead vociferously enough, 10 days.

       You see, lawyers, wealthy and politically connected people and their families get bitten too.

       I believe Upton Sinclair said it best :
       “It is difficult to get a man to understand something when his job depends on not understanding it.”
7. Claire February 23, 2012 at 2:37 pm Log in to Reply

   Thank you Phyllis and Lorraine for continuing support of Lyme disease patients. You’ve given us a very clear picture of what has gone in the past that has so negatively impacted so many of us and our families. What a shame that this study was not published at the appropriate time.
   • JC February 25, 2012 at 8:22 am Log in to Reply

     Yes, thank you to those who are fighting for improved testing and treatment of tick borne illness. Any action, no matter how small, will help change the course of this disease. For those impacted, change cannot come fast enough. Some of our courageous lawmakers understand the devastation of Lyme. They all need our encouragement to fight for everyone impacted by these diseases. Thanks again.
8. Cindy February 23, 2012 at 4:51 pm Log in to Reply

   Dr. Baker,
   Perhaps the question should be, did you know the results of the monkey study? Did anyone at the NIH know the results of this study? If so, what did you, or others that knew, do to help set the record straight? To help direct more research to build upon the incredible results of the monkey study? To help correct the sweeping notion that Lyme disease can not persist after 90 of treatment?
   • Phillip J. Baker February 24, 2012 at 10:04 am Log in to Reply

     I’ve already answered that question by saying that I didn’t know of these results until I read the Embers et al. paper a few days ago. I can’t speak for others at the NIH, but I’m sure that was the case for them as well. However, it is unclear whether the antibiotic therapy used (ceftiofur + doxycycline) was adequate to eliminate the massive disseminated infection produced, and whether the “persisters” are infectious and capable of producing disease.
9. Freda February 23, 2012 at 7:26 pm Log in to Reply

   Dr. Baker,

   I have a question for you.

   If the monkey study was intended as confirmation of the Klempner treatment trial, and if it was approved by NIH with you at the helm as program director for Lyme disease, then how did you happen to approve a protocol you now say is so inadequate the reviewers at PLOSone should have rejected the study on that basis alone?

   It seems like a gotcha: If the study confirms Klempner, it validates you. If, as happened, it opposes Klempner, then you say that the protocol –which you funded– was, in retrospect, inadequate.

   It reminds me of “heads I win and tails you lose.”

   Freda
   • Phillip J. Baker February 24, 2012 at 6:15 am Log in to Reply

     There was nothing wrong with the PROTOCOL, Freda. If you read my previous comments, you will see that the Embers study did not mimic the Klempner study. Embers et al. used ceftiofur — not ceftriaxone– in their studies. There are serious problems with doing that as I have noted.
     • Steven Gottschalk February 25, 2012 at 12:05 am Log in to Reply

       If there were serious problems with that protocol, why did you approve it for funding? It seems that you haven’t adequately responded to Freda’s question. Perhaps you’d like to try again.
   • Phillip J. Baker February 27, 2012 at 11:40 am Log in to Reply

     Because they depart form the protocol that they should have used, Freda. The NHPs were given ceftiofur + doxycycline, instead of ceftriaxone + doxycycline as was done in the human trials. Ceftikofur and ceftriaxone are not the same drugs.
10. barbara hower February 23, 2012 at 8:18 pm Log in to Reply

    ” I have no doubt that these people are suffering from something other than antibiotics is needed to cure. It is time to examine other possibilities, if one truly wishes to help these people.”–Dr. Baker
    Since there is ample evidence that there is some kind of persistent infection, then why has no other investigation been attempted? It seems to me that a logical extension of Klempner’s study (which I thought was criticized for numerous flaws) and Dr. Baker’s own observation quoted above would have been to have the NIH to serve its taxpayer-supported purpose by funding additional studies to investigate further. Why was this not done? Instead what we have had is a series of denials and a whole lot of excuses–very suspicious, if you ask me. So, prove those of us who believe in persistent borrelia infection wrong and provide the answers you claim are waiting in the wings. I dare you.
11. barbara hower February 23, 2012 at 8:31 pm Log in to Reply

    What I may not have made clear is this: Any scientist worth his or her salt would want to know, “Well if it is not borrelia, then what the hell is it??” Why stop at borrelia–keep at it until we know what is causing this persistent infection, this cascade of worsening conditions. Why would a scientist not find it fascinating and be deeply curious? This is what makes me suspicious. Just when it gets interesting, the spigot is turned off. Why?
    So many denials, but I have yet to hear any kind of scientific hypothesis as to what else it could be.
    • Phillip J. Baker February 24, 2012 at 5:16 am Log in to Reply

      The main point is that it is not clear all this is due to a persistent infection, just because you THINK it is. There is no evidence from human studies proving that’s the case.
12. tgrimes February 24, 2012 at 2:07 am Log in to Reply

    How typical of Phil Baker and the IDSA thugs who have hijacked the Lyme debate. Get results that you like (ie the Klempner study), rush them to publication using your editorial pull at a major medical journal. Get results that you don’t like (ie the Embers study), let them languish for 12 years using every excuse in the book why you were powerless to get them published. At the same time, you somehow find the power to go running around Capitol Hill telling Congress not to believe the results that you don’t like. How long will these criminals control the Lyme world?
13. Donna February 24, 2012 at 3:08 am Log in to Reply

    Nothing to add but tick tick tick tick tick tick… ironically, that’s the sound of the clock running out on the status quo.

    I’d also like to offer a heartfelt thank you to everyone who has fought and continues to fight for the truth to come out, for Lyme Disease patients to be taken seriously, and thank you to the POLICYWONK authors and their relentless commitment and courage to openly sharing it all. I can’t wait to hear more. This is a game changer. Sadly, this isn’t a game.

    It ain’t over til it’s over, but I hear that lady warming her vocal chords.
14. Paul Mall February 24, 2012 at 3:51 am Log in to Reply

    Kind of hard to find a cure when the persistent infection is being ignored.

    Antibiotics has cured about 5 percent of the patients with persistent infection that I have scene.

    So should we just die or take that chance? Find a cure already!
    • Phillip J. Baker February 24, 2012 at 9:36 am Log in to Reply

      Antibiotics have cured 5% of the patients? What is the significance of that when a placebo effect of 38% has been reported in studies on the efficacy of antibiotic therapy for the treatment of “chronic Lyme disease”. That’s why it’s extremely important to conduct placebo-controlled studies to be really sure that whatever therapy is being proposed is beneficial.
      • Rebecca February 25, 2012 at 9:03 am Log in to Reply

        We do not have the luxury of being part of a study. Placebos only work if you believe it’s real medicine. I don’t have anyone to lie to me and tell me I’m taking abx, when it’s really just a placebo. My Lyme Specialist found other things wrong, (food allergies and vit. D deficiency,) that were treated in conjunction with abx for Lyme. Have you studied that?
15. Freda February 24, 2012 at 6:04 am Log in to Reply

    Three more points:

    1. Should Dr. Baker be synonymous with NIH? After all, most NIH program directors don’t cross the line to become a lobbyist as Dr. Baker has for ALDF, going to Congress to try to influence bills that have economic impact on his organization’s funders and constituents. Most past program directors do not become political players on the same turf they formerly oversaw from a presumably neutral stance. Dr. Baker’s current political involvement throws his past regime as program director in charge of the Klempner study in a new light.

    2. The statement that antibiotics will not help: Well, let’s say that’s true. It certainly has proved true for some of the chronically ill Lyme patients. Yet it is a huge leap from that to the statement that these persistent spirochetes have no role in the disease. The immune system is nuanced and complex, and to say we have these extra foreign bodies in our systems and we are sick BUT there is no immunological connection between the two is an outrageous, leap that no real scientist, no pure scientist, would make. The remaining spirochetes are a clue. Do they have a role, immune or infectious? These are questions for science, for more science to be answer in research moving forward. They are NOT questions for a political operative to answer a priori before more research has been done. To conflate the efficacy of antibiotics with the possible role of these spirochetes in illness is sleight of hand.

    3. Dr. Baker has already gone on the record as to what these patients may have MUS-medically unexplained symptoms. In the parlance of the debunkers, this is yet another wastebasket whose sufferers are generally sent to cognitive therapists, not physicians. They are broadly seen as having a psychological not a physiological disease.
16. Jill Auerbach February 24, 2012 at 8:26 am Log in to Reply

    Dear Phil, Dr Baker,
    When you were at the NIH, I felt we had a good rapport and my biggest issue then, now and always is prevention. The NIH failed to fund the “anti tick” research that would prevent ticks ability to remain attached and block most if not all diseases they carry. But again, I keep getting dragged back into the patient issue. Personally, I am horrified that this research was not published in a timely manner.

    What I do not understand is that you criticize the Rhesus study when it holds so much more scientific validity and evidence than the Klempner study. Additionally, much animal research backs up these findings, and gives direct evidence, for example: Barthold, Straubinger, Chang . We all know how poor the antibody testing is to prove ongoing infection, however, with the Rhesus and other animal studies we have laboratory evidence of Bb surviving. In the Bartold research the naïve ticks fed on the mice, became infected and were able to transmit Bb. No such direct methods (tissue samples, etc) or laboratory results came from the Klempner study, nor can they be done on humans.

    Perhaps this demonstrates that even a low level of Bb is enough to keep some patient’s immune system triggered, and keep them ill. We are all different, with differing genetics, immune systems, and other infections (perhaps co-infections), etc. The truth here is that ‘we humans’ simply do not know the answers. It is evident that more research is needed to find a treatment protocol.

    We must realize that there are disease precedents of 6 months – 5.7 years with prolonged antibiotic therapy in the following chart. No such NIH sponsored research has been done for Lyme disease to find effective protocols beyond 90 days. Some such diseases are: TB, Leprosy, Brucella, Whipple. Actinomycosis, Q fever endocardosis, Alveolar echinococcosis.

    Let’s pull together and get the treatment research done! Also, we have to remember that ticks are cesspools of infections so, “when you are up to your elbows in alligators, you must remember to drain the swamp” – TICK PREVENTION RESEARCH!

    Jill
    • Phillip J. Baker February 24, 2012 at 11:41 am Log in to Reply

      Jill,
      I have stated my reasons why I have reservations about the Embers et al. study and won’t go through all of them again. Check my previous postings for all that I have said on the subject. Even Barthold has stated in his papers that there is no proof that these “persisters” can infect and cause disease — that’s really the main issue, and is what will have to be done next. If they are unable to cause disease — even though they can be transferred to other animals in the xenodiagnosis experiments– then what would be the advantage of more antibiotic therapy? I would prefer to focus on alternative approaches as I’ve mentioned in my FASEB article, and not put all of my eggs in one basket, i.e., antibiotics. How many people do you know that have been treated long-term with antibiotics and claim that they don’t work or work only for a short time?
      • Mike N. February 24, 2012 at 7:28 pm Log in to Reply

        What would be the advantage of more antibiotic therapy ?

        Hundreds of thousands of people have regained their lives through long-term antibiotic therapy. That’s the advantage.

        I know people all over the country that were treated long-term and have never relapsed. Many had to be treated for lyme, bartonella and babesia.
        • Phillip J. Baker February 25, 2012 at 8:41 am Log in to Reply

          Does this scene look familiar to you?

          “Near the beginning of the film entitled, “Under Our Skin”, there is a rather poignant scene in which a Forest Ranger, who has been told that he has Lyme disease, is sitting at a table, quixotically examining what appear to be hundreds of vials of prescribed medication. The scene prompts one to ask several questions:

          What type of physician, who we later learn is a Lyme literate physician (LLMD), is treating this man?

          What is the rationale for the treatment he is receiving? Does it appear that the LLMD is simply guessing, i.e., trying “a little bit of this and a little bit of that”, hoping that something will work? Does it look like good medicine is being practiced?

          If any of the medications being given happens to be of benefit, how would one know which one — of the many being taken– is beneficial?

          If the patient improves, how can one tell if the improvement is spontaneous (a placebo effect?) and has nothing at all to do with any of the medication taken?

          Is this treatment regimen typical of that usually recommended by a LLMD? If so, then what is the standard of judgment for their “literacy” with respect to Lyme disease?

          From what body of knowledge do LLMDs derive their literacy and self-assumed competence to treat Lyme disease? How many of them have peer-reviewed publications based on the clinical or basic research they have done on Lyme disease?

          How much is all this therapy costing the patient in out-of-pocket expenses? Does one honestly think that a health insurance company should be required to pay for such unorthodox — and obviously unproven– therapeutic approaches that are not evidence-based?

          In contrast to the scientific evidence provided in the guidelines for the treatment of Lyme disease by the Infectious Diseases Society of America (IDSA), is such a therapeutic approach based on the results of placebo-controlled clinical trials, or only solicited testimonials?

          That pile of pills at the beginning of the film hardly inspires confidence in the clinical knowledge and skills of LLMDs. “
          • Joanne Drayson February 26, 2012 at 6:50 am

            Dr Baker very many thanks for contributing to this ongoing debate in a forum that patients can participate in. I do hope that there can be many more opportunities in the future

            I have found so many of the comments interesting although not able to agree with all that has been said.

            It seems to me that so much of medicine is gained by hypothesis and doctor experience and not all the treatments doled out by our General Practitioners is based on Evidenced Based Guidelines or on a test result. Much is prescribed in a trial and error sort of way.

            I am sure there must be more of a middle ground that we should all be striving for, there will undoubtedly be good doctors on either side of this debate doing what they think best for their patients.

            I was fortunate to be treated long term on just oral antibiotics( through our NHS in UK) and made a good recovery but no doubt the 20 months steroids given for wrong ( assumed) diagnosis will have complicated my situation.

            Doctors treating patients with Lyme Disease do not believe they have all the answers they do their best. But doctors who believe that they know long term antibiotics do not help patients with Lyme Disease are making assumptions.

            All the RPCT did was show that those treatments for that period did not resolve all the symptoms for those patients nor did that treatment length resolve all my symptoms but longer courses did.

            The only decent thing that came out of the IDSA review hearing to me was that they recognised that European studies were not relevant to IDSA guidelines because of the different species and yet here in Europe all the various guidelines still depend on the IDSA guidelines, they are not as you suggest written independently and even have the guideline authors on some of the panels.

            You have made an issue over the differences of Ceftiofur and Ceftriaxone although it is not unusual to have a medication for animals and humans labeled differently but I will concede your point that the differences may be important. However you appear to overlook the fact that the animals were then given 60 days of Doxycycline and yet persisters were found. 60 Days of Doxycycline is considerably more than most people are prescribed for Lyme Disease following the IDSA Guidelines..
      • Jill February 25, 2012 at 8:45 am Log in to Reply

        Phil,
        To answer one of your questions, I for one was able to return to work full time as a programmer after long term antibiotics. So were many others.

        I totally agree with you that we should not be placing all of our eggs in one basket and that RESEARCH needs to be done to find a proper treatment protocol: whether they are differing antibiotic regimens, IVIG, among other, who knows what? I wonder why the Embers study did not go one step further to see if those ticks transmitted the disease. However, the Barthold study did. Additionally, the Straubinger and others found surviving Bb. That must lead a scientist to question!

        IMO, if this were a communicable disease the research would have been completed, yet tens of thousands of people are affected, and no treatment is given if they have remaining symptoms., how egregious and inhumane!

        One thing for certain is that EARLY treatment is important in preventing long term symptoms, and each person should be treated as an individual. However, in this chilling environment and the IDSA guidelines, too many physicians are wary about treating. This is detriment to and only compounds the numbers of patients being able to obtain timely and proper treatment to help prevent ongoing illness/symptoms.This needs to stop. The IDSA Guidelines need updating!

        As you see in my previous post, I think the Embers study to be more accurate than the Klempner. We cannot do to humans what we can to animals to actually find Bb. What I do not agree is that we know that antibiotics given longer than 2- 4 weeks does not work for many patients, and that has become the cookbook approach. It is wrong IMO. So, if the Embers/Philipp research in your and others opinion is not correct, then the Klempner is neither. The IDSA guidelines need updating!

        The LONG term answer of course are the TICKS; by preventing them from spreading infection to animals and humans. I ask why critical research such as was being done by Dr. Wikel to prevent ticks from being able to remain attached and spread most if not all tick borne disease was dropped (not funded)! Where is the common sense in all of this?

        Do the research, change the Guidelines, promote early and individual treatment in the beginning of the disease, check for co-infections!
        Just my opinion,
        Jill
        PS I’d call you to chat but can’t locate a number for you.
        • Phyllis Mervine February 26, 2012 at 12:41 am Log in to Reply

          I am another success story for long-term antibiotics. However if I go off my “maintenance therapy” for more than a few months, symptoms recur (e.g. vertigo, iritis). By all means, do the studies and find a better treatment. But until we have one, don’t try to take away the one thing that works.
          ps I notice my insurance company balked at paying for more than a month of IV, but doesn’t object to paying for years of orals. But $hhh!
    • Phillip J. Baker February 24, 2012 at 12:18 pm Log in to Reply

      Jill,
      You should ask Mario Philipp why it took so long for him to publish this work. When I was Program Officer, he was awarded a rather small, 4 year grant to conduct a study in NHPs that would mimic the clinical trial of Mark Klempner. Since it was a rather small grant, Mark was kind enough to arrange for the drug company to supply the ceftriaxone and doxycycline to be used in Mario’s work; as I recall, theye were even the same lots of antibiotics used in Mark’s clinical trials. Unfortunately, and for various reasons that Mario will have to explain to you if you really want to know, he was unable to obtain publishable results from his studies. What ever publishable results he obtained must have been acquired after that time. I retired from the government in October, 2007. As I said, the first time I saw the results was when the Embers et al. paper appeared in print a few days ago. I resent any implication that I or anyone else at the NIH had anything to do with suppressing or delaying the publication of these results. However, I must admit that I have reservations about their implications –as I have noted in other postings on this site. Also, the final product did not mimic the Klempner study as originally planned, since Mario used ceftiofur — not ceftriaxone– in his study. Once again, he will have to explain why that was done. Since these drugs differ significant in chemical structure, one can not assume that they have the same PK/PD properties or even the same MIC. So, my concerns are purely scientific, and not political in the least.
17. lou February 24, 2012 at 8:33 am Log in to Reply

    Antibiotics have not helped the chronic lyme cases? Says who? Most of us on these drugs are able to function with them, but when we stop, the symptoms come roaring back. So, if you think being able to function, and in some cases still being alive at all, is a waste of treatment, then you don’t belong in the medical field Dr. Baker. Turn in your license and go into some other line of work.

    If the two tier testing that has failed so many of us were not the standard, maybe we would never have become chronic in the first place. There is a lot of unnecessary suffering that is going on your record, and those others who have perpetrated this medical malpractice. I used to wonder if the official stance on lyme disease came out of ignorance, incompetence, or deliberate malfeasance. I have concluded it is the latter.
    • Phillip J. Baker February 24, 2012 at 11:45 am Log in to Reply

      You might be interested in this:

      Some patients who believe that they have “chronic Lyme disease” claim that prolonged treatment with antibiotics relieves their symptoms and makes them feel better. Does this mean that these beneficial effects must be due to the elimination of a chronic borrelial infection?
      [Response]

      That certainly could be the case if you were correctly diagnosed with such an infection, in the first place, and it is responsive to the antibiotic used. However, in the absence of such a diagnosis, at least three other explanations are possible.

      First, if another undiagnosed and unrelated infection that has nothing at all to do with Lyme disease is present (e.g., a urinary tract infection) and it is really the cause of the general symptoms experienced, its resolution by antibiotic therapy might then account for the relief of symptoms.

      Second, in a large double-blinded, placebo-controlled study on the benefits of extended antibiotic therapy for the treatment of patients with persistent symptoms believed to be due to “chronic Lyme disease”, improvement was noted in 38% of the patients given placebo alone (1). Obviously, because of the magnitude of such a placebo effect, it is not possible to determine the beneficial effects of therapy for the treatment of “chronic Lyme disease” without conducting a placebo-controlled trial using adequate numbers of enrolled patients and appropriate statistical analysis. It is generally accepted that 35% of patients with any of a wide variety of disorders can be treated successfully with placebo alone, and that cure rates of 70% – 100% have been reported in some studies (2). Testimonials, regardless of the numbers solicited, do not constitute proof of efficacy; for every patient who claims that a given therapeutic approach is beneficial, there may be just as many — if not more — who state that it is not.

      Third, several antibiotics often used to treat Lyme disease, e.g., ceftriaxone and doxycycline, have significant neuroactive effects that can impact ones sense of well being (3,4). In fact, ceftriaxone, which appears to be the most potent in that regard, is now being tested in clinical trials for its efficacy in treating amylotropic lateral sclerosis or ALS (6). The anti-inflammatory and pain-relieving effects of tetracycline and its derivatives (doxycycline, minocycline, and tigecycline) are well known and have been studied extensively (7). So have the anti-inflammatory effects of macrolides such as erythromycin and azithromycin (8-11). Perhaps other drugs that are not antibiotics might work just as well — or perhaps even better – in this regard and not contribute to the emergence of new and more difficult to manage infections by antibiotic resistant strains of bacteria.

      References:

      1. Klempner, M.S., Hu, L., Evans, J., et al. “Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease.” New Eng. J. Med. 345: 85-92, 2001.

      2. Kienle, G.S. and Kiene, H., “Placebo effect and placebo concept: a critical Methodological and conceptual analysis of reports on the magnitude of the placebo effect”. Altern. Ther. Health Med. 2: 39-54, 1996.

      3. Domercq, M. and Matute, C. “Neuroprotection by tetracyclines” Trends Pharmacol. Sci. 25: 609-612, 2004.

      4. Rothstein, J.D., Patel, S., Regan, M.R. et al. “Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433: 73-77, 2005.

      5. Clinical trials on the use of ceftriaxone in patients with ALS http://clinicaltrials.gov/ct2/results?term=ceftriaxone+and+ALS

      6. Bastos, L.F.S., de Oliveira, A.C.P., Watkin, L.R. et al. “Tetracyclines and pain”. Naunyn Schmiedebergs Arch. Pharmacol. 2012, Jan 27 [Epub ahead of print].

      7. Tkalcevic, I., Bosnjak, B., Hrvacic, B. , et al. “Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice.” Eur. J. Pharmacol. 539: 131-138, 2006.

      8. Tamaoki, J., Kadota, J., and Takizawa, H. “Clinical implication of the immunomodulatory effects of macrolides”. Amer. J. Med. 117: 5S-11S, 2004.

      9. Sanz, M.J., Nabah, Y.N., Cerda-Nicolas, M., et al. “Erythromycin exerts in vivo anti-inflammatory activity downregulating cell adhesion molecule expression”. British J. Pharmacol. 144: 190-201, 2005.

      10. Sadreddini, S., Noshad, H., Molaeefard, M. et al. “A double blind, randomized, placebo-controlled study to evaluate the efficacy of erythromycin in patients with knee effusion due to osteoarthritis”. Int. J. Rheum. Dis. 12: 44-51, 2009.
      • Mike N. February 24, 2012 at 5:41 pm Log in to Reply

        Phil

        Addressing your responses…………….

        1. A urinary tract infection has the same symptomology as lyme and tick-borne illness ? Sure, you bet, we push people around in wheelchairs constantly with urinary tract infections. Or the telltale bullseye rash, crushing migraines, knee cracking, memory loss associated with gas and bloating.

        2. 38% experienced improvement with placebo. You are aware that the bacteria is cyclical ? Symptoms wax and wane ? You then mention some studies show a 70-100% improvement on placebo alone ? Well, that settles it, let’s fold up the pharmaceutical industry. No need for them at all.

        3. Doxy can create a euphoria of health ? I wondered why my lyme infected labrador had that smile on his face ? Of course, the lyme patients that still experience massive pain while on 50mg fentanyl patches must not have achieved “Doxy Nirvana” yet ?
      • Steven Gottschalk February 25, 2012 at 1:02 am Log in to Reply

        You cite the ALS Study as one of your examples. The irony is truly staggering. Why? Because Lyme patients had to beg and plead to get you to approve a treatment protocol of a measly 30 days of ceftriaxone for an illness with a known bacterial origin, yet ALS, an illness of unknown origin, is awarded a treatment study that uses TWELVE MONTHS of ceftriaxone.

        Also, according to the proposal at the link you provided, the choice of ceftriaxone was not due to some nebulous effect like increasing a patient’s sense of well being, and it wasn’t due to anti-inflammatory effects, it was because:

        “…researchers want to study drugs that decrease glutamate levels near nerves. Ceftriaxone—a semi-synthetic, third generation cephalosporin antibiotic—may increase the level of a protein that decreases glutamate levels near nerves. Studies of ceftriaxone in the laboratory suggest that it may protect motor neurons from injury.”

        One wonders where the outcry is over antibiotic resistance with regard to this study.
        • Phillip J. Baker February 26, 2012 at 9:30 am Log in to Reply

          In view of the fact that ALS is a life-threatening, fatal disease and “chronic Lyme disease ” is not, that’s the reason.
          • Lauren February 27, 2012 at 7:42 am

            It’s interesting that I read somewhere that 150 ALS patients were randomly selected and tested for Lyme. Guess how many had it? 100%. 100% of the ALS patients tested had Lyme. Guess what? I don’t believe that to be coincidence. And no one else should, either. It’s amazing how all of the “new” diseases du jour are springing up AFTER the outbreak of Lyme in CT. And now the drug companies all have new meds to make and sell. Hoorah for them. And while they are rolling in our money, we are dying from a bacterial infection. When will right win over wrong? Well, as long as this place worships the almighty dollar, we will sit, infected, and fighting just to get treatment. Stop hiding behind loopholes and bunny trails. This is an epidemic and we are NOT the government’s guinea pigs.
          • Steven Gottschalk February 27, 2012 at 11:07 pm

            So an illness whose “deficits in physical health…” are “…equivalent to those observed in patients with congestive heart failure”[1] or whose “…patients are in a condition worse than patients with marked congestive heart failure. They are two and a half standard deviations [a statistical term] from normal – among the most deviant of any chronic illness,”[2] doesn’t qualify in your book as life threatening enough.

            You know where the first of those quotes came from, don’t you, Phil? It came from the same study that you love to cite repeatedly as the scientific gold standard for why long term antibiotics aren’t warranted. But apparently when it comes to your study defining the severity of the illness, not so much.

            We just don’t die in big enough numbers to be granted studies that are outside the box, apparently.

            [1] http://www.nejm.org/doi/full/10.1056/NEJM200107123450202#t=article

            [2] http://www2.lymenet.org/domino/nl.nsf/3e44eb21cca09829852565e900006f2a/204968e457c338bc8525660a00027cf0?OpenDocument
      • Lynne February 29, 2012 at 2:08 pm Log in to Reply

        Dr. Baker,

        Am I correct to conclude that neither you, your family nor your friends are currently suffering from Chronic Tick Borne Illness?
        I feel quite certain that if you, or someone close to you were suffering from Chronic Tick Borne Illness, then you would NOT be arguing over protocol for treatment. Instead, you would be on the front line of current global research finding ways to treat this life altering illness.
18. Jill Auerbach February 24, 2012 at 11:31 am Log in to Reply

    This is getting sidetracked about Phil Baker when it is NOT about him. It IS about the tens of thousands of people (I think 10% is the accepted percentage of CDC surveillance case Lyme patients who do not recover). These patients are left lingering without treatment, and many more will as the year pass.! I’d have to go figure out the exact numbers.
    Many do not get the treatment they need because of the, IMO, faulty information in the IDSA Guidelines which is based upon the Klempner study. Guidelines which ignores research such as this.
    Only animal studies can do such tissue samples and such to prove what really occurs. The Klemner human trial because of that was weak as compared with the many animal studies which demonstrate survival of Bb. Additionally, in the case of the Barthold mice study the ability of Bb after treatment was demonstrated to be passed to other animals via ‘naive’ ticks that fed on the treated amimals. This study showed that when ‘niave’ ticks were fed on the treated monkeys, they became infected with Bb.
    For these sick people, their lives are slowly eroded: loss of jobs, disabilities, helplessness causing depression, family breakups, bankruptcies, some even die from the many side effects caused by this non treatment of their illness.
    INOW is the time to do treatment protocol research, it is unconscionable IMO to ignore this and other animal research! It is just as URGENT to PREVENT tick-borne disease, which is the root cause of all of this suffering! I ask where is the basic common sense at the CDC and NIH in funding research?
    Jill
19. Pamela Weintraub February 24, 2012 at 1:46 pm Log in to Reply

    Dr. Baker comments that the results of Embers are suspect because of the specific antibiotic used. But Embers should not be viewed in a vacuum –it follows on the heels of publications by Barthold, Straubinger and others, all with similar results. Add this to the reporting I did in Cure Unknown, where quite a number of the mainstream researchers told me they had known about these persisting spirochetes for many years –in fact, decades. That these spirochetes can, at least sometimes, persist after treatment should no longer be in dispute. It really is no longer controversial except to die-hards living in a dream world. The real question is: What does do these persisters mean? What role if any do they have in continuing disease? How is the immune system involved? To insist that all these studies, in aggregate, be dismissed or ignored, and that we instead default to the two Klempner trials of more than a decade ago as the arbiters of truth –well, that should be unacceptable to anyone, even Dr. Baker, as the place we land after all this. We need more research to find out what is going on here because, to date, none of the studies –none of them, either alone or taken together– have revealed that to any satisfaction. If we had the answer, tick-borne disease patients would not be suffering so mightily and for so long. I would feel so good if Dr. Baker could respond by agreeing that more research must be done, and that that research must go to mechanism –at the biological level, what is going on?

    Pamela Weintraub
    Cure Unknown, 2008
    • Phillip J. Baker February 24, 2012 at 3:25 pm Log in to Reply

      Pam,
      I strongly agree that more research is needed. However, if you read my recent article in the FASEB Journal (http://www.fasebj.org/content/26/1/11.long), you will see that I favor a multi-disciplinary approach that moves the field in a different direction, rather than solutions based on the assumed yet to be proved existence of a persistent infection that can only be cured by antibiotics. I don’t really discount such a view; rather, I feel we are neglecting other possibilities that may provide the answers we all are looking for. A case in point, would be the recent work of good friend, Armin Alaedini — who I helped support when I was at the NIH– using specimens collected by Mark Klempner as part of his clinical trial. These valuable specimens are being maintained by Mark in a specimen repository for use in just such cutting-edge research. They are available free of charge on request.

      In other postings on this site, I have noted several flaws in the Embers et al. study. Of course it remains to be determined if these “persisters” can infect and cause disease. That is at the top of the list of things to do next. However, before that, one must establish that the treatment regimen used was adequate to eliminate the enormous disseminated infection induced deliberately by needle inoculation. Aside from numbers of bacteria, there are well known major differences between naturally acquired infections and those induced by needle inoculation. I fear that the unbridled enthusiasm for the work of Embers et al. — with all of its serious flaws– will cause the pendulum to swing too far in the direction of antibiotic therapy alone, i.e., give them even more antibiotics for longer periods of time — perhaps for life? That would not be good. How many people do you know that have given up on antibiotics and now believe that Lyme disease is incurable.

      I remind you of the fact that at one time, the work of Straubinger was accepted as evidence for active infection. It was based on the results of PCR tests. However, all PCR tests do is detect DNA — that of a specific microorganism, if done correctly. Although all live bacteria will be PCR positive because they have DNA, so will dead bacterial cells, as evidence by the detection of Borrelia DNA in museum specimens, hundreds of years old, as well as the prehistoric ice man, more than 5,000 years old (see recent issue of the National Geographic).

      Wrestling with the science is difficult enough, although I have faith — from my many years as a research investigator — that the truth will win out, in time. However, as indicated by the many unkind remarks made on this blog site, there is too much distrust and misinformation being spewed all over the internet. That is the biggest obstacle to progress. It is not going to be easy by any means — because of that alone.

      I think I have said quite enough on this topic and will rest my case.
      • Mike N. February 24, 2012 at 7:49 pm Log in to Reply

        Phil

        The biggest hindrance to research and progress is the IDSA, not the lyme community. The lyme community sees the devastation wrought by tick-borne illness on a daily basis. Children 2,3,4,5 years of age racked with pain and debilitation because the IDSA is so conflicted with financial concerns.

        Gary Wormser is really going to tell a mother pushing her 5 year old around in a wheelchair, crying themselves to sleep nightly, that 10 days of doxycycline is all you get ? However, the family pet can get 30 days ? That 5 year old needs help now. Not another decade of the IDSA authoring studies to support their insurance company hypothesis.

        Is long-term antibiotics the only answer ? Of course not but it’s the only answer that mother with an ill 5 year old has. The IDSA has no answers for her.

        The runaway infection rates of this illness has reached critical mass in many states. Either the medical/research community starts to address it from an ethical standpoint or the population will force them to through legislation or litigation. Debilitated 5 year olds are tired of talk, they want action.
      • Steven Gottschalk February 25, 2012 at 1:16 am Log in to Reply

        You discount the use of DNA evidence, yet exalt studies whose detection methods are far less conclusive of anything, specifically ELISA and WB antibody tests, and subjective patient evaluations. Of course, DNA positives in a vacuum, don’t prove or disprove active infection. But when you add in the constellation of symptoms, the many studies which have proven persisting infection in animals, and case studies of humans in which autopsy results found the Lyme bacteria in patient’s brains and other organs.

        Phil, I want you and the IDSA that you lobby for, to admit the fact that persisting infection is a potential cause of chronic Lyme disease, that no definitive claims can be made otherwise, and that until further research that can answer this question conclusively is conducted, that doctors are free to treat chronic Lyme with long term antibiotics if that is what they feel is in the best interest of their patient.

        Until you are willing to do that, your claim of acting in the name of progress rings false. You are, in fact, as you have been since the day you were selected as program officer for Lyme disease at NIH, a thorn in the side of progress.
      • Pamela Weintraub February 25, 2012 at 7:57 am Log in to Reply

        Just a couple of comments: First, I feel people could work with this response, Dr. Baker, so thank you. I am going to put this in the bank –it is someplace to start.

        But for the record on the possibly-substandard antibiotic, that is exactly the way most chronic Lyme patients were treated at first , with substandard antibiotic. Personally –I relapsed on and off for four years before I finally got better from a coinfection of Lyme and Babesia: And I got well with antibiotics –which I pulsed only after interviewing Dr. Barthold. He did not know I had Lyme disease, but he told me according to his observation of persisters that type of treatment should work (he was just answering a question from a journalist)–for me it did work, in 2004 and I have never relapsed again In years since, I have often thought that if ONLY my doctor had given me Rocephin up front, the abx with the right MIC, as you say, I might have kicked it early, in the first place. For me that is water under the bridge. Unfortunately, there is so much fear out there among local doctors, that Rocephin is the last, not the first, antibiotic they try –if they are ever willing to give it at all. I never DID have IV antibiotics and I am fine now but if we wanted the experiment to mimic the real world instead of Klempner, perhaps Embers actually got it right.

        In addition, should these persisters remain, they may be provoking an outsize immune response in some people with certain genetic profiles. We need to look at the generation of autoantibodies that might be crossing the BBB, which can open temporarily under certain circumstances, infections or exposures. We need to look at immune cascades that go way beyond just straight up autoimmunity. We need to look at feedback loops between even tiny amounts of infection (even if non-virulent and non-multiplying) and the immune system.

        I am with you in thinking that for those who do not respond to antibiotics, the answer is probably not more antibiotics –EVEN IF small amounts of persisters linger on, if we find the immune issues downstream, we can treat THOSE. We all live with tiny amounts of infection of all sorts, but it could be that tiny amounts of THIS infection make certain people immunologically ill. We need to investigate that. Since those persisters, if validated as you suggest, may be the stimulants that start the immune cascade, we cannot ignore them –and by sweeping these findings under the rug, we may never be able to follow the trail of “breadcrumbs” back to learn the biological mechanism behind the illness.

        It is time to look at all the evidence and not just some of it. It is time for scientists to look at this with open minds and without any agenda but the truth. At this point, these animal studies in aggregate provide too much evidence to be ignored, even if you find some flaws in them, they cannot be discounted -the results need to be investigated more, that is the only responsible stance –and thank you for agreeing on that point, above, along with your other research directions. They should all continue in parallel.

        Pam Weintraub
        Cure Unknown, 2008
      • Phyllis Mervine February 26, 2012 at 12:49 am Log in to Reply

        Dave Persing, who should know what he is talking about, once said that the body quickly clears foreign DNA in a matter of days. This should put positive PCRs in a different light.
20. Jack Renoud February 24, 2012 at 1:50 pm Log in to Reply

    Dr. Baker,
    I invite you to see my three kids and myself and the damage that has been done to my family because of a flawed approach in looking at this disease. I had a doctor friend say to me that he bases his treatment protocol , whatever it is he’s treating, on ‘evidenced based ‘ medicine. How the hell can he or any other doctor do this if a study as important as this was conveniently ignored or relegated to no-man’s land and was never put out there for my doctor’s to read and evaluate. You can not have it both ways. You can’t give part of the data out to the public, the part you agree with and forget about mentioning anything contrary and expect the public to take you or anyone else in your group seriously. Your involved with something very very wrong, here, something that has hurt many tens of thousands of people and you still don’t see what you have done wrong. I feel sorry for you and forgive you. That’s all I can do. The tide is changing. You got caught here in your own ‘logic’ trap. Thank you , Lorraine. My kids and many others are suffering as a result of you, Dr. Baker, and your group being wrong. . And you operate as a lobbyist now? Gee, that says a lot about your integrity, doesn’t it. I wonder what else is being spun out there in medical land at the detriment of the people. And you wonder why we are angry at you.
21. Jack Renoud February 24, 2012 at 3:26 pm Log in to Reply

    One more thing. Many years ago, a doctor, who treated many people for Lyme Disease told me that he and a fellow researcher had taken tissue samples from the preserved! body of a person who had Lyme disease , chronic , persistent Lyme disease , and who had agreed , if they succumbed , to allow tissue sampling . Mind you, this tissue had been soaked in formaldehyde for preservation purposes and was never subjected to any outside contamination.. Months after this person had died ( this person had also had been treated for years with numerous antibiotics), LIVE spirochetes were cultured from this dead person’s tissue. This doctor told this story to many people but was largely ignored for his brilliant findings.My point is that ignoring the plight of the masses, ignoring other doctor’s findings, picking and choosing what you want to hear , only reinforces people’s suspicions . Why hasn’t more research been done? Where are those inquisitive minds that should be the major driving force in all medicine, where is that wanting to know on the part of the I.D.S.A people? The fact that their has been almost ‘blind’ acceptance of a flawed protocol makes me and many other people suspicious of your actions and your organization’s actions and motives and especially of an organization that claims to have the public interest at heart . Dr Baker , can you see beyond yourself here, and understand that what is being done and not done by I.D.S.A looks so bad. Failure to present these results a timely manner is/was bad policy and bad medical practice.
22. observer February 24, 2012 at 4:24 pm Log in to Reply

    Dear all,

    I would like to point out a few things as briefly as possible. I am what you would call a scientist myself and have been curiously reading about (and later studying) various fields of science since childhood, and years ago I stumbled upon the debate of Lyme disease. Here began a journey I have in common with many other scientists once foreign to the field of medicine, who began investigating this issue.
    If I wanted to say anything in depth about the concepts and evidence I came to read, it would take far more time and text than fits here.

    Instead, I want to point out three things I have learned through the curiosity for the Lyme disease debate, which have since then have guided me:
    -All modern science is paradigm based: any fact is interpreted by the agreement on certain paradigms, meaning an interpretation will be sought that supports the paradigms and none will be accepted that contradicts them. The “review” and “production” of further evidence will be selective by the same criteria. A whole body of evidence and interpretation is built up by this means – all modern science thus is circular reasoning to a significant extent. The great advantage is the efficiency that is reached by not having to (re)answer questions that are regulated by the paradigms.
    (Thomas Kuhn’s well known critique of modern scientific method)
    -For long periods the advantage (efficiency) outweighs the disadvantage (bias with risk of wrong conclusions). When this disadvantage becomes dominant, when conclusions are drawn that are less well supported by the evidence than alternatives that are neglected, the period of “revolution” begins. In this period modern science is highly inefficient as it defends paradigms that hinder deeper and wider (or simply more elegant) concepts.
    -This paradigm change or revolution is often initiated and impelled by a non established minority, sometimes even foreigners to the field of debate.

    These conceptions were formulated by Thumas Kuhn and summarize some of his thoughts on modern science.

    My personal conclusions in the case of Lyme disease which I believe to have in common with numerous “observers” include the following:
    The medical community has for a long time been trapped in the state of “scientific revolution”. There is a significant body of evidence, that chronic disease in general, Lyme being an example, is caused by the interaction of the host and persistent microorganisms. These microorganisms are characterized as distinct subgroup of pathogens by the differences to infectious agents that cause acute disease: they have low doubling times, a low outer protein profile relative to the proteome of the host, further active and passive evasion mechanisms (including suppression of the hosts immune response and retreat to specific niches of the ecosystem which is the host), reduced metabolism (if any at all) and as consequences low virulence and low chances of transmission (with the latter being both, cause and consequence, depending on the time frame of observation). Some species have the ability to develop phenotypes that include examples for both: acute and chronic disease causing pathogens.
    I have so far not seen a more evident example for this then Borrelia burgdorferi (which alters its phenotype mostly due to a highly instable genotype leading to a dramatic variability of host-parasite interaction).

    Let me emphasize again, that there is a significant body of evidence in my opinion for all of the above. To anyone asking “where is that evidence?” I reply: start by reading everything that Dr. Lida Mattman has ever written and published. Then proceed.

    I am sorry that I cannot write more and still hope that some of my words might be of interest.
23. John S February 24, 2012 at 4:34 pm Log in to Reply

    If he is the president of a bias organization like the American Lyme Disease Foundation, how can he be in charge of anything related to Lyme at the NIH?
    • John S February 24, 2012 at 5:12 pm Log in to Reply

      Never mind, I see he has retired. Even so, how did someone with this bias get to control anything.
24. John S February 24, 2012 at 5:02 pm Log in to Reply

    Dr. Baker, you should look at Kim Lewis’s work on persisters causing chronic infections.
25. Mike N. February 24, 2012 at 5:14 pm Log in to Reply

    Phil

    Appears some of your buddies disagree with you. You guys really need to get your stories straight. Here’s Allen Barbour’s recent patent application. {8/9/2010} Seems Ol’ Allen thinks borrelia is a persistent infection just like Relapsing Fever. {Just go to Google Patents}

    Application number: 12/853,019
    Publication number: US 2010/0317026 A1
    Filing date: Aug 9, 2010

    This one statement is powerful. Alan Barbour in one paragraph summarizes strain variation, immune system evasion, persistent infection, failure of Lyme tests and the uniqueness of Borrelia among other pathogens.

    [0145]”This mechanism of genetic switching appears to be different from any other antigenic variation mechanism described in bacteria or protozoa and has important implications in Lyme disease. By combining different regions of the silent vls cassettes, it is possible for many different vlsE serotypes to coexist the same patient. It may be impossible for the host to mount a protective response against any one of these clonal populations, because of the small number of each type. Even mounting a response against one serotype would not protect against rapidly evolving, new serotypes.”

    Well, I’ll be darned ! Another vaccine ! Good Ol’ Allen juiced the patent application with some of these blurbs:

    [0006]..chronic manifestations including arthritis and neurologic disorders. Lyme disease is often difficult to diagnose because of shared manifestations with other disorders, and it can also be refractory to treatment during late stages of the disease………..

    ……..[0007] B. burgdorferi, the etiologic agent of Lyme disease, is able to persist for years in patients or animals despite the presence of an active immune response (Steere, 1989; Schutzer, 1992)………………

    [0009] Lyme disease may be disabling (particularly in its chronic form), and thus there is a need for effective therapeutic and prophylactic treatment.

    [0010]OspA vaccination may not be effective against all strains of Lyme disease Borreliae.

    [0020]that antigenic variation is virtually limitless. Multiclonal populations therefore can exist in an infected patient so that immunological defenses are severely tested if not totally overwhelmed.

    [0127] The present work discloses the identification and characterization of an elaborate genetic system in the Lyme disease spirochete Borrelia burgdorferi that promotes extensive antigenic variation of a surface-exposed lipoprotein, vlsE. A 28-kilobase plasmid of B. burgdorferi B31 (pBB28La) was found to contain a vmp-like sequence (vls) locus that closely resembles the variable major protein (vmp) system for antigenic variation of relapsing fever organisms.

    The resulting combinatorial variation will potentially produce millions of unique antigenic variants and thereby contribute to immune system evasion, long-term survival, and pathogensis in the mammalian host.

    Borreliae with the capability of antigenic variation analogous to the vmp system of B. hermsii (Barbour, 1993). The above similarities also indicate that the vlsE gene, silent vls cassettes, and large vmp genes of relapsing fever organisms, all evolved from a common ancestral gene.

    [0130] Lastly, each phase of B. hermsii infection is caused predominantly by organisms expressing a single vmp allele (Meier et al. 1985; Plasterk et al. 1985), whereas a high degree of vlsE allele variation occurs among organisms isolated even from a small ear biopsy specimen during B. burgdorferi infection.

    [0137]serotype expressing VmpB exhibited more severe arthritic manifestations, whereas another expressing VmpA had more severe central nervous system involvement (Cadavid et al, 1994). The numbers of Borreliae present in the joints and blood of serotype B-infected mice were much higher than those of mice infected with serotype A, consistent with a relationship between Vmp serotype and disease severity

    [0139] in vivo selection against Bb clones lacking pBB28La appears to occur early in infection (within the first week), before the adaptive immune response would be expected to exert significant selection pressure. Therefore, it is likely that vlsE plays an important role in some aspect of infection (e.g. colonization, dissemination, adherence, extravasation, evasion of innate immune mechanisms, or nutrient acquisition), and that antigenic variation merely permits surface expression of this protein without leading to elimination of bacteria by the host’s immune response.

    [0294] These results indicate that VlsE is expressed and is highly immunogenic in the mammalian host, but that genetic variation may generate unique VlsE variants which are no longer fully recognized by the immune response against the parental vlsE.

    Oh, what a tangled web we weave………………………………..
26. Paul Cayer February 24, 2012 at 5:48 pm Log in to Reply

    I have learned a lot about this disease in the 3 1/2 years since my diagnosis and start of treatment, after being misdiagnosed for decades. And I’ve learned a lot from the discussion on this forum. Most important: There are individuals in the medical profession and in the highest echelons of medical research who have no more business being in this profession than did Dr. Mengele.

    The scale of suffering and death caused by these evil, arrogant individuals is just cause, I believe, for a congressional investigation. Taxpayer dollars were used to promulgate guidelines that caused horrific pain, disability and death of Americans. Yes, America, your tax dollars hard at work killing you and your loved ones.

    After the Congressional Hearings, if it is found that certain individuals thwarted, obstructed, or manipulated the scientific process to further their own interests, let’s bring these individuals to justice
27. James Dawkins February 24, 2012 at 5:52 pm Log in to Reply

    My word this is interesting.
    Dr Baker gives the ok for a study, using tax payers money. The results are kept hidden for 12 years and now he claims that the results are meaningless because the antibiotic used was not the right one! Yes I admit I gave the go ahead….. Well at the very least you are guilty of knowingly wasting tax payers money AND deliberately running a trial you know to be useless.
    What I find interesting to note is the one tracked responses from this Dr: What I am not hearing is “wow this is interesting we may need to look into it further”.
    Also of note: I have only recently SEEN these results. Perhaps so….but were you made aware of them some time ago?
    You are now a lobbyist…..meaning you are paid persuade the lawmakers to pass laws to increase the profits of who? Please state.
28. Miguel Perez-Lizano February 24, 2012 at 6:41 pm Log in to Reply

    Who is Baker???

    http://lyme.kaiserpapers.org/memorable-quotes-by-lyme-disease-denialists.html#Baker_

    Philip J. Baker, Not a M.D., was for ten years the Program Officer for the NIH
    overseeing Lyme disease research grants. An overwhelming proportion of these
    grants were awarded to a few favored members of the Infectious Diseases Society
    of America (IDSA) who authored the controversial 2006 IDSA Lyme disease guidelines.

    Baker is now Executive Director of the American Lyme Disease Foundation (ALDF).
    The ALDF is clearly associated with the IDSA Lyme disease guideline authors and
    their cronies.The misinformation in the abstract below is not a quote, per se, but
    represents Baker’s biased and inaccurate views. The supporting statements
    can be found in the text of the article. It is unfortunate that many unknowledgeable
    people view this as fact.

    “There is no better example of a relentless attack on evidence-based biomedical
    research and the integrity of outstanding scientists than that associated with the
    treatment of a poorly defined condition called “chronic Lyme disease.” Here, a
    scientifically naive general population, the lay press, and legislators, who in most
    instances are unable to evaluate and judge scientific evidence properly, have been
    misled by patient advocate groups to believe that extended antibiotic therapy is the
    best and only solution to this condition. This has resulted in the unprecedented intrusion of government and the legal systems into the practice of medicine and scientific research. Because there is no clinical evidence that this condition is due to a
    persistent infection, advocating extended antibiotic therapy is not justified and has
    been shown to be harmful and of no benefit.”

    -American Lyme Disease Foundation – Chronic Lyme disease: in defense of the
    scientific enterprise – Baker, PJ, 2010
    http://www.ncbi.nlm.nih.gov/pubmed/20631327
    • Phillip J. Baker February 25, 2012 at 8:28 am Log in to Reply

      Why did you only show those portions of my publication? Read this — from the same paper–and you will understand how biased and isolated your views are.

      “It should be noted that the IDSA’s recommendations
      for the treatment of Lyme disease are in agreement
      with those of the European Federation of Neurological Societies (11), the European Union of Concerted Action on Lyme Borreliosis (12), the American Academy of Neurology (13), the Canadian Public Health Network (14), and the German Society for Hygiene and Microbiology (15). They also are in agreement with recommendations made by expert panels from 10 European countries, i.e., The Czech Republic, Denmark, Finland, France, The Netherlands, Norway, Poland, Slovenia, Sweden, and Switzerland. [An excellent summary of these expert panel recommendations may be found in the presentation by O’Connell in the guidelines section posted on the American Lyme Disease Foundation (ALDF) website at http://www.aldf. com.] None of these organizations or expert panels—as well as the Centers for Disease Control (CDC) and the
      NIH—recommends extended antibiotic therapy for
      the treatment of chronic Lyme disease.”
      • James March 1, 2012 at 9:19 am Log in to Reply

        Interesting argument Dr Baker:
        Because we have managed to co opt all these organizations into agreeing with us, then we are right with our hypothesis about Lyme.
        Just like all those countries who sided with the USA who actually went to WAR because they were convinced that IRAQ had weapons of mass destruction. Using your logic – they must have been right – so many countries agreed (heck if you use the democracy argument you could claims 500 million people agreed). They were all wrong. There were no weapons of mass destruction. Indeed, it was never about that at all.
        Just like this Lyme argument – I suggest you have an agenda to downplay the spirochete of mass destruction. The fact that a few influential people in a few countries have been brought onboard does not make this argument right. Power control money.
29. tgrimes February 25, 2012 at 2:05 am Log in to Reply

    Baker: “No PD/PK or an MIC were provided by the authors for ceftiofur, which was the antibiotic used in the study — not ceftriaxone.”

    Refresh my memory: Was PD/PK/MIC data provided in the Klempner study? What? It wasn’t? How come you didn’t complain about that and say the study was invalid? Too busy lobbying for the criminals from IDSA, I guess.

    And the difference between ceftriaxone and ceftiofur?
    Ceftriaxone: A third generation IV cephalosporin approved for use in humans.
    Ceftiofur: A third generation IV cephalosporin approved for use in animals.

    It amazes me that in every other field of medicine, animal models are considered valid and even exemplary tools for research. In Lyme disease, since those darn beasts refuse to give the results desired by the IDSA mafia (Baker included), we should just ignore the disturbing results that they yield. What a scientific travesty!
    • Phillip J. Baker February 25, 2012 at 7:58 am Log in to Reply

      Because there is LOTS of PK/PD/MIC data on the use of ceftriaxone in humans, which is why it has been approved by the FDA for use in humans at the doses used in the Klempner study. That is not the case for ceftiofur. It has not been approved for use in humans and its benefit for the treatment of borreliosis in animals has not been documented.
30. bettyg, iowa lyme activist February 25, 2012 at 4:03 am Log in to Reply

    Phil,
    I’m just getting involved in here, but I’d like to be able to read this link you refer to over and over:

    http://www.fasebj.org/content/26/1/11.long

    Phil, may I have your permission to break it up to user-friendly NEURO LYME paragraphs to post it here (1-2 sentences max; next paragraph)

    OR on the board where I’m a group leader:

    http://www.mdjunction.com lyme board

    We lyme/co-infection patients would be able to try to understand your point IF we could read it. We can’t as is!

    I just read you have ceased comments, but would you make ONE exception please?

    I’m hoping it’s a YES 😉
    ************************

    Also, everyone posting, remember us neuro lyme folks and have SHORT paragraphs and doublespace between each of them as I have done above.

    We’d like to read the informative/debating thread; thank you :|)

    42 yrs. chronic NEURO lyme; misdiagnosed 35 yrs. by 40-50 drs; UNACCEPTABLE!

    Bettyg, Iowa lyme activist/group leader
    • bettyg, iowa lyme activist February 26, 2012 at 12:59 am Log in to Reply

      phil,

      you may not have seen my request above as it took awhile to be posted.

      i hope you will say YES to my posting here on the lyme board where i’m an online lyme group leader at mdjunction.com site.

      I will be BREAKING IT UP into short paragraphs so we neuro lyme folks who lost our comprehension skills decades the opportunity to read it in full.

      thanks phil 😉

      bettyg, iowa lyme activist
      http://www.mdjunction.com lyme board
      group leader
31. Alan Burdge February 25, 2012 at 5:47 am Log in to Reply

    Dear Phillip Baker
    My wife Joy Mandrell Burdge testified in front of the Human Services Committee at the Capital in Harrisburg Pennsylvania on Aug 31 2012.
    Long term treatment SAVED MY WIFES LIFE!
    Watch her 10 minute testimony and see what 100’s of thousands of Americans and people around the world are going through because of the corrupt goings on with tick borne illnesses.
    SHAME ON ALL OF YOU !!!!
    39 years we paid into Health care and we get denied from the powers in control from being treated like a human being after a life of hard work !
    Joy Burdge’s Testimony Human Services Committee Pennsylvania
    http://www.youtube.com/watch?v=r0lwBuFAI20
    Dr. Harold Smith’s Testimony Human Services Committee Pennsylvania
    http://www.youtube.com/watch?v=JpPFKp3FXmQ&feature=player_embedded
32. Peter Kemp February 25, 2012 at 6:21 am Log in to Reply

    Embers et al indicates the need for studies in humans by gathering together a cohort of ‘adequately treated’ LB patients who continue to have symptoms; and thoroughly investigating them with a battery of methods. C6 and WB might be interesting to identify their limitations (if any) in humans. Culture methods have advanced and should be straightforward, and it might be possible to include tests such as CSF protein profiling and new diagnostic tools using spectrometry.

    If, as some believe, many of the patients that remain ill are still infected with bb and this were proven; the parallel with syphilis spirochete infection would indicate another direction for research and treatment experiments.

    What is horrifying to me (and I believe others) is that this obvious investigation has not been conducted on a large scale with commensurate funding and a determination to follow-up.

    That the IDSA appear satisfied to grasp at psychological explanations for patient’s ongoing illness is astounding when scientific research can answer the question.
33. Julie E February 25, 2012 at 6:24 am Log in to Reply

    I’ll reiterate Paul’s most insightful comment above:
    “Most important: There are individuals in the medical profession and in the highest echelons of medical research who have no more business being in this profession than did Dr. Mengele.”

    Phil Baker, with all due respect, you and Drs. Wormser, Steere, Klempner, and all the other IDSA cronies at Yale and elsewhere, have had a monopoly on the Lyme disease debate for decades. And in all those years, your good old boys club has done very little to help American people like me who are severely disabled by this illness, or the thousands more who are being infected every year. We simply can’t afford your status quo any longer.

    Your participation in the ALDF in an attempt to hang onto and prolong that monopoly is like belonging to the Flat Earth Society. Anyone can believe whatever they want, and spend years shouting at the top of their lungs trying to convince others they’re right, but in the end, THE EARTH IS STILL ROUND. And CHRONIC LYME PATIENTS ARE STILL SICK!

    No, we don’t know for sure (yet) whether chronic Lyme is due to persistant Borellia infection, immune activation issues, other coifections, (bladder infections, give me a break) or what. Sure placebos help some people, but they rarely get someone disabled by Lyme out of their wheelchair or give them their memory back! And years of denying patients access to antibiotics, which have been effective at improving the lives of many people, hasn’t solved anything. It’s time for you guys all to step aside in this debate (before the angry masses are forced to rise up and revolt — and I predict that day is fast approaching!)

    It’s time to throw out the IDSA guidelines, and throw out the worthless Eliza screening test (will someone follow the money on that one and see whose skeletons fall out of that closet?)

    This whole debate reminds me of Michael Douglas’ game-changing line in the movie, The American President:

    “We have serious problems to solve, and we need serious people to solve them. I promise you, [the IDSA] is not the least bit interested in solving [them]. This is a time for serious people, [Phil], and your fifteen minutes are up.

    (My sincere THANKS to Phyllis, Lorraine, Mike, Kris, Jill, Pamela and everyone working to “do the right thing” for Lyme patients everywhere. “In the end, the cream always rises to the top!”)
34. Ann Nouncer February 25, 2012 at 6:35 am Log in to Reply

    Dr. Baker,

    Why did you recruit scientists to study chronic neuroborreliosis in animals in the past if, as you say, it does not exist?
    • Phillip J. Baker February 25, 2012 at 7:51 am Log in to Reply

      There is a BIG difference between neuroborreliosis — that does exist and is studies in various animal models– and “chronic Lyme disease” for which there is no definition to enable one to identify it as a distinct clinical entity that differs from other medical conditions with the similar general symptoms. You are confusing the two.
      • Mike Nickel February 25, 2012 at 9:56 am Log in to Reply

        Phil,

        Please. Twisting yourselves into pretzels to deny that a clearly persistent infection doesn’t exist isn’t science. It’s insurance company shilling.

        Hundreds of thousands have regained their lives with long-term treatment and adequately addressing co-infections. This is undeniable. There’s semi loads of patient records to prove it.

        I noticed you didn’t address Barbour’s 2010 patent application where he clearly states it a relapsing infection. Let me get this straight, it’s a persistent infection when IDSA affiliates are trying to make a $buck. However, it’s NOT a persistent infection when insurance companies have to cough up a few $bucks for patient care.

        You can’t it have it both ways.
      • Ann Nouncer February 26, 2012 at 6:45 am Log in to Reply

        Dr Baker, I don’t think I am the source of the confusion here. After all, in 1997, you put out the announcement which I will paste below.

        Can you please explain why you were soliciting proposals for animal research aimed at monitoring and treating “persistent
        borrelial infections of the central and peripheral nervous system” when you don’t believe they exist?

        “the NIH monkey study:

        Animal Models in Chronic Lyme Disease

        Contact: Dr. Philip Baker
        Lyme Disease Program Officer
        Bacteriology and Mycology Branch
        Telephone: (301) 496-7728
        Internet: pb…@nih.gov

        Description of Project: To solicit proposals on the use of appropriate
        animal models, having neurologic abnormalities generally associated
        with
        chronic Lyme borreliosis, to characterize the mechanisms involved in
        the
        pathogenesis of chronic neuroborreliosis, as well as to develop novel
        and effective approaches to detect, monitor, and treat persistent
        borrelial infections of the central and peripheral nervous system.

        Objective: To supplement ongoing research on: [a] the pathogenesis of
        Lyme borreliosis; and [b] mechanisms involved in the expression of
        neurological symptoms characteristic of chronic Lyme borreliosis. The
        information derived from such studies ultimately will be used to devise

        rational and more effective clinical approaches for the treatment of
        chronic Lyme borreliosis in humans, as well as to assist in the
        interpretation of the results obtained in ongoing studies on the
        efficacy of antibiotic therapy for the treatment of chronic Lyme
        borreliosis.

        NIAID Council News – DMID Concepts September 1997
        http://www.niaid.nih.gov/ncn/conmid-s.htm#AMCLD “
35. Phillip J. Baker February 25, 2012 at 6:43 am Log in to Reply

    This started out as a discussion of the work of Embers et al. in which I was perfectly entitled — and had every right– to present my honest and objective comments as any other person. Unfortunately, it has degenerated into a personal attack upon me and my colleagues. It is a perfect example of why there has been so little progress in working together to find a solution to this problem. There is too much distrust and hate, that is driven by those who have little or no understanding of the complexity of the scientific issues and what constitutes evidence-based research. If someone says something counter to your point of view, then attack that person, his institution, his colleagues etc., instead of presenting a cogent argument based on fact, rather than misinformation or opinion widely circulated on the internet and elsewhere. You reap what you sow.
    • Bob February 25, 2012 at 5:12 pm Log in to Reply

      Phil –
      We have pointed out your various logic flaws. For example, i’ve pointed out that your statement regarding something needing to be “>90% successful to be effective”, as laughably wrong. It’s surreal that you hang your hat on that rule.

      It’s hard to get to a discussion on the ‘complexity of the scientific issues’, when you can’t even get basic logic correct. And you wonder why there is ‘distrust’ and ‘little progress’.
    • Phyllis Mervine February 26, 2012 at 1:11 am Log in to Reply

      Where were you when David Whelan (Forbes) called Lyme specialists “parasites” and David Grann (NYT) called crippled Lyme patients in wheelchairs “stalkers” for demonstrating on a sidewalk where they had a permit to do so?
      What about “Lyme hysteria” and “Axis of Evil”? Then there’s “Lyme is a yuppie disease that only rich suburbanites get.” (Dr. Steven Ostroff, CDC, during interview by Illinois legislators in June 1997). And your predecessor at ALDF, quoted by USA Today as saying, “Lyme is a socially acceptable disease. You can talk about it at any cocktail party.”

      This is a cakewalk.
    • Lauren February 27, 2012 at 8:11 am Log in to Reply

      Nice spin. So now you are blaming the afflicted for their misery? Wow. Do you think that maybe, just maybe, the better thing to do would be to LISTEN INTENTLY to the suffering and advocates for the suffering here, and then POSSIBLY just POSSIBLY make a game plan to HELP them, rather than to point fingers back at them for being angry that their plight keeps getting minimalized by the PTB… especially now that the PTB, with nothing better to say or no better way to detract from the truth, just throw their hands up and say “it’s your fault for being angry. That is why you are still sick. Because you are angry at us and spreading discontent.” Wow. OR maybe, just MAYBE we are still sick because we didn’t pay the higher price to get our agendas pushed through.
36. E Cook February 25, 2012 at 6:51 am Log in to Reply

    Dr Phillip Baker,

    The makers of the documentary “Under Our Skin” published this account of what occurred when they came to Dr Willy Burgdorfer’s home for a pre-arranged interview:

    -Just as we began filming, there was a pounding on the door, and we found ourselves facing someone who turned out to be a top researcher at the nearby Rocky Mountain Laboratories, a biolevel-4 NIH research facility. Standing on the porch, our uninvited guest said, “I’ve been told that I need to supervise this interview. This comes from the highest levels. There are things that Willy can’t talk about.” We were stunned. After all, Dr. Burgdorfer had been retired from the lab since 1986. We were there to talk to a private citizen, about the history of a very public discovery that had put him on the short list for a Nobel Prize. Earlier that year, the NIH had refused our requests to interview any of their Lyme researchers. What was going on? Why would the NIH want to censor information about the fastest growing bug-borne disease in the United States? …”

    Dr Baker, this incident took place in Feb 2007. You have stated that you left your position as Lyme Program Officer in October of that year. Who, then, would have been “at the highest levels” of Lyme Disease at NIH in February 2007? Who had the authority order the researcher from the NIH’s Biosafety Level 4 lab to obstruct a film crew wishing to question Dr Burgdorfer about persistence of the infection?

    Think carefully, Dr Baker, before you hit your keypad to deny, here on the public internet, that this incident really happened. Remember:

    a) There is not a soul in the Lyme community who disbelieves the Under Our Skin team’s assertion that this took place, and

    b) There were cameras and recording equipment present.
    Elena Cook
    • Phillip J. Baker February 25, 2012 at 7:45 am Log in to Reply

      I know nothing about the incident and suggest that you ask Dr. Burgdorfer — who was there– to elaborate on the incident that appears to have taken place at the Rocky Mountain Laboratory in Montana. My office was in the Bethesda. Also, all interviews with the media are arranged and approved by the NIAID’s Office of Information, not by the Program Officer for the Lyme Disease Basic Research Program whose duties relate solely to managing basic research (grants and contracts) on Lyme disease, not public relations.
37. Maria Pursel February 25, 2012 at 7:15 am Log in to Reply

    Seriously………. the past is the past. Lets move forward from here. I am not all that surprised with hiding important information. It did not work out as they had planned so therefore, it was never published. I have Chronic Lyme with several coinfections. My goal is to get better like everyone else. I want treatments that work, are covered by insurance companies and statistics showing the progress. As it stands now, I will only keep the bacteria from growing or reproducing. My treatment will not be able to kill off the lyme with their protective coating. I can not afford a $24,000.00 yrly bill so, I do the best that I can. My Lyme Physician is upset that I can not do the treatments as he prescribed as he states: Maria, you will either pay now or later. My response is, I will be homeless if I do my treatments as prescribed. So the number one thing for me is to get the state of PA to make into law that all insurance companies pay for the treatment of Chronic Lyme disease to those PA residents. I really don’t care about the cost to them because I have paid for insurance for over 35 or more yrs and now that I am truely sick, they are saying “NOT COVERED”. Treatments are considered investigational. Well, The FDA needs to update their information so that we can be treated. It is cheaper to pay for lyme treatments for 3 yrs than it is for a one month hospital stay for bacterial meningitis. Maybe insurance companies are hoping that we all die first. Which in my case almost happened.
38. Amber February 25, 2012 at 9:15 am Log in to Reply

    I am in tears as I read through all of this, the patients voice, my voice, is squandered by cowards afraid to admit mistake. I’m not a scientist and absorbing and trying to understand all the research jargon is difficult. However, I think it’s pretty clear and easy to conclude that MORE research needs to be done. Baker says the following, “Even Barthold has stated in his papers that there is no proof that these “persisters” can infect and cause disease — that’s really the main issue.” If there is no proof that these persisters can infect and cause disease, where is the proof that they can’t?

    I want to say thank you to those who are spending hours digesting this information and making their knowledgable voices clear.

    The anger, frustration, and suppression I feel bubbling up inside of me each time I see Chronic Lyme Disease in quotes only fuels my fire….. I will survive this disease, and will forever be an advocate…. I will fight.
39. Sheri Souch February 25, 2012 at 10:01 am Log in to Reply

    Dr. Baker,
    You explain, “For safety reasons, [treatment in the human study] could not have been longer due to the increased risk of sepsis — that could be life-threatening– in the placebo group. That is why we elected to do 30 days of IV ceftriaxone, followed by 60 days of oral doxycycline.” But it was only 30 days of IV. Why could the oral treatment not continue?
    Imagine if TB treatment studies ended at 3 months. Would we conclude that this disease is not cured with long-term antibiotic therapy? If this had happened, think of all the suffering and mortality that would have ensued. Kind of like what is happening right now with “Lyme.” TB treatment typically lasts 6 months or longer (18+ months before rifampin was created,) and there is a 2-3% relapse rate. Further to this, TB requires combination therapy. Doctors who are having success treating “Lyme” have found this disease requires combination, long-term antibiotics as well.
    If you are so convinced that “Lyme” cannot be chronic, perhaps you could infect yourself and a few of your buddies from the IDSA, wait 6+ months, then treat with 2 weeks of doxy. And don’t forget to test yourselves using the two tiered testing method. If it comes back negative, then you don’t get to be treated at all. Prove to us that testing is accurate and two weeks of doxy is adequate. Put your money where your mouth is.
40. Camp Other February 25, 2012 at 12:05 pm Log in to Reply

    Dr. Baker,

    First of all, I want to thank you for being here and presenting your view in the presence of Lyme disease patients who have different points of view than your own and who are at a minimum questioning your opinion about Lyme disease and at a maximum – quite angry.

    This isn’t an easy thing to do. I recognize that. But this is a necessary thing to do, and I wish that more dialog occurred between people with differing views even at the risk of it becoming contentious. It is often the only way opinions get aired and heard and questions get answered – even if we don’t like the answers we hear.

    I have a few questions for you, and hope I did not miss the boat on getting a response from you at this late hour:

    1) Just so the storyline is clear: Who determined that ceftiofur should have been used in Embers et al study on NHP and is this decision something that NIH would have had to give approval – or is this a decision that would have been made at the individual level of the PI/researcher and not require any approval from the NIH? Would any independent governing scientific board outside the NIH been expected to approve of the study design including methods and materials? It seems that in order to emulate the Klempner study, the antibiotic chosen should either be the same as used in the original study or have, as you’ve stated, PK and PD that are pretty much indistinguishable from ceftriaxone.

    2) In your opinion – and in the opinion of others at the ALDF – would you have to see studies separately completed on ceftiofur that provide you with evidence that its PK and PD in NHP are functionally equivalent to the use of ceftriaxone in humans? If these studies are conducted and they are found to be equivalent, then would you say that the results of the Embers et al study are valid? (Even if – according to your position – they don’t yet prove a persistent infection/persister cells are the cause of patients’ symptoms.)

    3) The central point on which a lot of this debate hinges is whether or not spirochetes which remain after antibiotic treatment are viable and infectious. I’ve never gotten the impression that the majority of researchers out there have debated the existence of spirochetes after abx treatment – the impression I’ve had is that they either didn’t think they were the cause of persisting symptoms in patients or did not know one way or the other if they were the case of persisting symptoms.

    Parallel to demonstrated survival of some spirochetes after abx treatment, some research has indicated that a combination of Borrelial strain, host genetics, immune system response, and in some cases, molecular mimicry – may be causative factors for persisting symptoms. I myself think that based on evidence I’ve read to date, both persisting spirochetes *and* immune system changes can lead to persisting symptoms. I am particularly intrigued by HLA-DRs and variable immune response in this regard (see “HLA-DR alleles determine responsiveness to Borrelia burgdoferi antigens” by Bettina Panagiota Iliopoulou, Mireia Guerau-de-Arellano, and Brigitte T. Huber. Arthritis Rheum. 2009 December; 60(12): 3831–3840.).

    My questions are: When is the NIH-NIAID going to conduct more studies aimed towards this end? And also, if you and others are convinced that chronic Lyme disease patients are not suffering from persisting infections – why hasn’t more *treatment* research been conducted that supports your point of view of what is or what are the causative factors for such symptoms? Why are patients, advocates, and Lyme disease advocacy organizations having to donate money to Dr. Karen Newell Rogers and Viral Genetics to find alternative treatments to long-term antibiotics – why isn’t the NIH-NIAID pursuing these alternative approaches now, if the argument is that long term antibiotics do not work and you consider them unsafe (Which in my opinion debatable in my eyes – I have personally benefited from more than the guidelines recommend – and I do not think the use for or against more abx is applicable to everyone because this is a heterogenous patient population. The patients need to be characterized into subgroups first rather than boxed into meeting CDC specific requirements before designing new trials.).

    I have been offended with the letter to the Lancet about Lyme disease patients and advocates supporting pseudoscience when so many of us have wanted to fund more research and get answers. When a number of our friends and families have donated their money to research even when they have already paid so much for treatment.

    Some of the answers are already there. If more than one hypothesis is solid enough for testing, I’m for it. Test different combinations of antibiotics. Create drugs which have the anti-inflammatory properties of these antibiotics and use them as a control against combinations of antibiotics. Use higher doses of orals, if the fear of line sepsis freaks you out (it does me, and I have not had a PICC line by choice). Try testing thymus peptides and altering the distribution of B cells to see if that helps patients.

    What I see as an observer is that Lyme disease treatment research has been shut down unless it’s for acute Lyme disease. We need more late stage untreated Lyme disease research, and I’m with Fallon on this one – more specific neuroborreliosis research. His suggestions for those trials seem worthwhile.

    But for God’s sake, something has to be done. Some people are seriously impaired. I am doing somewhat better now and have my mind back to a large degree and don’t need a wheelchair. But I am not yet well enough to work due to pain and fatigue with normal amounts of exertion. Something is broken there.
    • Phillip J. Baker February 26, 2012 at 7:19 am Log in to Reply

      Hi Campother,

      Even though I feel that some have their minds made up and will not believe anything that I have to say, I will try to answer your questions:
      1. Dr. Philipp received a small grant (AI042352) to conduct an experiment in NHPs to replicate the Klempner clinical trial, except of course for the manner in which the NHPs were infected. Because the grant was a small one (about $250K as I recall), Dr. Klempner was able — with support from the drug company– to provide him with the ceftriaxone and doxycycline to be used; these antibiotics were from the same lots used in the human study. Fair enough? That made working on a small grant a bit easier. Since NHPs are rather expensive to use and maintain, not too many could be used in the Philipp study because of limited funding. Furthermore, NHPs were in short supply at that time because of increase competition for use in studies on AIDS. The grant was funded for a 4 year period of time, during which time Dr. Philipp reported to me that he was having technical problems, especially with the strain of Borrelia that he had been using in past experiments; it appeared to have “lost its punch” and was no longer eliciting an infection of the same magnitude and character as noted in previous studies. This meant that he would have to re-drive the strain and test it in other NHPs to confirm that it was suitable for use in the definitive studies planned for the grant; that of course would take a great deal of time — and additional NHPs–to do. Although situations like this are unfortunate, they do happen and are part and parcel of the realities of doing scientific research — if you want to do it right. So, as far as Dr. Philipp’s original grant is concerned, it expired — after the 4 year period– with no data that he felt was was ready and complete for publication at that time.
      Obviously he continued with his NHP studies and apparentlt received funding from other sources; note that research Resources grants like RR00164 are designed for the purchase materials, equipment, and supplies, in this case, more NHPs I assume. But, I was “out of the picture” at that point — as far as Dr. Philipp’s research on NHPs was concerned. Keep in mind that as Program Officer, I was not the czar of NIH’s entire research program on Lyme disease, even though so people have the mistaken notion that I had such “power”.
      So, you ask who made the decision to use ceftiofur instead of ceftriaxone? I honestly don’t know. You will have to ask Dr. Philipp, whose e-mail address is provided in the Embers paper. During the time that Dr. Philipp was doing his work under AI042352, it was being done in accordance with the terms of that grant indicated above. Whatever else he did — or may have done– must have been accomplished afterwards and with other support that did not involve me or NIAID. I must say that I find it strange that the term ceftriaxone is used throughout the Embers et al. paper, and it is only in the first paragraph on page 9 that it is first mentioned that ceftiofur was actually used. I find that very strange indeed.

      As stated before and in other postings on this site, I have two major — and legitimate– concerns with the work reported by Embers et al. . First, since so little is known about the PK, PD, and MIC of ceftriofur, was the treatment adequate to eliminate the massive infection induced by needle inoculation? Since the author did not provide such assurances, that is a major and significant unknown. Second, if the therapy was adequate, there is no evidence to indicate that the “persistors” are able to infect other animals and produce disease. They might just be sitting there, for all we know, doing nothing harmful to the host. In view of these considerations, the PCR, RT-PCR, and xenodiagnosis data are not informative. In fact, there are no real differences between the antibiotic treated and sham-treated groups in terms of the objective signs of infection (pathology) noted ; that makes me wonder if the therapeutic regimen was truly effective. So, if I were reviewing this paper for publication in a journal, I would have to reject it publication for these and other deficiencies that I will not elaborate on at this time.
      2. Since ceftiofur and cetriaxone differ significantly in chemical structure, I would not be at all surprised if they had different PD/PK properties; those who do drug design research find that the addition of a single chloride atom is enough to alter the properties of some drugs. What is certain is that ceftiofur is not approved for use in humans and there is no published evidence on its efficacy for treating borreliosis in animal models. Obviously, the use of ceftiofur is a big unknown. My best advice, if someone wanted to replicate the Klempner studies in an animal model would be to use ceftriaxone and doxycycline in the same manner that he did and not introduce another variable like ceftiofur– unless you plan to get the FDA to approve the use of ceftiofur in human studies. That may take a long time to do….
      3. Since I have retired from the NIH, I don’t know what their plans are for future research on Lyme disease. But, I can tell you that about 90% of the research that NIH supports is driven by proposals submitted as investigator initiated grant applications — the RO1 grants. So, if anyone has any good ideas, they are always welcome to submit a grant application, although competition for grants is very keen and only about 25% of all applications submitted are funded. One has to be persistent as most of my colleagues are to make it in science. Although I am not opposed to conducting another clinical trial, the odds for such a proposal getting funded are rather slim, especially since NIH has already supported 4 trials indicating that extended antibiotic therapy is not beneficial. Obviously, I would like to see more work done on whether the “persistors” Bockenstedt and Barthold noted in mice are infective and can cause disease, as well as whether they can stimulate a local inflammatory response. But, I think we would be making a big mistake by not considering other possibilities as I’ve mentioned in a recent article (http://www.fasebj.org/content/26/1/11.long). There are MANY people who believe that they have “chronic Lyme disease” with no evidence that they ever had Lyme disease in the first place. Some have been misdiagnosed and are being subjected to all sort of unproven therapy. Also, there are individuals who go from one doctor to another seeking a “cure” and who often are victims of “quack” remedies. One reason we had so much difficulty enrolling patients into the Klempner study was that only about 5-8% of those who presented themselves for enrollment had unequivocal evidence in their medical record of having been diagnosed correctly for Lyme disease in the first place. Obviously, one can not have a chronic infection without first having an active and correctly diagnosed infection in the first place. That was made a criterion for enrollment to ensure that we would have a cohort of patients with a reasonably high — though still not absolutely certain– probability of having a persistent infection — if one were present. I assure you, and you can ask Brian Fallon and Lauren Krupp, such people are NOT easy to find.

      But, I have said enough. The biggest obstacle to making any progress is the lack of trust and the tendency to condemn anyone in the scientific community who disagrees with the unproven concept of others. Some simply have no understanding of evidence-based research and how it works, let alone things like the placebo effect. There is just too much misinformation being spread on the internet — and too many people gobbling it up as though it were fact. It’s an ideal environment for all the “quacks” to thrive — and they surely do. And that is what disturbs me the most………
      • Camp Other February 27, 2012 at 1:10 pm Log in to Reply

        Dr. Baker,

        Thank you for taking the time to write an extensive response to my questions. It was more extensive than I was expecting, too.

        “So, you ask who made the decision to use ceftiofur instead of ceftriaxone? I honestly don’t know.”

        It seems rather unusual that Dr. Klempner had ceftriaxone from the original lots used to treat patients that was to be used in Dr. Phillip’s study – and yet ceftiofur was used instead. Did something happen to that ceftriaxone? I could speculate about its shelf life of three years – maybe the switch was made because of that? Unanswered question. Regarding the Borrelia – it is difficult bacteria to “tame”, I know – it loses plasmids in the dish and through multiple passages. So I’m not surprised by his setback… I suppose the best thing one can do is as you suggested and contact the research team and see if they would be willing to comment. I think your earlier suggestion to contact them and ask them about the twelve year delay is also a good idea.

        “Keep in mind that as Program Officer, I was not the czar of NIH’s entire research program on Lyme disease, even though so people have the mistaken notion that I had such “power”.”

        Who would have been in charge? Are they still in that position today?

        “What is certain is that ceftiofur is not approved for use in humans and there is no published evidence on its efficacy for treating borreliosis in animal models.”

        No research? What about these papers?
        http://www.ncbi.nlm.nih.gov/pubmed/15863289
        http://cp.vetlearn.com/Media/PublicationsArticle/PV_23_04_375.pdf

        Behind pay wall – can’t confirm degree of relevance:
        http://www.sciencedirect.com/science/article/pii/S0737080609000653
        http://onlinelibrary.wiley.com/doi/10.1002/9781444302639.ch10/summary

        I admit, Scholar and Science Direct had limited returns on animal studies of ceftiofur for treating Bb infections. The vast majority of the papers found so far are on equine borreliosis, too.

        Barthold should know something about this, knowing his experience with equine models. I would trust his decision in choice of antibiotic use.

        “My best advice, if someone wanted to replicate the Klempner studies in an animal model would be to use ceftriaxone and doxycycline in the same manner that he did and not introduce another variable like ceftiofur– unless you plan to get the FDA to approve the use of ceftiofur in human studies. ”

        I think I’d choose the first and not the second piece of advice there, if I were to conduct another study. Still, Embers et al is notable.

        “Although I am not opposed to conducting another clinical trial, the odds for such a proposal getting funded are rather slim, especially since NIH has already supported 4 trials indicating that extended antibiotic therapy is not beneficial.”

        Yes, but what if the clinical trials were designed differently? What if there were also trials where two different treatment arms were compared? Those patients who have chronic Lyme disease/post treatment Lyme disease are still suffering with persisting symptoms with no specific treatment recommendation in the 2006 guidelines except to treat symptomatically. It’s not even clear to me WHAT the guidelines indicate is being treated because no one has stated distinct genetic backgrounds or biomarkers for my condition (although recent proteomic research has indicated that yes, there is a difference between CFS/ME and CLD/PTLDS patients that is objectively measurable).

        “Obviously, I would like to see more work done on whether the “persistors” Bockenstedt and Barthold noted in mice are infective and can cause disease, as well as whether they can stimulate a local inflammatory response.”

        I believe it’s “persisters” or “persister cells”, rather than “persistors”. Anyway – I’m glad to hear that. I think that more research definitely is required on the persistent infection angle. And not just that, but to see how much immune response to exposed and traveling antigens can trigger symptoms. Both.

        “But, I think we would be making a big mistake by not considering other possibilities as I’ve mentioned in a recent article” [article link removed]

        I think that many different aspects of Lyme disease should be examined in order to get a clear picture of the disease. I doubt anyone would disagree with that statement. One has to be very exacting in this work and be sure, though, that the truth is determined. If there is persistence, then treating patients as if it were an autoimmune condition could potentially be disastrous to their health. If there isn’t persistent infection – even in just a fraction of patients – then giving them long term antibiotics won’t help that specific subgroup of patients and some other treatment (Viral Genetics’ research?) may.
        I don’t know all there is to know. The issues here are complex. All I know is one has to be certain of what’s happening – people’s lives are at stake.
      • Dave February 27, 2012 at 6:36 pm Log in to Reply

        Hello All,

        “Obviously, one can not have a chronic infection without first having an active and correctly diagnosed infection in the first place.”

        “can not”!!?

        I just wanted to be a bit pedantic and correct this statement. I am sure ( at least I very sincerely hope) that – read literally – it is not what Dr Baker actually believes or intended to convey.

        Obviously the truth is that it is quite possible for a person to have a chronic infection and never to have been correctly diagnosed with either that chronic infection, or the early infection that preceded it, and from which the state of chronic of infection has subsequently developed. – Even in 2012 in a technologically advanced country like the USA!

        I guess what was meant was a statement more of the kind:
        “For the purposed of a scientific study, is it not safe to make the assumption that a subject as has a chronic infection, unless there is documented evidence to support that assumption.”
41. tgrimes February 25, 2012 at 1:51 pm Log in to Reply

    If Phil Baker were in charge of the AIDS program at NIH , we would still be using AZT monotherapy because combination antiviral therapy is “too dangerous”, and the IDSA would be wondering why everyone was dropping dead from a psychological illness. Thank goodness for the pharmaceutical industry that pushed the IDSA to develop better treatment for AIDS. We need the same push for Lyme disease based on the animal data from Embers, Barthold, Yrjanainen, Straubinger, Chang, Callister and others.
42. jerry leonard February 25, 2012 at 2:21 pm Log in to Reply

    The Lyme Disease Epidemic: CDC Tuskegee Experiment, Phase II
    http://www.publichealthalert.org/Articles/miscellaneous/tuskeegee%202.pdf

    ‘As a result of the use of treatment guidelines to deny treatment, America’s most egregious example of medical malpractice through treatment-denial is now an everyday reality, conducted on a grand scale, and run with the complicity of the CDC and other public agencies, which are exploiting the public instead of protecting them. I have referred to this as the institutionalization of the Tuskegee Experiment.’
43. Steve Eberbach February 25, 2012 at 2:27 pm Log in to Reply

    I am pleased to see that Dr. Baker is willing to come online and defend his position.
    I have had Lyme disease twice, maybe more times, and do not know if I have finally gotten rid of it. Then again maybe they were just similar, but no-named variety(s).

    I have learned to “manage” at least the symptoms through exercise, diet,saunas, various herbal remedies, and the originally recommended Doxycycline, administered too late after the last tick bite. I still sometimes have some of the symptoms, but they are gradually diminishing in intensity.

    I did a lot of online research while I was sick (for about ten years) and driven to look for answers when my doctors acted as if my problems were a “third rail” not to be touched. I found much helpful information, as well as what appears to be the effort of unscrupulous opportunists taking advantage of fear, uncertainty, and doubt to get my money.

    For example of possibly helpful info, try Google: “lyme morphogenesis”
    The scientific word rejects a lot of the crap out there.
    You might find there is a lot of serious work being done which is evidence that the shape-shifting bacteria in general are causing a lot of frustration among well meaning scientists, and you might conclude that so much effort would not be made without many researchers being very concerned about this problem. Also, evidence that our government is doing high level and not very “transparent” research costing millions (or billions?, who knows?) cannot mean that nobody cares, even if those researchers are tight-lipped on demands of their bosses paying for the work.

    My question to Dr. Baker is why don’t you and your colleagues offer some expert advice, according to your best opinions and hunches if science really has proven inadequate for your epistemic standards of validity, without having to officially disclose any sensitive data that might get you in trouble with your career, that could actually HELP these affected people lessen their pain and disability? Just disparaging some controversial or technically flawed research as being invalid does not seem helpful enough to me.

    I do agree with those who think it is a travesty that the medical community is so ruthlessly suppressed when doctors their best to treat victims of diseases for which there is no easily defined cure, let alone reliable, definitive, and affordable diagnostic tests. Necessity is the mother of invention, and it is a waste of human creativity to suppress or discourage it.

    Even if antibiotics go to waste when the bacteria hide from them, it may only mean that the antibiotics are not being utilized properly or efficiently, and not necessarily mean that antibiotics are necessarily a cure possibly worse than the disease, as they seem to be at the present state of the art. And what about innovative alternatives to mainstream “pharmaceutical/allopathic” medical practices?
44. Timothy Grey February 25, 2012 at 3:08 pm Log in to Reply

    Phil, We all know the Klempner study was designed for a specific outcome. By doing so under a 4.7 million dollar grant from the NIH, he effectively suppressed factual information regarding the existence of Chronic Lyme Disease. This was done when you were at the NIH. Moreover, Mark Klempner found a specific marker of Lyme bacteria infiltration in the central nervous system, MMP-130, a marker found in no other diseases of the central nervous system. That was in 1997…

    Why was this never pursued?

    What happened to Karen Forschner’s LDF?

    Why did you choose such an obviously similar, and horribly confusing name for your foundation?

    What interest in Lyme disease do your board members have?

    Other than a pamphlet, what actual services does this multi-million dollar non-profit offer Lyme patients?

    ~Timothy Grey
45. Lucy February 25, 2012 at 4:23 pm Log in to Reply

    People lash out when they feel threatened.

    Lyme patients, understandably, lash out because their lives and their children are being destroyed by a handful of people who have been proven to be extremely biased and riddled with conflicts of interest in their professional endeavors.

    Baker is lashing out here because he is plain, ordinary, every-day wrong and he is being exposed for it once again. As you watch his repeated attacks over the years, you have to ask yourself what kind of man, much less a so-called professional, attacks all opposing science presented to him with a vengeance- and takes it a step further by attacking sick patients, their doctors and the volunteers/organizations who help them? What kind of man uses that approach to prove a point?

    Only a threatened man would stoop so low.

    Lorraine obviously hit a sore spot- making Baker feel even more insecure, rattled, and uncertain as how to uphold his floundering position. He is trying to discredit the voice of reason, the sick patients (the witnesses to the crimes) and the scientific facts.

    I predict for as long as he lives, Baker will not change his point of view or concede he is wrong, no matter how many facts are presented or sick patients complain. NOTHING anyone can say or do will ever be “right” unless they uphold his position.
    Although I admit it is fun to watch him publicly squirm, our time may better be spent educating others to the truth and the facts
46. Matthew F. February 26, 2012 at 8:36 am Log in to Reply

    Interesting debate. Thank you Dr. Baker for your participation and trying to explain your point of view. Surely you must realize that what has taken place to date specific to Lyme disease cannot be explained away. I am not a doctor so I agree that I cannot appropriately debate the merits or not of these two studies from a medical point of view. There are those in dialog here who are professionally qualified to debate with you and so I will let their words stand.

    I will however, address the area of publicly funded grant programs of which I do have specific experience. In all of the publicly funded grant programs I have developed, all were based on approved legislation that spelled out clearly what the outcome of the grant program and project was to achieve. A grant program that resulted in an allocation for a project was most definitely done in a way to assure that the application process and scoring rubric used resulted in a funding award that was free of any conflict of interest or bias. This is public funding and as such is for the best use and outcome to benefit citizens whose taxes go to fund such programs. Clearly this did not take place in this instance.

    With what I have read here, there is no way that either study should have been published unless published at the same time. To do otherwise clearly may have created the distinct possibility of bias. I think from my ten years of following the Lyme disease debate that if the completion of the studies had been reversed, the long delayed study would not have been published. Any young intern I have trained over the years would have spotted the pitfalls of this situation without much difficulty.

    Any funding advances or reimbursements for any of these studies without verified completion of clearly defined outcomes could be considered mismanagement of public funds. To quote intellectual property rights and not being aware of the study until just recently, as the project lead, is unbelievable. This just does not add up Dr. Baker as someone who is suppose to be a competent program manager responsible to the public and for the public trust. At the very least it appears that you have given the government a bad name, the many public employees who do a good job a bad name and hurt what should be the most transparent and objective grant process, publicly funded, a bad name also. A person may conclude as well that what has transpired here could have caused many doctors to unintentionally violate the part of their professional oath to do no harm. What appears to have gone on here does not inspire confidence.

    Lastly, all publicly funded grant programs that are done well are subject to random auditing and audits can be specifically requested if warranted. Where are the auditors? How could this situation have been allowed to happen? I do not have all the inside information but from where I sit, this just does not add up.
    • Camp Other February 26, 2012 at 12:45 pm Log in to Reply

      “Any funding advances or reimbursements for any of these studies without verified completion of clearly defined outcomes could be considered mismanagement of public funds. To quote intellectual property rights and not being aware of the study until just recently, as the project lead, is unbelievable.”

      Good points. I would think one regularly has to check on milestones for continued funding, so in this respect one would think some progress report would be written sooner. The great thing about NIH-NIAID clinical trials is that you can read status reports, study results, and changes to clinical trials on their web site. The not-so-great thing is we don’t necessarily get status reports about research outside of trials – research which may affect us as patients.

      Who took Dr. Baker’s position after he retired in 2007, though? Would you hold them equally responsible for not reporting on this study sooner?

      “Lastly, all publicly funded grant programs that are done well are subject to random auditing and audits can be specifically requested if warranted. Where are the auditors? How could this situation have been allowed to happen?”

      Also good questions.
    • Phillip J. Baker February 27, 2012 at 5:35 am Log in to Reply

      Matthew,

      Doing basic research is a very difficult job. Although one submits an application in which an original research proposal is carefully designed and judged to be worthy of support after rigorous peer review, there is never any guarantee that the outcome will be successful, i.e., an unequivocal result — be it pro or con– will be obtained. Sometimes there will be technical difficulties that prevent the work from being completed; unfortunate as they may be, that does happen and is all part of during research. The most any program officer can expect is that the investigator can demand in an honest effort to complete the research project in the time and with the resources allotted. And that is exactly what was done in this particular case. Not being able to complete the work on time doesn’t reflect on an investigator’s abilities to conduct basic research, as evident by the fact that such individuals continue to be awarded grants in the future, in accordance with the same rigorous peer review process and under the same terms. Those who have never been involved in the demanding task of doing basic research, never have had to manage a complex research program, and have never participated in the review process have no right to criticize what others have done –or have failed to do– under such circumstances.
47. Light on Lyme February 26, 2012 at 8:44 am Log in to Reply

    Here is what Phil Baker said : It is a perfect example of why there has been so little progress in working together to find a solution to this problem. There is too much distrust and hate, that is driven by those who have little or no understanding of the complexity of the scientific issues and what constitutes evidence-based research. If someone says something counter to your point of view, then attack that person, his institution, his colleagues etc., instead of presenting a cogent argument based on fact, rather than misinformation or opinion widely circulated on the internet and elsewhere. You reap what you sow.

    To that I ask: Are you calling the entire ILADS misinformation? Are you saying the writer of this blog is not giving cogent arguments based on facts? That is really unbelievable. Have I been brainwashed by all these non-facts? I don’t think so. For the sake of me and my kids, I have looked at both sides with an open mind.

    I am not a scientist; however, it only takes common sense to see you and many like you are not one tiny bit concerned about the actual science that has gone on since this all started. Even someone as dumb as little ol me can tell the difference between a person who is all about making himself look good and a person who has the integrity and courage to think and say–out loud–that they made a mistake.

    The biggest mistake was deciding any tiny, tiny study could define a whole disease it was clear by the EVIDENCE (not lies, misinformation) was not understood fully. When it was found co-infections were involved–why were there not more questions about the basis of the IDSA guidelines? If anyone even wanted to FAKE integrity they could have at least asked.

    Yes, the biggest mistake is coming back into the light and many are going to reap what they sowed. They took the chance they could cover this up. They took the chance to build this monster on the basis of a fraction of the information they knew was out there, waiting to be found. They thought they could make no one find the rest, for whatever reason. They were wrong.

    Maybe no one meant for anyone to get hurt. Maybe they have convinced themselves of their own lies that they didn’t technically do anything wrong.

    But anyone, whether it be a doctor who took the IDSA guidelines blindly at their rules even after hearing rumbling of ILADS or even a patient who just didn’t get better, or it be a scientist involved who simply didn’t speak up when they should have–this is what you did. You own it. You can’t put it back on the people who are sick. You can’t say the arguments stop science. You can’t say sick people stop science. Why? Did we make someone mad by not getting better so they are taking their ball and going home? We didn’t ask for it. Any truth can stand up to questions, lies, and misinformation. Truth on the basis of one small part of the whole truth, however, cannot. I think most involved just cannot admit that they didn’t know what they didn’t know. And that makes them look a bit foolish. For the sake of more suffering–get over it.

    Human beings ARE suffering because of those involved in all of this through the years. And when they are sick and need them the most, they are mocked by their doctors, their family, their friends… And worse yet– it is spreading and getting more and more complex and you could have done something about it. Innocent people are being hurt every single day because of you. I hope every single one who had any involvement by being a coward will hear them screaming every single day until they speak the truth instead of more lies.

    And you, “Dr.” Baker will go down in the history books in a very bad light no matter what you say now.

    I hope the future of science will learn from this travesty that is Lyme disease and look at all the studies through years and say: This is exactly what NOT to do. Humans, because of greed and pride are not winning against these little invaders. Let the people who can win this war take over now.

    You’ve done enough.

    Shan Devine
    Light on Lyme
    • Camp Other February 26, 2012 at 1:01 pm Log in to Reply

      “There is too much distrust and hate, that is driven by those who have little or no understanding of the complexity of the scientific issues and what constitutes evidence-based research. If someone says something counter to your point of view, then attack that person, his institution, his colleagues etc., instead of presenting a cogent argument based on fact, rather than misinformation or opinion widely circulated on the internet and elsewhere.”

      Actually, I think that at its core, this statement is true. If you can’t think of Dr. Baker saying it – think of someone else saying it. Sapi. MacDonald. Barthold. Doctors you trust… I don’t see why people feel a need to engage in ad hominem attacks on others when they disagree with each other’s point of view. And I think that if the argument is about the science and research about Lyme disease, rather than attack the person or institution which holds a differing opinion – counter their argument. Otherwise, it just becomes a “he said, she said” kind of argument.

      One person I hold up as a good example of someone who can talk about the nuances and disagreements within Lyme research is Pamela Weintraub. There truly IS a lot of complexity to this disease (and coinfections) and how it affects us. She knows; she spent years working on “Cure Unknown” and talking to all these researchers. But never once have I heard her name call, threaten, or hurl negativity at those whom she disagreed with or which other patients disagreed with. And by doing so, I think she learned more about what is known and not known about Lyme disease as a whole – the gestalt.

      “The biggest mistake was deciding any tiny, tiny study could define a whole disease it was clear by the EVIDENCE (not lies, misinformation) was not understood fully. When it was found co-infections were involved–why were there not more questions about the basis of the IDSA guidelines?”

      I agree. No one study should define or characterize a disease. Multiple studies are needed, and confirmatory studies. And I think you are absolutely right: The affect of coinfections on patients requires more questions and more research. Polymicrobialism or coinfections can have a synergistic or additive effect – that is, they could have a harder impact on the immune system and make it more difficult to fight off infection. It is vital to study this.

      “I think most involved just cannot admit that they didn’t know what they didn’t know.”

      I think this sentence is perhaps the most insightful I have read in some time. I think some can’t admit they did not know what they did not know. And I also think that tickborne diseases are so complex that they are difficult to study and there really is a lot researchers do not know. They don’t know, and none of us know. That’s part of the problem.

      People who have a strong sense of ego and think they know it all about Lyme disease or the disease complex have to be humbled by its complexity. There is so much that isn’t known. Radolf and others who contributed to his master tome on Borrelia all pretty much say in that book that there is so much we don’t understand about these spirochetes – and they do this stuff for a living!
      • Light on Lyme February 28, 2012 at 10:30 am Log in to Reply

        Thank you, Camp Other, for the compliment.
        Shan Devine
        Light on Lyme
    • Phillip J. Baker March 1, 2012 at 5:35 am Log in to Reply

      I suggest that you read this: http://www.fasebj.org/content/26/1/11.long
48. jack renoud February 27, 2012 at 9:08 am Log in to Reply

    One more last thing. It has been so wonderful that once in a while, a layperson, a non ‘scientific’ expert , will come up with something that makes so much sense. Researchers should listen more to patients and what has been working for them. All a patient wants is to feel better, get back their lives.This young lady’s findings are, I believe , related to the phenomena called Occam’s razor. I was recently reading a blog on Lyme disease and the way this young lady was coping with her disease, the chronic aspect of it. She stated this; Lyme disease, for her, has never been killed by 100mg of Doxycyline twice a day. It’s purely a therapeutic dose at that low dose and at that low dose , often prescribed by doctors as a ‘cure’ that merely keeps the Lyme spirochetes at bay.Long term treatment with this dose will lessen bacteria load, not eliminate it.. Her theory is that Doxycyline is only bacteriostatic at 200 mg a day, and becomes bacteriacidal at 400-600mg a day. I tried the latter treatment recently and low and behold, I had Herxheimer reactions that were almost worthy of calling 911 and going to the emergency room. The reactions were massive. I still have Lyme spirochetes in my body after 30 years of infection!!!! I am feeling quite a bit better now after 6 days on this double dose.!!!! My point is that , finding a cure for this disease , even advancing our knowledge of it, can be greatly aided by doctors, both treating and researchers, listening more carefully to people like this young lady. This young lady is really on to something. Doxycycline is perhaps being prescribed incorrectly when trying to cure someone of this disease.Maybe the other drugs that are being used are also being used incorrectly. I would like all of researchers to get up off their butts and go and survey, talk , listen to all of us suffering people , rather than sit in a laboratory and try to figure out what is happening or arguing online about this and that. The patient will tell you most of everything you need to know about this disease and others , if you will only listen to us.
49. admin February 27, 2012 at 1:38 pm Log in to Reply

    We’ve been heartened by the number of responses to this blog posting. However, some of them have been quite lengthy. In the interest of providing a forum for a diversity of opinions, please limit your responses to 150 words. (And please, no vulgar language, no personal attacks, no spam.) Comments are moderated before they appear.
50. Mary February 27, 2012 at 3:56 pm Log in to Reply

    The PROOF is in MEDICAL RECORDS of suffering HUMAN BEINGS that long-term (IV) antibiotics for Lyme and co-infections HAS and DOES SAVE LIVES!!! PERIOD.
    • Phillip J. Baker March 2, 2012 at 6:50 am Log in to Reply

      If that were so obvious, there would be no controversy and we would not be debating all of this here. Why are so many people also complaining that even extended antibiotic therapy is not working and that this infection is incurable? For every person that claim to have benefited from such therapy, there are as many — if not more — who have not. Those are the ones that are seeking relief from Rife machines, herbal medicines, cyst busters, and other quack medicines. Some are even going to India to get stem cell infusions, for the mere price of $40K. What do you think about that?
      • nick July 9, 2013 at 9:48 am Log in to Reply

        If the answer is in the medical records researches would not know as there are privacy laws in place that preclude the release of that information without informed consent.

        Thus in essence Dr. you can not say truthfully whether we would or would not know this information and or debating it.

        The lack of researchers all over to access patient medical records for research has been a long standing complaint.
51. amy b gillis February 27, 2012 at 4:06 pm Log in to Reply

    Phil Baker: I would like to thank you for your input on this subject. I am one of the people out there that really wants to here the other side of the story. I have some serious doubts about the honesty of your responses, but I believe that you believe what you are saying. Thank you for putting yourself out there and offering your opinions from the other side of the isle. It will help me to make a more informed choice in the treatment of Lyme Disease.
    • Phillip J. Baker February 28, 2012 at 11:46 am Log in to Reply

      Thank you, Amy. I’m glad there is someone out there that is willing to listen to what I have to say and not think that I am lying to make money off of Lyme disease.

      Since I was a research scientist for more than 40 years, I am trained to examine data critically and have a high standard for scrutinizing not only my own work but that of my colleagues. As a public official and Program Officer for the Lyme Disease Program, I can not govern my conduct by a lesser standard. It would not be in the public interest for me to do so. So, while other can go by their “gut feelings”, I can not. They are not responsible for the consequences of their actions on the public health. I am and I take it seriously. .
52. Phyllis Mervine February 27, 2012 at 4:54 pm Log in to Reply

    Phil, I really would like an answer to my original question, which for your convenience I repost below. A related question is, why should we only accept RCTs? Surely you can’t simply dismiss the hundreds of cases reported in observational studies by people like Donta et al. or disregard Burrascano, who has treated over 10,000 patients.

    Then there is the matter of informed patient choice.

    Quote:

    … the point is, we know that long-term antibiotics help some people and until there are better treatments for chronic Lyme, patients should have the right to choose.

    If you take antibiotics for your strep throat and then relapse, your doctor is not afraid to give you more. If you have tuberculosis or endocarditis your doctor may prescribe months of treatment, no problem. If you have cancer, your doctor lets you choose between chemotherapy, radiation, surgery – none of them risk-free options. If you have HIV and you die, no one blames your doctor. No, the medical community supports providers who take on the most challenging patients. Why should chronic Lyme be different?

    Can you please give us your perspective on these important questions?
    • Phillip J. Baker February 28, 2012 at 10:24 am Log in to Reply

      Phyllis,

      Anyone who has the least bit of experience doing clinical studies knows about the placebo effect and the influence it has in interpreting the results obtained. In the Klempner studies, which were the largest placebo-controlled study done on the effect of antibiotic therapy on the treatment of PTLDS, a placebo effect of 38% was noted; this is sufficiently close to the probability for the result of a coin toss (50%) to make me very uncomfortable about accepting the results of any treatment study, that does not include a placebo control or comparison to the results obtained using an established standard of care regimen. The requirement for a placebo control is more important than ever when one has to rely on improvement of subjective symptoms (as noted by results of the SF-36 test), rather than overt, objective signs of infection (gram stain, culture etc.) which of course would enable one to more precisely assess improvement as would be the case for the other infectious diseases you mention. Although one would have to do a statistical analysis to arrive at the precise value, I estimate that with a placebo effect of 38%, there would have to be a benefit more than 90% to establish efficacy with the level of assurance demanded of most clinical studies. With respect to the treatment of “chronic Lyme disease”, I don’t know of any non-placebo-controlled study that can make such a claim. Do you?

      It is true that in the case of certain life-threatening disease and/or conditions (e.g., HIV-AIDS, cancer etc.), one is justified in using extraordinary approaches, where efficacy is much, much less. However, since “chronic Lyme disease” is not fatal or life-threatening, one is not justified in using such extraordinary approaches or regimens. It is not simply a matter of getting the consent of a patient who doesn’t know all of the medical facts and issues involved . It is a question of the integrity of the physician and whether he/she feels it ethical to subject his/her patient to such treatment under such circumstances.

      Of great concern to me is that there are MANY, MANY, individuals have been either misdiagnosed or false believe that they have “chronic Lyme disease”. That was clear when we had so much difficulty recruiting patients for the Klempner study.
      Since “chronic Lyme disease” or PTLDS has not yet been defined as a distinct clinical entity – so that one could distinguish it from other non-infectious conditions with similar symptoms – we had to devise enrollment criteria to ensure that we were enrolling the right kind of patients in the studies. The decision was made to enroll only those whose medical record/history indicated that, in the past, they had been correctly diagnosed for Lyme disease, received adequate recommended therapy, and developed symptoms commonly associated with PTLDS, 6 months or more later, whether they were seropositive or not at the time of enrollment. That seemed fair; how could one have “chronic Lyme disease” without having had an active case of Lyme disease in the first place. So, among the more than 1,000 individuals who presented themselves for enrollment, only about 8% were able to meet the enrollment criteria; a similar percentage was noted by Fallon and Krupp in their studies. This means that there are a lot more people who think that they have “chronic Lyme disease” than actually have it. Clearly, they are unlikely to benefit from antibiotic therapy. Other treatment options must be pursued if one really wants to help them. That was the crux of my FASEB Journal article on “The Pain of Chronic Lyme Disease”. Do you find that unreasonable?
      • Phyllis Mervine February 28, 2012 at 9:35 pm Log in to Reply

        Phil,

        1. To define the “only people who actually had chronic Lyme” as the “people who met the enrollment criteria” in a clinical trial is a great leap. The definition of this disease is hotly contested and because the NIH trial enrollment criteria were so restrictive, the results of these trials have been criticized as not being clinically relevant.

        The same goes for your statement: “MANY, MANY, individuals have been either misdiagnosed or falsely believe that they have ‘chronic Lyme disease.’” This is your belief or opinion. How do you know? You shouldn’t promote your own definition as if it were fact. This is another contested area. Please don’t say you know because of the testing because the fact is the testing for this disease is highly inaccurate as the Embers study shows.

        2. You entirely discount patient reports of improvement as no more than the placebo effect. Please. The placebo effect is a THEORY, not an evidence-based scientific fact. Placebo effects may be due to bias in reporting and observation. In their report, Hróbjartsson and Gøtzsche (Cochrane Database Syst Rev 2010) concluded: “
        We did not find that placebo interventions have important clinical effects in general.”
        That said, Fallon and Krupp showed improvement in the treatment group relative to placebo. And, observational studies (e.g. Donta 1997) showed substantial improvement with longer treatment approaches.

        3. Don’t overlook the reason there are so few RCTs in Lyme disease. Most RCTs are funded by pharma. But in Lyme, the fact is there is no pharmaceutical interest in treating this disease. The only RCTs were NIH-funded. Please don’t say the burden of remedying this is on the patient community. Without pharmaceutical or NIH funding, more RCTs will simply not be feasible.

        4. “Adequate recommended therapy” begs the question. “Adequate” therapy may actually be inadequate. There is no scientific evidence that it is effective or adequate, and considerable scientific evidence that it is NOT (in up to more than 50% in published studies).

        5. “Other treatment options must be pursued if one really wants to help them.” Good idea, what about trials of longer treatments, combinations, or pulsing? And not just RCTs, but observational studies and case reports are useful, too.

        Your statement implies that only certain doctors (presumably your friends at IDSA) REALLY want to help patients. In our survey, most of those responding said they had tried (and failed) IDSA treatment and 80% would never go to a doctor who followed IDSA guidelines.

        People who REALLY want to help patients don’t leave them without any effective treatment options pending research that may never come.

        6. I have to disagree that “extraordinary” treatment should be withheld. First of all, what is extraordinary about long-term antibiotics? Ask those with tuberculosis or acne. Second, are you saying that only those who are dying are entitled to treatment? Treating the chronically ill is a major portion of medical spending today. Restoring quality of life is the goal. These are the patients that Klempner described as “[in] a condition worse than patients with marked congestive heart failure. They are two and a half standard deviations from normal – among the most deviant of any chronic illness.” Fallon said patients had pain similar to post-surgical pain, fatigue comparable to multiple sclerosis, and physical disability comparable to congestive heart failure. Give me a break!
        • Phillip J. Baker February 29, 2012 at 7:59 am Log in to Reply

          As I have stated many times, there is no precise definition of “chronic Lyme disease” as a distinct clinical entity that would enable one to distinguish it from other noninfectious conditions with similar symptoms. Until that is done, if it is possible to do, there will always be these debates and disagreements. Why don’t you and you colleagues at ILADS give that a good try and include such a definition in their guidelines? Quite frankly, I don’t find the response that “chronic Lyme disease” is a clinical diagnosis — whatever that means– to be acceptable. Most clinical diagnoses are based on some body of evidence-based knowledge that is widely accepted by the medical community. So, the enrollment criteria used for the Klempner study were quite reasonable and the best we could do under such circumstances. Can you offer an alternative that would have been more precise and one that would not have enrolled individuals with symptoms not likely to be responsive to any antibiotic? Granted, the criteria were not perfect. But, they really weren’t all that bad.
53. John S February 28, 2012 at 3:50 am Log in to Reply

    You know I used to wonder why drug companies would not be investigating chronic Lyme. I can understand why insurance companies like to see it be unproven and deniable, but the motive of drug companies always baffled me. And if you really wanted to suppress research on a disease you’d have to have them on board. Then I came to the realization one day that if chronic Lyme was proven a persistent infection, that then the powers that be may be forced to look into an infectious cause for all the other autoimmune diseases, like arthritis, and this could threaten the huge revenue stream of drug companies from these diseases, like arthritis.
    Well how would they get away with this? Well, all the government agencies are headed usually by political hacks, like the EPA and where I work, that do what their masters tell them. And now I have to wonder if this study was discouraged by some political hack and if it is now being dismissed for the same reasons by the man in charge of overseeing the study.
    Maybe I’m just crazy. But I put this forth as food for thought.
    • Phillip J. Baker February 28, 2012 at 3:36 pm Log in to Reply

      You’re totally wrong, John. What I said are the facts and I should know. I was there and you weren’t. But some people like to invent conspiracies; it’s only when they start believing them that they have problems.
      • John S February 29, 2012 at 4:51 am Log in to Reply

        Well, when you let a serious disease fester and practically deny its existence, as you have, we have to wonder why. To us, it doesn’t seem like you’re too keen to get at the root of the problem. Maybe it is because the disease isn’t behaving in the way that you and your colleagues think it should and you don’t want to admit you’re wrong. Maybe it is something else, like I have mentioned. Or maybe we are wrong. Whatever it is, I believe that you and the IDSA have done us a disservice for so strenuously putting forth your view and impeding any attempt at investigating ours.
54. Donna February 29, 2012 at 4:21 am Log in to Reply

    Thank you so much to Phyllis Mervine for your vigilance in uncovering the truth. Your questions and your statements represent OPEN doors to learning, understanding, sharing ideas and constant refusal to accept “non answers” to crucial questions. NOTHING you say closes a door to learning more. EVERYTHING you say leaves an opening for considering the questions “What is really going on here?” and “What is it that we are not seeing now that we can see better somehow?” and “HOW might that be achieved?” and last but NOT least “How can we help patients?”

    Those who create CLOSED doors and then defend them have left science behind for the sake of ego, I fear. They have also left patients behind.

    To say Thank you feels inadequate, but our language is limited.
55. Phillip J. Baker February 29, 2012 at 7:00 am Log in to Reply

    The results reported by Embers et al. raises several interesting questions. If one assumes that the “persisters” found are capable of infecting and causing disease (which remains to be established), and that they survived adequate antibiotic therapy (which also remains to be established), would they still be present had treatment been longer or had other antibiotics been used (singly or in combination)? Is there ANY treatment regimen that would completely eliminate all of the “persisters”? If not, does it make any sense to keep treating with more antibiotics for longer periods of time? Is Lyme disease truly a disease that can never be cured by antibiotic therapy as the results of Embers et al. imply? Before jumping to such sweeping conclusions, it might make more sense to independently confirm the results obtained by Embers et al., or at least examine — in great detail– the ability of “persisters” to produce disease in the mouse model of borreliosis described by Bockenstedt et al. However, the key issue is what the results obtained in animal models of infection really mean in terms of human disease.
    • James March 1, 2012 at 10:13 am Log in to Reply

      Interesting Dr Baker – we maybe cannot cure chronic Lyme using ABX. So we should bot bother.
      A bit like HIV you mean? Perhaps we ought leave all those folk to die as well. No point in treating them if we cannot cure them, right? Not to mention the rest of the chronic diseases out there.
      Your logic is flawed on just about every reply I have read. I am still consistently amazed by your lack of openness to other points of view. No rational mind would defend your stance the way you do. Just go away and think of what an unbiased rational scientist would write here. Then compare that with your dogma you have written and make some very painful conclusions about yourself. Your lack of objectivity is NOT normal. Think about it!
    • Steven Gottschalk March 2, 2012 at 5:05 am Log in to Reply

      This is perhaps the most credible argument you’ve raised in the entire comment thread. Because it is certainly very possible that the Lyme disease bacteria can never be completely eliminated from the human body. I would bet that most of us who have failed to get completely well despite months or years of treatment, and/or have fully examined the science have considered that a very real possibility.

      But you then imply, through the question you raised, that because the bacteria cannot be eliminated, there’s no reason to treat with longer courses of antibiotics than the IDSA recommends. Here’s the problem with that logic. You don’t have one iota of proof that 30 days of antibiotics (or whatever arbitrary number you choose) is enough to reduce the number of bacteria to one that the immune system can control, or convert it to some non-disease causing infectious state. There is not a diagnostic test in existence that can answer that question currently.

      All you know is you have a sick patient who originally had Lyme disease, whose symptoms possibly improved but did not completely go away, and an arbitrary deadline at which antibiotics are declared to no longer be of use. Yet you have 3 animal studies as well as human case reports proving that the bacteria can persist beyond your arbitrary treatment protocol and you have plenty of anecdotal reports from the field, not to mention data from both the Fallon and Krupp studies showing that some patients continue to improve when antibiotics are extended.

      Without a definitive answer as to where the end point is that treatment is no longer effective, why on earth would you tie the hands of doctors and patients to continue treating as they see fit?

      James really hit the nail on the head with his AIDS analogy. Can you imagine following the same treatment limitations for AIDS? Sorry, patient but you only get 30 days of antiretrovirals and if you’re still sick after that, you must have something else. Oh you died? Too bad. Of course, that’s not what happens because there are credible diagnostic tests that measure the viral load, a knowledge of what that load needs to be cut down to for the patient’s immune system to control the disease, a far more militant patient community that wouldn’t have settled for the kind of crap that Lyme patients have been dealt by the IDSA side of the research community, and they die.

      We only suffer debilitation equivalent to, or worse than, congestive heart failure. But we look fine and the small percentage of related deaths and suicides don’t count, so what the hell, we can all just wait for science to give us better diagnostic tests and better treatment protocols. In the meantime, you and your IDSA colleagues can continue telling us we have “bad blood” and doing your best to see that no doctor anywhere can treat us outside the IDSA guidelines, and that no insurance company will reimburse for that extended care, even when it restores all or part of someone’s health.

      If the bacteria can’t be fully eradicated, let’s just stop treatment at 30 days and wash our hands of the patient. Here’s a question for you. If you can’t prove definitively that the Lyme bacteria doesn’t persist, and there is credible evidence that it may, why would you NOT allow a doctor to treat with longer courses of antibiotics if it appears to be helping the patient?
56. Pamela Weintraub February 29, 2012 at 11:59 am Log in to Reply

    There is not a lot of time in the day to continue debating, but I do feel compelled to add one thing: In all my years of researching Cure Unknown, I never interviewed anyone –not even you Dr. Baker– who mounted such an aggressive defense of the Klempner trials as you appear to be doing here on this blog. Even in the day, which by now is last century, in terms of technology and our capabilities, that study was routinely dismantled for me by virtually all the mainstream experts that I interviewed. Even YOU, Dr. Baker, had some very trenchant and extremely insightful and intelligent critiques.

    That was THEN.

    To suggest that the resonance of this limited little study, with all its flaws, has only deepened with time like a fine wine on the rack is ridiculous –if indeed that is what is being said. I do not want to put words into anyone’s mouth.

    One thing is for sure: Its time has past. It is old. It is low-tech. Patients are still sick and that little double-trial utilized almost none of the sophisticated pathogen-hunting tools available in 2012. More research is needed and we all need to move on.

    It would be better if we could move forward together instead of getting stuck here arguing over the relevance of work that is past its time and out of date.

    Pam Weintraub
    Cure Unknown, 2008
    • Camp Other February 29, 2012 at 1:10 pm Log in to Reply

      “It would be better if we could move forward together instead of getting stuck here arguing over the relevance of work that is past its time and out of date.”

      Agreed.

      Thank you, Pam, for all the hard work you have done on this issue and giving a thoughtful and intelligent voice to the Lyme disease patient community that is heard far and wide.
    • Phillip J. Baker February 29, 2012 at 5:05 pm Log in to Reply

      It makes no sense to apply a whole lot of modern sophisticated technology, without first developing a clear and precise definition of “chronic Lyme disease” — as a distinct clinical entity– so that one can distinguish it from other non-infectious medical conditions with similar symptoms. How can one recognize and treat ANY medical conditions without being able to define exactly what it is? It is not enough to say it is “a clinical diagnosis”. That could mean almost anything. I challenge ILADS to develop such a definition and include it in their next set of guidelines.
57. Pamela Weintraub February 29, 2012 at 7:17 pm Log in to Reply

    Dr. Baker,

    On the precise definition, I agree with you –especially now that we have so much more information on infective strains, on proteomic patterns (Schutzer), and even on persisters. One could come up with a definition that was far more precise than anything used in the NIH studies today…. I am completely on board. Be precise and let the chips fall where they may.

    But I think you might agree with me that we are not talking JUST about Lyme disease, chronic, acute or otherwise.

    The definitions must be precise, but alternatively, here, the net should be cast wide to see what we are dealing with, really. These days you can do high-volume pathogen discovery rapidly and to great precision, something impossible in the days that Klempner did his work. Similar technologies discover chemokines, cytokines, and the like –hundreds of molecules involved in the immune cascades, much of it automated today. Who knows what we might find? But if you are looking for one thing, only, in this situation your hands are tied. This is not 1980, it is not even 2000. We can do much more.

    I can’t imagine that you really disagree with this –in fact I think that to some degree, it is what you are saying, yourself, cast the net wide. Be precise.

    I find all the NIH studies vague to one degree or another, and I think we can do better. We can be more precise, more specific, more wide-ranging. It is imperative to do better, because so many remain ill. Whatever the answer, for anyone to claim they see some version of ultimate Truth in the Klempner study is absurd. We must move on.

    Pam Weintraub
    • Phillip J. Baker March 1, 2012 at 5:04 am Log in to Reply

      Sorry, but I must disagree with you about “casting a wide net”, Pam. Doing so might provide one with great satisfaction in appearing to be doing something useful and making progress; however, it could simply be a tremendous waste of scarce funds and resources that could be applied elsewhere with greater benefit. I say that for this reason. Not having a precise definition for “chronic Lyme disease” or PTLDS was a problem that we had to deal with before we could even think of initiating the Klempner studies. It had to do with ensuring that we enrolled only those who were MOST LIKELY to have “chronic Lyme disease” or PTLDS. As I noted in my response to Phyllis in a previous post on this blog, after surveying more than 1,000 individuals who presented themselves for enrollment, only 5-8% were eligible and met the restrictive enrollment criteria that we devised. It is interesting to note that Fallon and Krupp used the same enrollment criteria and found about the same percentage of prospective volunteers to be eligible. So, when you cast your net to do the sophisticated studies that I agree ought to be done, don’t you want to make sure that you are catching the 5-8% most likely to have “chronic Lyme disease” and not the 92-98% who may not have “chronic Lyme disease”, but some other medical condition that deserves proper treatment and care? That is what really concerns me and is the issue that I raised in my recent FASEB Journal paper on the “Pain of Chronic Lyme Disease” (see link to article in previous postings on this blog).

      One last point: Let’s suppose that the “persisters” described in Embers et al. really do occur in patients with Lyme disease after extended antibiotic therapy, which of course remains to be determined. Could they be present for long, long periods of time WITHOUT producing disease as evidenced by the expression of any of the symptoms associated with “chronic Lyme disease” or PTLDS? That is the big question, isn’t it?
58. Phyllis Mervine February 29, 2012 at 10:23 pm Log in to Reply

    Hear, hear, Pam. No one should be making sweeping conclusions based on the clinical trials that have been done so far. We need to give evidence-based – not opinion-based – guidance to doctors, including acknowledging where the evidence is inconclusive. Just because chronic Lyme has not been defined does not mean it does not exist. And until the day comes when we have a sure cure for Lyme, we need to give patients choices and let their doctors freely use their clinical expertise.
    • Pamela Weintraub March 1, 2012 at 5:49 am Log in to Reply

      Phyllis, Dr. Baker, and all:

      The idea that we have to start with the PATHOGEN in our search for a cause is obsolete today. See here interview I did with Ian Lipkin, probably the world’s expert in pathogen discovery and a pioneer in finding the immune and molecular footprints of disease.

      http://astralgia.com/pdf/ianlipkin.pdf

      He does not start with the pathogen –he works his way back from the disease itself. He starts by seeking its footprint and all the molecular tributaries it spawns ….whatever we are looking for here, be it Lyme, coinfections, other infections not-tickborne, autioantibodies, or any other immune effects caused by persisters or Borrelia long-gone or anything else, this is the kind of precision we need.

      Coming to conclusions from those NIH studies –done essentially, pardon my French, with 1980s technology– is irresponsible in light of the capacity we have to get to the bottom of things today:

      I am NOT advocating an answer in advance, I am suggesting that we look for one.

      Pam Weintraub
      Cure Unknown, 2008
      • Phillip J. Baker March 1, 2012 at 9:52 am Log in to Reply

        By all means look and good luck to you. But be sure that you are looking at the right population if you expect to get meaningful results.
    • Phillip J. Baker March 1, 2012 at 6:56 am Log in to Reply

      I agree, we must rely on the results of evidence-based research. That’s exactly what the IDSA guidelines, that are based on more than 400 peer-reviewed publications, are meant to do. Their recommendations certainly are evidence-based, and not based on opinion papers. Furthermore, they are endorsed by several prestigious organizations and expert panels throughout the world.
      • John S March 1, 2012 at 3:33 pm Log in to Reply

        Weintraub is saying we need new technology and this guy keeps endorsing guidelines based on the stone age. Obviously there is a disconnect or this guy is delibrately spreading propoganda, which wouldn’t surprise me with a lobbyist.
      • Steven Gottschalk March 2, 2012 at 4:28 am Log in to Reply

        The Barthold mouse studies, the Straubinger dog studies and the Embers monkey studies — are those opinion papers? At the very least such studies should cast enough doubt to eliminate the kind of declarative statements made in the IDSA treatment guidelines regarding diagnostic protocols and treatment durations.

        I realize that two of those studies were not available in 2006, but you continue to defend the IDSA Guidelines as valid and acceptable science despite the newly raised doubts, not to mention the changes recommended by the IDSA review panel and the findings of the IOM committee.

        So the question that begs to be asked here is which Phil Baker is it that continues to defend these outdated and biased guidelines? Phil Baker the scientist with 40 years of experience, or Phil Baker the IDSA lobbyist?
        • Phillip J. Baker March 2, 2012 at 3:32 pm Log in to Reply

          Straubinger was unable to culture Borrelia, from dogs even though they were PCR positive. Keep in mind that the PCR test only detects DNA; that could arise from living or dead bacteria, as evidenced from the detection of Borrelia DNA in the 5,000 year old Iceman. PCR positivity is not conclusive evidence for active infection.

          My criticism of the Barthold studies with mice are the same as those of Embers et al. It remains to be seen if “persisters” can infect other animals and — most important– cause disease. The authors of these papers acknowledge these caveats.

          But, let’s suppose “persisters” occur in humans treated with antibiotic. Would more prolonged antibiotic therapy eventually be able to get rid of them? If they do not produce disease, will they eventually just disappear in time? If that is the case, would it make much sense to continue to treat with antibiotics? The significance of these finding with respect to the human situation is far from clear. It is unclear if the antibiotic treatment used was adequate; that also remains to be determined.
59. Camp Other March 1, 2012 at 2:04 pm Log in to Reply

    How about characterizing the patient population first, based on history of a tick bite? Why not throw out the serology and look at the problem from a different angle – particularly if patients were bitten, never got a rash or don’t remember one, and symptoms showed up in late stage Lyme disease?

    Another angle: The proteomics study which found different proteins in the CSF of chronic Lyme/post treatment Lyme disease patients compared to those found in CFS/ME patients and healthy volunteers – as well as Alaedini’s recent study – may help to characterize the common ground in patients suffering with persisting symptoms. While some patients are not happy with Alaedini’s findings or how others have interpreted them, they note that Alaedini thought those with CLD/PTLDS might have had an infection for a very long time. And there have been other educated guesses at possible biomarkers for CLD/PTLDS and genetic backgrounds – including the HLA-DR4 for Lyme arthritis. Is there another genetic connection for this condition which applies to symptoms outside of Lyme arthritis? According to what I’ve read so far, a meta analysis said no, there isn’t – and one version or another of an autoimmune process is mentioned as a cause.

    I think there has to be more than one way to identify who has chronic Lyme disease/post treatment Lyme disease, beyond a blood test and evidence of a rash that may or may not have been visible. The rash is convenient if it shows up as long as the doctor identifies it properly – but absence of one or memory of one doesn’t mean the person didn’t contract Borrelia infection.
    • Phillip J. Baker March 2, 2012 at 7:10 am Log in to Reply

      Yes, I remember all of those spots that Steve Schutzer found using the specimens that he and Armin Alaedinin obtained from Mark Klempner’s valuable specimen repository. People forget that establishing a repository of valuable specimens derived from Mark’s clinical studies was also a major objective of his work and part of the contract that he was awarded. Few people realize that even though Mark’s clinical study has been completed, the work still continues to contribute to furthering research and acquiring new knowledge about Lyme disease.

      I have never been one to discourage bold and imaginative research approaches. However, as I told Steve myself, one must recognize that it is going to take a long, long time to determine which — and how many– of the hundreds of spots found are really relevant in telling us anything at all about Lyme disease. All one has to do is to look as Joost Oppenheim’s diagrammatic representation of cellular interactions involved and the cytokine cascades initiated during the course of an immune response and it becomes obvious that this is a daunting task indeed. Although we are not likely to get answers soon, I say “press on” and be persistent– and be hopeful about getting grant support in these extremely tough times.
      • Pamela Weintraub March 4, 2012 at 7:55 am Log in to Reply

        These days this kind of discovery can be done at vastly higher speed –despite the challenges– it is not the same game it was a decade ago. It is essential to find other ways, beyond the restrictive criteria of the three past NIH studies to identify patients, or we will never answer the question at hand –do the persisters cause the disease?– to any satisfaction. The early-stage treatment failures are an outlier group and it is even conceivable that the early-stage treatment failures and the late-stage treatment failures have distinct disease processes, even though the etiology was the same. Pamela Weintraub, Cure Unknown
60. Camp Other March 1, 2012 at 2:09 pm Log in to Reply

    And here’s to Raboud University, for not only conducting a double arm and placebo treatment trial for CLD/PLDS:

    http://clinicaltrials.gov/ct2/show/NCT01207739

    But for also working with Boulder Diagnostics on a blood test for chronic Lyme disease.

    Thank you for working on the problem of chronic Lyme disease, Raboud.
61. Lorraine Johnson March 1, 2012 at 2:57 pm Log in to Reply

    Dr. Embers has confirmed the antibiotic used was “Rocephin, ceftriaxone sodium, Hoffman-LaRoche Inc.”

    http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2Fdf4a8067-a119-41ce-8ecf-2868160fe41c&root=info%3Adoi%2F10.1371%2Fannotation%2Fdf4a8067-a119-41ce-8ecf-2868160fe41c
    • Phillip J. Baker March 2, 2012 at 5:38 am Log in to Reply

      I’m sorry but the citation only states that she was asked to confirm that ciftriaxone and not ceftriofur was used. I don’t see where she has actually done that. Please clarify. If that’s the case, then where in the study was ceftiofur used?
    • Camp Other March 2, 2012 at 7:58 am Log in to Reply

      Thanks, Lorraine. This is an important update.

      Dr. Baker now has one less argument against this study.

      It was ceftriaxone everywhere else in the paper except one mention. It may have just been a typo.
      • Phillip J. Baker March 3, 2012 at 5:49 am Log in to Reply

        Really ? A typo? Not even close. Ceftiofur and ceftriazone are manufacture by two different companies. In view of the reaction this paper has provoked I think the authors owe the scientific community a full explanation. Were both drugs were used in the studies as though they had the same properties? If so, then which animals got what drug? The other arguments that I raised are much more substantial and still hold.

        By the way, let’s just suppose that the “persisters” reported after extended antibiotic therapy are real live bacteria. The real question is do they produce disease and the symptoms associated with “chronic Lyme disease” in humans, which remains to be determined. If they don’t, and they just “sit there” until they eventually disappear, does it make any sense to continue to treat with antibiotics? What good would that do?
        • Pamela Weintraub March 3, 2012 at 6:17 pm Log in to Reply

          Regarding the antibiotic and confusion over it, I wish this would be addressed in the peer review, where it belongs –not that it isn’t interesting here, too. But I think experts should write up this critique in the appropriate forum, where it can be evaluated by scientific peers, and let the scientists respond –again, in the peer review. The antibiotic used seems like an important point and we should get to the bottom of it and clear it up once and for all.

          The second issue –what role if any do these persisters have in disease?– is indeed the $64 million question, and I totally agree with Dr. Baker –it needs to be answered through science. Only caveat I have is that the patient cohort must be those with disseminated, untreated infection like the rhesus monkeys –or, as suggested elsewhere here, we may be dealing with apples and oranges, divergent cohorts, and the debate over this will never end.

          Quite an interesting discussion.

          Pam Weintraub,
          Cure Unknown
62. Pamela Weintraub March 1, 2012 at 6:47 pm Log in to Reply

    Dr. Baker,

    What you say about defining chronic Lyme in a real way makes sense. Yes, you would have to do this for any study to be legitimate.

    But this brings up, to me, a question about the Klempner patients –are they not in some sense outliers? What is your view?

    I mean it like this: The rash-only seronegative group and perhaps many or even most of those in the seropositive group were treated adequately for acute early Lyme disease, correct? (And correct me if I am wrong, please!) But they failed that treatment and went on to have the entity Klempner calls PTLDS.

    If so, the Klempner group contrasts with most of the chronic Lyme patients –however we ultimately define them– because most in this group never had early adequate treatment; most were misdiagnosed for months to years as they got increasingly sick. For those chronic patients whose illness really derives from LD, we can guess that had they been treated early and adequately (and here I mean according to IDSA guidelines) most likely would have been cured. completely.

    Most of the chronic Lyme group instead had late diagnosis and no early adequate treatment and thus, advanced to the disseminated, late stage infection that Barthold and Embers and others allowed to develop before treating their animal models….

    So this chronic group –however we ultimately define it– is de facto different than the Klempner group. Isn’t a group in which (I am guestimating) at least 50 percent and possibly more failed treatment for early Lyme disease a group of outliers?

    That’s what confounds me…. most people do not fail adequate treatment for early Lyme disease unless they are immunologically compromised or something else is going on, some some kind of other exposure or stress.

    It begs the question of how much the Klempner patients tell us –even if the study is airtight– how relevant is this group to what is happening out there in the world?

    If you could address, I would appreciate it.

    On your second statement regarding the persister cells, of course, I absolutely agree: 100%. You are asking the right question as far as I am concerned. And answering it is what I would do next, as well, were it up to me.

    Thank you for hanging in and engaging in this dialog.

    Pam Weintraubt
    • Phillip J. Baker March 2, 2012 at 5:29 am Log in to Reply

      As I said previously and on many occasions, Pam. The Klempner study may have unintentionally excluded many patients that had “chronic Lyme disease”. However, our concern was to ensure — in the best way that we could– that those enrolled had a high probability of having “chronic Lyme disease” or PTLDS. We used the same enrollment criteria used by Krupp and Fallon. I admit that an important cohort was not included, namely, those who had NOT been diagnosed early for Lyme disease and in whom the infection was allowed to progress to the late stage where symptoms characteristic of “chronic Lyme disease”/PLDS are manifested. But, in all fairness, such a cohort would have been more appropriate for another study that focuses on the effect of prolonged, untreated infection, its consequences and resolution. In that context, I would like to call your attention to this case report (http://www.ncbi.nlm.nih.gov/pubmed/21173795). Granted, it is only a single case report, but it does indicate that an infection that has been allowed to progress –untreated– for more than 4 years, can be treat successfully with two short courses of oral antibiotics. Although the data are not presented in the publication, the author tells me that the patient was strongly positive by the CDC criteria for and IgG Western blot. So, all may not be lost if the infection is not diagnosed early, although I certainly agree that it is always best to treat this or any other infection as early as possible.

      One point that is often missed in these discussions is that the symptoms associated with Lyme disease that some time to disappear, well after the infection has been successfully cured by antibiotic therapy. That is certainly the case for the 6th nerve facial palsy, brain fog, and arthritis. There is a very informative figure in the above cited paper showing data published by Alan Steere. It shows that the percentage of patients with Lyme arthritis who experience recurrent episodes decreases by year of disease and does not reach zero until 9 years after successful antibiotic therapy — in the absence of further treatment. I think that is a significant point that must be kept in mind. It speaks to the issue of whether it is really wise or necessary to treat until symptoms disappear.
63. Sherrill Franklin March 3, 2012 at 4:20 am Log in to Reply

    At this juncture it might be useful to remember Alexander von Humboldt’s brilliant observation about the three stages of scientific discovery: First people deny that it’s true, then they deny that it is important. Finally, they credit the wrong person.

    We have just ventured into stage two, so this is progress. However, discussing this issue with those who are chronically dismissive is like trying to have a conversation with a table. We need to get into the passing lane on this broad highway to discovery.

    It is worth repeating Pam Weintraub’s quotation (above) highlighting the process of discovery used by pathogen pioneer Ian Lipkin : “He does not start with the pathogen –he works his way back from the disease itself. He starts by seeking its footprint and all the molecular tributaries it spawns ….whatever we are looking for here, be it Lyme, coinfections, other infections not-tickborne, autioantibodies, or any other immune effects caused by persisters or Borrelia long-gone or anything else, this is the kind of precision we need.”
    • Phillip J. Baker March 3, 2012 at 10:04 am Log in to Reply

      Agreed. Since, despite many attempts, there are no published data proving that extended antibiotic therapy is beneficial for the treatment of “chronic Lyme disease”, other new and exciting approaches certainly ought to be considered and pursued.
      • Cupcakesat March 23, 2012 at 9:31 pm Log in to Reply

        I have Lyme disease & am an aivcte member of a Lyme organization. Over the past several years, I have spoken to many people with Lyme disease. For those that did develop the bulls-eye rash, they claim the rash resulted after a mosquito, gnat, or yellow fly bite. TICKS ARE NOT THE ONLY TRANSMITTER OF LYME DISEASE ! Borellia burgdorferi aka Lyme bacteria, is a spirochete form of bacteria. It’s in the same family as the bacteria that causes Syphilis. Lyme disease CAN also be sexually transmitted.
64. Camp Other March 3, 2012 at 11:56 am Log in to Reply

    Dr. Baker said,

    “The real question is do they produce disease and the symptoms associated with “chronic Lyme disease” in humans, which remains to be determined. If they don’t, and they just “sit there” until they eventually disappear, does it make any sense to continue to treat with antibiotics? What good would that do?”

    That is a good question and it deserves an answer. More research is needed, and I’m glad Embers et al did this study.

    But in the meantime, I have wondered something: What is the evidence that infection cannot persist in the host if bacteria remains behind?

    Many times, Dr. Baker, you and your colleagues have stated you don’t think these remaining spirochetes are significant as a cause for people’s persisting symptoms – when it sounds like from the perspective of those working on persistence studies, they are not certain one way or the other. Why is it your position that these spirochetes are likely NOT related to persisting symptoms rather than your position matches that of a number of researchers, which is, “Hm, that’s interesting, I wonder if those spirochetes are related to persisting symptoms or not?”

    I get the impression that your position and that of many of your colleagues is that it is an autoimmune response driving patients’ persisting symptoms. That molecular mimicry is responsible, and the body’s immune system is attacking itself because our cells “read” to the immune system as if they are OspA.

    I’ve read “Antibodies against OspA epitopes of Borrelia burgdorferi cross-react with neural tissue”. I get that. That makes sense to me.

    But what doesn’t make sense to me is why you don’t seem to think that an infection can persist concurrently to this response or that you think it is highly unlikely. Would my perception on this be correct or incorrect: Do you think that persisting infection could occur alongside molecular mimicry?

    If you look at research such as “HLA-DR alleles determine responsiveness to Borrelia burgdoferi antigens” (by Bettina Panagiota Iliopoulou, Mireia Guerau-de-Arellano, and Brigitte T. Huber. Arthritis Rheum. 2009 December; 60(12): 3831–3840.), if this model could apply to humans – then it seems possible that a state could occur where some people with a specific genetic background have high inflammation as well as an inability to clear an infection as quickly as other people. Their immune reaction would be abnormal and inadequate as Alaedini has speculated. If so, they may need longer than standard courses of antibiotics – and possibly some immune modulating treatment, too.

    This is speculative, I realize that. But I want to know precisely what your position is on this.
    • Phillip J. Baker March 3, 2012 at 4:07 pm Log in to Reply

      I’ve said — many times– that it remains to be established that the “persisters” are infectious and can produce disease. I said that about both the mouse and NHP studies. The auto-immune aspects are an alternate mechanism that is now being examined.
      • Camp Other March 3, 2012 at 10:05 pm Log in to Reply

        Dr. Baker,

        Could you please answer the second question I asked?:

        Do you think that persisting infection could occur alongside molecular mimicry?

        Thank you.
        • Phillip J. Baker March 4, 2012 at 1:07 pm Log in to Reply

          I don’t know. My concern is whether the “persisters” occur in humans and whether they cause disease. Here, I am not referring just to “lesions” or overt signs of pathology, but to the symptoms usually ascribed to “chronic Lyme disease”. If they don’t, does it make sense to continue to treat with antibiotics?
          • Camp Other March 5, 2012 at 2:00 pm

            Dr. Baker,

            If you don’t know, I think it’s something worth looking into. There may be more than one reason patients have persisting symptoms. Persisters may play a role in it, but also patients’ genetic backgrounds and the strain of Borrelia with which they have been infected. Coinfections can also have an additive affect on the immune system. Much of the research I’ve read has pointed these items out in their role in the infection process, so I think it is worthwhile investigating them and their interplay.
65. Camp Other March 4, 2012 at 11:00 pm Log in to Reply

    Dr. Baker said,

    “One point that is often missed in these discussions is that the symptoms associated with Lyme disease that some time to disappear, well after the infection has been successfully cured by antibiotic therapy. That is certainly the case for the 6th nerve facial palsy, brain fog, and arthritis. There is a very informative figure in the above cited paper showing data published by Alan Steere. It shows that the percentage of patients with Lyme arthritis who experience recurrent episodes decreases by year of disease and does not reach zero until 9 years after successful antibiotic therapy — in the absence of further treatment. I think that is a significant point that must be kept in mind. It speaks to the issue of whether it is really wise or necessary to treat until symptoms disappear.”

    I am aware of this paper.

    But what about outliers such as Vicki Logan and Karl McManus then? They didn’t get better. They died. I don’t think going without treatment is advisable for anyone. Dr. Martz is another notable case study. He was diagnosed with atypical ALS and his symptoms worsened to a point where he was very dysfunctional and was advised to get his affairs in order. He was later determined to have neuroborreliosis. Positive for Lyme disease. He has been back to maybe 80% of his original baseline health and able to give presentations and put his own clothes on – which he could not do before antibiotic treatment.

    If there are a number of people out there who have Lyme disease who have very slowly improved without treatment, 9 years is an awfully long time to be out of work or not be able to go to school.

    And I have to wonder if those who improve without treatment aren’t outliers in the other direction. If what you say is true, I have not seen any online support forums for Lyme disease patients where they are sharing their joy at how much they’ve recovered without the use of antibiotics. To most people reading this, I suspect they would think the idea absurd.

    And if people experience their symptoms as being even half as pronounced as any of the above people I have mentioned, they will want to find relief and a way of regaining their functionality however they can. They are not going to want to wait and see if they get better without any treatment.
66. Pamela Weintraub March 5, 2012 at 6:28 am Log in to Reply

    Camp Other,

    I just want to step in here, again on the issue of outliers. I know I covered both Martz and Logan in Cure Unknown, but the fact is, they were both extreme outliers. Logan did not have a spleen, to: wit, no immune system, making her most unlike the rest of us. Martz –who still says he DID have ALS– well, the number of people with ALS who are treated with Lyme disease and come back… it is significant, of course, to individuals in that group, but unlike the overwhelming majority of chronic Lyme pateints.

    However, likewise, the early treatment failures in the Klempner study are ALSO OUTLIERS –they are unlike the overwhelming majority of chronic Lyme patients who simply were diagnosed LATE, developing late-stage, disseminated disease. According to Dr. Baker, the Klempner patients never had late-stage, disseminated disease, and for the purposes of academic argument, I am willing to say, perhaps that really is true. Perhaps in this group, infection was stanched and all that remains is an immune illness ….for this outlier group, it ispossible, so for argument’s sake, let’s concede that research should focus there FOR THEM.

    That leaves everyone else –the OVERWHELMING MAJORITY of the chronic Lyme population, folks who were never diagnosed and never treated until late in the game. These people had late-stage, disseminated infection. (And Dr. Baker, again for sake of academic argument, let us say we find a way to ID this group–probably more possible today in light of new studies and technologies.)

    These are the Embers monkeys.

    This is the group that needs to be studied to get any real answer to the question Dr. Baker has posed: Do the persisters cause disease. I just want to refocus this, because sure, Vicky Logan without a spleen should have been treated differently…. still doesn’t broadly apply to the SEMINAL question in front of us now.

    As to your other question, about active infection causing autoantibodies? Of course it can, that is well established in the literature for many diseases…. it is not controversial in the least. But the caveat is that autoantibodies can also be caused by the remnants of an infection, a toxin, and many other things –even stress in life.

    To sum up, for my tax money down, I want to find out what is going on for the MAIN group first.

    Pam Weintraub
    Cure Unknown
    • Camp Other March 5, 2012 at 1:01 pm Log in to Reply

      Pam,

      Your point is well taken. And I agree with you. I think that chronic Lyme disease patients are diagnosed late in the game, and have gone without proper diagnosis treatment for a long time. This is why I mentioned elsewhere that there is a need for more studies on treatment for late stage Lyme disease as well as antibiotic trials for neuroborreliosis which Dr. Fallon has recommended.

      I was only pointing out that Dr. Baker that his reference to Dr. Steere’s paper that people who were untreated for Lyme disease got better in 9 years is not something that I think is useful actionable information for people in general. And for those who are most vulnerable, even less so. It’s dangerous to apply such research and suggest people should go without antibiotic treatment when they have a serious infection.

      “To sum up, for my tax money down, I want to find out what is going on for the MAIN group first.”

      Me too. You won’t get any argument from me.

      So how do we make sure that of 25% of those RO1 NIH projects which get funded, a high percentage of them are for treatment and research on chronic Lyme disease patients?
      • Pamela Weintraub March 6, 2012 at 2:58 am Log in to Reply

        Well Camp other, the first thing is to differentiate between what I think of as the PLDS and CLD groups. Today, these are entirely conflated by most people, no matter what their POV.

        Let me explain my terminology and meaning. Dr. Baker has commented to me in the past –and point well-taken– that we have to be sure the study cohort had Lyme, and from the perspective of 2000, I accept that Klempner did the best he could –but nonetheless, the group was entirely PLDS, meaning, to me, that these were early treatment failures. Klempner’s argument that he is finding immune disease only could well hold true for this outlier group.

        But today we have better technology, we have the Schutzer findings in proteomics –and we have the capacity to obtain more like information on immune, protein and pathogen profiles from biosamples– meaning that these days, we can work toward identifying a real, late-diagnosed CLD cohort–in a way that would be rigorous enough to pass muster in the peer review.

        I feel that needs to be done first, before we undertake any more treatment studies –if we want the research to be broadly applicable, and in a way that will end this debate. If you try to research CLD by studying what could be a true PLDS group, then what do you really have?

        After the group is defined, we would need to determine the link between the persisters and disease.

        I don’t know how to get more of this money allocated to the CLD group if they are presumed not to exist or to be the same as the PLDS cohort –so establish that first.

        Pam Weintraub, Cure Unknown
67. Joel March 5, 2012 at 9:17 am Log in to Reply

    Dr. Baker,
    Thank you for your answers and allowing this debate.
    “…there are no published data proving that extended antibiotic therapy is beneficial for the treatment of “chronic Lyme disease”” :
    http://www.bada-uk.org/wordpress/?p=98
    http://www.em-consulte.com/article/200534
    http://www.researchgate.net/publication/23759251_Efficacy_of_a_long-term_antibiotic_treatment_in_patients_with_a_chronic_Tick_Associated_Poly-organic_Syndrome_(TAPOS)
    Chronic infection :
    http://www.lymekick.com/chroniclyme.pdf
    “…does not reach zero until 9 years after successful antibiotic therapy” : If only you were right, it would mean for me a complete recovery within the next year !
    It seems at least that everyone agrees that more research is needed for CLD, and we all hope it will happen very soon.
    Joel from France
68. Phillip J. Baker March 6, 2012 at 7:42 am Log in to Reply

    Schutzer used specimens derived from the Klempner studies in his proteomics work, Pam. The problem is one of too much background noise in his system, i.e., too many spots and no way –as yet– to sort out the relevant from the irrelevant; but, that may come later. Also, Alaedini used specimens from the Klempner studies in his published work on auto-antibodies vs nerve tissue antigens; those studies seem to be providing interesting information, and it would be most interesting to see if other auto-specificities can be detected in the remaining subsets of patients . So, whatever the cohort of patients used by Klempner , it is providing useful information, and the specimen repository is available to others to expand on these studies or pursue new approaches. That doesn’t require a whole lot of new money. You haven’t told me how you would distinguish between patients with PTLDS and CLD?
    • Pamela Weintraub March 6, 2012 at 4:00 pm Log in to Reply

      Dr. Baker,
      Thank you for this clarification –I had not been aware that these samples came from Klempner. As to your question, as you know, I am not a scientist but a science journalist. I would simply hope it could be done so that we could get on with it. As I speak to experts, I will ask them this question and if anyone has any helpful suggestions, I will absolutely let you know –useful though the Klempner work has been in some respects, I still think we need to answer the question about chronic patients with a late-diagnosed and late-treated group to understand what is going on there. It’s hard to believe that we can’t find a way of defining them toward this end.

      Pam Weintraub
      • Phillip J. Baker March 7, 2012 at 4:08 pm Log in to Reply

        Pam,
        Without examining the medical history of the patients who enrolled in the Klempner study, I don’t think one can say that any of them are treatment failures or to characterize the duration of their infection before they were in initially treated — and then apparently cured– as a condition of enrollment. All of those are very much unknowns. What Klempner did was to work with the situation as it exists in the real world. All of those who presented themselves for enrollment — including those who were not enrolled– believed that they had “chronic Lyme disease” based on their symptoms. In the absence of overt signs of infection and/or lesions, the symptoms are all that one has to work with in most cases. That makes it tough, but who said doing clinical research was easy anyway.

        In case you missed it, I’d like to call your attention to this case report (http://www.ncbi.nlm.nih.gov/pubmed/21173795). Granted, it is only a single case report, but it does indicate that an infection that has been allowed to progress –untreated– for more than 4 years, can be treat successfully with two short courses of oral antibiotics. Although the data are not presented in the publication, the author tells me that the patient was strongly positive by the CDC criteria for and IgG Western blot. So, all may not be lost if the infection is not diagnosed and treated early, although I certainly agree that it is always best to treat this or any other infection as early as possible.
        • Jill March 9, 2012 at 11:21 am Log in to Reply

          Yes, certainly not all people are alike, not all are infected by the same strain, etc., etc. So, as you describe, some may respond to a short course of treatment, but we know not everyone does. Therefore, a one fits all approach is not the answer and is damaging to many people who might otherwise respond. Research is needed, too many people are affected by this.
          Jill
          BTW, What about PREVENTION and why has the NIH canceled research such as was being done by Dr. Wikel?
          • Phillip J. Baker March 9, 2012 at 4:22 pm

            Jill,

            I don’t know that the research has been cancelled. It could be that Dr. Wikel was not able to get a high enough score for funding. Ask the program officer if you really must know.
69. Lyme in da Coconut March 6, 2012 at 7:45 am Log in to Reply

    Coming from a family with several generations of researchers, I have followed the ongoing debate regarding the persistence of Bb infection. I was diagnosed at long last with Lyme Disease many years after the onset of numerous symptoms including objective measures such as hematuria, lactation, hypothermia, and so forth.

    Although not unique, I am in a position to help with research. I had tissue expanders implanted six months and two months ago, respectively, and I suspect that these expanders will provide information regarding Bb, persistence, and biofilms. To date, of the few institutions I’ve contacted, none have expressed an interest in receiving and studying the expanders in spite of my willingness to follow whatever pre-op and peri-op protocols would be deemed the most advantageous for the furtherance of research.

    Is there any interest on this forum?
70. Camp Other March 6, 2012 at 9:24 am Log in to Reply

    Pam said,

    “If you try to research CLD by studying what could be a true PLDS group, then what do you really have?”

    You wouldn’t have data that represents reality, and we’d be back at square one.

    I understand what you’re saying – it’s important to distinguish between these two groups – those who are genuine treatment failures and have PLDS and those who have CLD.

    I’ve just wondered about the whole argument of “either/or”: either it’s a chronic infection or it’s an immune problem when it comes to people with persisting symptoms. Is it possible this a false dichotomy? This is why I brought up the paper I cited upthread. If its findings can be applicable to people – and if it’s possible part of what makes Lyme disease chronic in some people is a combination of genetic background regarding immune response plus persistent infection – then that is something that would be good to know. It also would unite people working on this problem from different approaches.

    In terms of proteomics, how does this work? Can one distinguish between acutely infected patients, convalescent patients who have no symptoms (and negative or significantly declined test results over time), and then those who have late stage Lyme disease by using proteomics? Could this or some other method somehow determine where patients are in the disease process? If this can work and be refined somehow to distinguish between these different states, it could lead to new diagnostic tools. (I have unanswered questions about the use of proteomics – more than I can put in this space at the moment.)

    You’re right in saying one has to have clear cut groups defined first to proceed in many ways.

    “After the group is defined, we would need to determine the link between the persisters and disease.”

    Finding transcription going on in the Embers study was compelling to me. I want to hear more about this study and any extension of it. Do you know who else is currently working in this area of research outside of Embers’ team? It would be good to see what their results are.
    • Pamela Weintraub March 6, 2012 at 4:06 pm Log in to Reply

      Camp Other: I have always said it is a false dichotomy; I am most interested in the work with B cells, and think there may be answers there for many. But patients may be at different places on the spectrum depending on their particular situation imo –just as with the mouse population created at the U of Utah. However, if you are trying to answer questions about the persisters found in the Embers monkeys, I don’t think a human group like Klempner’s is the place to start.
      Pam
71. Jill March 9, 2012 at 10:51 am Log in to Reply

    Dear Phil, Dr. Baker,

    Now that the issue of ceftriaxone being the antibiotic used is settled, we still need to determine if the ticks that ‘fed’ on the treated Rhesus are capable of infecting a new host. This I agree needs to be completed and I actually assumed it had been, so was surprised that additional/final step was not completed!

    We can however, look at the results of 2008 research at UC Davis, “Persistence of Borrelia burgdorpheri following Antibiotic Treatment in Mice” . In this the mouse study the ticks that were harvested (xenodiagnosis) from the antibiotic treated mice did re-infect skid mice that they fed on. This should give us a view into what will most likely occur when it is performed on the Rhesus monkeys. It is a shame that additional Rhesus should have to be used for experimentation again.

    Just my thoughts,
    Jill
72. Jill March 9, 2012 at 11:27 am Log in to Reply

    Dear Phil, Dr. Baker,
    What I do not understand is that you criticize the Rhesus study when, IMO, it holds so much more scientific validity and evidence than the Klempner study. Additionally, much animal research backs up these findings, and give direct evidence. We all now how poor the antibody testing is to prove ongoing infection, however, with the Rhesus study and others we have laboratory evidence of Bb surviving. In the Bartold study the naïve ticks fed on the mice, became infected and were able to transmit Bb. No such direct methods (tissue samples, etc) or laboratory results came from the Klempner study, nor can they be done on humans.

    Perhaps this demonstrates that even a low level of Bb, infectious or not, is enough to keep some patients’ immune system triggered, and keep them ill. We are all different, with differing genetics, immune systems, and other infections (perhaps co-infections), etc. The truth here is that ‘we humans’ simply do not know the answers. It is evident that more research is needed to find a treatment protocol. There are tens of thousands of people who are still symptomatic after treatment.

    IMO, if this were a communicable disease the research would have been completed.
    Just my thoughts,
    Jill
    PS Is there some manner in which we may speak directly?
    • Phillip J. Baker March 9, 2012 at 4:19 pm Log in to Reply

      Jill,

      The key issue is do these “persisters” cause disease (as evidenced by symptoms) or do they just “sit there” and eventually disappear. None of the animals studies can answer that question — they can’t tell us about their symptoms. Suppose the “persisters” don’t cause disease, but just “sit” there, eventually to disappear. Does that justify giving more antibiotics to get rid of “persisters” might not go away, but do not cause disease?
      • Mary March 16, 2012 at 5:57 pm Log in to Reply

        Do chronic AIDS, Cancer and TB patients “not” get proven evidence-based medicine because their “persisters” might just sit there, eventually to disappear”? –
        (“persisters” disappear upon cell, tissue and human death!)
73. Asclepius March 17, 2012 at 1:40 pm Log in to Reply

    I really don’t understand why you bother arguing with Baker. Allen Steere knew lyme disease was a chronic, relapsing brain disease that could persist after IV antibiotics, but could be treated with antibiotics way back in 1990. How he can claim that somehow its now “hard to catch and easy to cure” is beyond comprehension.

    http://www.nejm.org/doi/full/10.1056/NEJM199011223232102

    Results.

    Of the 27 patients, 24 (89 percent) had a mild encephalopathy that began 1 month to 14 years after the onset of the disease and was characterized by memory loss, mood changes, or sleep disturbance. Of the 24 patients, 14 had memory impairment on neuropsychological tests, and 18 had increased cerebrospinal fluid protein levels, evidence of intrathecal production of antibody to B. burgdorferi, or both. Nineteen of the 27 patients (70 percent) had polyneuropathy with radicular pain or distal paresthesias; all but two of these patients also had encephalopathy. In 16 patients electrophysiologic testing showed an axonal polyneuropathy. One patient had leukoencephalitis with asymmetric spastic diplegia, periventricular white-matter lesions, and intrathecal production of antibody to B. burgdorferi. Among the 27 patients, associated symptoms included fatigue (74 percent), headache (48 percent), arthritis (37 percent), and hearing loss (15 percent). At the time of examination, chronic neurologic abnormalities had been present from 3 months to 14 years, usually with little progression. Six months after a two-week course of intravenous ceftriaxone (2 g daily), 17 patients (63 percent) had improvement, 6 (22 percent) had improvement but then relapsed, and 4 (15 percent) had no change in their condition.
74. Linda April 29, 2012 at 4:51 pm Log in to Reply

    Can someone explain to me how a bacteria can “just sit there” especially in the brain whose chemical balance is so crucial.
    Bacteria compete with human cells for nutrients and excrete toxins, they don’t just sit there.
75. Alan MacDonald MD May 28, 2012 at 7:43 am Log in to Reply

    Re: Teratogenic effects of Borrelia sp. in babies mother with Pregnancy
    and active LymeBorreliosis

    by inmacdonald » May 27th, 2012, 9:36 am

    Gestational Lyme Borreliosis Implications for the Fetus – (annotated) 1989
    Rheum. Clinics North America, W.B.Saunders Publsher
    (Full Text available on http://www.molecularalzheimer.org)

    ___________________________________________________________

    Author’s note:
    The initial report of Transplacental Lyme Disease – with post partum fetal death due to Congential Heart Disease – was supported by a Pathologist who documented fragments of Borrelia burgodorferi spirochtetes in the Autopsy Fetal Tissues. Inflammation would have been expected inthe Autopsy fetal tissues. None was found.
    The Pathologist of the “Minnesota case” ( Schlesinger et al)
    was the renowned Yale Pathologist Dr Paul Harrison Duray.
    The Minnesota case
    ( Schlesinger,PA…Duray, H…and Steere,AC ; coauthored the article ) was the INDEX.
    Dr Duray over a distinguished career ,made many key contributions
    to the pathologic consequeces (with emphasis of finding Inflammatory infiltrates over the demonstration of Lyme spirochetes in tissues) of Lyme disease in various Tissues in the Adult Human with LB.
    Klaus Weber reported a second case of Fetal Death due to Intrauterine Lyme Infection of the Fetus.Again, No inflammatory infiltrates were found in the Fetal Autopsy, in spite of the fact the fact -that Dr. Weber and Associates documented Borrelia in autopsy tissues. The mother had an ECM during her pregnancy and received immediate antibiotic treatment.

    I published similar Autopsy observations proving the existence of Borrelia spirochetes in Autopsy fetal tissue. Again, no Inflammaory infiltrates were found in the organs which habored borrelia spirochetes.

    **********************************************************
    Dr Eugene Shapiro, who is certified only in Pediatrics ( and not Anatomic Pathology) at the Yale School of Medicine, has repeatedly stated
    that not a single case of Maternal Fetal Transmisssion of Borrelia burgdorferi has ever been proven.
    Why?? Because none of the fetal autopsies from Gestational Lyme borreliosis has demonstrated
    “inflammatory infiltrates”.
    He even has the temerity to reject the Index case of Dr. Schlesinger,Duray and Steere..
    Spirochetes in tissue ,demonstrated by multiple pathologists in autopsy work, apparently do not constitute “reasonable evidence” or”Credibility” to Dr Eugene Shapiro.
    The Authors of the Teratology Update article ( see above post) come to an opposite conclusion from the expert Opinion of Dr Eugene Shapiro.
    ***********************************************************
    I will post the full text of my 1989 Gestational Lyme manuscript From the Rheum. Clinics North America
    (peer reviewed and not a pay to publish journal) subsequently.
    The Image data – ie pictures of spirochetes in Autopsy fetal tissue ae the most important Data points
    for you the forum members to consider.
    ***********************************************************
    At the present time, due to the retirement of Dr Paul H.Duray and my retirement from medical practice there are NO Pathologists who perform Autopsies on stillborns,on miscarried fetuses with the application of tedious special techniques utilized to attempt spirochetes in tissue
    using special staining techniques.
    Respectfully,
    Alan B.MacDonald MD
    May27,2012
76. Alan MacDonald MD May 28, 2012 at 8:34 am Log in to Reply

    Re: Wormser et al cite flaws in Embers Rhesus Macaque Study

    by inmacdonald » May 28th, 2012, 10:32 am

    The Broad brush of Wormser regarding ALL PREVIOUSLY Studies using ANIMALS/ Laboratory acquired Lyme/Antibiotic Therapy.

    Wormser is predictable , in regard to the shortcomings, as he views in the broad brush
    of Negative , the relevance of any conclusions derived from thestudy of Laboratory animals –
    because of Absent PK/PD pharmacokinetic data for any of the previously published Animal
    LYME Antibiotic therapy studies.

    In Straubinger’s Canine Lyme Antibiotic studies from 1997:

    —- Straubinger published that significant variability of antibiotic blood levels was
    found for dogs treated with the same antibiotic dose.
    —–Individual Drug level variabilities HAPPEN – and they happen in the Human realm.
    —–Does Wormser derive PD/PK data for ALL human patients with LB who are under his
    ever so brief care?
    Strabinger was interested in FOLLOWUP of the patients (canine) who received care:
    ——

    “However, in dogs that were kept in isolation for 6 months after antibiotic treatment was discontinued, antibody levels began to rise again, presumably in response to proliferation of the surviving pool of spirochetes. Antibody levels in untreated infected control dogs remained high.” Straubinger, 1997

    We are witnessing through Straubinger’s eyes the PERSISTER and its RECRUDESCENCE after
    a “complete” course of antibiotic therapy.

    Link:
    http://jcm.asm.org/content/35/1/111.short

    Dr PJ Baker is the second author with Dr G. Wormser for the manuscript,”Clinical analysis of Treatment Trials of Rhesus macaques Infected with Bb Reveals IMPORTANT FLAWS in EXPERIMENTAL DESIGN” ,2012,Vector Borne and Zoo. Dis.,Vol12
    epub ahead of print.

    The EMBERS study flaws are,according to Wormser et al:
    1. No Symptoms in macaques to judge the severity of infection.
    2. Xenodiagnosis performed on only 3animals.
    3. 2 mRNA + cases but no corresponding Bb DNA found in tissues.
    4. IFA used in experiment #1 -Obsolete andprone to false +.
    5. Culture + cases (n=2) could not be subcultured.
    6. Some study animals were undertreated (dosage/freq of Drug)
    7. PD/PK issues exist between subjects,No contin blood level antibiotid monitoringby Embers.
    8. No PK data exists for Doxy in macaques.
    9. Variability of T1/2 blood levels For Ceftriax. in macaques.
    10.Embers used bioassays for Doxy levels but did notuse Bb in these bioassays.
    11.No Data for AUC for Ceftriax in Rhesus macaques.
    12. Huge dose of Bborganisms by needle delivery can’t be reconciled with doses of Bb via tick transmission.
    13. No Evidence for persisters in Embers study results.
    14. No reconciliation of “Consistent withtheresults of human studies” by Embers.
    15.Absence of tissue inflammation in EmbersRhesus macaques.
    16. Symptomatic disease “counterintiutive for Borrelia burdorferi”
    in absence of persisters or of tissue inflammation.
    17. “Even when present,persister microorganisms are largely IRRELEVANT CLINICALLY UNLESS THEY CAN BE SHOWN TO CAUSE DISEASE”
    18.Osp A human Vaccine (FDA approved) was not impartially reviewed.
    19. PK/PD parameters MUST BE ADDRESSED IN FUTURE STUDIES.

    Here we have our Fair and Impartial Dr P.J.Baker at his most articulate.
    Embers did Image a”persister” Bbinthe myocardium of a Rhesus
    and in the adjacent Image Panel – TISSUE INFLAMATION on autopsy heart. …”Counterintuitive” as a scientific impartial critique??…Reconciliation with human tick acquired disease???..
    Failure to Exsanguinate the Rhesus to procure enough blood to satisfy the PD/PK Taskmasters?…”No symptoms to Judge”..From
    well spoken Rhesus??…Disconnect between mRNAdetection and
    complementary DNA detection.(Dr Sukanya Narasimhan found
    excellent reception for her DECAL RT PCR data on Rhesus autopsy tissues in the Fikrig group Borrelia Transcriptome paper
    in the PNAS – demonstrating upreg and down reg of > 60 ORF’s
    from Medulla oblongata and autopsy heat.
    Dr Baker, you are a Taskmaster Facilitator in Your EMBERS Critiques #1-#19 above.
    Will you demand “serum porcelain levels”inyour next volley of salvoes?

    With Many Sad Regrets for your most recent (post-retirement)
    publication,

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