The recent Embers study on persistence of Borrelia Burgdorferi in Rhesus Macaques following antibiotics treatment here is opening up much needed debate.
Recently Lyme Policy Wonk has been running a series of posts about this research available here
The comments are well worth reading to the latest post on the above link.
So many questions need answering and Philip Baker doesn't seem to be convincing many in his answers.
Hopefully this Embers study proving persisters will start the process of who knew what and when?
No matter that Baker says '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.'
There has been an amendement to the original study saying that in fact it was Ceftriaxone that was used not Ceftiofur see PLoS ONE here
He might argue about the subtle differences of Ceftiofur and Ceftriaxone but he cannot argue over the fact that 60 days of Doxycycline followed 30 days of Ceftiofur and even with that was unable to clear persisters. Here in the UK even if you are lucky enough to be diagnosed you rarely get prescribed more than one or two weeks antibiotics.
Furthermore he questions if persisters -----are infective and cause disease. Patients are sick and some of us respond well to antibiotics given long term we didn't have time to wait for research to prove how and why.
Most importantly the study itself says 'Finally, the use of variable and pulse-dosing regimens of antibiotics may improve efficacy [43] and this warrants testing in an appropriate model.'
Allen Barbour one of the authors of this study is sufficiently convinced in the persistence of this organism that he quotes it in his applications for vaccines '[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.”
Application number: 12/853,019
Publication number: US 2010/0317026 A1
Filing date: Aug 9, 2010
Anyway less of my comments go to Lyme Policy Wonk here to get an idea of who knew what and when.
What has allowed this research to be suppressed for 12 years whilst patients have been denied treatment?
Here in the UK there are a growing number of patients being diagnosed with Lyme Disease and yet what efforts have been made by our Department of Health to raise awareness of this disease which can be avoided with simple precautions and can be treated more easily if caught in the early stages?
I was lucky my arthritis and muscle weakness responded well to antibiotics and led my GP to consider Lyme Disease as a differential diagnosis. I recovered, how many patients with Arthritis and muscle weakness get better on just oral antibiotics.
I was diagnosed with Fibromyalgia, ME/CFS, Musculo Skeletal Disease Polymyalgia Rheumatica none of the medications given for those illnesses made much difference thankfully antibiotics did.
How many more people will suffer while those responsible for our health play 'monkey business' with the science?
Joanne,
ReplyDeleteThank you for posting about the discussion on CALDA about this important study. I just left my own questions and comments for Dr. Baker over there, and reposted them to my blog.
Whether I like it or not, the issue of whether or not the use of ceftiofur was the correct treatment choice to make on the non-human primates studied is something that is going to be raised again by people outside of Dr. Baker - so I wouldn't expect to hear the end of this. You point out something, though, that I neglected and it seems others, too: 60 Days of doxycycline administered after the ceftiofur did not clear the infection...Why is that?
One thing I think Dr. Baker said was that the dosage of infectious spirochetes the non-human primates received was rather large relative to what one would experience via a tick bite. I do not know if his claim holds any water. What I do know, though, that different strains of Borrelia affect different animals differently - to the degree that needle innoculations have to have doses carefully calibrated for animal studies on Borrelia. I would think that Embers et al would be careful in this regard and use the right volume of specific strains of spirochetes for innoculating Rhesus macaques.
I think we definitely need to learn more about those persisters. Even if Dr. Baker wants to invalidate the results of Embers study on the grounds of the antibiotic used, there are other studies which show evidence spirochetes persist. That is without question. Someone has to go in there, though, and repeat Embers study and show RNA transcription is occurring in additional animals (that's really key) and that they are infectious.
Some people may consider that overly cautious - why isn't the evidence we have now enough to justify longer courses of antibiotics? That might be so, and people are going to work with their own doctors to figure out what's best for them - regardless of any guidelines. In the meantime, I'm pretty sure the research community is going to demand more studies like this before any official change to the guidelines would be made.
Regarding Barbour's patent: I posted the text of it last year and received many links to it and comments on it. I think everyone needs to read it. I also think everyone needs to keep in mind that there is nothing in it which mentions Borrelia survives antibiotic treatment. It does mention that Borrelia can and does persist without treatment, though, and that it can be hard to diagnose and treat.
More education, awareness, and prevention around Lyme and other tickborne diseases is desperately needed in the UK. You're sitting in a hotbed of tick activity, and the sooner more people are diagnosed and treated earlier, the better. I do hope that the word is getting out to more doctors there to change their attitude and practice towards Lyme disease.
Hi Camp Thanks for your thoughtful comments. I did read your comment to the CALDA website earlier this morning and will look back just in case Baker or others have given a response.
ReplyDeleteI did note Baker's comments about International societies supporting IDSA stance - from what researchers in UK have done it would appear they are not arrived at independent of IDSA or their authors but in fact base their stance predominantly on IDSA, more circular reasoning. Circular reasoning and opinion seems to have gotten us into this mess.
I look forward with interest to the research findings of the James Lind Alliance with Lyme disease Action - I note from my recent correspondence that Dept Health support the JLA and this research with LDA. I wonder how far they will go in supporting the findings if as I strongly suspect they differ from the established view held by our Health Protection Agency.
Meanwhile with growing UK case numbers for patients testing positive by NHS tests and knowing that a percentage do not recover after a short course of antibiotics my question to the Department of Health is where is the awareness to the public - their only response was that it was on the HPA website. Precious good that is if the public don't know to look there in the first place and the Doctors are so unfamiliar that they miss so many cases of early Lyme Disease despite presentation as in my case with the diagnostic Bulls Eye rash following an insect bite.
Peter Travis wrote an interesting comment about this Embers study which he was to post on Lymenet Europe but is having trouble signing in. I must get permission to post on my blog but in essence he said and I agree that here in Europe doctors will look at the Embers study and if patients are responding to antibiotics will more likely continue to prescribe. Thankfully our Health care is not dependent on Insurance in the same way that it is controlled in US.
In time the tipping point will reach and more people will find that antibiotics taken longer can improve their health, in time more research will maybe find treatments that help those who no longer respond to antibiotics maybe treatments that support the immune system. The current state of affairs can not go on for ever particularly when better testing is developed - the proteonics testing sounds promising although as yet only used in research. Whatever is needed to drive this forward won't come soon enough for the many thousands who suffer not knowing that antibiotics could help them and not aware of the controversy that is holding back scientific research in this field.