Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Lyme Wars: Tackling the Testing.
- Raphael B. Stricker, Lorraine Johnson (5 November 2007)
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Lyme Disease is not a simple infection
- David C Owen (7 November 2007)
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Conflicting Information on Lyme disease
- Stephanie F. Woodcock (8 November 2007)
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Rapid responses to this article
- Peter M English (10 November 2007)
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Call a truce to the 'war'
- Kathryn Walker (10 November 2007)
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Lyme survival in Europe
- Stella R Huyshe (10 November 2007)
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Real risks associated with long-term antibiotic treatment
- Donald Poretz, M.D., 22209 (10 November 2007)
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reputable science
- RUSSELL J HUXTABLE (10 November 2007)
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Lyme Disease - Another Perspective of a Scientist-Patient
- Alita J. Lyons (10 November 2007)
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If antibiotics are so "dangerous" then medicine needs to provide an alternative solution.
- Joan S. Crawford (11 November 2007)
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Antibiotics for pigs but not Lyme patients?
- Lou Overman (11 November 2007)
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Lyme Wars
- Sheila E Darbyshire (12 November 2007)
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Re: Real risks associated with long-term antibiotic treatment
- Sandy K Berenbaum, LCSW, BCD (12 November 2007)
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Re: "Lyme Wars"
- Susan O'Connell (23 November 2007)
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Re: "Lyme Wars"
- Stella R Huyshe (24 November 2007)
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Susan O'Connell Conflicts
- Miguel Perez-Lizano (24 November 2007)
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Lyme Wars: The Battle Continues.
- Raphael B. Stricker, Lorraine Johnson (24 November 2007)
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But still it moves, still we suffer
- Stewart Dean (24 November 2007)
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Borreliosis Testing
- Ria Heslop (24 November 2007)
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A partisan position by a public body is not appropriate on this issue
- Angela Kennedy (24 November 2007)
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Myalgic Encephlomylitis/Lyme
- Carole Stevens (25 November 2007)
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Re: Re: "Lyme Wars"
- Elena Cook (27 November 2007)
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Lyme Wars or Clinical Equipoise?
- Daniel Cameron (27 November 2007)
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Lyme Disease Testing and Treatment
- Duncan A Munro (27 November 2007)
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Borreliosis and Evidence
- Joel Spinhirne (27 November 2007)
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Children vs. Special Interests
- Robert C Bransfiield, MD, DFAPA (27 November 2007)
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Occam's Razor
- Rolf K. Taylor (28 November 2007)
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Haiku It's Not the Flu
- Hugh Mann (29 November 2007)
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Re: "Lyme Wars"
- Susan O'Connell (5 December 2007)
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Lyme Wars: More Conflicting Data and Deception
- Raphael B. Stricker, Lorraine Johnson (8 December 2007)
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Lyme Wars Redux
- William T. Harvey, MD, 5575 Wilson Road; Colorado Springs, CO 80919 (8 December 2007)
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Re: Lyme Wars Redux
- Elizabeth L Maloney (10 December 2007)
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Re: Haiku It's Not the Flu
- M. Marjorie (18 December 2007)
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Regarding Haiku its not the Flu
- david hart (22 December 2007)
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Lyme diagnosis
- david a lee, independent (13 January 2008)
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Where is the hope now?
- Gavin R Morrigan (4 April 2008)
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no hope in the UK...
- Mark G White (24 October 2008)
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Raphael B. Stricker, MD 450 Sutter Street, Suite 1504, San Francisco, CA 94108, Lorraine Johnson
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To the Editor: The generally balanced report by Alison Tonks about the "Lyme Wars" (3 November) fails to provide a balanced view of one issue: while the Centers for Disease Control and Prevention (CDC) warn practitioners about "various unvalidated tests", they fail to warn us about the Food and Drug Administration (FDA)-approved commercial tests for Lyme disease. The two-tier testing system endorsed by the CDC has a high specificity (99%), meaning that this approach yields few false- positives. But the tests have a uniformly miserable sensitivity (56%), meaning that they miss 88 out of every 200 patients with Lyme disease (Table). By comparison, AIDS testing has a sensitivity of 99.5%, meaning that these tests miss only one out of every 200 AIDS cases. In simple terms, the chance of a patient with Lyme disease being diagnosed using the FDA-approved and CDC-sanctioned commercial tests is about the same as a coin toss, and the poor test performance assures that many patients with Lyme disease will go undiagnosed. Until we scrap the worthless commercial tests for Lyme disease and find a better way to make the diagnosis of this protean illness, the "Lyme Wars" will continue unabated. Raphael B. Stricker, MD
Lorraine Johnson, JD, MBA
Sensitivity/Specificity of Commercial Two-Tier Testing for Lyme Disease Study/Year Sensitivity Specificity Schmitz et al, 1993 66% 100% Engstrom et al, 1995 55% 96% Ledue et al, 1996 50% 100% Trevejo et al, 1999 29% 100% Nowakowski et al, 2001 66% 99% Bacon et al, 2003 68% 99% MEAN TOTAL 56% 99% 1. Schmitz et al. Eur J Clin Microbiol Infect Dis. 1993;12:419-24. 2. Engstrom et al. J Clin Microbiol. 1995;33:419-27. 3. Ledue et al. J Clin Microbiol. 1996;34:2343-50. 4. Trevejo et al. J Infect Dis. 1999;179:931-8. 5. Nowakowski et al. Clin Infect Dis. 2001;33:2023-7. 6. Bacon et al. J Infect Dis. 2003;187:1187-99. Competing interests: RBS serves on the advisory panel for QMedRx Inc. |
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David C Owen, General Practitioner 30 The Parade, Cardiff CF24 3AD
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The article ‘Lyme wars’ written by Alison Tonks [1] reveals that the author has a shallow understanding of the topic of Lyme disease. Those who read the whole of the article will realise that the opening statement “Lyme disease is a simple bacterial infection spread by ticks” lacks credibility. Publications on Lyme disease are increasing at an exponential rate as any Medline search would reveal and there is plenty of evidence that Lyme disease is a complex and not a simple condition. Treatment of the condition sometimes requires prolonged antibiotic therapy particularly where diagnosis has been delayed. Unfortunately there is no laboratory marker of active disease at the present time and treatment decisions have to be made on clinical grounds. In some cases response to repeated or prolonged treatment is dramatic enabling resumption of a normal working life. Doctors who are members of the USA organisation ILADS appreciate this and it is my experience that they are not ‘self serving mavericks’ but sympathetic doctors who have the best interests of patients in mind. I have no doubt some patients receive inappropriate or ineffective treatment but the challenge is to try and determine those who will respond to treatment rather than to trivialise the condition as Alison Tonks has attempted to do in her article. Dr. David C Owen General Practitioner, Cardiff. Member of ILADS Medical Adviser to the UK Charity Lyme Disease Action. [1] Lyme Wars. Tonks A. BMJ November 2007: 335: 910-912 Competing interests: None declared |
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Stephanie F. Woodcock, Chair, Lyme Disease Action 53 Kernick Road, Penryn, Cornwall TR10 8NS
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Although it is important for science to understand the characteristics of the Borrelia burgdorferi sensu lato bacterium and whether or not it persists in the body of a human host, there is an even more important question that should take precedence. The question is 'What constitutes effective treatment for Lyme patients?' Even if the widespread reports by patients that they continue to have the sensation of active disease after treatment turn out to have a different explanation; nevertheless, solving the full biology behind these reports is less important than getting people better. The first paragraph of Alison Tonks' article might lead one to think that Lyme disease is a simple entity. However, the author's own descriptions later in the article indicate that all is not quite as straightforward as it at first seems. The first paragraph states that there is a fairly characteristic rash, only later does it become clear that some but not all patients actually develop this rash. According to a review of papers about early Lyme disease*, there is a rate of reporting the occurrence of Erythema migrans (EM) rash that varies between 35% and 59% of cases. Though an EM rash is the commonest visible sign of Borrelia burgdorferi s. l. infection, it is still quite possible that only a minority of patients have the rash. Patients are done a disservice if a doctor looks only for evidence of EM rash in considering a Lyme diagnosis. Symptom pattern is also less straightforward than at first appears. Firstly, we are assured that there is a well-documented pattern of symptoms but later, the symptoms are described as being common and non- specific. The article also raises the view that mainstream medical opinion thinks that the causative bacterium cannot survive initial treatment and continue to cause symptoms; contrastingly, the reader is also informed that the Centers for Disease Control (CDC) diagnostic process "cannot rule out persisting infection in patients with persisting symptoms. Nothing can." This is further borne out by the information that "blood tests for antibodies are unreliable, particularly in the long term." Against a background of these and other conflicting pieces of information, we know of many patients who are having to seek their own recoveries by a process of trial and error to find which antimicrobials work for them. Lyme Disease Action is finding that many of the long-term patients who contact us can, and do, recover with antibiotic treatment. Many of these recoveries occur in a manner not predicted by the very limited research that has so far been done upon antibiotic treatment protocols. These recoveries rely on the treating physician keeping faith with the patient and allowing them to persevere with treatment. We know of cases of months or years of treatment having been needed to bring a patient to recovery. The final reward of seeing a person able to re-engage with the world, children able to return to school, adults able to return to work, is completely worth all the obstacles that patients are currently obliged to overcome. The current controversy regarding Lyme disease as described in this article can, we believe, be resolved. We would be happy to strive for the goals mentioned at the end of the article since they are all amongst the measures that we have been calling for throughout our current 'Lobby for Lyme' campaign, full details of which can be found at: www.lymediseaseaction.org.uk Yours sincerely Stephanie Woodcock *Stricker RB, Lautin A. 'The Lyme wars: time to listen.' Expert Opin Investig Drugs 2003;12:1609-1614. Competing interests: None declared |
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Peter M English, Public Health Physician Leatherhead, Surrey, KT22 9AE
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I am interested to note that there have been three "rapid responses" to this article (http://www.bmj.com/cgi/eletters/335/7626/910, as at 16:55 on 8 Nov 07). All appear to come from special interest groups. One declares a competing interest, while the other two, from the Medical Advisor and the Chair of "the UK Charity Lyme Disease Action" fail to declare any competing interests. I wonder what the position of this charity is in the discussion initiated by Tonks? Competing interests: None declared |
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Kathryn Walker, Neuroborreliosis patient Unable to work as undergoing treatment
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The opening lines reveal a trivialisation of what is a very complex illness with a manifestly wide range of sympstoms. My personal experience and contact with other patients tells me that knowledge of what these varied symptoms is largely unknown to general practitioners, neurologists and psychiatrists. Neither are they aware of the unreliability of the tests currently available. Because of this the opportunity for "safe effective treatment" is often lost and the disease is allowed to develop. Why it should then become a political issue is a mystery to me. Also, referring to the problematic in terms of a 'war' does not help but only serves to pointlessly polarise the issue. The patients then become the casualties of this 'war' and many are exhausted and damaged by the 'fight' for treatment. More research, more information, more public awareness of this danger is what is needed. Call a truce and display a greater willingness to listen to patients. They will tell you if the treatment is being effective or not. Competing interests: None declared |
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Stella R Huyshe, Business Analyst Hexagon House, Pynes Hill, Exeter EX2 5SE
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Saying that there is a “growing and vociferous patient lobby” in the US that thinks the Lyme bacterium can survive initial treatment (Alison Tonks in Lyme Wars 3 November) implies that this is a view of patients only. Readers should be aware that in Europe researchers are increasingly questioning not whether Borrelia survives, but how (1). 1. Hunfeld at al Int J Med Microbiol. 2006 May;296 Suppl 40:233-41. Competing interests: None declared |
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Donald Poretz, M.D., President Infectious Diseases Society of America, 22209
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To the Editor: It is vital to understand the very real risks associated with long- term antibiotic treatment and the risks associated with misdiagnosis. In more than 20 years there has not been one scientifically valid study published in the peer-reviewed medical literature that proves that the benefit of long-term antibiotic treatment outweighs the risks, which are considerable. Calling an unexplained illness with non-specific symptoms “Lyme disease” when it’s actually something else can delay the appropriate treatment for patients. In fact, several points are worth clarifying in Alison Tonks' recent article about Lyme disease: • The Infectious Diseases Society of America (IDSA), the U.S.’s leading society of infectious disease experts, developed its guidelines on Lyme Disease based on the best currently available science and according to well-established rules of evidence-based medicine. There are many other credible, well-respected medical organizations whose view of Lyme disease is similar to IDSA's, including the American Academy of Pediatrics, the American Academy of Neurology, the American College of Physicians, the Centers for Disease Control and Prevention, and major ID textbooks. • The reason the IDSA guidelines do not support long-term antibiotic therapy is because there is not enough evidence to show it is effective, but there is evidence that it can be harmful for patients. • It is inappropriate – and a disservice for patients – to include unproven, experimental therapies in clinical practice guidelines for Lyme disease or any other medical condition. • IDSA supports continuing research into Lyme disease and a range of other infectious diseases. Our number one priority is to promote the best possible care and treatment for patients. And, as the oath taken by every physician emphasizes, “Above all, do no harm.” Sincerely, Donald Poretz, MD, FIDSA President, Infectious Diseases Society of America Competing interests: None declared |
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RUSSELL J HUXTABLE, writer france
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Tonks concludes her article by referring to the agreed perspective that more research is required. As an outsider, albeit one with a current lyme disease diagnosis, I have been bewildered by the fact that as yet no trial has been conducted which provides a clear measurable outcome offering unambiguous support to either entrenched position. Would it not be relatively straightforward to find 200 or more people with an agreed diagnosis based on serology, divide them into 2 groups, treat the first in accordance with mainstream guidelines and the second in accordance with the guidelines endorsed by 'patient groups'. Some subjects in the first group may be seen to require more treatment after the initial course and some patients in the second group may feel they have recovered within 12 months. However this likehood will provide further evidence in support of whichever hypothesis is chosen. The fact that as yet a study as outlined above has yet to be operationalised seems reprehensible when you consider the numbers of people involved and the level of disability which results from this complicated illness. This also fuels the widely held view amongest patients that there is something 'sinister' going on here blocking the necessary research. Competing interests: None declared |
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Alita J. Lyons, Lyme patient 120 W. 86th St. #12D, New York, NY, 10024 USA
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As a former HCV researcher and current Lyme patient, I am always surprised by new articles on the "Lyme Wars," though I think I am beginning to detect a pattern in them. These articles are usually opinion pieces, and they often manage to gloss over most of the really interesting microbiology, both new and old, that's been done on spirochetal infections. I can never understand why that is, but then scientists are always surprised when basic science is ignored for political reasons, which has been happening in the biological, climatological, and evolutionary fields lately. I suspect in the case of Lyme disease that dismissing the current science, as Ms. Tonks does by characterizing Lyme as "a simple bacterial infection", has more to do with real estate values than it does with moral ones. The more I review what is known about spirochetes, the more I respect them as disease causing agents. Studies are piling up on the incredible genetic complexity of Borrelia burgdorferi (1-3). Its remarkable strain diversity (4), along with differing morphological forms is well documented in studies dating back to the 1930's (5-6). Solid evidence shows that Bb and its relatives can easily evade the immune system via inter and intracellular sequestration, pleomorphism, and antigenic variability (7- 10). Clinically, it is well documented that spirochetal infections can and do cause serious, protean, multi-systemic infections (11-13). The literature is also full of examples of antibiotic resistance and persistence, seronegative infections, as well as relapsing and remitting symptomatology (14-17). In light of all this, I'll keep taking my antibiotics, thank you. I'd also like to keep the services of my physician, who actually treats chronic Lyme patients, many of them, and does not dogmatically turn away sick and symptomatic people. Ms. Tonk's article makes my continued access to successful treatment just ever so slightly more doubtful, while doing nothing to address a truly enigmatic, fascinating and potentially dangerous bug. A disease that is so profoundly debilitating should never be so profoundly marginalized. 1. Casjens S, Palmer N, van Vugt R et al. A bacterial genome in flux: the twelve linear and nine circular extrach romosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi. Mol. Microbiol. 35, 490–516 (2000). 2. Qiu WG, Schutzer SE, Bruno JF et al. Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing. Proc. Natl Acad. Sci. USA 101, 14150–14155 (2004). 3. Stewart PE, Hoff J, Fischer E, Krum JG, Rosa PA. Genome-wide transposon mutagenesis of Borrelia burgdorferi for identification of phenotypic mutants. Appl. Environ. Microbiol. 70, 5973–5979 (2004). 4. Younsi H, Sarih M, Jouda F, Godfroid E, Gern L, Bouattour A, Baranton G, Postic D. Characterization of Borrelia lusitaniae isolates collected in Tunisia and Morocco. J Clin Microbiol. (4):1587-93 (2005). 5. Sergent E; Foley H. - Des periodes de latence du spirille chez le malade atteint de fievre recurrent. Compt. rend. acad. sci., clviii, pp. 1926-1928 (1914). 6. Preac-Mursic V, Wanner G, Reinhardt S, Wilske B, Busch U, Marget W. Formation and cultivation of Borrelia burgdorferi spheroplast L-form variants. Infection 24, 218–226 (1996). 7. Aberer E, Koszik F, Silberer M. Why is chronic Lyme borreliosis chronic? Clin. Infect. Dis. 25(Suppl. 1), S64–S70 (1997). 8. Porcella SF, Schwan TG. Borrelia burgdorferi and Treponema pallidum: a comparison of functional genomics, environmental adaptations, and pathogenic mechanisms. J. Clin. Invest. 107, 651–656 (2001). 9.Stevenson B, von Lackum K, Wattier RL, McAlister JD, Miller JC, Babb K. Quorum sensing by the Lyme disease spirochete. Microbes Infect. 5, 991–997 (2003). 10. Embers ME, Ramamoorthy R, Philipp MT. Survival strategies of Borrelia burgdorferi, the etiologic agent of Lyme disease. Microbes Infect. 6, 312–318 (2004). 11. Pinto DS. Cardiac manifestations of Lyme disease. Med Clin North Am. Mar;86(2):285-96, (2002). 12. Gibbs RS, Roberts DJ. Case records of the Massachusetts General Hospital. Case 27-2007. A 30-year-old pregnant woman with intrauterine fetal death. N Engl J Med. Aug 30;357(9):918-25, ( 2007). 13. Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. Nov;151(11):1571-83, (1994). 14.Straubinger RK, Summers BA, Chang YF, Appel MJ. Persistence of Borrelia burgdorferi in experimentally infected dogs after antibiotic treatment. J. Clin. Microbiol. 35, 111–116 (1997). 15. Preac-Mursic V, Weber K, Pfister HW et al. Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Infection 17, 355–359 (1989). 16. Lawrence C, Lipton RB, Lowy FD, Coyle PK. Seronegative chronic relapsing neuroborreliosis. Eur. Neurol. 35, 113–117 (1995). 17. Stricker RB, Lautin A, Burrascano JJ. Lyme disease: point/counterpoint. Expert Rev Anti Infect Ther. Apr;3(2):155-65, (2005). Competing interests: None declared |
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Joan S. Crawford, Chemical Engineer unable to work due to ill health CH2 2AN
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I am a patient with symptoms identical to those described as chronic Lyme disease. For the last ten years mainstream medicine has had no answers to my condition, which has resulted in loss of my career, wealth and friends. Three years ago independent doctors, with no obvious vested interest apart from an eagerness to scientifically examine the evidence and act upon it, diagnosed me with chronic bacterial infections, which could clearly be seen using darkfield microscopy. Antibiotic treatment commenced in January 2005 and continues to this day. I am now significantly recovered to a point where I can now consider returning to full time employment. The alternative mainstream treatment on offer consisted of nothing more than symptom management, which incidentally did not work. The denial of the severity of ongoing symptoms along with subsequent disability caused by minimal, standardised, one-size fits all 2-4 weeks antibiotic therapy after an infected tick bite is shocking. That is if the patient ever receives antibiotic treatment at the time of infection, in the first place. Too few doctors know anything about Lyme disease to be sure that erythema migran rashes, Lyme disease and its co-infections are diagnosed correctly in a timely manner. “It’s hard to know when the current acrimonious stand off will end.” I can predict with certainty when this will occur. When the patient can rely on doctors to be knowledgeable about diagnosing and treating Lyme disease and its co-infections, especially in primary care, and when they are being listened too, diagnosed correctly and given the treatment, whatever that may be, to resume a normal life. Often the Lyme disease patient hears the mantra that antibiotics are “dangerous”. How can antibiotics be more dangerous than a disabling illness, which leaves the patient in constant pain and sometimes in a wheelchair? If antibiotics are so "dangerous" then I hope upcoming research provides less "dangerous" treatments to eradicate the bacteria and co-infections in a swift and timely fashion. Competing interests: None declared |
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Lou Overman, Lyme patient none
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What we have in the Lyme wars is a group of doctors who have ignored relevant medical literature, including their own previously published articles, actively working to prevent treatment of an infectious disease by another group of doctors. The first group helps to produce an ever increasing number of cases by supporting an inadequate testing procedure. Then they refuse adequate treatment for the chronic cases they have produced, ensuring that the burden of morbidity and mortality grows heavier every year. Some of them have benefited financially from testing, vaccines, patents, and work for insurance companies. It is astonishing that the behavior of these people is being called mainstream, while the doctors who try the hardest to correctly diagnose and adequately treat tickborne diseases are deemed mavericks! If this kind of behavior is really mainstream, we are in a lot of trouble, and not just with Lyme disease. Anyone who puts financial gain ahead of patient welfare is in the wrong profession. This kind of perversion in the healing arts does not stay conveniently in its lyme box, it spills over to tarnish the profession and medical research in general. If the government research funding agencies changed their practices and admitted the existence of chronic lyme, we might actually get some of the thorny problems resolved. Instead, they fund primarily those who will deny the disease and trivialize its symptoms and underestimate how much treatment is needed. The patients surely do not want treatment forever, if there is a better way. They also certainly do not want to be left without useful treatment for a treatable disease. How many more autopsies have to find borrelia spirochetes in brains before officials change course? Governments have got to recognize their responsibility, even if it is inconvenient to fight more than one infectious plague at a time. They came late to the AIDS epidemic and now are dragging their feet with Lyme and related tickborne diseases. They must listen to the patients, and find researchers who are willing to go wherever truth leads them. Dr. Osler, founder of Johns Hopkins, said of diagnosis that if you listen to the patients, they will tell you what is wrong with them. I think he would be astonished that the Lyme patients' voices are not being heard in diagnosis--and ignored in evaluating the efficacy of treatment--by too many doctors and medical researchers. We are frequently threatened with the specter of antibiotic resistance caused by longterm treatment of chronic lyme cases; meanwhile, the pigs and chickens and apple orchards are able to get vast amounts of antibiotics without any interference. Are patients the only ones to find this to be ludicrous and wrongheaded? Having observed the strange handling of tickborne diseases like Lyme, I have finally decided that this kind of behavior is apparently involved in other diseases, and is the reason why we have not made any significant progress in Parkinson's, Alzheimer's, ALS, chronic fatigue, autism, cancers, and any number of others. Competing interests: None declared |
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Sheila E Darbyshire, psychologist Stockport
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It is heartening to see the dilemmas facing patients and physicians concerning Lyme Disease being debated at long last in this journal. A rising ride of angry and disillusioned patients and their families, not to mention their confused and poorly informed doctors, are finally having the issues and controversy surrounding Lyme disease diagnosis and treatment aired and examined. This has been a long time coming - and the patient numbers are rising. The problem as I see it, is that medical authorities are relying on old and outdated research material. Knowledge about this devastating illness is developing apace, but little recent research is disseminated to doctors in the field, presumably because it is not seen as a 'British' problem. Of course, it is only a 'problem' if cases are recorded and in Britain they are often not. The Health Protection Agency (HPA)for example, appears to base its latest recommendations on guidelines produced recently by the Infectious Diseases Society of America, who based their work almost entirely on research by Klempner et al, whose seriously skewed sample groups were held to be representative of the actual patient population, leading to very unhelpful and retrograde guidelines for patient care. This is lazy medicine to say the least. When will such apparently worthy organisations learn that improved co -operation and collaboration with patients' groups, which usually possess considerable expertise in their field, encourages the flow of cutting edge knowledge, which has true relevance and therapeutic value for the long- suffering patients with Lyme and related diseases. Sheila Darbyshire Dip.SW, BA(Hons)Psych. Competing interests: None declared |
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Sandy K Berenbaum, LCSW, BCD, Psychotherapist - private practice Brewster, New York, USA
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Regardless of the spin coming from the Infectious Disease Society of America, they do not have the patients' best interests in mind when they refer to their new guidelines. They have ignored significant literature supporting the use of long term antibiotics, and dismissed the case histories of the thousands of patients whose health was restored by treatment for chronic Lyme disease and co-infections. In order to support their "conclusions", they refused to allow participation in the development of the guidelines by members of the International Lyme and Associated Disease Society or the Lyme Disease Association, and even refused to allow their own member doctors who disagreed with their point of view to participate. As a psychotherapist who has seen children and adults with debilitating Lyme disease for the past 16 years in my practice, I have witnessed their health and functioning restored by long term treatments, including antibiotics. I have seen children return to school, after months or years on homebound instruction. I have seen whole families return to functioning, and heard the stories of missed and delayed diagnosis and inadequate treatment that brought them to the point of disability, unremitting pain, and in some cases, a level of incapacity that left them bedridden or in a wheelchair, prior to finding a doctor that recognized the chronicity of the illness, and treated efficaciously. If long term antibiotics are so dangerous, why are years of tetrocycline used to treat acne in adolescents? Why is there so little respect coming from the leadership of the IDSA for the dedicated physicians who are treating the most severe cases of tick-borne illness, and so little interest in the success of those treatments? Competing interests: None declared |
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Susan O'Connell, Consultant Microbiologist Lyme Borreliosis Unit, HPA Microbiology Laboratory, Southampton General Hospital, Southampton SO16 6
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Issues of diagnosis and management of Lyme disease in the USA, highlighted in this article have also become contentious in Europe. Unfortunately, the misdiagnosis of Lyme disease in patients who have other serious, life-threatening or long-term conditions was not clearly addressed in the report. Patients with multiple sclerosis, motor neurone disease, scleroderma, polymyalgia rheumatica, systemic lupus erythematosis, Addison’s disease and other conditions have been diagnosed with “chronic Lyme disease” in the UK. Misdiagnoses led to delayed or inappropriate management, and were potentially life-threatening in several instances. Some of these patients were harmed by treatments that they had received for Lyme disease through intravenous line-associated sepsis, adverse reactions to antibiotics, hepatobiliary and renal damage and C difficile colitis. Others also suffered financially because of high treatment costs. Some misdiagnoses were made by clinicians who followed the nonspecific symptoms list and case descriptions in the International Lyme and Associated Diseases Society’s guidelines (1), which apparently had not undergone the peer review process of the journal in which they appeared as a supplement (E. Manzotti, Futuremedicine.com, personal communication 9th August 2006). Careful reading of the guidelines and their supporting references show numerous inaccuracies, selective quotation and reliance on early studies performed before modern diagnostic tests and treatments were available. The guidelines do a disservice both to misdiagnosed patients and to those with continuing symptoms following Lyme disease, who require careful clinical and laboratory evaluation for evidence of active infection and for other explanations for their symptoms, so that appropriate management may be selected. (2) It is incorrect that tests for antibodies to Borrelia burgdorferi are unreliable, particularly in the long term. Patients with late Lyme disease are rarely seronegative(3,4). Recently-infected patients may have negative antibody tests, because the antibody response can take some weeks to develop (3,4). It is unsurprising if patients diagnosed with “chronic Lyme disease” using the nonspecific ILADS criteria are seronegative, or that antibody test assessment panels using sera from such patients give misleading data about test performance. Conversely, tests from some commercial “Lyme-specialty” laboratories claiming a high degree of sensitivity in “chronic Lyme disease” patients have very poor specificity. Poorly validated tests used by some fringe practitioners were the focus of a report for the Department of Health (5). The two-tier approach to B burgdorferi antibody testing, recommended by the US Public Health Service and European experts 12 years ago, remains valid. Test methods have improved greatly in recent years, particularly with the introduction of recombinant and synthetic peptide antigens from different borrelial genospecies. The long term goal is to develop single stage tests that increase sensitivity in early infection and maintain the high sensitivity and specificity that the two-tier process currently provides at later stages of infections. Considerable progress has been made in applying proteomics and bioinformatics to Lyme disease diagnosis, as demonstrated by presentations at the second Banbury Conference on the Laboratory Diagnosis of Lyme Disease in September 2007. These new methods require further development and validation but hold out great promise for future diagnostic tests. 1. Cameron D , Gaito A, Harris N, Bach G, Bellovin S, Bock K et al. Evidence-based guidelines for the management of Lyme disease. Exp Rev Anti Infect Ther 2004;2(suppl1) S1-13. 2. Feder HM, Johnson BJB, O’Connell S, Shapiro ED, Steere AC, Wormser GP. A critical appraisal of chronic Lyme disease. N Engl J Med 2007;357:1422-30. 3. Wilske B, Fingerle V, Schulte-Sprechtel S. Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol 2007;49:13-21. 4. Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of Lyme borreliosis. Clin Microbiol Rev 2005;18:464-509. 5. Duerden BI. Unorthodox and unvalidated laboratory tests in the diagnosis of Lyme borreliosis and in relation to medically unexplained symptoms. Department of Health, London, UK, 2006. http://www.dh.gov.uk/assetRoot/04/13/89/17/04138917.pdf Competing interests: None declared |
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Stella R Huyshe, Business analyst Pynes Hill Exeter Ex2 5SE
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Susan O’Connell is right to highlight the misdiagnosis of Lyme disease in patients who have other conditions as this is as important as the reverse. However, the criticism heaped on a non specific symptom list produced by the International Lyme and Associated Diseases Society is somewhat unjust, particularly when considering the European manifestations of the disease. A study of European patients undertaken by Strle et al (1) concluded that “the clinical features associated with B. afzelii are much less specific (than with B. garinii) and more difficult to diagnose.” Now it is not known how many cases in the UK are due to B. afzelii but no one can put the figure at zero. This species is currently not known in the USA, so why is the NHS using US guidelines? We would seem in urgent need of specific UK clinical guidelines based on UK, or at least European, case studies. The statement that “Patients with late Lyme disease are rarely seronegative” acknowledges that some patients with late Lyme disease are seronegative. In the absence of clinical guidelines that recognise the findings of Strle’s paper, these patients are likely to remain misdiagnosed. Two tier testing can be considered a valid approach, particularly in a cash strapped NHS, as long as it is backed up by clinical judgement. However, in a climate where non specific symptoms are deemed to be not Lyme disease, this clinical judgement can not be well informed. If the current tests (including the existing single stage C6 test) were good enough to be reliable then the UK specialist Lyme Borreliosis Unit would not be investigating new diagnostic methods and tests that hold out great promise. 1. Strle F, Ruziæ-Sabljiæ E, Cimperman J, Lotric-Furlan S, Maraspin V. Comparison of findings for patients with Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid. Clin Infect Dis. 2006 Sep 15;43(6):704-10 Competing interests: None declared |
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Miguel Perez-Lizano, Retired 98604
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It is simply incredible that Susan O'Conell reports no conflicts of interest in her response supporting the Lyme disease guidelines by the Infectious Diseases Society of America. The New England Medical Journal article on chronic Lyme disease, which she coauthored, discloses "Dr. O'Connell reports serving as an expert witness related to Lyme disease issues in civil and criminal cases in England." She has coauthored many papers with other members of the Lyme cabal whose stranglehold on this disease will, hopefully, soon come to an end. Competing interests: None declared |
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Raphael B. Stricker, MD 450 Sutter Street, Suite 1504, San Francisco, CA 94108, Lorraine Johnson
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We wish to address the inaccuracies and misstatements in the communication from microbiologist Susan O’Connell concerning the “Lyme Wars” article (3 November). Dr. O’Connell states that the evidence-based guidelines of the International Lyme and Associated Diseases Society (ILADS) were not peer reviewed, citing a personal communication from an individual who is not associated with the publisher of the guidelines. Prior to publication, the ILADS guidelines underwent internal peer review by Expert Review of Anti- Infective Therapy, an independent medical journal (1). In contrast, the Lyme guidelines of the Infectious Diseases Society of America (IDSA) were self-published by IDSA in its own journal, Clinical Infectious Diseases (2). Self-publication implies a lack of independent peer review that probably contributed to the overly restrictive nature of the IDSA guidelines. Dr. O’Connell maintains that the two-tier approach to Lyme antibody testing remains valid, and she gives two references to support her view (3,4). The first reference relies on data from 1988 and 1989 using “home- brew” Lyme antibody testing in patients with acrodermatitis and lymphocytic meningoradiculitis, and the sensitivity of this irrelevant test system was only 50-77% in patients with chronic disease (3). The second article contains the following statement: “Relatively few studies using currently available commercial tests have evaluated the performance of the recommended two-tier testing on well-characterized sera from patients with extracutaneous manifestations of Lyme borreliosis” (4). The few studies that have been performed found a consistently poor sensitivity of the two-tier test system essentially equivalent to a coin toss, as outlined in our recent letter to BMJ (5). Thus the two-tier approach endorsed by IDSA and Dr. O’Connell is inadequate for the diagnosis of Lyme disease. Dr. O’Connell’s optimism about the wonderful new Lyme tests that are just around the corner is unwarranted. The only test that has become commercially available in recent years is the C-6 peptide ELISA, which was shown to have less sensitivity than the current two-tier test system (6). Until a “gold standard” test becomes available, physicians will need to rely heavily on their clinical judgment rather than commercial testing to support a diagnosis of Lyme disease. Raphael B. Stricker, MD Past President, International Lyme & Associated Diseases Society San Francisco, CA 94108 Lorraine Johnson, JD, MBA Executive Director, California Lyme Disease Association Los Angeles, CA 90068 References 1. Cameron D, Gaito A, Harris N, et al. Evidence-based guidelines for the management of Lyme disease. Expert Rev Anti-Infect Ther 2004;2(1 Suppl):S1-13. 2. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006; 41:1089- 1134. 3. Wilske B, Fingerle V, Schulte-Sprechtel S. Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol 2007;49:13-21. 4. Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of Lyme borreliosis. Clin Microbiol Rev 2005;18:464-509. 5. Stricker RB, Johnson L. Lyme Wars: Let’s tackle the testing. BMJ 2007;335:1008. 6. Gomes-Solecki MJ, Meirelles L, Glass J, Dattwyler RJ. Epitope length, genospecies dependency, and serum panel effect in the IR6 enzyme- linked immunosorbent assay for detection of antibodies to Borrelia burgdorferi. Clin Vaccine Immunol 2007;14:875-9. Competing interests: RBS serves on the advisory panel for QMedRx Inc. |
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Stewart Dean, Email system administrator Bard College, Annandale NY, USA, 12504
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When I first contracted Lyme (along with babesiosis, since ticks can carry numerous diseases), it was as if I'd aged years in 3 months. From vigorous health in my early 50's, I very nearly had to use a cane to walk. All sorts of diagnoses were proposed (no bulls-eye rash), but a month of antibiotics restored me to 85% of my prior health. Withdrawal of them brought a quick resumption of symptoms. After two years of varied antibiotic treatment, I was cured....until I was reinfected (this time with a bulls-eye rash). And so it has gone, with periods of health, followed by reinfection. The "First,do no harm" that Poretz quotes is, in practice, "Give no aid" to those whose symptoms and history conflicts with his beliefs. Much as with Semmelweiss so long ago, this is a war of entrenched belief and professional reputation against very real suffering and disability. What is the harm in restoring the life and vitality of people who respond to extended antibiotic treatment? Much like Galileo leaving the Inquisition, we say to those like Dr. Poretz, "Still we are sick, still we have the symptoms", but they refuse to see that or help us. Such doctors aren't scientists, but true believers, threatening our chances at treatment...and a life. Competing interests: Recurring (or chronically) Lyme infected since 1999 |
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Ria Heslop, Disabled CO3 9TA
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As a patient being miss-diagnosed in the UK for over 6 years and left to become disabled by the UK NHS I personally believe the Lyme disease testing in the UK is inadequate. Once diagnosed in the USA with Late stage Lyme disease I then came to realise that no person within the NHS was conversant with treating late stage Lyme disease. Not only are you left to be disabled by a failed UK system you are often then denied your treatment or funding for your treatment - in my case funding was given although no person knew how to manage this treatment. It is to this end that many UK Lyme sufferers have no choice than to fund private treatment in the USA. Whilst the medical profession are fightling about what is right and what is wrong they forget that there a patient behind this fighting, that needs urgent treatment. One thing doctors are taught in medical schools is to treat the patient, not the test result. It is mentioned here that UK testing is reliable although, please refer to the following information from my treating USA Consultant, who has over 20 years experience in treating Lyme Disease. Recent surveys Show as little as 5% of UK General Practitioners know how to diagnose Lyme disease and even this small percentage rely on the characteristic red bulls-eye rash (EM) at the site of the bite although, this is present in less than 40% of patients. When physicians do consider borreliosis, they often start with a screening test such as an EIA, ELISA, IFA or PCR-DNA probe. If the initial screening test is negative, many physicians tell patients they do not have borreliosis and the testing is stopped right there. Screening tests that are positive are often followed by the Western blot. The blot is a “confirmatory” test, as opposed to a screening test. (Blots are performed for other infections -- it is a type of test, not a test uniquely for the borreliosis bacteria.) Western blots are accomplished by breaking the Borrelia burgdorferi into pieces, and those parts of the Lyme bacteria are then embedded in a gel. Electricity is used to push antibodies made by the immune system through the gel. Antibodies that are made to attach to certain parts of the bacteria will bind to those exact parts that are embedded in the gel. When the antibodies bind to the parts of the bacteria, a black band is formed, which is then interpreted as IND, +, ++ or +++ depending upon the intensity or darkness of the band. Each part of the Lyme bacteria weighs a certain amount. For example, the tail of the Lyme bacteria weighs 41 kilodaltons (kDa). Think of kilodaltons like pounds, ounces or kilograms. The numbers on a Western blot such as 23, 31, 34 or 39 refer to how much that particular part of the bacteria weighs in kilodaltons. The significant antibodies, in my opinion, are the 18, 23-25, 28, 30, 31, 34, 39, 58, 66 and 93. It’s important to know that screening tests like the EIA, ELISA, IFA and PCR can be negative even when the Western blot (confirmatory test) is positive. Research that supported this at the 1994 International Lyme Borreliosis Conference held in Bologna, Italy supported this. For this reason the screening test are practically worthless, and is why the Western blot needs to be used to “screen” for borreliosis, even though it is a “confirmatory” test. Antibodies are very specific as to what they bind; consequently, in over 700 borreliosis patients’ false positive blot results occurred in only three percent of them, based upon research presented at the 2000 International Lyme Borreliosis conference. Data from those same 700 patients showed that if their Western blots had even one antibody significantly associated with the bacteria, there was a 97 percent chance they would feel better with antibiotics. One thing doctors are taught in medical schools is to treat the patient, not the test result. If someone has chronic pain, fatigue, cognitive problems, blurry vision and/or neurological problems, and also has a significant antibody on a borreliosis Western blot, that antibody should not be ignored, even if the ‘official’ interpretation is negative or equivocal. Remember, antibodies are very specific to what they bind, and borreliosis may cause virtually any symptom and any disease. Disease surveillance is close observation of a group of patients with the same disease, and it is one of the jobs of the Centres for Disease Control (CDC). Criteria used for disease surveillance is often different than criteria used to diagnose and treat patients. Surveillance criteria should not be used in day-to-day clinical medical practice. Unfortunately, many patients are told they do not have borreliosis because they do not meet CDC’s surveillance criteria. Surveillance criteria exclude some of the classic hallmark antibodies, such as the 31 kDa band (outer surface protein A or ospA) and the 34 kDa band (outer surface protein B or ospB). In fact, the 31 kDa band is so tightly associated with borreliosis that a vaccine was made from that outer surface protein. In other words, those criteria that exclude the ospA (31 kDa) band should not be used to tell a patient they do not have borreliosis. Common sense should tell anyone that prevalent antibodies like the 31 dKa and 34 dKa should be included in the criteria, not excluded. Remember, research supports that if just one antibody that is significantly associated with Borrelia burgdorferi is present on a Western blot, 97 percent of those patients with chronic symptoms or chronic diseases feel better with antibiotics. Same day head-to-head comparisons of borreliosis Western blot results revealed that reference laboratories do a better job of finding antibodies against Borrelia burgdorferi than regular laboratories. This raised the obvious concern that the reference labs might be over diagnosing patients with borreliosis. That is one of the reasons why 700 patients were researched. However, the false positive rate was just three percent. This concludes reference laboratories do not over-diagnose borreliosis. False negative test results, on the other hand, are a much bigger problem, in my experience. Negative Western blots convert to positive in 18 to 24 percent of cases, if four weeks of antibiotics are given, and then the patients go off antibiotics for 10 to 14 days before the repeat Western blots are done. In other words, a false negative Western blot converts to positive in about one out of five borreliosis patients. This is a much greater problem than a false positive rate of only three percent. Competing interests: None declared |
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Angela Kennedy, Social Sciences Lecturer and Researcher IG8 8DH
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Susan O Connell states that: "Unfortunately, the misdiagnosis of Lyme disease in patients who have other serious, life-threatening or long-term conditions was not clearly addressed in the report. Patients with multiple sclerosis, motor neurone disease, scleroderma, polymyalgia rheumatica, systemic lupus erythematosis, Addison’s disease and other conditions have been diagnosed with “chronic Lyme disease” in the UK. Misdiagnoses led to delayed or inappropriate management, and were potentially life-threatening in several instances.” I find it absolutely remarkable that, as a representative of the Health Protection Agency, apparently concerned about misdiagnosis, she has failed to address the ‘flip’ side of misdiagnosis, especially on a particular patient population, those who have been diagnosed as ‘Chronic Fatigue Syndrome’ and not been tested, let alone treated, for Lyme borreliosis at onset by the National Health Service, but who have exhibited both clinical and laboratory signs of this infection, both at onset, and later in their illness. Such patients are often extremely ill and disabled, and the lack of appropriate diagnosis and treatment at onset and even later in their illness, has “led to delayed or inappropriate management, and were potentially life-threatening in several instances“. Dr O Connell has been made aware of this problem by various parties over the years. However, it is obvious from her correspondence here and elsewhere that Dr O Connell and colleagues have taken a particular, highly partisan, position on the issue of Lyme in Europe, by opposing the ILADS position and supporting the IDSA position, despite its known problems. This partisan position is not appropriate for a representative of a body whose: “ …role is to provide an integrated approach to protecting UK public health through the provision of support and advice to the NHS, local authorities, emergency services, other Arms Length Bodies, the Department of Health and the Devolved Administrations.” (1) What is needed from the HPA and related agencies, to address what appears, from the evidence available, to be a growing health problem and its devastating effects on sufferers, is a careful, non-partisan, and scientific acknowledgement of the evidence available (including that which contradicts IDSA‘s position). What is NOT needed is carefully worded, but nevertheless inadequately substantiated, partisan discrediting of the position of others, a problem also present in the Duerden Report (referenced as supporting evidence by Dr O Connell in her response), a report that made various serious allegations about other parties, but managed to do so without including any substantiating evidence for those claims, or indeed any references at all, a remarkable omission for a government-commissioned report. (2) Footnotes 1. From the HPA website: http://www.hpa.org.uk/hpa/default.htm 2. Duerden BI. Unorthodox and unvalidated laboratory tests in the diagnosis of Lyme borreliosis and in relation to medically unexplained symptoms. Department of Health, London, UK, 2006. http://www.dh.gov.uk/assetRoot/04/13/89/17/04138917.pdf Competing interests: Critic of the psychiatric paradigm of ME/CFS and claims around 'medically unexplained symptoms'. Mother of a young woman who was diagnosed with 'ME/CFS'. |
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Carole Stevens, Retired Nurse wd186jy
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I was diagnosed with severe Myalgic Encephlomylitis 15 years ago after collapsing one day just after a flu vaccination. Symptoms were so severe I was unable to move and was bed ridden for years. General tests left doctors baffled. I was not diagnosed with MS or anything else. All physical and neurological symptoms were horrendous, and remain bad to this day. For many years I have had blood clots, venous cortical thrombosis at the age of 21 requiring a craineotomy, two DVTs, one PE, and other clots including this year one...ischaemic colitis! Yet I still seemed to baffle medicinal science. Thankfully I am now under the care of a Lyme/Borreliosis Dr, and finally have a diagnosis of Borreliosis. I now take medication and hopefully have a good chance of recovery. So what baffles me is that how can any microbiologist rule out Lyme disease with just their blood results and their personal beliefs about the illness, as a Lyme diagnosis requires clinical diagnosis AS WELL AS blood results. Competing interests: None declared |
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Elena Cook, Board member, UK Lyme www.uklyme.org.uk HA1 2AE
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Dr O’Connell claims that the two-tier serological test for Lyme is reliable. In this context, readers may find useful the 14 pages of abstracts from the peer-reviewed literature documenting seronegativity in Lyme Disease at URL http://www.lymeinfo.net/medical/LDSeronegativity.pdf, Contrary to Dr O’Connell’s assertion, seronegative Lyme in both early and late cases is discussed. Although that particular archive only covers the period up till 2003, evidence for seronegative Lyme continues to emerge. (1) The reasons for the insensitivity of Lyme serology are many and varied and include the abrogation of immune response after early antibiotic treatment; spirochaetal sequestration in immune-privileged sites; antibodies bound up in immune complexes; conversion of borrelia to cell-wall deficient “stealth” forms; lymphocyte tolerisation; antigenic variation in borrelia; and use of tests based on Borrelia burgdorferi sensu lato (Bb sl) strains too dissimilar from the infecting strain (2)(3)(4)(5)(6). Further, recent studies show that Lyme disease may result from Borrelia species which are not part of the Bb sl group altogether. (7) Borrelia lonestari, for example, is sufficiently distinct from burgdorferi genetically so as to render current Lyme serology and PCR useless in detection – yet it causes a syndrome identical to Lyme. Dr O’Connell implies that patients with MS, motor neurone disease and other syndromes are routinely being harmed by a misdiagnosis of chronic Lyme disease, but provides no references for her statement. On the other hand, the potential for harm in the reverse case has been amply documented in the peer-reviewed medical literature. So, for example, Lyme disease may be mistakenly labelled multiple sclerosis (8)(9)(10), motor neurone disease/ALS (11)(12) , autism (13) ,juvenile rheumatoid arthritis, SLE, ME/chronic fatigue syndrome, psychiatric illness, fibromyalgia, CNS lymphoma, and so on. Further, in the majority of these conditions, there is evidence to indicate that far from being a misdiagnosis, Lyme may actually be one of the causes of these and other poorly understood syndromes. Thus the UK Health Protection Agency has quietly admitted that Lyme is a trigger of chronic fatigue syndrome and fibromyalgia(14); studies have shown a three-way correlation between MS, Lyme and schizophrenia (15) , and even Alzheimers (16)(17) has now quite literally come under the microscope with studies reporting the presence of the cystic form of Lyme borrelia in autopsied brain tissue. There can be no excuse for a failure to address the issue of unrecognised Lyme disease when it is acknowledged as the most common vector-borne disease in Europe and North America.. Indeed the modern recognition of Lyme disease as a clinical entity in 1975 only came about when two Connecticut mothers realised that the number of “Juvenile rheumatoid arthritis” cases in their town was out of all proportion to the national average, and that many of the children concerned exhibited all manner of neurological and other symptoms not normally associated with JRA. Dr O’Connell’s role in the UK places her at the helm of provision of information on Lyme Disease to both the medical profession and the public. It is therefore remarkable that she should take such a one-sided approach., especially given the fact that she herself contributed to a report of a case involving Lyme disease misdiagnosed as spinal astrocytoma.(18) What, in human terms, does it mean when Lyme Disease is misdiagnosed? In the case of the man thought to have a glioma, it is likely he would have undergone spinal surgery entailing serious risks of permanent motor deficit. In the case of many of the conditions mentioned above, treatment involves the administration of steroids, the immunosuppressant effect of which may have grave consequences in the case of unrecognised Lyme infection .(19) Neuropsychiatric Lyme misdiagnosed as primary psychiatric illness could lead to forced confinement . . Paediatric Lyme misdiagnosed as Munchausen’s by Proxy results in parents being falsely labelled abusers and their children put up for fostering or adoption. (20) But apart from all the dangers outlined above, there is the question of the risks arising from the untreated Lyme disease itself. The potential sequelae of infection with Lyme and its associated co-infections are protean and well-documented in the literature. They include, but are not limited to, the following: crippling fatigue, pain and disability on par with chronic heart failure (21) , seizure, complete heart block (22), fatal pancarditis (23) , paraplegia (24)(25), tetraplegia (26), stroke- like syndromes (27) , optic neuropathy leading to permanent blindness (28) , deafness (29), cognitive deficits (30), miscarriage, stillbirth, and fetal deformity (31) , learning disability in children (32), and almost the entire range of psychiatric syndromes including dementia and florid psychosis (33), homicide and suicide arising from the latter. (34) To this physical toll we must add the emotional toll of relationship breakdown, social isolation, loss of job/school and self-esteem and despair at unrelieved suffering, all arising as a direct result of patients being denied diagnosis and treatment of their Lyme disease. . The victims of this disease who once voiced their pain on online Lyme disease boards , their voices now stilled through suicide, bear silent testimony to this shameful fact. 1 Holl-Wieden A, Suerbaum S, Girschick HJ. Rheumatol Int. Seronegative Lyme arthritis.2007 Sep;27(11):1091-1093. Epub 2007 Apr 4 2 Brunner M New method for detection of Borrelia burgdorferi antigen complexed to antibody in seronegative Lyme disease J Immunol Methods, 249(1-2):185-190 3 Aberer E, Koszik F, Silberer M., Why is chronic Lyme borreliosis chronic? Clin Infect Dis 1997 Jul;25 Suppl 1:S64-70. 4 Stricker R, Johnson, L Treatment of Lyme Disease: a Medicolegal Assessment, Expert Review of Anti-Infective Therapy 2004 Aug; Vol 2(4):533 -557 5 Huppertz HI, Horneff G, Neudorf U, Karch H. Acute childhood neuroborreliosis with a selective immune response to a low molecular weight protein expressed by Borrelia garinii. Eur J Pediatr. 1994 Dec;153(12):898-902. 6 Stricker R, Lautin A, Burrascano, J Expert Rev. Anti Infect. Ther. 2005 3(2) 7 Bacon et al, “Glycerophosphodiester phosphodiesterase gene (glpQ) of Borrelia lonestari identified as a target for differentiating Borrelia species associated with hard ticks”, J Clin Microbiol 2004 May;42(5):2326- 8. 8 Kubová Z, Szanyi J, Langrová J, Kremlácek J, Kuba M, Honegr K. Motion-onset and pattern-reversal visual evoked potentials in diagnostics of neuroborreliosis J Clin Neurophysiol. 2006 Oct;23(5):416-20. 9 Drozdowski W, Przegl Epidemiol. [Multifocal central nervous system lesions --multiple sclerosis or neuroborreliosis?] 2006;60 Suppl 1:39-45. 10 Brorson O, Brorson SH, Henriksen TH, Skogen PR, Schoyen R., Association between multiple sclerosis and cystic structures in cerebrospinal fluid. Infection 2001 Dec;29(6):315-9 11 Hänsel Y, Ackerl M, Stanek G. ALS-like sequelae in chronic neuroborreliosis Wien Med Wochenschr. 1995;145(7-8):186-8 12 Halperin JJ, Kaplan GP, Brazinsky S, Tsai TF, Cheng T, Ironside A, Wu P, Delfiner J, Golightly M, Brown RH, et al. Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease. Arch Neurol. 1990 May;47(5):586-94 13 Bransfield RC et al., The association between tick-borne infections, Lyme borreliosis and Autism-Spectrum Disorders Med Hypotheses(2007), doi:10.1016/j.mehy.2007.09.006 14 Health Protection Agency www.hpa.org.uk/infections/topics_az/zoonoses/lyme_borreliosis/faq.htm 15 Fritzsche M. Geographical and seasonal correlation of multiple sclerosis to sporadic schizophrenia. Int J Health Geogr. 2002 Dec 20;1(1):5. 16 Miklossy J, Kis A, Radenovic A, Miller L, Forro L, Martins R, Reiss K, Darbinian N, Darekar P, Mihaly L, Khalili K. Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes Neurobiol Aging. 2006 Feb;27(2):228-36 17 MacDonald AB. Alzheimer's disease Braak Stage progressions: reexamined and redefined as Borrelia infection transmission through neural circuits. Med H 2007;68(5):1059-64. Epub 2006 Nov 17 18 Dryden MS, O'Connell S, Samuel W, Iannotti F. Lyme myelitis mimicking neurological malignancy. Lancet. 1996 Aug 31;348(9027):624. 19 Pachner AR, Amemiya K, Bartlett M, Schaefer H, Reddy K, Zhang WF. Lyme borreliosis in rhesus macaques: effects of corticosteroids on spirochetal load and isotype switching of anti-borrelia burgdorferi antibody. Clin Diagn Lab Immunol. 2001 Mar;8(2):225-32. 20 Sherr VT Med Hypotheses. 2005;65(3):440-7. Munchausen's syndrome by proxy and Lyme disease: medical misogyny or diagnostic mystery? 21 Cameron DJ Generalizability in Two Clinical Trials of Lyme Disease, Epidemiologic Perspectives and Innovations, 2006 3:12 22 Verbunt RJ, Visser RF. [Total atrioventricular block following a tick bite] Ned Tijdschr Geneeskd. 2007 Sep 1;151(35):1941-4 23 Marcus LC, Steere AC, Duray PH, Anderson AE, Mahoney EB. Ann Intern Med. 1985 Sep;103(3):374-6. Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis. Demonstration of spirochetes in the myocardium. 24 Salonen R, Rinne JO, Halonen P, Puusa A, Marttila R, Viljanen MK., Lyme borreliosis associated with complete flaccid paraplegia. J Infect. 1994 Mar;28(2):181-4. 25 Oleson CV, Sivalingam JJ, O'Neill BJ, Staas WE Jr Transverse myelitis secondary to coexistent Lyme disease and babesiosis.. J Spinal Cord Med. 2003 Summer;26(2):168-71. 26 Merlo A, Weder B, Ketz E, Matter L. Locked-in state in Borrelia burgdorferi meningitis. J Neurol. 1989 Jul;236(5):305-6. 27 Scheid R, Hund-Georgiadis M, von Cramon DY. Intracerebral haemorrhage as a manifestation of Lyme neuroborreliosis? Eur J Neurol. 2003 Jan;10(1):99-101. 28 Rothermel H, Hedges TR 3rd, Steere AC. Optic neuropathy in children with Lyme disease Pediatrics..2001 Aug;108(2):477-81. 29 Peltomaa M, Pyykkö I, Sappälä I, Viitanen L, Viljanen M. Lyme borreliosis, an etiological factor in sensorineural hearing loss? Eur Arch Otorhinolaryngol. 2000;257(6):317-22. 30 International Lyme and Associated Diseases Society Evidence-based Guidelines for the Management of Lyme Disease, Expert Rev Anti-infect Ther. 2 (1) 2004 31 Carlomagno G, Luksa V, Candussi G, Rizzi GM, Trevisan G. Lyme Borrelia positive serology associated with spontaneous abortion in an endemic Italian area. Acta Eur Fertil. 1988 Sep-Oct;19(5):279-81 32 Lyme Borreliosis in Neurology and Psychiatry, Ed. VT Sherr MD, D Cameron MD online publication of Lyme Disease Action 2006 33 Fallon BA, Nields, JA, Lyme Disease: A Neuropsychiatric Illness, Am J Psychiatry 151:11 Nov 1994 p1571-1580 34 Statement by family of suicide victim and Lyme patient Prof Alasdair Crockett published at http://www.lymediseaseaction.org.uk/releases/lda_21.htm Competing interests: None declared |
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Daniel Cameron, President, International Lyme and Associated Diseases Society 175 Main Street, Mt. Kisco, New York 10549 USA
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The letter from Donald Poretz, the president of the Infectious Diseases Society of America (IDSA) (1), could be viewed as another example of the “Lyme Wars” described by Alison Tonks (1). Dr. Poretz cites the status of IDSA rather than the evidence as support for the IDSA guidelines recommendations. (2) The IDSA guidelines neither referenced the published International Lyme and Associated Diseases Society (ILADS) guidelines (3) nor did the IDSA include ILADS members in their guidelines committee. The IDSA guideline committee fail to address the concerns of ILADS that the IDSA places too much reliance on a single study that enrolled Lyme disease patients who had already been ill an average of 4.7 years, and had already had an average of three courses of previous treatment without success. (3) The results of this study are not generalizable to the patient population that clinicians see in their offices (4). The IDSA guideline committee also fail to resolve the ILADS guideline committee’s concern with the poor sensitivity of two-tier approach to B burgdorferi antibody testing, recommended by the US Public Health Service and European experts some 12 years ago. Dr. O’Connell in a follow-up letter to the BMJ cited Wilske and associates as evidence that the 2-tier diagnostic test is sensitive (5). But in actuality, Wilske and colleagues had concluded that neither the recombinant immunoblot nor the conventional whole-cell lysate immunoblot used in the 2-tier diagnostic tests was more than 52.7% and 63.8% sensitive respectively (5). Most controversies occur when there is little evidence. The total number of subjects enrolled in published RCTs to date amounted to only 221 subjects. This same size –is far too small to draw broad conclusions suppressing the only treatment option known to be effective for Lyme disease. Moreover, the results of the studies are limiting and conflicting. When evidence is uncertain and controversy exists, it is critical for the medical community to be able to evaluate conflicting positions, the basis for the medical evidence cited, study criteria, professional agendas and conflicts of interests that may exist. Only by airing these different points of view will the medical and scientific community reach a better understanding of controversial topics such as chronic Lyme disease. Meanwhile, physicians must be able to exercise their clinical judgment and patients should be provided with treatment options. It is time the medical community considers Lyme Disease as another example of a “clinical equipoise”-- absence of consensus within the clinical community—rather than resign themselves to “Lyme Wars”. References 1. Tonks A. Lyme wars. Bmj. 2007;335(7626):910-2. 2. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089- 134. 3. Cameron D, Gaito A, Harris N, et al. Evidence-based guidelines for the management of Lyme disease. Expert Rev Anti Infect Ther. 2004;2(1 Suppl):S1-13. 4. Cameron DJ. Generalizability in two clinical trials of Lyme disease. Epidemiol Perspect Innov. 2006;3:470-2. 5. Wilske B, Fingerle V, Schulte-Spechtel U. Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol. 2007;49(1):13-21. Competing interests: None declared |
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Duncan A Munro, LTD SFU Canada V5A 1S6
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Lyme Disease Testing and Treatment: A patient's perspective I was infected with Lyme Disease, on or around, May 10/11, 1990. I am not a doctor. I am currently on sick leave from Simon Fraser University. The most common, first tier, Lyme Disease Blood test is the ELISA. It is typically scored: 0-.89 = Negative, .90-1.09 = Equivocal, 1.1 or higher = positive. In the Province of British Columbia (BC), where I live, the numerical score of the test is deleted, and only the 3 qualitative scores are reported on the test result, to the requesting physician, by the BC Centre for Disease Control. This can result in situations, where one patient can have score of 1.1 and have a "positive" result, and receive treatment, and another patient, can score 1.09 and be equivocal, and I can tell you very honestly, that "equivocal" is regarded by most physicians as "negative" and, of course, another patient can score .89 and be reported as having a "negative" result, yet the variation between all three scores is very minimal, and each patient may have similar symptoms and a history of tick bite and a target rash, but only one patient "might" receive treatment: The patient who scores positive on the ELISA is then given a Western Blot test. In this test, the patient's antibody response is measured and they must have a "positive" result in at least 5 of 10 specific antibody categories. Again, the BC CDC does not report the actual results in each antibody category. So again, we have a situation where, one patient can have the full 5 positive scores, be pronounced infected, and receive treatment, yet another equally sick patient, might have 4 positive scores but only a faint return in a 5th antibody category...and they are "negative", so: 5 positive scores = "positive" and treatment given. 4 positive scores and one faint result = "negative" and no treatment given(!) Another patient may have 3 positive scores and 3 faint results and again are "negative" and receive no treatment. Quite frankly, this is an insane testing system. I could understand the needed for an extremely rigorous testing regime, designed to weed out anyone who might be a "false" positive, if the treatment for Lyme Disease consisted of multiple open heart surgeries and 6 months in an ICU...but this is not the case. Most patients can be treated with low cost, common, broad spectrum antibiotics, such as Tetracycline, Doxycycline or Minocycline. In my case, the cost of testing, to deny me 30 days of Doxycycline, probably far exceeded the cost of treatment,at that point in time. I have been reading with interest, the development of the C6 ELISA test, which probably is very accurate, except, once again, the same insane scoring system with arbitrary cut-off points is being utilized. The human immune system simply does not work on a "3 category scale" and if enough scores are graphed they will be plotted as a classic bell curve, with many patients scoring on the "negative" side of the curve, and thus are denied treatment, even though they are infected. All the available literature indicates that infected patients are scoring in a bell curve, since every comparative test of current testing methods, utilizing blood that is culture positive, results in 25 to 45% false negative scoring. So we have: 25 to 45% Negative, some equivocal, and ~50% positive. utilizing blood from culture positive patients. You don't have to be a rocket scientist, to see that this is a bell curve result. So Positive = Positive, but any other score should be considered equivocal, and must be diagnosed clinically, based upon symptoms and medical history. yours Duncan Munro Competing interests: None declared |
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Joel Spinhirne, President Verim Research, 97031
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To the Editor: The least convincing response to this article to date has come from Donald Poretz, the president of a professional society, the Infectious Disease Society of America (IDSA), which is currently under investigation for unfair trade practices(1). This letter continues the IDSA’s pattern of misstatement of fact. Contrary to Poretz' claim that, "In more than 20 years there has not been one scientifically valid study published in the peer-reviewed medical literature that proves that the benefit of long-term antibiotic treatment outweighs the risks", in 1997 one of the IDSA's own journals published a study showing the benefit of antimicrobial therapy of longer than three month duration(2). Rather than follow this paper with subsequent studies investigating the benefits of therapy extending beyond three months, the IDSA repeatedly endorses poorly performed clinical studies, none of which examined therapy beyond three months. The initial investigator of the 1997 paper published his follow-up paper in a European journal(3). This study again showed benefits of therapy longer than three months. Suggesting borreliosis is actually another unexplained illness, as Poretz does, is entirely dependent upon the physician’s inability or unwillingness to recognize the most likely cause of the presenting illness, persisting infection. There is no test or procedure that comes close to reliably indicating a patient is not infected with Borrelia burgdorferi. Any diagnosis denying infection lacks a scientific basis. Contrary to Poretz’ claims, there is a startling absence of validated studies showing quantification of harm caused by antimicrobial treatment, let alone correlation of this harm with borreliosis treatment. The study most often cited by the IDSA to justify non-treatment of borreliosis, at its fundamental level, demonstrated nothing.(4) The investigators reported their inability to detect anything of significance. The question then becomes how hard did they look for treatment effect? While the IDSA has long encouraged ignoring patient self-reporting, this study was entirely dependent on patient self-reports measured with an extremely insensitive measurement tool. There were zero post-treatment objective measures reported nor the result of any physician interview or examination. In addition, the number of subjects was exceedingly small and limited to subjects who had previously failed treatment much like the one being tested. At some point the critical reader needs to ask why the IDSA needs to ignore or misstate so much to make their case. And, at some point the “do no harm” shibboleth is entirely unconvincing. Competent mainstream medical care dictates antimicrobial therapy of a duration necessary to control the causative infection. Tens of thousands, maybe more, patients reporting benefit, and no harm, from more than three months of antimicrobials is evidence — and the best evidence we have. 1. Hamilton E. Lyme Disease Guidelines Focus Of Antitrust Probe. The Hartford Courant. November 17, 2006. 2. Donta ST. Tetracycline therapy for chronic Lyme disease. Clin Infect Dis 1997;25 Suppl 1:S52-6. 3. Donta ST. Macrolide therapy of chronic Lyme Disease. Med Sci Monit 2003;9(11):PI136-42. 4. Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92. Competing interests: None declared |
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Robert C Bransfiield, MD, DFAPA, President Elect International Lyme and Associated Diseases Society Red Bank, New Jersey, USA 07701
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It is encouraging to see the leading medical journal in the world provide an open forum to discuss this controversial issue. The highly restrictive paradigm advanced by the Infectious Disease Society of America committee assures the continuation of undisclosed research grant money and Lyme related patents for the authors of these guidelines and their colleagues, while being devastating to many patients with late stage tick- borne infections/Lyme Borreliosis. [1] [2] As a psychiatrist in a Lyme epidemic region I see many of these patients. Among the many previously recognized symptom and impairments, autism spectrum disorder is one more condition associated with inadequately diagnosed and treated chronic tick- borne infections and Lyme Borreliosis. [3] Should our children’s future be compromised to promote special interests? [1] Landers SJ, Lyme disease debate provokes treatment divide, legal action AMNews. Dec. 25, 2006. http://www.ama- assn.org/amednews/2006/12/25/hlsa1225.htm [2] Antitrust scrutiny of Lyme guidelines The National Law Journal. January 22, 2007 [3] Bransfield RC, Wulfman JS, Harvey WT, Usman AI. The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders. Med Hypotheses. 2007 Nov 1; [Epub ahead of print] Competing interests: None declared |
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Rolf K. Taylor, Engineer Cleveland, Ohio 44118
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Those MDs who have PhDs will know that one of the most fundamental rules of science is called Occam's Razor. Academic Physicians, who form much of one side in the "Lyme War", certainly should know it. If they do not they should retire. Occam's Razor is very simple. It states that when evaluating two hypotheses, with equal evidence (for example persistent infection vs some hypothetical post-infection sequalae), that the simpler explanation is given preference. It is alternately expressed: "When you hear hoof beats, think horses, not zebras". The simplest possible explanation for relapse after treatment for an infection is that the treatment was inadequate, so this places a very high bar indeed for conflicting theories. Therefore, until, and when, there is proof of "post-Lyme syndrome" (e.g. a test that can prove that the bacterial infection is no longer present) the only scientific explanation is persistent infection. Let's face it, while medicine should be about science, there is plenty of need for clinical judgment. How delightfully ironic that the science firmly supports those noble practitioners who are helping Lyme patients and not the so-called academic cabal. Now, I ask, please get on with treating us, and finding better tests. Competing interests: Patient with Chronic Lyme Disease |
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Hugh Mann, Physician Eagle Rock, MO 65641 USA
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The best way to cut Competing interests: None declared |
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Susan O'Connell, Consultant Microbiologist HPA Microbiology Laboratory, Southampton General Hospital, Southampton SO16 6YD
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Dr Cameron’s use of the term “clinical equipoise” related to Lyme borreliosis is inappropriate in view of the acceptance by most clinicians of diagnostic and treatment recommendations based on a body of evidence accrued from over 30 years of international research. These include guidelines developed by the Infectious Diseases Society of America, practice parameters of the American Academy of Neurology and similar recommendations from some European groups, which used carefully developed and specific case definitions, and do not recommend very prolonged courses of antibiotics.(1-5) Five double-blind randomised control studies failed to demonstrate long term benefits and showed significant risks from prolonged antibiotic therapy for patients with persistent symptoms following Lyme disease.(6-10) Such treatment cannot therefore be considered to be beneficial. It might be more appropriate for Dr Cameron to use the term “theoretical equipoise” to describe his position and that of his colleagues. (11) Dr Stricker and Ms Johnson’s concerns regarding the shortcomings of tests for antibodies to Borrelia burgdorferi have been addressed in detail by Dr Porwancher and colleagues. (Lyme wars: Critique misses the mark. http://www.bmj.com/cgi/eletters/335/7628/1008 ) Dr Stricker and Ms Johnson may also not be aware of the range of well-validated and commercially available antibody tests now approved for use in Europe. They include tests which use a variety of recombinant-derived antigens, including recombinant immunoblots, and others which add recombinant antigens from different borrelial genospecies to traditional whole-cell lysate-based tests in order to maximise sensitivity. They are useful additions to the diagnostic repertoire, and a broad range of tests can now be applied in cases where there is genuine diagnostic uncertainty. Further improvements are anticipated with other test methods currently under development and evaluation. With reference to my enquiry to the publishers of Expert Review of Anti-Infective Therapy regarding the peer-review process for the supplement in which the ILADS guidelines appeared (12), I received an email reply dated 9th August 2006 from the Editorial Director (on file). She wrote: “In this instance the guidelines represent a consensus document produced by a working group consisting of members of the International Lyme and Associated Disease Society (ILADS). As such, the document was not subject to our standard review procedures as applied to individual articles and the guidelines reflect the collective opinion of the ILADS working group, as set out in the introduction.”. I have no financial conflict of interests to declare to the BMJ as I have taken no payments for any medicolegal work as an expert witness, and have no other potential financial conflicts of interests. 1. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS et al. The clinical assessment, treatment and prevention of Lyme disease, human granulocytic anaplasmosis and babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006;43:1089-1134. 2. Halperin JJ, Shapiro ED, Logigian, E, Belman AL, Dotevall L, Wormser GP et al. Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review) Neurology 2007;69:1-12. 3. Halperin JJ, Logigian E, Finkel M, Pearl R. Practice Parameters for the diagnosis of patients with nervous system Lyme borreliosis (Lyme disease). Neurology 1996;46:619-627. 4. Expert Panel for Quality Standards in the Microbiological Diagnosis of Infectious Diseases (MiQ) MiQ 12 2000: Lyme Borreliosis. Authors: Wilske B, Zoller L, Brade V, Eiffert H, Gobel U, Stanek G, Pfister H-W. http://pollux.mpk.med.uni-muenchen.de/alpha1/nrz-borrelia/miq-lyme/miq- lyme.html . 5. European Concerted Action on Lyme Borreliosis http://meduni09.edis.at/eucalb/cms/index.php 6. Klempner MS, Hu LT, Evans J et al. Two controlled trial of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345:85-92. 7. Krupp LB, Hyman LG, Grimson R et al. Study and treatment of post Lyme disease (Stop-LD). A randomized double-masked clinical trial. Neurology 2003;60:1923-1930. 8. Kaplan RF, Trevino RP, Johnson GP et al. Cognitive function in post- treatment Lyme disease. Do additional antibiotics help? Neurology 2003;60:1916-1922. 9. Fallon BA, Keilp JG, Corbera KM et al. A randomized, placebo- controlled trial of repeated IV antibiotic treatment for Lyme encephalopathy. Neurology 2007; 10. Oksi J, Nikoskelainen J, Viljanen M et al. Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind randomized, placebo-controlled multicenter study. Eur J Clin Microbiol Infect Dis 2007;26:571-581. 11. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987;317:141-5. 12. Cameron D , Gaito A, Harris N, Bach G, Bellovin S, Bock K et al. Evidence-based guidelines for the management of Lyme disease. Exp Rev Anti Infect Ther 2004;2(suppl1) S1-13. Competing interests: None declared |
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Raphael B. Stricker, MD 450 Sutter Street, Suite 1504, San Francisco, CA 94108, Lorraine Johnson
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Microbiologist Susan O’Connell gives us more examples of the inaccuracies and misstatements that have fuelled the “Lyme wars”. She turns conflicting data into weighty pronouncements about the diagnosis and treatment of Lyme disease. Dr. O’Connell cites the Lyme guidelines of the Infectious Diseases Society of America (IDSA) and the American Academy of Neurology (AAN) as if these were independent documents that support narrow treatment recommendations for Lyme disease (1,2). In reality, these guidelines were developed by overlapping panels with the respective IDSA and AAN chairmen serving on both panels, assuring that the guidelines would be “like-minded” (3). In fact, the wording in the two guidelines is so similar that it precludes any sense of independent thought by the panel members. The IDSA tactic of using interlocking and exclusionary panels to induce other medical societies to rubber-stamp its Lyme guidelines helps to explain why IDSA is under investigation for anti-competitive practices in its Lyme guidelines development process (4). Dr. O’Connell states that “five double-blind randomised control studies failed to demonstrate long term benefits and showed significant risks from prolonged antibiotic therapy for patients with persistent symptoms following Lyme disease” (5-9). Of the studies cited, two (Klempner et al. and Kaplan et al.) describe the same patients and are not independent (5,7). The studies by Krupp et al. and Fallon et al. in fact demonstrated significant improvement in fatigue, cognitive function and/or physical function with longer courses of antibiotics in patients with chronic Lyme disease (6,8). The recent study by Oksi et al. was underpowered to draw conclusions about treatment efficacy because the study only enrolled 152 out of the required 200 patients necessary for adequate data analysis (9). Of note, the prevalence of an erythema migrans rash in the study patients was only 28%, significantly lower than the figure touted by the IDSA guidelines as a ubiquitous marker of Lyme disease. Dr. O’Connell claims that our analysis of the insensitivity of commercial Lyme testing has been addressed by Porwancher and colleagues (10). In spite of the mathematical gymnastics employed by those authors, the insensitivity of commercial Lyme testing remains an undisputed fact that has harmed thousands of Lyme patients who are denied appropriate diagnosis and treatment based on these inaccurate tests (11,12). Once again, it is misleading for Dr. O’Connell to tell us about the marvelous Lyme tests that are just around the corner while denying care for patients in her National Health Service based on the insensitive commercial tests that are currently available. Dr. O’Connell’s allegation that the evidence-based guidelines of the International Lyme and Associated Diseases Society (ILADS) were not peer reviewed is based on a misunderstanding of the review process. Although the guidelines were not subject to external review that is often employed for original scientific articles, they were subjected to in-house peer review by the editorial staff of the journal. In view of the prestigious membership of the journal’s editorial board at the time, this form of peer review by an independent journal trumps the nebulous review process of the self-published IDSA guidelines described in our previous communication (13). As a result, the ILADS guidelines provide a more balanced evidence-based approach to the complex issues surrounding the diagnosis and treatment of Lyme disease and associated tick-borne disorders (14). Raphael B. Stricker, MD Past President, International Lyme & Associated Diseases Society San Francisco, CA 94108 Lorraine Johnson, JD, MBA Executive Director, California Lyme Disease Association Los Angeles, CA 90068 References 1. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS et al. The clinical assessment, treatment and prevention of Lyme disease, human granulocytic anaplasmosis and babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006;43:1089-1134. 2. Halperin JJ, Shapiro ED, Logigian, E, Belman AL, Dotevall L, Wormser GP et al. Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review) Neurology 2007;69:1-12. 3. Stricker RB, Johnson L. Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review). Neurology, November 1, 2007. Available at http:// www.neurology.org/cgi/eletters/69/1/91. 4. Stricker RB, Johnson L. Lyme disease: A turning point. Expert Rev Anti-Infect Ther 2007;5:759-762. 5. Klempner MS, Hu LT, Evans J et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345:85-92. 6. Krupp LB, Hyman LG, Grimson R et al. Study and treatment of post Lyme disease (Stop-LD). A randomized double-masked clinical trial. Neurology 2003;60:1923-1930. 7. Kaplan RF, Trevino RP, Johnson GP et al. Cognitive function in post-treatment Lyme disease. Do additional antibiotics help? Neurology 2003;60:1916-1922. 8. Fallon BA, Keilp JG, Corbera KM et al. A randomized, placebo- controlled trial of repeated IV antibiotic treatment for Lyme encephalopathy. Neurology 2007; Oct 10 epub. 9. Oksi J, Nikoskelainen J, Viljanen M et al. Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind randomized, placebo-controlled multicenter study. Eur J Clin Microbiol Infect Dis 2007;26:571-581. 10. Stricker RB, Johnson L. Lyme Wars: Let’s tackle the testing. BMJ 2007;335:1008. 11. Johnson L, Stricker RB. Treatment of Lyme disease: A medicolegal assessment. Expert Rev Anti-Infect Ther 2004;2:533- 57. 12. Stricker RB. Counterpoint: Long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clin Infect Dis 2007;45:149-57. 13. Stricker RB, Johnson L. Lyme wars: The battle continues. BMJ Online, November 24,2007. Available at http://www.bmj.com/cgi/ eletters/335/7626/910. 14. Cameron D, Gaito A, Harris N, Bach G, Bellovin S, Bock K et al. Evidence-based guidelines for the management of Lyme disease. Exp Rev Anti Infect Ther 2004;2(suppl1) S1-13. Competing interests: RBS serves on the advisory panel for QMedRx Inc. In December 2007 he joined the editorial board of Expert Review of Anti-Infective Therapy. |
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William T. Harvey, MD, Clinician/Research Coordinator Rocky Mountain Chronic Diseases Specialists, 5575 Wilson Road; Colorado Springs, CO 80919
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Dear BMJ Editor, One notes with interest...and dismay... the number of responses to the “Lyme Wars” topic thirty years after Steere published the Lyme hypothesis[1, 2]. There should be little residual conflict given that the birth of critical thinking began centuries ago with the Renaissance via many European and UK thinkers, including physician William Harvey (reference intended). The arguments now appearing as BMJ “Lyme Wars” letters surprisingly ignore the insight shift of Harvey’s Padua University schoolmate, Nicolaus Copernicus. Although the essence of De motu cordis was that truth lay in the reality at hand, a century earlier Copernicus first made an even more fundamental point, that co-variants do not prove cause-and-effect. Unexpectedly, both concepts are ignored so frequently in the Lyme Wars thread that collectively they illustrate what has happened to recent scientific thinking and immediately clarify how such arguments can occur. Truth seems to lie in the simplest concepts, as Einstein had hoped. Here, brought to a grade school level is the concept that has invalidated most Borreliosis research over the past three decades: The finding of Borrelia in a chronically ill human does not prove Borrelia generated the illness. No one has ever elucidated the mechanism by which Borrelia exerts its claimed pathophysiology. When Willie Burgdorfer first encountered Borrelia (burgdorferi sensu lato) in acutely ill New England patients, the correlation was initially made. Subsequently, it was verified numerous times in endemic areas of the planet. Ultimately, the numbers reached mathematically validity and in time revealed a zoonosis cycle bridged by at least one arthropod vector. This correlation came from Epidemiology devoid of a pathologic mechanism, but was strong enough to make the case for an acute illness. This method, as weak as it was, gave rise to the present US CDC case criteria for Lyme disease as an acute, readily treatable illness with predictable (but not well understood) signs and symptoms. What then is the dilemma where acute Lyme disease and chronic Lyme disease are juxtaposed in a mortal face-off? Enter semantics. This dilemma did not occur in a vacuum. Outside the boundary of a relatively limited acute zoonosis, there must exist yet another illness; an illness so serious and pervasive that many astute clinicians and a few scientists would go to any means to give credibility to that illness. An NLM search taking only seconds will indeed uncover a veritable ocean of persistently ill humans with these similar characteristics: Their illness is chronic, multi-systemic, unpredictably varied, possibly life shortening, unsolved and appropriately kept outside the taxonomy of proven illnesses. The number of assigned labels is extraordinarily large, however, and vastly more inclusive than chronic Lyme disease is thought to be. If such an illness exists it necessarily would engender extreme clinical passion. And given no support by traditional science, labels would be found in large numbers, with similar descriptors, and would emerge as historical counterparts. This phenomenon has indeed occurred. Awareness began to appear between 1970-1980. New semantic identifiers such as Chronic Fatigue Syndrome, Fibromyalgia syndrome...and since the mid- 1980s, chronic Lyme disease…are only three.[3-13] If we follow the theme of similar intermittent laboratory abnormalities, basic abnormal physical findings and fundamental chronic symptoms, at least two-dozen other groups such as Bannwarth’s syndrome, Ekbom syndrome, Asperger’s syndrome and others emerge.[14-23] A short foray into the universe of illness labels above reveals similar “wars” underway since 1980: Chronic Fatigue Syndrome (CFS) VS chronic Fibromyalgia syndrome (Fibromyalgia); CFS VS chronic Lyme disease (Lyme); Lyme and CFS VS Gulf War Syndrome (GWS) are among the obvious. Clinicians fortunate enough to encounter this larger chronically ill group outside of New England (where vector prevalence of Borrelia is high) were not tempted by Borrelia as a generator of chronic illness.[24-29] Rather, their semantic choices emerged from such random events as participation in recent wars, or travel to high-humidity regions where fungi are rampant. In summary, Lyme Wars if followed to its root, is a failure of our medical education system to insist on teaching scientific method, and beginning that with the foundation of all truth: language (semantics). Something did likely occur in the world of human disease some 30 years ago as these “wars” attest to. “It” could be attributed to the population explosion, global warming, excess computer use, or even larger numbers of vaccines. But, I choose to wait until science shows us the mechanism rather than join the twenty first century’s trust in celebrity (trust papers from the most notable journals…or be pulled into the current “matrix” of popular mindset) rather than face the factual illness only where it exists: the patient. Even medical wars are cognitive constructs, generated by the human mind. If we are ever to get the term “evidence based medicine” correct, this is our wake up call. The “evidence” as Harvey showed us in the sixteenth century is in the ill (or deceased) human, not textual material often outdated before it reaches print. (812 words) References 1. Steere, A.C., J.A. Hardin, and S.E. Malawista, Erythema chronicum migrans and Lyme arthritis: cryoimmunoglobulins and clinical activity of skin and joints. Science, 1977. 196(4294): p. 1121-2. 2. Steere, A.C., et al., Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum, 1977. 20(1): p. 7-17. 3. Eidelman, D., Fatigue: towards an analysis and a unified definition. Med Hypotheses, 1980. 6(5): p. 517-26. 4. Ballow, M., et al., Familial chronic mononucleosis. Ann Intern Med, 1982. 97(6): p. 821-5. 5. Uretsky, B.F., Does mitral valve prolapse cause nonspecific symptoms? Int J Cardiol, 1982. 1(5-6): p. 435-42. 6. DuBois, R.E., et al., Chronic mononucleosis syndrome. South Med J, 1984. 77(11): p. 1376-82. 7. Yunus, M.B., Primary fibromyalgia syndrome: current concepts. Compr Ther, 1984. 10(8): p. 21-8. 8. Caligiuri, M., et al., Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J Immunol, 1987. 139(10): p. 3306-13. 9. Byrne, E. and I. Trounce, Chronic fatigue and myalgia syndrome: mitochondrial and glycolytic studies in skeletal muscle. J Neurol Neurosurg Psychiatry, 1987. 50(6): p. 743-6. 10. McLaughlin, T.P., et al., Chronic arthritis of the knee in Lyme disease. Review of the literature and report of two cases treated by synovectomy. J Bone Joint Surg Am, 1986. 68(7): p. 1057-61. 11. Kriuchechnikov, V.N., [Chronic migrant erythema or Lyme disease--a new tick-borne Spirochaetales infection]. Zh Mikrobiol Epidemiol Immunobiol, 1985(9): p. 101-9. 12. Eschard, J.P., et al., [Lyme disease without arthritis: presence of antiBorrelia burgdorferi antibodies in meningoradiculitis following chronic erythema migrans]. Presse Med, 1985. 14(28): p. 1517-8. 13. Ryberg, B. and I. Thelin, [Lyme disease in Sweden. A patient with arthralgia associated with chronic erythema migrans]. Lakartidningen, 1984. 81(30-31): p. 2758-60. 14. Calabresi, P.A., et al., Ekbom's syndrome: lipomas, ataxia, and neuropathy with MERRF. Muscle Nerve, 1994. 17(8): p. 943-5. 15. Sojka, E. and Z. Afeltowicz, [Ekbom's syndrome in a patient with mitral valve disease and subacute endocarditis]. Pol Tyg Lek, 1978. 33(17): p. 691-2. 16. Harriman, D.G., D. Taverner, and A.L. Woolf, Ekbom's syndrome and burning paraesthesiae. A biopsy study by vital staining and electron microscopy of the intramuscular innervation with a note on age changes in motor nerve endings in distal muscles. Brain, 1970. 93(2): p. 393-406. 17. Fox, W.B., Ekbom's syndrome. J Am Inst Homeopath, 1967. 60(1): p. 26. 18. Roelcke, U., et al., Untreated neuroborreliosis: Bannwarth's syndrome evolving into acute schizophrenia-like psychosis. A case report. J Neurol, 1992. 239(3): p. 129-31. 19. Henriksson, A., et al., Immunoglobulin abnormalities in cerebrospinal fluid and blood over the course of lymphocytic meningoradiculitis (Bannwarth's syndrome). Ann Neurol, 1986. 20(3): p. 337-45. 20. Tantam, D., Asperger's syndrome. J Child Psychol Psychiatry, 1988. 29(3): p. 245-55. 21. Bowman, E.P., Asperger's syndrome and autism: the case for a connection. Br J Psychiatry, 1988. 152: p. 377-82. 22. Wing, L., Clarification on Asperger's syndrome. J Autism Dev Disord, 1986. 16(4): p. 513-5. 23. Kerbeshian, J. and L. Burd, Asperger's syndrome and Tourette syndrome: the case of the pinball wizard. Br J Psychiatry, 1986. 148: p. 731-6. 24. Harvey, W.T. and P. Salvato, "Lyme disease": ancient engine of an unrecognized Borreliosis pandemic? Medical Hypotheses, 2003. 60(5): p. 742 -759. 25. Burgdorfer, W., Discovery of the Lyme disease spirochete and its relation to tick vectors. Yale J Biol Med, 1984. 57(4): p. 515-20. 26. Pokorny, P., [Incidence of the spirochete Borrelia burgdorferi in arthropods (Arthropoda) and antibodies in vertebrates (Vertebrata)]. Cesk Epidemiol Mikrobiol Imunol, 1989. 38(1): p. 52-60. 27. Burgdorfer, W., Vector/host relationships of the Lyme disease spirochete, Borrelia burgdorferi. Rheum Dis Clin North Am, 1989. 15(4): p. 775-87. 28. Burgdorfer, W., et al., Relationship of Borrelia burgdorferi to its arthropod vectors. Scand J Infect Dis Suppl, 1991. 77: p. 35-40. 29. Baranton, G., N. Marti Ras, and D. Postic, [Borrelia burgdorferi, taxonomy, pathogenicity and spread]. Ann Med Interne (Paris), 1998. 149(7): p. 455-8. 30. Williamson, P.K. and J.J. Calabro, Lyme disease--a review of the literature. Semin Arthritis Rheum, 1984. 13(3): p. 229-34. 31. Berger, B.W., O.J. Clemmensen, and A.B. Ackerman, Lyme disease is a spirochetosis. A review of the disease and evidence for its cause. Am J Dermatopathol, 1983. 5(2): p. 111-24. Competing interests: None declared |
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Elizabeth L Maloney, physician 25611 W. Comfort Dr Wyoming, MN 55092
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In decrying the “Lyme Wars”, Dr. Harvey writes: “But, I choose to wait until science shows us the mechanism” (1). That is his choice, but if every clinician decided to “sit this one out” what would happen to the ill? Is it his position that patients must wait until all the evidence is in before their illnesses can be addressed? Such a position is folly, especially if it were expanded to include other, poorly understood conditions. And, even in circumstances where the evidence points in one direction and clinical methods/treatments appear agreed upon and settled, new breakthroughs often demonstrate errors in the previous evidence-based construct. Thus, no one would be treated for fear that the future would prove the current therapy wrong. But patients live and die in the present. One charge to physicians, and all health care professionals, is the relief of suffering. Scientific evidence may enlighten our medical paths but when the evidence dims we would be wrong to stop walking. Fumbling in the dark will take some of us off the trail but others will manage to reach their destination and patients will be better because of those efforts. Even the mistakes add to our experiential knowledge; insights we would not gain from standing still. Dr. Harvey is right in that moving beyond a "war" mentality would allow us to focus more completely on the clinical problem. But, until a truce is declared, those of us who see patients improve with longer courses of treatment utilizing novel antibiotic combinations must resist all efforts to push us to the margins, even from colleagues who have taken to the sidelines. References 1. Harvey W. http://www.bmj. com/cgi/eletters /335/7626/ 910#182692 Competing interests: None declared |
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M. Marjorie, tick sick 94915
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memories of health the bite that keeps on giving bitter pills galore Competing interests: None declared |
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david hart, On long term antibiotics w1
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The best way to cut the Gordian knot of Burgdorfers nematamorph, and mine for that matter, is not with Occam's razor. Competing interests: None declared |
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david a lee, unemployed sp5 4db, independent
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Until 4 years ago, I was a very fit and active individual. I ran my own successful Company and lived in a large 7 bedroom House. I am now unemployed (not by choice) and suffer daily from chronic fatigue and paraesthesias in my hands and feet, and neuralgia at night on the side of my face. I have had in the last 4 years, 2 sets of blood tests under the NHS to determine my illness,both of which have come back negative from my GPs. They have both proudly explained that there is nothing wrong with me and treat me as if I am suffering from some sort of delusional depressive illness. Why is this disease so difficult to diagnose? and why is it such a hot potato amongst the medical profession? Surely all you medical experts realize that individuals like myself simple fall between the cracks of the conventional medical diagnostic system and are left to flounder with an increasingly debilitating illness. As I cannot work with my illness, then I cannot generate the £50K Plus of corporation tax I was previously paying into the "system" every year. Does this count for anything? Isn't it time for the medical profession to stop speculating about this illness and for someone within the NHS to set up a funded body to fully investigate? Competing interests: None declared |
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Gavin R Morrigan, Chronic Lyme sufferer Stockton-on-Tees, TS19 8FD
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After suffering at least 7 years of this debilitating illness wreaking havoc on my physical and mental health and my family’s well- being, I was finally diagnosed as having Chronic Lyme disease in April 2007 clinically and by blood specimen by a Professor who has successfully treated a number of other Lyme patients. I have been offered bespoke treatment for Chronic Lyme Disease and my additional abnormalities elsewhere in the UK by a private provider at cost. I approached my local Primary Care Trust (PCT) for funding with the full backing of my GP. My physical and neurological problems are degenerating which have left me unable to work but I always retained hope that those who could, would. I feel now that I have no hope anymore. Today I received two letters. The first was from the PCT refusing my own and my diagnosing consultant’s application for out of area treatment funding citing this BMJ report as the reason. It has taken an exact year for me to receive the final answer! Appalling in itself. The second letter was from my employer where I used to act as a Senior Manager covering roughly 8,000 staff looking at new ways of working and cost improvement strategies with the view of reducing a £multi-million deficit . The letter was to invite me to discuss my employer’s frustration that I can’t return to work within any given timescale due to lack of treatment by the NHS. My employer is instead having to suffer the direct, indirect and opportunity costs of me not being able to contribute in my normal capacity. Guess who is my employer? Correct, the NHS! Farcical! I feel in a state of abandonment by the NHS and overall medical profession. Any empathetic patient focus by the powers that be seems to have been totally lost. I have no competing interests – just someone who has had the absolute misfortune to have been bitten by a tick – diagnosed with having Chronic Lyme disease and then being refused any treatment whatsoever. If these ‘medical professionals’ believe they have my best interests in mind by abandoning me to sink with my ever deteriorating condition under the auspices of protecting me by ‘doing no harm’, then they are, in my opinion, completely deluded as to the meaning of their vocation. To do nothing is the greatest shame. Where do I go from here? Competing interests: None declared |
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Mark G White, Patient's Father TN119LQ
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Unless you are able/prepared to pay up for the full Western blot and co-infection tests obtainable in the USA.
Harsh statement perhaps but in my opinion perfectly justified.
I have witnessed the deterioration of my 5 year old son to this condition over the last 6 months and recommend others follow our example (if they can afford to do so ) and send blood and serum to the US for full lab testing - we took this decision prior to receiving the results from a lab in the south-eastern area of the UK (due to poor feedback from others regarding the Elisa test performed). There are many on this site far more experienced than me and i am not qualified to comment other than to say it is obvious to me that Elisa alone is not adequate to rule out Lyme.
It is a sad sign of the times that we as parents took the initiative (a tick bite 4 years ago and recent iritis led us to pursue this line ) and then, armed with the +ive tests for borrelia and +ve FISH for babesia, have had to justify/insist on our our decision to treat with zithromax and atovoquone.
I am not blaming anyone in this letter , our "medical team" have been superb - just highlighting issues we have faced and wonder if general medical awareness of this disease needs to be increased in this country along with the treatment methods adopted in countries who have had far more experience....
Competing interests: None declared |
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