Lyme Disease Action letter 17th October 2007
To: Rt Hon Alan Johnson MP
Secretary of State for Health
From: Stephanie Woodcock
Lyme Disease Action
53 Kernick Road
17th October 2007
In reply to:
From the Department of Health
Dated: 15th June 2007
Dear Mr Johnson,
Lyme Disease Action (LDA) has recently been in correspondence with Caroline Flint MP, regarding our concerns about Lyme borreliosis (Lyme disease) in the UK. We look forward to a constructive discussion of the issues involved.
We were very concerned by the last letter we received from Ms Flint, as it contained much that we felt was misleading and of the many questions we put forth in that exchange, we find that few have been addressed, and those that have been, have only been given partial answers.
Please find below our further response to the letter we received from Ms Flint on 15/06/07. (The text of Ms Flint’s letter is bold). We still seek answers to many of these questions. Please see Appendix.
Dear Ms Woodcock
Thank you for your further letter of 10 May about Lyme disease.
I note that you disagree with the internationally accredited scientific and medical opinion on how best to diagnose Lyme disease correctly and the appropriate treatment for this condition. However, we do share a desire to ensure that those suffering from Lyme disease are properly recognised and treated.
We are troubled by your statement that we disagree with the internationally agreed accredited opinion regarding the diagnosis of Lyme disease when we have nowhere made such a statement nor can it be inferred from our communication with yourselves dated 10/5/07. Our reservations regarding the current diagnostic procedure in the UK relate to how accredited diagnostic opinion is applied in the cases of individual patients. The position regarding diagnosis as expounded by the Department in our correspondence so far appears not to take account of European statistics and research that show (1) not all patients with Lyme disease have positive serology(1)(2)(3) and (2) Borrelia burgdorferi can survive 2 – 4 week courses of antibiotics.(4)(5)(13)
The Department’s response of 15/6/07 continues to refer to Lyme disease with no further explanation as to how the term ‘Lyme disease’ is defined by the Department. In our letter to the Department dated 10/5/07, we enquired whether the Department’s definition would include all active, pathogenic, tick-borne, borrelial infection whether caused by the currently known genospecies or by other similar entities.(A/1) We need an answer regarding this point, otherwise there is a danger that different interpretations of what constitutes Lyme disease could hinder further dialogue about the disease. Please see the Appendix, (A).
There is plenty of peer-reviewed literature that indicates that testing for known genospecies may not be reliable.(3) Such a situation would be compounded were there to be other genospecies of pathogenic borreliae present in the UK that are not recognised and therefore not tested for at the present time. It would however, be inhumane in the extreme to deny treatment to people with an active, pathogenic borrelial infection, solely because they did not have one of the known pathogenic genospecies.
Your stated belief that existing tests are not reliable enough to rule out the presence of Lyme infection does not help those who suffer from Lyme disease, nor those who are incorrectly led to believe they have Lyme disease through mis-diagnosis based upon invalid diagnostic methods performed in non-accredited laboratories. GPs are well aware of the correct, validated and accredited diagnostic tests for Lyme disease that are freely available within the NHS and which are the only reliable diagnostic tests for Lyme disease. I will repeat what has been stated in earlier correspondence, that diagnosis of Lyme disease is made based upon:
* the clinical picture, such as the manifestations of the disease; and
* an individual’s medical history, including possible exposure to ticks; and
* the results of validated tests carried out in an accredited laboratory.
LDA has never supported invalid diagnostic methods so we do not understand why this issue is raised here.
A reliable diagnosis can be made by taking these three starred points into account but official sources do not require all three to be positive in order to make a reliable diagnosis. Not all clinicians are aware that if a patient has walked on a rural footpath or sat on the grass in Hyde Park then that patient has had possible exposure to tick bites. The Health Protection Agency (HPA) states that blood tests are rarely positive in the first few weeks of infection and rarely negative in the late stages. It can be inferred from this that there is always a possibility of a false negative.
That “existing tests are not reliable enough to rule out the presence of Lyme infection” is not LDA’s stated belief per se, it is a view expressed repeatedly in the peer-reviewed literature.(3) LDA concurs with the world authority on infectious diseases, the Centers for Disease Control and Prevention (CDC) on the point that laboratory tests are helpful to a diagnosis of Lyme.(6) However, lack of a positive test cannot, with certainty, rule it out. In your letter of 15/6/07 (below) the Department applies the expression that the two-stage test is ‘in support’ of the clinical picture. We note that the first two sentences of the Department’s above paragraph imply a degree of certainty regarding the status of blood test results that is not indicated by other official statements nor justified by all the available information.(1)(2)(3) Both patients and doctors need clarity on this issue. Is the Department stating that the current, two-stage laboratory test procedure is 100% reliable in detecting all pathogenic borrelial disease occurring in the UK? (A/2)
Validation of any test for Lyme disease is problematic because there is no sensitive gold standard test against which other tests can be compared. The Infectious Disease Society of America (IDSA) diagnostic guidelines promoted by the HPA(7) define cases of Lyme disease, in part, by positive serology. A test that is part of the definition of an illness cannot be properly validated. Such a test may detect only a small proportion of cases, yet false negative cases would be wrongly discounted as they would fall outside the definition of the illness. The only reasonably certain claim that can be made for the current serology tests is their ability to detect antibodies matching a limited number of reference strains. If validation has been made on this basis then many genuine cases of pathogenic borrelial disease may test falsely negative. As this is a matter of public interest, the validation protocols should be open to public scrutiny. LDA is therefore requesting detailed information on how the current test validation was carried out. Please can you supply us with this data? (A/3)
As Lyme borreliosis occurs only in people who have been bitten by an infected tick, it is important that a patient’s risk of exposure to ticks is properly assessed and the clinical history evaluated for features compatible with Lyme borreliosis before diagnostic tests are requested.
Yes, it is important that a patient’s risk of exposure to ticks is properly assessed. However, LDA feels that aspects of this assessment are not weighted enough in favour of realising that any person can be bitten by a tick anywhere in the UK. HPA provisional figures for 2006 record that tick bites were reported by only 38% of confirmed cases.
In addition to the tests that look for the presence of antibodies to Borrelia burgdorferi, specific immunoblot (Western blot) tests are then performed on all specimens reacting in preliminary tests and the significance of the results carefully assessed in the light of the patient’s clinical and tick exposure history. Detailed interpretive criteria for Western blots differ between Europe and the USA, to take into account differences in the geographic distribution of the infecting genospecies. As you may be aware, different genospecies are known to have different health impacts. This two stage diagnostic test in support of the clinical picture enables the most accurate diagnosis to be made. Reliance upon the clinical picture alone may not be sufficient especially where the initial bite and resultant rash might have been missed by the patient.
The above paragraph states “and the significance of the results carefully assessed in the light of the patient’s clinical and tick exposure history.” Thus, the result of the test for any one patient is a scientist’s assessment and not a clear-cut ‘yes’ or ‘no’ based solely upon the objective results of laboratory procedures.
In the 15th paragraph of your letter of 15/6/07 there is a statement that when the clinical symptoms are obvious and the history of recent tick bite proven these circumstances would result in a diagnosis of Lyme disease (regardless of test status). This is also implied in your above (5th) paragraph. However, in our experience, in these circumstances, this is often not happening owing to complete reliance on the laboratory test.
That the criteria that laboratories use to interpret test results differ between Europe and the USA is illustrative of the complexity of this group of bacteria. Similar variation occurs within Europe also. It is widely accepted that different interpretations of laboratory test results have to be made depending upon global location. However, the stream of recent findings relating to the global distribution of tick-borne diseases and their vectors fuels a need for continual review of the position. Compiling hard and fast interpretive criteria, a process that at least in part relies upon human judgement, will be problematic under such circumstances.
With reference to the above points, assessments and interpretations that have involved human judgement and are not totally objectively based carry an inevitable risk of human error.
Throughout your correspondence you make the assertion that the clinical picture is all that is required to confirm a diagnosis of Lyme disease, and on this point I fundamentally disagree with you. Particularly, when the list of presentations and symptoms that some websites, such as the International Lyme and Associated Diseases Society (ILADS) website, attribute to ‘chronic Lyme disease’ is so non-specific as to lead to misdiagnosis of Lyme disease in patients with many other conditions.
In the words of the former minister, Caroline Flint, or one of her scientific advisors, (paragraph five of your letter of 15/6/07), it is stated “Reliance upon the clinical picture alone may not be sufficient.” This means therefore that, in certain circumstances, the clinical picture alone may be sufficient. A similar statement occurs again in the 15th paragraph of this same letter. Indeed, in the letter we received on 29/3/07,(8) it was stated that in the case of the clinical manifestation of erythema migrans (EM) rash, then the clinical diagnosis could be confirmed and treatment started without delay. These statements contradict the above paragraph (your paragraph 6), thus we shall presume, that the Department is here referring solely to patients who have not had an early episode of EM rash. In these circumstances, it is more difficult for a physician to assess the clinical picture but, regardless of EM status, patients with Lyme disease should not be denied treatment.
The clinical picture alone may be sufficient, or may, along with the patient’s history, be the only evidence available to the treating physician when there is no conclusive laboratory evidence either way. We do not assert that this is a desirable situation, far from it; whilst we acknowledge that improvements have been made, LDA would like to see far more research into diagnostic methods.
At no point have we advocated that patients with symptoms that give rise to a suspicion of Lyme disease should not seek diagnosis by a knowledgeable doctor, supported by testing if that turns out to be conclusive. This is as stated in the Department’s last letter of 29/3/07, paragraph 2, section 2, as an acceptable method of diagnosis. LDA is asking for more doctors to be so trained.
No evidence has been provided that Lyme disease is being over-diagnosed in patients with other conditions. In fact, some peer-reviewed studies appear to indicate the involvement of Borrelia spp in conditions such as Alzheimer’s disease(9) and Multiple Sclerosis.(10)
The symptoms listed by ILADS are essentially the same as those referred to by the IDSA guidelines,(7) so there is little doubt that Lyme disease can cause these symptoms. A multi-symptomatic presentation therefore does indicate that Lyme disease should be considered in differential diagnosis. Each of the many symptoms may be non-specific when considered individually, but this diverse, concurrent symptomatology does contribute to the clinical picture that a physician must take into account in assessing the probability of a Lyme diagnosis.
Related spirochaetal illnesses such as Syphilis also present in a very varied, multi-symptomatic and long-term way.(11) Thus there is a precedent for diverse, non-specific presentations to be spirochaetal in origin. However, a clinician who has gained the experience to discern the commonalities in the presentations of patients will have the expertise to recognise the possibility of a spirochaetal diagnosis.
The treatment for early stage Lyme disease consists of a short course of antibiotics. Oral antibiotics such as doxycycline, amoxycillin or cefuroxime axetil for two to three weeks are recommended for erythema migrans, for three weeks to treat isolated facial palsy, and for four weeks when treating patients with Lyme arthritis. Turning to your question about the criteria for longer term use of antibiotics, although Lyme arthritis is not a common effect of Lyme disease it does justify the longer period of four weeks use of antibiotics.
Prudent use of antibiotics is essential for the wellbeing of patients. The inappropriate use of long courses of antibiotics for patients diagnosed as suffering from Lyme borreliosis by unorthodox and unvalidated tests when there is no objective or validated evidence of infection with Borrelia burgdorferi can have serious consequences for the health of such patients.
The failure to treat possible or probable Lyme disease can also have serious consequences for the health of such patients, if it turns out they genuinely have Lyme disease. Clinicians are accustomed to prescribing on the basis of this balance. Whilst we agree that antibiotics are a resource that should be used very prudently, Lyme Disease Action knows of many cases of people who only recovered from diagnosed Lyme disease or clinically identical illness after having taken antibiotics for longer periods than outlined here by the Department. Often this occurred under the direction of NHS clinicians. Our question remains that the Department needs to find a credible explanation for the cases of unpredicted recovery.(A/4)
It should be noted that other drugs prescribed for this cohort of patients for long-term treatment of individual symptoms also have risks. Patients prescribed steroidal anti-inflammatories, anti-viral drugs or psychoactive drugs, for instance, are put at arguably greater risk than with antibiotics. Why is it that these drugs are given with little question, yet antibiotics are not?(A/5)
Clinicians on both sides of the current controversy agree that short courses of antibiotics, such as described by the Department, can be successful when the disease is recognised early enough. There is, however, another side to the question. All sides acknowledge that there is a cohort of patients who have Lyme but who remain unrecognised.(12) The Department does not address the question of appropriate treatment for those patients in this category who have developed active disease. We continue to ask about the welfare of these patients and what the Department intends to do about the treatment that they need?(A/6) The balance of peer-reviewed research shows that short courses of treatment are frequently ineffective for patients who are not diagnosed with Lyme until later in their disease, leaving no current alternative but longer-term treatment.
There is also the possibility that other diagnoses may be missed through reliance upon inappropriate long term antibiotic use. You say that certain patients have experienced some benefit from such long term use. One possible explanation is that some antibiotics (including doxycycline) have anti-inflammatory benefits as well as anti-microbial effects. Patients who have an inflammatory condition may respond to treatment with doxycycline, but this response is not related to infection, and their condition will worsen when treatment with antibiotics ceases.
This above theory seems to be based in very little peer-reviewed science. We are aware of medical literature that suggests some anti-inflammatory properties in a number of antibiotics. However, the mechanisms that might be involved are not understood and rely on hypothesis. This explanation therefore is an unproven position that would require further specific evidence to be tenable.
If a patient worsens after ceasing antibiotic treatment, the most straightforward explanation would be that the treatment had not succeeded in overcoming a bacterial infection, which then flares up again.
There is a great deal of peer-reviewed literature that shows that Borrelia can survive short courses of antibiotics.(13)
When very great patient benefit ensues from antibiotic treatment it tends to point to the involvement of infection.
I note that you have enclosed an ILADS paper with your letter. Diagnostic guidelines produced by ILADS reject the findings of validated tests performed in accredited laboratories and base their conclusions upon opinion and unsubstantiated hypothesis. The ILADS guidelines themselves have not been subjected to peer review and much of the information they contain in relation to Lyme borreliosis has been shown to be inaccurate.
No evidence has been provided that the ILADS guidelines have been shown to be inaccurate. ILADS is a professional body of doctors and medical researchers. Their guidelines are peer-reviewed and published in a medical journal and reference many other peer-reviewed studies.(14) Recent papers in support of long-term antibiotic treatment such as is recommended by ILADS, in appropriate cases, for treatment of Lyme borreliosis have recently been published in the prestigious, peer-reviewed journals ‘Clinical Infectious Diseases’ and ‘Neurology’. (15)(16) The principles set forth by ILADS correspond with our first-hand experiences as patients and carers and therefore we consider the ILADS position to be justified.
In addition, the Chief Medical Officer has serious concerns about the opinions put forward by ILADS and by some medical practitioners in the UK that Lyme borreliosis is a much underdiagnosed disease that is responsible for chronic fatigue syndrome (CSF/ME).*
This is not a view that has been put forward by Lyme Disease Action except insofar as we have heard the views of patients who have contacted us about this matter. Many of these patients who have improved on antibiotic treatment say that they have received a variety of other diagnoses before being diagnosed with Lyme disease. Amongst the other diagnoses they have received is the illness that you specifically refer to. We do not, and have never attempted to, quantify the extent of any link, and will not do so until clear evidence emerges. Lyme Disease Action is not responsible for the private views expressed by medical practitioners to their patients.
The way in which a minority of practitioners use a range of unorthodox and unvalidated tests to make a diagnosis of chronic Lyme disease, in patients whose accredited and validated laboratory test results are negative for evidence of Borrelia burgdorferi infection by established international criteria, is cause for alarm and has been the subject of a detailed investigation by the Department’s Inspector of Microbiology, Professor Brian Duerden. The report of his findings The use of unorthodox and unvalidated laboratory tests in the diagnosis of Lyme borreliosis and in relation to medically unexplained symptoms has been published on the Department’s website at: www.dh.gov.uk (type ‘lyme’ into the search bar and follow the links).
LDA has already replied to this point in our reply of 10th May 2007. LDA does not promote any particular laboratory test or testing procedure at present because there is evidence that, although they have advanced considerably in the last 10 years, no laboratory test is reliable enough to command total confidence. Lyme Disease Action has never made recommendation of the tests that Professor Duerden has criticised.
You ask whether the Health Protection Agency (HPA) provided clinical advice and expertise to physicians. I can assure you that the HPA does advise clinicians directly in relation to both diagnosis and treatment of Lyme disease. The HPA also has a national network of wider expertise that it can draw on when advising clinicians on patient care. This is a routine function of the HPA and the Lyme disease reference laboratory is frequently consulted by clinicians about patients for whom a diagnosis of Lyme disease is being considered. Such advice is a confidential matter as it relates specifically to individual patients.
We note that the HPA gives clinical advice in relation to both diagnosis and treatment of Lyme disease to clinicians and that this relates specifically to individual patients. Is this clinical advice relating to diagnosis and treatment given to the enquiring clinicians by practising clinicians who have direct experience of dealing with patients with Lyme borreliosis? Does the HPA see the patient when providing additional clinical advice? We would like to receive your assurance that this is always the case. (A/7/i/ii/iii)
With regard to the reporting of Lyme disease and estimates of disease in the UK, laboratory confirmed reports of Lyme borreliosis have risen steadily since reporting began in 1986. Several factors have contributed to the increase, including greater awareness of the disease, greater access to diagnostic facilities, more sensitive diagnostic methods and the introduction of the enhanced surveillance scheme in late 1996. Over 3,000 reports have been received since 1986, almost 2,800 of which have been completed since the introduction of enhanced surveillance in 1997. Mean annual incidence rates for laboratory confirmed cases have risen from 0.06 per 100,000 total population for the period 1986 to 1992, to 0.64 cases per 100,000 total population in 2002, to 1.1 cases per 100,000 total population in 2005.
It is accepted that there is under reporting of Lyme disease, as a clear diagnosis is sometimes possible and appropriate antibiotic treatment given, without the need for laboratory confirmation when clinical symptoms are obvious and the history of recent tick bite proven. Such cases, and those where infection is asymptomatic or results in only mild symptoms that do not require medical attention, are not included within the national figures. Making Lyme disease a ‘notifiable disease’ would not solve this problem of under reporting. Comparisons of incidence of disease in other European countries does not help to estimate possible incidence in the UK, as the distributions of tick and the differences in the species of ticks and the genotypes of Borrelia burgdorferi vary so greatly between countries.
The increase in cases cannot be attributed in any part to the enhanced surveillance as this only gathers additional information on cases already confirmed by testing. Given that recent research has shown dramatic rises in tick numbers, why does the Department not address the possibility that more people are being infected?(A/8) We agree that the true number of cases is higher than the number confirmed by laboratory testing. We do not agree that all the unrecorded cases are either those that are clinically obvious, or that are mild in degree, as we know of many severely ill patients who improve or even recover on Lyme treatment despite negative or equivocal tests. We also know of patients whose EM rash was unrecognised and whose illness remains undiagnosed and untreated. In these circumstances, there will be an unknown but potentially significant number of severely affected people who are not being diagnosed. A more reliable means of assessing the true number of cases is urgently required, whether this is by notifiable status or otherwise. We repeat our previous request for information on how the HPA estimate is derived. As this is a matter of public interest, please will the Department supply this information? (A/9)
That estimates are made of possible disease incidence in the UK and that these estimates relate to incidence of tick species and the presence of Borrelia burgdorferi genotypes can be inferred from the above paragraph. LDA feels the public would be entitled to presume that reasonably frequent, proactive checks are made to try and ascertain whether any new species of ticks or new tick-borne diseases have entered the UK. LDA is aware that the HPA has recently started running a tick collection scheme whereby ticks are collected from all over the country and sent in for identification. Whilst this scheme would, we hope, help to identify any new tick species in the UK, it appears that the ticks are not checked for carriage of pathogens. In addition, there is no guarantee that viable ticks or their eggs are not being imported into the country in some way not predicted and therefore not collected or examined. LDA is concerned that the current arrangements may still prove inadequate both to monitoring known dangers and to the detection of new ones.
The prevalence of the tick Ixodes ricinus is known to be greatest in Scotland. The presence of this tick is an indicator of the presence of other ticks and thus of the greater potential for Borrelia burgdorferi to be present than elsewhere in England and Wales.
We accept that Ixodes ricinus probably represents the major risk of tick bite that may be received by human beings when outdoors. However, both HPS and HPA figures show many more confirmed cases in England and Wales than in Scotland, with numbers tending to increase towards the south of the country.
The Department of Health has given very serious consideration to the issue of Lyme disease, particularly to the issue of diagnosis of Lyme disease. I am satisfied that the NHS has adequate diagnostic capability for Lyme disease, and I wholly reject the suggestion that a broad, non specific set of clinical symptoms should be relied upon for the diagnosis of infections with Borrelia burgdorferi.
LDA has stated that cases of Lyme disease including Erythema migrans manifestations going unrecognised are known to the charity. We cannot therefore see how the Department is satisfied with current NHS diagnostic capability for Lyme disease.
We note the Department’s position of wholly rejecting the suggestion that a broad, non-specific set of clinical symptoms should be relied upon for the diagnosis of infections with Borrelia burgdorferi. As a broad, non-specific set of clinical symptoms has been documented in patients with culture confirmed Borrelia burgdorferi infection,(1) the Department might do well to review this position.
As previously stated, our position is based on sound, peer-reviewed research. Ms. Flint’s advisors appear to create an image of a body of patients who are unwilling to accept the facts. However, the facts of Lyme disease are not fully established yet and there are many outstanding questions amongst medical practitioners themselves. In such circumstances, patients have the right to choose avenues that help them to make clinical progress out of their pain and disability. Current paradigms are still not adequate to explain the realities experienced by patients. Lyme Disease Action advocates that this situation is unsatisfactory and we continue to ask for full and complete answers to our questions. For your convenience, the questions we await answers upon are listed in the Appendix.
Lyme Disease Action
Appendix: Questions asked or restated in this letter of 10/10/07.
1. In our letter to the Department dated 10/5/07, we enquired whether the Department’s definition would include all active, pathogenic, tick-borne, borrelial infection whether caused by the currently known genospecies or by other similar entities? We still need an answer to this question.
(Unknown or less known tick-borne, pathogenic, borrelial genospecies or mixed infections including these entities, occurring in the UK, would in all probability produce near-identical illness manifestations to Lyme borreliosis. Manifestations such as these, in our view, if found to be occurring, should also be termed Lyme disease or Lyme borreliosis since there is no other suitable term at present).
2. Is the Department stating that the current, two-stage laboratory test procedure is 100% reliable in detecting all pathogenic borrelial disease occurring in the UK?
3. LDA is therefore requesting detailed information on how the current test validation was carried out. Please can you supply us with this data?
4. Whilst we agree that antibiotics are a resource that should be used very prudently, Lyme Disease Action knows of many cases of people who only recovered from diagnosed Lyme disease or clinically identical illness after having taken antibiotics for longer periods than outlined here by the Department. Often this occurred under the direction of NHS clinicians. Our question remains that the Department needs to find a credible explanation for the cases of unpredicted recovery, which we feel the anti-inflammatory theory does not adequately explain.
5. Patients prescribed steroidal anti-inflammatories, anti-viral drugs or psychoactive drugs, for instance, are put at arguably greater risk than with antibiotics. Why is it that these drugs are given with little question, yet antibiotics are not?
6. All sides acknowledge that there is a cohort of patients who have Lyme but who remain unrecognised.(12) The Department does not address the question of appropriate treatment for those patients in this category who have developed active disease. We continue to ask about the welfare of these patients and what the Department intends to do about the treatment that they need?
7. We note that the HPA gives clinical advice in relation to both diagnosis and treatment of Lyme disease to clinicians and that this relates specifically to individual patients.
7i. Is this clinical advice relating to diagnosis and treatment given to the enquiring clinicians by practising clinicians who have direct experience of dealing with patients with Lyme borreliosis?
7ii. Does the HPA see the patient when providing additional clinical advice?
7iii. We would like to receive your assurance that this is always the case.
8. Given that recent research has shown dramatic rises in tick numbers, why does the Department not address the possibility that more people are being infected?
9. A more reliable means of assessing the true number of cases (of Lyme disease) is urgently required, whether this is by notifiable status or otherwise. We repeat our previous request for information on how the HPA estimate is derived. As this is a matter of public interest, please will the Department supply this information?
Questions outstanding from our communication of 10th May 2007.
10. We would like to be informed of the advice the HPA gives to physicians regarding the possible causes and levels of false seronegativity and false seropositivity that they should consider when interpreting a serology result in the case of an individual patient. Please can the Department supply this information?
11. We note that Lyme disease is notifiable in Scotland and we are asking why there is considered to be a difference between England/Wales and Scotland over this issue? Ixodes ricinis may be high in Scotland, but absolute case numbers are higher in England and Wales and represent an increasing problem.
12. LDA notes the great genetic complexity of B. burgdorferi genospecies and we question whether it can be certain that all relevant information regarding pathogenicity and pathogenic genospecies within this group of bacteria has been discovered?
13. LDA would find it helpful to understand upon what information or advice the Department’s confidence that “many of the syndromes currently attributed to Lyme disease are not, in fact, due to this infection” is based?
14. We ask what can be learnt from the unpredicted recoveries to improve clinical outcome for all UK patients in the future? (Corollary of 4).
1. Clin Infect Dis. 2006 Sep 15;43(6):704-10. Epub Aug 8.
Comparison of findings for patients with Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid.
Strle F, Ruzic-Sabljic E, Cimperman J, Lotric-Furlan S, Maraspin V.
2. J Med Microbiol. 2000 Oct;49(10):911-5.
False-negative serology in patients with neuroborreliosis and the value of employing of different borrelial strains in serological assays.
3. A non-exhaustive list of abstracts of 84 peer-reviewed papers on Seronegativity in Lyme borreliosis and other spirochaetal infections can be found at the following website:
4. Wien Klin Wochenschr. 2006 Nov;118(21-22):659-68.
Antimicrobial susceptibility of Borrelia burgdorferi sensu lato: what we know, what we don’t know, and what we need to know.
Hunfeld KP, Brade V.
5. Arthritis Rheum. 1993 Nov;36(11):1621-6.
Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis.
Haupl T, Hahn G, Rittig M, Krause A, Schoerner C, Schonherr U, Kalden JR, Burmester GR.
7. (IDSA Guidelines)
Clin Infect Dis. 2006 Nov 1;43(9):1089-134
The clinical assessment, treatment and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America.
Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB.
8. From second paragraph of Department’s letter of 29/3/07: “Most effects of infection are mild and if the GP is confident of a positive diagnosis on the basis of obvious clinical signs then there is no obligation to submit for a laboratory confirmation.”
9. Neuroreport 1993 Jul;4(7):841 – 848.
Alzheimer’s disease – a Spirochetosis?
10. J Neurol. 1987 Jan;234(1):40-3.
Chronic progressive neurological involvement in Borrelia burgdorferi infection
Weder B, Wiedersheim P, Matter L, Steck A, Otto F.
11. “Know syphilis in all its manifestations and relations, and all things clinical will be added unto you.” Sir William Osler, 1897.
John H. Stokes, Modern Clinical Syphilology, 3rd Edition, (Philadelphia: Saunders, 1944).
12. How common is Lyme borreliosis? HPA estimates suggest that between 1000 and 3000 cases occur annually in the UK of which several hundred are laboratory confirmed cases. The HPA suggest an average of 600 confirmed cases in their current information. (768 were actually reported in 2006). http://www.hpa.org.uk/infections/topics_az/zoonoses/lyme_borreliosis/faq.htm
13. Abstracts of 67 peer-reviewed papers on “Relapse/Persistence of Lyme disease despite antibiotic therapy” can be found at the following website: http://www.lymeinfo.net/medical/LDPersist.pdf
14. Expert Rev Anti Infect Ther. 2004;2(1 Suppl):S1-13. Suppl.(2004).
Evidence-based guidelines for the management of Lyme disease.
Cameron D, Gaito A, Harris N, Bach G, Bellovin S, Bock K, Bock S, Burrascano J, Dickey C, Horowitz R, Phillips S, Meer-Scherrer L, Raxlen B, Sherr V, Smith H, Smith P, Stricker R.
International Lyme and Associated Diseases Society working group.
15. Clin Infect Dis. 2007 Jul 15;45(2):149-157.
‘Counterpoint: Long term antibiotic therapy improves persistent symptoms associated with Lyme disease.
16. Neurology October 10, 2007 as doi: 10.1212/01.WNL.0000284604.61160.2d (Epub ahead of print)(Abstract) (PDF)
A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.
Fallon BA, Keilp JG Corbera KM, Petkova E, Britton CB, Dwyer E, Slavov I, Cheng J, Dobkin J, Nelson DR, Sackheim HA.