LDA position statement on Department of Health Standard Letter

Letter from Ivan Lewis MP, Under Secretary of State at the Department of Health, dated 20th June 2006, but almost identical to other letters received by those enquiring about Lyme Disease. (Available in )

“I would like to assure [the letter writer] that the Government takes the incidence of Lyme disease very seriously. It is accepted by the Department of Health and the Health Protection Agency (HPA) that Lyme disease is the most common vector-borne human infection in England and Wales. For this reason, we have had in place a surveillance system to detect Lyme disease across England and Wales since 1986. This surveillance was expanded in 1996 and has been very successful in providing us with a more complete clinical picture as well as increasing our knowledge of the spread of this disease across the UK.

[The letter writer] may be interested to know that there are highly sensitive tests that can be used for the detection of Lyme Disease and these tests are available and accessible to the whole of the NHS. These tests will detect even low levels of antibodies that are present in the blood of patients that have been exposed to infection with Borrelia burgdorferi (B.burgdorferi), the causative agent of Lyme Disease. These test will identify whether somebody has been infected, even if they are not showing any signs or symptoms of the disease.

Interestingly, in people who have certain conditions such as glandular fever, rheumatoid arthritis and other autoimmune conditions, these sensitive tests will also show a positive result (false positive) even if the person has not been infected with B. burgdorferi. In these cases, where there is no history of exposure to ticks/tick bites, further supplementary tests are done to confirm or discount B. burgdorferi infection. Thus, it is more likely that Lyme disease will be flagged up in those with underlying conditions than it is that the condition would be missed. That is, false positive results are more likely than false negative results.

There are a number of unorthodox tests promoted by laboratories and clinicians in Europe and North America. The Lyme urinary antigen test (LUAT), which purports to detect B. burgdorferi antigens in urine from patients with suspected Lyme borreliosis is very unreliable, with a high incidence of false positive results. A rapid culture method (RIBb) uses special medium and fluorescent microscopy to identify B. burgdorferi in blood. This special medium on which the test is based has been assessed by the American National Institutes for Health, which showed that it was not useful and could not support the growth of B. burgdorferi.

It is known that Lyme disease can lead to other conditions and complications: neuroborreliosis is the most common; Lyme arthritis is rare in UK acquired infection; Post-Lyme syndrome, which resembles chronic fatigue syndrome, or fibromyalgia also occurs in a small proportion of patients. However, these same symptoms can be triggered by other infections and non-infectious conditions.

I should also add that there is no vaccine available for Lyme disease. A vaccine was available in the USA but was withdrawn in 2002; it was unlikely to have been effective against European borrelial species, and currently treatment is with antibiotics.”

Each paragraph of the Department of Health standard letter to enquiries on Lyme Disease is presented below, with the LDA response following in bold. (Available in )

“I would like to assure [the letter writer] that the Government takes the incidence of Lyme disease very seriously. It is accepted by the Department of Health and the Health Protection Agency (HPA) that Lyme disease is the most common vector-borne human infection in England and Wales. For this reason, we have had in place a surveillance system to detect Lyme disease across England and Wales since 1986. This surveillance was expanded in 1996 and has been very successful in providing us with a more complete clinical picture as well as increasing our knowledge of the spread of this disease across the UK.”

The claim of “very successful” expanded surveillance cannot be verified. The surveillance system consisted of sending questionnaires to doctors treating cases already confirmed by testing. As the disease is not notifiable in England and Wales there can be no way of knowing the number of clinically diagnosed cases, let alone any that have been misdiagnosed as other conditions.

“[The letter writer] may be interested to know that there are highly sensitive tests that can be used for the detection of Lyme Disease and these tests are available and accessible to the whole of the NHS. These tests will detect even low levels of antibodies that are present in the blood of patients that have been exposed to infection with Borrelia burgdorferi (B.burgdorferi), the causative agent of Lyme Disease. These test will identify whether somebody has been infected, even if they are not showing any signs or symptoms of the disease.”

Testing is certainly useful, but the confidence in its performance is misplaced. The two stage serology test as defined by the US Centre for Disease Control (CDC) et al has been widely criticised as being too strict [1], and many patients with a strong clinical case, or positive testing by other methods such as PCR, test negative by this method [2][3].

There are at least three species of Borrelia currently known to cause disease in the UK, usually referred to collectively as Borrelia burgdorferi s.l. (sensu lato, “in the broad sense”). Within each species there are many strains with considerable genetic variation[4]. The current test looks for antibodies that match a limited number of laboratory-cultured strains and may, therefore, be insensitive to the majority of antibodies. B. burgdorferi s.l. is difficult to culture in the laboratory and it has been reported that cultured forms show changes in their plasmids and surface proteins which could further reduce the sensitivity of the test to wild strains[5].

It is widely accepted that short duration or low dose antibiotic treatment before a test may abrogate a normal immune response and prevent the formation of antibodies[6]. Many sufferers may have had short courses of antibiotics before being tested for Lyme Disease, and are, therefore, more likely to falsely test negative. B. burgdorferi s.l. are by far the most genetically complex bacteria known[7], and they have evolved to avoid detection by the immune system.

“Interestingly, in people who have certain conditions such as glandular fever, rheumatoid arthritis and other autoimmune conditions, these sensitive tests will also show a positive result (false positive) even if the person has not been infected with B. burgdorferi. In these cases, where there is no history of exposure to ticks/tick bites, further supplementary tests are done to confirm or discount B. burgdorferi infection. Thus, it is more likely that Lyme disease will be flagged up in those with underlying conditions than it is that the condition would be missed. That is, false positive results are more likely than false negative results.”

In practice, people with the other conditions mentioned would generally have other tests done before Lyme would be considered, so these conditions would be picked up or eliminated first. It is likely that most sufferers are never tested at all, and many only have tests after years of misdiagnosis. It is also possible that many of the 'false positives' attributed to other conditions are really genuine positives. Given the wide range of known symptoms it would be easy to misdiagnose Lyme as a viral or autoimmune condition.

Ixodes ricinus ticks are very small and the bites are usually painless. They will, therefore, go unnoticed by many who are bitten. To use the history of tick bites and exposure to ticks to rule out Lyme disease is unacceptable.

It is illogical to warn only of the dangers of false positives. Any test may have false positives and false negatives. In the case of Lyme Disease the risk from a false positive is giving unnecessary treatment. Serious complications associated with antibiotic treatment are rare and the more common but less serious complications can be minimised if basic precautions are taken. A false negative leading to a refusal of treatment can potentially lead to lifelong disability with extremely unpleasant and unpredictable illness. A false negative, therefore, risks a far worse outcome than a false positive.

“There are a number of unorthodox tests promoted by laboratories and clinicians in Europe and North America. The Lyme urinary antigen test (LUAT), which purports to detect B. burgdorferi antigens in urine from patients with suspected Lyme borreliosis is very unreliable, with a high incidence of false positive results. A rapid culture method (RIBb) uses special medium and fluorescent microscopy to identify B. burgdorferi in blood. This special medium on which the test is based has been assessed by the American National Institutes for Health, which showed that it was not useful and could not support the growth of B. burgdorferi.”

The very reason alternative tests are being developed is the unreliability of conventional tests. There is no completely reliable test for the presence of B. burgdorferi s.l. against which different testing methods can be compared, therefore assessment of the reliability of any test is open to question. Sensitivity and specificity vary amongst all types of test, so test results should only be used by trained Lyme clinicians to support the clinical diagnosis, not to supplant it. This highlights the need for research into improving testing methods.

“It is known that Lyme disease can lead to other conditions and complications: neuroborreliosis is the most common; Lyme arthritis is rare in UK acquired infection; Post-Lyme syndrome, which resembles chronic fatigue syndrome, or fibromyalgia also occurs in a small proportion of patients. However, these same symptoms can be triggered by other infections and non-infectious conditions.”

Neuroborreliosis and Lyme arthritis are not 'other conditions'. They are all directly caused by infection with B. burgdorferi s.l., and are subsets of the same condition[8].

There is no direct evidence for the existence of Post Lyme Syndrome, yet it is presented as fact. This notion is based on the assumption that a short course of antibiotics will remove the infection, so any ongoing symptoms must be a separate aseptic condition with an assumed autoimmune or psychological cause. This is illogical. The overwhelming balance of evidence shows that B. burgdorferi s.l. can survive even after months of antibiotic treatment[9][10][11]. With any other condition, if a patient is treated, but continues to have the original symptoms, you would conclude that the treatment was ineffective. Why not with Lyme?

“I should also add that there is no vaccine available for Lyme disease. A vaccine was available in the USA but was withdrawn in 2002; it was unlikely to have been effective against European borrelial species, and currently treatment is with antibiotics.”

This paragraph is not disputed. The US vaccine was withdrawn due to concerns that it caused many cases of illness, possibly due to reactivation of latent infection.

References

1. (a) Aguero-Rosenfeld, ME, Nowakowski, J, McKenna, DF, Carbonaro, CA, and GP Wormser. "Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans." Journal of Clinical Microbiology 34 (1996): 1-9

2. “Seronegativity in Lyme borreliosis and Other Spirochetal Infections” Abstracts of 84 peer-reviewed papers on B. burgdorferi s.l. testing can be found at http://www.lymeinfo.net/medical/LDSeronegativity.pdf

3. R Lange, S Seyyedi “Evidence of a Lyme borreliosis infection from the viewpoint of laboratory medicine.” Int J Med Microbiol, 2002

4. http://www.pasteur.fr/recherche/borrelia/Bb_strains_alphabetic.html

5. Changes in infectivity and plasmid profile of the Lyme disease spirochete, Borrelia burgdorferi, as a result of in vitro cultivation”

6. Dattwyler RJ, Volkman DJ, Luft BJ et al. “Seronegative Lyme disease: dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi” . N Engl J Med 1988;319:1441-6.

7. Steven E Phillips, Nick S Harris, Richard Horowitz, Lorraine Johnson, Raphael B Stricker, “ Lyme disease: scratching the surface” The Lancet Vol 366 November 19, 2005

8. International Lyme and Associated Diseases Society, “Evidence based guidelines for the management of Lyme Disease” Expert Rev. Anti-infect.Ther. 2(1), Suppl.(2004)

9. “Relapse/Persistence of Lyme Disease Despite Antibiotic Therapy” Abstracts of 67 peer-reviewed papers on this topic can be found at http://www.lymeinfo.net/medical/LDPersist.pdf

10. Hunfeld KP, Brade V. “Antimicrobial susceptibility of Borrelia burgdorferi sensu lato: what we know, what we don't know, and what we need to know.” Wien Klin Wochenschr. 2006 Nov;118(21-22):659-68.

11. Hunfeld KP et al “Risk of culture-confirmed borrelial persistence in patients treated for erythema migrans and possible mechanisms of resistance.” Int J Med Microbiol. 2006 May;296 Suppl 40:233-41*

*This paper is flawed in its use of a poor quality reference to support the existence of Post Lyme Syndrome, but acknowledges that Bb can survive short courses of antibiotics.