indicated 45% of infected ticks were co-infected with up to 5 pathogens (Moutailler et al,
2016). This has many implications including increased difficulty in diagnosis and
complications related to treatment. Whilst the guidelines relate to Lyme borreliosis they
should mention the confounding implications of co-infection.
Thank you for your comment. While
people with co-infections will not be
excluded from the evidence reviews,
the focus of this guideline is the
diagnosis and management of Lyme
disease and the specific management
of any co-infection will not be
addressed. However, the guideline
committee will give mention to any
groups who require special
consideration when linking evidence
to recommendations.
|
Lyme Research UK
|
gener
al
|
gene
ral
|
Special patient groups:
We think that the NICE guideline should include a section on special patient groups,
including people who are immunocompromised, those who are more at risk of
complications (e.g. the elderly and people with comorbid conditions), and pregnant women.
|
Thank you for your comment. As
outlined in the equality impact
assessment for this guideline, the
guideline committee will review the
evidence about diagnostic test
accuracy and management strategies
in pregnant women and
immunocompromised people. It is
anticipated that these populations will
form sub-groups in each of our
evidence reviews to ensure that,
where evidence exists on these
issues, the committee are able to
make evidence-based
recommendations to the NHS. These
subgroups have been included in the
equality impact assessment for this
guideline.
|
Lyme Research UK
|
gener
al
|
gene
ral
|
Intravenous antibiotic treatment:
We are very concerned that there are Lyme borreliosis patients who need but are not
getting intravenous ceftriaxone or cefotaxime once the disease has progressed to later
stages. They may not be getting this treatment because a diagnosis of their
neuroborreliosis has not been made.
Before treating Lyme borreliosis patients with intravenous antibiotics, a positive diagnosis
of neuroborreliosis is necessary. The British Infection Association Position Statement
(2011) says that serology testing for Lyme neuroborreliosis should include intrathecal
specific antibodies and specific cerebrospinal fluid/serum antibody index. The guidelines
from the European Federation of Neurological Societies guidelines (Mygland et al, 2010)
state that antibody tests for cerebrospinal fluid “are useful” in the diagnosis of Lyme
neuroborreliosis, but they do not state that a positive result is essential. Unfortunately, the
sensitivity of the current tests of cerebrospinal fluid is relatively low.
Djukic et al (2012) reported that, of 118 patients with acute neuroborreliosis, intrathecal
immunoglobulin synthesis was found in the Reiber nomograms for IgM in 70.2% and for
IgG in 19.5% of patients. Isoelectric focussing detected an intrathecal IgG synthesis in
70.3%. Elevation of the Borrelia burgdorferi antibody index in the cerebrospinal fluid was
found in 82.2%. The sensitivity was particularly low in patients with a meningitis course
(44.4% to 61.1%).
Therefore many patients with Lyme neuroborreliosis who need intravenous antibiotics may
not receive a positive diagnosis because the laboratory test is inadequate. We think that,
until better diagnostic tools are available, the criteria for intravenous treatment should be
relaxed and not require evidence of antibodies in the cerebrospinal fluid.
|
Thank you for your comment. The
Guideline Committee will carefully
consider the evidence when making
recommendations on management
strategies including the role of
intravenous antibiotics.
|
Lyme Research UK
|
gener
al
|
gene
ral
|
Guideline scope:
We would like to see NICE address uncertainty in existing knowledge (where relevant),
and recommend what kind of research is needed to improve patient outcomes
(Parliamentary Office of Science and Technology, 2004).
|
Thank you for your comment. The
Guideline Committee will make
research recommendations (if
appropriate) at a later stage of the
guideline development once the
evidence reviews have been
conducted and important gaps have
been identified.
|
Lyme Research UK
|
gener
al
|
gene
ral
|
Lyme borreliosis:
We think the term 'Lyme borreliosis' should be used rather than 'Lyme disease' to be
consistent with the rest of Europe.
|
Thank you for your comment. We
have decided to use the term Lyme
disease as it is a widely accepted term
which we feel is more accessible to
non-healthcare professionals than
Lyme borreliosis. In addition it directly
reflects the commission received from
NHS England.
|
Lyme Research UK
|
gener
al
|
gene
ral
|
REFERENCES CITED ABOVE:
Aucott JN, Seifter A, Rebman AW (2012). Probable late lyme disease: a variant
manifestation of untreated Borrelia burgdorferi infection. BMC Infect Dis 2012;12(1):173
Bettridge J, Renard M, Brown KJ, et al (2013). Distribution of Borrelia burgdorferi sensu
lato in Ixodes ricinus populations across central Britain. Vector Borne and Zoonotic
Diseases13(3):139–146
Bouquet J, Soloski MJ, Swei A et al (2016). Longitudinal transcriptome analysis reveals a
sustained differential gene expression signature in patients treated for acute Lyme
disease. mBio 7(1): e00100-16
British Infection Association (2011). The epidemiology, prevention, investigation and
treatment of Lyme borreliosis in United Kingdom patients: A position statement by the
British Infection Association. Journal of Infection 62:329-338
Cairns V, Godwin J (2005). Post-Lyme borreliosis syndrome: a meta-analysis of reported
symptoms. Int J Epidemiol 34:1340-1345
Centers for Disease Control and Prevention in the United States (2016a). Transmission.
http://www.cdc.gov/lyme/transmission/index.html
Centers for Disease Control and Prevention in the United States (2016b). Post-treatment
Lyme disease syndrome. http://www.cdc.gov/lyme/postlds/
Centers for Disease Control and Prevention in the United States (2016c). How many
people get Lyme disease?
http://www.cdc.gov/lyme/stats/humancases.html
Chandra A, Wormser GP, Klempner MS, et al (2010). Anti-neural antibody reactivity in
patients with a history of Lyme borreliosis and persistent symptoms. Brain, Behavior and
Immunity 24(6):1018-1024
Cook MJ (2015) Lyme borreliosis: a review of data on transmission time after tick
attachment. Int J Gen Med 2015:8 1–8
Couper D, Margos G, Kurtenbach K, et al (2010). Prevalence of Borrelia infection in ticks
from wildlife in south-west England. The Veterinary Record 167:1012-4
Djukic M, Schmidt-Samoa C, Lange P et al (2012). Cerebrospinal fluid findings in adults
with acute Lyme neuroborreliosis. J Neurol 259(4):630-636
Djukic M, Schmidt-Samoa C, Nau R et al (2011). The diagnostic spectrum in patients with
suspected chronic Lyme neuroborreliosis--the experience from one year of a university
hospital’s Lyme neuroborreliosis outpatients clinic. Eur J Neurol 18(4):547-55
Durovska J, Bazovska S, Ondrisova M et al (2010). Our experience with examination of
antibodies against antigens of Borrelia burgdorferi in patients with suspected Lyme
disease. Bratisl Lek Listy111(3):153-5
Elsner RA, Hastey CJ, Olsen KJ et al (2015). Suppression of long-lived humoral immunity
following Borrelia burgdorferi infection. PLOS Pathog 11(7):e1004976
Fallon BA, Keilp J, Prohovnik I et al (2003). Regional blood flow and cognitive deficits in
chronic Lyme disease. J Neuropsychiatry Clin Neurosci 15(3):326-32
Faulde MK, Rutenfranz M, Hepke J et al (2014). Human tick infestation pattern, tick-bite
rate, and associated Borrelia burgdorferi s.l. infection risk during occupational tick
exposure at the Seedorf military training area, northwestern Germany. Ticks Tick Borne
Dis 5(5):594-9
Horowitz R (2016). Horowitz Lyme-MSIDS Questionnaire.
http://lymeontario.com/wp-content/uploads/2015/03/Horowitz-Questionnaire.pdf
Kurtenbach K, De Michelis S, Sewell HS, et al (2001). Distinct combinations of Borrelia
burgdorferi sensu lato genospecies found in individual questing ticks from Europe. Applied
and Environmental Microbiology 67(10):4926-4929
Lakos A, Solymosi N (2010). Maternal Lyme borreliosis and pregnancy outcome. Int J
Infect Dis 14(6): e494 – e498
Leeflang MMG, Ang CW, Berghout J et al (2016). The diagnostic accuracy of serological
tests for Lyme borreliosis in Europe: a systematic review and meta-analysis. BMC Infect
Dis 16:140
Lindgren E, Jaenson TGT (2006). WHO Report. Lyme borreliosis in Europe: influences of
climate and climate change, epidemiology, ecology and adaptation measures.
http://www.euro.who.int/__data/assets/pdf_file/0006/96819/E89522.pdf
MacDonald AB, Benach JL, Burgdorfer W. (1987). Stillbirth following maternal Lyme
disease, N Y State J Med 87(11):615-6
Maheshwari P, Eslick GD (2015). Bacterial infection and Alzheimer's disease: a meta-
analysis. J Alzheimers Dis 43(3):957-66
Middelveen MJ, Burke J, Sapi E et al (2015). Culture and identification of Borrelia
spirochetes in human vaginal and seminal secretions [version 3; referees: 1 approved, 2
not approved]. F1000Research 2015, 3:309
Moutailler S, Valiente Moro C, Vaumourin E et al (2016). Co-infection of ticks: the rule
rather than the exception. PLoS Negl Trop Dis10(3):e0004539
Mueller I, Freitag MH, Poggensee G, et al (2012). Evaluating Frequency, Diagnostic
Quality, and Cost of Lyme Borreliosis Testing in Germany: A Retrospective Model
Analysis. Clinical and Developmental Immunology 2012, Article ID 595427, Epub.
Mygland A, Ljostad U, Fingerle V, et al (2010). EFNS on the diagnosis and management of
European Lyme neuroborreliosis. Eur J Neurology 17:8-16
Pancewicz SA, Garlicki AM, Moniuszko-Malinowska A et al (2015). Diagnosis and
treatment of tick-borne diseases. Recommendations of the Polish Society of Epidemiology
and Infectious Diseases. Przegl Epidemiol 69:309-316)
Parliamentary Office of Science and Technology (2004). Handling uncertainty in scientific
advice. Postnote June 2004, Number 220.
http://www.parliament.uk/documents/post/postpn220.pdf
Preac-Mursic, Weber K, Pfister HW et al (1989). Survival of Borrelia burgdorferi in
antibiotically treated patients with Lyme borreliosis. Infection 17(6):355-359
Schlesinger PA, Duray PH, Burke BA et al (1985). Maternal-fetal transmission of the Lyme
disease spirochete, Borrelia burgdorferi. Annals of Internal Medicine 103(1):67-68
Stanek G, Reiter M (2011). The expanding Lyme Borrelia complex-clinical significance of
genomic species? Clin Microbiol Infect 17:487-93
Stricker RB, Middelveen MJ (2015). Sexual transmission of Lyme disease: challenging the
tickborne disease paradigm. Expert Rev Anti Infect Ther 13(11):1303-6
Strle F, Nelson JA, Ruzic-Sabljic E, et al (1996). European Lyme borreliosis: 231 culture-
confirmed cases involving patients with erythema migrans. Clin Infect Dis 23(1):61 – 65
Strle F, Ruzić-Sabljić E, Cimperman J (2006). Comparison of findings for patients with
Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid. Clin Infect Dis
43(6):704-10
Thorp AM, Tonnetti L (2006). Distribution and survival of Borrelia miyamotoi in human
blood components. Transfusion 56(3):705-11
Trevejo RT1, Krause PJ, Sikand VK et al (1999). Evaluation of two-test serodiagnostic
method for early Lyme disease in clinical practice. J Infect Dis 179(4):931-8
Tylewska-Wierzbanovska S, Chmielewski T (2002). Limitation of serological testing for
Lyme borreliosis: evaluation of ELISA and western blot in comparison with PCR and
culture methods. Wien Klin Wochenschr 114(113-14):601-5
Venclíková K, Betasova L, Sikutova S et al (2014). Human pathogenic borreliae in Ixodes
ricinus ticks in natural and urban ecosystem (Czech Republic). Acta Parasitol 59(4):717-20
ViraMed Laboratory Diagnostics (2016). Borrelia ViraStripe® IgG, IgM Test Kit.
http://www.viramed.de/en/bacteria/borrelia-species/borrelia-virastripe
Wang G, Liverus D, Mukherjee P et al (2014). Molecular Typing of Borrelia burgdorferi.
Weber K, Bratzke, HJ, Neubert U et al (1988). Borrelia burgdorferi in a newborn despite
oral penicillin for Lyme borreliosis during pregnancy. Pediatr Infect Dis J 7(4):286–289
Wormser GP, Dattwyler RJ, Shapiro EG, et al (2006). The clinical assessment, treatment
and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis:
Clinical practice guidelines by the Infectious Diseases Society of America. Clinical
Infectious Diseases 43:1089-1134
|
Thank you for your comment and the
helpful list of references provided.
|
|
|
NHS England
|
|
|
Thank you for the opportunity to comment on the above Clinical Guideline. I wish to
confirm that NHS England has no substantive comments to make regarding this
consultation.
|
Thank you for your comment.
|
NHS England
|
|
|
Thank you for the opportunity to comment on the above Clinical Guideline. I wish to
confirm that NHS England has no substantive comments to make regarding this
consultation.
|
Thank you for your comment.
|
NHS Highland
|
3
|
67 to
82
|
The key to ensuring that the NICE recommendations are clinically useful is to have clear
and relevant clinical case definitions at each stage. European clinical case definitions
(Stanek, G) are narrow including no category for a flu like illness, and stringent laboratory
confirmation for neuroborreliosis (requiring lumber puncture). In my opinion these are too
narrow.
Suggest NICE guidance divides patients into clinically defined presentations, and makes
testing and management recommendations for each presentation (presentation categories
that should be included given below). I appreciate that ‘Flu like’ is not an ideal label and
care should be taken defining the symptoms that would qualify for this presentation.
1/ Tick exposure, no symptoms
2/ Seropositive, no symptoms
3/ Chronic tick exposure non-specific chronic symptoms (fatigue, arthralgia, parasthesia)
4/ ECM, atypical rash
5/ Flu like presentation without respiratory component
6/Symptoms consistent with early neuroborreliosis including radiculitis, meningitis, cranial neuropathy and mononeuritis multiplex
7/Symptoms consistent with late neuroborreliosis including encephalomyelitis, encephalopathy, cerebral vasculitis (could be called late neuroborreliosis) *IDSA includes peripheral neuropathy in late neuroborreliosis, while European guidelines state peripheral neuropathy without achrodermatitis chronicum atrophicans is vanishingly rare – this needs to be addressed as peripheral neuropathy very common in the elderly and in endemic regions many of these people will be seropositive. Geography of exposure may influence recommendation.
8/Arthritis
9/Carditis
10/Lymphocytoma
11/Achrodermatitis chronicum atrophicans
12/Ocular manifestations
|
Thank you for your comment on the
issue of the classification of Lyme
disease as described in the
consultation version of the scope. We
now propose to present the guideline
committee with the stakeholder
feedback on this issue to allow them
to determine the best approach for the
guideline to take. As such, we have
removed the detail linked to the
definitions of Lyme disease from the
final scope.
|
NHS Highland
|
3
|
69
|
Suggest delete ‘to confirm or rule out Lyme disease’.
|
Thank you for your comment. This has
now been amended to ‘Diagnostic
testing for Lyme disease’.
|
NHS Highland
|
3
|
71
|
Role of CSF tests in diagnosis of lyme neuroborreliosis. When are they indicated and how
interpreted (my current practice is usually not to perform LP in borrelia seropositive
radiculopathy or cranial nerve palsy in absence of meningitis)
|
Thank you for your comment. The
Guideline Committee will consider
relevant diagnostic tests and
procedures in the context of differing
clinical presentations when defining
the review questions and protocols.
We will ensure that they are informed
of your comment.
|
NHS Highland
|
3
|
77
|
Delete ‘or without’ as not disease if asymptomatic
|
Thank you for your comment. We had
intended for ‘without symptoms or
signs’ to refer to the absence of either
clinical signs or symptoms, and not
the absence of both. For example a
person could have a clinical sign
(something than can be easily
measured by someone else, e.g. a
rash) but no symptoms (something
that cannot be easily measured by
someone else, e.g. feeling unwell or a
headache) or vice versa. This was to
reflect the issue around the difficulty of
diagnosing or ruling out Lyme disease
using clinical signs only. However, we
now propose to present the guideline
committee with the stakeholder
feedback on the issue of clinical
scenarios and presentations to allow
them to determine the best approach
for the guideline to take. As such, we
have removed the detail linked to the
definitions of different clinical
scenarios and presentations.
|
NHS Highland
|
3
|
83
|
Management recommendations could be further targeted by dividing patients into
Possible/probable/definite Lyme disease depending on strength of clinical presentation and
test results.
I appreciate that this adds complexity, but until lab diagnostics improve we will be
operating in an area of diagnostic uncertainty and these labels make that explicit and allow
physician and patient to appreciate the balance of risks between overtreatment and under-
treatment. These distinctions become most helpful when discussing pros / cons of repeat
courses of antibiotics where first line therapy has failed to improve symptoms
|
Thank you for your comment. Whilst
we do not feel that any changes to the
scope are required in this area, we will
bring the detail of your comment to the
committee’s attention when they draft
their protocol for this question
|
NHS Highland
|
3
|
83
|
Management may also include referral to specialist (eg rheumatologist). Guidance on
which presentations of suspected arthritis with positive Lyme serology should be referred
would be useful.
|
Thank you for your comment. We
acknowledge that where
complications of Lyme disease occur
referral for specialist NHS opinion may
be desirable if the evidence supports
this. Management strategies including
specialist referral in different clinical
scenarios/presentations will be
explored in more detail by the
Guideline Committee through the
evidence reviews.
|
NHS Highland
|
4
|
88
|
As for comment no. 4
|
Thank you for your comment.
We had intended for ‘without
symptoms or signs’ to refer to the
absence of either clinical signs or
symptoms, and not the absence of
both. For example a person could
have a clinical sign (something than
can be easily measured by someone
else, e.g. a rash) but no symptoms
(something that cannot be easily
measured by someone else, e.g.
feeling unwell or a headache) or vice
versa. This is to reflect the issue
around the difficulty of diagnosing or
ruling out Lyme disease using clinical
signs only.
|
NHS Highland
|
4
|
90 to
96
|
These are important questions. Suggest may be helpful to divide symptoms into objective
and subjective (indicated in some papers)
|
Thank you for your comment. We will
ensure that this information is brought
to the guideline committee’s attention
when they are developing the review
questions and protocols.
|
NHS Highland
|
4
|
Figu
re
|
Cannot have Lyme disease without symptoms and signs (mentioned in both boxes of
figure)
|
Thank you for your comment.
We had intended for ‘without
symptoms or signs’ to refer to the
absence of either clinical signs or
symptoms, and not the absence of
both. For example a person could
have a clinical sign (something than
can be easily measured by someone
else, e.g. a rash) but no symptoms
(something that cannot be easily
measured by someone else, e.g.
feeling unwell or a headache) or vice
versa. This is to reflect the issue
around the difficulty of diagnosing or
ruling out Lyme disease using clinical
signs only.
|
NHS Highland
|
6
|
134
|
You state ‘Lyme disease can be asymptomatic’. I disagree. Infection with Borrelia
burgdorferi can be asymptomatic, but I would reserve the term ‘Lyme disease’ for
symptomatic infection.
|
Thank you for your comment. We
have amended the text in the scope to
distinguish between asymptomatic
infection and Lyme disease as a
symptomatic infection.
|
NHS Highland
|
7
|
141
|
Delete ‘frequently’ and replace with ‘can be’ and ‘resolves’ with ‘may resolve’.
|
Thank you for your comment.
The wording of the scope has been
altered.
|
NHS Highland
|
8
|
170
|
Repeat testing to assess for relapse is recommended by PHE but is controversial as
antibody levels persist even when patient cured and therefore ongoing positive test not
helpful. May be helpful in looking for re-infection in the re-exposed with new symptoms as
different blot bands may be present. Suggest unhelpful to state that blood test can
diagnose relapse.
|
Thank you for your comment. The
‘current practice’ section is a standard
section in NICE guideline scopes and
aims to describe current standard
practice (in this case the PHE
guidance) rather than critiquing the
guidance. We acknowledge the
concerns about repeat serological
testing; however the aim of this
section is to summarise the PHE
guidance.
|
NHS Highland
|
DQ1&
2
|
|
Relating to guideline committee’s Q1 and 2 above.
Distinction between early and late is only of importance if different management strategies
are recommended on the basis of this distinction. Many patients have ongoing exposure
and fluctuating symptoms making use of these timelines impractical. The time periods are
arbitrary and cannot be definitive due to various factors (eg host factors, infectious dose,
strain). Six month timeline is mentioned in literature and may be reasonable but the
arbitrary nature of it must be stated.
|
Thank you for your response and
detailed comments on our questions.
We will bring the detail of your
response to the Guideline
Committee's attention. The
information will be used to inform the
Committee's decision making as they
develop the review protocols that
guide the searches for and review of
the evidence for the questions
outlined in the guideline scope.
|
NHS Highland
|
DQ3
|
|
Relating to guideline committee’s Q 3 above.
(Use of BIA position paper to determine range of presentations).
I would also like NICE to consider patients with ongoing tick exposure and :
1) Flu like illness as mentioned in comment no.1.
2) Fatigue and arthralgia
3) Peripheral neuropathy or mononeuritis multiplex
4) Objective memory loss but without tetraspastic syndrome, spastic-ataxic gait
disorder and disturbed micturition
I think these presentations should be included in the guidance as many people with these
symptoms present for testing, and a proportion are seropositive. The committee may
conclude that these presentations should not lead to testing, and if inadvertently tested,
should not be treated for possible Lyme disease, even if seropositive. Guidance on this
would be very useful.
|
Thank you for your response and
detailed comments on our questions.
We will bring the detail of your
response to the Guideline
Committee's attention. The
information will be used to inform the
Committee's decision making as they
develop the review protocols that
guide the searches for and review of
the evidence for the questions
outlined in the guideline scope.
|
NHS Highland
|
DQ4
|
|
Relating to guideline committee’s Q 4 above. Borrelia spielmanii, Borrelia bavariensis,
Borrelia bissettii, Borrelia lusitaniae, Borrelia kutchenbachii and Borrelia valaisiana also
have pathogenic potential (see Borchers A, journal autoimmunity for useful table). Review
of evidence to assess relevance to diagnostics of some of these may be worthwhile.
|
Thank you for your response and
detailed comments on our questions.
We will bring the detail of your
response to the Guideline
Committee's attention. The
information will be used to inform the
Committee's decision making as they
develop the review protocols that
guide the searches for and review of
the evidence for the questions
outlined in the guideline scope.
|
NHS Highland
|
DQ4
|
|
Relating to guideline committee’s Q4 above.
Diagnostic test should include tests and testing strategies. All tests should be included:
EIA, IF, Immunoblot, western blot, CSF/serum parallel testing by EIA/Blotting, lymphocyte
transformation test, PCR and culture (joint fluids, skin biopsy, CSF, urine), direct
microscopy and non-specific tests such as CXCL13, CD57+, CSF biochemistry and
cytology. The committee may find many of these tests lack standardisation, sensitivity and
specificity but it is still useful to have them assessed.
|
Thank you for your response and
detailed comments on our questions.
We will bring the detail of your
response to the Guideline
Committee's attention. The
information will be used to inform the
Committee's decision making as they
develop the review protocols that
guide the searches for and review of
the evidence for the questions
outlined in the guideline scope.
|
Royal College of Genera Practitioner s (RCGP)
|
2
|
43
|
The RCGP hopes that the medications recommended in the guideline are those that
a) Experts recommend (even if not licensed). If the guideline recommends a
medication that is contrary to expert opinion then that severely will undermine the
entire guideline.
b) Are (where clinically appropriate) medications that are familiar to GPs- most of
these patients will present to primary care. If these are medications that generally
speaking GPs won’t feel confident with then it will mean more referral to secondary
care with the delay and cost that that entails. (MJ)
c)
|
Thank you for your comment. The
Guideline Committee will consider
which medications should be included
in the evidence review. As stated in
the scope, recommendations are
generally only made within their
licensed indications unless there is
strong evidence for an unlicensed
indication. The Guideline Committee
will also consider any potential issues
around prescribing (such as the lack
of familiarity in prescribing that you
outline) in various settings when
formulating recommendations.
|
Royal College of Genera Practitioner s (RCGP)
|
2
|
51
|
There is clearly a link being made between chronic fatigue syndrome and Lyme disease by
the support groups for suffers of chronic fatigue. Some GPs have seen a few patients who
are desperate to pursue a diagnosis of Lyme disease to explain their fatigue symptoms.
The RCGP feels that it would be invaluable if this guideline helped to differentiate on
clinical grounds those fatigue suffers who need further investigation and those that we can
reassure without recourse to blood tests, investigations and/or referrals. (MJ)
|
Thank you for your comment. This
guideline only covers Lyme disease.
We acknowledge that the clinical
presentations of Lyme disease and
chronic fatigue syndrome (CFS) can
be very similar and that it can be
difficult to make a definitive diagnosis
of one or the other. Following
systematic review of the evidence
available in the scope areas of
assessment diagnosis and
management, the Guideline
Committee will make
recommendations in regards to Lyme
disease and may wish to cross-refer
to other guidelines if appropriate. The
reference to the CFS / myalgic
encephalomyelitis (or
encephalopathy) NICE guideline
(CG53) is included as an example of
another available NICE guideline and
will not be covered by this Lyme
disease guideline.
|
Royal College of Genera Practitioner s (RCGP)
|
6
|
147
(que
stion
2)
|
What is the role of epitope mapping of antibodies to VlsE protein of Borrelia burgdorferi in
post-Lyme disease syndrome. (MH)
|
Thank you for your response and
detailed comments on our questions.
We will bring the detail of your
response to the Guideline
Committee's attention. Where
relevant the information will be used to
inform the Committee's decision
making as they develop the review
protocols that guide the searches for
and review of the evidence for the
questions outlined in the guideline
scope.
|
Royal College of Genera Practitioner s (RCGP)
|
Gener
al
|
Gen
eral
|
The draft scope is an excellent working document and covers the essential areas and
difficulties. (PS) and points 1-5 in the first page all seem reasonable. (MJ)
|
Thank you for your comment.
|
Royal College of Genera Practitioner s (RCGP)
|
Gener
al
|
Gen
eral
|
Overall there seems to be an increasing awareness amongst the population of this
condition and yet a great deal of uncertainty amongst non-specialist clinicians as to how to
diagnose and treat.
Therefore the RCGP feels that this guideline is much needed.
The scope seems appropriate and focussed. (MJ)
|
Thank you for your comment.
|
|
Royal College of Nursing
|
|
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This is just to inform you that the feedback I have received from nurses working in this area
of health suggests that there are no comments to submit on behalf of the Royal College of
Nursing to inform on the consultation of the draft scope of Lyme Disease.
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Thank you for your comment.
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Royal College of Nursing
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This is just to inform you that the feedback I have received from nurses working in this area
of health suggests that there are no comments to submit on behalf of the Royal College of
Nursing to inform on the consultation of the draft scope of Lyme Disease.
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Thank you for your comment.
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Royal College of Paediatrics and Child Health
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Thank you for inviting the Royal College of Paediatrics and Child Health to comment on the
Lyme Disease draft scope. We have not received any responses for this consultation.
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Thank you for your comment.
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The British Society for Antimicrobi al chemothera py (BSAC)
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Members of The British Society for Antimicrobial Chemotherapy (BSAC) have no
comments for this Guideline on Lyme disease.
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Thank you for your comment.
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VIRAS Vector- borne Infection, Research – Analysis - Strategy
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DQ1&
2
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VIRAS response to NICE request for comments on 6 month ‘phase’
(including observations on why this might have been suggested):
“1) Is the time period of ‘< than 6 months since tick bite or first symptoms or signs’ an
acceptable interpretation for ‘early Lyme borreliosis’?
2) Is the time period of ‘> 6 months since tick bite or first symptoms or signs’ or an
acceptable interpretation for ‘late Lyme borreliosis’?”
Pertains to Draft Scope document Page 3. Lines 74 to 77
Abbreviations
CFS, Chronic Fatigue Syndrome
GDG Guideline Development Group
HPA, Health Protection Agency (now part of PHE)
IDSA, Infectious Disease Society of America
ILADS, International Lyme and Associated Diseases Society
LB, Lyme Borreliosis
NHS, UK National Health Service
PHE, Public Health England
M.E., Myalgic Encephalomyelitis
NICE, National Institute for Health and Care Excellence
An arbitrary time limit deemed to be a transformation point from one Lyme borreliosis
phase to another has no medical or scientific logic.
Miklossy (2012) states in The Open Neurology Journal:
“Late Lyme neuroborreliosis is accepted by all existing guidelines in Europe, US and
Canada. The terms chronic and late are synonymous and both define tertiary neurosyphilis
or tertiary Lyme neuroborreliosis. The use of chronic and late Lyme neuroborreliosis as
different entities is inaccurate and can be confusing. Further pathological investigations
and the detection of spirochetes in infected tissues and body fluids are strongly needed.”
In Lyme borreliosis, the time between infection (or re-infection) and the appearance of
symptoms/signs which a patient or physician might associate with LB is highly variable and
could be months or years. The U.S. Library of Medicine, MedlinePlus (2015) states:
“Symptoms of early disseminated Lyme disease (stage 2) may occur weeks to months
after the tick bite, and may include …”
“Symptoms of late disseminated Lyme disease (stage 3) can occur months or years after
the infection. The most common symptoms are muscle and joint pain…”
Clearly the stages of LB infection do not conform to a predetermined timescale. Different
stages depend upon variables impossible to compute and more rationally deduced by
careful evaluation of each individual patient’s symptoms and laboratory tests, if indeed a
physician considers determination of a ‘stage’ or ‘phase’ to be a worthwhile exercise.
What purpose is served by attempting to define the progression of a disease by a fixed
time period and how would it help doctors in making their clinical decisions?
It seems unlikely that re-labelling patients at 6 months is considered a useful way to
suggest the best tests for a patient’s infection. According to Public Health England (2014),
the weaknesses they acknowledge for their tests relate to cross reactivity with other
infections and “antibody tests in the first few weeks of infection may be negative”. These
problems would not be improved by a 6 month deadline.
Once a patient has been diagnosed and treated, further standard NHS two-tier testing is
rendered useless because as West (2014) states: “Both IgM and especially IgG antibodies
can remain positive for years after successful therapy with antibiotics.” So the
determination of treatment success or failure by standard testing would not be helped by a
6 month time limit.
There are no tests for LB at any stage which can reliably exclude infection or confirm that
treatment or time has eradicated an infection. If such a test (or combination of tests)
existed, it is certain that PHE, the CDC, the IDSA and others would have used the test in
support of their opinion that persistent infection does not occur beyond what they claim is
‘adequate’ treatment. In contrast, the scientists and doctors of ILADS (2012) who declare
that persistent LB infection does occur, provide a list of 700 peer-reviewed scientific papers
indicating persistence, in ‘Peer Reviewed Evidence of Persistence of Lyme Disease
Spirochete Borrelia burgdorferi and Tick-Borne Diseases’.
Furthermore, treatment considerations are guided by disease manifestations and
sometimes supported by laboratory test results. E.g., neuroborreliosis is a diagnosis of the
spread of LB spirochaetes to the central nervous system (CNS). It is suspected by
symptoms, supported by examination and testing of cerebrospinal fluid (CSF) and treated
by intravenous antibiotics. Neuroborreliosis can occur at any time in infected individuals
because it relates to the spread of the infection. If the bacteria’s 6 month ‘VISA’ runs out,
that would not prevent it crossing the barrier into the CNS.
Therefore determining the choice of tests or treatment cannot be the motive for trying to
determine the phase of a patient’s infection according to a calendar.
A 6 month phase could not apply to an infant born infected or an infant with an immature
immune system that becomes infected. How would 6 months apply to a child which is
quite simply, a much smaller mammal than an adult human? Would the transformation
from ‘early’ to ‘late’ infection happen at the same time in a person initially infected with a
few spirochaetes compared to someone infected via multiple heavily infected tick bites
which also transmitted ehrlichia and bartonella? In some regions, 10% to 20% of healthy
blood donors are seropositive for Lyme antibodies. If they become ill in the future, will that
be ‘early’ or ‘late’ Lyme? (Mygland, Skarpaas and Ljøstad, 2006; Hjetland et al 2014)
Dr Willy Burgdorfer, who discovered the borrelia burgdorferi spirochaete in 1982, stated
(Under Our Skin, 2007): “I am a believer in persistent infections because people suffering
with Lyme disease, ten or fifteen or twenty years later, get sick [again]. Because it appears
that this organism has the ability to be sequestered in tissues and [it] is possible that it
could reappear, bringing back the clinical manifestations it caused in the first place.”
When asked about the similarities between Borrelia burgdorferi and syphilis, Dr. Burgdorfer
stated: “The similarities that I know of are associated with the infection of the brain, the
nervous system. The syphilis spirochete, Treponema pallidum has an affinity for nerve
tissues. The Borrelia burgdorferi spirochete very likely has that too. Children are especially
sensitive to Borrelia burgdorferi. The Lyme disease spirochete is far more virulent than
syphilis.” (Under Our Skin, 2007).
Since early and late stages for Lyme borreliosis reflect similarities with syphilis, they must
recognise that stages are determined by the spread and manifestation of the infection and
not by a calendar. NHS Choices, (2014) remarks on Syphilis:
Primary syphilis: “The initial symptoms of syphilis can appear any time from 10 days to
three months after you have been exposed to the infection.”
Secondary syphilis: “The symptoms of secondary syphilis will begin a few weeks after the
disappearance of the sore.”
Latent phase: “The latent stage can continue for many years (even decades) after you first
become infected.”
Tertiary syphilis: “The symptoms of tertiary syphilis can begin years or even decades after
initial infection.”
Specifying a 6 month or other arbitrary time-point between phases is so illogical, that one
could be excused for questioning the motives behind even contemplating such a notion.
Perhaps it is a coincidence that the CDC/Fukuda (1994) criteria for a diagnosis of Chronic
Fatigue Syndrome requires 6 months of symptoms with fatigue criteria (which is common
in LB). There is evidence which suggests that Public Health England intend that chronic
LB patients should be re-diagnosed as having CFS or some other contrived ‘syndrome’,
e.g., ‘chronic arthropod neuropathy syndrome’. The HPA (now part of PHE) informed the
Health and Safety Executive (2012) of their plans:
“RIPL and HPA staff will discuss with Simon Wesseley’s [sic] group and other interested
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