part of the context is intended to be
very inclusive and reflect the
uncertainties and difficulties around
clinical presentations of Lyme
disease. As such, the sentence you
are referring to is intentionally very
broad. We have chosen not to make
the edit you suggest.
Lyme Disease Action
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7
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145
|
Suggest replace “heart problems” with “carditis”. The symptoms (heart problems) may
include palpitations and heart block, but the basic pathology is inflammation in cardiac
tissue which is Lyme carditis.
|
Thank you for your comment. The
term ‘heart problems’ has been used
because we try to write the scope in
plain English as far as possible. We
feel that the term ‘heart problems’
covers carditis.
|
Lyme Disease Action
|
7
|
146/
147
|
Remove quotes round chronic Lyme disease. Perhaps rephrase that sentence to “There is
uncertainty about the cause of persistent symptoms, hence disagreement amongst experts
and some controversy.
The cause of persistent symptoms after antibiotic treatment is poorly understood. There is
scientific proof of concept for persistence of Borrelia, immune dysfunction/auto-immunity
and
damage to tissues and neural networks. However, current diagnostic tests are not capable
of determining which factor(s) cause chronic illness and symptoms on an individual patient
basis. Current research is aimed at characterising panels of biomarkers that may assist
diagnosis and inform treatment choice.
|
Thank you for your comment. We
have removed the quote marks and
changed ‘controversy’ to ‘uncertainty’
as you suggested.
|
Lyme Disease Action
|
7
|
152
|
The only evidence we can find for Public Health England’s estimate
of 2000-3000 is a poster at the HPA 2007 conference. Given
subsequent, also unpublished, studies it might be more accurate to
simply say "The true incidence of Lyme disease remains unknown
and a large proportion are not diagnosed.”
• An audit at a Scottish GP practice (Aberfeldy) found a rate in
the practice population of 370/100,000 confirmed with a
Tayside reported rate of 17/100,000.
• A recent Norwegian project found a rate of 449/100,000 - 22
times the reported laboratory confirmed rate.
• In the USA when figures from insurance claims were included
with the laboratory confirmed rate, the incidence of Lyme
borreliosis increased x10 from 30,000 to 300,000/year.
|
Thank you for your comment. NICE
guidelines are for the NHS in England
only and so we look for figures that
are directly relevant to this population.
The figures provided by Public Health
England are an estimate only. We
note that the actual number of
infections might be much higher, and
further acknowledge that the true
incidence in England remains
unknown.
|
Lyme Disease Action
|
7
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154
|
This should read “The distribution of laboratory confirmed cases”. Erythema migrans are
confirmed cases, but are not included in the reported figures.
|
Thank you for your comment. We
have made the change as you
suggest.
|
Lyme Disease Action
|
7
|
155
|
“with over 50% diagnosed in…” should read “with 50% of these in..”. We have no data on
the distribution of clinically diagnosed cases.
|
Thank you for your comment. We
have made the change as you
suggest.
|
Lyme Disease Action
|
7
|
157/
8
|
People with outdoor occupations tend to be more informed and thus reduce their risk of
exposure (chainsaw leggings, working boots etc). Add to this sentence “.. as are those who
visit these areas for recreation”.
|
Thank you for your comment. We
have amended the text in the scope
as follows: “People who spend a lot of
time outdoors in these areas for work
or recreational purposes are at
increased risk of tick exposure.
Infection is more likely if the tick
remains attached to the skin for more
than 24 hours”
|
Lyme Disease Action
|
7
|
158
|
Insert “A significant number of people may be infected abroad and this increases the risk of
mixed infection.” The percentage of ticks with co-infections is greater in many countries in
continental Europe and in the USA.
|
Thank you for your comment. The
sentence ‘A number of people may
also have been infected abroad.’ has
now been added.
|
Lyme Disease Action
|
7
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158/
9
|
So that this is not taken to exclude the possibility of infection in a shorter duration of
attachment, this should be re-phrased to “Some tick-borne infections can be passed
immediately on tick attachment, but the risk of Lyme disease increases with duration of
attachment.”
In Europe research seems to suggest that it takes less time for Lyme borreliosis
transmission from the tick compared to American studies. Transmission has been known
to occur in under 12 hours.
|
Thank you for your comment. We
agree that the statement ‘An infection
is more likely if a tick remains
attached for longer periods’ is not
intended to imply that Lyme disease
requires a tick to be attached for more
than 24 hours in order to develop. We
do not feel a change to the scope is
required.
|
Lyme Disease Action
|
7
|
161
|
Note that although Public Health England have issued the suggested referral pathway,
most GPs are unaware it exists. The wording in this section says the patients are treated,
are tested etc, whereas in reality this may or may not happen. Current practice is very
variable and erythema migrans have been diagnosed as cellulitis, ringworm and reaction to
insect bite.
|
Thank you for your comment. The
‘current practice’ section is a standard
section in NICE guideline scopes and
describes current standard practice.
We acknowledge that not all patients
are receiving the same care, a fact
which has been highlighted in the
following paragraphs. This is an
important purpose for this work and
we are keen to ensure that this
guideline, once developed, improves
this situation.
|
Lyme Disease Action
|
8
|
169
|
Suggest rephrase to “… serology may be repeated to shed light on relapse and other
causes are considered”. Serology may show evidence for relapse but it is unclear how
reliable an indicator this is.
|
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 level of uptake
of guidance. We acknowledge the
concerns about repeat serological
testing; however the aim of this
section is to summarise the PHE
guidance and not comment on its
implementation.
|
Lyme Disease Action
|
8
|
170
|
Suggest replace the sentence starting “Neurologists or..” with “Consultants are involved in
patient care in cases of significant neurological, rheumatological, cardiac or ophthalmic
complications”.
|
Thank you for your comment. This
sentence has now been amended to
address your comment.
|
Lyme Disease Action
|
8
|
175
|
Lyme borreliosis is an emerging disease in the UK and so an additional factor of “a
consequence of the bacteria spreading through wildlife and therefore ticks” should be
added. It is important to stress that the incidence of Lyme borreliosis is actually increasing
as ticks expand their geographic spread to new areas and higher altitudes. Key ecological
drivers are considered to be climate change, changes in land management eg.
Fragmentation of forest habitats, resulting changes in biodiversity, changes in the
way humans interact with nature eg outdoor pursuits.
|
Thank you for your comment. The
context of the scope is intended to
provide a short overview of what is
currently known about Lyme disease.
This section mentions that the
incidence of Lyme disease is
increasing for various reasons. Some
additional text has been added to this
section.
|
Lyme Disease Action
|
8
|
180
|
This is misleading. Suggest rephrase to “In 2012 Lyme Disease Action published the top
10 research priorities reached through a process facilitated by the James Lind Alliance.”
http://www.lymediseaseaction.org.uk/what-we-aredoing/research/jla-process/
|
Thank you for your comment. We
have amended the text in the scope.
We have maintained the James Lind
alliance hyperlink to outline the
methods used in the process of this
Priority Setting Partnership.
|
Lyme Disease Action
|
8
|
181
|
Add “transmission” and remove “the long term consequences of the diseases” - this latter
does not feature in the top 10 research priorities.
|
Thank you for your comment.
Interested parties can follow the URL
to see the complete information about
the priorities. We have included
transmission for accuracy. We have
amended the text about long term
consequences to say ‘long term
outcomes’ to reflect priorities 6 and 8.
|
Lyme Disease Action
|
DQ1
|
|
In principle yes, but it should be made clear that these are arbitrary stages and some
people may progress to the manifestations of late-stage disease more quickly.
|
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.
|
Lyme Disease Action
|
DQ2
|
|
In principle, yes, but see comment above.
|
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.
|
Lyme Disease Action
|
DQ3
|
|
No; this is simply a “position paper” and not an appropriate resource for this use. The
clinical manifestation section and Table 1 contain misleading information - eg in that
erythema migrans centres on the bite; that incidence of erythema migrans is 90% (based
on a selected group of highly aware practitioner and public in Germany; a low incidence (5-
8%) of Lyme neuroborreliosis is quoted which is not supported by other European literature
(25%). They also lack detail, for example focusing on the erythemamigrans at the apparent
expense of more serious aspects of Lyme borreliosis and there is only one small
paragraph to cover the whole range of late stage disseminated disease. A more
appropriate resource would be Stanek et al 2011 which includes Opthalmic manifestations
omitted from Table 1 of the
British Infection Association statement. Stanek et al 2011 Clinical case definitions for
diagnosis and management in Europe Clin Microbiol and Infect. EFNS guidelines could be
used for Lyme neuroborreliosis - Mygland et al 2010 EFNS guidelines on the diagnosis
and management of European Lyme neuroborreliosis. Eur J Neurol.
|
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.
|
Lyme Disease Action
|
DQ4
|
|
Note that these are not strains, they are genospecies. In the review other known, though
possibly rare, human pathogenic genospecies B spielmanii and B bavariensis should be
included. Antigens from
these are included in the immunoblot used in Scotland. See also comment on Q5 re
immunoblot antigens.
The review should also include Borrelia miyamotoi. Although this is more nearly related to
the relapsing fever group of Borrelia, it is present in UK ticks and causes a similar clinical
presentation.
|
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.
Thank you for your response and
|
Lyme Disease Action
|
DQ5
|
|
The appropriate diagnostic tests for consideration: Serology, Polymerase Chain Reaction
(PCR), cerebrospinal fluid studies (microscopy for cells, with assay of protein level, IgM
and IgG Borrelia immunoblot, Antibody index, CXCL13, PCR), tissue biopsy (standard
pathology plus PCR), magnetic resonance imaging (MRI) brain and spinal cord (possibly
enhanced), single-photon emission
computed tomography (SPECT) scan, cognitive neuropsychology, autonomic function
tests, nerve conduction studies (which are usually normal), sural nerve biopsy (small fibre
damage). Also
cardiac MRI, electrocardiogram (ECG) and 24 hour ECG (Lyme carditis).Specific
consideration should be given to which immunoblots are suitable for detecting infections
due to the Borrelia genospecies present in UK ticks and also whether reference
laboratories should use a different immunoblot if infection is likely to have occurred outside
the UK.
Consideration should be given to tests that are not currently used in the UK, but which are
under investigation for their potential. This includes culture, tests of T cell response to
infection with Lyme
Borreliosis, urine antigen assays and metabolomics.
|
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.
|
|
|
|
|
|
|
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Lyme Disease UK
|
2
|
50
|
Co-infections in Lyme disease patients appear to be common and should always be
considered as part of the clinical picture, particularly in immunocompromised patients.
‘Ticks transmit more pathogens than any other arthropod, and one single species can
transmit a large variety of bacteria and parasites’ (Moutallier et al, 2016).
This study states, ‘in the past, reports of pathology due to Babesia, Anaplasma, Ehrlichia,
and Bartonella species have focused on the fulminant acute forms of infection that are
relatively easy to diagnose and often fatal in immunocompromised patients. More recently,
these organisms have been associated with chronic persistent infection in animal models
and humans. The presence of coinfecting organisms has been shown to enhance the
symptoms and exacerbate the severity of Lyme disease. Thus recognition of chronic
coinfections supports the concept of unresolved illness due to persistent infection with the
Lyme spirochete’ (Stricker and Johnson, 2011).
In a patient survey conducted by the charity Caudwell LymeCo, preliminary results show
that over 30% Lyme disease patients who participated also appear to have Babesia and
over 15% have Bartonella henselae.
According to another survey done by Lyme Research UK in 2011, co-infections were also
common in patients with Lyme disease. Out of 189 people diagnosed with Lyme
borreliosis, 19 were diagnosed with Bartonella henselae, 7 with Bartonella quintana, 15
with Erhlichia, 8 with Mycoplasma and 15 with Babesia (based specifically on positive tests
with clinical assessment). Over 50% of this main group were not tested for each of these
co-infections and therefore the possibility of even higher infection rates, is considerable.
The scope should consider the evidence relating to co-infections, as they could be a
potential cause of comorbidity or complex conditions, rendering poorer treatment outcomes
for Lyme disease patients. Considering and testing for other potential tick-borne infections
should be included in the Lyme disease guidelines, particularly when there are indications
of more varied or persistent symptoms or when standard Lyme disease treatment has
failed.
Even if the management of other tick-borne infections is not included in the guidelines,
there should be some reference to the possible complications they may cause in Lyme
disease patients so that healthcare workers and the public are at least aware of their
existence.
The patient experience appears to be that co-infections do not normally form part of the
NHS diagnostic process, even if Lyme disease is detected, however, the ILADS guidelines
state that ‘the possibility of co-infections should not be casually dismissed’ (Cameron et al,
2014).
References:
1: Moutailler S, Valiente Moro C, Vaumourin E, Michelet L, Tran FH, Devillers E, et al.
(2016) Co-infection of Ticks: The Rule Rather Than the Exception. PLoS Negl Trop Dis
10(3): e0004539. doi:10.1371/journal.pntd.0004539
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004539
2. Stricker, R.B, Johnson, L. Lyme disease: the next decade. Infect Drug Resist. 2011; 4:
1–9. doi: 10.2147/IDR.S15653
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108755/
3. Caudwell LymeCo patient survey, 2016
http://lymediseaseuk.com/2016/03/21/caudwell-lymeco-surveys-results-sneak-peek/
4. Lyme Research UK patient survey, 2011 (unpublished)
5. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline
recommendations in Lyme disease: the clinical management of known tick bites, erythema
migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014 Sep;12(9):1103-
35. doi: 10.1586/14787210.2014.940900
http://www.tandfonline.com/doi/full/10.1586/14787210.2014.940900
|
Thank you for your comment and the
references you have provided. The
focus of this guideline is the diagnosis
and management of Lyme Disease.
We will bring your comments on the
issue of co-infection to the guideline
committee’s attention to ensure that
this issue is appropriately addressed
as part of our evidence reviews or in
our sections where we link the
consideration of the evidence to the
recommendations made as
appropriate. We will not however
address the specific management of
any co-infection and as such have
made no change to the scope.
|
Lyme Disease UK
|
2
|
51
|
Lyme disease can mimic many other conditions, including chronic fatigue syndrome (CFS).
Why is CFS being singled out in this draft scope as a managed condition when there is no
100% accurate serological test for either Lyme disease or CFS and therefore the two
cannot be easily separated? If the two are separated, this may lead to CFS patients being
unable to have their diagnosis reconsidered even if they might have Lyme disease.
Furthermore, the way in which CFS is managed could potentially be harmful to an
undiagnosed Lyme disease patient.
Even if the risk of Lyme disease is properly investigated before diagnosing CFS (which
does not always appear to be happening based on shared patient experience),
weaknesses of current tests mean that some might nevertheless, actually have Lyme
disease. Additionally, CFS patients who do not have Lyme disease may be at extra risk if
they do happen to catch the disease because of the similarity in symptoms and the
possibility that the infection may be dismissed as an 'exacerbation of existing CFS'.
Discriminating against CFS patients who, if anything, may have a greater need to be
further investigated for Lyme disease, could put these patients at risk.
Preliminary results from a patient survey conducted by VIRAS show that out of 44
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