Stakehold

participants, 16 people with Lyme disease have also been diagnosed with M.E.

The 2011 BIA position statement acknowledges that Lyme disease symptoms can overlap

with other conditions - ‘late neurological sequelae of undertreated infection include a

chronic encephalomyelitis, which can present with clinical features resembling multiple

sclerosis.’

ILADS guidelines state, ‘in addition to the possible presence of co-infections, many other

illnesses and conditions have clinical features which may overlap with those of Lyme

disease; some examples are: infections due to Epstein–Barr virus or syphilis; autoimmune

diseases such as rheumatoid arthritis, multiple sclerosis and vasculitis; metabolic and

endocrine disorders such as diabetes, hypo- or hyperthyroidism and adrenal dysfunction;

degenerative neurologic diseases such as Parkinson’s disease and amyotrophic lateral

sclerosis and neurologic conditions such as peripheral neuropathy and dysautonomia;

musculoskeletal diseases including fibromyalgia and osteoarthritis, psychiatric disorders,

especially depression and anxiety and other conditions such as chronic fatigue syndrome

and sleep apnea’ (Cameron et al, 2014).

Singling out CFS as an area that will not be covered may affect the literature review in

terms of excluding investigations into the possibility that some CFS patients may have

Lyme disease.

A recent patient survey by Caudwell LymeCo involving around 500 patients revealed that

over 34% of patients who have a Lyme disease diagnosis obtained privately have only

been given a CFS diagnosis by the NHS.

References

1. VIRAS patient survey 2016 http://counsellingme.com/VIRAS/IsabelSymptomCheckerSurvey.PDF

2. British Infection Association. The epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients: A position statement by the British Infection Association. J Infect. 2011 May;62(5):329-38. doi: 10.1016/j.jinf.2011.03.006. http://www.aldf.com/pdf/BIA%202011statement%20on%20Lyme%20disease.pdf

3. 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-doi: 10.1586/14787210.2014.940900 http://www.tandfonline.com/doi/full/10.1586/14787210.2014.940900

4. Caudwell LymeCo patient survey, 2016

http://lymediseaseuk.com/2016/03/21/caudwell-lymeco-surveys-results-sneak-peek/

Thank you for your comment. The remit of this guideline is the diagnosis and management of Lyme disease. We recognise that some people may have both Lyme disease and chronic fatigue syndrome (CFS) or other diagnoses and as such any evidence found in these groups will be considered by this guideline if it relates to the specific management of their Lyme Disease. The management of CFS is covered by another NICE guideline: www.nice.org.uk/CG53.
Lyme Disease UK	3	54	Transmission of the disease between people should not be excluded from the scope when there are so many important issues in this area. The CDC states, in this fact sheet that, ‘untreated, Lyme disease can be dangerous to your unborn child.’ The scope should include points relating to the following questions: Can Lyme disease be transmitted via blood transfusions or organ donations? Can Lyme disease be transmitted sexually or via breast milk? Furthermore, is it ethical for people not to know how infectious they are, in particular women planning pregnancy? There is no definitive test that can prove that Lyme disease has been eradicated and yet there are many studies that show that Lyme disease can be a chronic, persistent infection. There is a great deal of uncertainty in the patient community in terms of how safe it is to become pregnant or to have unprotected sex. Transmission via other biting insects and vectors such as horse-flies and mosquitoes should also be explored in the interests of public health and safety. There have been a number of new research publications in these areas since the BIA position statement published in 2011 and therefore a review of the evidence would be highly beneficial both in terms of educating the medical profession and the public. References: 1. Centers for Disease Control and Prevention Fact Sheet http://www.cdc.gov/lyme/resources/toolkit/factsheets/10_508_Lyme%20disease_Pregnant Woman_FACTSheet.pdf 2. List of 700 Articles Citing Chronic Infection Associated with Tick-Borne Disease Compiled By Dr Robert Bransfield http://www.ilads.org/ilads_news/2015/list-of-700-articles- citing-chronic-infection-associated-with-tick-borne-disease-compiled-by-dr-robert- bransfield/ 3. British Infection Association. The epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients: A position statement by the British Infection Association. J Infect. 2011 May;62(5):329-38. doi: 10.1016/j.jinf.2011.03.006. http://www.aldf.com/pdf/BIA%202011statement%20on%20Lyme%20disease.pdf	Thank you for your comment. We have discussed your comment in detail and reviewed the decision to exclude other ways of transmission. Person-to-person transmission is now included as a key question in the scope and the points you raise will be discussed by the Guideline Committee who will decide the final review question and protocol.
Lyme Disease UK	3	55	Prevention should be included in the key areas that will be covered, including the issue of whether prophylactic treatment following a known tick bite is helpful in certain cases, especially as the BIA position statement, published 2011, mentions that antimicrobial prophylaxis ‘may be used in immunocompromised individuals following a tick bite.’ The ILADS guidelines recommend that ‘clinicians should promptly offer antibiotic prophylaxis for known Ixodes tick bites in which there is evidence of tick feeding, regardless of the degree of tick engorgement or the infection rate in the local tick population’ (Cameron et al, 2014). It would be worth doing a literature review on the effectiveness of prophylaxis treatment and the economic costs and savings associated. People with Lyme disease, may present without a rash (or known tick bite) and without prior basic knowledge of their risk of tick exposure. If a doctor asks them if they have been exposed to ticks and they are not even aware of their own risk (i.e. that ticks have been found in urban parks and gardens and not just geographical hotspots around the country), they may state that the chance of tick exposure is low. This could result in the patient not being tested for Lyme disease. Prevention, in terms of patient knowledge, is therefore not entirely distinct from diagnostic pathways. Education about risks and knowledge of protection should be made available to healthcare workers and the public to reduce people’s chances of contracting Lyme disease. Leaflets and notices educating people about the disease should be visible in clinics and distributed widely in communities. According to this study, ‘encouraging a thorough check for ticks and promptly removal of ticks are the key public health strategies to reduce the risk of LB and other tick-borne diseases’ (Dehnert et al, 2012). The ILADS guidelines recommend that when patients have been diagnosed with Lyme disease, ‘during the initial visit, clinicians should educate patients regarding the prevention of future tick bites’ (Cameron et al, 2014). References: 1. British Infection Association. The epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients: A position statement by the British Infection Association. J Infect. 2011 May;62(5):329-38. doi: 10.1016/j.jinf.2011.03.006. http://www.aldf.com/pdf/BIA%202011statement%20on%20Lyme%20disease.pdf 2. 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 3. Dehnert M, Fingerle V, Klier C, Talaska T, Schlaud M, Krause G, et al. (2012) Seropositivity of Lyme Borreliosis and Associated Risk Factors: A Population-Based Study in Children and Adolescents in Germany (KiGGS). PLoS ONE 7(8): e41321. doi:10.1371/journal.pone.0041321 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0041321	Thank you for your comment. While we understand the importance of public awareness, this is a clinical guideline on the diagnosis and management of Lyme disease and it would therefore not be appropriate to review evidence on prevention. Preventing Lyme disease as outlined in the scope refers to the prevention of tick bites and prevention of Lyme disease in the absence of a tick bite. The role of prophylactic treatment with antibiotics after a tick bite will be considered. We believe that the evidence considered and the recommendations made as part of this guideline could be used to develop resources by relevant groups to inform healthcare workers but this is not the remit of this committee. We will be reviewing the evidence around the information needs of people with suspected or confirmed Lyme disease.
Lyme Disease UK	3	69	It is important to note that the presentation of Lyme disease can vary significantly in terms of symptoms and clinical signs. Therefore, Lyme disease testing should be routinely included as part of the differential diagnostic process for any nonspecific symptoms which could have an infectious cause and for which another cause has not been found. However, there also needs to be awareness amongst medical professionals that there is currently no 100% accurate test available for the disease and so it cannot be ruled out based purely on serology unless a more accurate test is brought to market in the UK. Doctors need to be made aware of the shortcomings of current testing methods so that they can accurately inform patients and consider making a clinical diagnosis if applicable.	Thank you for your comment. This guideline will cover the question of which symptoms or clinical signs should lead to diagnostic testing for Lyme disease. We would like to draw your attention to a NICE guideline on symptoms with unknown causes that has not yet been commissioned, which may cover differential diagnostic processes for conditions with unknown causes. While the guideline is not listed on the NICE website yet, we would advise that you register as a stakeholder for this guideline development process and submit your comments as part of its scoping processes in due course.
Lyme Disease UK References:	3	70	The question of how doctors can make an accurate clinical diagnosis of Lyme disease should be included in the scope as well as an exploration into how often this actually occurs in reality, especially in the absence of a 100% reliable test. Are doctors really comfortable making a clinical diagnosis of Lyme disease, particularly in the absence of an EM rash? This study states ‘modern medical practice expects to rely on evidence. Most physicians would not consider diagnosing Lyme disease without serological proof' (Perronne, 2014) and this appears to reflect the general patient experience. If an EM rash is present, are doctors sufficiently aware that it is diagnostic of Lyme disease without the need for serology? Patient experience would suggest that GPs often misdiagnose EM rashes. Should effects and signs of damage consistent with Lyme disease be included as part of the clinical picture? Patients who have received a clinical diagnosis of Lyme disease from qualified medical professionals either in the UK or abroad (often with accompanying positive overseas test results) are also having the diagnosis of Lyme disease frequently dismissed. As a result, they are being denied treatment in this country. Simply running the arguably flawed UK two-tiered testing should not be used as a way to override a clinical diagnosis of Lyme disease obtained privately from a qualified doctor or positive overseas test results. UK doctors should also be allowed to use their own clinical judgement when assessing patients with signs and symptoms of Lyme disease, especially if they have a private clinical diagnosis and/or a positive test result from an overseas laboratory. According to the ILADS panel, ‘guidelines should not constrain the treating clinician from exercising clinical judgment in the absence of strong and compelling evidence to the contrary’ (Cameron et al, 2014). The result of the confusion surrounding diagnosis is that many Lyme disease patients are not treated at all. Preliminary results from a patient survey conducted by Caudwell LymeCo reveal that 52% of the participating Lyme disease patients were prescribed no antibiotics whatsoever on the NHS for this condition. 1. 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 2. Caudwell LymeCo patient co-infection survey, 2016 http://lymediseaseuk.com/2016/03/21/caudwell-lymeco-surveys-results-sneak-peek/	Thank you for your comment. The assessment and diagnosis of Lyme disease are covered by the key areas of “assessment (history and examination)” and “diagnosis (first-line investigations and confirmatory tests)”. A review of performance in clinical practice is outside of the remit of NICE guidelines. However, we would hope that this guideline will provide health care professionals with evidence based recommendations to support them in making a diagnosis of Lyme Disease in the context of practice in England. NICE guidelines provide recommendations to clinical practice but they do not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of each patient, in consultation with the patient (or if appropriate their family or carer).
Lyme Disease UK	3	71- 82	References: 1. 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/ 2. British Infection Association. The epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients: A position statement by the British Infection Association. J Infect. 2011 May;62(5):329-38. doi: 10.1016/j.jinf.2011.03.006. http://www.aldf.com/pdf/BIA%202011statement%20on%20Lyme%20disease.pdf 3. Burrascano, Advanced Topics in Lyme Disease: Diagnostics Hints and Treatment Guidelines for Lyme and other Tick Borne Illnesses, Sixteenth Edition, October, 2008. http://www.ilads.org/lyme/B_guidelines_12_17_08.pdf 4. Horowitz, R. The Horowitz Lyme - MSIDS Questionnaire http://www.cangetbetter.com/symptom-list 5. Perronne C (2014) Lyme and associated tick-borne diseases: global challenges in the context of a public health threat. Front. Cell. Infect. Microbiol. 4:74. doi: 10.3389/fcimb.2014.00074 http://journal.frontiersin.org/article/10.3389/fcimb.2014.00074/full 6. Caudwell LymeCo patient survey, 2016 http://lymediseaseuk.com/2016/03/21/caudwell-lymeco-surveys-results-sneak-peek/	Thank you for your comment and the references provided. The review protocols for each review question will inform the specific search strategy for that question. We will hold the references you provide for cross checking.
Lyme Disease UK	3	74- 78	The 2011 BIA position statement mentions that ‘some patients with previously untreated infection can develop features of late-stage disease, months or years later.’ This disease cannot be easily divided into two 6 month phases as proposed in the draft scope and it isn’t useful to do this, especially if people are unaware of when they were bitten or if their symptoms have a delayed onset. At present, there is no 100% accurate serological test to define any of these phases of the illness. A new, more precise list of patient categories and clinical scenarios needs to be composed by the committee and used to form the basis of evidence reviews. Possible terms include; Acute Lyme disease - recently infected, seronegative due to lack of antibody production (usually less than 6 weeks). Secondary/2nd stage Lyme disease - seropositive unless treated in acute stage with antibiotics. Disseminated infection but no lasting damage if treated adequately. Tertiary/3rd stage Lyme disease - disseminated infection with permanent damage or complications. Latent Lyme disease - seropositive but no current symptoms (as demonstrated by studies showing that a percentage of forestry workers have antibodies to Borrelia whilst being asymptomatic). It is unknown whether these people will go on to become symptomatic following stress on their immune system of any kind. Refractory Lyme disease - standard treatment given but symptoms persist. With clearly defined terminology which covers a wide range of scenarios, suitable evidence reviews can take place. Terms like ‘chronic Lyme disease’ and even ‘early’ and ‘late’ Lyme disease cannot be properly defined in medical contexts and are open to interpretation which leads to overall confusion both for physicians and patients. . References: 1. British Infection Association. The epidemiology, prevention, investigation and treatment