Stakehold

7

156	It is important to include the fact that ticks can be found in a variety of environments including urban parks (Jennett et al, 2013). Anecdotal evidence in the patient community also demonstrates that people have been bitten in urban gardens. References: 1. Jennett, AL, Smith, FD & Wall, R, 2013, ‘Tick infestation risk for dogs in a peri-urban park’. Parasites and Vectors, vol 6. http://www.bristol.ac.uk/biology/people/richard-l-wall/pub/32548259	Thank you for your comment. We do not consider that the text in the scope needs changing because it does not specify urban or rural environments.
Lyme Disease UK	7	163- 164	Anecdotal evidence from patients suggests that many doctors fail to recognise the EM rash. Many people with EM rash appear to be diagnosed with cellulitis, a bite allergy or ringworm instead and therefore the window for early treatment is frequently missed. This study highlights this issue by stating ‘this lesion may go unrecognized, or be mistaken for an “insect bite” or an “allergic rash.” Mini-erythema migrans are less likely to be diagnosed’ (Perronne, 2014). References: 1. 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	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 rash recognition; however the aim of this section is to summarise the PHE guidance and not comment on its implementation. We have added text about lack of recognition of rash to section 3.1
Lyme Disease UK	8	169	When there is currently no test available to distinguish past infection from ongoing infection or new infection, the evidence and tests that the term ‘relapse’ is based on, should be reviewed. Additionally, anecdotal evidence exists to suggest that patients who still have a positive test following ‘standard’ treatment for Lyme disease are told it is likely to be a false positive, even when clinical signs would suggest an ongoing infection.	Thank you for your comment. Testing will be addressed by an evidence review (as outlined in section 1.5). The review question and protocol will be developed by the guideline committee, based on the scope.
Lyme Disease UK	Gener al	Gen eral	Lyme Disease UK is a patient support network with nearly 4000 members and bears witness daily to thousands of patients who are suffering on an inhumane scale. Many have been ridiculed by medical professionals in various disciplines, dismissed, belittled, neglected and left with increasingly frightening and painful symptoms for which no help or guidance is offered. Many people have lost their jobs, their homes, their life savings and their relationships and are now living in isolation and poverty. Others are left with no other option but to fundraise or in order to seek private Lyme disease and co-infection treatment (often overseas) or fund it themselves in an attempt to reverse the decline in their health and save their lives. The NHS guidance currently in use is failing these patients. The general overview is that EM rashes are frequently being ignored by GPs and that people aren’t being asked about potential tick exposure. Furthermore, it often appears that people are not being offered Lyme disease testing despite presenting with numerous symptoms consistent with the disease. Some people even report hostility from doctors if they request a test and many are told that Lyme disease is either very rare or that it does not exist in this country and that they should not be researching the disease online. There have been accounts of patients, who were previously told that their Lyme disease tests were negative, discovering that they were in fact positive when they requested a copy of the laboratory report, sometimes months or years later. It also appears that people are all too readily being turned away or misdiagnosed with CFS, fibromyalgia and mental health issues without tick-borne infections even being considered. As Cameron et al point out in the ILADS guidelines, a survey involving Lyme disease patients, conducted by Johnson et al, reveals that ‘71.6% rated their health as fair or poor. This rate is higher than that seen in other chronic diseases including congestive heart failure, fibromyalgia, post- stroke and post-myocardial infarction status, diabetes and multiple sclerosis’. It is important to note from shared patient experience that many people who have sought ongoing private treatment for Lyme disease are seeing improvements in their health after being essentially abandoned by the NHS. References: 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. Johnson L, Wilcox S, Mankoff J, Stricker RB. Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey. Peer J 2014;2:e322 https://peerj.com/articles/322/	Thank you for your comment which supports the need for developing a NICE guideline in this topic area. We hope that this guideline will provide clarity for NHS healthcare providers and patients linked to the diagnosis and management of Lyme disease based on the best available evidence.
Lyme Disease UK	Gener al	Gen eral	All known pathogenic strains of Borrelia should be covered in the scope and not just Borrelia afzelii, Borrelia garinii and Borrelia burgdorferi. One in five patients is thought to be infected abroad and so could potentially be affected by different species which should also be covered by UK testing and come under the term ‘Lyme disease’. Borrelia valaisiana has been found in UK ticks according to the BIA position statement on Lyme borreliosis, although it states that Borrelia valaisiana is not regarded as pathogenic. However, in this study, Borrelia valaisiana was suspected of causing infection (Saito et al, 2007). In this study, after culturing ‘live Borrelia bissettii-like strain from residents of North America,’ the ‘results support the fact that B. bissettii is responsible for human Lyme borreliosis worldwide along with B. burgdorferi s.s. The involvement of new spirochaete species in Lyme borreliosis changes the understanding and recognition of clinical manifestations of this disease’ (Rudenko et al, 2016). Borrelia miyamotoi also needs to be taken into consideration and incorporated into testing as it has been found in the UK (Hansford et al) and it is known to cause disease (Molloy et al, 2015). The brief for the scope should include a review of the literature on other pathogenic strains of Borrelia, especially as there has been a number of new research papers since the BIA position statement was issued in 2011. 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. Saito K, Ito T, Asashima N, Ohno M, Nagai R, Fujita H, Koizumi N, Takano A, Watanabe H, Kawabata H. Case report: Borrelia valaisiana infection in a Japanese man associated with traveling to foreign countries. Am J Trop Med Hyg. 2007 Dec;77(6):1124-7 http://www.ajtmh.org/content/77/6/1124.long 3. Rudenko, N et al.Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis. Clin Microbiol Infect. 2016 Mar;22(3):267.e9-267.e15. doi: 10.1016/j.cmi.2015.11.009. http://www.ncbi.nlm.nih.gov/m/pubmed/26673735/ 4. Hansford, K. M., Fonville, M., Jahfari, S., Sprong, H., & Medlock, J. M. (2014). Borrelia miyamotoi in host-seeking Ixodes ricinus ticks in England. Epidemiology and Infection, 1– 9. doi:10.1017/S0950268814001691 http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=9595260&fileId =S0950268814001691 5. Molloy PJ, Telford SR 3rd, Chowdri HR, Lepore TJ, Gugliotta JL, Weeks KE, Hewins ME, Goethert HK, Berardi VP (2015). Borrelia miyamotoi Disease in the Northeastern United States: A Case Series. Annals of Internal Medicine. doi:10.7326/M15-0333 http://annals.org/article.aspx?articleid=2301402	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 Research UK	3	54	Transmission of Lyme borreliosis between people is not covered: This was covered in the previous version of the Guideline scope, and we think it should remain. There is published evidence for transmission between infected mothers and babies in-utero (Schlesinger et al, 1985; Weber et al, 1988; MacDonald et al, 1987). Untreated pregnant women with Lyme borreliosis have a higher incidence of adverse outcomes of pregnancy than treated women (Lakos et al, 2010). Therefore treatment of pregnant women should be included in the scope. The appropriate treatment for pregnant women should be reviewed. What constitutes appropriate antibiotic treatment in pregnant patients has yet to be determined. The U.S. Centres for Disease Control and Prevention (2016a) state "Lyme disease acquired during pregnancy may lead to infection of the placenta and possible stillbirth; however, no negative effects on the fetus have been found when the mother receives appropriate antibiotic treatment." Surviving babies born to untreated mothers may be infected and if so may need treatment, which should also be covered in the scope. There is also some evidence suggesting that sexual transmission may be possible (Middelveen et al, 2015 in review). The evidence for sexual transmission is limited and inconclusive (Stricker et al, 2015) but we suggest adopting a precautionary principle and that clinicians should inform sexually active, infected patients of the potential risks, whilst acknowledging the knowledge in this area is uncertain. Many patients are concerned about donating or receiving blood that may be contaminated with Lyme borreliosis, and we believe that this issue should be addressed. At least one study shows B. miyamotoi's ability to survive standard blood storage (Thorp et al, 2006).	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. The review question and protocol will be developed by the Guideline Committee. Pregnant women, will be included in our evidence reviews as a special subgroup and any direct evidence for this group, if available, will be analysed and presented separately allowing the committee to make specific recommendations in this population. (this is also the case in those people who are immunocompromised).
Lyme Research UK	3	55	Preventing Lyme borreliosis is not covered: Does this only refer to ways to prevent tick bites? We think that prophylactic treatment with antibiotics after a tick bite should be considered.	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. Prophylactic treatment with antibiotics after a tick bite will be considered.
Lyme Research UK	3	56	“Economic aspects”: We hope that you will include the potential costs of misdiagnosis and inadequate antibiotic treatment leading to chronic long-term disease in your economic analysis.	Thank you for your comment. The details of the economic analyses that may be performed for this guideline will be decided in collaboration with the Guideline Committee and will depend on the availability of data. We will take your suggestion in to consideration when developing our economic analysis.
Lyme Research UK	3	70	"2.2 Starting treatment?": When Lyme borreliosis is suspected, treatment should start immediately and be based on symptoms, since rapid treatment is important to help prevent long-term problems.	Thank you for your comment. The Guideline Committee will formulate recommendations on the timing of treatment based on the evidence identified through evidence reviews.
Lyme Research UK	3-4	79, 82, 90, 93	“Definitive treatment”: be given more powerful intravenous antibiotics. A milder term such as the “recommended antibiotic treatment” would be more suitable here.	Thank you for your comment. The term ‘definitive’ has been removed.
Lyme Research UK	4	95- 96	The NICE guideline should give guidance to the testing laboratories that in communications to clinicians and patients they should: a/ Report clearly the results of the test in the manner described by test kit manufacturers. b/ Inform clinicians of the test limitations and the kit manufacturers' statements that a negative result does not indicate absence of Lyme borreliosis. c/ The laboratories should not reinterpret the test results in a manner not supported by the test kit manufacturers. d/ The laboratories should confine themselves to reporting the test results and should not give clinical advice on specific cases without seeing the patient, and definitely not with the very basic data sent by clinicians. e/ Provide clear dates for taking samples and testing samples to ensure specimens are ‘fresh’ as defined by the manufacturer. f/ Patients should have access to their full laboratory results if they request them.	Thank you for your comment. This is a clinical guideline for the NHS. While the points you have raised are very important, we would not usually go into this level of detail from a particular evidence review for this guideline. The committee may choose to comment on reporting issues as part of the planned diagnostic test accuracy review.
Lyme Research UK	6	135	“Incubation period”: The use of the phrase "incubation period" in the context of human infection with Borrelia is not valid. The pathogen is infectious immediately. Symptoms develop as the pathogen multiplies and disseminates.	Thank you for your comment. We use the phrase ‘the incubation period’ to refer to the time between infection and the onset of symptoms.
Lyme Research UK	7	134- 141	You write "... in approximately two thirds of people this is followed by a circular, target-like rash centred on the bite, known as erythema migrans": We have not found the source of this estimate of two thirds and think it may actually be lower. There are difficulties in getting representative patient samples which include all types of patients. We hope that that you will look into this. This estimate can of course only be based on patients diagnosed with Lyme borreliosis. Undiagnosed patients, of whom there may be many, are less likely to have had an erythema migrans aiding diagnosis.	Thank you for your comment. We have changed the wording in the scope to read: “ …..in some people this is followed by …..” to reflect the uncertainty about the true proportion of people.
Lyme Research UK	7	141, 144	You write “Lyme disease is frequently self-limiting and resolves spontaneously” and “If Lyme disease does not resolve spontaneously, ...”: This implies that it often resolves without any antibiotic treatment. We do not know of any evidence for this, so think that the statements should not be made.	Thank you for your comment however we do not feel any change is required