Chronic Lyme Disease

The Australian Department of Health (DoH) are currently uncomfortable with associating patients' illness with Lyme disease. This is partly because they are concerned that international controversy about chronic Lyme disease (CLD) will negatively influence our cause.1

We appreciate this view, and agree that there appears to be a bias towards patients of Lyme-like illness, based on this controversy.   However, we believe that CLD is perceived to be more controversial and complex than it actually is. The stigma has resulted from a lack of education and clear communication. As more information is made readily available, the stigma is lessening. We are confident that this trend will continue. Accordingly, we remain comfortable with using the term Lyme-like illness.

The aim of this page is to provide an overview of the issues surrounding CLD. We hope this assists in reducing the stigma here in Australia.

The Definition of Lyme Disease  

Currently, there is no universally recognised definition for symptoms of Lyme disease that remain after a short course of antibiotics. This makes discussions between authorities confusing; each one thinks of CLD and its cause as something slightly different. Even the terms used to describe the illness vary; from 'CLD' to ‘Post-Lyme Disease Treatment Syndrome’, ‘late stage Lyme’, ‘post Lyme disease syndrome’ and ‘post-infectious Lyme disease.2

Only the International Lyme and Associated Diseases Society (ILADS) and the Infectious Diseases Society of America (IDSA) appear to have suggested detailed definitions. Both organisations agree that the illness occurs when symptoms persist for at least six months after treatment.3 The ILADS’ definition also includes untreated patients who have been sick for six months or more.

In Australia, the Federal Government does not provide a CLD definition at all. The Australian Chronic Infectious and Inflammatory Diseases Society (ACIIDS) agree with the ILADS’ definition.4

For the purposes of this page, we need to stick with a single term. Like the ACIIDS, we agree with the ILADS definition, and so will use 'chronic Lyme disease'.

The Cause of Lyme Disease 

CLD and its cause is still being debated; that’s why agreeing on a definition has been so difficult.

The ILADS believe that CLD is usually due to the Borrelia infection surviving short-term antibiotic treatment. This may occur for the following reasons:

  • Borrelia exists in three forms; spirochete, L form/cell wall deficient, and Cyst. The bacteria is capable of changing form to avoid the effects of certain antibiotics. Currently, no single antibiotic kills all forms of Borrelia. Therefore, if treatment has not included a variety of antibiotics, it will not be successful.5
  • Borrelia may produce a sticky substance called a ‘biofilm’ to hide in. Antibiotics and/or responses from the immune system may not be able to penetrate this.6
  • The immune system’s cells are not able to access every part of the body. Borrelia may hide in these inaccessible sites, which include the central nervous system, eyes, joints, connective tissues, and the genital tract.7
  • Borrelia can evolve into ‘persister cells.’ These are mutant cells that have developed the ability to become dormant or ‘sleep’ during antibiotic treatment.8  Because most antibiotics only kill bacteria that is growing and multiplying, they are unable to affect the persister cells.
  • The  likely presence of other tick-borne infections, commonly referred to as ‘co-infections’, may make Borreliamore difficult to eradicate” and “prolong the duration of infection.”9

ILADS also acknowledge that not all patients with symptoms remaining after treatment have ongoing infections. Other causes may be a dysfunctional immune system, damage to tissues and/or secondary conditions caused by the Borrelia.10

For many years the IDSA have strongly opposed the concept of an ongoing infection. They have not updated this stance in light of the recent research that has helped shape ILADS’ beliefs. Instead, they suggest that symptoms after short-term antibiotic treatment may be “related to the emotional state of the patient” or “aches and pains of daily living.”11

The American Government provides no clear guidance, and often contradicts itself:

  • The National Institute of Allergy and Infectious Diseases (NIAID) state that long-term treatment doesn’t work.  However, the studies they refer to as evidence of this actually indicate it does work (see Lyme Research below);  Their opposition of long-term treatment implies their disbelief in ongoing infection. However, they admit that ongoing infection is a possibility based on recent studies;12
  • Centres for Disease Control and Prevention (CDC) oppose long-term antibiotic treatment, stating that the cause is “not known;13
  • The Agency for Healthcare Research and Quality (AHRQ) promotes the ILADS treatment guidelines, which recognise ongoing infection by recommending long term antibiotic treatment where appropriate.14

The European Centre for Disease Prevention and Control suggests that symptoms are due to tissue damage caused prior to treatment.15

Authorities in the UK simply say the reason is unknown.16  Public Health England is open to the possibility of ongoing infection.17

Australia’s NSW Health Department does not provide an explanation for CLD and raises concerns that some patients don’t even have laboratory evidence of Lyme disease.18  This point seems irrelevant given NSW Health also states that “Laboratory tests are rarely definitive.”19  In fact, the manufacturer of tests used by a laboratory specifically endorsed by NSW Health,20 state that definitive “diagnosis of Lyme disease is difficult. Only early detection permits efficient control by antibiotics, since in the chronic phase borreliae are nearly inaccessible.” 21

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Treatment for Lyme Disease  

Given the debate regarding the cause of CLD, it is unsurprising that treatment recommendations are also a controversial topic.

Below, we outline the guidelines of the IDSA, who do not believe in persistent Borrelia infections, and the ILADS, who do.

The IDSA’s Guidelines for Lyme Treatment

In the past, many governments exclusively recommended the 2000 IDSA guidelines for treating Lyme disease.  The guidelines recommended two to four weeks of antibiotic treatment for most cases of Lyme disease, and a maximum of eight weeks treatment.22  Doctors who had successfully treated patients with long-term antibiotic regimes were alarmed by this. The ILADS stated “The duration of therapy should be guided by clinical response, rather than an arbitrary (ie 30 day) treatment course.” They protested that the guidelines “… fall short of meeting the needs…of individuals with chronic Lyme disease” and “fail to take into account the compelling, peer-reviewed, published evidence confirming persistent, recurrent and refractory Lyme disease and, in fact, deny its existence."23

Although the IDSA guidelines are voluntary, some authorities incorrectly assumed they were mandatory.  As a result, some American states have introduced laws to ensure health insurance agencies covered long-term treatment, and to protect prescribing doctors.

The IDSA reviewed their guidelines in 2006, but unfortunately did not make any significant changes.  Corruption within the IDSA was suspected, and an anti-trust investigation was launched by the Connecticut Attorney General (CAG).24 The CAG and the IDSA agreed to the creation of a new panel to review the guidelines.  This new panel however excluded doctors who treated CLD, as “…a financial or other beneficial interest… might bias his or her judgement.” 25 Most of the Panel members eventually selected were IDSA members - in fact, the Panel’s Chairperson was previously employed as the IDSA’s President!

Lorraine Johnson, CEO of America’s largest patient advocacy group, lymedisease.org, and co-author of the ILADS guidelines is an attorney advocate on issues related to the medico-legal and ethical aspects of Lyme disease. She commented that the selection process “was anything but 'independent'. Imagine a jury trial where the defendant selects a jury of friends. 26  The Panel decided that no changes to the guidelines were necessary. Ultimately, the Panel dismissed successful case studies with the unconvincing explanation that “Some patients were abnormal hosts and not representative of the general population.” 27  This outcome was even worse than expected. Lorraine wrote “…we had our reservations about the ability of a panel stacked with IDSA members to impartially review the guidelines, but there were 1,600 pages of peer reviewed evidence that had been presented to the panel and independent scientists had attested to the persistence of the Lyme bacteria and the low quality of the tests. How could they ignore the weight of such evidence?” 28

Congressmen and Senators unsuccessfully wrote to the AHRQ to request the removal of the IDSA guidelines from their treatment guidelines database.29

In an unrelated activity, Congress asked the Institute of Medicine (IOM) to review treatment guidelines in general and advise how they might be improved.The IOM’s resulting 2011 report, ‘Clinical Guidelines We Can Trust’, highlighted the IDSA guidelines as an example of bad practice.30

The AHRQ eventually removed the guidelines from their database, called the National Guidelines Clearinghouse (NGC), in early 2016, as they had not been “developed, reviewed or revised within the last five years.31 

The IDSA are currently rewriting their guidelines; a lengthy process considering the IOM’s stringent recommendations. They estimate this will take two to five years.32

Since the IDSA’s guidelines were first introduced, at least ten American states have taken legal action to formally recognise long-term antibiotic treatment as a legitimate approach. Actions include:

  • Protection to ensure doctors cannot be disciplined for using long-term antibiotic treatment;33
  • Requirements for health insurers to cover long-term antibiotic treatment;34
  • Education of healthcare professionals, governmental agencies, insurers and patients on different treatment options;35
  • Requirements for government sites to provide links to the ILADS guidelines, as well as those of the IDSA.36

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The ILADS Guidelines for Lyme Disease Treatment 

ILADS’ most recent guidelines met the IOM and NGC’s stringent inclusion criteria and were published in the database in 2015.  They are currently the only Lyme disease guidelines in the NGC. They do not provide rigid protocols like the IDSA, but rather, give options for healthcare practitioners and patients to consider. There are numerous references to minimising the risk of CLD, as caused by an ongoing Borrelia infection. The ILADS panel explain the significance of CLD as follows:

“…the panel placed a high value on reducing patient risks for developing the chronic form of the disease... Thus, the panel’s values align with the Institute of Medicine goal of reducing the impact of chronic illness at the individual and national levels by, among other things, treating the treatable."

 “The panel placed a high value on reducing the morbidity associated with chronic Lyme disease and improving the patient’s QoL [Quality of Life] as well as on the need for individualised risk/benefit assessment and informed shared decision-making.

Shared decision-making takes into account the best scientific evidence available, clinical expertise and the role of patient’s values and preferences in deciding among available treatment options. Despite the terminology, decision-making is not truly shared between clinician and patient; the responsibility for choosing between options remains with the clinician.  To effectively engage in shared decision-making, patients need to understand the implications of their choices. Physicians should not assume that patients share their values in making risk/benefit determinations…. Patients may also tolerate more risk when they have severe presentations of disease or when there are no other treatment options available.”37 

The ILADS recommend considering long-term antibiotic treatment when short term regimes have proved insufficient.  The panel said “…we moved away from designating a fixed duration for antibiotic therapy and instead encourage clinicians to tailor therapy based on the patient’s response… We not only recommend that clinicians perform a deliberate and individualised assessment of the potential risks and benefits of various treatment options before making their initial selection, we also recommend careful follow-up because this allows them to adjust therapy as circumstances evolve. This patient-centred approach should reduce the risk of chronic illness due to inadequate antibiotic therapy.”38   Their guidelines state For patients who improve yet continue to have persistent manifestations…following 4–6 weeks of antibiotic retreatment, decisions regarding the continuation, modification or discontinuation of treatment should be based on several factors… length of time between the initial and subsequent retreatment, the strength of the patient’s response to retreatment, the severity of the patient’s current impairments, whether diagnostic tests, symptoms or treatment response suggest ongoing infection and whether the patient relapses when treatment is withdrawn.” 39 

You can read the summarised guidelines on the NGC here. The detailed ILADS guidelines are located here.

The 2008 ILADS guidelines, replaced by the version on the NGC database, also include some recommendations that are still valid today.  In our experience, the following advice is invaluable:

“Many collateral conditions result in those who have been chronically ill so it is not surprising that damage to virtually all bodily systems can result. Therefore, to fully recover not only do all of the active infections have to be treated, but all of these other issues must be addressed in a thorough and systematic manner. No single treatment or medication will result in full recovery of the more ill patient. Only by addressing all of these issues and engineering treatments and solutions for all of them will we be able to restore full health to our patients.”40

“If treatment can be continued long-term, then a remarkable degree of recovery is possible. However, attention must be paid to all treatment modalities for such a recovery - not only antibiotics, but rehab and exercise programs, nutritional supplements, enforced rest, low carbohydrate, high fibre diets, attention to food sensitivities, avoidance of stress, abstinence from caffeine and alcohol, and absolutely no immunosuppressants, even local doses of steroids.” 41

International Approaches to Lyme Treatment

In 2008, the UK Parliament acknowledged that Lyme is a “potentially chronic disease” with “a growing body of evidence that suggests patients are frequently subject to…under-treatment.” 42  However, the lack of funding for related investigation has recently led English researchers to report that there is insufficient evidence available to produce “a useful or meaningful” analysis of effective treatment.43

In 2018, the UK's National Institute for Health and Care Excellence stated that "Further antibiotic treatment (beyond 21-28 days) is now recommended as an option if persisting infection is a possibility."44

The French Government has been investigating a new national treatment protocol, due to be published by mid 2018. Infectious Diseases Specialist Dr Christian Perronne, who was involved in the investigation, has said “…there will be no maximum for the duration of an antibiotic treatment. It will be left to the discretion of the doctor.45

The German Borreliosis Society are a group of doctors and scientists who aim to “develop and promote the scientific and practical knowledge of the complex and diverse disease of Lyme disease, especially in the advanced stage.”46  They promote the ILADS guidelines, and have also written their own guidelines, which support long term use of antibiotics in chronic cases. These guidelines state that “The duration of treatment is of decisive importance for the success of antibiotic treatment. There are now a few studies available which provide evidence of the positive effect and the safety of long-term antibiotic therapy.” 47

Australian Approaches to Lyme Treatment

The Australian DoH specifically and repeatedly directs readers to the IDSA website for treatment advice, rather than the NGC.48

NSW Health also refers to the IDSA recommendation of “a few weeks of antibiotics.49 They refer only indirectly to the ILADS guidelines, which they vaguely attempt to discredit, by saying  The chronic Lyme disease term is used by a small number of doctorsto describe patients whom they believe have a persistent B. burgdorferi infection, a condition they suggest requires long-term antibiotic treatment and/or a range of other treatments with little evidence of clinical benefit but with a significant risk of harm.50

NSW Health seems unaware that the term CLD has been used by Australian scientists since the 1980s.51

A 1994 paper that states “Treatment of chronic cases of LB [Lyme Borreliosis] is problematic as persistent symptoms and relapses are seen often in the Northern Hemisphere. Similar problems have been observed in Australian cases…where repeat courses of oral and intravenous antibiotics have been givenphysician-observed reoccurrences…are best explained by failure of antibiotic therapy.”52

The ACIIDS have documented their own “consensus-based treatment guidelines for the treatment of borreliosis and related co-infections,” which they say “are closely aligned with those of ILADS.” They state ACIIDS doctors are aware of the possible dangers of long-term antibiotic treatment…Our patients are closely monitored…ACIIDS considers that the risk of not treating this illness is greater than the risk of potential adverse reactions to treatment.”53 

This approach is consistent with one written by the Tick-borne Diseases Research Unit of Sydney’s Royal North Shore Public Hospital.54  Dated 2001, it warns that “Prompt treatment of early suspected Lyme-like disease may prevent chronic debilitating infection.” It suggests that if symptoms are not resolved via an initial antibiotic regime, and no alternative diagnosis is suspected, antibiotics are repeated. Unfortunately, that advice is not currently being followed by the mainstream medical profession.

In 2015, Australia’s Chief Medical Officer claimed that no one was preventing doctors from treating CLD.55 We dispute this. We believe, as do professional medical organisations, that the Australian Health Practitioner Regulation Agency (AHPRA) are specifically targeting these doctors for disciplinary action.56

We also believe that the DoH’s repeated focus on controversy is an attempt to delay action. This opinion was shared by Senator Bilyk, who said to the DoH’s Dr Gary Lum “You have used that term a few times…Why is it so controversial if people have symptoms and illnesses? I do not think we are denying that there is actually some disease…Why can't whoever is causing the controversy just sort it so that people's lives are not so disrupted and ruined?”57 

Senator Bilyk’s frustration is understandable; there is action our Government could have taken on this issue, but has not. The National Health and Medical Research Council (NHMRC) state “NHMRC has a very particular role with [treatment] guidelines—that is, where we have been specifically asked to develop guidelines, we will pull together an expert committee to do that, to review the full body of evidence that would provide guidelines for best clinical practice. We are also sometimes asked to endorse guidelines. We review what needs to be re-evaluated every five years and decide whether to undertake another exercise of examining whether there is new evidence that would alter the guidelines.”58 This service has not been utilised, and the Government’s resulting ignorance is obvious.

While we do agree that CLD is controversial, we believe the issues can be broken down very simply:

  • The IDSA guidelines have been considered highly controversial for almost 20 years. They were the subject of an anti-trust investigation, and American laws were created to ensure long-term treatment outside the guidelines could still be provided. These guidelines, now over a decade old, are no longer endorsed by America’s leading authority on evidence-based treatment guidelines, the NGC. They were also criticised by the IOM;
  • ILADS guidelines, whilst also controversial, are the only Lyme disease guidelines endorsed by the NGC. They meet the IOM’s standards for trustworthy clinical guidelines, and actively promote the IOM’s commitment to patient-centred care. They also reflect the findings of current research. Therefore, they are indisputably best practice.The DoH’s claim that “…the concept of chronic Lyme disease is disputed and not accepted by most conventional medical practitioners, not only in Australia but around the world 59 is incorrect. The NGC, by its very nature, is “conventional” and serves a conventional audience.

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Lyme Research

Research related to CLD falls into two key areas, both of which are covered below.  For the purpose of this page, we’ll focus only the studies specifically mentioned by the NIAID, as these are often used in the CLD debate.

Chronic Borrelia infection after antibiotic treatment

Although the NIAID do not recommend long-term antibiotic treatment, they admit that “Several recent studies suggest that B. burgdorferi may persist in animals after antibiotic therapy… Additional research is needed and continues to be supported by NIAID to learn more about persistent infection in animal models and its potential implication for human disease.”60  Three studies found Borrelia DNA in the tissues of infected monkeys and mice after 28-90 days antibiotic treatment.61 On the basis of this, the NIAID investigated whether Borrelia DNA could be found in treated humans. To do so, they raised ticks in a laboratory to ensure they were disease-free. They then allowed the ticks to feed on volunteers, including patients who had already received antibiotic treatment.  The ticks were then tested to see for Borrelia DNA.  This was found in ticks that fed on a patient who had already been diagnosed with ‘Post-treatment Lyme Disease Syndrome.’62

It is no wonder that the NIAID is maintaining an open mind on the idea of ongoing infection.

The Impact of Long-term Antibiotic Treatment on Chronic Borrelia Infections 

The NIAID refers to the three studies when discrediting long-term antibiotic treatment.63  In each, patients who experienced chronic symptoms despite earlier treatment were given either further treatment, or a placebo for 28-90 days.

Atlhough the NIAID use the studies as evidence long-term treatment doesn’t work, every study actually reports improvement in the treated patients.64  This is a remarkable result, particularly considering the studies were criticised for flaws that skewed the results towards the opposite conclusion.65

Some of the co-authors of one of the studies later reviewed all three studies, and stated “The conclusions of this analysis of the chronic Lyme trials emphasise the benefits of repeated antibiotic therapy for patients with specific chronic symptoms…the majority of published guidelines… overlook and/or dismiss the evidence that demonstrates that additional antibiotic therapy can lead to sustained benefit. We hope that our review will lead to more carefully detailed and balanced summaries in future guidelines.”

“Treatment guidelines that dismiss the research findings do an injustice to the evidence and are not helpful to clinicians and patients.”66 

We believe the fact that the NIAID continue to promote the outdated IDSA guidelines, using these studies as justification, shows that their position is a weak one. Not only are they unable to reference any studies with no improvements, but they ignore the findings of the above analysis.

Lorraine Johnson of lymedisease.org wrote of the studies “Even though there are over 100 000 cases of chronic Lyme each year…only three government treatment trials have ever been conducted. And those three trials didn’t look at treatments actually used by physicians treating chronic Lyme disease, but were instead limited to 90 days of a single form of antibiotics. And they didn’t study ordinary patients. One screened over 32 000 patients to finally enrol just 23, who met the researchers’ highly specific criteria. Patients in these treatment trials are by definition not typical.” 67

As a result, lymedisease.org launched its own research initiative, called MyLymeData. They describe this as “a new survey tool that tracks patient progress over time. It allows patients to use today’s computer technology to quickly and privately pool diagnosis and treatment experiences. When large amounts of data are combined, we can see patterns that help us determine which treatments work best.

“Patients with Lyme disease tell us about their experience, symptoms, treatments, and results. Periodically, they update their information to let us know what has changed. This allows us to better understand the progression of the disease and what works—and doesn’t work—to help people get better. It lets patients learn from each other and provides data that can drive research to improve patients’ lives.

“MyLymeData expects to gather more data about Lyme disease than any research study has done before. Consider this: The largest Lyme disease trial funded by the National Institute of Health enrolled only 64 patients in the treatment group. Our patient surveys draw over 9,000 responses! We’ll use the information provided by patients to help figure out how to prevent and treat all stages of Lyme disease. It’s that simple.”68 

The international patient community, together with the Lyme Disease Association of Australia, are looking forward to MyLymeData’s findings.

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Footnotes

  1. Lum, Official Committee Hansard, Emerging Tick-borne disease, 20 Apr 2016, p5,  http://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/Lyme-like_Illness/Public_Hearings
  2. National Institute of Allergy and Infectious Diseases, Chronic Lyme Disease, accessed Mar 2018 https://www.niaid.nih.gov/diseases-conditions/chronic-lyme-disease Centres for Disease Control and Prevention, Post-Treatment Lyme Disease Syndrome, accessed Mar 2018 https://www.cdc.gov/lyme/postlds/index.html National Health Service UK, Lyme disease, accessed Mar 2018, https://www.nhs.uk/conditions/lyme-disease/ European Centre for Disease Prevention and Control, Factsheet about Borreliosis, accessed Mar 2018, https://ecdc.europa.eu/en/borreliosis/facts/factsheet
  3. International Lyme and Associated Diseases Society, Chronic Lyme Disease: A Working Case Definition, 2007, p1, http://www.associationlymesansfrontieres.com/wp-content/uploads/Chronic-Lyme-Working-Case-Definition.pdf Infectious Diseases Society of America, The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the IDSA, 2006,Table 5 http://cid.oxfordjournals.org/content/43/9/1089.full
  4. Australian Chronic Inflammatory and Infectious Diseases Society, Growing Evidence of an Emerging Tick-borne Disease that causes a Lyme-Like Illness for many Australian Patients, Senate Submission 370, p 15, http://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/Lyme-like_Illness/Submissions
  5. Horowitz, Official Committee Hansard – Emerging tick-borne disease, 2 Nov 2016, p6 http://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/Lymelikeillness45/Public_Hearings International Lyme and Associated Diseases Society, Chronic Lyme Disease: A Working Case Definition, 2007, p3, http://www.associationlymesansfrontieres.com/wp-content/uploads/Chronic-Lyme-Working-Case-Definition.pdf
  6. Sapi et al, Characterisation of Biofilm Formation by Borrelia burgdorferi In Vitro, PLOS, 2012, http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0048277
  7. International Lyme and Associated Diseases Society, Chronic Lyme Disease: A Working Case Definition, 2017, p3, http://www.associationlymesansfrontieres.com/wp-content/uploads/Chronic-Lyme-Working-Case-Definition.pdf
  8. Sharma et al, Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells, 2015, http://aac.asm.org/content/59/8/4616.full Feng et al, Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoparazone and Doxycycline, 2015, http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117207 Feng et al, Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library, 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126181/ Horowitz et al, The Use of Dapsone as a Novel “Persister” Drug in the Treatment of Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome, 2016 https://www.researchgate.net/publication/304000313_The_Use_of_Dapsone_as_a_Novel_Persister_Drug_in_the_Treatment_of_Chronic_Lyme_DiseasePost_Treatment_Lyme_Disease_Syndrome
  9. International Lyme and Associated Diseases Society, Chronic Lyme Disease: A Working Case Definition, 2017, p4-5, http://www.associationlymesansfrontieres.com/wp-content/uploads/Chronic-Lyme-Working-Case-Definition.pdf
  10. International Lyme and Associated Diseases Society, Chronic Lyme Disease: A Working Case Definition, 2017, p5, http://www.associationlymesansfrontieres.com/wp-content/uploads/Chronic-Lyme-Working-Case-Definition.pdf International Lyme and Associated Diseases Society, Advanced Topics in Lyme disease – diagnostic hints and treatment guidelines for Lyme and other tick-borne illnesses, 2008, p3, http://www.ilads.org/lyme/B_guidelines_12_17_08.pdf
  11. Infectious Diseases Society of America, The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the IDSA, 2006, http://cid.oxfordjournals.org/content/43/9/1089.full
  12. National Institute of Allergy and Infectious Diseases, Chronic Lyme Disease, accessed Mar 2018, https://www.niaid.nih.gov/diseases-conditions/chronic-lyme-disease
  13. Centres for Disease Control and Prevention, Post-Treatment Lyme Disease Syndrome, accessed Mar 2018, https://www.cdc.gov/lyme/postlds/index.html
  14. International Lyme and Associated Diseases Society, Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease (summarized version), Recommendation 3c, 2014, https://www.guideline.gov/summaries/summary/49320/evidence-assessments-and-guideline-recommendations-in-lyme-disease-the-clinical-management-of-known-tick-bites-erythema-migrans-rashes-and-persistent-disease
  15. European Centre for Disease Prevention and Control, Factsheet about Borreliosis, accessed Mar 2018, https://ecdc.europa.eu/en/borreliosis/facts/factsheet
  16. Public Health England, Lyme disease: signs and symptoms, accessed Mar 2018, https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/463701/LymeDisease_SignsAndSymptoms.pdf
  17. Public Health England, Lyme disease: diagnosis and treatment, accessed Mar 2018, https://www.gov.uk/government/publications/lyme-disease-diagnosis-and-treatment/lyme-disease-diagnosis-and-treatment
  18. NSW Health, Growing Evidence of an Emerging Tick-borne Disease that causes a Lyme-Like Illness for many Australian Patients, Senate Submission 457,  p 2, http://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/Lyme-like_Illness/Submissions
  19. NSW Health, Lyme disease fact sheet, accessed Mar 2018, http://www.health.nsw.gov.au/Infectious/factsheets/Pages/Lyme_disease.aspx
  20. The ICPMR lab is specifically endorsed by NSW Health on this site - NSW Health, Lyme disease testing advice for clinicians, accessed Mar 2018, http://www.health.nsw.gov.au/Infectious/factsheets/Pages/lyme-disease-testing-advice.aspx  According to the following document, the ICPMR use the NovaTec NovaLisa ELISA test - National Serology Reference Laboratory, Final Report: Investigation of the Performance of Assays for Lyme Disease in Australia, 2017, p12 http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-lyme-disease.htm/$File/NRL-2017.pdf
  21. NovaTec, NovaLisa Borrelia burgdorferi IgG – ELISA (recombinant), p2. This document is no longer available online, but the LDAA can provide a copy on request.
  22. Infectious Diseases Society of America, The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the IDSA, 2006, http://cid.oxfordjournals.org/content/43/9/1089.full
  23. International Lyme and Associated Diseases Society, Evidence-based guidelines for the management of Lyme disease, 2014 https://www.tandfonline.com/doi/full/10.1586/14787210.2014.940900 
  24. Until recently, the CAG’s Press Release regarding this was published on the site of Connecticut’s Office of the Attorney-General. It has since been removed, but a copy is included as Attachment 2 of Senate Submission 122, http://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/Lyme-like_Illness/Submissions
  25. Infectious Diseases Society of America, Final Report of the Lyme Disease Review Panel of the Infectious Diseases Society of America, 2010, p1, http://www.idsociety.org/uploadedFiles/IDSA/Topics_of_Interest/Lyme_Disease/IDSALymeDiseaseFinalReport.pdf
  26. Lymedisease.org, Publication Alert: IDSA Review Hearing Report – Lipstick on a Pig, accessed Mar 2018, https://www.lymedisease.org/600/
  27. Infectious Diseases Society of America, Final Report of the Lyme Disease Review Panel of the Infectious Diseases Society of America, 2010, p20, http://www.idsociety.org/uploadedFiles/IDSA/Topics_of_Interest/Lyme_Disease/IDSALymeDiseaseFinalReport.pdf
  28. Lymedisease.org, Publication Alert: IDSA Review Hearing Report – Lipstick on a Pig, accessed Mar 2018, https://www.lymedisease.org/600/
  29. Lymedisease.org, Congressmen Call For Removal of Outdated IDSA Guidelines from National Guideline Clearinghouse, accessed Mar 2018, https://www.lymedisease.org/898/ Lymedisease.org, Senators Request Removal of IDSA Lyme Guidelines from National Guidelines Clearinghouse, accessed Mar 2018,  https://www.lymedisease.org/lymepolicywonk-senators-request-removal-of-idsa-lyme-guidelines-from-national-guidelines-clearinghouse/
  30. Institute of Medicine, Clinical Practice Guidelines We Can Trust – Trustworthy Clinical Practice Guidelines: Challenges and Potential, 2011, https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0079461/
  31. Lyme Disease Association Inc, Official Word on IDSA Guidelines’ Removal from NGC, accessed Mar 2018, https://www.lymediseaseassociation.org/index.php/lda-news-a-updates/1456-official-word-on-idsa-guidelines-removal-from-ngc
  32. Lymedisease.org, IDSA say revision of Lyme disease guidelines expected to take 2-5 Years, accessed Mar 2018, https://www.lymedisease.org/lymepolicywonk-idsa-says-revision-of-lyme-disease-guidelines-expected-to-take-2-5-years/
  33. State of New York, Assembly Resolution 2155, 2002, http://www.lymeinfo.net/nyresolution.html
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