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Training, Education, Access to Care, and Reimbursement Subcommittee Report to the Tick-Borne Disease Working Group

Disclaimer

Information and opinions in this report do not necessarily reflect the opinions of the working group, the U.S. Department of Health and Human Services, or any other component of the federal government. Readers should not consider the report or any part of it to be guidance or instruction regarding the diagnosis, care, or treatment of tick-borne diseases or to supersede in any way existing guidance. All subcommittee members actively participated in the development of this report. Members voted to approve submission of the report to the Working Group and on the wording of each of the possible actions contained in the report. The vote to submit the report indicates general agreement with the content of the document, but it does not necessarily indicate complete agreement with each and every statement in the full report.

Background

Focus of the Report

The formation of the Tick-Borne Disease Working Group, as outlined in the 21st Century Cures Act, was driven by patients and patient advocates, determined to shine a light on the issues outlined in this report and to seek Federal assistance to bring about resolution. Many of these individuals live with debilitating chronic illness because they are unable to get the diagnosis, treatment, and care they need to restore their health. This report is written to give voice to their plight and that of the clinicians who understand their struggles and risk their livelihoods to help them.

Why It's Important

Patients with chronic Lyme disease, coinfections, and other tick-borne diseases experience a highly compromised quality of life. In the large-scale MyLymeData survey of over 12,000 patients with chronic Lyme disease, 72% reported their health status as fair or poor, and 75% reported experiencing severe or very severe symptoms (Johnson, Wilcox, Mankoff, & Stricker, 2014).

Many chronically ill patients are unable to regularly attend school or hold down a job, which puts considerable strain on their families and society at large (Johnson, Aylward, & Stricker, 2011). The cost of illness for individuals with late-stage Lyme disease is approximately $24,000 per year, with loss of productivity accounting for more than half of those costs (Zhang et al., 2006; Johnson, Chart Book, 2019). Table 1 outlines the cost of direct, indirect, and non-medical costs, and loss of productivity in 2006 and 2018 (Zhang et al., 2006; Johnson, 2018)

Table 1: Lyme disease cost per patient in 2006 and 2018 (inflation adjusted)

Costs Zhang 2006 study Zhang 2006 study (inflation adjusted to August 2018)
- $ cost (% of total) $ cost (% of total)
Early LD Late/chronic LD Early LD Late/chronic LD
Direct medical $801 (61%) $1,872 (12%) $1,196 (61%) $2,796 (12%)
Indirect medical $259 (20%) $434 (3%) $387 (20%) $648 (3%)
Non-medical $52 (4%) $5,109 (32%) $78 (4%) $7,631 (32%)
Productivity loss $198 (15%) $8,785 (54%) $296 (15%) $13,123 (54%)
Total $1,310 $16,200 $1,957 $24,198

The overall cost to society is yet to be determined; however, studies indicate that Lyme disease costs as much as $1.3 billion each year in direct medical costs alone (Adrion, Aucott, Lemke, & Wiener, 2015; Zhang et al., 2006).

Clinicians who attempt to treat chronically ill patients until they have returned to a baseline of acceptable health are often penalized by both insurance companies and medical review boards. As a result, many health care providers will not treat chronically ill patients, leaving them with few to no options to obtain the diagnosis and treatment they need to get well (Johnson et al., 2011).

Major Challenges

Delayed Diagnosis

When diagnosed early and given appropriate treatment, most Lyme disease patients make a full recovery. However, up to 35% of patients experience chronic, often debilitating, symptoms (Aucott, Rebman, Crowder, & Kortte, 2012). The exact cause of these symptoms is not fully understood, yet receiving an early diagnosis seems to be a key factor in whether or not a patient will make a full recovery. Moreover, delayed diagnosis appears to contribute to the risk for chronic illness.

In a recently published study of the results from patients enrolled in the MyLymeData patient registry (which has enrolled over 12,000 patients with persistent Lyme disease), 78% report a delay in their diagnosis (Johnson, 2018). In another patient survey published in 2011, 36% of respondents stated that it had taken more than six years to receive a diagnosis, and a majority of patients reported seeing seven or more clinicians before being diagnosed (Johnson, et al, 2011). These patients often report that they found themselves handed from clinician to clinician as they sought a diagnosis for their severe symptoms (Johnson et al., 2014).

For example, Nicole Malachowski, retired Air Force Colonel, did not get diagnosed for four years and after seeing more than 24 doctors, both civilian and military. After 21 years as a fighter pilot, she was medically retired, deemed unfit for duty due to neurologic damage from tick-borne diseases (Congressionally Directed Medical Research Programs, 2018).

A major factor in delayed diagnosis relates to the clinical presentation of symptoms. In just a single tick bite, a human can become infected with more than just one pathogen. The deer tick, Ixodes scapularis, for example, can transmit Borrelia burgdorferi (which causes Lyme disease), Anaplasma phagocytophilum, Babesia species, Borrelia miyamotoi, Ehrlichia muris subsp. eauclairensis and Powassan virus. The presence and combination of these infections can vary depending on the geographic region. Coinfections of Babesia and B. burgdorferi have been frequently observed in a number of studies in regions endemic for those pathogens, such as the Northeast (Hersh et al., 2014). In a retrospective chart review and data analysis of 200 patients on a combination treatment study for chronic Lyme disease/post-treatment Lyme disease syndrome (PTLDS), the researchers observed that chronically ill patients had often been exposed to many tick-transmissible infections over the course of their lives. Using direct and indirect testing, they found that 13.5% of patients tested positive for Anaplasma, 52% for Babesia, and 14.5% for Ehrlichia (Horowitz & Freeman, 2019).

An individual bitten in the U.S. by the lone star tick, Amblyomma americanum, can be exposed to Ehrlichia, Heartland virus, southern tick-associated rash illness (STARI), and tularemia. They can also develop tick paralysis and alpha-gal syndrome, a mild to severe allergic reaction to mammalian meat and other mammal-derived products. The general public, clinicians, and manufacturers of various food, pharmaceutical, and cosmetic products are not generally aware of alpha-gal syndrome.

A recent study conducted in Suffolk County, New York, demonstrates the need for public health officials and health care providers to become more educated about the increasing number of tick-borne diseases their patients can be exposed to and may need to be evaluated for when bitten or when tick-borne disease is suspected as part of a differential diagnosis. Researchers tested three tick species for 12 different microbes and found that 63 percent of I. scapularis, deer ticks, contained at least one agent—the most prevalent of which was the Lyme disease-causing B. burgdorferi—and 22 percent of I. scapularis were co-infected. Table 2 outlines the pathogens found in the deer ticks (Sanchez-Vicente, Tagliafierro, Coleman, Benach, & Tokarz, 2019).

Table 2: Percentage of microbes found in deer ticks tested in New York State

Microbe Detection rate
Borrelia burgdorferi 27% nymphs; 57% adults
Babesia microti 14% nymphs; 15% adults
Anaplasma phagocytophilum 2% nymphs; 14% adults
Borrelia miyamotoi 3%
Powassan virus 2%
Coinfection of B. burgdorferi and B. microti 9%
Coinfection of B. burgdorferi and A. phagocytophilum 7%

In the same study, four percent of A. americanum, lone star ticks, contained three Ehrlichia species. In addition, the rickettsiae constituted the largest biomass of organisms of all the ticks tested (Sanchez-Vicente et al., 2019).

It is not surprising, then, that people with Lyme disease, coinfections, and other tick-borne diseases and conditions experience a wide range of reactions after being bitten by an infected tick. Most are unaware of ever having been bitten (Berger, 1989). Some patients present with an erythema migrans (EM) rash, which may or may not take the shape of a bull's eye; and some have no rash at all. A patient may experience a combination of symptoms such as fever, fatigue, and joint pain; headaches, nerve pain, and cognitive impairment; heart palpitations and shortness of breath; or abdominal pain and nausea. When Lyme disease treatment is delayed, patients may develop disseminated or late Lyme disease which may present with a myriad of symptoms with severe quality of life impairment (Centers for Disease Control and Prevention, Signs and Symptoms of Untreated Lyme, 2019; Klempner, 2002; Johnson, 2014). The percentage of patients who are diagnosed late is unknown, but Hirsch suggests that delayed diagnosis may occur in as many as 40% of cases given that CDC surveillance reports include 32% of Lyme disease cases diagnosed with arthritis, 12% with neurological conditions and 1%–2% with carditis (Hirsch 2018; Mead, 2015).

Misdiagnosis

Given the vast array of potential non-pathognomonic signs and symptoms that occur during the different stages of illness, clinicians commonly mistake the symptoms of Lyme disease for other illnesses and conditions, with 72% of those diagnosed late reporting that they were previously misdiagnosed with another illness (Johnson, 2018). According to Aucott et al. (2009), more than half (54%) of Lyme disease patients who present without a rash are misdiagnosed. The diverse symptoms may also lead to fragmented care as patients are referred to a variety of specialists and sub-specialists who operate within treatment silos, impeding recognition of the full scope of the underlying multi-systemic disease.

Geography also plays a key role in misdiagnosis. The Centers for Disease Control and Prevention (CDC) uses Lyme disease surveillance data collected from individual states to determine which states are "high incidence" and which are "low incidence" for Lyme disease (Centers for Disease Control and Prevention, Lyme Disease Maps, 2018). Based on this information, CDC and the Infectious Diseases Society of American (IDSA) advise clinicians to limit Lyme disease testing and diagnosis by EM rash to high incidence states. However, this restriction interferes with the ability of patients from "low-incidence" states from being diagnosed and treated promptly, when treatment is more likely to be effective. Clinicians relying on CDC maps may believe that there is no Lyme disease in their state and fail to consider it in the differential diagnosis. Significant data from other sources have determined that the CDC incidence rate information and maps are inaccurate and should not be used, as they are a barrier to timely diagnosis and treatment.

Quest Diagnostics shows a more extensive geographic incidence distribution of B. burgdorferi based on population. Between 2010 and 2017, there were positive test results identifying infection with B. burgdorferi in all 50 states, with many areas traditionally considered low incidence, such as California, Florida, and Texas, reporting higher numbers of cases (Quest Diagnostics, 2018).

A recent Harvard Medical School study using positive lab test rates from Quest Diagnostics for the period between 2010 and 2016 shows a dramatic geographic expansion in the positive rate for Lyme disease across the nation, with high positivity rates in many states previously considered low incidence (Lee-Lewandrowski, Chen, Branda, Baron, & Kaurman, 2019). This is supported by an examination of the FAIR Health database of over 23 billion privately billed healthcare insurance claims, which showed significant discrepancies in three low-incidence states between the number of cases reported in and the number of healthcare claims for a Lyme disease diagnosis (Table 3). All three are considered low-incidence states, yet they rank in the top 5 for Lyme disease-related insurance claims (McGinty, 2018).

Table 3: Discrepancies between reported Lyme disease cases to CDC and health care claims for Lyme disease in three states considered low incidence by CDC

State Reported cases to CDC Healthcare claims for a Lyme diagnosis
North Carolina 32 88,539
California 90 46,820
Texas 31 31,129

Similar to the challenges of surveillance data on Lyme disease, CDC surveillance studies in Wisconsin and Connecticut for human granulocyctic anaplasmosis (HGA; previously, human granulocytic ehrlichiosis, HGE) show significant variance from active surveillance of the disease (from 1990-1999) versus passive surveillance (2017). Since HGA passive surveillance, or state-level reporting to the CDC, relies on voluntary reporting by clinicians based on pre-defined disease criteria, under-reporting of the disease is likely (Bakken et al., 1996; IJado, Meek, & Carter, 2000; Centers for Disease Control and Prevention, National Notifiable Diseases Surveillance System, 2018).

Victims of Rocky Mountain spotted fever (RMSF), which has a high fatality rate, sometimes go without a diagnosis or treatment because clinicians are under the impression that the infection does not occur in their state. In the Midwest, Tony and Liz Galbo lost their five-year-old daughter, Gabby, when the clinicians caring for her failed to consider RMSF in their diagnosis. She died 10 days after her first visit to the emergency room (Sepsis Alliance, n.d.).

Dermacentor variabilis, the American dog tick, is a vector of the RMSF agent, Rickettsia rickettsii. Although surveillance studies rarely report R. rickettsii in the American dog tick, the number of reported cases of spotted fever rickettsiosis (SFR) in the U.S. has increased from 1,713 in 2004 to 4,269 in 2016. This suggests that other species of Rickettsia contribute to the increased incidence of SFR (Sanchez-Vicente et al, 2019), and CDC now groups and reports RMSF and other rickettsial diseases into a single, SFR category.

Conflicting Guidelines

If the health care provider is fortunate enough to have either a clear set of signs and symptoms pointing toward Lyme disease or a high index of suspicion, he or she is then challenged by the fact that there are two different sets of clinical guidelines sponsored by the medical societies that developed them (Cameron, Johnson, & Maloney, 2014; Wormser et al., 2006). One guideline was developed by the Infectious Diseases Society of America (IDSA), and the other was developed by the International Lyme and Associated Diseases Society (ILADS). Table 4 outlines the differences between the two guidelines.

Table 4: Comparison of IDSA and ILADS Guidelines

Infectious Diseases of America (IDSA) Guidelines International Lyme and Associated Diseases Society (ILADS) Guidelines
Research-oriented diagnosis Clinical diagnosis
Erythema migrans rash alone or physical findings consistent with Lyme disease accompanied by positive two-tier test results Lab test supportive
Short-term treatment protocols Longer treatments may be appropriate
No persisting infection (do not treat) Persisting infection may be present
Research-oriented outcomes Patient-oriented outcomes
Limited clinical judgment Clinical judgment
Limited shared medical decision-making Shared medical decision-making

In late or persistent Lyme disease, conflicting disease definitions create additional challenges for clinicians. The IDSA definition emphasizes objective findings (for example, physician-observed rash or joint swelling, or test results), while the ILADS definition is broader and recognizes that Lyme disease patients may also present with multi-systemic symptoms (Wormser et al., 2006; Shor et al., 2019).

In the face of uncertainty, the ILADS guidelines provide for the exercise of clinical judgment and shared medical decision-making. This is consistent with the definition of evidence-based medicine which provides: "Evidence-based medicine is the integration of best research evidence with clinical expertise and patient values" (Sackett, Strauss, Richardson, Rosenberg, & Haynes, 2000). In its hallmark report, Clinical Practice Guidelines You Can Trust, the National Academy of Medicine (NAM), previously the Institute of Medicine (IOM), also recognizes the role of clinical judgment and patient preferences, as does the widely used evidence assessment scheme GRADE (IOM, 2011; Guyatt et al., 2008). In contrast, the IDSA severely restricts the use of clinical judgment. For example, the IDSA guidelines require a positive lab test for diagnosis, limit diagnosis in non-endemic areas, and provide only short-term treatment and no further treatment options for patients who remain ill.

According to NAM, conflicting guidelines most often arise when evidence is weak, organizations use different assessment schemes, or when evidence developers place different values on the benefits and harms of intervention (IOM, 2011). Given these distinctions, the various sectors involved tend to subscribe to one set of guidelines or the other. So, while Federal agencies like CDC, medical boards, and insurers reference the IDSA guidelines, clinicians that treat the majority of chronically ill patients tend to follow the ILADS guidelines.

"Evidence is never enough—it is always evidence in the context of values and preferences that influence guidelines and clinical care."

–Dr. Gordon Guyatt, 2011 Debate with Montori

"Informed choice under uncertainty is an ideal to strive for, especially because it enhances the exercise of the patient's right of self-determination, which is a cornerstone of medical ethics."

–Institute of Medicine, 2011

Flawed Laboratory Tests

After a thorough review of patient history, symptoms and signs, and a determination that Lyme disease is the likely diagnosis, diagnostic testing is often done to lend additional support to the clinical diagnosis. Unfortunately, available serologic tests, which look for antibodies to B. burgdorferi and not the bacterium itself, are unreliable and often inaccurate, and cannot distinguish between past and active infection (Reed, 2002; Glatz, Golestani, Kerl, & Mullegger, 2006). During the early stage of the illness, over 50% of Lyme disease cases are missed (Stricker & Johnson, 2010). Serologic tests can also be negative in late neurologic Lyme disease (Logigian, Kaplan, & Steere, 1999). Additionally, serologic tests cannot be used as tests of cure because the antibody response following antibiotic therapy in a given individual is unpredictable and does not necessarily correlate with infection status (Reed, 2002; Glatz et al., 2006; Rebman, Crowder, Kirkpatrick, & Aucott, 2015). Other, more invasive tests can detect active infection; for example, biopsies have shown B. burgdorferi can persist in brain, liver, synovial fluid, spleen, skin, blood, bladder, and cerebrospinal fluids (Stricker & Johnson, 2011). However, because of their invasiveness, these tests are not typically used for clinical diagnosis.

Without adequate diagnostic tests, it is difficult to determine 1) who has the disease; 2) whether a course of treatment is effective; and 3) when the disease has been "cured"—the end point of treatment.

High Treatment Failure Rates

Patients who receive a Lyme disease diagnosis and are treated appropriately do not always return to a baseline of health. Retrospective studies of patients who were previously treated for Lyme disease found that 34-53% of patients reported persistent or recurrent symptoms following treatment (Shadick et al., 1994; Asch, Bujak, Weiss, Peterson, & Weinstein, 1994). More recent trials in ideally treated patients show improved outcomes but continue to document persistent or recurring symptoms in as many as 17% of patients up to 12 months after treatment (Wormser, 2003).

Disproportionate research funding and inadequate research trials

Lyme disease is a research-disadvantaged disease. Although the incidence of Lyme disease is nearly eight times higher than the number of people diagnosed with HIV/AIDS each year in the U.S. (38,500), the number of clinical studies for Lyme disease rank behind leprosy, which has an incidence of fewer than 200 cases per year (Centers for Disease Control and Prevention, HIV Surveillance Report, 2016; Centers for Disease Control and Prevention, National Notifiable Diseases Surveillance System, 2018; Goswami et al., 2013; National Institute of Allergy and Infectious Disease, 2017; Health Resources and Services Administration, 2018). Moreover, the pharmaceutical industry has lacked interest in investing in research because the disease is treated with off-label generic antibiotics.

Just four randomized controlled trial studies (generating three papers) on the retreatment of persistent Lyme disease have been funded by the National Institutes of Health (NIH), and the last retreatment trial was funded over 15 years ago (Klempner et al., 2001; Krupp et al., 2003; Fallon et al., 2007). The trials were quite small, ranging from 37 to 129 participants. The enrolled patients represented a highly selective group, as 89% to 99% of the patients who applied for the trial were excluded from participating. (Klempner et al., 2001; Krupp et al., 2003; Fallon et al., 2007; Johnson, Chart Book, 2019). The trials, which relied on average treatment effects of the overall samples as their measure of success (Fallon, 2012), produced conflicting results. Clinical trials are generally powered only to detect treatment differences on the overall sample population level (Wilke, Zheng, Subedi, Althin, & Mullins, 2012; Kravitz, Duan, & Braslow, 2006). Studies that use small sample sizes in a heterogenous population, such as that of persistent Lyme disease, are unable to detect moderate treatment effects that patients would deem clinically meaningful (Fallon, 2012).

Reliance on trial outcomes data for real-world decision-making assumes that the study population reflects the patients seen in real-world clinical practice. Yet, a "real" patient likely differs from the average trial patient in disease severity, presence of coinfections, duration of illness, stage of illness at diagnosis, and treatment responsiveness (Kravitz et al, 2006). Recognition of heterogeneity of treatment effect is highly dependent on the distribution of individual patient characteristics. Trials that exclude most patients seen in clinical care and use small sample sizes, cannot reflect treatment response heterogeneity—for example, high responders, low responders and non-responders. Big data research uses large sample sizes and emphasizes personalized medicine based on subgroup treatment effect averages reflecting the heterogeneity of the patient population. (Wilke et al., 2012; Kravitz et al., 2006; Lombardo, Lai, & Baron-Cohen, 2019).

As Dr. Gordon Guyatt, one of the founders of evidence-based medicine and the galvanizing force behind the establishment of the GRADE evidence assessment criteria states:

"Providing definitive answers in the face of low event rates and small-to-moderate treatment effects necessitates sample sizes in the thousands or tens of thousands.... Funding for such mega-trials is very limited, and is often restricted to industry sources."

--Dr. Gordon Guyatt, 2008

Barriers to accessing health care insurance: coverage and reimbursement

Beyond the challenges of diagnosis and treatment are the issues of patient access to care involving both providers and insurers, as well as the need for shared medical decision-making in the face of uncertainty. At the heart of this issue are the conflicting treatment guidelines.

IDSA is widely recognized as the preeminent infectious disease specialty society in the United States and publishes two of the three most influential infectious disease journals. Its members exert strong influence on peer review for medical journals by serving as peer reviewers and editors. Because the IDSA guidelines are frequently used, clinicians who treat outside them can become a target; some lose their licenses, and others have restrictions placed upon them, or have their reputations sullied through medical board action (Wolfram, 2008). Others may be excluded from insurance networks on which they depend to sustain their business.

The combination of legal risks and inability to participate in an insurance network have resulted in fewer clinicians willing to diagnose and treat Lyme disease. This has created an extreme access to care issue for patients who cannot find treating physicians and do not have insurance coverage. According to the MyLymeData patient survey, 50% of participants report that their clinicians do not accept insurance coverage; 26% report that they cannot find a clinician who treats persistent Lyme disease; and 18% report that they do not use antibiotics because their insurance will not cover them (Johnson, Chart Book, 2019).

Three things are essential to improving health care quality and patient outcomes in Lyme disease:

  1. Primary prevention (by effectively treating a tick bite);
  2. Secondary prevention (by promptly diagnosing and treating an EM rash and other early manifestations of Lyme disease sufficiently so as to restore health and prevent disease progression); and
  3. Tertiary prevention (by treating patients whose illness may be responsive to additional therapy, thereby reducing the morbidity associated with the chronic forms of the disease) (Cameron et al., 2014).

Achievement of these goals would prevent the disease from occurring, restore those who contract the disease to their pre-morbid health baseline, reduce the burden of disease and increase patient quality of life, and reduce health care costs.

The fact that so many patients with persistent Lyme disease report significant diagnostic delays; that they suffer a severe symptom burden and quality of life impairment; and that over 50% report having remained ill for over 10 years reflects an avoidable crisis that can be addressed by providing patients with the information they need to pursue all diagnostic and treatment options as early as possible (Johnson et al., 2011; Johnson et al., 2014).

Goals of this Report

In the context of this uncertainty and the lack of research being conducted on the treatment of Lyme disease, the question becomes: How do you treat patients who are sick today and cannot wait for tomorrow's research? Addressing this question is one of the primary goals of this report. Specifically, the report describes the following major themes and issues, and identifies potential actions that can be taken to address them.

  • Access to Care for patients with Lyme disease, coinfections, and other tick-borne diseases and conditions
  • Diagnostic errors: factors related to delayed diagnosis and misdiagnosis, including inappropriate psychiatric diagnosis
  • Shared medical decision-making
  • Clinician training, continuing education, and resources used in the diagnosis and treatment of Lyme disease, coinfections, and other tick-borne diseases and conditions
  • Patient and public health education on Lyme disease, coinfections, and other tick-borne diseases and conditions

Methods

The purpose of this section is to provide the methods used by the Training, Education, Access to Care and Reimbursement Subcommittee to prepare its report to the Tick-Borne Disease Working Group.

Membership

The Subcommittee consisted of seven members including two Co-Chairs, one from the Federal and one from the public sector. The remaining five members were part of the public, although one is employed by the Federal government. The Subcommittee is representative of all regions of the country: Northeast, Southeast, Midwest, and West Coast. (See Table 5 for the complete list of members.)

Subcommittee expertise is derived not only from the civilian sector, but also from the military sector and runs the gamut from those whose experience comes from their profession to those whose personal experiences drive their expertise. There are several advocates who run non-profit organizations and additionally may be patients or family members of patients. Health care providers, including a clinical psychologist dealing with tick-borne diseases and a representative from public health, round out the Subcommittee.

Several members are public educators, physician educators, and school educators; and one develops tick-borne disease continuing medical education courses for clinicians. Several educate government officials on the needs of patients and treating physicians to help shape public tick-borne disease health care policy. A few have experience reviewing the available scientific literature as grant reviewers for non-profit organizations and/or government programs. One has a global perspective on tick-borne diseases in the military, and another has experience working within the area of government health care policy.

Meetings

The Subcommittee scheduled a total of 13 meetings from mid-July 2019 until early January 2020 (Table 6). The Co-Chairs initially identified several areas that they felt required expert presenters to inform the report and proposed that list at the first meeting. Members discussed what information the speakers on the list could provide and what order would be best. Additionally, while brainstorming, Subcommittee members came up with additional topics and speakers. Since most members were already familiar with the field of Lyme disease and other tick-borne diseases, they knew the experts and the literature (authors) that would support areas the committee would address in its report (Table 7). The first speaker discussed the historical perspective on Lyme disease, which informed much of the report's Background Section, as did subsequent meeting discussions on the issue. The Co-Chairs volunteered to begin drafting the Background with help from the support writer and to compile the Methods section, the latter of which was begun after the first meeting. At Meeting 6, the Subcommittee reached a consensus to submit the Methods Section, with the understanding that more information would be forthcoming in this report as the Subcommittee continued its work. High-level summaries were written for each meeting held (see Appendix B).

Literature Selection

The literature used to support the data presented in this report was selected from peer-reviewed journals, expert presentations to the Subcommittee, and from Subcommittee members themselves who have relevant backgrounds and experience related to the content they have written. Additionally, the individual sections and entire Results and Potential Actions report were thoroughly discussed and read by the Subcommittee members, who often added other citations to strengthen the content. A Subcommittee Co-Chair also read all versions of the final report to ensure as many relevant and up-to-date citations as possible were included.

Limited literature searches were done on the topics that have little or no research associated with them. Literature that might contradict works cited in the report was identified by members of the Subcommittee with expertise in those areas or from expert presentations. Once the Results and Potential Actions report was drafted, Subcommittee members reviewed their respective sections with the goal of addressing divergent perspectives and including relevant literature.

Inclusion of Federal Inventory Results

The results from the Federal Inventory were not available to the Subcommittee while this report was being drafted. They are, therefore, not reflected in the Potential Actions herein.

Acquisition and Use of Public Comments

The Public Comments Subcommittee summarized and categorized all public comments received by the Tick-Borne Disease Working Group and sent them to the Subcommittee Co-Chairs to review and distribute to the Subcommittee. One member analyzed the comments pertaining to this Subcommittee and categorized them as either already addressed, not needing to be addressed, or missing in the report. Members then reviewed the sections they had written to determine if comments that had not been addressed could be covered in their sections. Additionally, at Meeting 11 (on 12/06/2019), the subcommittee reviewed the comments that were not addressed in the report but that were considered relevant and significant to the report. The Subcommittee then developed language for the report that addressed the missing topics.

Development of the Subcommittee Report

During the earlier meetings, the Subcommittee discussed what the goals of the report should be, what speakers should be invited to present to the Subcommittee, what order of presentations would be beneficial, and when those presentations would be feasible. The meeting schedule was set up, and agendas were developed to keep the Subcommittee on task and on schedule (see Appendix A). Priority issues were identified by the Subcommittee, and individuals volunteered to participate in writing groups devoted to each priority issue.

In developing the complete Subcommittee report, the report section writers were asked to evaluate any divergent viewpoints where stakeholders do not have consensus (for example, the Lyme disease treatment guidelines), to ensure inclusion as much as possible of different perspectives in the report.

The Subcommittee went over all of the revisions submitted for the Results and Potential Actions using screen share technology to go over comments and revisions and to refine the language in its report, with minor revisions made.

The subcommittee reviewed a document containing only the Priorities and Potential Actions, "at-a-glance." Examining each Potential Action one-by-one, members refined the verbiage to enhance concision, clarity, and consistency. They also discussed and agreed upon ways to consolidate the Potential Actions. Also, as necessary, presenters were contacted to seek permission to include their content in the report.

On the last phone meeting of the Subcommittee, January 3, 2020, the members went over each of the individual Potential Actions again. Several were shortened, and a few were clarified. Votes were taken on each Potential Action, and all were adopted by unanimous vote. The entire Results and Potential Actions report was unanimously adopted for presentation to the Working Group, subject to non-substantive minor edits which might be uncovered before actual submission (Table 8).

Development of the PowerPoint briefings for the Tick-Borne Disease Working Group

The PowerPoint for the September 12, 2019 Tick-Borne Disease Working Group public meeting on the Subcommittee's progress to date was initiated by one of the Co-Chairs who created a draft presentation based on the guidance slides provided and what had transpired in the first four meetings of the Subcommittee. The other Co-Chair then provided input which was incorporated into the slides. At that point, the presentation was provided to the Subcommittee members for their input. Any relevant input from the Subcommittee was then incorporated into the final product. The Co-Chairs decided to share presenting the PowerPoint to the Tick-Borne Disease Working Group.

To develop the Powerpoint for the January 28-29, 2020 briefing of the Tick-Borne Disease Working Group, the Subcommittee were asked—during the development of their report—to think about the most important information to include in the presentation to the Working Group. Between meetings, the Subcommittee was shown the beginning draft of the PowerPoint, which was being developed by the Co-Chair and two subcommittee members. The Subcommittee's PowerPoint was completed and submitted to the Working Group on January 10, 2020.

Membership Composition, Meetings, Presentations, and Decisions

The following tables reflect the work of the Training, Education, Access to Care and Reimbursement Subcommittee.

Table 5: Members of the Education, Training, Access to Care and Reimbursement Subcommittee

Name/Organization(s) Type Stakeholder Group Expertise

Co-Chair
Pat Smith, BA

President, Lyme disease Association, Inc.

CDMRP Programmatic Panel Member

New Jersey

Public Advocate (non-profit); Family Member Lyme/TBD public educator; physician CME educator; government & schools educator; advocate for legislation, school issues, patient services, doctors right to use clinical discretion; research, education, patient support grantor; federal advisory com. experience.

Co-Chair
Rebecca Bunnell, MPAS,PA-C

CDR, United States Public Health Service

Senior Advisor, Learning & Diffusion Group, CMS Innovation Center

Maryland

Federal Public Health Federal and public health policy, federal grants/contracts; health care provider; patient centered care; emergency preparedness & response.

Co-Chair
Elizabeth Maloney, MD

President, Partnership for Tick-Borne Diseases Education

Minnesota

Public Health Care Provider (family physician) Medical education Provider; CME course developer; Lyme/TBD Community educator; government & schools educator; TBD grant reviewer; healthcare admin.

Megan DuLaney, MS

Senior Interagency Liaison & Policy Advisor, Henry M. Jackson Foundation,

in support of DoD Health Affairs & Center for Global Health Engagement, USU

Virginia

Public Patient Patient experience; military health, global health, federal interagency coordination, policy analysis.

Doug Fearn

President, Lyme Disease Association of Southeastern Pennsylvania, Inc.

Pennsylvania

Public Advocate (non-profit); Patient; Family Member Community educator; government educator; author of "Lyme Disease: The Basics;" research grant reviewer.

Lorraine Johnson, JD, MBA

CEO, LymeDisease.org

Principal investigator, MyLymeData

California

Public Advocate (non-profit) Health care policy & ethics; patient-centered care; GRADE; evidence-based medicine; big data; data, patient registries; treatment guidelines; federal advisory panels; government officials' educator; researcher.

Sheila M. Statlender, PhD

Clinical Practice - Private Practice

Massachusetts

Public Health Care Provider, Family Member Patient support; community and mental health educator; advocate for legislation, government policy, school and disability rights.

Stakeholder Types = Patient, Family Member, Advocate (nonprofit), Health Care Provider, Public Health, Other (if other please type in description).

Table 6: Meetings of the Education, Training, Access to Care and Reimbursement Subcommittee

Meeting No. Date Present Topics Addressed
1 7/15/19 Smith, Bunnell, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call, member introduction, expertise brought to table; milestones & deliverables expected & due; report topics to be included; potential speakers; background & methods sections; meeting schedule, adjournment.
2 7/29/19 Smith, Bunnell, DuLaney, Johnson, Maloney, Statlender Roll call; speakers notified/confirmed; Speaker presentation, Lorraine Johnson, CEO, LymeDisease.org, Historical perspective on Lyme disease issues, Q&A; Share Point; individuals for topics; background & methods; meetings; adjournment.
3 8/16/19 Smith, Bunnell, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call; speaker lineup, length/discussed; Clinical resources being used (CDC, Up to Date); guidelines, military provider & patient perspectives & testing data; military vs. Veterans Affairs; insurance & access to care; Medicare/ Medicaid ; uninsured patients; homelessness-lack of insurance; state insurance commissioners; Methods & Background discussed; new LD diagnostic; adjournment.
4 8/30/19 Smith, Bunnell, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call; speaker presentation, Sue Partridge, MPH, CDC, Communicating About TBD, Q&A; discussed addressing accuracy in CDC content; name change of committee to Training & Education, Access to Care and Reimbursement; CDC featured Zeus test in MMWR; upcoming speakers; adjournment.
5 9/13/19 Smith, Bunnell, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call; Speaker presentation, Elizabeth Maloney, MD, President, Partnership for Tick-Borne Diseases Education, ILADSs & NICE Lyme Treatment Guidelines, Q&A; presentation of stories; review meeting 10 of Working Group; possible meeting with Working Group members; timeline; speaker request; future meetings; division of work; adjournment.
6 9/27/19 Smith, Bunnell, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call; Speaker presentation, John Aucott, MD, Johns Hopkins University, Cost of Illness Study, Q&A; Upcoming speakers, mtgs., WG news; procedures & discussion on subcom. Writing Groups; Next steps; Methods Section: consensus to submit; Background discussed, to be given to subcommittee for comments before submission; adjournment.
7 10/11/19 Smith, Bunnell, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call; speaker presentation, Elliott Pollack, LL.B Pullman-Comley, Lyme Disease: An Attorney's Perspective; Q&A; Background section discussion & vote; announcements on upcoming meetings/speakers; Email from CDC on resource to contact on CDC communications; submission of methods report announced; Sharepoint discussion; Results & Potential section actions timeline discussed; adjournment.
8 10/18/19 Bunnell, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call; speaker presentation, Robin Gelburd, JD, President Fair Health & Ali Russo, Chief Information Officer; Using Claims Data to Illuminate Trends and Patterns in Lyme Disease; Q&A; follow-up discussion; review of Results & Potential Guidance document; presentation of timeline template; Writing Group updates; SharePoint demonstration; next meeting; adjournment.
9 11/01/19 Smith, Bunnell, DuLaney, Fearn, Johnson, Maloney, Statlender

Roll call; speaker presentations, Nicole Malachowski, Testimony to the Department of Health and Human Services, Tick Borne Disease Working Group: Training & Education, Access to Care and Reimbursement Subcommittee, & Megan

DuLaney, The Military Health System Overview, Observations, Opportunities; Q&A; follow-up discussion; Results & Potential Actions Writing Group updates; review of next steps and next meeting date/time; adjournment.

10 11/15/19 Smith, Bunnell, DuLaney, Johnson, Maloney, Statlender Roll call; speaker presentation, Paul Auwaerter, MD, Johns Hopkins University, Updated Lyme disease guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and the American College of Rheumatology (ACR); Q&A; follow-up; discussion of the Results and Potential Actions section; Speaker presentation, Elizabeth Lee-Lewandrowski, PhD, MPH, Massachusetts General Hospital, Harvard Medical School (with Kent B. Lewandrowski, MD, Pathologist, Massachusetts General Hospital Associate Chief for Laboratory and Molecular Medicine) Laboratory blood-based testing for Lyme disease at a National Reference Laboratory: A 7-year experience; Q&A; follow-up; consideration/inclusion of public comments in the subcommittee's report; literature selection & inclusion process; Writing group updates; next steps, next meeting; adjournment.
11 12/06/19 Smith, Bunnell, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call; next subcommittee meeting 12/20, 1/3/20; Results Draft v5 was submitted to WG; Methods Section update and collect data; divergent perspectives /literature-- sections need to review for inclusion; Public comments- review summary; additions to Results sections; Writing Groups reports v5, review each area for short adds, edits, by section leader; Background, edits or adds; discussion of a summary of Background; next steps, adjournment.
12 12/20/19 Smith, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call; next subcommittee meeting 1/3/20; Review and discussion of the complete draft Subcommittee Report (version 2); Review and discussion of the Priorities and Potential Actions; Discussion of the Subcommittee Report presentation to the Tick-Borne Disease Working Group; Next steps; adjournment
13 01/03/20 Smith, DuLaney, Fearn, Johnson, Maloney, Statlender Roll call; Final subcommittee meeting; Review and discussion of complete draft Subcommittee Report v3—reviewed revisions made since v2, made minor content revisions; Finalization of Potential Actions—further refined language; Vote on Potential Actions; Vote on final report content; Announcement about alternate Federal member stepping in on WG for CMS; Decision to review the Powerpoint presentation to the Working Group and submit feedback by email; adjournment

Table 7: Presenters to the Education, Training, Access to Care and Reimbursement Subcommittee

Meeting No. Presenter Topics Discussed Ok to Share?
2

Lorraine Johnson, JD, MBA

CEO LymeDisease.org

Historical perspectives of Lyme disease issues; LymeDisease.org: focus, mission, data collected, research published, collaborations; Illness/quality of life; TB pathogens; Early/late stage symptoms; Treatment failure rates; Patients with persistent disease; Delayed diagnosis/persistent Lyme; Flawed diagnostic tests; Biopsies; Lack of pharmaceutical interest; Disproportionate funding; Lack of research to support clinical judgement; Conflicting treatment guidelines. Yes
4

Sue Partridge, MPH

Centers for Disease Control & Prevention

Communications Issues; Division of Vector-Borne Diseases vision, mission, and goals, Focus on prevention; 3 of 4 branches devoted to communicating about ticks & TBD: Arborviral, Bacterial, Rickettsial; Content creation process, Role of communications lead & subject matter experts, Types of content; Use of web metrics to determine what topics people search for online; Raising awareness through social media; Public inquiry process & 2019 inquiries so far; Media activities, Webinars, videos, training; Drivers of new/updatedcontent; Clearance chain; Soliciting stakeholder input. Yes
5

Betty Maloney MD

Family Physician

President, Partnership for Tick-Borne Diseases Education

ILADS, NICE Guidelines; Background of guidelines; IOM guidelines standards; Review of GRADE-based guidelines standards; Comparison of guidelines; Comments on draft guidelines. Yes
6

John Aucott, MD

Johns Hopkins University

Cost of Illness Study; Advantages & disadvantages of data; Post-treatment outcomes of stages of Lyme; Claims data; Insurance Claims data; Chart reviews & surveys; Direct medical; Indirect medical; Johnson study; Severity compared to other chronic conditions; Delong estimate of PTLD; Cost to society; Cost as obstacle to care. Contact for permission
7

Elliott Pollack

LL.B Pullman-Comley

Lyme Disease: An Attorney's Perspective; Typical source of concerns and complaints: Parents—non-custodial, State health departments, State/county medical societies, State medical boards, Insurance companies, Institutional medical staffs; Support for claims against providers: Standards of care—burden of proof (statutory & regulatory), Peer-reviewed literature (expert testimony), Impact of IDSA/AAN and ACR (draft) 2019 guidelines and 2014 IDSA guidelines; Types of discipline sought: Licensure termination, Licensure suspension/probation; Sequela (Medical liability insurance, Third-party payers, Institutional privileges, Data bank report, Court of public opinion); Example cases. Yes
8

Robin Gelburd, JD

President, Fair Health

Ali Russo, Chief Information Officer, FAIRHealth

Report stats on geographic diversity, urban & suburban; Overview of FAIRHealth; Comparisons of Lyme disease and other tick-borne diseases; Comparisons of Lyme disease patients and all other patients; Comparisons of Lyme disease patient vs. all other patient diagnoses of; FAIRHealth platform overview; FAIRHealth honors. Yes
9

1. Colonel Nicole Malachowski, USAF, Ret.

2.Megan DuLaney, patient,

military health professional experience

Testimony to the Department of Health and Human Service, Tick-Borne Disease Working Group: Training, Education, Access to care, and Reimbursement; 1. Lack of consideration off TBD in differential; Misdiagnosis of TBD patients w/FM,CFS,MS,GWS (now chronic multisystemic illness); Med. Retirement of service members due to misdiagnosis: psychosomatic & mental health; effects of misdiagnosis/delayed dx on readiness & taxpayer return on investment; personal TBD experience; challenges related to military health system; opportunities w/i system.

2. Personal struggle with TBD; Personal work w/DoD; Military Health System: Overview, Observations, and Opportunities; Overview of military health system; Health policy & strategy of military health system; Possible opportunities.

Contact for permission

No

10

Paul Auwaerter, MBA, MD, Clinical Director, Division of Infectious Diseases; Professor of Medicine, Johns Hopkins Medicine

Elizabeth Lee-Lewandrowski, PhD, MPH, Massachusetts General Hospital, Harvard Medical School

(on Q &A) Kent B. Lewandrowski, MD, Pathologist, Massachusetts General Hospital Associate Chief for Laboratory and Molecular Medicine)

Updated Lyme disease guideline by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and the American College of Rheumatology (ACR); Background on Guidelines: Prevention, diagnosis, and treatment, Scheduled ~ release date, Organizations involved, Target audience; Chair & Panel selection: Diverse stakeholder group, Process for approval, Conflict-of-interest disclosures & review; Panel composition, Experience /background of stakeholders, Patient representation, Methods, Identif./rating: outcomes of interest, Development of clinical questions, Literature search; Applications of Grade Approach, Preparation & review of evidence summaries, Confidence rating, Presentation to panel, Drafting of recommendations, "Strong" or "weak" designations, Recommend w/ low-quality evidence, Wording of good practice statements; Post publication review, Time frame for reviewing & potentially update Lyme disease guideline, Process for review & potential revision.

Laboratory blood-based testing for Lyme disease at a National Reference Laboratory: A 7-year experience;Background: Reported cases over time,

Clinical features of LD, Reporting by 7 commercial labs, CDC perspective on incidence; Regional Data from Massachusetts Gen: Volume & + of EIA,

Volume & + of WB; National Data from Quest: Background on Quest, Total LD tests & +/yr., Avg. LD tests & +/mo./7 yrs., Total LD + over 7 yr. by gender, test type, age group, Volume & + by yr. for LD blood PCR, Changing demographics of LD+ in US.

Yes

Contact for permission

Table 8: Votes taken by the Training, Education, Access to Care, and Reimbursement Subcommittee

Meeting No. Motion Result
Accept/Object/Abstain/Absent
Minority Response
7 Preliminary approval of the Background section for submission to the Tick-Borne Disease Working Group, with the understanding that it could be revised at a later date Passed
7 / 0 / 0 / 0
None
13 Approval of Potential Action 1—final wording< 6 / 0 / 0 / 1 None
13 Approval of Potential Action 2—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 3—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 4—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 5—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 6—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 7—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 8—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 9—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 10—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 11—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 12—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 13—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 14—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 15—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 16—final wording 6 / 0 / 0 / 1 None
13 Approval of Potential Action 17—final wording 6 / 0 / 0 / 1 None
13 Approval of the complete Subcommittee Report to the Tick-Borne Disease Working Group, with the understanding that minor non-substantive revisions may be made before the final submission on 01/10/2020 6 / 0 / 0 / 1 None

Results and Potential Actions

For consideration by the Tick-Borne Disease Working Group, the Training, Education, Access to Care, and Reimbursement Subcommittee has identified seven prioritized issues and seventeen potential actions to achieve them.

Priorities and Potential Actions At-A-Glance

Prioritized Issue: Access to Care

Potential Action 1:

Increase public awareness that there are two divergent approaches reflected in guidelines to the diagnosis and treatment of Lyme disease. Encourage the disclosure that there are two diagnostic and treatment approaches on all state and Federal government web pages that discuss Lyme disease or tick-borne illness, including CDC, NIH, and the Agency for Healthcare Research and Quality (AHRQ); and encourage inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Potential Action 2:

Encourage all state and Federal government committees and panels, including the CDC, NIH, DoD, the Agency for Healthcare Research and Quality (AHRQ), and medical specialty societies to use authentic and meaningful representation of patients with persistent Lyme disease in health care policy matters, the determination of research grants, and in the development of diagnostic and treatment guidelines.

    • To serve as a meaningful representative, patients or advocates representing the persistent Lyme disease community should: a) have or have had persistent Lyme disease or be someone who serves or has served as a caregiver to a persistent Lyme disease patient; and b) should be an officer or director of a recognized and trusted patient advocacy organization representing patients with persistent Lyme disease, or someone vetted and approved by such a group.
    • To ensure process integrity in the selection of patient representatives through open and transparent selection processes, including public calls for nominations and soliciting nominations through recognized and trusted patient advocacy groups representing patients with persistent Lyme disease.

Prioritized Issue: Reducing Diagnostic Errors and Delays in Lyme Disease

Potential Action 3:

Renew and expand the recommendation for CDC to develop a multi-leveled curriculum on Lyme disease for clinicians. This should include instructional programs for medical students, residents, physician assistants, mental health professionals, and nurse practitioners. Ongoing education via continuing medical education programs should also be included. In addition to providing background information on all aspects of these infections, the content should highlight the most frequent sources of diagnostic errors identified in this report, including:

  • Inappropriately excluding Lyme disease from the initial differential diagnosis because of geographic exclusions that inaccurately reflect the geographic scope of the disease;
  • Failing to recognize the full spectrum of Lyme disease-related symptoms;
  • Failing to identify erythema migrans rashes and/or other Lyme disease-related findings on physical exam; and
  • Cautioning clinicians against over-reliance on inaccurate diagnostic tests.

The training should also emphasize the inclusion of Lyme disease as part of a relevant differential diagnosis.

The curriculum development team should include representatives of all stakeholder groups, including patients. Clinicians and research scientists with expertise in this field should be selected such that the team represents the spectrum of scientific and clinical perspectives on tick-borne diseases.

Potential Action 4:

Recommend that CDC provide input to the Council of State & Territorial Epidemiologists, CSTE, that the Lyme disease surveillance case definition be revised such that it abandons the use of geographic parameters for Lyme disease.

Potential Action 5:

Recommend funding CDC to conduct periodic studies using big data technology tools that are now available using laboratory data from a number of the major diagnostic labs. Findings from these studies would not replace the current surveillance system but would provide an additional information source that would increase our understanding of the geographic exposure and growth in the incidence of Lyme disease.

Potential Action 6:

Recommend that CDC, NIH, and other government agency websites, brochures, and educational materials abandon the use of geographic parameters for the diagnosis of Lyme disease and that clinicians and the public be made aware that Lyme disease has been reported in all states.

Potential Action 7:

Recommend that CDC, NIH, and other government agency websites, brochures, and educational materials acknowledge the diagnostic limitations of clinically available laboratory tests for all stages of Lyme disease.

Prioritized Issue: Reducing Psychiatric Misdiagnosis In Lyme Disease

Potential Action 8:

Provide information and training to health care professionals regarding the full spectrum of Lyme disease symptoms, including the potential impact on brain function. Lyme disease should be included in the differential diagnosis of patients with neuropsychiatric symptoms in order to promote appropriate diagnostic evaluations and subsequent treatment. Clinicians should be cautioned not to default to a psychiatric diagnosis when the cause of symptoms has not yet been determined.

Potential Action 9:

Provide education and training to neuropsychologists, clinical and school psychologists, social workers, and other pertinent school personnel regarding the extent and complexity of the emotional, physical, cognitive, sensory, and other aspects of brain dysfunction that may be experienced by students with Lyme disease.

Potential Action 10:

Encourage the development of multidisciplinary treatment teams that recognize medical, neuropsychiatric, and neuropsychological symptoms that may be experienced by some patients. Recommend funding for NIH to develop an in-patient unit for multidisciplinary treatment of Lyme disease patients who present with neuropsychiatric symptoms.

Prioritized Issue: Shared Medical Decision-Making

Potential Action 11:

Increase public awareness that there are two divergent approaches to the diagnosis and treatment of Lyme disease. Encourage the disclosure that there are two diagnostic and treatment approaches on all state and Federal government websites that discuss Lyme disease or tick-borne diseases, including CDC, NIH, AHRQ, and encourage inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Potential Action 12:

Encourage the disclosure that the state of the science in Lyme disease, particularly for persistent Lyme disease, is limited, emerging, and unsettled on all state and Federal government websites that discuss Lyme disease or tick-borne diseases, including CDC, NIH, AHRQ, and encourage inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Potential Action 13:

Encourage the use of shared decision-making in Lyme disease on all state and Federal government websites that discuss Lyme disease or tick-borne diseases, including CDC, NIH, AHRQ, and encourage inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Prioritized Issue: Reimbursement And Coverage

Due to circumstances beyond the control of the Subcommittee, this portion of the report was not able to be completed and should be deferred for consideration until the next Tick-Borne Disease Working Group convenes.

Prioritized Issue: Patient And Public Health Education On Lyme Disease And Other Tick-Borne Diseases

Potential Action 14:

Recommend that CDC, NIH, and other government agency websites, brochures, and educational materials on Lyme disease and other tick-borne diseases be developed by a curriculum development team and, given the differences in scientific perspectives regarding tick-borne diseases, that this team should include clinical and research experts that represent a broad range of scientific and clinical perspectives.

Potential Action 15:

Improve public information about occupational risks of tick-borne diseases and the risks associated with blood transfusions and organ transplants.

Prioritized Issue: Clinician Training on Tick-Borne Diseases

Potential Action 16:

Renew the recommendation for CDC to develop a multi-leveled curriculum on tick-borne diseases for clinicians that could be used throughout the U.S. There should be instructional programs for medical students, residents, physician assistants, and nurse practitioners. While the emphasis should be on training the clinical specialists most likely to encounter patients during their initial presentation of TBD (e.g. family practitioners, pediatricians, general internists, and emergency medicine physicians), specialty and subspecialty-specific training should be developed for other clinician groups. Ongoing education via continuing medical education programs should also be included. In addition to providing background information on all aspects of these infections, the content should highlight frequently misunderstood or underappreciated concepts, such as the consequences of overly restrictive geographic characteristics of the infection, variations in the appearance of erythema migrans rashes, and limitations of serologic testing that are associated with misdiagnoses as well as diagnostic and therapeutic delays. The training should also emphasize the inclusion of tick-borne diseases as part of a relevant differential diagnosis and offer examples of clinician examination questions.

The curriculum development team should include representatives of all stakeholder groups, including meaningful patient representation. Clinicians and research scientists with expertise in this field should be selected such that the team represents the spectrum of scientific and clinical perspectives on tick-borne diseases.

Potential Action 17:

Recommend to DoD:

  • Develop stand-alone educational modules for Uniformed Services University students that cover the spectrum of tick-borne disease from prevention, to diagnosis, to treatment. Training should specifically highlight the risks of military occupational hazards from tick-borne diseases as a result of training environments (both domestic and overseas), deployments, and reassignments. Training should also emphasize the transient nature of military assignments that can increase the risk of misdiagnoses and diagnostic delays for both service members and military dependents. The curriculum development team should include representatives of all stakeholder groups, including meaningful patient representation. Clinicians and research scientists with expertise in this field should be selected such that the team represents the spectrum of scientific and clinical perspectives on tick-borne diseases.

Institutionalize tick-borne diseases training and education via the Defense Health Agency (DHA). Standardize training, education, and force health protection guidelines across the Military Services. Implement continuing medical education programs via existing forums such as the DHA Primary Care Clinical Community Speaker Series, and disseminate information on relevant tick-borne diseases programs (for example, the Army Public Health Center's Human Tick Test Program). The curriculum development team should include representatives of all stakeholder groups, including meaningful patient representation. Clinicians and research scientists with expertise in this field should be selected such that the team represents the spectrum of scientific and clinical perspectives on tick-borne diseases.

Prioritized Issue: Access to Care

The Institute of Medicine (IOM)—recently renamed the National Academy of Medicine (NAM)—defines access to health care as "the timely use of medical care to obtain the best possible outcome" and frames the issue as follows:

The most important consideration is whether people have the opportunity for a good outcome—especially in those instances in which medical care can make a difference. When those opportunities are systematically denied to groups in society, there is an access problem that needs to be addressed (IOM, 1993).

According to the Office of Disease Prevention and Health Promotion (ODPHP) (2019), under the Assistant Secretary of Health, access to care promotes and maintains health, prevents and helps manage disease, and reduces unnecessary disability and premature death. The ODPHP Healthy People 2020 initiative views improving access to care as one of the most important ways to reduce health disparities. "Every person in every community across the Nation deserves equal access to comprehensive, culturally competent, community-based health care systems that are committed to serving the needs of the individual and promoting community health" (U.S. Department of Health and Human Services, 2010). Patients with Lyme disease, particularly those with persistent Lyme disease, face significant barriers to accessing care, including finding a physician who is reasonably nearby, financial burdens arising from insurance denials, inability to obtain in-network care, limitations on ability to work or go to school, stigma, and discrimination.

Importance

Access to health care can reduce the incidence of preventable diseases, provide early detection and diagnosis of treatable diseases, and reduce mortality and morbidity of chronic diseases (IOM, 1993). Achievement of these goals for Lyme disease would help patients avoid contracting the disease in the first place, restore health through prompt diagnosis and effective treatment, help prevent the development of persistent Lyme disease, and improve the quality of life for those who do develop persistent Lyme disease.

Access to care issues in Lyme disease arise in two areas. The first is the ability to obtain prompt diagnosis and treatment, which is effective in restoring health. Eighty-four percent of respondents to a 2011 survey of over 2,400 Lyme disease patients were not diagnosed within the first four months of symptom onset (Johnson et al., 2011). Another study based on responses of over 3,000 patients with persistent Lyme disease from the MyLymeData registry showed that more than half (51%) reported that it took them more than three years to be diagnosed, and roughly the same proportion (54%) saw five or more practitioners before diagnosis (Johnson, 2018).

The second area where access to care issues arise relates to persistent Lyme disease. When diagnosed early and given appropriate treatment, most Lyme disease patients make a full recovery. Even so, up to 35% of patients diagnosed and treated early develop persistent Lyme disease, experiencing chronic, often debilitating, symptoms (Aucott, Rebman, Crowder, & Kortte, 2012). When Lyme disease is not diagnosed early, it is much more difficult to treat effectively, and treatment failures are much more likely.

In a cost-of-illness study published by Centers for Disease Control and Prevention (CDC) in 2006, Zhang and colleagues found that the mean annual cost of illness was $1,310 per patient for early Lyme disease, but was $16,199 for late Lyme disease—roughly a 12-fold increase (Zhang et al., 2006). A Johns Hopkins study of a large insurance database found increased health care utilization and costs for acute Lyme disease patients who failed treatment and developed persistent Lyme disease (Adrion, 2015). Another study of over 3,000 persistent Lyme disease patients also reported increased utilization of health care services, and greater out-of-pocket medical costs (Johnson, 2014).

Patients with persistent Lyme disease experience significant quality of life impairment when measured using the CDC nine-item "Healthy Days Measure," a self-reported health questionnaire (Centers for Disease Control and Prevention, Measuring Healthy Days, 2000; Johnson, 2014). Respondents to a study of over 3,000 persistent Lyme disease patients reported very poor health-related quality of life, with 72% reporting fair or poor health status, significantly exceeding the 62% rate reported by those with congestive heart failure and the 16% rate of the general population (Johnson, 2014; Johnson, 2018; Burns, 1997). In addition, respondents reported many days when they were physically and mentally unhealthy, with activity limitations and lack of rest, compared to the general population (Johnson et al., 2014). (See Appendix C.) Patients with persistent Lyme disease also report impairment in their ability to work or go to school, and greater out-of-pocket medical costs (Johnson et al., 2014). Two studies found that roughly a quarter of patients had been on disability at some point in their illness (Johnson et al., 2014; Johnson, 2011). The majority reported that they had been ill for 10 or more years.

Unfortunately, patients with persistent Lyme disease report that they are systematically denied access to the care they need. For example, 67% report that they have postponed or avoided medical treatment due to discrimination, disrespect, or difficulty obtaining care, and nearly half (47%) report that they have been denied treatment (Johnson & Stigma, 2019). Many of the barriers to care in Lyme disease are the result of structural imbalances among medical societies, insurers, government agencies, and providers.

Identifying and reducing barriers to care for this population should increase health care equity, reduce medical costs and symptom burden, improve quality of life and access to care, and restore these patients' ability to become productive members at work or school, as well as reduce disability.

Summary of evidence and findings

Introduction and background

Access to care issues may include financial barriers, including lack of health insurance, insufficient health insurance to cover needed services, or not having the financial capacity to cover out-of-pocket health costs. Structural barriers include the lack of competent health care professionals to provide the care patients need to obtain satisfactory health outcomes. Personal barriers include concerns about stigma, confidentiality, and discrimination.

According to the Agency for Healthcare Research and Quality (AHRQ), access to care requires three key factors: gaining entry into the health care system, accessing a location (geographically) for care, and finding a trusted clinician to provide care (AHRQ, 2014).

The widely followed Penchansky and Thomas model of access to care breaks down the essential components into the "5 A's":

  • Affordability: Patients' ability to pay for services;
  • Accessibility: Geographic accessibility;
  • Availability: Supply and demand;
  • Acceptability: Patients' ability to gain access to satisfactory health outcomes; and
  • Accommodation: Patients can obtain access in usual care settings (Penchansky & Thomas, 1981; McLaughlin & Wyszewianski, 2002).

Persistent Lyme disease patients face substantial access to care barriers

Many patients with persistent Lyme disease report substantial barriers to access health care as well as stigma and discrimination, which may include outright denial of care, provision of sub-standard care, and physical and verbal abuse (Nyblade, 2019). Although we often associate stigma and discrimination with race and sexual orientation, it also arises in the context of health care conditions, including, for example, leprosy, mental illness, epilepsy, disability, HIV, Lyme disease, tuberculosis, substance use, and hepatitis.

LymeDisease.org conducted a survey of over 1,900 patients enrolled in its Institutional Review Board- approved MyLymeData Patient Registry on the topic of access to care, discrimination, and stigma between November 5, 2018 and February 2, 2019 (Johnson & Stigma, 2019). The survey showed that patients face disrespect and discrimination both within and outside the health care system. Patients reported that they have encountered the following barriers to accessing care:

  • 74% had been treated disrespectfully by a health care provider;
  • 67% had postponed or avoided medical treatment due to discrimination, disrespect, or difficulty obtaining care;
  • 47% had been denied treatment;
  • 47% had been denied insurance coverage for their Lyme disease treatment;
  • 86% found it hard to find a health care provider who would treat or prescribe appropriate treatment;
  • 74% of those looking for work were either very concerned (50%) or somewhat concerned (24%) that if a potential employer knew they had Lyme disease it would limit their job opportunities; and
  • Over 80% were concerned that an insurer might use their health care data to deny coverage in the future citing a pre-existing condition.

Structural access-to-care barriers make it difficult for persistent Lyme disease patients to obtain care through their usual health care channels and relegate patients to marginalized health care

Access to care may be affected by institutional and structural health care barriers as well as by hidden barriers, such as non-physician gatekeepers, and stigma, disrespect, or discrimination associated with medical care (Nyblade et al., 2019). Structural imbalances are largely driven by power imbalances (Nyblade et al., 2019).

One of the contributing factors to the access to care issues faced by persistent Lyme disease patients is the uncharacteristic structural imbalances between the profit-driven interests of the pharmaceutical industry and health care insurers. Typically, insurers try to keep costs down to increase profits and do so by limiting or denying care through medical necessity determinations or requiring that a patient fail one therapy before approving a more expensive option. Dr. David Eddy, a highly regarded health care policy thought leader, puts it this way: "In a field filled with uncertainty and doubt, the difference between "when in doubt, do it" and "when in doubt, stop" could easily swing $100 billion in revenue" (Eddy, 1993) In contrast, pharmaceutical companies increase profits by driving up demand (for example through direct-to-consumer ads) and expanding market size by promoting additional uses for their medications.

Because the interests of pharmaceuticals and insurers are both powerful and typically adverse, they tend to counter-balance each other in the marketplace. However, in persistent Lyme disease, the common interest of insurers in cost reduction is not offset by the powerful interests of pharmaceutical companies because antibiotics are not seen as a lucrative market compared to the other drugs in their portfolio or in development. Generic antibiotics are short-term treatments (compared to drugs like cholesterol medications that may be taken for life), their price is low (compared to patented medications), and their potential target market is inherently smaller (infectious diseases are not as prevalent as heart disease). Hence, pharmaceutical company incentives to develop, patent, and market antibiotics are quite small. This has led to a recognized crisis in antibiotic development generally (Paavola, 2018).

Treatment of Lyme disease is primarily off-label generic antibiotics. Although insurers remain incentivized to cut costs through restrictive guidelines, such as those promulgated by the Infectious Diseases Society of America (IDSA), there is no counter-vailing incentive on the part of pharmaceuticals to expend funds to expand a market it views unfavorably. This has not only affected patients struggling for insurance to cover the costs of their illness, it has also diminished the incentives for drug companies to develop new treatments for Lyme disease. This makes Lyme disease analogous to rare diseases, which are similarly research-disadvantaged or orphaned. Physicians who treat Lyme disease are also left without pharmaceutical support to promote their professional conferences because the incentives to do so do not exist.

Another contributing factor to the structural imbalance that creates the access to care issue in Lyme disease is the unusual relationship between the IDSA and persistent Lyme disease patients. Typically, the interests of the medical society creating guidelines governing patient care represent—to a large extent—the interests of the front-line practitioners who treat that disease. This is not the case in persistent Lyme disease, where almost all patients select practitioners who follow the guidelines of a competing medical society, the International Lyme and Associated Diseases Society (ILADS). Very few (6%) report being treated by infectious disease physicians (Johnson, 2018). The primary difference between the two sets of guidelines is that the IDSA guidelines impose restrictive diagnostic criteria and provide limited treatment options, while the ILADS treatment guidelines recognize a significant role for the exercise of clinical judgment and shared medical decision-making. Sick patients simply want to get well. When the only treatment approach offered by the IDSA for persistent Lyme disease—short-term antibiotics—fails, patients vote with their feet and find another practitioner who is clinically innovative and will work with them to try to restore their health.

Prominent members of the IDSA and the American Lyme Disease Foundation (which has close ties to the IDSA and espouses its views) have an unfortunate tendency to trivialize patient concerns and have been quoted making disparaging remarks and joking inappropriately about Lyme disease patients (Pfeiffer, 2014; Sholtis, 2019; Scharfenberg, 2019). This has fomented a culture of disrespect and distain toward patients that appears to be unparalleled in other diseases.

Nyblade explains the issue of stigma and its impact in health care clearly: "Stigma is a powerful social process that is characterized by labeling, stereotyping, and separation, leading to status loss and discrimination, all occurring in the context of power" (Nyblade et al., 2019). Stigmatization and discrimination may be institutionalized in policies, procedures, or practices (such as guidelines) and may also result in "verticalization" of care—where patients cannot access the care they need to get well at mainstream facilities, but must instead, seek care outside mainstream medical centers with individual clinicians who offer care out-of-network from their insurance provider (Nyblade et al., 2019). Practitioners who treat persistent Lyme patients may be excluded from insurance networks—which results in patients incurring higher out-of-pocket costs and siloed care as patients seek out-of-network physicians who are experienced and willing to treat them (Wolfram, 2008).

The IDSA is the largest infectious disease specialty society in the world, publishes the two largest medical journals in the field, dominates related peer review, and often functions as a gatekeeper for hospital staff privileges. Its restrictive Lyme disease guidelines—which make it difficult for patients to achieve diagnosis and receive care—have been adopted by many insurers and are often referred to as an authoritative source by many physicians who do not specialize in the disease. In addition, members of the IDSA provide expert testimony to enforce its views through medical board disciplinary actions against practitioners who do not comply with its guidelines (Connecticut Attorney General's Office, 2008; Stricker & Johnson, 2009; Johnson & Stricker, 2010; Wolfram, 2008).

These factors create structural barriers to patients obtaining access to care by:

  • Creating a shortage of practitioners willing to treat patients with persistent disease;
  • Increasing travel distances patients must drive to obtain care;
  • Reducing the ability of patients to obtain in-network care;
  • Creating a verticalization or siloed care structure—where marginalized patients often need to seek care outside their customary sources of care; and
  • Increasing the cost of care through higher direct medical costs.

Although anti-competitive actions in medicine are not common, when medical guidelines create access to care issues that interfere with patient care, they may be subject to antitrust actions or RICO (Racketeering Influenced and Corrupt Organizations Act) actions (Wolfram, 2008). These causes of action may arise when organizations use their power in the marketplace to "sit in judgment of their competitors" by enforcing their guidelines against their competitors (Johnson & Stricker, 2010). The IDSA has been the subject of two anti-competitive legal actions. The first was an investigation by the Connecticut Attorney General in connection with the IDSA's 2006 Lyme disease guideline development process, which the National Academy of Medicine highlighted in its report on creating trustworthy guidelines (IOM, 2011).

The second action is an on-going RICO action that maintains that the IDSA has conspired and colluded with insurers to deny patients access to care (Torrey et al. vs. IDSA, BlueCross et al., 2017). This case was recently settled against Kaiser Permanente, but is on-going with respect to the other defendants. The factual issues in these cases is contentious and are beyond the scope of this report. However, it bears noting that these types of legal actions are highly unusual for patients to engage in and take an enormous amount of effort and resources. The fact that two such actions have been undertaken with respect to the IDSA guidelines reflects a severe access to care crisis with the disease.

Availability: The patient demand for care exceeds the supply of practitioners who are knowledgeable and willing to provide care

Because the IDSA is so influential in the medical community and many physicians, medical boards, and insurers are not aware that divergent Lyme disease guidelines exist, IDSA guidelines are often given the force of law by medical boards and insurers (Connecticut Attorney General's Office, 2008; Stricker & Johnson, 2009; Johnson & Stricker, 2010; Wolfram, 2008). IDSA members testify at unprofessional-conduct hearings against practitioners who do not follow its guidelines, and in support of insurance denials of care. Practitioners who do not follow the IDSA guidelines may be excluded from participating as "in-network" providers for insurance organizations and may have hospital privileges denied (Wolfram, 2008). Although the IDSA states that it does not intend for its guidelines to be applied as mandatory treatment protocols, its guidelines do not acknowledge the existence of divergent treatment approaches and severely restrict the exercise of clinical judgment. Patients have responded by passing "physician protection" legislation in a number of states as they have watched their treating practitioners come under legal attack (Lyme Disease Association, 2019).

These constrictions on Lyme disease care have resulted in scarcity of practitioners willing to treat outside the IDSA guidelines, particularly since their medical license may come under attack and they may lose their ability to provide in-network care. This issue reduces "in-network" health care provision and increases the cost of care for patients.

Affordability: Patients' ability to pay for services is difficult because costs may be artificially high, insurance coverage is limited, and many have a reduced capacity to work

Affordability "is determined by how the provider's charges relate to the client's ability and willingness to pay for services" (McLaughlin & Wyszewianski, 2002). The affordability of care is a barrier to health care for Lyme disease because insurance coverage is limited, patient out-of-pocket costs are higher, much care is provided "out-of-network" where fees are higher and must account for the longer visits that accompany complex care required of these patients, and the potential legal exposure practitioners face. In addition, the ability of patients to pay for these increased costs may be impaired by their inability to be productive members in the workforce. As discussed more fully below in the section on loss of productivity, 25% of patients report being on disability at some point and many patients report having to cut back or stop work entirely due to their illness.

Insurance coverage for persistent Lyme disease is limited. According to the ODPHP Healthy People 2020 initiative, uninsured people are:

  • More likely to have poor health status;
  • Less likely to receive medical care;
  • More likely to be diagnosed later; and
  • More likely to die prematurely (Office of Disease Prevention and Health Promotion, 2019).

Fifty percent of patients enrolled in the MyLymeData patient registry who remain ill, reported that the health care provider treating their Lyme disease does not accept their health insurance (Johnson, 2018). These patients are likely being treated out-of-network and given a superbill that they can submit to their insurer for reimbursement. This means that the patient incurs charges for the visit immediately, receives lower rates of reimbursement that are not pre-negotiated (as they are with in-network providers), and carries the risk of non-reimbursement.

Many insurers exclude practitioners who treat persistent Lyme disease from their network. In addition, 39% of those surveyed in the 2011 study who applied for medical insurance reported that their application was denied as having a pre-existing condition (Johnson et al., 2014). Lapse in health insurance is the primary predictor of medical bankruptcy in the United States (Himmelstein, Warren, Thorne, & Woolhandler, 2005; Himmelstein, Thorne, Warren, & Woolhandler, 2009). Himmelstein and colleagues found that 62% of all domestic bankruptcies have a medical cause, with medical costs and income loss playing a large role.

Lyme disease patients incur high out-of-pocket expenses.In a study of over 3,000 patients with persistent Lyme disease, respondents reported incurring high out-of-pocket expenses compared with other diseases (Johnson et al., 2014). Out-of-pocket expenses included deductibles, copayments, and payments for services not covered by health insurance that were paid by respondents or their families in the past year for costs related to Lyme disease. They did not include over-the-counter remedies. The percentage of persistent Lyme disease patients spending in excess of $5,000 in out-of-pocket costs was 46% compared to 6% in the general population (Johnson et al., 2014; National Center for Health Statistics, 2012).

Loss of productivity and disability rates for persistent Lyme patients are high.Many Lyme patients report that their ability to work has been impaired by their disease. Loss of productivity results when chronically ill workers are unable to work, reduce their work hours, take excessive sick days, or perform below par while at work. Diminished work performance exacts a toll on the worker, the worker's family, and the employer (Devol & Bedroussian, 2007). Ultimately, the government and society also suffer because of the reduction in productivity of these compromised workers.

In a survey of over 3,000 patients with persistent Lyme disease, 46% reported being employed compared to 81% of the general population of the same age (Johnson et al., 2014; Toossi, 2012). Approximately 42% of respondents reported that they stopped working as a result of Lyme disease, while 25% reported having to reduce their work hours or change the nature of their work. These figures compare with 6.3% of the U.S. population that is unable to work due to health problems and 3.1% that is limited in work due to health problems. Persistent Lyme disease also robs school children of their ability to participate fully in school, which is discussed in greater detail in the "Reducing psychiatric misdiagnoses in Lyme disease" section.

Respondents to the survey who were able to continue working reported missing 15 days of work during the preceding 240-day work year, and they reported an inability to concentrate while at work during 42 days of work in the preceding year due to illness.

In a 1993 study by Vanderhoof and Vanderhoof-Forschner, 19% of Lyme disease patients in their survey reported that they had lost a job due to the illness (Vanderhoof & Vanderhoof-Forschner, 1993). In a more recent study, a quarter of over 2,400 survey respondents reported receiving disability benefits at some point in their illness. Over half of these respondents reported that they had received disability for two years or more, indicating significantly compromised ability to function in their work capacities (Johnson et al., 2011). Another published study of over 3,000 patients with persistent Lyme disease found that 24% of respondents had been on disability at some point in their illness (Johnson et al., 2014). These studies are consistent with those of Zhang and colleagues, who found that loss of productivity—such as lost work time—constituted over half of the costs associated with late Lyme disease (Zhang et al., 2006).

Geographic accessibility: Patients travel long distances to receive care

The majority of over 2,400 survey respondents in a 2011 study reported traveling more than 50 miles and a substantial minority traveling more than 500 miles for Lyme disease treatment (Johnson et al., 2011). These travel distances likely reflect the fact that there are too few physicians to meet patient demand for care, as well as the fact that some states are considered safer for practitioners to provide care. Previous access-to-care studies have defined a high travel burden as more than 30 miles or 30 minutes per trip (IOM, 1993). Patients traveling long distances for care incur greater travel costs, inconvenience, and lost work productivity, and they may elect to forego necessary care (IOM, 1993).

Acceptability: Patients need the ability to gain access to satisfactory health outcomes

In one survey, 61% of over 3,000 patients participating in MyLymeData had already failed to improve under the short-term protocols permitted under the IDSA guidelines (Johnson, 2018). Like many research-disadvantaged diseases, almost all treatments of Lyme disease are off-label.

The U.S. Food and Drug Administration (FDA) recognizes the important role that clinical innovation plays in patient care, stating: "Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic innovations, subsequently confirmed by well-planned and executed clinical investigations" (U.S. Food and Drug Administration, 1982). The benefits related to therapeutic flexibility are quite evident in research-disadvantaged diseases (such as rare diseases and Lyme disease), where research incentives for treatment development are lacking. For these diseases, roughly 90% of all prescribed medications represent off-label use; and if not for that practice, clinicians would often have no effective therapies to employ (Fugh-Berman, 2008). As reflected in the American Medical Association (AMA) Code of Medical Ethics Opinion 1.2.11, innovative therapies include the use of unconventional dosages of standard medications, a novel combination of currently accepted practices, new applications of standard interventions, and the use of accepted therapy or approved drugs for non-approved indications (American Medical Association, 2019). The reason that most patients with persistent Lyme disease choose to be treated outside the IDSA guidelines is so that they have an opportunity to try the type of clinical innovation necessary to cure or improve their quality of life.

Accommodation: Patients need to be able to obtain access to care in usual care settings

The majority of those seeking care at their local hospitals reported difficulty obtaining care (Johnson et al., 2011). IDSA is highly influential in developing hospital protocols related to infectious diseases, and these protocols may result in denying patients antibiotic treatment (Stricker & Johnson, 2009; Johnson & Stricker, 2010; Wolfram, 2008). Patients who cannot obtain care at their local hospitals may need to either travel to a hospital where their treating physician has practice privileges, or forego such services. Some hospitals, however, deny hospital privileges to physicians who do not follow the IDSA Lyme disease guidelines (Stricker & Johnson, 2009; Johnson & Stricker, 2010; Wolfram, 2008). In a study of over 2,400 patients with persistent Lyme disease, 40% had sought medical services at their local hospital, but 82% reported that they had difficulty obtaining treatment (Johnson, 2011). A study by Hirsch et al. (2018) found that 78% of those who reported an initial misdiagnosis had initially sought care in an emergency department or urgent care center.

In these circumstances, particularly when insurance coverage is not provided, patients may elect to either forego care entirely or be more inclined to use home remedies or alternative treatments (Johnson et al., 2011). For example, in the MyLymeData Patient Registry, roughly half of the enrolled patient use antibiotic treatments, and half either report not treating the disease or using alternative treatments exclusively (Johnson, 2019, Chart Book). When those not using antibiotic therapy were asked why, respondents reported the following major reasons:

  • Have no access to doctors who treat (26%)
  • Insurance company constraints (18%)
  • Other non-insurance cost considerations (14%)

Patient Representation

One way that patients can attempt to remedy some of the access to care issues identified above is through effective patient engagement with government entities and on guidelines panels. Representation is a fundamental principle in a pluralistic democracy. The now well-known slogan "Nothing About Us Without Us!" embodies the idea that no policy should be decided by any representative without the full and direct participation of members of the group(s) affected by that policy. To a large extent, the divisiveness between persistent Lyme disease patients and health care policy makers reflects the fact that patients have been excluded from meaningful participation in the health care policies that directly impact their lives by imposing substantial barriers to access to care.

The need for meaningful engagement in health care policy by patients who bear the consequences of these policies is now being recognized. The Patient-Centered Research Outcomes Institute (PCORI) has taken a lead on patient engagement in grant funding by developing a patient engagement rubric that specifies the qualifications of patient representatives (Patient-Centered Research Outcomes Institute, 2016). Meaningful patient engagement requires more than simply providing patients with an opportunity to participant; it requires that their participation is early enough and robust enough to make a difference in the outcome (Johnson & Smalley, 2019)

(The PCORI Patient Engagement Rubric 2016 can be accessed at the following link: https://www.pcori.org/sites/default/files/Engagement-Rubric.pdf.)

The NAM recognizes the need for representation in its standards on creating trustworthy guidelines when it specifies "those affected" by the decision be represented in guideline development (IOM 2010). As it explains, patient representatives can ensure process integrity by:

  1. Providing a window into the process and some assurance that guidelines were not developed "behind closed doors" to suit special interests;
  2. Providing sensitivity to what matters most to those living with disease;
  3. Acting as a safeguard against conflicts of interest that may skew judgment of clinical and scientific experts; and
  4. Identifying evidence gaps and weighing in on the balance of benefits and harms from the viewpoint of the patient (IOM, 2010).

Opportunities for persistent Lyme disease patient engagement include government panels, grant funding committees, and guidelines panels. However, the path to achieving meaningful representation for patients with persistent Lyme disease has been difficult. Although government is now moving toward greater inclusion through processes such as the Tick-Borne Disease Working Group, historically the IDSA viewpoints have been reflected in government health care policy, and persistent Lyme disease patients have been excluded from these processes. This has played a pivotal role in creating an acrimonious and combative rift (the so-called "Lyme wars") between health care policy makers (and the IDSA), on the one hand, and persistent Lyme disease patients on the other, because the policies that create access to care barriers have not incorporated the patient perspective. It has also led to patient distrust of policy makers.

In diagnostic and treatment guidelines, the extent of engagement has depended on which medical specialty society is involved. While ILADS engaged persistent Lyme disease patient advocates in both its 2004 guidelines and its most recent 2014 guidelines using the GRADE evidence assessment process recommended by the National Academy of Medicine (IOM, 2011), the IDSA excluded patients from its 2006 guideline process and, as explained below, representation on its guidelines currently under development is regarded as tokenism by the patient advocacy community (IOM, 2011; Cameron et al, 2004; Cameron et al., 2014; Wormser et al., 2006).

Although the IDSA is in the process of revising their 2006 IDSA/AAN/ACR Lyme Disease Guideline and states that they have three patient representatives on their guideline panel, the patient community does not know their identity, what stage of the disease they have, or whether or not they have the ability to represent patients with persistent Lyme disease (Infectious Diseases Society of America, 2019). Accordingly, they are not accountable or responsible to the community or authorized to speak on the community's behalf. The selection process for these patients was not by open nomination, and patient advocacy groups were not contacted for nominations. As a result, community trust in the process has not been forthcoming.

What is the best process for selecting persistent Lyme disease patient representatives?

Health care policies are developed through governance processes that relate to power, authority, and accountability (Huberts, 2018). Process integrity refers to the manner in which policies are made, decided on, and implemented. The moral quality of the governance process (for example openness, transparency, and fairness), determines the legitimacy and credibility of the exercise of public power. This is important for government processes as well as those by other influential groups such as medical specialty societies that develop diagnosis and treatment guidelines that impact access to care. While not regulatory, treatment guidelines of authoritative influential medical societies, such as the IDSA, can carry considerable weight and may be essential determinants of access to care for patients (Johnson, Patient Engagement, 2019).

Hence, the process for selecting those most affected by these policies that will participate in them is critical. In Lyme disease, those most affected by these policies are the patients with persistent Lyme disease. The goal in choosing patient stakeholders is to ensure that affected patients are adequately represented and can meaningful influence the ultimate outcomes of those processes (Johnson & Smalley, 2019).

Effective representation by patients with persistent Lyme disease is most easily accomplished through open nomination processes that involve patient advocacy groups who are known to represent these patients. For example, the Congressionally Directed Medical Research Programs (CDMRP), under the Department of Defense, reaches out to Lyme disease patient advocacy groups for nominations when it has an opening for a patient representative. Similarly, the first TBDWG also reached out publicly as well as to patient advocacy groups for nominations on that panel. In addition, its panel included a sufficient number of patients representing those with persistent Lyme disease to create a vibrant process that help build public trust in the process. These types of processes should be encouraged.

Unfortunately, the implementation of these "best practices" has been erratic. For example, the current Tick-Borne Disease Working Group panel selection process has been criticized in written and verbal comments at the public meetings because a) the number of patients representatives has been reduced; b) one patient is not regarded by the community as being able to meaningfully represent its interests; c) the nomination process was not as robust as the first time; and d) and patient advocacy groups were not contacted.

Implementing consistent robust processes for selecting representatives for those with persistent Lyme disease would improve meaningful representation on government panels and promote an atmosphere of trust. These processes should include open nominations and out-reach to the patient advocacy organizations representing patients with persistent Lyme disease. In addition, as explained below, the selection process should assure that a sufficient number of authentic representatives (two or more) are selected to influence policy making on the panel.

Who can represent patients with persistent Lyme disease?

When a disease has created patient advocacy organizations to represent its interests, patient representatives should be selected from that community and acknowledged by the community as being capable of representing their interests (Johnson & Smalley, 2019; Johnson, Patient Engagement, 2019) Hence, it would not be appropriate to select a consumer with no lived experience of HIV/AIDS to represent the concerns, values, and preferences, and characteristics of that community. In contrast, acute conditions like the common cold have no such community, and the concept of representation does not carry the same weight (Johnson, Patient Engagement, 2019).

With Lyme disease, patients may have either acute Lyme disease or late/persistent Lyme disease. Patients with acute disease that recover quickly have no need for patient representation—they simply move on with their lives. The patients that need effective representation in Lyme disease to address access to care issues are patients with persistent Lyme disease—those who are negatively impacted or "affected" by treatment guidelines and policies that limit their access to care and are interested in having their research priorities addressed.

In addition to identifying the group of patients requiring representation, there are three prerequisites that lead to informed and empowered decision-making: accountability, responsibility, and authority. The existence of these elements allows patient engagement to be meaningful rather than token. Hence, one consideration is whether or not the patient is actually a recognized representative of the disease community who is authorized to speak for the community with both the knowledge required and with some form of accountability to the community (Johnson & Smalley, 2019). To effectively represent patients with persistent Lyme disease, the patient must be sufficiently involved with the disease to be able to speak knowledgeably about the issues—not as experts, but from the patient perspective. Patient representatives must also understand the nature and methods of the deliberative process that they will be involved in (Johnson & Smalley, 2019).

It is also critical that a sufficient number of patients representing chronic Lyme disease be selected to compensate for the inherent power imbalance between patients and researchers generally. It is not realistic, for example, to believe that a single patient can hold their own in a group of researchers. Therefore, two or more patients are typically recommended to achieve meaningful engagement on a panel (Johnson & Smalley, 2019).

The importance of the general principles outlined above were confirmed by a patient survey of over 4,000 patients with persistent Lyme disease in February of 2019 by LymeDisease.org (Johnson, 2019). The survey asked patients who they would regard as being able to provide meaningful representation for patients with persistent Lyme disease. The majority of patients responded that, for representation to be meaningful, patients selected needed to have each of the following qualifications:

  • Someone who has had or currently has persistent Lyme disease
  • Someone vetted and approved by a recognized Lyme disease patient organization
  • An officer or director of a recognized patient advocacy organization that represents patients with persistent Lyme disease

Hence, to serve as a meaningful representative, patients or advocates representing the persistent Lyme disease community should: a) have or have had persistent Lyme disease, or be someone who serves or has served as a caregiver to a persistent Lyme disease patient; and b) should be an officer or director of a recognized and trusted patient advocacy organization representing patients with persistent Lyme disease, or someone vetted and approved by such a group. The latter ensures that the representative is recognized in the community as representing the interests of those with chronic Lyme disease. Patient advocacy organizations are unlikely to give their stamp of approval to someone who lacks the knowledge and ability to hold their own among a group of researchers and to be outspoken about the interests of patients with persistent Lyme disease.

Access to care in other tick-borne diseases

Patients who have tick-borne diseases other than or in addition to Lyme disease have the same access to care difficulties as those who have Lyme disease but can also have additional difficulties. According to the 2019 National Institutes of Health NIH Strategic Plan for Tickborne Disease Research, there are currently 20 tick-borne diseases and conditions found in the U.S (National Institutes of Health, NIH Strategic Plan for Tick-Borne Disease Research, 2019). Many physicians do not consider coinfections or may test for only select coinfections. However, coinfections appear to be common among those with persistent Lyme disease and were reported by 60% of respondents in the MyLymeData Patient Registry (Johnson, 2018). It is difficult for patients to find doctors who are familiar with the other tick-borne diseases or who know how to manage them. In particular, this applies to patients in states traditionally considered to have a low incidence of Lyme disease. (See also Background, Misdiagnosis.)

Possible opportunities

  • There is an opportunity to improve the access to care for persistent Lyme disease patients. This would permit patients to receive treatment that could either restore their health or at least improve their quality of life. Identifying and addressing the barriers to care identified above is essential to provide quality health care that would reduce unnecessary suffering, decrease health care utilization levels and costs, and permit patients to resume their roles as productive members of the workforce, family, and community. Increasing patient access to care is an achievable goal if specific targeted actions are taken.
  • There is an opportunity to heal the divisiveness that exists between the Lyme disease patient community and the government and others by providing effective representation to patients with persistent Lyme disease. To a large extent, the divisiveness between persistent Lyme disease patients and health care policy makers reflects the fact that they have been excluded from meaningful participation in the health care policies that directly impact their live by imposing substantial barriers to access to care.

Threats or challenges

Practitioners are reluctant to treat persistent Lyme disease out of fear of professional retribution.

Vested stakeholders, such as insurers and the IDSA, may be unlikely to embrace change of the status quo. Failure to acknowledge the existence of two treatment approaches, as well as token patient representation, allows the status quo to remain unchallenged.

Bridging the gap and structurally reducing the marginalization of health care for Lyme disease patients may take time and involves many different stakeholders, for example, government agencies, medical specialty societies, physicians, and insurers.

The Federal government may be unwilling to take a more active role in de-escalating the long-standing controversy and tension (so-called "Lyme Wars") between patients and healthcare policy makers and guideline developers.

Potential Actions 1 and 2

The subcommittee proposes the following actions for the Tick-Borne Disease Working Group to consider.

Potential Action 1: Increase public awareness that there are two divergent diagnostic and treatment approaches reflected in guidelines for Lyme disease. Encourage the disclosure on all state and Federal government web pages that discuss Lyme disease or tick-borne illness, including CDC, NIH, and the Agency for Healthcare Research and Quality (AHRQ), that there are two diagnostic and treatment approaches; and encourage inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Potential Action 2: Encourage all state and Federal government committees and panels, including the CDC, NIH, DoD, the Agency for Healthcare Research and Quality (AHRQ), and medical specialty societies to use authentic and meaningful representation of patients with persistent Lyme disease in health care policy matters, the determination of research grants, and in the development of diagnostic and treatment guidelines.

    • To serve as a meaningful representative, patients or advocates representing the persistent Lyme disease community should: a) have or have had persistent Lyme disease or be someone who serves or has served as a caregiver to a persistent Lyme disease patient; and b) should be an officer or director of a recognized and trusted patient advocacy group representing patients with persistent Lyme disease, or someone vetted and approved by such a group.
    • To ensure process integrity, the selection of patient representatives should be through open and transparent selection processes, including public calls for nominations and soliciting nominations through recognized and trusted patient advocacy group representing patients with persistent Lyme disease.

Vote of subcommittee members on Potential Actions 1 and 2

Vote on Potential Action 1 as written above

Number in Favor Number Opposed Number Abstained Number Absent
6 0 0 1

Vote on Potential Action 2 as written above

Number in Favor Number Opposed Number Abstained Number Absent
6 0 0 1

Minority responses

There were no minority responses.

Prioritized Issue: Reducing Diagnostic Errors and Delays in Lyme Disease

Errors stemming from delayed or inaccurate diagnosis are generally the number one cause of serious medical harms (Newman-Toker et al., 2019). The Agency for Healthcare Research and Quality (AHRQ) has made reduction of diagnostic errors one of its three strategic priorities (Khanna, 2019). A diagnostic error is defined by the National Academy of Medicine (NAM) as "the failure to (a) establish an accurate and timely explanation of the patient's health problem(s) or (b) communicate that explanation to the patient" (NAM, 2015). Three types of diagnostic errors occur: patients may have their diagnosis delayed; they may be given an incorrect diagnosis; or they may have their diagnosis missed entirely (NAM, 2015).

Diagnostic errors related to infectious diseases are among the top three sources of diagnostic errors (Newman-Toker et al., 2019). Diagnostic errors in Lyme disease permit a disease that most patients fully recover from to disseminate instead throughout the body causing cardiac, neurologic, and musculoskeletal symptoms that may be severe, debilitating, and, at times, deadly (Klempner et al., 2001; Krupp et al., 2003; Maes, 1998; Johnson et al., 2014; Marx et al., 2019). Many patients with persistent Lyme disease report substantial misdiagnosis or diagnostic delays—ranging from six or more months to years (Johnson, 2018; Fallon et al., 2008).

Importance

The majority of Lyme disease patients who are promptly diagnosed and treated are restored to health. However, between 10-35% of those diagnosed early do not return to their pre-Lyme disease health status (Aucott et al., 2013; 2006; Cameron et al. 2014; Wormser et al.). In addition, roughly 60% of those left untreated develop late stage Lyme disease, which is more difficult to treat and may produce severe symptoms (Arvikar & Steere, 2015; Steere, 2001; Weinstein, Rebman, Aucott, Johnson-Green, & Bechtold, 2018.) Although the number of Lyme disease patients who have delayed diagnosis is unknown, one study estimates that delayed diagnosis may occur in as many at 40% of patients (Hirsch et al., 2018).

Late untreated and Lyme disease that persists after a short-term course of treatment can cause severe symptoms, reduced quality of life, and losses in work productivity (Johnson et al., 2014; Klempner et al. 2001; Krupp et al., 2003; Rebman et al., 2017). One study of patients who were treated for erythema migrans (EM) rash, found that in the first year following treatment, those who had one or more persisting symptoms of Lyme disease incurred $3,798 more in health care costs compared to those who were asymptomatic (Adrion et al., 2015). A CDC Lyme disease cost-of-illness study by Zhang et al. (2006) found that the total cost of treating late Lyme disease (including loss of productivity) is 12 times higher than the cost of treating early Lyme disease. Therefore, avoiding diagnostic errors is important to ensure the prompt diagnosis and treatment required to prevent unnecessary patient suffering, improve patient quality of life, increase work productivity, and reduce the cost of illness for Lyme disease.

Summary of evidence and findings

Introduction

Both NAM and AHRQ have identified diagnostic errors as strategic priorities (NAM, 2015; Khanna, 2019). In addition, NAM has developed a schematic to identify points in the medical care system where diagnostic errors occur (National Academies of Sciences, Engineering, and Medicine, 2015).

(The schematic entitled "The Diagnostic Process" can be viewed here: http://www.nationalacademies.org/hmd/reports/2015/improving-diagnosis-in-healthcare/figures

Diagnostic medical errors are the failure to establish and communicate to the patient an accurate and timely diagnosis. NAM looks at errors that occur when the patient first encounters the health care system, when clinical history is taken, during physical exam, and when diagnostic testing is being conducted. It then looks at the consequences and costs of the diagnostic errors. Identifying the places that diagnostic errors occur provides the opportunity to remedy the errors that cause diagnostic delays and misdiagnosis to restore patient health and improve quality of life.

Diagnostic delays in Lyme disease are not uncommon. Applying the NAM schematic to the diagnosis of Lyme disease, sources of clinical errors include:

  • Inappropriately excluding Lyme disease from the initial differential diagnosis because of geographic exclusions that inaccurately reflect the geographic scope of the disease;
  • Failure to recognize the full spectrum of Lyme disease-related symptoms;
  • Inability to identify EM rashes and/or other Lyme disease-related findings on physical exam; and
  • Over-reliance on inaccurate diagnostic tests.

Taken together, it appears that clinicians are not sufficiently trained to reliably diagnose Lyme disease when it is present.

[The schematic entitled "Sources of Diagnostic Errors in Lyme Disease" can be viewed here: https://doi.org/10.6084/m9.figshare.10262537

In analyzing the causes of diagnostic delays, we considered the peer-reviewed literature as well as the results from Phase 1 of the MyLymeData patient registry. MyLymeData is a patient registry developed by LymeDisease.org that enables patients to pool their health care data. Since its launch in November 2015, over 12,000 patients have enrolled. The results presented in this report include 3,903 U.S. residents clinically diagnosed with Lyme disease who completed the Phase I Survey, which ran from November 2015-2016. Most participants (79%) have late or persistent Lyme disease, and 78% report that their diagnosis is supported by positive lab test results. Survey questions included time to diagnosis, early symptoms, inaccurate lab tests, and whether their diagnosis relied on the perception of the existence of Lyme disease in their state (Johnson, Chart Book, 2019; Johnson, 2018).

Prevalence of diagnostic errors in Lyme disease

Diagnostic errors in Lyme disease are believed to be common. One researcher estimates that as many as 40% of patients are not diagnosed in a timely manner based on the CDC statistics for arthritis, neurological, and cardiac manifestations (Hirsh et al., 2018). Early diagnosis of Lyme disease relies heavily on the presence of an EM rash, yet in one prospective study, 16% of patients with early Lyme disease lacked an EM and presented with flu-like symptoms accompanied by IgM or IgG seroconversion. (Steere, 2003). Those who do not present with an EM rash are often misdiagnosed. A retrospective case series demonstrated that 54% of those without an EM rash were misdiagnosed; 83% of those with neither an EM nor other CDC extra-cutaneous presentations were misdiagnosed. In this study, 13% presented with flu-like symptoms alone (Aucott et al., 2009). It is important to recognize that many patients without EM rashes are unlikely to be identified by antibody-based diagnostic tests, which are known to be very inaccurate in early Lyme disease when the antibody response that they measure has not yet developed.

Patients presenting with the EM rash may also be misdiagnosed initially; the previously mentioned study documented a 23% misdiagnosis rate. (Aucott et al., 2009). This study also found that patients misdiagnosed are likely to receive initial antibiotics that are not effective against Lyme disease, but may abrogate the patient's development of antibodies necessary to test positive on the Lyme disease antibody tests that are commercially available and widely used (Aucott et al., 2009). They may also be treated with steroids, which have the potential to suppress the immune response and reduce a patient's ability to test positive using current lab technology. These diagnostic delays, misdiagnoses, treatment with steroids, or ineffective or inadequate doses of antibiotic are important because when the disease is not effectively treated early in the infection (ideally within the first month), the disease usually disseminates and may cause patients serious sequelae (Aucott et al., 2009).

Patients with persistent Lyme disease report substantial diagnostic delays and misdiagnosis (Fallon et al., 2008; Johnson, 2018). For example, patients enrolled in Fallon's retreatment trial had been ill for a mean of 1.7 years before their initial diagnosis (Fallon et al., 2008). The inability of clinicians to recognize early disease was also a significant cause of diagnostic delays for participants in the MyLymeData registry. Although 74% report having had early symptoms and 34% recalled having a rash, only 12% were diagnosed within the first month when treatments are most effective (Johnson, 2018; Johnson, 2019). Seventy percent were not diagnosed until six or more months after symptom onset. Additionally:

  • 51% took more than three years to be diagnosed;
  • 54% saw five or more clinicians before diagnosis; and
  • 72% were misdiagnosed with another condition (Johnson, 2018).

Other diagnostic delays identified by participants in MyLymeData include false negative lab tests (37%) and positive test results (13%) that were dismissed as "false positives"—largely because their clinician believed there was no Lyme disease in the state.

Missed diagnosis by inaccurate geographic exclusions

Some diagnostic delays and misdiagnosis are caused by the misperception that Lyme disease only exists in a handful of states. The use of CDC geographic surveillance criteria related to endemicity is inappropriate for clinical diagnosis because it excludes a large portion of the clinical population of patients who have Lyme disease. In addition, ticks carrying the disease have spread geographically and are now in half of all U.S. counties (Eisen et al., 2016). In addition, two big-data studies, one by Quest Diagnostics (one of five major Lyme disease diagnostic labs) and one by FAIR Health (an insurance database that includes over 23 billion health care claims), indicate that CDC surveillance cases do not accurately reflect the geographic distribution of the disease (Quest Diagnostics, 2018; Gelburd, 2018).

This geographic inaccuracy is important because many clinicians rely on CDC surveillance criteria and will not diagnose an EM rash if that patient does not have exposure in a state that the CDC considers a high-incidence state—defined as a state with an average Lyme disease incidence of 10 confirmed cases out of 100,000 for the previous three reporting years. A low-incidence state is defined as fewer than 10 confirmed cases out of 100,000 over same time period. Clinicians often look at the maps provided by CDC showing these two categories: https://www.cdc.gov/lyme/datasurveillance/maps-recent.html. However, the CDC map of low-incidence versus high-incidence states identifies only 16 high-incidence states. This means that even though Lyme disease has been reported in every state in the nation, these maps incorrectly indicate to physicians that Lyme disease is not a problem in most states. In addition, population based averaging for Lyme disease does not accurately reflect risk (as the FAIR Health and Quest Laboratories data above reflect). Lyme disease exposure is largely driven by geographical terrain, tends to run in "hot spots," and exposure risk is not uniform within a state. For example, Connecticut is one-thirtysecond the size of California and, therefore, has a relatively homogenous in terrain and exposure risk. Yet as Lane et al. note (1992), portions of California are as endemic as Connecticut.

Geographic inaccuracy is also important because CDC and IDSA advise clinicians to limit Lyme disease testing and diagnosis by EM rash to high-incidence states. This restriction interferes with the ability of patients from "low-incidence" states to be promptly diagnosed and treated, when treatment is more likely to be effective. Clinicians relying on CDC maps may believe that there is no Lyme disease in their state and fail to consider it in the differential diagnosis.

In addition, clinicians are sometimes encouraged not to test for Lyme disease on the basis of symptoms alone under the assumption that in the absence of objective findings of Lyme disease, the incidence of the infection in the symptomatic group was no higher than that of the general population. However, a 2012 study of patients in a Lyme disease-endemic area demonstrated that this is not the case (Aucott et al., 2012). The authors suggested that "... the possible diagnosis of probable late Lyme disease is reasonable to consider in the setting of an unexplained illness and a history highly suggestive of Lyme disease exposure. These patients may benefit from testing for IgG antibodies to confirm exposure to B. burgdorferi and to suggest the possibility of late untreated infection (Aucott et al., 2012)."

A recent study from Quest Diagnostics reports positive Lyme disease serology results on patient specimens from every state in the nation. In addition, it notes that on a nationwide basis, Lyme disease increased steadily from 6.7% in 2014 to 11.2% in 2017. Quest Diagnostics reported a large number of positive lab tests in 28 states, 20 of which the CDC classifies as low-incidence states based on surveillance case reports (Quest Diagnostics, 2018; CDC, Maps, 2017). Its report states: "Outside of the northeastern U.S., which is historically associated with Lyme disease, the two states with the largest absolute increases in the number of positive test results from 2015 to 2017 were Florida and California. Notable increases were also observed in Georgia, Arizona, Ohio, Texas, Tennessee, and Virginia" (Quest Diagnostics, 2018). With the exception of Virginia, none of these states are considered high incidence by CDC website maps. To view the Quest Diagnostics heatmap associated with this study, visit: https://questdiagnostics.com/dms/Documents/health-trends/Quest_LymeDiseaseTrendsReport_2018.pdf

Quest Diagnostics is one of the seven large commercial laboratories that the CDC estimates account for greater than 76% of Lyme disease tests reported to health departments in the four endemic states (Hinckley et al., 2014). (The other six laboratories are ARUP Laboratories, Clinical Laboratory Partners, Focus Diagnostics, Laboratory Corporation of America [LabCorp], Mayo Clinic Laboratories, and Specialty Laboratories). Hence, the number of positive lab tests Quest Diagnostics reports constitutes a fraction of the total positive tests from all labs.

Dr. Lee-Lewandrowski at Harvard Medical School used Quest Diagnostics data from 2010 and 2016 to create a heat map of Lyme disease-positive serologic test rates by state (Lee-Lewandrowski et al., 2019). The volume of performed tests and the rate of positivity for these Lyme disease serologic tests increased dramatically throughout the U.S. from 2010 to 2016, suggesting that the actual incidence of Lyme disease increased during this time period. Unlike other geographic-based maps of Lyme disease, which look at the incidence of Lyme disease by state based on the general population, this map instead reflects the rate of positivity in patients who were assessed by clinicians to have a clinical suspicion of the disease. This means:

  • A patient has actually gone to a doctor because they are ill;
  • The patient's history has been taken;
  • A physical examination has been conducted;
  • The doctor has considered Lyme disease in their differential; and
  • The physician has ordered a lab test based on the clinician's clinical suspicion of Lyme disease.

Positivity rates for all states ranged from 4% to 20%. Only three states had positivity rates below 5%. Many states that the CDC considers to be low incidence for risk, showed a high positivity rate.

"Over the study period, the positivity rates increased in many states that reportedly do not have many cases of Lyme disease. Texas saw a significant increase in test volume (8,856 to 13,505) and an increase in the percentage of positive tests, from 7.7% to 12.1%. California saw an increase in test volume from 772 to 3,002, with an increase in the positivity rate from 4.5% to 10.8%. Florida saw an increase in test volume from 19,435 to 35,705, with an increase in positivity from 7.9% to 11.4% (Lee-Lewandrowski et al., 2019)."

The study also notes that a negative lab test does not preclude the presence of Lyme disease, as Lyme disease is often diagnosed based on clinical presentation alone (for example, when there is an EM rash).

In a similar vein, the Wall Street Journal (WSJ) recently reported on a study by FAIR Health—using their claims database of 150 million privately insured individuals—that found that some states considered by CDC to be low incidence reported far higher rates of insurance claims than suggested by surveillance data. Insurance claims data is not comparable to surveillance statistics because one patient may file a number of claims in a given year. However, comparing insurance claims rates among states does provide a comparison of the relative health care utilization of those states. Therefore, the states with the highest reported incidence should also have the largest number of insurance claims. Yet the article points out that some of the states believed to be low incidence have some of the highest number of insurance claims:

"North Carolina reported 32 Lyme [disease] cases to the CDC in 2016 but in the same year made 88,539 health-care claims for a Lyme [disease] diagnosis. California reported 90 cases to the CDC but had 46,820 claims. Texas reported 31 cases to the CDC but had 31,129 claims. All three are considered low-incidence states." (McGinty, 2018)

A chart accompanying the article shows California and North Carolina as being among the states with the largest number of insurance claims—states that are not considered by CDC to be high incidence.

In addition, a research study of a rural subdivision in northern California found that 24% of the residents had positive Lyme disease tests, and 37% had definite or probable Lyme disease (Lane et al., 1992). Tick flagging surveys of the area (which reflect human risk of contracting the disease) revealed that the nymphal tick infection rate was as high as 41%, comparable to or higher than hyperendemic areas in the northeastern U.S. (Talleklint-Eisen & Lane 1999). Most areas of the country lack tick flagging studies, and migratory bird activity coupled with climate change are rapidly expanding ticks to new areas (Sonenshine, 2018).

The inaccuracy caused by placing diagnostic restrictions based on inaccurate geographic range is apparent from the above studies. For example, in California in 2016, there were only 90 CDC surveillance cases, while Quest Diagnostics (which is just one of the seven most-used Lyme disease testing labs) reported 483 positive tests, and FAIR Health Data showed insurance claims in the state at close to 47,000, making California one of the top five highest states for Lyme disease insurance claims in the U.S. The fact that these independent data points are so incongruent indicates that it is time to abandon the "diagnosis by geography." Using inaccurate geographic endemicity data to restrict diagnosis will leave many patients with Lyme disease undiagnosed and untreated. The greatest opportunity in Lyme disease is to achieve earlier diagnosis and treatment for those who contract the disease to prevent the development of persistent Lyme disease.

Diagnostic errors in gathering and interpreting clinical data

The clinical evaluation of a patient who potentially has Lyme disease and/or other tick-borne infections is a time-consuming process. Yet, clinician schedules often relegate only 15 to 20 minutes for these complex cases, leaving insufficient time to conduct a thorough history and physical exam. Additionally, clinician education on tick-borne diseases in school and post-graduate training is typically quite limited, and point-of-care resources are scarce. Popular resources, including the CDC website, may be subject to editorial bias because they are not peer-reviewed by experts representing a broad range of scientific and clinical perspectives.

Insufficient training can lead to diagnostic delays that may significantly impact a patient's health in the near and long-term future. Many clinicians look to the CDC surveillance case definition of Lyme disease to guide their diagnostic thinking, although CDC specifically advises against this:

Note: Surveillance case definitions establish uniform criteria for disease reporting and should not be used as the sole criteria for establishing clinical diagnoses, determining the standard of care necessary for a particular patient, setting guidelines for quality assurance, or providing standards for reimbursement (CDC, 2017).

The surveillance case definition focuses on a restricted set of clinical symptoms and findings under specific geographic conditions, which, as noted above, may inappropriately discourage clinicians from reaching a Lyme disease diagnosis. For example, an EM rash in a CDC-identified high incidence state qualifies as Lyme disease on that basis alone, but EM rashes in nonendemic/low-incidence states must be accompanied by positive results on two-tier testing (see "Diagnostic errors due to an over-reliance on serologic testing") in order to meet the CDC definition. Yet two-tier testing is known to produce many false negatives early on as the immune response the test detects has not yet developed. In addition, waiting until the immune response has developed and tests are more likely to be positive may mean missing the optimal therapeutic window for effective treatment of the disease.

Other CDC-designated manifestations of the illness must also have positive serologic results in order to be counted as a surveillance case. Although the clinical manifestations are quite diverse, the list of non-EM conditions that fulfill the surveillance case definition is limited to the following: 1) cardiac—acute onset of high-grade (second- or third-degree) atrioventricular conduction defects that resolve in days to weeks and are sometimes associated with myocarditis; 2) neurologic—lymphocytic meningitis; cranial neuritis, particularly facial nerve palsy (may be bilateral); radiculoneuropathy; or, rarely, encephalomyelitis; and 3) arthritis—recurrent brief attacks of objective joint swelling.

Clinicians who seek out only the historical and exam data that meet the surveillance case definition are doing a disservice to patients with Lyme disease. Misuse of the surveillance definition for diagnostic purposes will unfortunately mean that actual cases of Lyme disease that do not satisfy the surveillance definition will go undiagnosed, be misdiagnosed, or have a delayed diagnosis. As CDC epidemiologist Dr. Paul Mead explains, surveillance case definitions serve a very different purpose from clinical diagnostic criteria:

A clinical diagnosis is made for the purpose of treating an individual patient and should consider the many details associated with that patient's illness. Surveillance case definitions are created for the purpose of standardization, not patient care; they exist so that health officials can reasonably compare the number and distribution of "cases" over space and time. Whereas physicians appropriately err on the side of over-diagnosis, thereby assuring they don't miss a case, surveillance case definitions appropriately err on the side of specificity, thereby assuring that they do not inadvertently capture illnesses due to other conditions (Mead, 2004).

A recent CDC survey study asked clinicians if they used the CDC surveillance definition for diagnosis, clinical judgment for diagnosis or did not diagnose many patients with Lyme disease. After eliminating those who do not diagnose Lyme disease, 80% of those who treat Lyme disease responded that they do not use the surveillance definition, while 20% responded that they do (Perea, Hinckley, & Mead, 2020). However, many clinicians who respond that they use clinical judgment to diagnose are unlikely to realize that when they evaluate a rash in the context of states the CDC regards as low incidence or high incidence, they are using the CDC surveillance criteria for diagnosis. Moreover, the IDSA guidelines for diagnosing and treating Lyme disease rely heavily on the "objective findings" the CDC uses in its surveillance definition and many clinicians diagnosing Lyme disease rely on the IDSA recommendations (Wormser et al., 2006). In response to the Tick-Borne Disease Working Group 2018 Report to Congress, the IDSA states: "While IDSA acknowledges that the CDC case definition for Lyme disease is intended for use as an epidemiological tool, it is incorrect to promulgate the notion that the components of the surveillance definition should not be used for clinical diagnosis" (IDSA, 2018). Commonly used online diagnostic tools, such as UpToDate, are essentially derived from the IDSA guideline criteria, as the Lyme disease Diagnostic section is edited by one of the authors of the current IDSA guidelines as well as the proposed IDSA guidelines (Wormser et al., 2006; Hu, 2019).

The process for gathering a patient's medical history in cases of potential Lyme disease is similar to taking a history for other illnesses. However, because Lyme disease can mimic other illnesses, and other illnesses can look like Lyme disease, there are Lyme disease-specific questions that clinicians must ask. To assess the potential for tick exposure, clinicians need to know if the patient lives, works, recreates, or vacations where blacklegged ticks have been found, bearing in mind that not all areas have been flagged for ticks. A positive family history of a blacklegged tick-transmitted disease is also useful information as family members often have similar exposure risks. A history of a blacklegged tick bite is significant, but only about 20% of patients with Lyme disease were aware of the bite that made them ill (Berger, 1989; Nadelman et al, 1996). Clinicians should ask if the patient experienced any rashes in the course of his or her illness, recognizing that many patients either will not have had or noticed an EM rash during their illness and that the appearance of EM rashes is quite variable. In fact, while EM rashes are most commonly solid-colored and oval-shaped, the color can range from a faint salmon to a deep scarlet, and the shape can be distorted due to its location on the body. Less than 20% of all EM rashes have the classic "bull's-eye" appearance (Smith et al., 2002; Tibbles & Edlow, 2007).

Common symptoms of early Lyme disease include fever, chills, joint and muscle pain, headache, and malaise. Subjects in one EM rash trial reported: headache (56%), stiff neck (42%), pain with neck flexion (19%), abnormal sensations (14%), light sensitivity (11%), and facial nerve palsy (4%) (Massarotti, 1992). Similarly, patients with persistent Lyme disease enrolled in MyLymeData reported the following symptoms in the early stage of their Lyme disease infection.

"Within days to weeks after exposure, I developed..."

  • Flu-like symptoms (64%)
  • Headaches/neck stiffness (44%)
  • Rash (34%)
  • Joint pain (30%)
  • Lightheadedness (29%)
  • Shortness of breath/chest pain (28%)
  • Shooting pains (25%)
  • Facial nerve (Bell's) palsy (10%)

It bears noting, however, that the types and frequency of early Lyme disease symptoms reported by those with persistent Lyme disease may differ from the symptoms reported by a sample of patients with acute disease. For example, among patients with persistent Lyme disease, the reported rate for EM rashes is significantly lower than the rates seen in surveillance data. The absence of an EM rash, which is associated with high rates of misdiagnosis and, presumably, diagnostic and treatment delays, may explain why some of these patients went on to develop persistent disease (Aucott et al., 2009).

Lyme disease, with the exceptions of early Lyme disease and isolated Lyme arthritis, is a multisystem illness, capable of producing a wide array of symptoms. Because Lyme disease symptoms overlap with symptoms of other diseases, none of the reported symptoms are unique (pathognomonic) to Lyme disease, which makes arriving at the correct diagnosis more challenging. However, the multisystemic nature is a useful diagnostic clue (Citera et al., 2017; Maloney, 2009; Shor, 2019); Lyme disease is less likely if a patient's symptoms involve only one body system (Maloney, 2009).

Common symptoms are myriad and extensive. A complete list with references is included in Appendix D (Maloney, 2009). Some of the more common symptoms and conditions include:

  • Rash
  • Systemic
    • Flu-like symptoms (fever, chills, myalgia)
    • Swollen lymph nodes
    • Fatigue
  • Digestive
    • Abdominal pain
    • Nausea
    • SIBO (small intestinal bacterial overgrowth)
    • Irritable bowel syndrome
    • Intestinal hyperpermeability ("leaky gut")
    • Gastroparesis
  • Neurologic
    • Headaches and stiff neck
    • Psychiatric
    • Memory loss
    • Cognitive impairment
    • Neuropathy (nerve pain or tingling)
    • Facial nerve palsy
    • Sleep impairment
  • Heart
    • Lightheadedness
    • Shortness of breath
    • Heart palpitations
    • Chest pain
  • Musculoskeletal
    • Arthritis
    • Muscle aches
    • Joint swelling
    • Joint pain

Neurologic symptoms of late Lyme disease are numerous, seemingly unrelated, and unusual. Not surprisingly, they are often misattributed to other causes. Patients may complain of headache, pain, numbness, weakness, memory or concentration difficulties, gait disturbances, clumsiness, bladder or bowel dysfunction, light and/or sound sensitivity, visual loss, among other symptoms (Arav-Boger et al., 2002; Coyle & Schutzer, 2002; Fallon & Nields, 1994; Logigian et al., 1990). Additionally, neurologic symptoms are often associated with nonspecific symptoms (Logigian et al., 1990). A study of chronic neurologic Lyme disease found that chronic peripheral and chronic central nervous system complaints developed 16 and 26 months, respectively, post-rash (Logigian et al., 1990). Patients had the following types of symptoms.

Encephalopathic Polyneuropathy Other
Memory loss - 81% Sensory loss - 44% Fatigue - 74%
Depression - 37% Pain: spinal or radicular - 41% Headache - 48%
Sleep disturbance - 30% Distal paresthesias 26% Hearing loss - 15%
Extreme irritability - 26% - Fibromyalgia - 15%
Difficulty finding words - 19% - -

In persistent disease, respondents in MyLymeData report the following as among their three worst symptoms (Johnson, 2019):

  • Fatigue (62%)
  • Joint pain (40%)
  • Muscle aches (31%)
  • Cognitive impairment (30%)
  • Neuropathy (nerve pain, numbness, tingling) (29%)
  • Sleep impairment (20%)
  • Psychiatric (for example, depression, mood change) (18%)
  • Gastrointestinal (stomach/digestive) (17%)
  • Headache (16%)
  • Memory loss (16%)
  • Heart-related (8%)
  • Twitching (4%)

Physical exam findings

Lyme disease is "symptom rich, exam poor." Common findings of Lyme disease include:

  • Solitary or multiple EM lesions;
  • Manifestations of cranial neuritis such as facial muscle weakness similar to what is seen in Bell's palsy, extraocular palsies, drooping eyelids, decreased facial sensation, decreased hearing;
  • Joint swelling and tenderness;
  • Decreased sensation, which is often patchy; and
  • Changes in pulse and/or blood pressure in response to standing.

Although cognitive deficits are a frequent symptom, they are usually not obvious on routine mental status testing.

When obvious physical exam findings are absent, ancillary testing—EMG, autonomic batteries, and neuropsychometric testing—can be quite helpful in terms of investigating and identifying the cause of a patient's symptoms. For example, a study of patients who had normal exams despite having clear symptoms of distal sensory changes found "significant neurophysiologic findings" in 13 of 14 patients (Halperin et al., 1987). Another researcher identified cognitive deficits on detailed neuropsychometric testing that were not apparent on routine mental status testing (Logigian et al., 1990).

Misdiagnoses

In Aucott's retrospective chart review study of diagnostic challenges, he noted that patients who did not present with an EM rash and were misdiagnosed had been given the following prior diagnoses: diverticulitis, acute coronary syndrome, sciatica, and lymphoma (Aucott et al., 2009). Seventy-two percent of persistent Lyme disease patients in MyLymeData report also being misdiagnosed, many with diseases that lack a known cure. The most common misdiagnoses reported included:

  • Psychiatric disorder (for example, depression, mood changes) (52%)
  • Fibromyalgia (44%)
  • Chronic fatigue syndrome (43%)
  • Thyroid disorder (26%)
  • Rheumatoid arthritis (17%)
  • Multiple sclerosis (12%)
  • Systemic lupus (9%)
  • Learning disabilities (6%)
  • Motor neuron disease, multiple systems atrophy, Parkinson's disease (5%)

These patients may be prescribed costly palliative care for life and suffer the side effects associated with potentially unnecessary medications. The most common misdiagnoses among those misdiagnosed include fibromyalgia, chronic fatigue syndrome, and rheumatoid arthritis.

Psychiatric misdiagnoses are common. Although 52% of MyLymeData patients were initially misdiagnosed with having a psychiatric disorder, only 18% rank psychiatric symptoms as being among their three worst symptoms. (See Prioritized Issue: Reducing Psychiatric Misdiagnoses in Lyme Disease.)

Diagnostic errors related to Erythema migrans (EM) rash

Clinicians may fail to recognize and diagnose EM rashes for a variety of reasons, including the following.

  • The rash may be absent at the time of the exam or obscured under clothing or hair.
  • The patient may not recall having had an EM rash.
  • The clinician may not recognize EM rashes that lack the appearance of the classic "bull's-eye" appearance. This may result in misdiagnoses such as cellulitis, allergic reaction to tick saliva, contact dermatitis, spider bite, and tinea (ringworm).
  • The clinician may dismiss the patient's rash either because information regarding travel history and exposure activities were not asked or because the clinician is under the false impression that there is no Lyme disease in the patient's state of residence.

The findings from the Quest Diagnostics study suggest that clinicians may not be comfortable diagnosing Lyme disease on the basis of an EM rash alone. Test volume by month was highest during June and August (Lee-Lewandroski et al., 2019), which coincides with the peak incidence of case reporting and, presumably, the peak occurrence of EM rashes (Scwartz, Hinckley, Mead, Hook, & Kugeler, 2017). Given that there is broad acceptance that EM rashes do not need laboratory confirmation in high-incidence states (Wormser et al., 2006), the summer testing peak implies that clinicians do not recognize that fact; they are uncertain about their ability to correctly identify EM rashes; or they have identified an EM rash in a low-incidence state.

Geographical variations in disease presentations and the potential for diagnostic errors

The presence of objective findings of Lyme disease that satisfy the CDC surveillance case definition varies significantly between states. The following CDC-generated table (Table 8) documents the percentage of reported symptoms from each of the included states where patients had one or more of the following findings: EM rashes, Lyme arthritis, neurologic Lyme, and Lyme carditis from 1992-2006 in nine states (Bacon, Kugeler, & Mead, 2008).

Table 8: Percentage of reported symptoms among Lyme diseases patients by state

State EM rash Arthritis Neurologic Cardiac
Connecticut 74% 23% 10% 0.5%
Delaware 51% 50% 16% 0.9%
Massachusetts 68% 33% 15% 1.5%
Maryland 60% 36% 21% 1.0%
Minnesota 87% 19% 6% 0.4%
New York 74% 25% 9% 0.8%
Pennsylvania 61% 47% 15% 0.8%
Rhode Island 65% 37% 9% 0.7%
Wisconsin 70% 37% 11% 0.7%

It is not known whether these clinical and demographic variations reflect reporting anomalies or geographical strain diversity of B. burgdorferi. These state manifestation variations may be important, however. For example, when diagnosing Lyme disease, clinicians in Delaware may need to take into account that their state reports lower rash rates. It also has the highest case reports for arthritis and neurologic Lyme disease, suggesting that delayed diagnosis may be an issue, or Delaware may have more virulent strains.

Diagnostic errors due to an over-reliance on serologic testing

In the absence of an EM rash, many clinicians rely on test results in order to make or rule out a diagnosis of Lyme disease. However, as noted in the Tick-Borne Disease Working Group 2018 Report to Congress, serologic testing, which measures a person's antibody response to exposure to B. burgdorferi, the bacterial cause of Lyme disease, is insensitive and often inaccurate (Tick-Borne Disease Working Group, 2018).

Serologic testing in Lyme disease employs a sequential (two-tier) testing strategy. In theory, this sequence—a very sensitive first-tier test followed by a highly specific second-tier test—captures as many positive specimens as possible without generating too many false positive results. However, if the second-tier test is too specific, over-all sensitivity will drop significantly, and the number of false negative results will rise. In Lyme disease testing, the most commonly used sequence is an EIA test followed by IgM and/or IgG Western blotting. The Quest Diagnostics study raises concerns regarding the clinical effectiveness of this two-tier strategy. Of the 387,597 EIA positive specimens that subsequently underwent Western blotting, slightly less than half were positive (Lee-Lewandroski et al., 2019). While it is expected that some of the positive EIA results would be negative on the more specific IgM and IgG Western blots, this degree of discordant results is concerning. Potential explanations include: the EIA is overly sensitive, the Western blotting is insufficiently sensitive, or both. In any event, the results cast doubt on the reliability and sensitivity of two-tier testing for Lyme disease.

For these reasons, negative results do not rule out the infection (Tick-Borne Disease Working Group, 2018). While some clinicians recognize this to be the case in early Lyme disease, too few understand that many patients with late, non-arthritic manifestations of Lyme disease, and those who have been previously treated but remain ill, will be seronegative.

Seronegativity in late, untreated disease may be due to a waning antibody response. Animal studies in untreated Lyme disease-infected monkeys documented that results of a commonly used serologic test were positive early in disease but subsequently reverted to normal although the bacteria remained in the tissues (Embers et al., 2012). Patients who are treated for Lyme disease early in the infection but who remain ill may also be seronegative (Dattwyler et al., 1988; Lawrence, Lipton, Lowy, & Coyle, 1995; Luft et al., 1996). This situation can arise when administration of antibiotics early in the infection removes enough of the bacteria to prevent a full antibody response to the organism yet leave sufficient numbers behind to cause ongoing disease (Dattwyler et al., 1988).

Additionally, it has been demonstrated that antibodies to B. burgdorferi can become bound up in immune complexes with Bb antigens.(Schutzer, Coyle, Belman, Golightly, & Drulle, 1990; Schutzer, Coyle, Reid, & Holland, 1999). If a large number of antibodies are sequestered in immune complexes, there may not be enough free antibodies available to bind with test antigens, thereby resulting in negative test results (Schutzer et al., 1990).

Conclusion

Patients with persistent Lyme disease report frequent misdiagnosis. Despite the fact that 74% of those enrolled in MyLymeData report early symptoms, 70% are not diagnosed until six or more months after symptom onset (Johnson, Chart Book, 2019). Misdiagnosis is reported to be common even among those being evaluated for early Lyme disease, particularly if the EM rash is absent or the CDC objective findings are not present. Early diagnosis and treatment of acute Lyme disease usually prevents the progression to persistent Lyme disease. Diagnostic barriers include: using inaccurate geographic risk maps; failing to consider the most common early manifestations of the disease; and over-reliance on imperfect lab tests. Remedying these identified diagnostic errors may significantly improve patient outcomes as early diagnosis and treatment are associated with greater treatment success.

Possible opportunities

  • The greatest opportunity in Lyme disease is to achieve earlier diagnosis and treatment for those who contract the disease to prevent the development of persistent Lyme disease. Equally important is the opportunity for CDC, clinicians, and patients to promote a common agenda—namely, the early diagnosis and treatment of Lyme disease. Initiating treatment during the first month of the infection is critical to the prevention of disease progression and the development of persistent Lyme disease. To achieve this goal, the causes of diagnostic errors and misdiagnosis identified in this report would need to be addressed.
  • The development and dissemination of more robust training and education programs via medical schools, residencies, and continuing medical education (CME) programming that enhance clinician understanding of tick-borne diseases is another opportunity worth pursuing. Enhancing clinician understanding of Lyme disease has the potential to alleviate patient suffering through timely and accurate diagnosis.
  • The development and dissemination of more robust education programs for the general public and high-risk groups that focuses on prevention and disease awareness is much needed. Such programs may result in potentially infected individuals seeking medical care at the earliest possible moment.
  • There is an opportunity to expand our understanding of prevalence of Lyme disease by using big data technology tools that are now available to better gauge the geographical scope and growth of the disease periodically using laboratory data from a number of the major diagnostic laboratories.

Threats or challenges

  • The limited recognition of the magnitude and the potential for significant health and quality of life impairments due to Lyme disease as well as the limited recognition of the emerging science, particularly with regard to the potential for persistent manifestations of the illness, may reduce the willingness to develop comprehensive educational programs.
  • The selection of a curriculum development team that fails to include a wide spectrum of medical and scientific viewpoints could undermine the content development process and result in educational programs that do not meet the needs of patients, clinicians and the public.
  • Inherent resistance to change may keep patients, clinicians and the public from acting on new information.

Potential Actions 3-7

The subcommittee proposes the following actions for the Tick-Borne Disease Working Group to consider.

Potential Action 3: Renew and expand the recommendation for CDC to develop a multi-leveled curriculum on Lyme disease for clinicians. This should include instructional programs for medical students, residents, physician assistants, mental health professionals, and nurse practitioners. Ongoing education via continuing medical education programs should also be included. In addition to providing background information on all aspects of these infections, the content should highlight the most frequent sources of diagnostic errors identified in this report, including:

  • Inappropriately excluding Lyme disease from the initial differential diagnosis because of geographic exclusions that inaccurately reflect the geographic scope of the disease;
  • Failing to recognize the full spectrum of Lyme disease-related symptoms;
  • Failing to identify erythema migrans rashes and/or other Lyme disease-related findings on physical exam; and
  • Cautioning clinicians against over-reliance on inaccurate diagnostic tests.

The training should also emphasize the inclusion of Lyme disease in the differential diagnosis of complex illnesses.

The curriculum development team should include representatives of all stakeholder groups, including meaningful patient representation (as defined in Potential Action 2). Clinicians and research scientists with expertise in this field should be selected such that the team represents the spectrum of scientific and clinical perspectives on tick-borne diseases.

Potential Action 4: Recommend that CDC provide input to the Council of State and Territorial Epidemiologists, CSTE, that the Lyme disease surveillance case definition be revised such that it abandons the use of geographic parameters for Lyme disease.

Potential Action 5: Recommend funding CDC to periodically conduct studies using available laboratory data from a number of the major diagnostic labs utilizing big-data technology methods. Findings from these studies would not replace the current surveillance system but would provide an additional information source that would increase our understanding of the geographic exposure and growth in the incidence of Lyme disease.

Potential Action 6: Recommend that CDC, NIH, and other government agency websites, brochures, and educational materials abandon the use of geographic parameters for the diagnosis of Lyme disease and that clinicians and the public be made aware that Lyme disease has been reported in all states.

Potential Action 7: Recommend that CDC, NIH, and other government agency websites, brochures, and educational materials acknowledge the diagnostic limitations of clinically available laboratory tests for all stages of Lyme disease.

Vote of subcommittee members on Potential Actions 3-7

Vote on Potential Action 3 as written above

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Vote on Potential Action 4 as written above

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Vote on Potential Action 5 as written above

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Minority responses

There were no minority responses.

Prioritized Issue: Reducing Psychiatric Misdiagnoses in Lyme Disease

Importance

Unreliable diagnostic testing and a lack of consensus among experts leave patients with Lyme disease at risk for misdiagnosis with a primary psychiatric disorder. This results in inadequate medical treatment and poses a serious barrier to patients' access to effective care.

Summary of the evidence and findings

Numerous peer-reviewed articles have demonstrated an association between tick-borne diseases and brain dysfunction (Bransfield, 2018; Chavda & Patel, 2019; Hajek et al., 2002; Pachner et al., 1989; Reik, Smith, Khan, & Nolan, 1985). As many as forty percent of patients with Lyme disease develop neurologic involvement of either the peripheral or central nervous system (Fallon & Nields, 1994). Neuropsychiatric and neuropsychological symptoms caused by Lyme disease may include depression, anxiety and panic disorders, sleep disturbances, and more (Bransfield, 2012; Chabria & Lawrason, 2007; Fallon et al., 1992; Fallon et al., 1993; Garakani & Mitton, 2015; Greenberg, 2018; Pachner, 1989; Sherr, 2000). Publications also attest to the neurocognitive impairments experienced by patients diagnosed with Lyme disease (Adams et al., 1999; Bloom et al., 1998; Tager et al., 2001). Auditory and visual processing impairments may occur (Lucker, 2015; Leventhal, 2015, 2017; Padula et al., in press; Stricker & Winger, 2003). A study at Columbia University documented IQ improvement of twenty-two points in a sixteen-year-old after intravenous treatment for Lyme disease (Fallon et al., 1998).

These neuropsychiatric and neuropsychological symptoms have been less well recognized than other manifestations of this multisystemic disease (Fallon et al., 1995). Because they may emerge at a later stage, the possibility of an underlying infection may be overlooked (Fallon et al., 1995; Fallon et al., 1999; Logigian et al., 1999). Unreliable diagnostic testing contributes to this error, especially if the treating clinician is unaware of the full range of symptoms possible, and fails to understand that Lyme disease must be diagnosed according to clinical criteria and not laboratory testing. In one large study of Lyme disease based on self-report data, more than half of the respondents were initially misdiagnosed with another disorder; fifty-two percent of those were incorrectly diagnosed with having a psychiatric disorder, despite that only eighteen percent ranked psychiatric symptoms among their three worst concerns (Johnson, Chart Book, 2019). When these symptoms do become severe enough to warrant hospitalization, the care may become fragmented because most psychiatric hospitals are not equipped to provide the necessary medical treatment.

Lack of consensus among experts has contributed to confusion over appropriate diagnosis and treatment. For example, the Lyme disease treatment guidelines of the Infectious Diseases Society of America (IDSA) do not address neuropsychiatric and neuropsychological symptoms (Wormser et al., 2006). The current draft of their revised treatment guidelines recommends against testing for Lyme disease in patients with psychiatric disturbances; it includes only four citations to support this recommendation, and none of the guidelines panelists were mental health professionals (Bransfield et al, 2019). In contrast, the practice guidelines of the American Psychiatric Association (APA) recommend that the initial psychiatric evaluation include an assessment of locally endemic infectious diseases, and specifically mention Lyme disease (Sexton, 2016). The International Lyme and Associated Diseases Society (ILADS) also includes psychiatric symptoms and cognitive dysfunction in its list of common symptoms and signs of disseminated and late Lyme disease. They note that "classic" symptoms of Lyme disease are not always apparent, and diagnostic blood tests are highly unreliable. For these reasons, the diagnosis of Lyme disease must be made on a clinical basis (International Lyme and Associated Diseases Society, Lyme Disease Basics for Providers, 2019). The National Institute of Mental Health (NIMH), the lead Federal agency for research on mental disorders, is encouraging new applications to advance research activities into the following areas, which recognize an association between Lyme disease or other tick-borne diseases and psychiatric complications:

  • Basic mechanistic neuroscience studies of persistent effects of Lyme disease on brain signaling, circuits, and proximal effects on functional processes such as cognition that are impaired in mental illnesses;
  • Research to illuminate the mechanisms by which tick-borne diseases lead to specific psychiatric complications;
  • Research to understand the neurobiological basis of the impact of tick-borne diseases on specific domains of functions relevant to mental health, as informed by the Research Domain Criteria (RDoC) approach; and
  • Research to decrease the burden of acute and chronic psychiatric complications of Lyme disease and other tick-borne diseases. (National Institutes of Health, Notice of Special Interest: Advancing Research for Tickborne Diseases, 2019)

Children ages 0-19 represented 29% of CDC reported Lyme disease cases from 2001-2017 (Lyme Disease Association, 2019). In children, Lyme disease may adversely affect academic achievement. In the absence of an appropriate medical diagnosis, impaired performance may be misdiagnosed as behavioral, anxiety, or mood issues, or as a primary learning disability (Statlender & Levanthal, 2017; Statlender, 2019). Children who are unable to attend school due to illness have been charged with truancy; this is more likely to occur when schools rely on a medical consultant who lacks adequate experience with Lyme disease and disputes the diagnosis of the treating physician (Berenbaum & Leland, 2015; Smith, 2019). These students must receive appropriate academic accommodations to address the broader, more complex impact of the underlying infection. School nurses and other personnel have a potentially vital role to play and must be encouraged, not deterred, from considering Lyme disease as a possibility among students who struggle to succeed in school (Hamlen & Kliman, 2007; Hamlen & Kliman, 2009; Smith, 2003; Smith, 2004).

Parents of children with Lyme disease have been accused of Munchausen Syndrome by Proxy (MSBP), also known as Factitious Disorder by Proxy, a highly controversial diagnosis that has been widely discredited (Bransfield, Cook, & Bransfield, 2019; Sherr, 2005; Weintraub, 2007). In numerous cases, children have been forcibly removed from their homes, leaving families to fight for custody in the courts. These accusations are based in the belief that the illness in question has been knowingly fabricated or induced by an attention-seeking parent, usually the mother, and are more likely to occur in cases of contested or poorly understood diseases: "Physicians unfamiliar with the ‘shifting, seemingly vague, emotional, and/or bizarre-sounding complaints, frequently know little about [Lyme disease]' (Sherr, 2005). These families must be allowed to choose a physician who will treat Lyme disease according to their preferred standard of care.

Possible Opportunities

Better recognition of the full range of potential Lyme disease symptoms will promote more accurate diagnosis and more complete treatment of its infectious etiology.

Threats or Challenges

Scientific uncertainty increases the risk of diagnostic inaccuracies, especially in the hands of practitioners who lack familiarity with the full spectrum of symptoms possible with this disease. Some patients, for example, may be misdiagnosed with a psychiatric disorder by default, by practitioners who solely rely on flawed blood tests rather than on clinical criteria. The absence of positive test results should never be used to confirm the presence of a primary psychiatric disorder (Bransfield et al., 2019; Burke, 2019). These patients may be prescribed unnecessary psychotropic medications, which cause adverse side effects (for example, excessive weight gain, loss of libido) and will not treat the underlying infection.

In patients who do experience neuropsychiatric symptoms, psychotherapeutic and psychopharmacologic strategies may play an important role, but only in the context of appropriate medical attention, a multidisciplinary treatment plan, and mental health practitioners who understand the nature of the underlying infection. Unfortunately, today's medical practice is highly subspecialized. As a result, patients with multisystemic illnesses are at risk to receive fragmented care in treatment silos that fail to recognize the underlying disease. According to Fallon and his colleagues, "Lyme disease has a vast array of multisystem manifestations, including neuropsychiatric ones. Failure to recognize Lyme disease early in its course can result in the development of a chronic illness that is only temporarily or partially responsive to antibiotic therapy" (Fallon et al., 1998).

These combined factors present significant obstacles to patients' access to accurate diagnosis and effective treatment. Treatments focused only on symptom management may mask the underlying infection and allow it to progress unchecked.

Potential Actions 8-10

The subcommittee proposes the following actions for the Tick-Borne Disease Working Group to consider.

Potential Action 8: Provide information and training to health care professionals regarding the full spectrum of potential Lyme disease symptoms, including the potential impact on brain function. Lyme disease should be included in the differential diagnosis of patients with neuropsychiatric symptoms in order to promote appropriate diagnostic evaluations and subsequent treatment. Clinicians should be cautioned not to default to a psychiatric diagnosis when the cause of symptoms has not yet been determined.

Potential Action 9: Provide education and training to neuropsychologists, clinical and school psychologists, social workers, and other pertinent school personnel regarding the extent and complexity of the emotional, physical, cognitive, sensory, and other aspects of brain dysfunction that may be experienced by students with Lyme disease.

Potential Action 10: Encourage the development of multidisciplinary treatment teams that recognize medical, neuropsychiatric, and neuropsychological symptoms that may be experienced by some patients with Lyme disease. Recommend funding for NIH to develop an in-patient unit for multidisciplinary treatment of Lyme disease patients who present with neuropsychiatric symptoms.

Vote of subcommittee members on Potential Actions 8-10

Vote on Potential Action 8 as written above

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Vote on Potential Action 9 as written above

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Vote on Potential Action 10 as written above

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Minority responses

There were no minority responses.

Prioritized Issue: Shared Medical Decision-Making

The term shared decision-making (SDM) was popularized by the 1982 President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research as a necessary evolution of informed consent (President's Commission, 1982). As the President's Commission makes clear, the practitioner's obligation to "explain the facts and uncertainties that will give the patient a working understanding so they can participate effectively in the decision-making process" is an ethical imperative. Some experts trace its roots back further to the origin of evidence-based medicine (EBM), which Dr. David Sackett seminally defined as "the integration of best research evidence with clinical expertise and patient values" (Sackett, 1981; Sackett et al., 2000), and point out that there can be no EBM without SDM (Scheibler et al., 2012).

Shared medical decision-making is a key component of patient-centered health care. It is a process in which practitioners and patients work together to make decisions and select tests, treatments, and care plans based on clinical judgment that balances risks and expected outcomes with patient preferences and values (HealthIT.gov, 2013). The National Academy of Medicine (NAM) regards shared medical decision-making as central to good quality health care (IOM, 2011).

Importance

In Lyme disease, there is no optimal diagnostic or treatment pathway. Instead, two sets of divergent diagnostic and treatment guidelines have been published in peer-reviewed journals: one promulgated by the Infectious Diseases Society of America (IDSA) and the other developed by the International Lyme and Associated Diseases Society (ILADS) (Wormser et al., 2006; Cameron et al., 2014).

Conflicting guidelines are not uncommon. NAM notes that at least 25 conditions have conflicting guidelines; however, it observes that the conflicting guidelines between IDSA and ILADS are among the most contentious (IOM, 2011). The ILADS guidelines meet the rigorous standards imposed by NAM for guidelines development, including the use of the GRADE evidence assessment scheme, while IDSA is in the process of developing guidelines aimed toward meeting these criteria. Hence, shared decision-making would involve advising patients of the different treatment approaches and engaging in a dialogue regarding the appropriate approach for this individual.

There are many differences between the two sets of guidelines; however, the primary difference is that the IDSA guidelines impose restrictive diagnostic criteria and provide limited treatment options, while the ILADS treatment guidelines recognize a significant role for the exercise of clinical judgment and shared medical decision-making. Although IDSA is aware that two standards of care exist in the treatment of Lyme disease, their treatment guidelines do not disclose this fact and patients are generally not aware that other treatment approaches exist. In contrast, the ILADS guidelines note the IDSA guidelines and recommend that the clinician discuss the divergent treatment options with the patient to ensure informed shared medical decision-making (Wormser et al., 2006; Cameron et al., 2014).

Shared medical decision-making has the most value when evidence is uncertain as the National Academy of Medicine makes plain: "Informed choice under uncertainty is an ideal to strive for, especially because it enhances the exercise of the patient's right of self-determination, which is a cornerstone of medical ethics" (IOM, 2011).

The Office of the National Coordinator for Health Information Technology (ONC) explains the necessity for shared medical decision-making in the context of individual preferences and treatment response variation:

"In many situations, there is no single ‘right' health care decision because choices about treatment, medical tests, and health issues come with pros and cons. Shared decision-making is especially important in these types of situations:

  • When there is more than one reasonable option, such as for screening or a treatment decision;
  • When no one option has a clear advantage; and
  • When the possible benefits and harms of each option affect patients differently." (HealthIT.gov, Shared Decision Making Fact Sheet, 2013).

A pivotal problem with the implementation of shared decision-making in Lyme disease is that many of the stakeholders in health care do not know that there are two sets of treatment guidelines reflecting divergent diagnostic and treatment approaches in Lyme disease. Hospitals, insurers, medical boards, practitioners, and patients, are typically aware of the IDSA diagnosis and treatment approach, but they are often unaware of the existence of ILADS or its divergent diagnostic and treatment approaches.

Shared medical decision-making would provide patients with the knowledge essential to navigate and more quickly obtain prompt diagnosis and treatment to improve health outcomes. However, it is impossible for shared decision-making or informed choice to occur unless all of the stakeholders— patient, clinician, clinical institution or hospital, and insurance company—are aware that divergent approaches to diagnosis and treatment exist.

Summary of evidence and findings

Background: Patient-centered health care and shared medical decision-making

Patient-centeredness as a cornerstone of high-quality health care gained national recognition in the National Academy of Medicine report Crossing the Quality Chasm: A New Health System for the 21st Century. There, patient-centeredness is defined as "providing care that is respectful of and responsive to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions" (IOM, 2001).

Shared medical decision-making is part of the patient-centeredness initiative and rests on the ethical imperative of autonomy in medial decision-making. A widely cited New England Journal perspective explains that shared medical decision-making is the highest form of patient-centered care because, unlike other health care stakeholders, patients alone must live with the consequences of the medical intervention taken or declined (Edgman, 2012). Because of this, patients are sometimes referred to as the "ultimate stakeholder" (deBronkart, 2013).

Shared medical decision-making is also a key policy initiative in the Patient Protection and Affordable Care Act of the U.S. Federal Government, which seeks in part to "facilitate collaborative processes between patients ... and practitioners that engage the patient ... in decision-making, provides patients ... with information about trade-offs among treatment options, and facilitates the incorporation of patient preferences and values into the medical plan" (H. R. 3590 (111th): Patient Protection and Affordable Care Act (2010). A number of government and health care agencies funded by Congress have embraced shared medical decision-making initiatives, including:

  • The Agency for Healthcare Research and Quality (AHRQ, The SHARE Approach, 2018);
  • The Centers for Medicare & Medicaid Services (Merchant, 2018);
  • HealthIT.gov (HealthIT.gov Shared Decision Making Fact Sheet, 2013);
  • National Quality Forum (National Quality Partners, Shared Decision Making: A standard of Care for All Patients, 2017); and
  • The Patient Centered Outcomes Research Institute (PCORI, Topic Spotlight: Shared Decision Making, 2019).

That National Quality Forum (NQF), a not-for-profit, nonpartisan, membership-based organization that works to catalyze improvements in health care, has issued a call to action to make shared medical decision-making part of the customary standard of care (NQF, 2017). They note that because most health care decisions are preference-sensitive (where evidence does not clearly identify one treatment option as better than another), individual health care goals and values about particular set of outcomes should play a major role in their choices about which treatment option is best for them.

In addition, a number of states, including Maine, Minnesota, Oregon, Vermont, and Washington, have taken legislative action promoting shared medical decision-making. The Washington law also established a shared decision-making demonstration project and designated it as one strategy to be used in a governor-appointed collaborative aiming to improve quality and outcomes (Shafir & Rosenthal, 2012).

The interplay between clinical judgment, shared decision-making, and medical ethics in Lyme disease

Shared decision-making and the exercise of clinical judgment are interrelated processes. Clinical judgment is informed by a clinician's training, clinical experiences, and interactions with colleagues. The exercise of clinical judgment is especially important when the therapeutic evidence is limited and evolving, the patient population and disease manifestations are heterogeneous, and current treatment outcomes are far from ideal (Maloney, 2009).

Clinical judgment does not exist in a vacuum; valid judgments must be informed by the patients at the heart of these judgments, hence the need for shared decision-making. Within the context of shared decision-making, clinicians weigh risk-benefit concerns with individual patients. For a given individual, decisions regarding whether and how to treat depend on an array of clinical factors, the patient's values and preferences as well as the patient's ability to tolerate different regimens, severity of illness, potential adverse events, lifestyle impact, and costs. Once identified, these elements are considered in light of the potential benefits of treating and the risks associated with failing to treat, and balanced against the risks posed by the individual potential therapies. Clinical judgment and shared decision-making can be limited by a clinician's unacknowledged or uncontrolled biases and knowledge deficits regarding the disease at hand (Saposnik, Redelmeier, Ruff, & Tobler, 2016).

Medical ethics principles exert a strong influence over clinical judgments and shared decision-making conversations. For this reason, it is important to understand the principles that are involved. Key principles include the need to act in the patient's best interest (beneficence); the duty not to harm patients (non-maleficence); and respect for patient autonomy, which protects the patient's right to choose between therapeutic options (Beauchamp & Childress, 1994). In shared decision-making, patient autonomy is viewed as the patient's right to make informed decisions about their own care without undue influence or external manipulation (Martinez, Kurian, Hawley & Jagsi, 2015). These core principles, among others, are reflected in the American Medical Association Principles of Medical Ethics (2016).

The duty not to harm typically aligns with the duty to act in the patient's best interest, but when this is not the case, the duty not to harm has priority ("first, do no harm"). However, this guidance is not absolute, and clinicians are expected to weigh the potential harms and benefits of acting versus not acting. Every medical intervention involves risks and benefits. The question that practitioners and their patients must consider is whether the potential benefits outweigh the harms for this patient given their circumstances. For example, surgery for colon cancer may result in the need for a colostomy, yet few clinicians would withhold the procedure on that basis.

Unlike the duty not to harm, the precautionary principle, which was developed to address environmental toxicity policies on a population-wide basis, is inappropriate for guiding medical decisions which involve trade-offs in the context of individualized care (ter Meulen, 2005; Peterson, 2007). Although the goal of the precautionary principle is to avoid serious and plausible risk by verifying the safety of a proposed intervention (such as pesticides) before permitting use, most medical care involves individualized care where decisions are made in the grey zones (IOM 2001; ter Meulen, 2005). While the precautionary principle would seemingly encourage a clinician not to act when the safety of an intervention is unknown, adherence to that principle would fail to respect patient autonomy by imposing the clinician's value judgment regarding unknown risks, and it would weaken shared decision-making by arbitrarily limiting options (ter Meulen, 2005).

Another reason that applying the precautionary principle to medicine would be inappropriate is that it would essentially foreclose clinical innovation. Like many research-disadvantaged diseases, almost all treatments of Lyme disease are off-label and rely heavily on innovative clinicians to develop treatments that improve health and reduce morbidity (Fugh-Berman, 2008; FDA, 1982). Innovative therapies include the use of unconventional dosages of standard medications, a novel combination of currently accepted practices, new applications of standard interventions, and the use of accepted therapy or approved drugs for non-approved indications (American Medical Association, Code of Medical Ethics Opinion 1.2.11, 2019).

Shared decision-making assumes greater importance when the evidence base is weak and considerable heterogeneity exists among patients, making a one-size-fits-all approach inappropriate (Akins Siegel, & Slutsky, 2005). Although many conditions that involve trade-offs use shared decision-making approaches, perhaps the most well-known examples of shared decision-making are breast cancer and prostate cancer, where patients are provided with information about available treatment options and make decisions in consultation with the practitioners (Mully & Barry, 1998; Martinez et al., 2015).

In Lyme disease, uncertainty arises from two factors: the lack of a robust evidence base and the heterogeneity of patient clinical presentation and treatment response (Fallon, 2012; Cameron, 2014; Johnson, 2018). The evidence base is sparse compared to other infectious diseases (Goswami, 2013). NIH has funded just three research grants for persistent Lyme disease, with the last one being funded over 15 years ago (Fallon, 2008, Krupp, 2003, Klempner, 2001). Hence, the state of the science on Lyme disease is limited, unsettled, and emerging. A review of the three NIH funded studies describes the state of the science on persistent Lyme disease as follows:

"Based on the evidence cited above, one cannot conclude that repeated antibiotic therapy is ineffective in improving certain symptoms associated with post-treatment Lyme disease syndrome. Nor can it be concluded that repeated antibiotic therapy is robustly effective. One can conclude however that approximately 60% of patients with persistent posttreatment Lyme fatigue may experience meaningful but partial clinical improvement in fatigue with antibiotic retreatment. Guidelines for Lyme disease that address patients with chronic symptoms therefore need to clarify that the controlled trials of additional antibiotic therapy for posttreatment Lyme symptoms have revealed conflicting results, with some studies demonstrating efficacy and others not showing benefit to repeated treatment. "(Fallon, 2012)

The fact that medical interventions may be necessary when evidence is uncertain is widely recognized and is acknowledged by the IOM:

"The committee is well aware that for many aspects of health care, scant or no evidence of either effectiveness or ineffectiveness exists... . It is clearly not possible to base all care on sound scientific evidence, and certainly not exclusively on randomized controlled trials, which narrowly define study populations and exclude or control for factors that are inevitably relevant in real-world care settings."
–Institute of Medicine, 2001

In addition, pharmaceutical interest in treatment approaches has not been robust because the disease is treated with generic antibiotics, and antibiotic development interest has not been a prioritized profit center (Paavola, 2018). Because there have been few NIH treatment trials, which have yielded conflicting results, and there is a lack of pharmaceutical interest, Lyme disease is a research-disadvantaged disease.

The IOM's recommendations on creating trustworthy guidelines note that guidelines developed "where high quality evidence is lacking or even nonexistent", should reflect the sparsity of evidence and permit individualized care:

"Rather than dictating a one-size-fits-all approach to patient care, [guidelines] are able to enhance clinician and patient decision making by clearly describing and appraising the scientific evidence and reasoning (the likely benefits and harms) behind clinical recommendations, making them relevant to the individual patient encounter" (IOM, 2011).

The interplay of clinical judgment, shared decision-making and medical ethics in Lyme disease is complex and sometimes misconstrued. AMA holds that shared decision-making is an ethical obligation (American Medical Association, Code of Medical Ethics Opinion 1.1.3, 2019). Clinicians are expected to discuss benefits, risks, and costs of available therapeutic options individually and comparatively. In conditions such as Lyme disease, where the evidence is uncertain and diagnostic tools lack the ability to directly detect active infection, conflicting viewpoints as to the best approach may arise among practitioners and even among patients (Atkins et al., 2005).

As noted previously, in Lyme disease two professional societies, IDSA and ILADS, have published conflicting guidelines reflecting different diagnostic and treatment approaches for Lyme disease. In these circumstances, although clinicians may disagree about whether intervention is the best approach, neglecting to advise the patient that conflicting recommendations exist fails to respect patient autonomy and weakens shared decision-making by arbitrarily limiting information to the patient about treatment options. For example, even in matters of conscience, AMA ethical standards require that the clinician "uphold standards of informed consent and inform the patient about all relevant options for treatment, including options to which the physician morally objects" adding that "physicians should refer a patient to another physician or institution to provide treatment the physician declines to offer" (American Medical Association, Code of Medical Ethics Opinion 1.1.7, 2019). AMA further explains that "[p]hysicians' fiduciary obligation to promote patients' best interests and welfare can include ... referring patients to other professionals to provide care" (American Medical Association, Code of Medical Ethics Opinion 1.2.3, 2019). This type of clinician-clinician referral, from one who does not provide a desired therapeutic option to one who does, is common. The treatment of prostate cancer (for example, surgery versus radiology) is one such example.

Applying ethical standards in Lyme disease involves weighing ethical considerations of beneficence, maleficence, and respect for patient autonomy. The balancing of these factors is perhaps most difficult with regard to patients with persistent manifestations of Lyme disease despite prior antibiotic therapy. The small but real risks of additional antibiotic therapy in the face of uncertain benefits may persuade some clinicians to forego this option (Wormser et al., 2006). However, other clinicians recognize that doing so may allow an infection to go unchecked, which is certainly not in the patient's best interest (Cameron et al., 2014; Donta, 2012). These clinicians realize that all medical interventions involve some risk and may choose to proceed with caution—prescribing antibiotics while anticipating and, when possible, mitigating their associated risks.

To summarize, the complexities and nuances of clinical judgment, shared decision-making, and medical ethics are accentuated in light of the scientific and medical uncertainties that are part and parcel of Lyme disease. Clinicians may or may not choose to be actively involved in the care of this patient population, but medical ethics require that they prioritize their patient's needs and—if they decline to provide care—inform the patient of other available diagnostic and treatment approaches to ensure that the patient's right of autonomy is respected.

Possible opportunities

There is an opportunity to reduce diagnostic delays by providing patients with the information that there are different approaches to the diagnosis and treatment of Lyme disease. Currently patients are shuffled from clinician to clinician, and diagnosis may take years to achieve. By providing patients with the knowledge of different diagnosis and treatment approaches, patients have more resources available to them to expedite the diagnosis and treatment of Lyme disease.

Major challenges

Physician time constraints

Physicians who are pressed for time, may be reluctant to extend the additional effort to engage in shared decision-making. However, printed materials and video materials can be used to decrease this burden. One study on prostate cancer, for example, found that 38% of the men provided with shared decision-making materials on PSA screening were comfortable making the decision on their own without further consultation with their clinician (Barry, Edgman-Levitan, & Sepucha, 2018).

In addition to saving time, experts point out that many practitioners do not have all the information that patients need to know and may lack the skill of communicating complex information in a clear way (Wegwarth, Schwartz, Woloshin, Gaissmaier, & Gigerenzer, 2012).

Fear that patients will be confused or overwhelmed by information

Practitioners may fear that communicating uncertainty in medical decisions will overwhelm or confuse patients. However, a recent study found no evidence of a reluctance on the part of patients to collaborate with physicians in making decisions; however, the same study found a widespread perception that physicians did not want patient participation and that patients were concerned about being perceived as "difficult" if they spoke up about their own views and preferences when decisions were made (Frosch, May, Rendle, Tietbohl, & Elwyn, 2012). Another study found that, despite clinician concerns about patients' ability to understand numeric material, the majority of patients could understand statistics when presented clearly (Galesic, Gigerenzer, & Straubinger, 2009).

Beneficent paternalism

Clinical guidelines have shifted in recent decades from a paternalistic model to one based on respect for patient autonomy and, more recently, to shared decision-making. Nevertheless, practitioners may believe that they understand their patients' concerns and are capable of making better decisions on their behalf (beneficent paternalism). According to the American Medical Association, paternalism is "an action performed with the intent of promoting another's good but occurring against the other's will or without the other's consent" (Virtual Mentor, 2012).

The difficulty with paternalism for a legally competent adult is that even a sincere belief about what is good for another person may be wrong. People may be incorrect about what harms or benefits others (Virtual Mentor, 2004). These differences in values and preferences are at the heart of the ethical construct of autonomy. For example, a recent study regarding breast cancer found major differences between physicians and patients in what they thought was important (Lee, 2010). Mulley and colleagues make the point that practitioners often make decisions unaware of patients' preferences. They call this type of error "silent misdiagnosis" in analogy to clinical misdiagnosis (Mulley, Trimble, & Elwyn, 2012).

Potential Actions 11-13

The subcommittee proposes the following actions for the Tick-Borne Disease Working Group to consider.

Potential Action 11: Increase public awareness that there are two divergent diagnostic and treatment approaches reflected in guidelines for Lyme disease.Encourage the disclosure on all state and Federal government websites that discuss Lyme disease or tick-borne diseases, including CDC, NIH, AHRQ, that there are two diagnostic and treatment approaches, and encourage inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Potential Action 12: Encourage the disclosure on all state and Federal government websites that discuss Lyme disease or tick-borne diseases, including CDC, NIH, AHRQ, that the state of the science in Lyme disease, particularly for persistent Lyme disease, is limited, emerging, and unsettled. Encourage the inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Potential Action 13: Encourage the use of shared decision-making in Lyme disease on all state and Federal government websites that discuss Lyme disease or tick-borne diseases, including CDC, NIH, AHRQ, and encourage inclusion of the two diagnostic and treatment approaches for Lyme disease in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Vote of subcommittee members on Potential Actions 11-13

Vote on Potential Action 11 as written above

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Vote on Potential Action 12 as written above

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Vote on Potential Action 13 as written above

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6 0 0 1

Minority responses

There were no minority responses.

Prioritized Issue: Reimbursement and Coverage

Due to circumstances beyond the control of the Subcommittee, this portion of the report was not able to be completed and should be deferred for consideration until the next Tick-Borne Disease Working Group convenes.

Prioritized Issue: Patient and Public Health Education on Lyme Disease and Other Tick-Borne Diseases

Importance

Better education of the public would encourage individuals who are bitten by a tick and develop symptoms to access treatment in the early stage of Lyme disease and other tick-borne diseases. Most of these diseases respond well to early treatment, preventing patient suffering and reducing cost. Current information available to patients does not always reflect the latest scientific and medical knowledge, leading to delayed treatment. For example, some state health departments claim there are no cases of Lyme disease or other tick-borne diseases within their state, when confirmed cases exist.

Some patients receive a delayed diagnosis due to missed early signs and symptoms of infection, misdiagnosis, low reliability of currently available laboratory tests, or clinician denial of illness. Some have been undertreated. Often these patients turn to the Internet for answers about tick-borne diseases. The information they will find, like any web information on any topic, is often contradictory, incomplete, or reflects a certain viewpoint or agenda. Finding reliable information online is challenging, and this is compounded by the fact that many people seeking answers are ill and compromised in their ability to process complex medical information.

Evidence and Findings

A review of ten state health department websites—chosen to represent high- and low-incidence states—and geographic diversity, revealed that all were quite consistent in their recommendations for prevention of tick bites.

The state health departments reviewed were: California, Colorado, Connecticut, Florida, Maine, Missouri, New York, North Carolina, Oregon, and Pennsylvania.

Many states quote the "36- to 48-hour" tick-attachment time required for Lyme disease transmission, which may lead patients to believe that they are safe after promptly removing a tick. This estimation is based on the assumption that Lyme disease bacteria have to migrate from the midgut of the tick to the salivary glands; yet researchers, including Wilhelm Burgdorfer himself, have long known that the bacteria may be in the salivary glands at the time of the bite:

Studies done so far suggest that it takes about two days of attachment and feeding before spirochetes are being transmitted to a host animal. This is referred to as the "safety period," during which a person could remove a tick without becoming infected. I personally don't subscribe to this theory, because there are about 5 to 10 percent of infected ticks that have a generalized infection, including salivary glands and saliva at the time of attachment. In such cases, transmission of spirochetes would and does occur immediately at time of attachment (W. Burgdorfer, Deirdre Boggs Interview with Willy Bergdorfer finalized by him October 2001). https://history.nih.gov/archives/downloads/wburgdorfer.pdf).

A more recent literature review (Cook, 2015) has determined that "in animal models, transmission can occur in less than 16 hours, and the minimum attachment time for transmission of infection has never been established." According to researchers at CDC, "...the possibility that transmission of Lyme disease spirochetes could occur within 24 hours of nymphal attachment under unusual circumstances should not be discounted... Partially fed ticks able to re-attach could result from detachment from dead animals or possibly by host grooming" (Eisen, 2018). Additionally, some other tick-borne diseases, such as Powassan virus, have been documented to require only 15 minutes of tick-attachment time for transmission (Columbia University Irving Medical Center, 2019).

Most of the prevention information on the state websites reviewed, and many of the other topics covered, are based on CDC recommendations. Some states simply linked to the CDC for the majority of their information. If the information published by the CDC does not reflect all the credible research on tick-borne diseases, this omission will percolate down to state and local health department websites.

Almost all states list the most common tick-borne diseases as reportable in their state. Anaplasmosis, babesiosis, ehrlichiosis, Lyme disease, Rocky Mountain spotted fever, B. miyamotoi, and tularemia were listed on most states under reportable tick-borne diseases. However, specific information on diagnosis and treatment of many of the reportable tick-borne diseases is often lacking. For example, Colorado lists five reportable tick-borne diseases (Colorado tick fever, tick-borne relapsing fever, tularemia, and Rocky Mountain spotted fever), but only offers diagnosis and treatment information for one disease (tularemia). The Colorado state website makes the claim that all cases of Lyme disease in the state were acquired by residents traveling to another state: "Ticks that carry Lyme disease are not native to Colorado. No confirmed cases of the disease have originated here; however, residents who travel out of state are at risk..." (State of Colorado, 2019).

Some of the Southern and Midwestern states list Southern Tick-Associated Rash Illness (STARI), although all states surveyed indicated that this disease is not well understood. States in the Lower-Midwest list Heartland virus and Bourbon virus, two emerging tick-borne diseases. However, none of the surveyed state websites mention bartonellosis, a bacterial infection often found in Lyme disease patients, although the route of infection is unclear (Breitschwerdt, 2017). Numerous molecular surveys have been conducted to detect Bartonella DNA in ticks, yet there is little evidence that Bartonella can replicate within ticks and no definitive evidence of transmission by a tick to a vertebrate host (Angelakis et al., 2010). Nonetheless, there is some laboratory evidence that Ixodes rincinus, a European tick, is a competent vector for Bartonella henselae (Cotte et al., 2008). CDC's position on tick-borne Bartonella is that ticks may carry some species of the bacteria, but there is currently no causal evidence that ticks can transmit Bartonella infection to people through their bites (Centers for Disease Control and Prevention, Bartonella Infection: Transmission, 2019).

All states recommend the CDC two-tiered testing surveillance protocol for Lyme disease (ELISA followed by Western Blot), although some states suggest that the results may not be reliable. Most states report that testing in the first few weeks of infection is likely to miss positive cases (Centers for Disease Control and Prevention, Lyme Disease: Diagnosis and Testing, 2019; Mayo Clinic, Lyme disease: Diagnosis, 2019; Depietropaolo, Powers, Gill, & Foy, 2005; Aguero-Rosenfeld & Wormser, 2014).

Pennsylvania offers free Lyme disease blood testing for in-state residents, and will also test ticks for anaplasmosis, Lyme disease, and Rocky Mountain spotted fever, at no cost. The laboratory blood testing for Lyme disease uses the state's own laboratory, which utilizes the CDC two-tiered surveillance testing protocol (Pennsylvania Department of Health, Lyme Serology Test, 2019; Tick Research Lab of Pennsylvania, n.d).

The Pennsylvania Department of Health website publishes the report of the Task Force on Lyme Disease and Related Tick-borne Diseases (2015), which lists 18 specific recommendations to the Commonwealth Task Force on Lyme Disease and Related Tick-Borne Diseases. Several of these recommendations have been put into place, including updated printed and web literature; a public awareness campaign using billboards and public service announcements; and expanded surveillance of tick populations. The Pennsylvania state legislature approved increased funding for tick-borne disease surveillance and education. In 2019, a public health advisory was sent to all relevant agencies urging an improved response to tick-borne disease, noting that the state has more reported cases of Lyme disease than any other state, and the number of cases is increasing (Pennsylvania Department of Health, Health Advisory, 2019). The Pennsylvania Department of Health website could be a useful model for other states.

CDC's website has extensive information on tick-borne diseases. For many years, the CDC website specifically referenced the Infectious Diseases Society of America (IDSA) Lyme Guidelines. Although CDC recently removed the specific reference to IDSA Lyme Disease Guidelines, its website now has a section that largely follows the tenants of the IDSA diagnostic and treatment guidelines from 2006. There has never been any mention on the website of the more recent guidelines published by the International Lyme and Associated Diseases Society (ILADS), which follow the National Academy of Medicine, formerly Institute of Medicine, guidelines for guidelines' development. There is no mention of the two standards of care for Lyme disease that are addressed by the two different sets of guidelines.

The CDC reportable tick-borne diseases are anaplasmosis, babesiosis, ehrlichiosis, Lyme disease, Powassan virus, spotted fever rickettsioses—including Rocky Mountain spotted fever, 364D, Rickettsia parkeri rickettsiosis—and tularemia. State-by-state statistics are available for the reportable tick-borne diseases, with historic data going back at least a decade for most of the diseases.

Occupational Risk for Tick-Borne Diseases

As of the writing of this report, the CDC website has an undated list of hazardous activities that may put works at risk for tick-borne diseases, including: construction, landscaping, forestry, brush clearing, land surveying, farming, railroad work, oil field work, utility line work, parks or wildlife management, and other outdoor work.

Of the state health departments surveyed, only California offers any guidance on occupation-related risk of tick-borne diseases. Their website duplicated the CDC list of hazardous activities.

The Occupational Safety and Health Administration (OSHA) has an undated memorandum to Regional Administrators that offers guidance for workplace safety, largely derived from the 2000 IDSA guidelines. OSHA noted that left untreated, Lyme disease can become "severe, chronic, and disabling" (Occupational Safety and Health Administration, n.d). The prevention advice follows the CDC guidance.

Blood Supply

The CDC lists babesiosis as the only tick-borne disease known to potentially infect those getting a blood transfusion with blood donated by someone with the disease. None of the reviewed state health department sites mentions blood transfusions.

The American Red Cross lists a total of nine illnesses that they always test for, including three vector-borne diseases, one of which is babesiosis. (The others are West Nile Virus and Zika virus.) However, published data includes multiple papers on B. microti, A. phagocytophilum, and Ehrlichia ewingii (Goel et al., 2018).

There was no mention found on the American Red Cross website of danger of blood infected with Lyme disease or other tick-borne diseases other than babesiosis.

Organ Donation

Documented cases of tick-borne disease transmission from infected donor organs are rare, but the danger is real. Ehrlichia species have been spread through blood transfusion and organ transplant (Centers for Disease Control and Prevention, Ehrlichiosis Transmission, 2019), including two kidney recipients who both developed E. chaffeensis infections after receiving blood from the same donor who later tested positive for the infection (Sachdev, Joshi, Cox, Amoroso, & Palekar, 2013). In another example, an organ recipient contracted B. microti "from an organ donor who received a blood transfusion that was positive for B. microti" (Brennan et al., 2016).

Web Search

Most people will use a web search engine to find online information on tick-borne diseases. This can be overwhelming and leave people with incomplete, inaccurate, or confusing information. A search using Google on the term "Lyme disease" will result in 38 million references, and few people will search past the first page or two of results. In a recent search (October 24, 2019), the first page of results displayed paid-for ads in the top three results. Of those, the first one was for a commercial walk-in health clinic, targeted to the searcher's geographic area. The next two were patient advocacy groups. The fourth was Wikipedia, which had typical information, but with a combination of mainstream (CDC) and somewhat fringe information. The Infectious Diseases Society of America (IDSA) is quoted extensively, along with CDC. There is no mention of the guidelines published by the International Lyme and Associated Diseases Society (ILADS). Prevention information reflected commonly accepted suggestions.

The next two search links were to the CDC information on Lyme disease, followed by a duplicate link to Wikipedia. The next results were Medline, WebMD, Mayo Clinic, Healthline, which all offered mainstream, CDC/IDSA information. The last entry on the first search page was the American Lyme Disease Foundation (ALDF). The information on the ALDF website was largely based on the IDSA guidelines.

The Infectious Diseases Society of America (IDSA) appears on the third page of the Google search, and the International Lyme and Associated Diseases Society (ILADS) is on the fourth page.

There are large differences in the information presented by the Lyme disease advocacy groups versus the CDC and most other organizations in the top twelve search results. The most glaring difference observed was that the advocacy group sites were much more up to date in quoting the latest in medical research on tick-borne diseases.

Opportunities

Improving the tick-borne disease information on ticks, symptoms, long-term effects, and treatment available to the public would benefit patients and health-care professionals. The information on the CDC website focuses on Lyme disease. The other tick-borne diseases and conditions in the U.S. can be serious, and more information about them would be helpful. Since much of the information available to the public from both state health departments and from a web search is derived from the CDC information, improving the quality of the CDC information would eventually be reflected on the other sites.

Threats or Challenges

In medicine, there is often inertia among health care professionals in utilizing new research in their practice, perhaps due to lack of time and/or the huge amount of new information available daily (Prasad & Cifu, 2011; Reed-Guy, 2013). This appears to apply to many diseases and conditions, not just tick-borne diseases. There are well over 20,000 medical journal articles on Lyme disease and other tick-borne diseases, and many of them go beyond the knowledge presented by CDC and many other sources. Many of the studies have been replicated and verified. Yet, the information revealed does not break through to the medical community. Improving access to the latest research would benefit both patients and health care professionals.

Potential Actions 14 and 15

Since most of the general information presented on state and local health department websites, printed literature, and social media content is derived from CDC and other Federal agencies, the first step is to ensure that those Federal sites have the most up-to-date information.

Potential Action 14: Recommend that CDC, NIH, and other government agency websites, brochures, and educational materials on Lyme disease and other tick-borne diseases be developed by a curriculum development team. This team should include representatives of all stakeholder groups, including meaningful patient representation (as defined in Potential Action 2). Clinicians and research scientists with expertise in this field should be selected such that the team represents the spectrum of scientific and clinical perspectives on tick-borne diseases.

Potential Action 15: Improve public information about 1) occupational risks of tick-borne diseases; and 2) the risks associated with blood transfusions and organ transplants.

Vote of subcommittee members on Potential Actions 14 and 15

Vote on Potential Action 14 as written above

Number in Favor Number Opposed Number Abstained Number Absent
6 0 0 1

Vote on Potential Action 15 as written above

Number in Favor Number Opposed Number Abstained Number Absent
6 0 0 1

Minority responses

There were no minority responses.

Prioritized Issue: Clinican Training on Tick-Borne Diseases

Importance

Clinical errors in the diagnosis and treatment of tick-borne diseases may result from limited clinician training on tick-borne diseases. At present, the number of clinicians who have received comprehensive training on Lyme disease and other tick-borne illnesses is insufficient to meet the needs of this growing patient population. It is important to note that the majority of patients with tick-borne diseases initially present and receive care from primary care clinicians, not infectious diseases specialists. As the Tick-Borne Disease Working Group 2018 Report to Congress highlighted and this sub-committee's work affirms, in-depth educational programs appear to be limited in both availability and content, resulting in situations where many clinicians are unable to recognize general and stage-based manifestations of common tick-borne diseases.

Introduction

When Lyme disease is promptly diagnosed at its earliest stage—localized to the skin and properly treated with three weeks of an appropriately selected antibiotic—patients are more likely to experience favorable outcomes. However, some ideally diagnosed and treated patients will continue to experience debilitating effects from the illness, and others will not fully return to their pre-Lyme disease health status (Aucott et al., 2013; Cameron et al., 2014). Unfortunately, opportunities for early diagnosis are often missed (Feder & Whitaker, 1995; Fallon et al., 2008). These delays may be due to clinicians failing to include Lyme disease in their differential diagnosis, and exacerbated by limited recognition of important Lyme disease-related findings on physical exam and an over-reliance on serologic testing (Feder & Whitaker, 1995; Reed, 2002). Once the infection has spread beyond the skin, it appears to become more challenging for clinicians to recognize Lyme disease as the correct diagnosis (Hirsch et al., 2018). Therapeutic errors, including delaying treatment pending test results, use of antibiotics known to be ineffective for Lyme disease, and treatment regimens of insufficient duration are not uncommon. One NIH-sponsored antibiotic retreatment trial for Lyme disease excluded 43% of all applicants because they had not received a sufficient course of antibiotics for their initial stage of illness (Fallon et al., 2008).

A recently published case report highlights some of these concerns (Marx et al., 2019). A 57-year-old man from a Lyme disease-endemic area sought medical care for fever, fatigue, shortness of breath, and chest pain. The patient had what appeared to be multiple erythema migrans rashes, and his electrocardiogram documented a mild conduction abnormality. Although the physician suspected Lyme disease, appropriate therapy was not begun, presumably pending the results of Lyme disease serology. Positive results were reported two days after that visit, but antibiotic therapy was not initiated. Eight days later he sought emergency room care for worsening symptoms of his untreated Lyme disease. Although an infectious diseases specialist was consulted and a follow-up visit scheduled, antibiotics were not begun. The patient died twelve days after his first presentation, without ever being treated for his Lyme disease.

Similar diagnostic and therapeutic problems exist with regard to other tick-borne diseases. In 2017, an Indiana toddler died from Rocky Mountain spotted fever. Although she had been seen twice at other medical facilities, she was not correctly diagnosed until she was admitted to a children's hospital. Although the appropriate antibiotic was initiated, it was too late to save her (Congressionally Directed Medical Research Program, n. d.).

Tick-Borne Diseases and the U.S. Military

The military population and their family members present with unique tick-borne disease risks due to the occupational hazards and transient nature of their duty stations, assignments, and deployments. In their "Technical Guide No. 26 for Tick-Borne Diseases: Vector Surveillance and Control," the Armed Forces Pest Management Board (AFPMB) acknowledges the serious health threats to troops, civilian employees, and residents at military installations worldwide, and highlights both direct (service member morbidity) and indirect effects (illness of family members, costs of health care) of tick-borne diseases (Armed Forces Pest Management Board, 2012).

Military readiness is considered a strategic priority for the Department of Defense, and includes substantial investment in skills and abilities; however, tick-borne diseases can present considerable challenges to the careers and quality of life for military members and their families (Weis et al., 2019). Inconsistent application of precautionary measures and inadequate communication regarding tick-borne diseases across the military network increases the risk of negative outcomes related to tick-borne diseases. Military members are often required to participate in both domestic and overseas training exercises that place them at higher risk for exposure to ticks; however, preventative measures and standard precautions vary depending on Service associations. There is limited messaging via military base public health leadership regarding prevention techniques and location-specific risks to tick-borne diseases. Further, the transient nature of military families and their military health providers increases challenges related to the diagnosis and continuity of care for tick-borne diseases. Each of these factors highlight the need for a well-trained military health provider network to support the prevention, accurate diagnosis, and treatment of tick-borne diseases for military members and their families.

Summary of evidence and findings

Detailed information regarding instructional programming for Lyme disease and other tick-borne diseases at the medical school, residency, and practicing physician levels is not readily available. As of October 27, 2019, this committee was able to obtain the following information via document requests, examination of relevant website content, and/or conversations with leaders in these areas:

  • National Board of Medical Examiners—Develops and manages the United States Medical Licensing Examination. The content outline includes babesiosis under the blood and lymphoreticular system section. Lyme disease, anaplasmosis, ehrlichiosis, rickettsiosis (Rocky Mountain spotted fever), brucellosis, tularemia, and Q fever are included in the multisystem processes and disorders section.
  • American Board of Family Medicine—No specific training requirement for obtaining and maintaining board status.
  • Department of Defense—At the Uniformed Service University of the Health Sciences (USU), tick-borne diseases are generally covered in sporadic, one-hour lectures that include discussion of non-tick-borne diseases as well. Subject matter experts fulfill lecture requests via a variety of different university departments. Continuing medical education on tick-borne diseases is currently not offered through the military health system.
  • There is no uniform medical school curriculum on tick-borne diseases. One medical school in a Lyme disease-endemic area of the country reported that their curriculum for first- and second-year students included the following coursework:
  • First Year Sessions:
  • One-hour, large group lecture—Introduction to Tick-Borne Infections, covering B. burgdorferi, A. phagocytophilum, R. rickettsii, B. microti, and tick-borne encephalitis.
  • One-hour, large group lecture—Lyme Disease and Other Tick-Borne Infections, given by a local physician to provide the clinical perspective. Pathogens covered include B. burgdorferi, A. phagocytophilum, B. microti, R. rickettsii. Short mentions of ehrlichiosis, tularemia, and Powassan virus are included.
  • Two-hour, large group lecture—Encephalitis. Many infectious diseases covered with some time spent on tick-borne encephalitis and Powassan virus.
  • Second Year Sessions:
  • Two-hour, large group lecture followed by an independent learning exercise on cardiovascular infectious disease, which covers many infections. Rocky Mountain spotted fever is reviewed in this section.

Possible opportunities

  • The inclusion of more robust training and education programs via medical schools, residencies, and continuing medical education (CME) can strengthen clinician knowledge and awareness of tick-borne diseases and alleviate patient suffering through timely, accurate diagnosis and treatment.
  • The development of comprehensive training materials and resources on Lyme disease and other tick-borne diseases for medical professionals will ensure a more robust appreciation for tick-borne diseases and its manifestations.
  • Emphasizing training and education for primary care and other "front-line" clinicians, such as emergency medicine physicians, can increase clinician confidence in the incorporation of tick-borne diseases into relevant differential diagnoses.

Threats or challenges

  • The limited recognition of the magnitude and significance of tick-borne diseases will be an obstacle to commanding the time and resources necessary to develop comprehensive educational curricula.
  • The rapidly emerging science and the introduction of new tick species and pathogens will necessitate frequent revisions of educational curricula.
  • Should the past emphasis and reliance on infectious diseases specialists, who are rarely the "front-line" clinicians in tick-borne diseases, be continued in the development of new curricula, then resulting educational content may not meet the clinical realities and needs of primary care and other "front-line" clinicians.
  • Inherent resistance to change may keep medical educators and medical professionals from developing and acting on new information.

Potential Actions 16 and 17

The subcommittee proposes the following actions for the Tick-Borne Disease Working Group to consider.

Potential Action 16: Recommend that CDC develop a multi-leveled curriculum on U.S. tick-borne diseases for clinicians. There should be instructional programs for medical students, residents, physician assistants, and nurse practitioners. While the emphasis should be on training the clinical specialists most likely to encounter patients during their initial presentation of tick-borne diseases (for example, family practitioners, pediatricians, general internists, and emergency medicine physicians), specialty and subspecialty-specific training should be developed for other clinician groups.

The curriculum development team should include representatives of all stakeholder groups, including meaningful patient representation (as defined in Potential Action 2). Clinicians and research scientists with expertise in this field should be selected such that the team represents the spectrum of scientific and clinical perspectives on tick-borne diseases.

Potential Action 17: Recommend to DoD:

  • Develop stand-alone educational modules for Uniformed Services University students that cover the spectrum of tick-borne diseases. Training should specifically highlight the risks of military occupational hazards from tick-borne diseases as a result of training environments (both domestic and overseas), deployments, and reassignments. The transient nature of military assignments, which increases the risk of misdiagnoses and diagnostic delays for both service members and military dependents, should also be emphasized.
  • Institutionalize tick-borne diseases training and education via the Defense Health Agency (DHA). Standardize training, education, and military force health protection guidelines across the Military Services. Implement continuing medical education programs via existing forums such as the DHA Primary Care Clinical Community Speaker Series, and disseminate information on relevant tick-borne diseases programs (for example, the Army Public Health Center's Human Tick Test Program).

The curriculum development team should include representatives of all stakeholder groups, including meaningful patient representation (as defined in Potential Action 2). Clinicians and research scientists with expertise in this field should be selected such that the team represents the spectrum of scientific and clinical perspectives on tick-borne diseases.

Vote of subcommittee members on Potential Actions 16 and 17

Vote on Potential Action 16 as written above

Number in Favor Number Opposed Number Abstained Number Absent
6 0 0 1

Vote on Potential Action 17 as written above

Number in Favor Number Opposed Number Abstained Number Absent
6 0 0 1

Minority responses

There were no minority responses.

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Johnson, L. (2019, August 23). MyLymeData 2019 Chart Book. Retrieved from https://doi.org/10.6084/m9.figshare.8063039.v1

Klempner, M. S., Hu, L. T., Evans, J., Schmid, C. H., Johnson, G. M., Trevino, R. P., ... Weinstein, A. (2001). Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease. New England Journal of Medicine, 345(2), 85–92. doi: 10.1056/nejm200107123450202

Kravitz, R. L., Duan, N., & Braslow, J. (2006, December 4). Erratum: Evidence-Based Medicine, Heterogeneity of Treatment Effects, and the Trouble with Averages: Milbank Quarterly. Retrieved from https://www.milbank.org/quarterly/articles/erratum-evidence-based-medicine-heterogeneity-of-treatment-effects-and-the-trouble-with-averages/

Krupp, L. B., Hyman, L. G., Grimson, R., Coyle, P. K., Melville, P., Ahnn, S., ... Chandler, B. (2003). Study and treatment of post Lyme disease (STOP-LD): A randomized double masked clinical trial. Neurology, 60(12), 1923–1930. doi: 10.1212/01.wnl.0000071227.23769.9e

Lee-Lewandrowski, E., Chen, Z., Branda, J., Baron, J., & Kaufman, H. W. (2019). Laboratory Blood-Based Testing for Lyme Disease at a National Reference Laboratory: A 7-Year Experience (2010-2016). American Journal of Clinicalal Pathology, 152(1), 91-6. doi:10.1093/ajcp/aqz030

Lombardo, M. V., Lai, M. C., & Baron-Cohen, S., (2019). Big data approaches to decomposing heterogeneity across the autism spectrum. Molecular Psychiatry, 24(10):1435-50. https://doi.org/10.1038/s41380-018-0321-0

McGinty, J. C. (2018, June 22). Lyme Disease: An Even Bigger Threat Than You Think. The Wall Street Journal. Retrieved from https://www.wsj.com/articles/lyme-disease-an-even-bigger-threat-than-you-think-1529672401

Mead, P. S. (2015). Epidemiology of Lyme disease. Infectious Disease Clinics of North America, 29, 187-210. doi: 10.1016/j.idc.2015.02.010

National Institute of Allergy and Infectious Diseases. (2017, February 14). HIV Infections Drop 18 Percent in Six Years. Retrieved from https://www.hiv.gov/blog/new-hiv-infections-drop-18-percent-in-six-yearsNew

Quest Diagnostics. (2018). Health Trends: Lyme Disease. Retrieved from https://mma.prnewswire.com/media/724151/Quest_LymeDiseaseTrendsReport.pdf?p=original

Rebman, A. W., Crowder, L. A., Kirkpatrick, A., & Aucott, J. N. (2015). Characteristics of seroconversion and implications for diagnosis of post-treatment Lyme disease syndrome: acute and convalescent serology among a prospective cohort of early Lyme disease patients. Clinical Rheumatology, 34(3), 585-9. doi: 10.1007/s10067-014-2706-z

Reed, K. D. (2002). Laboratory testing for Lyme disease: possibilities and practicalities. Journal of Clinical Microbiology, 40(2), 319-24. doi: 10.1128/JCM.40.2.319-324.2002

Sackett, D. L., Strauss, S., Richardson, W., Rosenberg, W., & Haynes, R. G. (2000). Evidence-based medicine: how to practice and teach. New York: Churchill Livingstone.

Sanchez-Vicente, S., Tagliafierro, T., Coleman, J. L., Benach, J. L., & Tokarz, R. (2019). Polymicrobial Nature of Tick-Borne Diseases. American Society for Microbiology. doi: 10.1128/mBio.02055-19

Sepsis Alliance. (n.d.) Tribute: Gabriella (Gabby) Galbo. Retrieved from https://www.sepsis.org/faces/gabriella-galbo/

Shadick N. A., Phillips, C. B., Logigian, E. L., Steere, A. C., Kaplan, R. F., Berardi, V. P., ... Liang, M. H. (1994). The long-term clinical outcomes of Lyme disease. A population-based retrospective cohort study. Ann Intern Med, 121(8):560-7. doi: 10.7326/0003-4819-121-8-199410150-00002

Stricker, R. B., & Johnson, L. (2010). Lyme disease diagnosis and treatment lessons from AIDS epidemic. Minerva Medica. 12(6): 419-25.

Stricker, R. B., & Johnson. (2011). Lyme disease: the next decade. Infection and Drug Resistance, 4, 1-9. doi: 10.2147/IDR.S15653

Willke, R. J., Zheng, Z., Subedi, P., Althin, R., & Mullins, C. D. (2012). From concepts, theory, and evidence of heterogeneity of treatment effects to methodological approaches: a primer. BMC Med Research Methodology, 12(185). doi: https://doi.org/10.1186/1471-2288-12-185

Wolfram, R. (2008). Connecticut Attorney General Investigation and Settlement Highlights Possible Applicability of Antitrust Standard Setting Law to the Development of Clinical Practice Guidelines. Antitrust Health Care. Retrieved from http://www.rwolframlex.com/yahoo_site_admin/assets/docs/Lyme_-_ABA_Antittrust_Health_Care_Chronicle_RW_article_-_Nov_08.133140727.pdf

Wormser, G. P., Ramanathan, R., Nowakowski, J., McKenna, D., Holmgren, D., Visintainer, P., ... Nadelman, R. B. (2003). Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine, 138(9), 697-704. doi: 10.7326/0003-4819-138-9-200305060-00005

Wormser, G. P., Dattwyler, R. J., Shapiro, E. D., Halperin, J. J., Steere, A. C., Klempner, M. S., ... Robert B. Nadelman. (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(9), 1089–1134. doi: https://doi.org/10.1086/508667

Zhang, X., Meltzer, M. I., Peña, C. A., Hopkins, A. B., Wroth, L., & Fix, A. D. (2006). Economic Impact of Lyme Disease. Emerging Infectious Diseases, 12(4), 653–660. doi: 10.3201/eid1204.050602

Prioritized Issue: Access to Care

Adrion, E. R., Aucott, J., Lemke, K. W., & Weiner, J. P. (2015). Health Care Costs, Utilization and Patterns of Care following Lyme Disease. Plos One, 10(2). doi: 10.1371/journal.pone.0116767

Agency for Healthcare Research and Quality. (2018). 2015 National Healthcare Quality and Disparities Report and 5th Anniversary Update on the National Quality Strategy. Chapter 10: Access and Disparities in Access to Health Care. Retrieved from http://www.ahrq.gov/research/findings/nhqrdr/nhqdr15/access.html

Ali, A., Vitulano, L., Lee, R., Weiss, T. R., & Colson, E. R. (2014). Experiences of patients identifying with chronic Lyme disease in the healthcare system: a qualitative study. BMC Family Practice, 15(1), 79. doi: 10.1186/1471-2296-15-79

American Medical Association. (2019). AMA Code of Medical Ethics Opinion 1.2.11. Retrieved from https://www.ama-assn.org/delivering-care/ethics/ethically-sound-innovation-medical-practice

Aucott, J. N., Rebman, A. W., Crowder, L. A., & Kortte, K. B. (2012). Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Quality of Life Research, 22(1), 75–84. doi: 10.1007/s11136-012-0126-6

Cameron, D., Gaito, A., Harris, N., Bach, G., Bellovin, S., Bock, K., ... ILADS Working Group. (2004). Evidence-based guidelines for the management of Lyme disease. Expert Review of Anti-Infective Therapy, 2(1 Suppl):S1-13. doi: 10.1586/14789072.2.1.s1

Cameron D. J., Johnson L. B., & Maloney E. L. (2014, September 12). Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Review Anti-Infective Therapy, 12(9), 1103-35. doi: 10.1586/14787210.2014.940900

Chan, L., Hart, L. G., & Goodman, D. C. (2006). Geographic access to health care for rural medicare beneficiaries. Journal of Rural Health, 22, 140–6. doi: 10.1111/j.1748-0361.2006.00022.x

Centers for Disease Control and Prevention. (2000). Measuring Healthy Days. Atlanta, Georgia: CDC. Retrieved from https://www.cdc.gov/hrqol/pdfs/mhd.pdf

Centers for Disease Control and Prevention. (2004). The burden of chronic diseases and their risk factors. Retrieved from http://www.cdc.gov/nccdphp/burdenbook2004

Centers for Disease Control and Prevention. (2010). Behavioral risk factor surveillance survey data. Retrieved from https://www.cdc.gov/brfss/annual_data/annual_2010.htm

Cameron, D. J. (2007). Consequences of treatment delay in Lyme disease. Journal of Evaluation in Clinical Practice, 13, 470–2. doi: 10.1111/j.1365-2753.2006.00734.x

Connecticut Attorney General's Office. (2008, May 5). Attorney General's investigation reveals flawed Lyme disease guideline process, IDSA agrees to reassess guidelines, install independent arbiter. [Press Release] Retrieved from https://www.prohealth.com/library/connecticut-attorney-generals-investigation-reveals-flawed-lyme-disease-guideline-process-idsa-agrees-to-reassess-guidelines-install-independent-arbiter-28433

Devol, R., & Bedroussian, A. (2007). An Unhealthy America: The Economic Burden of Chronic Disease—Charting a New Course to Save Lives and Increase Productivity and Economic Growthy. [Technical Report] Retrieved from: https://assets1b.milkeninstitute.org/assets/Publication/ResearchReport/PDF/chronic_disease_report.pdf

Eddy, D. M. (1993). Three battles to watch in the 1990's. JAMA, 270(4), 520-26. doi: 10.1001/jama.1993.03510040124050

Gulliford, M., Figueroa-Munoz, J., Morgan, M., Hughes, D., Gibson, B., Beech, R., & Hudson, M. (2002, July 1). What does 'access to health care' mean? Journal of Health Services Research Policy. 7(3), 186-8. doi: 10.1258/135581902760082517

Donta, S. T. (1997). Tetracycline therapy for chronic Lyme disease. Clinical Infectious Disease, 25(Suppl. 1), S52–6. doi: 10.1086/516171

Freed, C. R., Hansberry, S. T., Arrieta, M. I. (2013). Structural and hidden barriers to a local primary health care infrastructure: autonomy, decisions about primary health care, and the centrality and significance of power. Research in the Sociololgy of Health Care, 31, 57-81. doi: 10.1108/S0275-4959(2013)0000031006

Fugh-Berman, A., & Melnick, D. (2008). Off-Label Promotion, On-Target Sales. PLOS Med, 5(10), e210. doi: 10.1371/journal.pmed.0050210

Himmelstein, D. U., Warren, E., Thorne, D., & Woolhandler, S. (2005). Illness and injury as contributors to bankruptcy. Health Affairs (Millwood), (Suppl. Web Exclusives), W5-63–73. doi:
https://doi.org/10.1377/hlthaff.w5.63

Himmelstein, D. U., Thorne, D., Warren, E., & Woolhandler, S. (2009). Medical bankruptcy in the United States 2007 results of a national study. Ameican Journal of Medicine, 122, 741–6. doi: 10.1016/j.amjmed.2009.04.012

Hirsch, A. G., Herman, R. J., Rebman, A., Moon, K. A., Aucott, J., Heaney, C., & Schwartz, B.S. (2018). Obstacles to diagnosis and treatment of Lyme disease in the U.S.A.: a qualitative study. BMJ Open, 8(6), e021367. doi: http://dx.doi.org/10.1136/bmjopen-2017-021367

Huberts, L. W. J. C. (2018) Integrity: What it is and Why it is Important. Public Integrity, 20(1), S18-S32. doi: 10.1080/10999922.2018.1477404

Infectious Diseases Society of America. (2019). IDSA/AAN/ACR Lyme Disease Guideline (proposed) Retrieved from: https://www.idsociety.org/practice-guideline/idsaaanacr-lyme-disease-guideline/

Institute of Medicine. (1993). Committee on Monitoring Access to Personal Healthcare Services. Access to healthcare in America. Washington, DC: National Academies Press.

Johnson, L., & Stricker, R. B. (2010). The Infectious Diseases Society of America Lyme guidelines: a cautionary tale about development of clinical practice guidelines. Philosophy, Ethics, and Humanities in Medicine, 5, 9. doi: 10.1186/1747-5341-5-9

Johnson, L., Aylward, A., Stricker, R. B. (2011). Healthcare access and burden of care for patients with Lyme disease: a large United States survey. Health Policy, 102(1), 64-71. doi: 10.1016/j.healthpol.2011.05.007

Johnson, L., Wilcox, S., Mankoff, J., & Stricker, R.B. (2014). Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey. PeerJ, 2. doi: 10.7717/peerj.322

Johnson, L., Shapiro, M., & Mankoff, J. (2018). Removing the Mask of Average Treatment Effects in Chronic Lyme Disease Research Using Big Data and Subgroup Analysis. Healthcare, 6(4). doi: 10.3390/healthcare6040124

Johnson, L. (2019). MyLymeData Stigma and Privacy in Lyme Disease Data: A project of LymeDisease.org 2.11.19.xlsx. figshare. Dataset. https://doi.org/10.6084/m9.figshare.7704167.v1

Johnson, L. (2019). Who can meaningfully represent the interests of patients with persistent Lyme disease? figshare. Figure. https://doi.org/10.6084/m9.figshare.11093999

Johnson, L. B., & Smalley, J. B. (2019). Engaging the Patient: Patient-Centered Research. In: Hall K., Vogel A., Croyle R. (eds) Strategies for Team Science Success. Springer, Cham.

Lyme Disease Association, Inc. (2019). Legislative Actions Chart. Retrieved from https://lymediseaseassociation.org/wp-content/uploads/2019/02/State_Legislative_Actions_Chart.pdf

McLaughlin, C. G. & Wyszewianski, L. (2002). Access to care: remembering old lessons. Health Services Research, 37(6), 1441-3. doi: 10.1111/1475-6773.12171

National Institutes of Health. (2019). NIH Strategic Plan for Tickborne Disease Research. Retrieved from https://www.niaid.nih.gov/sites/default/files/NIH-Strategic-Plan-Tickborne-Disease-Research-2019.pdf

Nyblade, L., Stockton, M. A., Giger, K., Bond, V., Ekstrand, M.L ., Lean, R,M., ... Wouters, E. (2019). Stigma in health facilities: why it matters and how we can change it. BMC Medicine, 17(1), 25. doi: https://doi.org/10.1186/s12916-019-1256-2

Office of Disease Prevention and Health Promotion. (2019) Healthy People 2020: Access to Health Services. Retrieved from https://www.healthypeople.gov/2020/topics-objectives/topic/Access-to-Health-Services#2

Paavola, A. (2018). Big pharma backs off superbug: Why 5 drug makers bailed on antibiotic research. Becker's Hospital Review. Retrieved from: https://www.beckershospitalreview.com/pharmacy/big-pharma-backs-off-superbug-why-5-drugmakers-bailed-on-antibiotic-research.html

Pachner, A. R. (1988). Borrelia burgdorferi in the nervous system: the new "great imitator". Annals of the New York Academy of Sciences, 539, 56–64. doi: 10.1111/j.1749-6632.1988.tb31838.x

Patient-Centered Outcomes Research Institute. (2016). Engagement Rubric for Applicants. Retrieved from https://www.pcori.org/sites/default/files/Engagement-Rubric.pdf

Penchansky, R., & Thomas, J. W. (1981). The concept of access: Definition and relationship to consumer satisfaction. Medical Care, 19(2), 127-40. doi: 10.1097/00005650-198102000-00001

Pfeiffer, M. B. (2015). The war over Lyme disease: Is it chronic? Poughkeepsie Journal. Retrieved from: https://www.poughkeepsiejournal.com/story/news/health/lyme-disease/2014/03/26/so-called-lyme-wars/6907209/

Sholtis, B. (2019, June 14). PA's Lyme Disease Bill Would Change Coverage Amid Controversy Over ‘Chronic' Condition. WSKG: Transforming Health. Retrieved from: https://wskg.org/news/pas-lyme-disease-bill-would-change-coverage-amid-controversy-over-chronic-condition/

Schor, S., Green, C., Szantyr, B., Phillips, S., Leigner, K., Burrascano, J. J., ... Maloney, E. L. (2019). Chronic Lyme Disease: An Evidence-Based Definition by the ILADS Working Group. Antibiotics, 8, 269.

Scharfenberg, D. (2019, August 22). IDEAS. Is ‘chronic Lyme disease' real? Boston Globe. Retrieved from: https://www.bostonglobe.com/ideas/2019/08/22/chronic-lyme-disease-real/82qGnp5GmQbLE42nlb4otJ/story.html

Stricker, R. B., & Johnson, L. (2009). The Infectious Diseases Society of America Lyme guidelines: poster child for guidelines reform. South Medical Journal, 102, 565–6. doi: 10.1097/SMJ.0b013e3181a594e9

Torrey et al. v. Infectious Diseases Society of America et al., Civil Action No. 17-cv-190 (E.D. Tex. 2017). Retrieved from

https://www.courthousenews.com/wp-content/uploads/2017/11/LymeDisease.pdf

U.S. Department of Health and Human Services. (2010). Healthy People 2010: Understanding and Improving Health. 2nd ed. Washington, DC: U.S. Government Printing Office. Retrieved from https://www.healthypeople.gov/2010/document/pdf/uih/2010uih.pdf

Vanderhoof, I. T., & Vanderhoof-Forschner, K. M. (1993). Lyme Disease: The Cost to Society. Contingencies, 42-8.

Wolfram, R. (2008). Connecticut Attorney General Investigation and Settlement Highlights Possible Applicability of Antitrust Standard Setting Law to the Development of Clinical Practice Guidelines. Antitrust Health Care Chronicle, 22(2), 8-16. Retrieved from http://www.rwolframlex.com/yahoo_site_admin/assets/docs/Lyme_-_ABA_Antittrust_Health_Care_Chronicle_RW_article_-_Nov_08.133140727.pdf

Wormser, G. P., Dattwyler, R. J., Shapiro, E. D., Halperin, J. J., Steere, A.C ., Klempner, M. S., ... Nadelman, R. B. (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(9), 1089-134. doi: https://doi.org/10.1086/508667

Zhang, X., Meltzer, M. I., Pena, C. A., Hopkins, A. B., Wroth, L., & Fix, A. D. (2006). Economic impact of Lyme disease. Emerging Infectious Diseases, 12, 653–60. doi: 10.3201/eid1204.050602

Prioritized Issue: Reducing Diagnostic Errors and Delays in Lyme Disease

Adrion, E. R., Aucott, J., Lemke, K. W., & Weiner, J. P. (2015). Health Care Costs, Utilization and Patterns of Care following Lyme Disease. Plos One, 10(2). doi: 10.1371/journal.pone.0116767

Arav-Boger, R. Crawford, T., Steere, A. C., Halsey, N. A. (2002). Cerebellar ataxia as the presenting manifestation of Lyme disease. Pediatric Infectious Disease Journal, 21(4), 353-6. doi: 10.1097/00006454-200204000-00021

Arvikar, S., Steere, A. (2015). Diagnosis and treatment of Lyme arthritis. Infectious Disease Clinics of North America, 29(2), 269-80. doi: 10.1016/j.idc.2015.02.004

Aucott, J., Morrison, C., Munoz, B., Rowe, P. C., Schwarzwalder, A., & West, S. K. (2009). Diagnostic challenges of early Lyme disease: Lessons from a community case series. BMC Infectious Diseases, 9, 79. doi: 10.1186/1471-2334-9-79

Aucott, J. N., Crowder, L. A., Yedlin, V., & Kortte, K. B. (2012). Bull's-Eye and Nontarget Skin Lesions of Lyme Disease: An Internet Survey of Identification of Erythema Migrans. Dermatololgy Reseaserch and Practice, 2012, 451727. doi: 10.1155/2012/451727

Aucott J., Rebman, A. W., Crowder, L. A., & Kortte, K. B. (2013). Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Quality of Life Research, 1, 75-84. doi: 10.1007/s11136-012-0126-6

Bacon, R. M., Kugeler, K. J., & Mead, P. S. (2008, October 3). Surveillance for Lyme disease--United States, 1992-2006. MMWR Surveillance Summaries, 57(10), 1-9. Retrieved from https://www.cdc.gov/mmwr/preview/mmwrhtmL/ss5710a1.htm

Berger, B. W. (1989). Dermatologic manifestations of Lyme disease. Review of Infectious Diseases, 11(6), S1475-S1481. doi: 10.1093/clinids/11.supplement_6.s1475

Cameron, D. J. (2007). Consequences of treatment delay in Lyme disease. Journal of Evaluation in Clinical Practice, 13(3), 470-2. doi: 10.1111/j.1365-2753.2006.00734.x

Cameron, D. J., Johnson, L. B., & Maloney, E. L. (2014). Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Review of Anti-Infective Therapy, 12(9), 1103–1135. doi: 10.1586/14787210.2014.940900

Centers for Disease Control and Prevention. (2008). Lyme disease–United States, 1992–2006. MMWR, Mobid Mortal Wkly Rep 57 (SS10); 1-9. Table 3 Healthy People 2010. Retrieved from https://www.cdc.gov/mmwr/preview/mmwrhtml/ss5710a1.htm#tab3

Centers for Disease Control and Prevention. (2009). Lyme Case Report. Retrieved from www.cdc.gov/lyme/resources/LymeDiseaseCaseReportForm.pdf

Centers for Disease Control and Prevention. (2017). Lyme Case Definition and Report Form. Retrieved from https://www.cdc.gov/lyme/stats/forms.html

Centers for Disease Control and Prevention. (2018). Map of Lyme disease incidence categories—United States 2018. [Map] Retrieved from https://www.cdc.gov/lyme/datasurveillance/maps-recent.html

Centers for Disease Control and Prevention. (2019) Guidance for Clinicians: Recommendations for Clinicians after a Tick Bite. [Brochure] Retrieved from https://www.cdc.gov/lyme/resources/FS-Guidance-for-Clinicians-Patients-after-TickBite-508.pdf

Citera, M., Freeman, P. R., & Horowitz, R. I. (2017). Empirical validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for suspected Lyme disease. International Journal of General Medicine, 10, 249-273. doi: 10.2147/IJGM.S140224. eCollection 2017

Coyle, P. K., Schutzer, S. E. (2002). Neurologic aspects of Lyme disease. Medical Clinics of North America, 86(2), 261-84. doi: 10.1016/s0025-7125(03)00086-5

Dattwyler, R. J., Volkman, D. J., Luft, B. J., Halperin, J. J., Thomas, J., & Golightly, M. G. Seronegative Lyme disease. (1988). Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi. New England Journal of Medicine, 319(22), 1441-1446. doi: 10.1056/NEJM198812013192203

Eisen, R. J., Eisen L., & Beard, C. B. (2016). County-Scale Distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the Continental United States. Journal of Medical Entomology, 53(2), 349-86. doi: 10.1093/jme/tjv237

Embers, M.E., Barthold, S. W., Borda, J. T., Bowers, L., Doyle, L. Hodzic, E., ... Philipp, M. T. (2012). Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PLOS ONE, 7(1), e29914. doi: 10.1371/journal.pone.0029914

Fallon, B. A. & Nields, J. A. Lyme disease: a neuropsychiatric illness. (1994). American Journal of Psychiatry, 151(11). 1571-83. doi: 10.1176/ajp.151.11.1571

Fallon, B. A., Keilp, J. G., Corbera, K. M., Petkova, E., Britton, C. B., Dwyer, E., ... Sackeim, H. A. (2008). A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008 Mar 25:992-1003. doi: 10.1212/01.WNL.0000284604.61160.2d

Gelburd, R. A. (2017, July 27). Window Into Lyme Disease Using Private Claims Data. American Journal of Managed Care. Retrieved from https://www.ajmc.com/contributor/robin-gelburd-jd/2017/07/a-window-into-lyme-disease-using-private-claims-data

Glatz, M., Golestani, M., Kerl, H., & Mullegger, R. R. (2006). Clinical relevance of different IgG and IgM serum antibody responses to Borrelia burgdorferi after antibiotic therapy for erythema migrans: long-term follow-up study of 113 patients. Archives of Dermatology, 142(7), 862-8. doi: 10.1001/archderm.142.7.862

Halperin, J. J., Little, B. W, Coyle, P. K., & Dattwyler, R. J. (1987). Lyme disease: Cause of a treatable peripheral neuropathy. Neurology, 37(11), 1700-6. doi: 10.1212/wnl.37.11.1700

Hinckley, A. F., Connally, N. P., Meek, J. I., Johnson, B. J., Kemperman, M. M., Feldman, ... Mead, P.S. (2014). Lyme Disease Testing by Large Commercial Laboratories in the United States, Clinical Infectious Diseases, 59(5), 676–681. doi: 10.1093/cid/ciu397

Hirsch, A. G., Herman, R. J., Rebman, A., Moon, K. A., Aucott, J., Heaney, C., Schwartz, B. S. (2018). Obstacles to diagnosis and treatment of Lyme disease in the USA: A qualitative study. BMJ Open, 8, e021367. doi: 10.1136/bmjopen-2017-021367

Infectious Diseases Society of America. (2018, November 26). Letter to the Tick-Borne Disease Working Group. Retrieved from https://www.idsociety.org/globalassets/idsa/policy--advocacy/current_topics_and_issues/emerging_infections_and_biothreats/agency-efforts/112618-idsa-comments-on-tickborne-disease-working-group-report.pdf

Johnson, L. (2019). MyLymeData 2019 Chart Book. figshare. Book. doi: 10.6084/m9.figshare.8063039

Johnson, L. (2019). Sources of Diagnostic Errors in Lyme Disease. figshare. Figure. doi: 10.6084/m9.figshare.10262537

Khanna, G. (2015). AHRQ's Road Ahead: Seizing Opportunities in Three Essential Areas to Improve Patient Care. Improving Diagnosis in Medicine. doi:10.17226/21794.

Klempner, M., Hu, L., Evans, J., Schmid, C., Johnson, G., Trevino, R., ... Weinstein, A. (2001).Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. New England Journal of Medicine, 12, 85-92. doi: 10.1056/NEJM200107123450202

Krupp, L. B., Hyman, L. G., Grimson, R., Coyle, P. K., Melville, P., Ahnn, S., ... Chandler, B. (2003). Study and treatment of post Lyme disease (STOP-LD): A randomized double masked clinical trial. Neurology, 60(12), 1923-30. doi: 10.1212/01.wnl.0000071227.23769.9e

Lane, R. S., Mannweiler, S. A., Stubbs, H. A, Lenette, E. T., Madigan, J. E., & Lavoie, P. E. (1992). Risk factors for Lyme disease in a small rural community in northern California. American Journal of Epidemiology, 136, 1358-1368. doi: 10.1093/oxfordjournals.aje.a116448

Lawrence, C., Lipton, R. B., Lowy, F. D., & Coyle, P. K. (1995). Seronegative chronic relapsing neuroborreliosis. European Neurology, 35, 113–7. doi: 10.1159/000117104

Lee-Lewandrowski, E., Chen, Z., Branda, J., Baron, J., & Kaufman, H. W. (2019). Laboratory Blood-Based Testing for Lyme Disease at a National Reference Laboratory: A 7-Year Experience (2010-2016). American Journal of Clinicalal Pathology, 152(1), 91-6. doi:10.1093/ajcp/aqz030

Logigian, E. L., Kaplan, R. F., & Steere, A. C. (1990). Chronic neurologic manifestations of Lyme disease. New England Journal of Medicine, 323, 1438–44. doi: 10.1056/NEJM199011223232102

Luft, B. J., Dattwyler, R. J., Johnson, R. C., Luger, S. W., Bosler, E. M., Rahn, D. W., ... Gadgil, S. D. (1996). Azithromycin compared with amoxicillin in the treatment of erythema migrans. Annals of Internal Medicine, 124, 785-91. doi: 10.7326/0003-4819-124-9-199605010-00002

Maloney, E. L. (2009). The Need for Clinical Judgment in the Diagnosis and Treatment of Lyme Disease. Journal of American Physicians and Surgeons, 14(3), 28-89.

Massarotti, E. M., Luger, S. W., Rahn, D. W., Messner, R. P., Wong, J. B., Johnson, R. C., & Steere, A.C. (1992). Treatment of early Lyme disease. American Journal of Medicine, 92(4), 396-403. doi: 10.1016/0002-9343(92)90270-L

Marx, G. E., Leikauskas, J., Lindstrom, K., Mann, E., Reagan-Steiner, S., Matkovic, E., ... Brown, C. (2019, October 22). Fatal Lyme carditis in New England: Two case reports. Annals of Internal Medicine. doi: 10.7326/L19-0483.

McGinty, J. (2018, June 22). Lyme Disease: An Even Bigger Threat Than You Think: A look at why cases of the tick-borne illness are undercounted. Wall Street Journal. Retrieved from https://www.wsj.com/articles/lyme-disease-an-even-bigger-threat-than-you-think-1529672401

Nadelman, R. B., Nowakowski, J., Forseter, G., Goldberg, N. S., Bittker, S., Cooper, D., ... Wormser, G. P. (1996). The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. American Journal of Medicine, 100(5), 502-8. doi: 10.1016/s0002-9343(95)99915-9

National Academies of Sciences, Engineering, and Medicine. (2015). Improving Diagnosis in Health Care. Washington, DC: The National Academies Press. "Diagnostic Process" figures retrieved from http://www.nationalacademies.org/hmd/reports/2015/improving-diagnosis-in-healthcare/figures

National Institutes of Health. (2019). Notice of Special Interest: Advancing Research for Tick-Borne Diseases (TBDs). Retrieved from https://grants.nih.gov/grants/guide/notice-files/NOT-AI-20-005.html

Newman-Toker, D., Schaffer, A., Yu-Moe, C., Nassery, N., Saber Tehrani, A. S., Clemens, G. D., ... Siegal, D. (2019). Serious misdiagnosis-related harms in malpractice claims: The "Big Three"– vascular events, infections, and cancers. Diagnosis, 6(3), 227-240. doi: 10.1515/dx-2019-0019

Quest Diagnostics. (2018, July 30) New Quest Diagnotics data show Lyme disease prevalence increasing and is now present in new U.S. state. Retrieved from https://newsroom.questdiagnostics.com/2018-07-30-New-Quest-Diagnostics-Data-Shows-Lyme-Disease-Prevalence-Increasing-and-is-Now-Present-in-New-U-S-States

Perea, A.E., Hinckley, A.F., & Mead, P.S. (2020). Evaluating the Potential Misuse of the Lyme Disease Surveillance Case Definition. Public Health Reports, 135(1), 16-17. doi: 33354919890024.

Rebman, A. W., Crowder, L. A., Kirkpatrick, A., & Aucott, J. N. (2015). Characteristics of seroconversion and implications for diagnosis of post-treatment Lyme disease syndrome: acute and convalescent serology among a prospective cohort of early Lyme disease patients. Clinical Rheumatology, 34(3), 585-9. doi: 10.1007/s10067-014-2706-z

Rebman, A. W., Bechtold, K. T., Yang, T., Mihm, E. A., Soloski, M. J., Novak, C. B., & Aucott, J. N. (2017). The clinical, symptom, and quality-of-life characterization of a well-defined group of patients with post-treatment Lyme disease syndrome. Frontiers in Medicine, 4, 224. doi: 10.3389/fmed.2017.00224

Reed, K. D. (2002). Laboratory testing for Lyme disease: possibilities and practicalities. Journal of Clinical Microbiology, 40(2), 319-24. doi: 10.1128/JCM.40.2.319-324.2002

Schwartz, A. M., Hinckley, A. F., Mead, P. S., Hook, S. A., & Kugeler, K. J. (2017). Surveillance for Lyme Disease - United States, 2008-2015. MMWR Surveillance Summaries, 66(22), 1-12. doi: 10.15585/mmwr.ss6622a1

Schutzer, S. E., Coyle, P. K., Belman, A. L., Golightly, M. G., & Drulle, J. (1990). Sequestration of antibody to Borrelia burgdorferi in immune complexes in seronegative Lyme disease. Lancet, 335(8685), 312-5. doi: 10.1016/0140-6736(90)90606-6

Schutzer, S. E. (1999). Borrelia burgdorferi–Specific Immune Complexes in Acute Lyme Disease. Jama, 282(20), 1942. doi: 10.1001/jama.282.20.1942

Smith, R. P., Schoen, R. T., Rahn, D. W., Sikand, V. K., Nowakowski, J., Parenti, D. L., ... Steere, A. C. (2002). Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Annals of Internal Medicine, 136(6), 421-8. doi: 10.7326/0003-4819-136-6-200203190-00005

Sonenshine, D. (2018). Range Expansion of Tick Disease Vectors in North America: Implications for Spread of Tick-Borne Disease. International Journal of Environental Research and Public Health, 15(3), 478. doi: 10.3390/ijerph15030478

Steere, A. C., Malawista, S. E., Bartenhagen, N. H., Spieler, P. N., Newman, J. H., Rahn, D. W., ... Taylor, E. (1984). The Clinical Spectrum and Treatment of Lyme Disease. Yale Journal of Biology and Medicine, 57(4), 453-61. PMCID: PMC2590003

Steere, A. C. (2001). Lyme disease. New England Journal of Medicine, 345, 115-25. doi: 10.1056/NEJM200107123450207

Steere, A. C., Dhar, A., Hernanadez, J., Fischer, P. A., Sikand, V.K., Schoen, R. T., ... Persing, D. H. (2003). Systemic symptoms without erythema migrans as the presenting picture of early Lyme disease. American Journal of Medicine, 114(1), 58-62. doi: 10.1016/s0002-9343(02)01440-7

Talleklint-Eisen, L., & Lane, R. S. (1999). Variation in the Density of Questing Ixodes pacificus (Acari: Ixodidae) Nymphs Infected with Borrelia burgdorferi at Different Spatial Scales in California. J Parasitol, 85(5), 824-31. PMID: 10577716

Tibbles, C.D., & Edlow, J. A. (2007). Does this patient have erythema migrans? JAMA, 297(23), 2617-2627. doi: 10.1001/jama.297.23.2617

Tick-Borne Disease Working Group. (2018). 2018 Report to HHS Secretary and Congress. Retrieved from https://www.hhs.gov/sites/default/files/tbdwg-report-to-congress-2018.pdf

Weinstein, E. R., Rebman, A. W., Aucott, J. N., Johnson-Greene, D., & Bechtold, K. T. (2018). Sleep quality in well-defined Lyme disease: a clinical cohort study in Maryland. Sleep, 41(5). doi: 10.1093/sleep/zsy035

Wormser, G. P., Dattwyler, R. J., Shapiro, E. D., Halperin, J. J., Steere, A. C., Klempner, M. S., ... Nadelman, R. B. (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(9), 1089-1134. doi: 10.1086/508667

Zhang, X., Meltzer, M. I., Pena, C. A., Hopkins, A. B., Wroth, L., & Fix, A. D. (2006). Economic impact of Lyme disease. Emerging Infectious Diseases, 12(4): 653-660. doi: 10.3201/eid1204.050602

Prioritized Issue: Reducing Psychiatric Misdiagnoses in Lyme Disease

Adams, W., Rose, C, Eppes, S, and Klein, J. (1996). Long-term cognitive effects of Lyme disease in children. Applied Neuropsychology, 6(1), 39-45. doi: 10.1207/s15324826an0601_6

American Psychiatric Association. (2019). Clinical Practice Guidelines. Retrieved from https://www.psychiatry.org/psychiatrists/practice/clinical-practice-guidelines

Berenbaum, S. & Leland, D. (2015). When Your Child Has Lyme Disease: A Parent's Survival Guide. Lyme Literate Press, 2015.

Bloom, B., Wyckoff, P., Meissner, H. & Steere, A. (1998). Neurocognitive abnormalities in children after classic manifestations of Lyme disease. Pediatric Infectious Disease Journal, 17, 189-196. doi: 10.1097/00006454-199803000-00004

Bransfield, R. C. (2012). The psychoimmunology of Lyme/tick-borne diseases and its association with neuropsychiatric symptoms. Open Neurology Journal, 6, 688–693. doi: 10.2174/1874205X01206010088

Bransfield, R. (2018). Neuropsychiatric Lyme borreliosis: An overview with a focus on a specialty psychiatrist's clinical practice. Healthcare, 6(3), 104. doi: 10.3390/healthcare6030104

Bransfield, R. C., Cook, M. J., & Bransfield, D. R. (2019). Proposed Lyme disease guidelines and Psychiatric Ilness. Healthcare (Basel), 7(3), 105. doi: 10.3390/heatlthcare7030105

Bransfield, R., & Friedman, K. (2019). Differentiating psychosomatic, somatopsychic, multisystem illnesses and medical uncertainty. Healthcare, 7(4), 114. doi: 10.3390/healthcare7040114

Burke, M. (2019). It's All in Your Head – Medicine's Silent Epidemic. JAMA Neurology, 76(12), 1417-1418. doi: 10.1001/jamaneurol.2019.3043

Chabria, S., & Lawrason, J. (2007). Altered mental status, an unusual manifestation of early disseminated Lyme disease: A case report. Journal of Medical Case Reports, 1, 62. doi: 10.1186/1752-1947-1-62

Chavda, V., & Patel, S. (2019). Lyme Neuroborreliosis – The Mystifying Pitfall: "Neuropathology and Current Therapeutics." Recent Patents on Anti-Infective Drug Discovery, 14(1), 49-68. doi: 10.2174/1574891X14666190327114641

Fallon, B.A., Kochevar, J.M., Gaito, A., & Nields, J.A. (1998). The underdiagnosis of neuropsychiatric Lyme disease in children and adults. Psychiatric Clinics of North America, 21, 693–703. doi: 10.1016/s0193-953x(05)70032-0

Fallon, B. & Nields, J. (1994). Lyme disease: A neuropsychiatric illness. American Journal of Psychiatry, 151, 1571-1583. doi: 10.1176/ajp.151.11.1571

Fallon, B. A., Nields, J. A., Burrascano, J. J., Liegner, K., DelBene, D., & Liebowitz, M.R. (1992). The neuropsychiatric manifestations of Lyme borreliosis. Psychiatric Quarterly. 1992, 63, 95–117. doi: 10.1007/bf01064684

Fallon, B. A., Nields, J. A., Parsons, B., Liebowitz, M. R., & Klein, D.F. (1993). Psychiatric manifestations of Lyme borreliosis. Journal of Clinical Psychiatry, 54, 263–268. PMID: 8335653

Fallon, B. A., Schwartzberg, M., Bransfield, R., Zimmerman, B., Scotti, A., Weber, C. A., & Liebowitz, M. R. (1995). Late-stage neuropsychiatric Lyme borreliosis. Differential diagnosis and treatment. Psychosomatics, 36, 295–300. doi: 10.1016/S0033-3182(95)71669-3

Garakani, A., & Mitton, A. G. (2015). New-onset panic, depression with suicidal thoughts, and somatic symptoms in a patient with a history of Lyme disease. Case Reports in Psychiatry. 2015(457947). doi: 10.1155/2015/457947

Greenberg, R. (2017). Infections and childhood psychiatric disorders: Tick-borne illness and bipolar disorder in youth. Bipolar Disorders, 3(1). doi: 10.4172/2472-1077.1000113

Hájek, T., Pasková, B., Janovská, D., Bahbouh, R., Hájek, P., Libiger, J., & Höschl, C. (2002). Higher prevalence of antibodies to Borrelia burgdorferi in psychiatric patients than in healthy subjects. American Journal of Psychiatry, 159, 297–301. doi: 10.1176/appi.ajp.159.2.297

Hamlen, R., & Kliman, D. (2007). Lyme disease: Etiology, neuropsychological sequelae and educational impact. Pediatric School Psychology Communiqué. Newspaper of the National Association of School Psychologists, 36(5), 34-35.

Hamlen, R. & Kliman, D. (2009). Pediatric Lyme disease: Tips for school nurses. NASN School Nurse, 24, 114. doi: 10.1177/1942602X09333901

Infectious Diseases Society of America. (Proposed, 2019). IDSA/AAN/ACR Lyme Disease Guideline Retrieved from: https://www.idsociety.org/practice-guideline/idsaaanacr-lyme-disease-guideline/

International Lyme and Associated Diseases Society. (2019). Lyme Disease Basics for Providers. Retrieved from https://www.ilads.org/research-literature/lyme-disease-basics-for-providers/

Johnson, L. (2019). MyLymeData 2019 Chart Book. Figshare. Book. doi: 10.6084/m9.figshare.8063039

Leventhal, J. (2015, November 6). The neuropsychological evaluation in assessing brain dysfunction. Presented at the conference sponsored by the Leir Retreat Center and Lyme Connection: Brain and Behavior: The Impact of Lyme and Other Infectious Diseases, Ridgefield, Connecticut.

Logigian, E. L., Kaplan, R. F., & Steere, A.C. (1990). Chronic neurologic manifestations of Lyme disease. New England Journal of Medicine, 323, 1438-1444. doi: 10.1056/NEJM199011223232102

Lucker, J. (2015) Auditory hypersensitivity in children with Lyme disease. Annals of Pediatrics and Child Health 3(1), 1035.

Lyme Disease Association, Inc. (2019, September 21-22). Scientific Update for Clinicians & Researchers. Columbia University/Lyme Disease Association's 20th Annual Lyme & Other Tick-Borne Diseases, Philadelphia, PA

McAuliffe, P., Brassaard, M, & Fallon, B. (2008). Memory and executive functions in adolescents with post-treatment Lyme disease. Applied Neuropsychology, 15, 208-219. doi: 10.1080/09084280802324473

Pachner, A. (1989). Neurological manifestations of Lyme disease: The new "Great Imitator." Review of Infectious Diseases, 11(6): S1482-S1486. PMID: 2682960

Pachner, A., Duray, P., & Steere, A. (1989). Central nervous system manifestations of Lyme disease. Archives of Neurology, 56(7), 709-795. doi: 10.1001/archneur.1989.00520430086023

Padula, W. (2019, November 2). Managing the visual consequences of Lyme disease. Presented at the Twentieth Annual Scientific Conference of the International Lyme and Associated Diseases Society: Chronic Disease = Chronic Infections? Boston, Massachusetts.

Padula, W., Frid, E., Jeness, J., Spurling, A., & Sayyed, A. (n.d.) Visual Evoked Potential N-75 Biomarker to Predict Lyme Disease and Visual Processing Dysfunction: An Experimental Design, (Submitted for publication).

Reik, L., Smith, L., Khan, A. & Nelson, W. (1985). Demyelinating encephalopathy in Lyme disease. Neurology, 35, 267-269. doi: 10.1212/wnl.35.2.267

Schutzer, S. E. (1999). Borrelia burgdorferi–Specific Immune Complexes in Acute Lyme Disease. Jama, 282(20), 1942. doi: 10.1001/jama.282.20.1942

Sexton, S., Editor. (2016, July). APA Updates Guidelines on Psychiatric Evaluation in Adults. American Family Physician, 94(1). Retrieved from https://www.aafp.org/afp/2016/0701/p62.html

Sherr, V. T. (2000). Panic attacks may reveal previously unsuspected chronic disseminated Lyme disease. Journal of Psychiatric Practice, 6, 352–356. doi: 10.1097/00131746-200011000-00005

Sherr, V. (2005). Munchausen's syndrome by proxy and Lyme disease: Medical misogyny or diagnostic mystery? Medical Hypotheses, 65(3), 440-447. doi: 10.1016/j.mehy.2005.04.009

Smith, P. (2003). Address to the Rhode Island School Nurses Association, www.lymediseasassociation.org

Smith, P. (2004, April 16). The Effects of Lyme disease on students, schools and school policy. New Jersey School Boards Association "School Leader" Journal. Retrieved from https://lymediseaseassociation.org/about-lyme/lyme-kids-a-schools/nj-school-boards-association-qschool-leaderq-journal/

Smith, P. (2019). Personal communication.

Statlender, S. & Leventhal, J. "Lyme and Tick-borne infections: Implications for School-based health practitioners." Presented at the conference of the Connecticut Association of School Based Health Centers: Protecting a Vulnerable Population, Southbury, Connecticut, May 5, 2017.

Statlender, S. "The Impact of Lyme on Brain and Behavior: Perspectives of a Clinical Psychologist." Presented at the Fall conference of the Massachusetts Association of Physician Assistants, Worcester, Massachusetts, October 19, 2019.

Stricker, R., & Winger, E. (2003). Musical hallucinations in patients with Lyme disease. Southern Medical Journal, 96(7), 711-715. doi: 10.1097/01.SMJ.0000053458.21691.2E

Tager, F. A., Fallon, B. A., Keilp, J., Rissenberg, M., Jones, C. R., & Liebowitz, M. R. (2001). A controlled study of cognitive deficits in children with chronic Lyme disease. Journal of Neuropsychiatry and Clinical Neurosciences. 2001, 13, 500–507. doi: 10.1176/jnp.13.4.500

Weintraub, P. (2007, September). Munchausen: Unusual Suspects. Psychology Today. Retrieved from https://www.psychologytoday.com/us/articles/200709/munchausen-unusual-suspects

Wormser, G. P., Dattwyler, R. J., Shapiro, E. D., Halperin, J. J., Steere, A. C., Klempner, M. S., ... Nadelman, R. B. (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. doi: 10.1086/508667

Prioritized Issue: Shared Medical Decision-Making

H. R. 3590 (111th): Patient Protection and Affordable Care Act (2010). Affordable Care Act Provisions, Sec. 936. Program to facilitate shared decisionmaking. Retrieved from https://www.govtrack.us/congress/bills/111/hr3590/text

Agency for Healthcare Research and Quality. (2018). The SHARE Approach. Retrieved from https://www.ahrq.gov/health-literacy/curriculum-tools/shareddecisionmaking/index.html

American Medical Association. (2016) AMA Principles of Medical Ethics. Retrieved from https://www.ama-assn.org/about/publications-newsletters/ama-principles-medical-ethics

American Medical Association. (2019) AMA Code of Medical Ethics Opinion 1.1.3. Retrieved from https://www.ama-assn.org/delivering-care/ethics/patient-rights

American Medical Association. (2019) AMA Code of Medical Ethics Opinion 1.1.7. Retrieved from https://www.ama-assn.org/delivering-care/ethics/physician-exercise-conscience

American Medical Association. (2019) AMA Code of Medical Ethics Opinion 1.2.11. Retrieved from https://www.ama-assn.org/delivering-care/ethics/ethically-sound-innovation-medical-practice

American Medical Association. (2019) AMA Code of Medical Ethics Opinion 1.2.3. Retrieved from https://www.ama-assn.org/delivering-care/ethics/consultation-referral-second-opinions

Atkins, D., Siegel, J., & Slutsky, J. (2005). Making policy when the evidence is in dispute. Health Affairs (Millwood), 24(1), 102-13. doi: 10.1377/hlthaff.24.1.102

Barry, M. J., & Edgman-Levitan, S. (2012). Shared decision making–pinnacle of patient-centered care. New England Journal of Medicine, 366(9), 780-1. doi: 10.1056/NEJMp1109283

Barry, M., Edgman-Levitan, S., & Sepucha, K. (2018, September 6). Staying Focused on the Ultimate Goal. NEJM Catalyst. Retrieved from https://catalyst.nejm.org/shared-decision-making-patient-decision-aids/

Beauchamp, T. L., & Childress, J. F. (1994). Principles of biomedical ethics. Vol. 4. New York: Oxford University Press.

Cameron D. J., Johnson, L. B., & Maloney, E. L. (2014). Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Review Anti-Infective Therapy, 12(9), 1103-35. doi: 10.1586/14787210.2014.940900

Congressionally Directed Medical Research Programs (2018). Consumer Involvement: Nicole Malachowski: Unfit for Duty from Debilitating Tick-Borne Disease. Retrieved from https://cdmrp.army.mil/cwg/stories/2018/nicole_malachowski_profile

deBronkart, D. (2013). How the e-patient community helped save my life: An essay by Dave deBronkart. BMJ, 346, f1990. doi: 10.1136/bmj.f1990

Donta, S. T. (2012). Issues in the diagnosis and treatment of lyme disease. Open Neurology Journal, 6, 140-5. doi: 10.2174/1874205X01206010140

Frosch, D. L., May, S. G., Rendle, K. A., Tietbohl, C., & Elwyn, G. (2012). Authoritarian physicians and patients' fear of being labeled ‘difficult' among key obstacles to shared decision making. Health Affairs (Millwood), 31(5), 1030-8. doi: 10.1377/hlthaff.2011.0576.

Fugh-Berman, A., & Melnick, D. (2008). Off-Label Promotion, On-Target Sales. PLOS Med, 5(10), e210. doi: 10.1371/journal.pmed.0050210

Galesic, M., Gigerenzer, G., & Straubinger, N. (2009). Natural frequencies help older adults and people with low numeracy to evaluate medical screening tests. Medical Decision Making, 29(3), 368-71. doi: 10.1177/0272989X08329463

HealthIT.gov. (2013, December) National Learning Consortium, Shared Decision Making Fact Sheet. Retrieved from https://www.healthit.gov/sites/default/files/nlc_shared_decision_making_fact_sheet.pdf

Institute of Medicine (2001). Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academies Press. doi: 10.17226/10027

Institute of Medicine. (2011). Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press. Available from http://books.nap.edu/openbook.php?record_id=13058

Johnson, L., Aylward, A., & Stricker, R. B. (2011). Healthcare access and burden of care for patients with Lyme disease: a large United States survey. Health Policy, 1, 64-71. doi: 10.1016/j.healthpol.2011.05.007

Johnson, L., Shapiro, M., & Mankoff, J. (2018). Removing the Mask of Average Treatment Effects in Chronic Lyme Disease Research Using Big Data and Subgroup Analysis. Healthcare, 6(4). doi: 10.3390/healthcare6040124

Johnson L. MyLymeData 2019 Chart Book. figshare Book. 2019. doi: 10.6084/m9.figshare.8063039.v1

Johnson, L. (2019). Outcomes Important to Lyme Patients: Results of a LymeDisease.org patient survey conducted in 2015. figshare. Book. doi: 10.6084/m9.figshare.10010534

Lee, C. N., Dominik, R., Levin, C. A., Barry, M. J., Cosenza, C., O'Connor, A. M., ... Sepucha, K. R. (2010). Development of instruments to measure the quality of breast cancer treatment decisions. Health Expect, 3, 258-72. doi: 10.1111/j.1369-7625.2010.00600.x.

Maloney, E. L. (2009). The Need for Clinical Judgment in the Diagnosis and Treatment of Lyme Disease. Journal of American Physicians and Surgeons, 14(3), 28-89.

Martinez, K. A., Kurian, A. W., Hawley, S. T., & Jagsi, R. (2015). How can we best respect patient autonomy in breast cancer treatment decisions? Breast Cancer Management, 4(1), 53-64. doi: 10.2217/bmt.14.47

Merchant, F. M., Dickert, N. W., Jr, & Howard, D. H. (2018). Mandatory Shared Decision Making by the Centers for Medicare &amp; Medicaid Services for Cardiovascular Procedures and Other Tests. JAMA, 320(7), 641-2. doi: 10.1001/jama.2018.6617

Mulley, A.G, Trimble, C., & Elwyn, G. (2012). Stop the silent misdiagnosis: patients' preferences matter. BMJ, 345, e6572. doi: 10.1136/bmj.e6572.

Mulley, A. G., & Barry, M. J. (1998). Controversy in managing patients with prostate cancer. BMJ. 316(7149), 1919-20. doi: 10.1136/bmj.316.7149.1919

Moyer, B., McAllister, J., & Finley, M. L. (2001). Doing Democracy: The MAP Model for Organizing Social Movements. New Society Publishers: Gabriola Island, BC.

National Quality Parnters (2017). Shared Decision Making: A Standard of Care for All Patients. [Action Brief]. Retrieve from https://www.qualityforum.org/Publications/2017/10/NQP_Shared_Decision_Making_Action_Brief.aspx

Noble, A., Brennan, T. A., Hyams, A. L. (1998). Snyder v. American Association of Blood Banks: a re-examination of liability for medical practice guideline promulgators. Journal of Evaluation in Clinical Practice, 4, 49-62. doi: 10.1046/j.1365-2753.1998.t01-1-00005.x

Patient-Centered Outcomes Research Institute. (2019). Topic Spotlight: Shared Decision Making. Retrieved from https://www.pcori.org/topics/shared-decision-making

President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. (1982, October) Making Health Care Decisions: A Report on the Ethical and Legal Implications of Informed Consent in the Patient Practitioner Relationship. Volume One: Report. Retrieved from https://repository.library.georgetown.edu/bitstream/handle/10822/559354/making_health_care_decisions.pdf?sequence=1&isAllowed=y

Peterson, M. (2007). Should the precautionary principle guide our actions or our beliefs? Journal of Medical Ethics, 33(1), 5-10. doi: 10.1136/jme.2005.015495

Sackett, D. (1981). How to read clinical journals: I. why to read them and how to start reading them critically. Canadian Medical Association Journal, 124(5), 555-558. PMID: 7471000

Sackett, D., Straus, S., Richardson, W., Rosenberg, W., & Haynes, R. (2000). Evidence-based medicine: how to practice and teach EBM. 2nd ed. Edinburgh: Churchill Livingstone.

Saposnik, G., Redelmeier, D., Ruff, C. C., & Tobler, P. N. (2016). Cognitive biases associated with medical decisions: a systematic review. BMC Medical Informatics and Decision Making, 16(1), 138. doi: 10.1186/s12911-016-0377-1

Scheibler, F., Müller, H., Légaré, F., & Kasper, J. (2012). No EBM without SDM: Give us a measure to capture patient involvement and we will move the health system. Zeitschrift für Evidenz, Fortbildung und Qualität im Gesundheitswesen, 106(4), 235-7. doi: 10.1016/j.zefq.2012.04.006

Shafir, A. & Rosenthal, J. (2012) Shared Decision Making: Advancing Patient-Centered Care through State and Federal Implementation. National Academy for State Health Policy.

ter Meulen, R. H. (2005). The ethical basis of the precautionary principle in health care decision making. Toxicolology and Applied Pharmacology, 207(2), 663-7. doi: 10.1016/j.taap.2004.11.032

Thera, R., Carr, D. T., Groot, D. G., Baba, N, & Jana, D.K. (2018). Understanding Medical Decision-making in Prostate Cancer Care. American Journal of Men's Health, 12(5), 1635-47. doi: 10.1177/1557988318780851

U.S. Food and Drug Administration. (1982). FDA Drug Bulletin. Use of approved drugs for unlabeled indications. FDA Drug Bulletin, 12(1), 4-5. Retrieved from www.circare.org/fda/fdadrugbulletin_041982.pdf

Wormser, G. P., Dattwyler, R. J., Shapiro, E. D., Halperin, J. J., Steere, A. C., Klempner, M. S., ... Nadelman, R. B. (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(9), 1089-134. doi: 10.1086/508667

Virtual Mentor. (2004). On distinguishing justifiable from unjustifiable paternalism. AMA Journal of Ethics, 6(2), 72-74. doi: 10.1001/virtualmentor.2004.6.2.medu1-0402

Virtual Mentor. (2012) Selective Paternalism. AMA Journal of Ethics, 14(7), 582-588. doi: 10.1001/virtualmentor.2012.14.7.oped2-1207

Wegwarth, O., Schwartz, L. M., Woloshin, S., Gaissmaier, W., & Gigerenzer, G. (2012). Do physicians understand cancer screening statistics? A national survey of primary care physicians in the United States. Annals of Internal Medicine, 156(5), 340-9. doi: 10.7326/0003-4819-156-5-201203060-00005.

Prioritized Issue: Patient and Public Health Education on Lyme Disease and Other Tick-Borne Diseases

Aguero-Rosenfeld, M. E., & Wormser, G. P. (2015). Lyme disease: diagnostic issues and controversies. Expert Review of Molecular Diagnostics, 15(1), 1-4. doi: 10.1586/14737159.2015.989837

Brennan, M. B., Herwald, B. L., Kazmierczak, J. J., Weiss, J. W., Klein, C. L., Leith, C. P., ... Gauthier, G. M. (2016). Transmission of Babesia microti Parasites by Solid Organ Transpantation. Emerging Infectious Diseases, 22(11). doi: 10.3201/eid2211.151028

Breitschwerdt, E. B. (2017). Bartonellosis, One Health and all creatures great and small. Veterinary Dermatology, 28, 96–e21. doi: 10.1111/vde.12413

Centers for Disease Control and Prevention. (2019). Ehrlichiosis: Transmission. Retrieved from https://www.cdc.gov/ehrlichiosis/transmission/index.html

Centers for Disease Control and Prevention. (2019). Lyme Disease: Diagnosis and Testing. Retrieved from https://www.cdc.gov/lyme/diagnosistesting/index.html

Columbia University Irving Medical Center. (2019). Powassan Virus. Retrieved from https://www.columbia-lyme.org/powassan-virus

Cook, M. J. (2015). Lyme borreliosis: a review of data on transmission time after tick attachment. International Journal of General Medicine, 8, 1-8. doi: 10.2147/IJGM.S73791

Depietropaolo, D. L., Powers, J. H., Gill, J. M., & Foy, A. J. (2005). Diagnosis of Lyme disease. American Family Physician, 72(2), 297-304. PMID: 16050454

Eisen, L. (2018). Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks. Ticks and Tick-Borne Diseases, 9(3), 535-542. doi: 10.106/j.ttbdis.2018.01.002

Mayo Clinic. (2019). Lyme disease: Diagnosis. Retrieved from https://www.mayoclinic.org/diseases-conditions/lyme-disease/diagnosis-treatment/drc-20374655

Occupational Safety and Health Administration. (n.d.) Safety and Health Information Bulletin: Potential for Occupational Exposure to Lyme Disease. Retrieved from https://www.osha.gov/dts/shib/shib021103.html

Pennsylvania Department of Health. (2019). Lyme Serology Test, Specimen Collection and Submission Guidance. Retrieved from https://www.health.pa.gov/topics/Documents/Laboratories/Lyme%20Testing%20and%20Collection%20Guidance%20Final.pdf

Pennsylvania Department of Health. (2019). Health Advisory: Lyme Disease and Other Tickborne Diseases in Pennsylvania. Retrieved from https://www.health.pa.gov/topics/Documents/HAN/2019-PAHAN-443-04-12-ADV-Lyme%20Disease.pdf

Prasad, V., & Cifu, A. (2011). Medical Reversal: Why We Must Raise the Bar Before Adopting New Technologies. Yale Journal of Biological Medicine, 84(4), 471-478. PMID: 22180684

Reed-Guy, L. (2013). Older Doctors Less Likely to Abandon Ineffective Therapies. Penn Leonard Davis Insititute of Health Economics. Retrieved from https://ldi.upenn.edu/news/older-doctors-less-likely-abandon-ineffective-therapies

Sachdev, S. H., Joshi, V., Cox, E. R., Amoroso, A., & Parker, S. (2013). Severe life-threatening Ehrlichia chaffeensisinfections transmitted through solid organ transplantation. Transplant Infectious Disease, 16(1), 119–124. doi:10.1111/tid.12172

State of Colorado. (2019). Tick Season. Retrieved from https://www.colorado.gov/pacific/saguachecoclerk/news/tick-season

Task Force on Lyme Disease and Related Tick-Borne Diseases. (2015). Lyme Disease in Pennsylvania. Retrieved from https://www.health.pa.gov/topics/Documents/Diseases%20and%20Conditions/Lyme/Lyme%20Disease%20in%20Pennsylvania%20(2).pdf

Tick Research Lab of Pennsylvania (n.d.) Pennsylvania Tick Research Lab. Retrieved from https://www.ticklab.org

State health departments reviewed:

California Department of Public Health. (n.d.). Retrieved from https://www.cdph.ca.gov

Colorado Department of Public Health & Environment. (n.d.). Retrieved from https://www.colorado.gov/cdphe

Connecticut State Department of Public Health. (n.d.). Retrieved from https://portal.ct.gov/dph

Florida Department of Health. (n.d.). Retrieved from www.floridahealth.gov

Maine Department if Health & Human Services. (n.d.). Retrieved from https://maine.gov/dhhs

Missouri Department of Health & Senior Services. (n.d.). Retrieved from https://health.mo.gov

New York State Department of Health. (n.d.). Retrieved from https://www.health.ny.gov

North Carolina Division of Public Health. (n.d.). Retrieved from https://publichealth.nc.gov

Oregon Health Authority. (n.d.). Retrieved from https://www.oregon.gov/oha/Pages/index.aspx

Pennsylvania Department of Health. (n.d.). Retrieved from https://www.health.pa.gov/Pages/default.aspx

Prioritized Issue: Clinician Training on Tick-Borne Diseases

Angelakis, E., Billeter, S. A., Breitschwerdt, E. B., Chomel, B. B., & Raoult, D. (2010). Potential for Tick-Borne Bartonelloses. Emerging Infectious Diseases, 16(3), 385-391. doi: 10.3201/eid1603.091685

Armed Forces Pest Management Board. (2012). Tick-Borne Diseases: Vector Surveillance and Control. Office of the Under Secretary of Defense. Retrieved from https://www.acq.osd.mil/eie/afpmb/docs/techguides/tg26.pdf

Aucott, J., Rebman, A. W., Crowder, L. A., & Kortte, K. B. (2013). Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Quality of Life Research, 22(1):75-84. doi: 10.1007/s11136-012-0126-6

Cameron, D. J., Johnson, L. B., & Maloney, E. L. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Review of Anti-Infective Therapy, 12(9), 1103-35. doi: 10.1586/14787210.2014.940900.

Centers for Disease Control and Prevention. (2019). Bartonella Infection: Transmission. Retrieved from https://www.cdc.gov/bartonella/transmission/index.html

Congressionally Directed Medical Research Program. (n. d.). Consumer Involvement: A 5-Year-Old Gone Too Soon from Untreated Rocky Mountain Spotted Fever. Retrieved from https://cdmrp.army.mil/cwg/stories/2019/tony_galbo_profile

Cotte, V., Bonnet, S., Le Rhun, D., Le Naour, E., Chauvin, A., Boulouis, H. J., ... Vayssier-Taussat, M. (2008). Emerging Infectious Diseases, 14(7), 1074-80. doi: 10.3201/eid1407.071110

Fallon, B. A., Keilp, J. G., Corbera, K. M., Petkova, E., Britton, C. B., Dwyer, E., ... Sackeim, H. A. (2008). A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology, 70(13), 992-1003. doi: 10.1212/01.WNL.0000284604.61160.2d

Feder, H. M. Jr, & Whitaker, D. L. (1995). Misdiagnosis of erythema migrans. American Journal of Medicine, 99, 412–9. doi: 10.1016/s0002-9343(99)80190-9

Goel, R., Westblade, L. F., Kessler, D. A., Sfeir, M., Slavinski, S., Backenson, B., ... Cushing, M. M. (2018). Death from Transfusion-Transmitted Anaplasmosis, New York, USA, 2017. Emerging Infectious Diseases, 24(8), 1548-1550. doi: 10.3201/eid2408.172048

Hirsch, A. G., Herman, R. J., Rebman, A., Moon, K. A., Aucott, J., Heaney, C., & Schwartz, B. S. (2018). Obstacles to diagnosis and treatment of Lyme disease in the USA: a qualitative study. BMJ Open, 8(6), e021367. doi: 10.1136/bmjopen-2017-021367

Marx, G.E., Leikauskas, J., Lindstrom, K., Mann, E., Reagan-Steiner, S., Matkovic, E., ... Brown, C. (2019). Fatal Lyme Carditis in New England: Two Case Reports. Annals of Internal Medicine. doi: 10.7326/L19-0483.

Reed, K.D. (2002). Laboratory Testing for Lyme Disease: Possibilities and Practicalities. Journal of Clinical Microbiology, 40(2), 319-24. doi: 10.1128/JCM.40.2.319-324.2002

Weiss, T., Zhu, P., White, H. Posner, M., Wickiser, J. K., Washington, M. A., & Barnhill, J. (2019). Latent Lyme Disease Resulting in Chronic Arthritis and Early Career Termination in a United States Army Officer. Military Medicine, 184(7-8), e368-e370. doi:10.1093/milmed/usz026.

Appendixes

Appendix A: Meeting Agendas

The following are theAgendas for all meetings except Meetings 3, 4, 5, and 8. For reasons outside the control of the Subcommittee, those agendas were not provided and are, therefore, not included here.

Note: The agendas are in their original format and have not been copyedited.

Agenda July 15, 2019 2:00pm-4:00pm

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05) Pat

Welcome/Phone (2:05-2:10) rules: Please give name before you speak Pat

Introduction (2:05-2:35) What you have done, expertise brought to this committee

Milestones & Deliverable-what is expected & when due (2:35-2:45) Pat

Outline 2020 TBDWG Subcommittee Reports to WG (p. 9-12) [Also below] (2:45-3:30) Pat

  • Suggestions for included topics
    • Training and education include access to care-reimbursement, - focus on gaps, public health and physician/clinicians, military
      • Access to care
      • Two standards of care
      • Medical board actions
      • Reimbursement issues
      • Diagnosis by geography issues
      • Shared medical decision-making
      • Prevent delayed diagnosis
      • Prevent development of chronic Lyme disease
      • Provide treatment options

Speakers (3:30-3:45) Can be subcommittee person (recommended 8-10 hours) Pat

  • Topics
  • Suggested people
  • Possible dates

Background & Methods Section (3:45-3:55) Pat

  • Background Section for 2018 – Ideas for 2020

Next Meetings & Questions July 29, 2015, 2:00-4:00; August 16 (3:55-4:00) Pat

Adjournment (4:00)

Agenda July 29, 2019 2:00pm-4:00pm

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05) Pat

Speakers for upcoming meetings (2:05- 2:15) Pat

  • Maloney 8/16 ILADS & IDSA guidelines (1hour) OK?
  • Johnson 8/30 Quality of Care (1 hour) YES
  • Aucott 9/27 Cost of Illness (1/2 hour) YES
  • Pollack 10/4 Doctors/Medical Board Issues (1 hour) YES
  • Megan (& maybe Nicole Malachowsky) Military perspective (no date yet) (1Hour?)
  • Rebecca CMS perspective (no date yet)
  • Other Speakers no contacts- who can try to reach them? Quest, Robyn Gelberg

Speaker (2:15-2:45) Lorraine Johnson on Background

Speaker Q&A (2:45-3:00) Pat

Share Point Discussion (3:00-3:15pm) Rebecca T & E report (Rebecca, Lorraine, Betty, Pat)

T&E & A&R Discuss individuals for each section (3:15-3:30) Pat

Background & Methods Section (3:45-3:55) Pat

  • Background Section from 2018 (sent last mtg.) – Ideas for 2020 begin discussion Next Meetings Subcommittee (3:55-4:00) Pat
  • 8/16, 8/30, 9/13, 9/27 10/4, 10/18, 11/1,11/15, 12/6, 12/20, 1/3 2pm-4pm-zoom
  • Next Working Group Meeting (9:00-5:00pm) 9/12 9:00-5:00pm (chg. 9/13 subcommittee)

Adjournment (4:00)

Agenda September 27, 2019 2:00pm-4:00pm

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05) Pat

Speaker: John Aucott (JHU) 9/27 Cost of Illness (30 min) 2:05-2:35

  • Speaker Q & A (15 min) 2:35-2:50

Announcements 2:50-2:55 Pat

  • Speakers for upcoming subcommittee meetings (2:05-2:10)
    • Elliott Pollack (Pullman & Comley) 10/11 2:30-3:30 Legal issues (1h)
    • Robin Gelburd (Fair Health) 10/18 2:15-3:15 Stats: Geographic diversity, urban/suburban (1h)
    • Megan DuLaney & Nicole Malachowski 11/1 2:15-3:15 Military & patient perspective (1h)
    • Paul Auwaerter, MD (JHU) 11/15 IDSA Guidelines (1h)
  • Meeting 5 subcommittee awaiting review by Rebecca
  • Subcommittee Meeting Link & ID Change beginning 10/18
  • Next Meeting Subcommittee 10/11
  • Topic Development briefs accessible on TBDWG Report Webpage Topic Development Briefs
  • Next Working Group Meetings in person 1/28 & 29/20 (DC); 3/3 & 4/20 (Phila.)

Writing Groups Procedures, Discussion (2:55-3:30) Pat

  • Background Cat will start draft based on Lorraine's presentation; Rebecca will polish
  • Methods Pat
  • Results
    1. Access to Care for patients with Lyme and TBD: Lorraine, Doug
    2. Reimbursement for patients with Lyme and TBD: Rebecca
    3. Clinician Training for Lyme and TBD: Rebecca, Betty
    4. Patient/Public Health Education on Lyme and TBD: Doug
    5. Diagnostic errors: factors related to delayed diagnosis and misdiagnosis including inappropriate psychiatric diagnosis: Sheila (mental health will likely overlap with several other areas) Lorraine (diagnostic errors, incl. misdiagnosis by geography; will provide MyLymeData stats on diagnostic errors in psychiatric)
    6. Shared medical decision-making: Lorraine, Betty

Next steps (3:30-3:40) Pat

  • Begin reviewing & discussing draft Results and Potential Actions section as a group; All subcommittee members; October 1, 2019
  • Finalize & submit Results and Potential Actions section to WG Core for review; Subcommittee Co-chairs w/help of support writer; November 1, 2019

Background (10 min.) 3:40-3:50) Rebecca Submit Oct 1 VOTE NEEDED TO ACCEPT

Methods (10min) (3:50-4:00) Pat Submit Oct 1

Adjournment (4:00)

Agenda October 11, 2019 2:00pm-4:00pm

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05) Pat

Background Section discussion, vote to submit (2:05-2:30) Rebecca

[Pat] intro Speaker: Elliott Pollack (Pullman & Comley) 10/11 2:30-3:15 Legal issues

  • Speaker Q & A (15 min) 3:15-3:30

Information Items 2:50-2:55 [Pat]

  • Speakers for upcoming subcommittee meetings 2:05-2:10
    • Robin Gelburd (Fair Health) 10/18 2:15-3:15 Stats: Geographic diversity
    • Megan DuLaney/Nicole Malachowski 11/1 2:15-3:15 Military & patient perspective (1h)
    • Meeting Extension on 11/15, extend until 4:45 to get all business + 2 speakers
      • Paul Auwaerter, MD (JHU) 11/15 IDSA Guidelines (1h)
      • Dr. Lee-Lewandrowski 11/15
    • Procedures for working on reports Share Point? Attachments?
    • The 9/12 WG meeting summary is posted on the TBDWG website
    • Email update from Sue Partridge, CDC
    • Pat submitted the Methods Report on October 1
  • Next Subcommittee Meeting (Link/ID Change) 10/18 Rebecca will Chair

Writing Groups Reports 2:55-3:30 [Pat]

  1. Access to Care for patients with Lyme and TBD: Lorraine, Doug
  2. Reimbursement for patients with Lyme and TBD: Rebecca
  3. Clinician Training for Lyme and TBD: Rebecca, Betty
  4. Patient/Public Health Education on Lyme and TBD: Doug
  5. Diagnostic errors: factors related to delayed diagnosis and misdiagnosis including inappropriate psychiatric diagnosis: (Sheila/ mental health will likely overlap with several other areas) Lorraine (diagnostic errors, incl. misdiagnosis by geography; will provide MyLymeData stats on diagnostic errors in psychiatric)
  6. Shared medical decision-making: Lorraine, Betty, Rebecca

Next step-- due in 3 weeks from today's meeting

Finalize & submit Results and Potential Actions section to WG Core for review Subcommittee Co-chairs w/help of support writer November 1, 2019

Adjournment (4:00)

Agenda Nov. 1, 2019 2:00pm-4:00pm

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05) Pat

Intro Speakers [Pat]: 2:05

  • Nichole Malachowski 2:05-2:35
  • Megan DuLaney 2:35-3:05
  • Combined Q & A 3:05-3:20

Information Items 3:20 Pat

  • Speakers for upcoming subcommittee meetings
    • 11/15 Meeting extended 2:00-4:45
      • Paul Auwaerter, MD (JHU) IDSA Guidelines
      • Dr. Lee-Lewandrowski, PhD, MPH Trends in Lyme disease testing

Writing Groups Reports 3:20-4:00 [Pat] (remaining time will be divided up among groups to discuss/actions

  1. Access to Care for patients with Lyme and TBD: Lorraine, Doug
  2. Reimbursement for patients with Lyme and TBD: Rebecca
  3. Clinician Training for Lyme and TBD: Rebecca, Betty
  4. Patient/Public Health Education on Lyme and TBD: Doug
  5. Diagnostic errors: factors related to delayed diagnosis & misdiagnosis Lorraine
  6. Psychiatric misdiagnosis Sheila
  7. Shared medical decision-making: Lorraine, Betty, Rebecca

Next steps—Between today & step below, online work & vote on draft to submit 11/7

11/7 Co-Chairs submit draft results section to TBDWG w/o upcoming speaker input

11/7-11/14 All members provide feedback on submitted draft, CAT Compiles

11/15 mtg. All members decide on final results content 2 speakers

11/15-11/21 Members finish writing results, CAT compiles

Adjournment (4:00)

Agenda Nov. 15, 2019 2:00pm-4:45pm

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05) Pat

Intro Speaker 1 (2:05) Pat

  • Paul Auwaerter, MD JHU 2:05-2:50
    • IDSA Guidelines
    • Q&A 2:50-3:05

Intro Speaker 2 (3:05) Pat

  • Dr. Elizabeth Lee-Lewandowski PhD, MPH Mass Gen, Harvard 3:05-3:50
    • Laboratory Blood-Based Testing for Lyme Disease at a National Reference Laboratory: A 7 Year Experience
    • Q&A 3:50-4:05 (joined by Kent B Lewandrowski, MD Pathologist, Mass General Hospital and Harvard Medical School)

Information Items (4:05-4:10) Pat

  • Next subcommittee meeting 12/6
  • Speakers for upcoming subcommittee meetings
    • No more scheduled speakers
    • We had Lorraine for possible Quality of Life talk but most likely not able to put into report
  • Military paragraphs for report?

Compilation of Results (4:10-4:25) CAT

Use of public comments Volunteer(s) to review public input and pull together items (how used) 4:25-4:30

Need to answer (4:30-4:35) Pat

  • The literature selection
  • And literature which might contradict that which was selected was identified

Writing Groups Reports (4:35-4:45) Pat

  1. Access to Care for patients with Lyme and TBD: Lorraine, Doug
  2. Reimbursement for patients with Lyme and TBD: Rebecca
  3. Clinician Training for Lyme and TBD: Rebecca, Betty
  4. Patient/Public Health Education on Lyme and TBD: Doug
  5. Diagnostic errors: factors related to delayed diagnosis and misdiagnosis Lorraine
  6. Psychiatric misdiagnosis Sheila
  7. Shared medical decision-making: Lorraine, Betty, Rebecca

Next steps 4:45

  • 11/15 mtg. All members decide on final Results content from CAT 2 speakers
  • 11/15-11/21 Members finish writing Results with speaker adds, etc. CAT compiles
  • Begin compiling complete Subcommittee Report to the WG All subcommittee members w/help of support writer (specific writing assignments TBD by subcom) These sections should be worked on as you move through your calls
  • Begin reviewing & discussing the complete Subcommittee Report to the WG as a group All subcommittee members December 1, 2019
  • Finalize and submit complete Subcommittee Report to the WG Core for review Subcommittee Co-chairs w/help of support writer January 10, 2020

Adjournment 4:45

Agenda Dec. 6, 2019 2:00-4:00pm ET

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05) Pat

Information Items (2:05-2:10) Pat

  • Next subcommittee meeting 12/20, 1/3/20
  • Results Draft v5 was submitted to WG on 12/1/19
  • Methods Section- Pat continues to update and collect data
  • Divergent perspectives/literature-- sections need to review for inclusion

Public comments- review Betty's summary (2:10-2:25) Betty

  • Adds to Results sections?

Writing Groups Reports v5 [Pat] Review each area for short adds, edits, by section leader (2:25-3:30)

  • Military comments-Megan
  1. Access to Care for patients with Lyme and TBD: Lorraine, Doug
  2. Clinician Training for Lyme and TBD: Rebecca, Betty
  3. Patient/Public Health Education on Lyme and TBD: Doug
  4. Diagnostic errors: factors related to delayed diagnosis and misdiagnosis Lorraine
  5. Psychiatric misdiagnosis Sheila
  6. Shared medical decision-making: Lorraine, Betty, Rebecca
  7. Reimbursement for patients with Lyme and TBD: Rebecca

Background (3:30-3:55) Rebecca

  • Edits, adds
  • Summary?

Next steps (3:55-4:00)

  • Begin reviewing & discussing the complete Subcommittee Report to the WG as a group All subcommittee members December 1, 2019
  • Review your section for including divergent perspectives and relevant literature Subcommittee (pertinent to each section) BEGIN NOW-Finish Dec. 13
  • Finalize and submit complete Subcommittee Report to the WG Core for review Subcommittee Co-chairs w/help of support writer January 10, 2020
  • Develop Presentation to subcommittee by PowerPoint

Adjournment (4:00)

Agenda Dec. 20, 2019 2:00-4:00pm ET

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05) [Pat]

Information Items (2:05-2:10) [Pat]

  • Next subcommittee meeting 1/3/20 Rebecca will do agenda and run meeting

Draft Subcommittee Report v1 -Go over final copy from CAT sent 12/18/19 (2:10-3:00)

  • Background (Rebecca)
  • Methods (Pat)
  • Results section (Pat)
    1. Access to Care for patients with Lyme and TBD: Lorraine, [Doug]
    2. Clinician Training for Lyme and TBD: Rebecca, [Betty]
    3. Patient/Public Health Education on Lyme and TBD: [Doug]
    4. Diagnostic errors: factors related to delayed diagnosis and misdiagnosis [Lorraine]
    5. Psychiatric misdiagnosis [Sheila]
    6. Shared medical decision-making: [Lorraine], Betty, Rebecca
    7. Reimbursement for patients with Lyme and TBD: [Rebecca]
  • Appendix
  • References

Results & Potential Action-Priorities & Potential Actions at a Glance-(CAT) ex. she sent 12/13 Discuss (3:00-3:30)

Powerpoint development? (3:30-3:50)

Next steps & Adjournment (3:55-4:00)

  • Finalize and submit complete Subcommittee Report to the WG Core for review Subcommittee Co-chairs w/help of support writer January 10, 2020

Develop Presentation to subcommittee by PowerPoint

Agenda Dec. 20, 2019 2:00-4:00pm ET

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05) [Pat]

Information Items (2:05-2:10) [Pat]

    • Next subcommittee meeting 1/3/20 Rebecca will do agenda and run meeting

Draft Subcommittee Report v1 -Go over final copy from CAT sent 12/18/19 (2:10-3:00)

  • Background (Rebecca)
  • Methods (Pat)
  • Results section (Pat)
    1. Access to Care for patients with Lyme and TBD: Lorraine, [Doug]
    2. Clinician Training for Lyme and TBD: Rebecca, [Betty]
    3. Patient/Public Health Education on Lyme and TBD: [Doug]
    4. Diagnostic errors: factors related to delayed diagnosis and misdiagnosis [Lorraine]
    5. Psychiatric misdiagnosis [Sheila]
    6. Shared medical decision-making: [Lorraine], Betty, Rebecca
    7. Reimbursement for patients with Lyme and TBD: [Rebecca]
  • Appendix
  • References

Results & Potential Action-Priorities & Potential Actions at a Glance-(CAT) ex. she sent 12/13 Discuss (3:00-3:30)

Powerpoint development? (3:30-3:50)

Next steps & Adjournment (3:55-4:00)

  • Finalize and submit complete Subcommittee Report to the WG Core for review Subcommittee Co-chairs w/help of support writer January 10, 2020

Develop Presentation to subcommittee by PowerPoint

Agenda Jan. 3, 2020 2:00-4:00pm ET

Training & Education/Access & Reimbursement Subcommittee

Call to order (2:00-2:05)

Information Items (2:00-2:10) [Pat]

  • Next subcommittee meeting: None scheduled
  • WG Jan. 28,29 (Pat & Betty will present PowerPoint)

Draft Subcommittee Report v3-Go over final copy from CAT (2:10-3:00) [Pat]

  • Background-under goals, remove? " Reimbursement for patients with Lyme disease, coinfections, and other tick-borne diseases and conditions"
  • Methods (Pat)
  • Results section (Pat)
    1. Access to Care for patients with Lyme and TBD: Lorraine, [Doug]
    2. Clinician Training for Lyme and TBD: Rebecca, [Betty]
    3. Patient/Public Health Education on Lyme and TBD: [Doug]
    4. Diagnostic errors: factors related to delayed diagnosis/misdiagnosis [Lorraine]
    5. Psychiatric misdiagnosis [Sheila]
    6. Shared medical decision-making: [Lorraine], Betty
    7. Reimbursement for patients with Lyme and TBD: [Rebecca] STATEMENT INCLUSION
  • Priorities & Potential Actions at a Glance-(CAT) Where to put in report
  • Appendix
  • Reference

Votes on Report (3:00-3:30) [Pat]

    • Recommendation(s) of each section
    • Entire report-- contingent upon methods table update/other if necessary
      • Will Submit complete Subcommittee Report to the WG Core for review

PowerPoint development [Pat, Betty, Lorraine] (3:30-3:55)

Next steps & Adjournment (3:55-4:00)

Appendix B: Top-Line Meeting Summaries

Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 1

July 15, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

+Commander Rebecca Bunnell, MPAS, PA-C, Subcommittee Co-Chair (Regular Government Employee)

+Patricia V. Smith, Subcommittee Co-Chair (Patient Advocate)

+Megan DuLaney, MS (Patient Representative)

+Doug Fearn (Patient Advocate)

+Lorraine Johnson (Patient Advocate)

+Elizabeth Maloney, MD (Health Care Provider)

+Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

+Debbie Seem, RN, MPH Federal Representative

+Jennifer Gillissen(contractor)

+Cat Thomson, MA (contractor)


Topic Areas Discussed

Member Introductions

Milestones, Deliverables, and Timeline

Subcommittee Report Outline

Scope of the Subcommittee and Its Report

How to Accomplish the Work

Potential Speakers

Next Meeting and Questions

Adjournment


Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 2

July 29, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

+ Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia V. Smith, Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

x Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

+ Nicole Greene Federal Representative

+ Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Presentation—Lyme Disease: What You Need to Know

Lorraine Johnson, CEO, LymeDisease.org

Speakers for Upcoming Meetings

Clarification on Training and Education

Division of Work

Background and Methods Section

Next Meetings

Adjournment


Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 3

August 16, 2019

Attendance

+ Present

x Not Present

Working Group and Subcommittee Members

+ Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia V. Smith
Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

+ Nicole Greene Federal Representative

+ Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Speakers for Upcoming Meetings

Background and Methods Sections of the Subcommittee Report

Introduction of Another Two-Tier Diagnostic Assay for Lyme Disease

Next Meeting

Adjournment

Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 4

August 30, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

+ Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia V. Smith, Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

+ Nicole Greene Federal Representative

+ Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA ((Contractor Support)


Topic Areas Discussed

Presentation: Communicating about Tick-borne Diseases

Sue Partridge, MPH, Associate Director for Communications, Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention

Presentation Q & A Session

Addressing accuracy issues in CDC content

Officially changing the name of the Subcommittee to "Training and Education, Access to Care, and Reimbursement"

ZEUS ELISA diagnostic test for Lyme Disease

Upcoming Speakers

Next Meeting

Adjournment


Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 5

September 13, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

+ Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia V. Smith, Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)


+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

+ Nicole Greene Federal Representative

+ Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Presentation: In Guidelines We Trust? Not All Are Created Equal

Elizabeth Maloney, MD

Presentation Q & A Session

Presentation of Patient Stories

Subcommittee member Doug Fearn, President, Lyme Disease Association of Southeastern Pennsylvania, Inc.,

Review and Discussion of Meeting 10 of the Tick-Borne Disease Working Group

Subcommittee Timeline and Upcoming Tick-Borne Disease Working Group Meetings

Upcoming Speaker Request

Schedule of Upcoming Meetings

Division of Work

Next Meeting

Adjournment


Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 6

September 27, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

+ Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia (Pat) V. Smith, Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

+ Debbie Seem, RN, MPH Federal Representative

+ Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Presentation: All-Cost Analysis of Lyme Disease and Chronic Lyme/Post-Treatment Lyme Disease (CLD/PTLD)

John Aucott, MD, Associate Professor of Medicine; Director, Lyme Disease Research Center, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine

Presentation Q & A Session

Announcements

Methods section update

Background section update

Results and Potential Actions writing group updates

Graphics/images and tables in the subcommittee report

Next Meeting

Adjournment

Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 7

October 11, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

+ Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia (Pat) V. Smith, Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

+ James Berger, MS, Designated Federal Officer

+ Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Background section update

Motion, vote, decision: Lorraine Johnson made a motion to approve the submission of the Background section to the Tick-Borne Disease Working Group once the changes discussed are incorporated. Betty seconded the motion. The Training, Education, Access to Care, and Reimbursement Subcommittee voted unanimously to approve the submission.

Presentation: Lyme Disease—An Attorney's Perspective

Elliott B. Pollack, Esq., Pullman & Comley, LLC

Presentation Q & A Session

Announcements

Collaborating on documents and version control

Results and Potential Actions writing group updates

Next Meeting

November 1, 2019 from 2:00pm to 4:00pm

Adjournment

Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 8

October 18, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

+ Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

x Patricia (Pat) V. Smith, Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

x James Berger, MS, Designated Federal Officer

x Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Presentation: Using Claims Data to Illuminate Trends and Patterns in Lyme Disease

Robin Gelburd, President, and Ali Russo, Chief Information Officer, FAIRHealth

Presentation Q & A Session

Follow-up discussion of the presentation

Review of Results and Potential Actions guidance document

Presentation of Timeline template

Writing Group Updates

Sharepoint demonstration

Next Meeting

Adjournment

Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 9,

November 1, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

+ Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia (Pat) V. Smith,Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

x Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

x James Berger, MS, Designated Federal Officer

+ Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Presentation: Testimony to the Department of Health and Human Service, Tick-Borne Disease Working Group: Training, Education, Access to care, and Reimbursement Subcommittee

Colonel Nicole Malachowski, USAF, Ret.

Presentation: The Military Health System: Overview, Observations, Opportunities

Megan DuLaney, Senior Interagency Liaison, Henry M. Jackson Foundation for the Advancement of Military Medicine in support of DOD and Center for Health Engagement, Uniformed Services University for the Health Sciences

Q & A for both presentations

Results and Potential Actions writing group updates

Review of next steps

Next Meeting

Adjournment

Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 11

December 6, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

+ Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia (Pat) V. Smith, Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

x James Berger, MS Designated Federal Officer

+ Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Review of current status and upcoming meetings

Addressing divergent perspectives in the subcommittee report

Review of public comments received by the Tick-Borne Disease Working Group

Discussion of revisions to the Results and Potential Actions section

Update on phone call with CDC lawyer

Next steps

Review of the Background section and discussion of a Big Picture Summary

Next Meeting

Adjournment

Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 12

December 20, 2019

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

x Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia (Pat) V. Smith, Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

+ James Berger, MS Designated Federal Officer

x Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Review and discussion of the complete draft Subcommittee Report

Review and discussion of Priorities and Potential Actions

Discussion of the subcommittee report presentation to the Tick-Borne Disease Working Group

Next steps

Next Meeting

Adjournment

Training and Education, Access to Care, and Reimbursement Subcommittee, Meeting Summary 13

January 3, 2020

Attendance

+ Present

x Not Present


Working Group and Subcommittee Members

x Commander Rebecca Bunnell, MPAS, PA-C Subcommittee Co-Chair (Regular Government Employee)

+ Patricia (Pat) V. Smith, Subcommittee Co-Chair (Patient Advocate)

+ Megan DuLaney, MS (Patient Representative)

+ Doug Fearn (Patient Advocate)

+ Lorraine Johnson (Health Care Policy Expert)

+ Elizabeth (Betty) Maloney, MD (Health Care Provider)

+ Sheila M. Statlender, PhD (Health Care Provider)


Non-Member Coordination and Support

+ James Berger, MS Designated Federal Officer

+ Jennifer Gillissen (Contractor Support)

+ Cat Thomson, MA (Contractor Support)


Topic Areas Discussed

Review and discussion of the complete draft Subcommittee Report (version 3)

Vote on Potential Actions

Vote on Final Report

Announcement

Next steps

Next meeting

Adjournment

Appendix C: Nine-item CDC HRQoL Health Days Measurements for Persistent Lyme Disease Patients

Variable Mean (S.D.)
4-item Healthy Days Core Module
General health rating (Excellent = 1, Poor = 5) 4.0 (1.0)
Physical health not good (# days out of 30) 20.1 (10.5)
Mental health not good (# days out of 30) 15.5 (10.8)
Physical or Mental health limited usual activities (# days out of 30) 16.8 (11.2)
5-item Healthy Days Symptoms Module
Pain limited activities (# days out of 30) 16.5 (11.7)
Sad, blue or depressed (# days out of 30) 12.4 (10.5)
Worried, tense or anxious (# days out of 30) 15.8 (11.1)
Not enough rest (# days out of 30) 20.3 (10.1)
Very healthy/full of energy (# days out of 30) 3.5 (6.2)

Source: Johnson, J. Wilcox, S., Mankoff, J., & Stricker, R. B. (2014) Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey. PeerJ, PubMed: 24749006. doi: 10.7717/peerj.322/table-3

Appendix D: Extensive Lyme Disease Symptom List from Peer Reviewed Literature

General

Fever

Night sweats

Fatigue, lack of endurance

Unexplained weight gain/loss

Generalized, unprovoked pain

Migratory pain


Head, Face, Neck

Headache, mild or severe

Facial flushing

Pressure in head

Jaw pain or stiffness

Unexplained hair loss

Dental problems/pain (unexplained)

Facial muscle fasciculations

Stiff or painful neck

Facial paralysis (Bell's Palsy)

Sore throat, hoarseness

Tingling of nose, tongue, cheek


Eyes/Vision and Ears/Hearing

Diplopia or blurry vision

Difficulty with night vision

Increased floating spots

Pain in eyes, or swelling around eyes

Photophobia

Flashing lights/Peripheral waves/phantom images

Change in color vision

Decreased hearing in one or both ears

Tinnitus

Pain in ears, hyperacussis

Auditory hallucinations


Gastrointestinal and Genito-urinary Systems

Nausea/pain/GERD

Recurrent vomiting

Diarrhea/ constipation

Irritable bladder or interstitial cystitis

Testicular or pelvic pain

Decreased libido

Unexplained menstrual irregularity

Unexplained galactorrhea


Musculoskeletal System

Bone pain, joint pain or swelling

Carpal tunnel syndrome

Stiffness of joints, back, neck

Frequent tendonitis, lateral epicondylitis

Myalgia or cramps, muscle spasms

Sore soles, especially in am


Respiratory and Circulatory Systems

Shortness of breath, cough

Endocarditis, myocarditis, heart failure

Chest pain or rib soreness

Peripheral vascular abnormalities

Rhythm disturbances- PVCs, PACs,

SVTs, palpitations, heart block


Psychological

Mood swings, irritability

Patient feels like he/she is "losing my mind"

Over-emotional reactions, cries easily

Depression

Bi-polar disorder

Panic attacks, anxiety

Obsessive-compulsive disorder

Psychosis


Mental Capability

Memory loss (short or long term)

Disorientation (getting or feeling lost)

Confusion, difficulty in thinking

Apraxia

Difficulty concentrating or reading

Dementia


Nervous System

Burning, stabbing, aching or shock sensations

Lightheadedness, syncope

Paresthesias

Increased motion sickness

Peripheral neuropathies

Abnormalities of vision, hearing, smell, taste or touch

Muscle weakness

Muscle atrophy

Muscle fasciculations

Speech difficulty (slurred or slow)

Stammering speech

Word searching, misspeaking

Poor balance

Dizziness

Difficulty walking, gait problems

Tremors

Seizures

Sleep problems: excessive sleep, insomnia, sleep apnea, narcolepsy, unusual sleep behaviors


Symptom References

Individual symptoms listed on the symptom checklist have been validated by one or more of the references listed below.

Ackermann, R., Rehse-Kupper, B., Gollmer, E., & Schmidt, R. (1988). Chronic neurologic manifestations of erythema migrans borreliosis. Annals of the New York Academy of Sciences, 539, 16-23. doi: 10.1111/j.1749-6632.1988.tb31834.x

Arav-Boger, R., Crawford, T., Steere, A. C., & Halsey, N. A. (2002). Cerebellar ataxia as the presenting manifestation of Lyme disease. Pediatric Infectious Disease Journal, 21(4), 353-6. Retrieved from https://journals.lww.com/pidj/Fulltext/2002/04000/Cerebellar_ataxia_as_the_presenting_manifestation.21.aspx

Bhambhani, N., Disla, E., & Cuppari, G. (2006). Lyme disease presenting with sequential episodes of ruptured baker cysts. Journal of Clinical Rheumatology, 12(3), 160-162. doi: 10.1097/01.rhu.0000222056.09133.83

Bloom, B. J., Wyckoff, P. M., Meissner, H. C., & Steere, A.C. (1998). Neurocognitive abnormalities in children after classic manifestations of Lyme disease. Pediatric Infectious Disease Journal, 17(3), 189-96. doi: 10.1097/00006454-199803000-00004

Cassarino, D. S., Quezado, M. M., Ghatak, N. R., & Duray, P. H. (2003). Lyme-associated parkinsonism: a neuropathologic case study and review of the literature. Archives of Pathology and Laboratory Medicine Online, 127(9), 1204-6. doi: 10.1043/1543-2165(2003)127<1204:LPANCS>2.0.CO;2

Chancellor, M. B., McGinnis, D. E., Shenot, P. J., Kiilholma, P., Hirsch, I. H. (1993). Urinary dysfunction in Lyme disease. Journal of Urology, 149(1), 26-30. doi: 10.1016/s0022-5347(17)35989-x

Dinerman, H., & Steere, A. C. (1992). Lyme disease associated with fibromyalgia. Annals of Internal Medicine, 117, 281-5. doi: 10.7326/0003-4819-117-4-281

Duray, P. H., & Steere, A. C. (1988). Clinical pathologic correlations of Lyme disease by stage. Annals of the New York Academy of Sciences, 539, 65-79. doi: 10.1111/j.1749-6632.1988.tb31839.x

Faller, J., Thompson, F., & Hamilton W. (1991). Foot and ankle disorders resulting from Lyme disease.

Foot and Ankle International, 11(4), 236-238. doi: 10.1177/107110079101100411

Fallon, B. A., Kochevar, J. M., Gaito, A., & Nields, J. (1998). The underdiagnosis of neuropsychiatric Lyme disease in children and adults. Psychiatric Clinics of North America, 21(3):693-703. doi: 10.1016/s0193-953x(05)70032-0

Fallon, B. A., & Nields, J. A. (1994). Lyme disease: a neuropsychiatric illness. American Journal of Psychiatry, 151(11), 1571-83. doi: 10.1176/ajp.151.11.1571

Fallon, B. A., Nields, J. A., Liegner, K., DelBene, D., & Liebowtitz, M. R. (1992). The neuropsychiatric manifestations of Lyme borreliosis. Psychiatric Quarterly, 63(1):95-117. doi: 10.1007/bf01064684

Gasser, R., Horn, S., Reisinger, E., Fischer, L, Pokan R. Wendelin, I., & Klein, W. (1998). First description of recurrent pericardial effusion associated with Borrelia burgdorferi infection. International Journal of Cardiology, 64(3), 309-310. doi: 10.1016/s0167-5273(98)00046-1

Halperin, J. J, Little, B. W, Coyle, P. K, & Dattwyler, R. J. (1987). Lyme disease: cause of a treatable peripheral neuropathy. Neurology, 37(11), 1700-6. doi: 10.1212/wnl.37.11.1700

Halperin, J. J, Volkman, D. J, Luft, B. J, & Dattwyler, R. J. (1989). Carpal tunnel syndrome in Lyme borreliosis. Muscle & Nerve, 12(5), 397-400. doi: 10.1002/mus.880120510

Halperin, J. J, Kaplan, G. P, Brazinsky, S., Tsai TF, Cheng T, Ironside A, ... Luft, B. J. (1990). Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease. Archives of Neurology (JAMA), 47(5), 586-94. doi: 10.1001/archneur.1990.00530050110021

Halperin, J. J. (1995). Neuroborreliosis. American Journal of Medicine, 98(4A), 52S-56S. doi: 10.1016/s0002-9343(99)80044-8

Haupl, T., Hahn, G., Rittig, M., Krause A, Schoerner C, Schonherr, U., ... Burmester, G. R. (1993). Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Arthritis & Rheumology, 36(11), 1621-6. doi: 10.1002/art.1780361118

Horowitz, H.W., Sanghera, K., Goldberg, N., Pechman, D., Kamer, R., Duray, P., & Weinstein, A. (1994). Dermatomyositis associated with Lyme disease: case report and review of Lyme myositis. Clinical Infectious Diseases, 18(2), 166-71. doi: 10.1093/clinids/18.2.166

Karma, A., Seppala, I., Mikkila, H., Kaakkola, S., Viljanen, M., & Tarkkanen, A. (1995). Diagnosis and clinical characteristics of ocular Lyme borreliosis. American Journal of Ophthalmology, 119(2), 127-35. doi: 10.1016/s0002-9394(14)73864-4

Kirsch, M., Ruben, F. L., Steere, A. C., Duray, P. H., Norden, C. W., & Winkelstein, A. (1988). Fatal adult respiratory distress syndrome in a patient with Lyme disease. JAMA, 259(18), 2737-9. PMID: 3357244

Krupp, L. B, Masur, D., Schwartz, J., Coyle, P. K., Langenbach, L. J., Fernquist, S. K., ... Halperin, J.J. (1991). Cognitive functioning in late Lyme borreliosis. Archives of Neurology, 48(11), 1125-9. doi: 10.1001/archneur.1991.00530230033017

Lader, E. (1990). Lyme disease misdiagnosed as a temporomandibular joint disorder. Journal of Prosthetic Dentistry, 63(1), 82-5. doi: 10.1016/0022-3913(90)90272-e

Lo, R., Menzies, D. J., Archer, H., & Cohen, T. J. (2003). Complete heart block due to Lyme carditis. Journal of Invasive Cardiology, 15(6), 367-9. PMID: 12777681

Logigian, E. L., Johnson, K. A., Kijewski, M. F., Kaplan, R. F., Becker, J. A., Jones, K. J., ... Steer, A. C. (1997). Reversible cerebral hypoperfusion in Lyme encephalopathy. Neurology, 49(6), 1661-1670. doi: 10.1212/wnl.49.6.1661

Logigian, E. L., Kaplan, R. F., & Steer, A. C. (1990). Chronic neurologic manifestations of Lyme disease. New England Journal of Medicine, 323(21), 1438-44. doi: 10.1056/NEJM199011223232102

MacDonald, A. B. (1988). Concurrent neocortical borreliosis and Alzheimer's disease: Demonstration of a spirochetal cyst form. Annals of the New York Academy of Sciences, 539, 468-470. doi: 10.1111/j.1749-6632.1988.tb31909.x

Mikkila, H.O., Seppala, I. J., Viljanen, M. K., Peltomaa, M. P., & Karma, A. (2000). The expanding clinical spectrum of ocular Lyme borreliosis. Ophthalmology, 107(3), 581-7. doi: 10.1016/s0161-6420(99)00128-1

Mormont, E., Esselinckx, W., De Ronde, T., Hanson, P., Deltombe, T., & Laloux, P. (2001). Abdominal wall weakness and lumboabdominal pain revealing neuroborreliosis: a report of three cases. Clinical Rheumatology, 20(6), 447-50. doi: 10.1007/s100670170015

Moscatello, A. L., Worden, D. L., Nadelman, R. B., Wormser, G., & Lucente, F. (1991). Otolaryngologic aspects of Lyme disease. Laryngoscope, 101(6 Pt 1), 592-5. doi: 10.1288/00005537-199106000-00004

Nord, J. A., & Karter, D. Lyme disease complicated with pseudotumor cerebri. (2003). Clinical Infectious Diseases, 37(2), E25-6. doi: 10.1086/375691

Oksi, J., Marjamaki, M., Nikoskelainen, J., & Viljanen, M. K. (1999). Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme Borreliosis. Annals of Medicine, 31(3), 225-32. doi:

Oksi, J., Voipio-Pulkki, L. M, Uksila, J., Pulkki, K., Laippala, P., & Viljanen, M. K. (1997). Borrelia burgdorferi infection in patients with suspected acute myocardial infarction. Lancet, 350(9089), 1447-8. doi: 10.1016/s0140-6736(05)64208-0

Pachner, A. R., & Steere, A. C. (1985). The triad of neurological manifestations of Lyme disease: meningitis, cranial neuritis, and radiculoneuritis. Neurology, 35(1), 47-53. doi: 10.1212/wnl.35.1.47

Pachner, A. R., & Steiner, I. (2007). Lyme neuroborreliosis: infection, immunity, and inflammation. Lancet Neurology, 6, 544–52. doi: 10.1016/S1474-4422(07)70128-X

Reik, L., Steere, A. C., Bartenhagen, N. H., Shope, R. E., & Malawista, S. E. (1979). Neurologic abnormalities of Lyme disease. Medicine, 58(4), 281-94. doi: 10.1097/00005792-197907000-00001

Richardson, H., Birchall, J. P., Hill, J., & McMaster, T. (1994). Should we routinely screen for Lyme disease in patients with asymmetrical hearing loss? British Journal of Audiology, 28(2), 59-61. doi: 10.3109/03005369409077915

Riedel, M., Straube, A., Schwarz, M. J., Wilske, B. M., & Muller, N. (1998). Lyme disease presenting as Tourette's syndrome. Lancet, 351(9100), 418-419. doi: 10.1016/S0140-6736(05)78357-4

Rosenhall, U., Hanner, P., & Kaijser, B. (1988). Borrelia infection and vertigo. Acta Oto-Laryngologica, 106(1-2), 111-6. doi: 10.3109/00016488809107377

Shadick, N. A., Phillips, C. B., Logigian, E. L., Steere, A. C., Kaplan, R. F., Berardi, V.P., ... Liang, M. H. (1994). The long-term clinical outcomes of Lyme disease. Annals of Internal Medicine, 121, 560-567. doi: 10.7326/0003-4819-121-8-199410150-00002

Shamim, E. A., Shamim, S. A., Liss, G., Nylen, E., Pincus, J. H., & Yepes M. (2005). Constipation heralding neuroborreliosis: an atypical tale of 2 patients. Archives of Neurology, 62(4), 671-3. doi: 10.1001/archneur.62.4.671

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Content last reviewed on January 24, 2020