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•
Office of the Assistant Secretary for Health
Tick-Borne Disease
Working Group
2018 Report to Congress
Information and opinions in this report do not necessarily reflect the opinions of each member of the Working Group,
the U.S. Department of Health and Human Services, or any other component of the Federal Government.
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Table of Contents
Executive Summary . . . . . . . . . . . 1
Chapter 1: Background . . . . . . . . 5
Congressional Action . . . . . . . . . . . . . . 5
Establishment of the Tick-Borne
Disease Working Group . . . . . . . . . . . . 6
Report Structure . . . . . . . . . . . . . . . . . 7
Chapter 2: Methods of the
Working Group . . . . . . . . . . . . . . . 9
Subcommittees. . . . . . . . . . . . . . . . . . . 9
Federal Inventory . . . . . . . . . . . . . . . . 10
Public Input. . . . . . . . . . . . . . . . . . . . . 10
Minority Responses . . . . . . . . . . . . . . 12
Chapter 7: Access to Care,
Patient Outcomes . . . . . . . . . . . 59
Chapter 8: Looking Forward . . . 77
Chapter 9: Conclusion . . . . . . . . 83
Appendices . . . . . . . . . . . . . . . . 85
Appendix A. Tick-Borne Disease
Working Group . . . . . . . . . . . . . . . . . . 85
Chapter 3: Epidemiology
and Ecology . . . . . . . . . . . . . . . . 13
Chapter 4: Prevention . . . . . . . . 23
Chapter 5: Diagnosis . . . . . . . . . 36
Chapter 6: Treatment . . . . . . . . 45
Appendix B. Acronyms and
Abbreviations . . . . . . . . . . . . . . . . . . . 87
Appendix C. . . . . . . . . . . . . . . . . . . . . . 89
C.1: U.S. Tick-Borne Diseases and
Associated Pathogens . . . . . . . . . . . . . 89
C.2: Annual Reported Tick-Borne Disease
Cases by Year, U.S.: 2004-2016 . . . 89
Appendix D. Federal Inventory . . . . . . 90
Appendix E.
21st Century Cures Act
. 93
Appendix F. Working Group Charter . 96
Appendix G. References . . . . . . . . . . 100
Contributions
U.S. Department of Health and Human Services
James J. Berger, MS, MT (ASCP), SBB
Working Group Members
John N. Aucott, MD (Chair)
Kristen T. Honey, PhD, PMP (Vice-Chair)
Captain Estella Jones, DVM
Lise E. Nigrovic, MD, MPH
Allen L. Richards, PhD
Robert Sabatino
B. Kaye Hayes, MPA
Captain Scott Cooper, PA, MMS
Dennis M. Dixon, PhD
Richard I. Horowitz, MD
Wendy A. Adams, MBA
Charles Benjamin (Ben) Beard, PhD
Vanila M. Singh, MD, MACM
Patricia V. Smith
Robert Smith, MD, MPH
DISCLAIMER:
Readers should not consider the report or any part of it to be guidance or instruction regarding the
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diagnosis, care, or treatment of tick-borne diseases or to supersede in any way existing guidance.
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Executive
Summary
ICK-BORNE DISEASES
have rapidly become a serious and growing threat to
public health in the United States. Despite many scientific unknowns, experts
agree that the incidence and distribution of tick-borne diseases are increasing.
Over the past 25 years, reports of Lyme disease have increased steadily with estimated
annual cases approximating 300,000 (Hinckley et al., 2014; Nelson et al., 2015). The
number of U.S. counties now considered to be of high incidence for Lyme disease has
increased by more than 300% in the Northeastern states and by approximately 250% in
the North-Central states. The Centers for Disease Control and Prevention (CDC) currently
recognizes 18 tick-borne pathogens in the United States. However, researchers and
health care practitioners continue to discover emerging disease agents and new medical
conditions associated with tick bites.
While most Lyme disease patients who are
diagnosed and treated early can fully recover,
10 to 20% of patients suffer from persistent
symptoms, which for some are chronic and
complications. Today, available diagnostic tests
can be inaccurate and complex to interpret,
especially during the earliest stage of infection
infectious disease settings, tests to directly
such as cultures or tissue biopsies, are not
T
disabling. Studies indicate that Lyme disease
costs approximately $1.3 billion each year in
A comprehensive understanding of the full
direct medical costs alone in the United States.
economic and societal cost remains unknown. It is
likely orders of magnitude higher and potentially
a $50- to $100-billion-dollar problem for the
(Vanderhoof & Vanderhoof-Forschner, 1993;
Zhang et al., 2006).
United States, although more research is needed
when treatment is most effective. Unlike in other
measure the presence of the infecting organism,
available for some tick-borne diseases such as
the tools needed to diagnose; and without an
to provide early treatment.
Lyme disease. This leaves physicians without
accurate diagnosis, it is challenging for physicians
Persistent symptoms after treatment of Lyme
unknown and debated. There are currently
Prompt diagnosis and treatment of tick-borne
diseases are crucial to prevent long-term
disease can be severe, yet their cause(s) remains
no uniformly accepted or validated treatment
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LYME DISEASE
Lyme disease has increased by more than
300%
in the
Northeastern states
and by approximately
250%
in the
North-Central states
.
options for patients with these chronic symptoms.
As a result, uncertainty surrounding appropriate
clinical care has led to polarization within the
medical community, and patients are often left
resolution or even symptom management
suffering in limbo without a clear path to illness
(Rebman et al., 2017). The lack of a clear path
for treatment of persistent symptoms in some
patients with Lyme disease and other tick-borne
diseases not only amplifies patient suffering but
also significantly increases health care costs.
To understand tick-borne diseases, we need
to first understand tick ecology and how
ticks transmit diseases. Due to the lack of a
coordinated national surveillance program,
currently there are significant gaps in information
on local distribution of infection-causing ticks,
especially in regions beyond the Northeast
approaches for tick, animal, and human
and Upper Midwest. Nationwide, standardized
surveillance are needed to understand the
geographic distribution of infectious ticks in order
to understand the spread of disease and predict
and systematic studies are also needed to
where people are at risk. Advanced technologies
This report outlines an integrated, multipronged
posed by tick-borne diseases in the United
Background; Methods; Epidemiology and
approach to the growing public health challenges
States. It contains nine main chapters, including
Ecology; Prevention; Diagnosis; Treatment;
Access to Care, Patient Outcomes; Looking
Forward; and Conclusion. The Background and
rapidly identify new disease agents that pose
emergent risks to public health, including to the
blood supply. Given that seven new tick-borne
the United States since 2004, this is a priority.
Effective prevention relies on multipronged
pathogens have been shown to infect people in
Methods chapters explain how the report was
challenges, key issues, and recommendations
specific to the broader topics.
developed. The other chapters present the main
a comprehensive understanding of the biological
strategies. To reduce exposure to ticks, we need
drivers behind the continued spread of tick-borne
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diseases, so that effective tick- and infection-
control methods can be identified and validated.
changes are also required to help patients already
suffering from tick-borne diseases; to protect
them from discrimination; and to address the
Need also exists for the transparent development
disease, the most common of these illnesses. In
of a safe, effective human vaccine to prevent Lyme
inflexible, inconsistent, and often unaffordable
care that patients frequently encounter in the
current health care system.
Increased Federal funding, prioritization, and
trends associated with tick-borne diseases.
the absence of effective strategies for controlling
ticks and blocking the transmission of tick-borne
pathogens, it is crucial to educate health care
professionals and the public about tick-borne
protection from tick bites. Outreach efforts to
physicians and the public must be expanded
at both the Federal and state level to ensure
Clinical research priorities must include
leadership are needed to reverse the alarming
Despite several decades of research, prevention,
and educational activities, Federal funding for
tick-borne diseases is less per new surveillance
disease prevention, especially best practices for
promote prevention and raise awareness among
case than that of other diseases. The U.S. National
and $20,293, respectively, per new surveillance
accurate, effective, and consistent messaging.
the development of new technologies and
Institutes of Health (NIH) and CDC spend $77,355
case of HIV/AIDS, and $36,063 and $11,459 per
new case of hepatitis C virus, yet only $768 and
funding for tick-borne diseases today is orders
of magnitude lower, compared to other public
problem has grown.
$302 for each new case of Lyme disease. Federal
approaches to improve diagnosis of tick-borne
diseases and monitor response to treatment.
There is a critical need for sensitive and specific
direct-pathogen detection strategies that are
broad enough to cover multiple potential tick-
health threats, and it has failed to increase as the
It is also essential that funding and resources
be allocated to support a comprehensive,
interagency program to address the mounting
pathogenesis of ongoing symptoms after initial
treatment should be a clinical research priority.
roles of immunologic responses, bacterial
borne pathogens. Understanding the etiology and
Investigations are also needed into the potential
persistence, and coinfecting pathogens in order
improve outcomes and care for patients with
ongoing symptoms.
Americans need help, yet progress has been
level and by divisions within the field. The
challenges identified in this report. All research,
prevention, and education initiatives should be
who suffer disproportionately from tick-borne
diseases. Patients whose lives continue to be
inclusive of special populations such as children,
to design and test new therapies and, ultimately,
disrupted by the lasting effects of these illnesses
are counting on emerging scientific research,
evidence-based policy, and the health care
hampered by a lack of attention at the Federal
recommendations in this 2018 report of the Tick-
Borne Disease Working Group represent a long-
diseases in this country. However, immediate
term investment in tackling the rise of tick-borne
establishment—including the Federal Government
provide solutions. We must act now.
with Congressional and Executive leadership—to
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Figure1: Federal Funding for Selected Infectious Diseases
Disease
Reported
a
Annual
Cases in the U.S.
(year)
2,967 (2016)
1
38,782 (2016)
2
9.2-35.6 million
3
(2010-2011 to
2016-2017 seasons)
59,646 (2016)
4
36,429 (2016)
4
291,430 – 437,150
(2016)
e
NIH FY 2017
Appropriations
b
$107 million
$3 billion (9.5% of
total NIH budget)
$263 million
CDC FY 2017
Appropriations
b
$34 million
$787 million
(domestic only)
$187 million
Hepatitis C
HIV/AIDS
Seasonal
Influenza
c
Vector-Borne
Diseases
d
$46 million
$26 million
Lyme Disease
$28 million
$11 million
Federal funding for each new case of Lyme disease is small relative to other diseases.
a.
Reported cases of many diseases and conditions are substantially lower than total estimated
cases. This has been documented for hepatitis, influenza, and Lyme disease, among other dis-
eases and conditions.
b.
Rounded to the nearest million.
c.
CDC estimates for the national burden of seasonal influenza represent a range from low to high
over seven seasons.
d.
Lyme disease has a separate funding line at CDC and is not included in “vector-borne diseases”;
reported cases of Lyme disease are excluded from this row.
e.
Lyme disease estimates are based on surveillance case reporting to CDC multiplied by an
8- to 12-fold factor to account for estimated underreporting.
1.
https://www.cdc.gov/hepatitis/statistics/2014surveillance/commentary.htm
2.
https://www.cdc.gov/hiv/statistics/overview/index.html
3.
https://www.cdc.gov/flu/about/disease/burden.htm
4.
https://www.cdc.gov/mmwr/volumes/67/wr/mm6717e1.htm
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Chapter 1
Background
Diseases transmitted by ticks are a serious and
growing public health concern. At least 20 known
conditions can result from tick bites, including
13 illnesses caused by at least 18 tick-borne
infectious pathogens, as well as other conditions
such as alpha-gal allergy. Over the past 25 years,
reports of Lyme disease to CDC have increased
steadily (see Figure 2). Lyme disease is the most
common tick-borne disease with approximately
300,000 new cases diagnosed in the United
States each year (see Figure 3; Hinckley et al.,
2014; Nelson et al., 2015). As tick populations
continue to grow and infected ticks expand
geographically, the threat to human health
intensifies.
understood and often results in significant
deterioration in the quality of life of patients and
their caregivers.
borne diseases, paired with loss of productivity,
represent a significant economic burden for
individual patients, their families, and the
American public. The recommendations in this
report are intended to address these and many
other issues identified by the Tick-Borne Disease
Working Group as having a deleterious effect on
tick-borne disease sufferers and public health.
The expense of diagnosis and treatment of tick-
Tick-borne diseases can cause severe health
complications and are often difficult to diagnose.
Congressional Action
In December 2016, Congress passed the
21st
Century Cures Act
(see Appendix E), designed
to promote new health care innovations for
addressing an array of public health issues.
Section 2062 of the legislation pertains to
The current diagnostic approach relies on clinical
diagnosis and serological measurement of
antibody responses. However, the limitations of
the tests, coupled with scientific uncertainty and
gaps in knowledge and education about how
to use them, frequently result in misdiagnosed
tick-borne diseases. Lyme disease may be
complicated by simultaneous infection with
other tick-borne pathogens, such as
Babesia
or
Anaplasma,
a condition called coinfection.
Moreover, many patients experience chronic and
recurring symptoms after antibiotic treatment
for Lyme disease, other tick-borne diseases,
and coinfections. This chronic illness is poorly
advancing research on tick-borne diseases. The
Act requires the U.S. Department of Health and
Human Services (HHS) Secretary to establish a
Federal advisory committee to review current
research efforts and help identify priorities related
to tick-borne disease. In response, the HHS
Secretary formed the Tick-Borne Disease Working
Group (hereafter “Working Group”) to identify
gaps in research, education, prevention, and
access to care.
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Figure 2: Tick-Borne Diseases in the
United States, 2004-2016
Establishment of the
Tick-Borne Disease
Working Group
The Working Group represents diverse
stakeholders, including Federal and
public members representing various
perspectives and areas of expertise
(see Appendix A). The Working Group
comprises 14 individuals appointed
by the HHS Secretary in December
2017. Seven are public voting
Top 20%
(more than 12,856)
2nd 20%
(2,141-12,856)
3rd 20%
(1,099-2,140)
4th 20%
(183-1,098)
Bottom 20% of states
(117-182)
None: 0
Maps show case counts, not disease risk.
N= 17,029
members and seven are Federal
voting members. Public members
include scientists, researchers,
physicians, patients and their family
members, and patient advocates.
Federal appointees to the Working
Group represent HHS, the Department
of Defense (DoD), and the Office of
Management and Budget (OMB).
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A charter approved by the HHS
Secretary (see Appendix F) governs
the Working Group’s structure and
activities. In compliance with
Federal
Advisory Committee Act
(FACA)
requirements, Working Group
meetings are open to the public, and
N= 36,429
Geographic Expansion of Lyme Disease in Upper Midwest, Northeast, and
Mid-Atlantic States (Lyme disease in western states not shown)
Chair and Vice-Chair, appointed by
the HHS Secretary, conduct Working
Group meetings.
meeting materials and summaries are
posted publicly. The Working Group
Tick-borne diseases affect the entire population in the continental United States. The
geographic range of Lyme disease cases has expanded since its first appearance in
Lyme, Connecticut, in 1975 and has consistently spread northward, southward, and
westward. The high-risk regions of the Northeast and Upper Midwest appear to be
converging over time in the Ohio River Valley to form one contiguous range. Lyme
disease on the West Coast (not shown in the 2001 and 2016 maps) continues to be
an important concern, as are risks from other tick-borne diseases.
1
The Office of Management and Budget transitioned its Federal voting seat in June 2018 to the HHS Office
of the Chief Technology Officer within the Immediate Office of the Secretary, which is more aligned with the
mission of this Working Group’s charter.
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Report Structure
This report describes a potential path forward for addressing the spread of tick-borne diseases. It is
structured according to the priority areas identified by the Working Group, which are:
•
•
•
Epidemiology and Ecology;
Prevention;
Diagnosis;
•
•
•
Treatment;
Access to Care and Patient Outcomes; and
Looking Forward.
Most sections provide a background overview, discuss controversies surrounding the topic, highlight
stories from patients about their experiences, and outline research related to tick-borne diseases as
well as current gaps in Federal research and activities. Sections also present recommendations to the
U.S. Congress and the HHS Secretary for addressing tick-borne diseases.
Figure 3. Annual Number of Lyme Disease Cases
Across all 50 states and over time, Lyme disease is a growing public health threat with approximately 300,000 new cases each
year, based on case reporting to CDC multiplied by an 8- to 12-fold factor to account for estimated underreporting (Hinckley et
al., 2014; Nelson et al., 2015). Most Lyme disease patients diagnosed and treated early can fully recover, yet an estimated 10 to
20% of patients suffer from persistent symptoms that are potentially chronic and disabling. Using a research definition of and data
on post-treatment Lyme disease syndrome (PTLDS), the number of PTLDS cases may approach 30,000-60,000 each year in the
United States. A precise definition does not yet exist for chronic Lyme disease, so uncertainty is extremely large. The number of
U.S. patients with a clinical diagnosis of chronic Lyme disease may be larger, but is unknown.
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Patient
Stories
Lyme disease is most often identified at its earliest stage when characteristic skin lesions are frequently present and
an accurate early diagnosis is possible. With early diagnosis and appropriate antibiotic treatment, the prognosis for
Lyme disease and other tick-borne infections can be excellent. In the majority of patients, early treatment can
resolve the acute illness and prevent later manifestations that could occur without timely treatment. In contrast,
Ruben Lee Sims’ case illustrates what can go wrong when early diagnosis is missed. Such cases do not portray the
typical course of most Lyme disease cases but do serve to emphasize the critical importance of accurate diagnosis
and early treatment, as well as the complexity of chronic illness that can result from untreated Lyme disease.
Ruben Lee Sims
Ruben Lee Sims is a Vietnam Veteran who served our country, earned the
Vietnam War Campaign Ribbon, and was recognized as the “USAF Comptrollers
Top Enlisted Management Analyst of the Year” in 1977. Five years later, multiple
tick bites, however, derailed his life. The U.S. Department of Veterans Affairs
(VA) was not equipped to diagnose Lyme disease at that time. The military
discharged Mr. Sims in 1984, citing “hypochondriasis with psychogenic pain
disorder.” In 1985, a non-military doctor in San Diego suspected Lyme disease.
However, because Mr. Sims had not traveled to New England, the doctor
decided that the symptoms could not be caused by Lyme disease. In the words
of Mr. Sims, an American hero:
“I
have had Lyme disease while under the direct care of both military and
VA healthcare systems. I was misdiagnosed for over three decades and left
untreated for Lyme disease. This led to homelessness. Survived attempted
suicides. Untreated patients can lose everything, as I did, and become part of
the unemployed, under-employed, disabled, and homeless populations that die
by suicide and commit violent acts related to the psychological impact of Lyme
disease. This is a treatable condition. Please review all emerging science and help
prevent Lyme-disease-related deaths and suicides.”
Mr. Sims’ psychogenic pain is now confirmed as a symptom of Lyme disease,
based on VA’s diagnosis. With accurate diagnosis and appropriate treatment, Mr.
Sims’ physical and mental symptoms have resolved. He shares his story to reach
and help other Veterans, especially homeless Veterans, who may be affected by
tick-borne diseases.
Ruben Lee Sims
Disabled United States Vietnam
Veteran
Lyme Disease Advocate
Moreno Valley, California
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Chapter 2
Methods of the
Working Group
The Working Group used information from the subcommittee reports, the Federal inventory of
activities, public comments, patient testimonies, and the latest available science as a basis for
inventory, and the public comments received.
developing this report. This section reviews the subcommittees involved in this work, the Federal
Subcommittees
To leverage member expertise, balance a range
aspects of diagnosing, treating, and preventing
tick-borne diseases, in February 2018, the
subcommittees:
Working Group established the following six
Disease Vectors, Surveillance, and
Prevention;
Pathogenesis, Transmission, and Treatment;
Testing and Diagnostics;
Access to Care Services and Support to
Patients;
Vaccine and Therapeutics; and
Other Tick-Borne Diseases and
Coinfections.
of perspectives, and thoroughly examine several
from nine to 13 individuals, not including the
leadership team (that is, the Working Group
Chair, Vice-Chair, and Designated Federal Officer)
that oversaw progress of all six subcommittees.
Each subcommittee was led by two Co-Chairs,
at least one of whom was a public member
or non-government volunteer. Over a three-
month period, weekly subcommittee meetings
offered opportunities for open dialogue and
presentations from subject matter experts. Each
up into writing groups, and developed a report
to the Working Group that described current
efforts, gaps in research, and potential actions
•
•
•
•
•
•
subcommittee identified several priorities, broke
to address each priority. In drafting their reports,
the subcommittees compiled information from
expert, advocate, and patient presentations;
collective subcommittee member knowledge;
and literature reviews. In finalizing their reports,
subcommittee members voted on the potential
by subcommittee members. During Public
their findings to the Working Group.
actions and included minority opinions expressed
Meeting 4, subcommittee Co-Chairs presented
Subcommittee membership encompassed
one patient or patient advocate on each
a broad range of perspectives, with at least
subcommittee. Subcommittee size ranged
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Methods of the Working Group
It is important to note that the subcommittees
Based on the Federal inventory results, the
Working Group identified the following needs
and gaps in research:
were established to conduct preparatory work for
the Working Group to consider, and their work
Group. For example, the subcommittees were
not required to follow the same transparency
process, each subcommittee drafted a report
potential actions for the Working Group to
requirements of the FACA. Through its work
process differed from the process of the Working
•
•
•
Improve early and accurate diagnosis and
treatment.
Strengthen national surveillance.
Understand the immunological mechanism
(for example, the pathogen-host
interaction) of immune protection for Lyme
disease and other tick-borne diseases.
Develop new rapid and accurate lab tests.
Develop antibiotic combination and/or
therapeutic options for treating acute and
persistent illness.
Encourage the development of strategic
plans for tick-borne disease Federal
investments.
Dedicate funding to tick-borne diseases
and evaluate related activities using
performance indicators and clear metrics
for success.
Characterize how tick-borne disease affects
U.S. national security, military readiness,
and the health and wellness of active
duty Servicemembers, Veterans, and their
families.
that synthesized relevant science and identified
consider. The subcommittees' reports were vetted
at a public meeting by the Working Group (41
C.F.R. § 102–3.35; 41 C.F.R. at § 102–3.160(a))
and are all available to the public online at:
tickbornedisease/reports/index.html.
•
•
•
•
https://www.hhs.gov/ash/advisory-committees/
Federal Inventory
To gather information on Federal activities that
address tick-borne disease, the Working Group
developed a Federal project inventory survey,
which was distributed to HHS, DoD, and the
U.S. Department of Veterans Affairs (VA). As
detailed in Appendix D, the Working Group
received inventories from CDC, NIH, and DoD.
They reported that for fiscal years (FY) 2010
through 2018, the total number of past and
•
Public Input
In compliance with FACA requirements, the
Working Group solicited public comments on
issues related to the Working Group’s charge
through the following channels:
current projects is 1,493; and for FY2010 through
FY2017, they produced 743 publications.
Of the Working Group’s focus areas, CDC and
NIH have addressed all but access to care. DoD
has addressed disease vectors and surveillance
as well as vaccines. CDC and NIH have engaged
in human surveillance, while CDC, NIH, and DoD
have participated in animal surveillance.
•
Verbal comments given at Working
Group public meetings –
At each of the
seven Working Group meetings, time
was allocated for the public to provide
comments in person or over the phone.
Each commenter was limited to three
minutes to accommodate as many speakers
as possible.
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•
Written comments submitted prior to the
Working Group public meetings –
Prior
to the Working Group meetings, the public
was invited to send their written comments
to the Working Group. This method
provided an opportunity for those who
could not participate in the meetings to
have their public comments reviewed and
considered in advance.
Email comments –
In addition, the public
had an opportunity to email their comments
to the Working Group (tickbornedisease@
hhs.gov)
at any time, on any day between
November 24, 2017, when the email
account was established and announced,
and July 1, 2018. Emails received before
July 1, 2018 were reviewed and addressed
in this report. Those received after July 1,
2018 will be considered for the second
Working Group report.
•
•
There was a general consensus among public
commenters that Lyme disease and tick-
borne diseases are insufficiently addressed
by mainstream medicine and government
Prevention –
The public emphasized that
success will stem from awareness and
recognition of Lyme disease and other
tick-borne diseases. They would like to
see renewed prevention efforts but want
to avoid another failed vaccine attempt,
as there is little trust in the U.S. Food and
Drug Administration (FDA) process of
fast-tracking vaccines. Prevention efforts
should focus on the easiest actions with
the highest payoff potential. In the short
term, the public would like to see more
education, behavioral changes, and
effective tick repellents. In the medium
term, they would like to see tick repellents
and tools further improved, continued
education and research, and growing trust
from acknowledgment of past mistakes.
And in the long term, they would like a safe
and effective vaccine for humans and/or
vectors against ticks. Vaccine safety was a
common concern.
Diagnosis –
The public would like
clarification that “Lyme disease is
diagnosed by a combination of medical
history, physical exam, and if needed,
diagnostic testing.” They recommend
developing a table that identifies the pros
and cons of currently available testing
(especially serology) and diagnostics.
They also recommend partnering and/or
learning from best practices elsewhere,
such as:
◊
◊
Technologies applied to other
diseases;
•
programs. The public would like to see increased
research funding, further scientific exploration,
and unbiased and fresh reviews of the latest
information across all related sectors. Public
comments are summarized below by Working
Group priority area and for the overall process.
•
Epidemiology and Ecology –
The public
would like three or more tick experts,
entomologists, ecologists, or vector
biologists included in the Working Group
and its subcommittees. They would also
like to see funding for comprehensive
cost-of-illness studies. They ask that
CDC highlight Lyme disease and tick-
borne disease distribution across the
contiguous 48 states and update the CDC
tick distribution map. They also ask that
CDC provide weekly, rather than annual,
statistics on Lyme disease.
◊
Science applied from different
disciplines, including fields beyond
medicine and those not yet engaged
in Lyme disease research; and
Successful programs and potential
solutions used by state and local
governments and organizations that
could be enhanced with Federal
collaboration.
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•
Treatment –
The public said they need
ways to determine if or when Lyme disease
infection is resolved. They would like an
integrated, interdisciplinary systems-
biology approach to understanding Lyme
disease, tick-borne diseases, and related
to revise Western medicine’s medical
immune suppression. They noted the need
be addressed, including children, pregnant
mothers, Veterans, Servicemembers,
migrant workers, farmers, hunters, and
outdoor enthusiasts. They would like
evidence-based care and policies based
place.
on rigorous scientific evidence to be put in
construct of Lyme disease and tick-borne
diseases to match the science. They also
noted the need to go beyond Lyme disease
and conduct research into combinations of
coinfections.
•
Process –
The public would like more
when responding to emails, making
responsiveness and timeliness from HHS
announcements, posting meeting minutes,
They would also appreciate increased
transparency. They noted that trust is
and updating the Working Group’s website.
•
Access to Care and Patient Outcomes –
The public stressed that insurance needs
to cover treatment, including long-term
antibiotics and immunotherapy, which
would be patient-centered and at the
essential for success, and there is currently
public comments expressed hope that this
Working Group will be the “reset” needed
to move forward.
little trust in the Federal Government. Many
treating clinician’s discretion. Patients also
need to participate in Lyme- and tick-borne
current medical practices are often harmful
suicide rate is high among Lyme disease
and tick-borne disease patients. For this
report, they asked that extra care be taken
to avoid victim-blaming by ensuring that
disease expertise review the language.
mental health professionals with tick-borne
They also asked that special populations
and often re-traumatizing patients. The
diseases–related decisions. They noted that
Minority Responses
There were a few recommendations that had
opposing viewpoints. These are expressed as
minority responses within the relevant chapters.
The Tick-Borne Disease Working Group entails a
six-year process, which will evolve and improve
over time by incorporating input from diverse
stakeholders and emerging science.
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Chapter 3
Epidemiology
and Ecology
Recommendations at a Glance: Epidemiology
and Ecology
Recommendation 3.1:
Fund studies and activities on tick biology and tick-borne
disease ecology, including systematic tick surveillance efforts particularly in regions
beyond the Northeast and Upper Midwest.
Recommendation 3.2:
Fund systematic studies and activities to identify and
characterize novel tick-borne disease agents in the United States.
Recommendation 3.3:
Support economic studies and activities to estimate the total
cost of illness associated with tick-borne diseases in the United States, beginning first
with Lyme disease and including both financial and societal impacts.
Recommendation 3.4:
Have public health authorities formally recognize
complementary, validated systematic approaches to tick-borne disease surveillance
for humans, such as systematic sampling of tick-borne disease reports for
investigation that reduce the burden on tick-borne disease reporting but allow for
comparability of surveillance findings across states and over time.
Recommendation 3.5:
The Lyme disease surveillance criteria are not to be used alone
for diagnostic purposes; public health authorities shall annually and when opportune
(such as during Tick-Borne Disease Awareness Month) communicate this and inform
doctors, insurers, state and local health departments, the press, and the public
through official communication channels, including the CDC’s
Morbidity and Mortality
Weekly Report
(MMWR).
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Background
In order to understand tick-borne diseases, it
is essential to understand ticks, their ecology,
and the environment. Despite many scientific
Clinical treatment of tick-bite victims is further
complicated due to potential for coinfections
with pathogens such as
Anaplasma
and
Babesia.
While not all of these diseases and conditions
are nationally notifiable, they are of concern
to the public and warrant further attention by
the Federal Government due to the increasing
frequency and growing threat of tick-borne
diseases to public health.
unknowns, experts agree that the incidence and
distribution of Lyme disease and other tick-borne
illnesses are increasing across the United States.
This may be due in part to ecological changes
in North America since the middle of the 20th
century, such as climate and habitat changes,
which have set the stage for expansion of tick
vectors over large, heavily populated regions.
Beyond conventional biology and ecology
methods, tools in microbiology and genetics
are essential to understanding tick distribution,
disease ecology, and risks to human health.
Effective disease characterization and prevention
relies on reducing exposure to ticks and disease
transmission by identifying and validating
effective prevention and control methods
and strategies. To track the effectiveness of
Major Challenges and
Issues
Surveillance and Burden of Illness
In 2016, Lyme disease was the most common
vector-borne disease reported and the sixth most
common of all nationally notifiable diseases.
While about 35,000 cases of Lyme disease
are reported each year to CDC, recent studies
indicate that the actual number of annual cases
is approximately 300,000 (Hinckley et al., 2014;
Nelson et al., 2015). Under-reporting is a common
phenomenon for most high-incidence diseases,
and Lyme disease under-reporting is further
complicated by a surveillance case definition
that requires both laboratory and supportive
burden and trends against which to measure
the success of national prevention strategies
such measures, it is essential to maintain an
accurate understanding of current disease
and efforts. Controlled field trials that measure
both entomologic and epidemiologic outcomes
are needed to provide data-driven prevention
recommendations.
CDC currently recognizes 13 unique human
tick-borne illnesses caused by 18 different
clinical data for confirmation of all but the earliest
manifestations of the illness. Accurate and up-to-
date incidence data for all tick-borne diseases,
including Lyme disease, are critical to establish
baselines against which to measure prevention
efforts and to monitor disease emergence in
new geographic areas, as well as to estimate the
burden of illness in terms of both economic costs
and human suffering.
pathogens in the United States. Seven of those
diseases are nationally notifiable (see Appendix
C.1). Researchers and health care practitioners
continue to discover new disease agents and
conditions, which affect increasing numbers of
people each year, including novel pathogens
like
Borrelia mayonii
and conditions like alpha-
gal syndrome (also known as the “meat allergy”).
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Figure 4: 1996 – Distributions of Two Tick Species
2015 – Distributions of Two Tick Species
The distributions of two tick species, the deer or blacklegged tick (Ixodes
scapularis)
and the western blacklegged
tick (Ixodes
pacificus),
are shown in U.S. counties between (a) 1907 and 1996 (top image) and between (b) 1907 and
2015 (bottom image). Counties in red or green are "established" for a given tick species, defined as having at least
six ticks or two life stages recorded within a single calendar year. Counties in blue or yellow are "reported" for the
tick species with one to five reported ticks of a single life stage. Counties shown in white indicate “no records” (Eisen
et al. 2016, Dennis et al. 1998). Two previously distinct foci for
Ixodes scapularis
in the Northeast and North-Central
states appear to be merging in the Ohio River Valley to form a single contiguous focus.
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Figure 5:
Ixodes scapularis
Tick Life Cycle and the
Transmission of Lyme Disease (Borrelia
burgdorferi)
The tick transmission cycle sustains the bacteria,
B. burgdorferi,
that cause Lyme
disease. Lyme disease risk is greatest in spring and summer, but can occur during all
four seasons. Nymphs, which feed in the late spring and early summer, are responsible
for transmitting the majority of infections to humans.
Disease Vectors
Due to the lack of a coordinated national tick vector surveillance program, there are significant gaps
in information on local distribution of tick vectors. This information is a priority and is required to
educate the public health community, health care providers, and the general public about local disease
risk. Scientists agree that the distribution of tick vectors transmitting human and animal illnesses has
increased steadily and significantly in recent decades. The deer, or blacklegged, tick (Ixodes
scapularis)
is the vector for Lyme disease, anaplasmosis, babesiosis, tick-borne relapsing fever caused by
Borrelia
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doubled in the last 20 years (Eisen, Eisen, & Beard, 2016. See Figure 3). Additionally, the number of
300% in the Northeastern states and by approximately 250% in the North-Central states (Kugeler,
found in approximately 50% of counties in the U.S., including many counties on the West Coast.
miyamotoi,
and Powassan virus disease. The number of U.S. counties where it is established has
U.S. counties now considered to be of high incidence for Lyme disease has increased by greater than
Farley, Forrester, & Mead, 2015. See Figure 4). In addition,
I. scapularis
and
I. pacificus
ticks have been
Recommendations
The Working Group recommends increased
which address the need for a better
Federal investment in the following initiatives,
understanding of vector distribution, disease
To predict where people are at risk for tick-borne
pathogens, it is paramount to understand the
geographic distributions of vector ticks. There
Wasser et al., 2006; Diuk-Wasser et al., 2010;
of the current distributions of vector ticks is
have been very few systematic tick surveys (Diuk-
Diuk-Wasser et al., 2012), and thus knowledge
heterogeneous in effort and method. Lack of
surveillance data in certain regions, or even
localities within regions, gives a potentially false
patients’ access to prevention education and
timely, accurate diagnosis and care.
ecology, vectorial capacity, as well as the need
reporting with shared standards across all 50
trends.
for improved national disease surveillance and
states to define disease burden, patterns, and
perception of tick-borne disease risk and hinders
and activities on tick biology and tick-borne
disease ecology, including systematic tick
surveillance efforts, particularly in regions
beyond the Northeast and Upper Midwest.
Accurate, current knowledge of the diversity,
distribution, relative abundance, and impact of
ticks and their associated pathogens is critical
for guiding practices aimed at the prevention,
Recommendation 3.1:
Fund studies
When the maps of tick geographic distributions
1945), four of the most important tick vectors in
or mid-central regions of the country. However,
were first published in 1945 (Bishopp & Trembley,
the United States were all located in the southern
scientific experts agree that, since then, ticks have
been expanding their geographic ranges (Clow
et al., 2017; Eisen, Eisen, & Beard, 2016; Hahn,
Jarnevich, Moaghan, & Eisen, 2016; Medlock et
tick,
Dermacentor variabilis,
now covers almost
diagnosis, and treatment of tick-borne diseases.
of tick transmission risk of various pathogens
across states is highly uneven. Standardized
Unfortunately, the current (2018) understanding
al., 2013; Sonenshine, 2018). The American dog
approaches at the Federal level are needed to
achieve the goal of obtaining consistent and
reliable data on tick distribution, tick abundance,
seasonal activity, and all aspects of tick behavior
for the different tick vectors.
tick,
I. scapularis,
has expanded northward into
all of the Eastern United States. The blacklegged
northern New York, all of New England, and parts
of southeastern Canada. Similarly, lone star ticks,
Amblyomma americanum,
the major vector of
human monocytic ehrlichiosis (HME), now cover
most of the Eastern United States as well as large
areas of the Mid-Central United States (Monzon,
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Atkinson, Henn, & Benach, 2016). The Gulf
Coast tick,
Amblyomma maculatum,
a vector of
Rickettsia parkeri,
the causative agent of a spotted
fever-like illness, has now spread northward along
the Atlantic coast as far as Delaware, into the Mid-
West to Oklahoma and Kansas, and into parts of
southern Arizona. In addition,
Ixodes pacificus
has been discovered in new counties on the West
Coast and has been found to harbor the newly
recognized human pathogen,
B. miyamotoi
(Nieto
et al., 2018).
Risk of tick-borne diseases increases over time
determination of tick transmission risk to humans.
been shown to infect people in the United States
Since 2004, seven new tick-borne pathogens have
(Rosenberg et al., 2018), and these discoveries
were made largely in the absence of any
coordinated effort. These observations highlight
the need for standardized systems and methods
using advanced technologies to determine the
full scope of disease agents that are potentially
The examination of the tick microbiome is
transmitted through the bite of an infected tick.
essential for understanding the relationship
due to the complex mix of multiple ecological
drivers. Tick range expansion is affected by
factors such as climate change, bird migrations,
anthropogenic changes in the landscape,
increasing populations of suitable host species
and suitable tick habitat (Mixson, Lydy, Dasch,
& Real, 2006; Ogden et al., 2006; Ogden et al.,
2008), reduced populations of predators (Levi,
Kilpatrick, Mangel, & Wilmers, 2012; O’Bryan et
al., 2018), as well as the introduction of exotic
species. Furthermore, the variation in the spatial
and temporal risk of acquiring a tick-borne
pathogen is impacted by tick-host preferences;
host-seeking behaviors; tick vector competency
between microbes and their tick hosts and to
facilitate the identification of new tick-borne
pathogens. The conventional methods for
detecting and identifying causative agents for
tick-borne diseases should be supplemented
with novel, powerful molecular approaches.
These should include metagenomics, which has
been shown to be very useful for detecting and
identifying pathogens in complex environmental
use in identifying novel tick-borne pathogens.
of transmitting can help address problems
and clinical specimens and has great potential for
Understanding which pathogens ticks are capable
associated with the geographic diversity of ticks
and the breadth of pathogens they potentially
understanding could also help the Federal
transmit in a specific location of risk. This
(a tick species’ ability to transmit disease-causing
pathogens); reservoir hosts (vertebrates capable
of hosting tick-pathogens); and the interactions
between these diverse factors, which can
influence local abundance of infected tick-borne
disease vectors.
Government properly allocate resources to further
investigate unsolved problems, such as the eco-
epidemiology of human Lyme disease in the
associated rash illness (STARI).
South, and the causative agent of Southern tick-
Recommendation 3.2:
Fund systematic
studies and activities to identify and
characterize novel tick-borne disease agents
in the United States.
Safeguarding human health is dependent on early
detection, identification, and characterization
of novel and emerging pathogens as well as
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Recommendation 3.3:
Support economic
studies and activities to estimate the total
cost of illness associated with tick-borne
diseases in the United States, beginning
first with Lyme disease and including both
financial and societal impacts.
claims, disability claims, and all of the indirect and
intangible costs incurred by tick-borne disease
patients and their caregivers.
Recommendation 3.4:
Have public health
To fully understand the impact of tick-borne
diseases in the United States, it is important to
identify and quantify the significant financial and
societal burdens that are associated with them.
This may be done with cost-of-illness (COI), or
burden-of-disease, studies, which provide an
economic analysis to identify and measure the
costs of a particular disease to society. Such
studies generally include the direct, indirect, and
intangible dimensions of the disease. The result or
output is often expressed in monetary terms (for
example, in U.S. dollars per year) to characterize
the total burden of a particular disease to society,
communities, families, and individuals. Such
methods to assess the financial impact and
societal burden can help to inform policy and
guide decision makers who must prioritize public
health needs, research, and interventions.
Comprehensive COI studies do not exist yet for
authorities formally recognize complementary,
validated systematic approaches to tick-
borne disease human surveillance, such as
systematic sampling of tick-borne disease
reports for investigation that reduce the
burden on tick-borne disease reporting but
allow for comparability of surveillance findings
across states and over time.
Tick-borne disease is an interdisciplinary
challenge and a national priority that warrants
broader data access to facilitate information
exchange and more rapidly advance scientific
progress. Scientific information and data today
are frequently collected and published in white
valuable context for human case data and
papers or peer-reviewed literature, which provide
enhance our understanding of changing tick-
borne disease risks. However, they are not yet
readily shared or easily applicable across different
with requirements to make Federally funded
disciplines. Establishing shared data repositories
Lyme disease and other tick-borne diseases.
Preliminary studies of direct medical expenses
science and data open by default and available to
States. According to Adrion, Aucott, Lemke,
and Weiner (2015), individual Lyme disease
patients pay an average of $3,000 in medical
costs throughout their course of treatment. These
estimates do not include indirect and nonmedical
costs, for example, the costs of traveling to and
from doctor appointments, lost wages, loss of
employment, and the financial cost to caretakers
or services for care. Additional research is
needed to fully characterize the drain of tick-
borne disease to U.S. society, including medical
indicate that Lyme disease alone may cost as
much as $1.3 billion per year to treat in the United
the public has the potential to accelerate scientific
Disease surveillance is a state responsibility,
Epidemiologists (CSTE) in conjunction with
surveillance is a passive process whereby health
care providers and laboratories report positive
diagnoses or laboratory tests to public health
CDC. Traditional public health and disease
led by the Council of State and Territorial
insights and evidence-based mitigation strategies.
agencies. Passive surveillance systems work best
for diseases that are rare, involve hospitalized
patients, or for which there are definitive
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EPIDEMIOLOGY AND ECOLOGY
are less effective for diseases that are typically
diagnostic laboratory tests. Passive systems
Another alternative surveillance approach could
could include regular sampling of tick-borne
be the use of systematic validated samples. This
diagnosed in outpatient settings and for which
there are no definitive laboratory tests (Cartter,
as Lyme disease.
Lyme disease cases (and to a lesser degree
Lynfield, Feldman, Hook, & Hinckley, 2018), such
disease reports for subsequent public health
current example takes place in New York State,
where a 20-percent sample of all reports is
investigated.
investigation or laboratory-only reporting. A
other tick-borne disease cases) are significantly
to burdensome reporting requirements. Under-
reporting and inconsistencies in surveillance
data, from state to state and from year to year,
under-reported in the United States largely due
significantly hamper efforts to evaluate prevention
awareness on the part of the public and the health
effectiveness. Additionally, it can result in a lack of
in diagnosis with potentially fatal consequences.
sources and emerging technologies holds
Pooling diverse interdisciplinary information
in a particular geographic area, leading to failures
care community that tick-borne diseases are a risk
disease surveillance criteria are not to be
used alone for diagnostic purposes; public
health authorities shall annually and when
opportune (such as during Tick-Borne
Disease Awareness Month) communicate this
and inform doctors, insurers, state and local
health departments, the press, and the public
through official communication channels,
including the CDC’s
Morbidity and Mortality
Weekly Report (MMWR).
The Lyme disease surveillance case definition
is frequently misunderstood and misused
throughout the medical community. According to
uniform criteria used to define a disease for public
used by health care providers for making a clinical
diagnosis or determining how to meet an
individual patient’s health needs” (Centers for
treating practitioners routinely use the Lyme
health surveillance… [and is] not intended to be
CDC, a surveillance case definition is “a set of
Recommendation 3.5:
The Lyme
promise for enhancing surveillance, although
borne diseases. Systematic synthesis of data
this approach has not yet been applied to tick-
across nested scales (from local to regional, state,
country, and global) is required to understand
health.
Creative and novel interdisciplinary approaches
required to improve public health surveillance of
approach that could complement traditional
surveillance would be the collection of
that are financially sustainable will also be
disease ecology and the implications for human
Disease Control and Prevention, 2017). However,
disease case definition to diagnose patients, and
insurance companies often require that patients
cover their care. Compounding the issue is the
broad misunderstanding in the medical
community that patients who do not meet the
meet the surveillance criteria before agreeing to
Lyme disease and other tick-borne diseases. One
interdisciplinary datasets across diverse sectors,
companion animal tick-borne disease testing data,
geospatial data, tick-borne disease reports,
crowdsourcing and citizen science data,
electronic
health records, and insurance claims.
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case definition cannot have Lyme disease. Those
patients who have tick-borne disease-related
chronic illness yet do not meet the surveillance
distances, often paying out-of-pocket, to seek
diagnosis and treatment from practitioners in high
incidence states (Johnson, Aylward, & Stricker,
2011) (see chapter 7 on Access to Care and
Patient Outcomes).
criteria often face difficulties obtaining diagnosis,
treatment, and medical insurance reimbursement
(see chapter 7 on Access to Care and Patient
Outcomes).
The Lyme disease case definition requires a
To prevent further patient suffering and societal
clarify and reiterate the message that the Lyme
burden, it is critical that public health authorities
disease surveillance criteria are only intended for
Linked Immunosorbent Assay (ELISA) test and, if
the ELISA is positive or equivocal, a subsequent
western blot test. With input from CDC, the CSTE
“two-tiered system” for verification: an Enzyme
disease surveillance and are not to be used alone
is urged to broadcast that message annually,
especially during Lyme Disease Awareness
for diagnostic purposes. The Federal Government
adopted these criteria in 1994 to verify cases of
Lyme disease for surveillance purposes across
all 50 states, allowing health officials to compare
the number and distribution of cases over space
Month, using websites, social media, publications,
and other outlets. It is recommended that CDC, in
and Mortality Weekly Report,
a respected
particular, publish this clarification in its
Morbidity
government publication that is widely read by
health care providers.
and time (see the minority response in chapter
5 on Diagnosis). The surveillance criteria define
areas of the United States as being high or low
incidence for Lyme disease.
Complicating the issue, health care providers
the West Coast, are often under the impression
that Lyme disease does not occur in their state
and therefore do not conduct the two-tiered
in low incidence regions, such as the South and
test on patients with symptoms consistent with
Lyme disease. As a result, those patients and
their family members may need to travel long
Epidemiology and ecology help us understand the
magnitude, geographic distribution, and dynamic
nature of tick-borne diseases, so we may inform and
improve prevention efforts.
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Patient
Stories
Dr. Neil Spector
Dr. Neil Spector’s healthy outdoor lifestyle as a jogger and
marathon runner increased his exposure to and risk for tick-
borne disease. In the late 1980s and early 1990s Dr. Spector
lived in New England, which is a highly endemic area for
Lyme disease. Dr. Spector first began to experience a bizarre
constellation of symptoms in 1993, which included cardiac
arrhythmias and profound fatigue (“I went from running 10
miles a day, six days a week to barely being able to walk 10
yards without feeling exhausted”). Doctors could find nothing
wrong with him. In his own words,
“I
was confused. Should I believe a team of doctors assuring me
that nothing was wrong? Or follow my gut instinct exhorting me
to unearth the mystery responsible for my downwardly spiraling
health? I was beginning to question my sanity.”
Dr. Spector’s symptoms worsened with time: cardiac rhythm
disturbances, migratory muscle pains, weight loss, malaise,
Dr. Neil Spector
insomnia, brain fog, severe fatigue, and more. In 1997, doctors
Lyme Disease Survivor and
prescribed him antibiotics for an unrelated condition—and,
Patient Advocate
unexpectedly, many of his symptoms, including arthritis,
Associate Professor of Medicine
improved. It was also in 1997 that he was diagnosed with
Duke University School of Medicine
third-degree heart block and ventricular arrhythmias requiring
Durham, North Carolina
a permanent pacemaker/defibrillator. A diagnosis of Lyme
disease was confirmed in late 1997 and despite an aggressive
course of antibiotic therapy, the heart block and ventricular arrhythmias did not resolve. He then
progressed to a dilated cardiomyopathy.
Dr. Spector was undiagnosed and misdiagnosed for years. Even as a well-trained, academic physician-
scientist with access to the best medical resources in the United States, Dr. Spector’s symptoms were
dismissed as “stress” related. As a result, Dr. Spector’s heart suffered irreversible damage. Lyme
carditis
—
when Lyme disease bacteria enter the tissues of the heart
—
is considered rare yet serious
and potentially fatal. This manifestation of Lyme disease brought Dr. Spector to the brink of death. He
needed a heart transplant to save his life.
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Chapter 4
Prevention
Recommendations at a Glance: Prevention
Recommendation 4.1:
Fund additional studies and activities on the development and
evaluation of novel and traditional tick-control methods that have shown promise in
other areas of public health entomology.
Recommendation 4.2:
Build trust via a transparent mechanism by which all stakeholders
examine and discuss past vaccine activities and potential adverse events to inform
future vaccine development in Lyme disease.
Recommendation 4.3:
Support the development of safe and effective human vaccines
to prevent Lyme disease with transparent mechanisms by which all stakeholders
examine and discuss past vaccine activities and potential adverse events to inform
future vaccine development.
Recommendation 4.4:
Prioritize education by informing clinicians and the general
public about the regional and specific risks related to tick-borne diseases.
Background
Despite decades of research evaluating tick- and host-targeted interventions, the incidence of tick-
borne diseases in the United States continues to rise. Scientists have identified a variety of bacterial,
parasitic, and viral disease-causing agents that are transmitted to humans by multiple species of ticks.
New tick-borne pathogens continue to be identified, further implicating ticks as an important threat to
ticks, Rocky Mountain wood ticks, Pacific Coast ticks, Gulf Coast ticks, brown dog ticks, and soft-bodied
human health nationwide. Blacklegged ticks, Western blacklegged ticks, lone star ticks, American dog
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PREVENTION
Enjoy the outdoors while taking precautions to prevent tick-borne diseases. Know where to expect
ticks and how they behave. Ticks live in grassy, brushy, or wooded areas and often wait in leaf litter
and at the end of branches and leaves for hosts to brush against them. Stay on the hiking paths,
wear proper clothing, and use repellents. For more information on repellents and avoiding ticks, visit
https://www.cdc.gov/ticks/avoid/on_people.html
and
https://www.epa.gov/insect-repellents.
Figure 6: Enjoying the Outdoors
ticks all play important roles as vectors of a variety
of agents that cause human disease, with several
tick species capable of carrying and transmitting
multiple pathogens to humans in a single bite.
A review of the scientific literature and expert
presentations has identified the following
crucial needs: (1) reducing human exposure to
vector ticks, (2) identifying novel methods for
(3) conducting further study and adequately
validating strategies (including vaccination)
pathogens to humans and animals.
controlling ticks and tick-borne pathogens, and
Major Challenges and Issues
Personal protective measures, such as performing
tick checks or wearing tick repellent, are widely
recommended for reducing transmission of the
aimed at blocking the transmission of tick-borne
simple to perform and inexpensive, they require
implementation on a daily basis to be most
effective. Also, ticks are tiny and easily missed.
Finally, while most people know something about
ticks, their current knowledge or well-intentioned
practices are frequently not grounded in evidence
or justified by science, so they remain at risk for
tick exposure.
pathogens that cause Lyme disease and other
tick-borne diseases. Although such measures are
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Compared with personal protective measures,
household and peridomestic (backyard)
preventive measures, such as residential pesticide
applications or landscape modifications, require
more effort and cost up front, but do not rely on
daily action for effectiveness. Community-wide
interventions, such as deer management, tick
management, and educational programming,
respect to vaccines in general, and Lyme disease
vaccines in particular, especially vaccines that
are OspA-based. Addressing current barriers to
acceptance by the general public and industry
introduction of human vaccines against Lyme
is likely to require a combination of scientific
engagement; and patient advocacy.
will be essential to helping ensure the successful
disease and other tick-borne infections. Success
progress; company, public, and Federal agency
recipients. Yet public concerns persist with
have the potential for maximum impact on tick
populations or disease transmission. However,
possible barriers to the implementation of
such interventions include municipal and state
labor required for sustainable impact.
regulations as well as a significant investment of
Effective vaccines against Lyme disease are
Recommendations
The Working Group has identified four initiatives
that the Federal Government could spearhead
other tick-borne diseases.
to improve the prevention of Lyme disease and
feasible, as demonstrated by LYMErix, an outer
surface protein A- (OspA) based vaccine for
the United States between 1998 and 2002.
human Lyme disease, which was available in
LYMErix had an efficacy rate of nearly 80%.
However, it was voluntarily withdrawn from the
market because of low public demand. Factors
that helped limit uptake of LYMErix included a
complicated vaccination schedule, permissive
recommendations that required patients and
health care professionals to assess risk and
environmental exposure, and a theoretical
Recommendation 4.1:
Fund additional
studies and activities on the development
and evaluation of novel and traditional tick-
control methods that have shown promise in
other areas of public health entomology.
Repellents
In general, skin repellents serve as the first line
of protection against tick bites, and several
compounds have been identified that effectively
repel ticks. However, barriers to using repellents
persist and should be evaluated. Also, despite
concern that OspA could cross-react with human
susceptible vaccine recipients (Steere et al.,
tissue and evoke persistent arthritis in genetically
1998). A major challenge to vaccine development
continues to be a concern among some patient
groups and practitioners over the lack of
transparency in the handling of potential side
Scientific studies and analyses have found no
who received LYMErix compared to placebo
increased public interest in using natural products
as tick repellents (Gould et al., 2008a), very few
data have been published with respect to the
effectiveness of natural products specifically
marketed for the prevention of human-tick
effects from the LYMErix vaccine (Poland, 2011).
evidence of elevated rates of arthritis in patients
encounters or tick-borne diseases. Furthermore,
active ingredients commonly found in natural
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Figure 7: Treat Your Clothing
with Permethrin
products with repellent properties, such as red
cedar oil, soybean oil, and peppermint oil, have
little or no published data supporting their use
for repelling ticks.
Nootkatone, a botanical extract found in
grapefruit skin and Alaskan yellow cedar,
prevention. It repels blacklegged ticks, a
has shown particular promise for tick bite
primary Lyme disease vector (Dietrich et al.,
2006); is safe and commonly used in food
and fragrances; and can be mass produced
using a yeast fermentation process. In 2017,
Read instructions
CDC entered into a licensing agreement
with the biotech company Evolva to further
develop nootkatone as an active ingredient
such as repellent soaps and lotions to repel
in commercially available repellent products,
vector mosquitoes. Creating safe formulations
of nootkatone has great potential for effective
shampoo, or spray for consumer use.
tick bite prevention in the form of soap, lotion,
Protective Clothing
Clothing treated with a pesticide called
permethrin has been shown to provide long-
lasting protection from blacklegged tick and
lone star tick bites (Miller, Rainone, Dyer,
Apply in ventilated area
González, & Mather, 2011; Vaughn et al., 2014).
Multiple studies of military uniforms support
the use of permethrin-treated clothing as
an effective method of repelling and killing
multiple tick species (See Figure 7) (Evans,
Korch, & Lawson, 1990; Fryauff, Shoukry,
Wassef, Gray, & Schreck, 1998; Schreck, Mount,
& Carlson, 1982; Schreck, Snoddy, & Spielman,
1986).
Hang to dry
To repel and kill ticks, treat boots, clothing, and
camping and hiking gear with products containing
0.5% permethrin, which remains protective through
several washings.
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Rodent-Targeted Transmission-
Blocking Vaccines
management strategies involving vaccines
Some researchers have advocated for tick
on the role of mice or other targeted rodent
pathogen transmission. The relative importance
depending on their abundance and that of other
wildlife hosts. Thus, replicate studies should be
conducted to understand how the effects of host-
contexts. Furthermore, any intervention that acts
as a selection factor on ticks or pathogens may
select for resistance. Thus, research is required
to better understand the population biology
of mice may also vary spatially and temporally,
species in the processes of tick feeding and
containing
B. burgdorferi
OspA. In one study, a
that are administered orally to mice via bait
rodent-targeted vaccine reduced the incidence
hosts and blacklegged ticks in an area where
of infection among white-footed mouse reservoir
targeted interventions vary in different ecological
Lyme disease was endemic (Gomes-Solecki,
2014; Richer et al., 2014). In another study,
oral vaccination of white-footed mice with bait
containing
B. burgdorferi
OspA was shown to
of ticks and pathogens (for example, migration
prevent infection in mice and reduce spirochete
prior to oral immunization) to the ticks feeding
rates) to help predict the evolution of resistance
contexts.
transmission from mice (which had been infected
on those mice (Voordouw et al., 2013). According
to data from a five-year study, a rodent-targeted
vaccine resulted in cumulative anti-OspA
antibody production and significantly reduced
tick infections in the field (Richer et al., 2014).
These studies suggest that rodent-targeted
under different selection scenarios and ecological
Novel Genetic Approaches
The development of new genetic and molecular
tools is leading to the generation of tick-
borne disease prevention tools, including
modified organisms or disrupting gene
expression in ticks and reservoir hosts.
methodologies aimed at creating genetically
vaccines could be effective tools for decreasing
the incidence of infection with the Lyme disease
spirochete among blacklegged tick nymphs,
the primary vector of Lyme disease bacteria to
The concept of releasing transgenic organisms
material, also known as genetically modified
such vaccines would not reduce tick abundance.
rodent-targeted vaccines containing subolesin,
a tick protein. Such vaccines could help reduce
tick abundance and disrupt the transmission of
Bhattacharya, Clark, & Hu, 2012).
would only prevent Lyme disease, and the use of
Thus, another possible approach would be to use
use of rodent-targeted OspA-based vaccines
humans. However, it should be noted that the
(for example, animals that have modified genetic
organisms, or GMOs) has long been discussed
mosquitoes and crop pests, and may also
and tested for controlling populations of vector
offer great promise for effective vector control
in regions where ticks are highly abundant.
Transgenic ticks are currently in development
at the University of Nevada-Reno, with a goal
of using a new genetic tool known as CRISPR
several types of tick-borne pathogens (Bensaci,
The ability of any rodent-targeted intervention to
reduce the density of infected nymphs depends
to disrupt insulin signaling, which plays a role
in nutrient metabolism and, therefore, parasite
survival in ticks (Feinberg, 2018). Researchers at
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PREVENTION
Figure 8: Create a Tick-Safe Zone Through Landscaping
Make your yard less attractive to ticks and reduce tick populations by clearing tall grasses and brush around the
house. Mow the lawn frequently and keep leaves raked. Create a "tick safe zone" with these tips.
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the Massachusetts Institute of Technology are also
they use to genetically engineer white-footed
investigating the use of CRISPR technology, which
mice so they are unable to serve as competent
The use of GMOs may go a long way toward
areas.
RNA interference (RNAi) is a powerful reverse-
genetic approach used to determine gene
function and silence tick genes (Fire et al.,
hosts for tick-borne pathogens (Harmon, 2016).
eradicating blacklegged ticks in highly abundant
via a transparent mechanism by which all
stakeholders examine and discuss past
vaccine activities and potential adverse
events to inform future vaccine development
in Lyme disease.
Recommendation 4.2:
Build trust
Recommendation 4.3:
Support the
1998). Studies of ticks using RNAi technology
encompassed the topics of pathogen acquisition
and transmission, protective antigens, structural
and metabolic proteins, reproduction, digestion,
and the roles of salivary gland proteins (Galay et
al., 2016). This technology can be used to assess
potential targets for pesticides, repellents, anti-
development of safe and effective human
vaccines to prevent Lyme disease with
transparent mechanisms by which all
stakeholders examine and discuss past
vaccine activities and potential adverse
events to inform future vaccine development
in Lyme disease.
tick vaccines, and other strategies to disrupt ticks’
physiologic processes and tick-borne pathogen
interface. It can potentially be used to disrupt
virus infection within the tick (Hajdusek et al.,
2013).
interactions within the tick vector and at the host
Short of access to clean water, the most effective
means for preventing infectious diseases is
vaccination. Scientific opportunities abound for
human Lyme disease vaccines that would target
microbial antigens and/or tick salivary-gland
antigens. Avenues that merit exploration include
newer approaches to enhance immunogenicity,
the removal of components thought by some to
harbor autoimmune potential, and protection
against multiple species of pathogens.
Practical, widescale application technologies and
new ways of prolonging the mode of action of
this tool could help lead to the discovery of
RNAi in the tick need to be investigated because
molecules that are essential to tick control and
Building Trust
For any vaccine to be successful today, diverse
stakeholder engagement and trust building are
essential. Vaccine activities must be reviewed with
ticks’ ability to transmit disease-causing microbes.
a transparent process open to all stakeholders
in order to address historical problems and
current concerns about potential adverse events.
Proactively addressing trust and transparency
issues surrounding vaccines—especially
surrounding Lyme disease vaccines—will
help to
inform and improve future vaccine development
(Poland, 2011).
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PREVENTION
Prospects for New OspA- and
OspA/OspC-Based Vaccines
against Lyme Disease
B. burgdorferi,
the spirochete that causes Lyme
the infected tick has been exposed to a blood
and production of outer surface protein C
(OspC) and other spirochete antigens is
upregulated—a
process that allows
B. burgdorferi
to be transmitted to, and establish infection
meal, OspA production is downregulated
disease, produces OspA in unfed ticks. Once
Anti-Tick Vaccines for Humans:
Another Area of Promise
Tick feeding is a slow, multi-stage process that
begins with a bite and ends a few days later with
causes Lyme disease resides in the tick’s gut prior
pathogen migrates to the tick’s salivary glands,
host.
Ticks are most vulnerable during the blood meal.
For that reason, the ideal anti-tick vaccine would
interfere with tick physiology during feeding or
full engorgement of the tick. The pathogen that
to a blood meal. After tick feeding has begun, the
and the tick injects salivary gland antigens into its
leading to the health problems associated with
Lyme disease.
Experts suggest that OspA- and/or OspA/OspC-
other types of human Lyme disease vaccines are
based vaccines could become available while
Ultimately, that process supports infection,
host immunity, disseminate, and colonize tissue.
has other adaptive features that help it evade
remarkably effective corkscrew motility and
in humans. The spirochete demonstrates a
prevent feeding altogether. An advantage of such
an approach is that it could theoretically prevent
transmission of Lyme disease, anaplasmosis,
and babesiosis, and potentially other tick-borne
infections by interruption of tick feeding. Most
pathogens that are transmitted by the
Ixodes
species of tick usually require more than 24 hours
methods by which vaccines could prevent Lyme
disease.
being developed. For example, a new OspA-
tolerated and performed well in early trials.
of feeding to infect a host. Table 1 summarizes the
based vaccine is in development that was well
It has the advantage of providing protection
against strains of
B. burgdorferi
that are common
the component that was thought by some to
in Europe and the United States, and it lacks
tick-borne infections as well.
and, perhaps, be adapted to prevent additional
developed to prevent Lyme disease in humans
VANGUARD crLyme, a similar vaccine may be
by modifying the approach used to develop
Lyme disease in dogs. Researchers hope that
OspA/OspC-based vaccine that helps prevent
example is VANGUARD crLyme, a subcutaneous
be arthritogenic in LYMErix recipients. Another
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Table 1: How Vaccines Can Potentially Prevent Lyme Disease
Rodent-Targeted Vaccines
•
•
Kill the spirochete in ticks that feed on mice
Reduce the prevalence of infection among ticks and mice in the treated environment
Human Vaccines
OspA-Based Vaccines
•
Block transmission of
Borrelia burgdorferi
by killing the spirochete in ticks
OspA/OspC-Based Vaccines
•
Block transmission of
B. burgdorferi
by killing the spirochete in ticks and mammals
Anti-Tick Vaccines
•
•
feeding
Neutralize the tick’s attachment proteins that facilitate a blood meal, which impairs tick
Target the tick’s immunomodulatory proteins that affect host immune response, which
◊
Reduces transmission and/or acquisition of the causative organism
◊
Reduces or partially controls the spirochete load
◊
Impairs tick feeding
•
Target allergy or physiology proteins that facilitate tick engorgement or regulate
important functions, which impacts pathogen transmission
Recommendation 4.4:
Prioritize
of tick-borne pathogens, we can improve efforts
to educate health care professionals and the
public about tick-borne disease prevention, and
especially about tick biology and best practices
for protection from tick bites.
Accurate education on tick-bite prevention is
important for all U.S. residents, regardless of
where they live, work, travel, or enjoy recreational
education by informing clinicians and the
general public about the regional and
specific risks related to tick-borne diseases.
Education to Increase Awareness
of Tick-Borne Disease Risk and
Prevention
In the absence of effective strategies for
controlling ticks and blocking the transmission
activities. Currently, there is little coordination
or consistency in message selection or source,
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PREVENTION
delivery emphasis, or sensitivity to seasonal or
spatial dynamics of tick encounter risk. Moreover,
few programs use concepts promoting behavioral
change in a consistent or effective way.
Also, few of the recommended educational
interventions to prevent tick encounters or tick-
borne diseases have been thoroughly assessed.
Disparities exist in the level of knowledge,
perceived personal risk, and use of preventive
measures across the human land-use gradient.
Thus, targeted tick prevention programs may be
best suited for addressing behaviors that increase
the risk for exposure. Additionally, studies are
needed to determine specific gaps in knowledge
and prevention among different segments of the
population.
managers, ranchers, farmers, and researchers),
or travel to areas where the risk for exposure to
ticks is unknown (for example, military personnel,
wildland firefighters, disaster relief workers,
transmission line workers, and landscapers).
Although many prevention programs have
Numerous actions could be taken to improve
prevention education at all levels, from individual
actions to national interventions. Ample evidence
suggests that people who live in areas where
Lyme disease is endemic are well aware of the
problem and believe that they are familiar with
many of the recommended preventive best
practices. Based on these studies, initiatives that
increase knowledge do not appear to be effective
in getting people to consistently engage in
behaviors that prevent Lyme disease. Barriers to
implementing tick-bite prevention may be related
been developed specifically for Lyme disease,
too few programs address the risk of tick bites
in general. Much of what has been developed
lacks regional relevance for areas of the country
where blacklegged ticks are not known to be
endemic, yet the risks for many other serious
and potentially deadly diseases from other
species of tick exist in those regions. The lack of
perceived risk has hindered surveillance activities,
awareness, and prevention education. That is why
the public needs prevention education that is
region-specific and addresses travelers’ elevated
risk for Lyme disease and other tick-borne
diseases.
Additionally, public lands that are managed
by various state and Federal departments and
agencies provide opportunities for increased tick
exposures to members of the public who use
those lands for livestock grazing, woodcutting,
hunting, outfitting and guiding, and general
outdoor recreation, such as hiking, fishing,
camping, and tourism. Public land managers,
key stakeholder groups (for example, parents,
travelers, English as a Second Language school
nurse educators, and advocacy groups).
However, other segments of the population that
be identified through the use of focus group
and social marketing surveys conducted with
to age, culture, gender, language, perception of
risk, and personal experience. Such barriers might
live outside of areas where Lyme disease is highly
endemic remain at increased risk for exposure
to ticks due to work outdoors, close contact
with wildlife (for example, natural resource land
education on tick-bite prevention to reduce
exposure to tick-borne diseases (Johnson et
al., 2014). The lack of knowledge about Lyme
disease and other tick-borne infections may put
unsuspecting visitors at increased risk for disease
and decrease their adherence to prevention
practices. There is also a significant need for
better awareness of ongoing education that takes
a regionally relevant approach to prevention.
visitors to public lands, and military personnel
are other stakeholder groups in need of more
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Minority Response
This minority response is driven by the Working Group’s recommendation to support the
development of human vaccines to prevent Lyme disease. This initiative was proposed in the
Vaccines and Therapeutics subcommittee report, which includes the statement that human
vaccines against Lyme disease should be “a top priority focus.” The dissenting minority stresses
that all concerns related to the prior vaccine failure need to be understood and addressed before
moving ahead to a new vaccine. This process will ensure that the public can make informed
health care decisions about the safety and efficacy of any new vaccine.
Yet there are unsettled issues surrounding the failure of LYMErix, an OspA-based vaccine that was
withdrawn from the market in 2002. Researchers had indicated that OspA might trigger arthritis,
especially in people with an HLA DR4 allele. (HLA genes have different alleles, which are two or more
Center for Biologics Evaluation and Research Open Meeting of: The Vaccines and Related Biologics
Products Advisory Committee, 1994; Steere, 2006].)
A multiplex
B. burgdorferi
OspA-based vaccine, fast-tracked by FDA, is now in phase two trials.
alternative forms of a gene found at the same place on a chromosome [Food and Drug Administration
who, within several days to two months following receipt of LYMErix, developed either cognitive
Other concerns relate to possible neurologic complications of the vaccine. One study reported patients
impairment, including white matter lesions and damage to the myelin sheaths surrounding nerve cells,
or cognitive impairment with sensory axonal neuropathy. Later studies focused on additional patients
in the Vaccines and Therapeutics Subcommittee report, nor have they been adequately studied or
addressed anywhere to our knowledge (Alaedini & Latov, 2005; Latov et al., 2004; Marks, 2011).
who had reported neurologic adverse events after LYMErix vaccination. These issues were not raised
At several FDA hearings, individuals testified about becoming crippled after receiving the vaccine.
“causing” Lyme disease, and many thought that the vaccine was retriggering Lyme disease in
Doctors and some researchers were looking at causal connections. There were reports of the vaccine
individuals who had previously been infected. When vaccinated patients reported their symptoms to
the physicians who had administered LYMErix, their concerns and other issues were often brushed
off as unrelated to the vaccine and were not reported to the Vaccine Adverse Event Reporting System
reports. The FDA’s own analysis of VAERS data on LYMErix includes mention of nosologists (rather
that depended on the use of certain words or phrases that required cautious interpretation. It also
concerns.” To our knowledge, those data have not been released publicly (Ball, 2001).
(VAERS) (Smith, 2001). Additionally, VAERS did not include some of the issues raised in physicians’
than physicians) taking data, a lack of standardized case definitions, and coding for adverse reactions
alludes to phase four data, which according to the analysis, will “be important to help evaluate safety
According to Smith (2013), “Questions related to the safety and efficacy of the prior vaccine do not
appear to have been fully explored nor answered, but have been met publicly instead with blame
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PREVENTION
being laid at the door of the Lyme disease community for failure of the first vaccine. In this climate, it is
not really a surprise that Lyme disease patients and the public are concerned about a new rollout.” The
search for a new vaccine should only commence when the science behind the past vaccine failure is
understood. That process needs to happen in a transparent meeting of all stakeholders.
Meanwhile, vaccines combining both tick-derived and pathogen-derived antigens with the potential
stakeholders until consumers are fully aware of the mechanisms of past vaccine failures.
to control many different tick-borne diseases might be a good option for public discussion among all
References
with neural tissue.
J Neuroimmunol, 159(1-2),
192-195. doi:10.1016/j.jneuroim.2004.10.014
Alaedini, A., & Latov, N. (2005). Antibodies against OspA epitopes of Borrelia burgdorferi cross-react
Ball, R. (2001).
LYMErix Safety Data Reported to the Vaccine Adverse Event Reporting System (VAERS).
Government/Vaccines/2001_fda_powerpoint_RobertBall.pdf
[PowerPoint Presentation] Retrieved from
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Food and Drug Administration Center for Biologics Evaluation and Research. (1994).
Open Meeting of: The Vaccines and Related Biologics Products Advisory Committee.
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Vaccines/1994vaccinemeetingfdacdcskbconnaughts.pdf
Latov, N., Wu, A. T., Chin, R. L., Sander, H. W., Alaedini, A., & Brannagan, T. H., 3rd. (2004). Neuropathy
Peripher Nerv Syst, 9(3),
165-167. doi:10.1111/j.1085-9489.2004.09306.x
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89-96. doi:10.3233/JRS-2011-0527
and cognitive impairment following vaccination with the OspA protein of Borrelia burgdorferi.
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Marks, D. H. (2011). Neurological complications of vaccination with outer surface protein A (OspA).
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Smith, P. (2001). Remarks of Pat Smith, President, Lyme Disease Association, Inc., before the Vaccines
https://lymediseaseassociation.org/about-us/speeches-a-positions/
testimonies/459-md--vaccines-a-
related-biological-products-advisory-committee
Smith, P. V. (2013). The LYMErix Story: FDA Approval to Market Withdrawal—Learning from History.
and Related Biological Products Advisory Committee, January 31, 2001, Bethesda, MD. Retrieved from
Vaccines/2013_Vaccine_Article_Learning_From_History.pdf
Lyme Times.
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Steere, A. C., Klitz, W., Drouin, E. E., Falk, B. A., Kwok, W. W., Nepom, G. T., & Baxter-Lowe, L. A.
burgdorferi peptide.
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(2006). Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia
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Prevention strategies include behavioral
modifications, repellents, protective clothing,
vaccines, and emerging technologies—all
important, yet they do not help those already
infected with tick-borne disease who need
proper diagnosis and treatment today.
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Chapter 5
Diagnosis
Recommendations at a Glance: Diagnosis
Recommendation 5.1:
Evaluate new technology or approaches for the diagnosis of
Lyme disease and other tick-borne diseases.
Recommendation 5.2:
Include special populations, especially children, in Lyme
disease and other tick-borne diseases diagnostic studies.
Background
Tick-borne infections are an emerging public
commonly reported tick-borne infection is Lyme
health epidemic in the United States. The most
challenges with respect to diagnosis of tick-
borne infections, especially Lyme disease. As a
treatment of tick-borne infections are limited.
the infection may be diagnosed without
result, opportunities for early identification and
In areas where Lyme disease is highly endemic,
laboratory testing if patients develop a diagnostic
skin lesion, known as erythema migrans (EM;
See Figure 9). However, 20% of patients may not
develop this specific rash, and sometimes the
rash is not seen or recognized. Additionally, the
eye appearance and instead may be uniformly
the ring-within-a-ring appearance. Laboratory
testing to provide evidence of infection with
are not limited to, anaplasmosis, ehrlichiosis,
disease. Other tick-borne infections include, but
than one tick-borne pathogen at a time. Such
coinfections often confound diagnosis and
treatment.
Despite Federal, state, and local efforts to
Notably, people can be infected with more
Bourbon virus disease, and
B. miyamotoi
disease.
babesiosis, rickettsioses, Powassan virus disease,
rash does not always have the stereotyped bull’s
red or reddish-blue without central clearing, or
prevent and control the spread of tick-borne
infections, the number of cases has continued to
is exacerbated by technical and biological
increase over the last few decades. This problem
B. burgdorferi,
the organism that causes Lyme
show an identifiable EM rash but have symptoms
disease, is recommended for patients who do not
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Figure 9: Skin Rashes of
Lyme Disease
suggestive of Lyme disease. Other tick-borne
diseases and coinfections do not necessarily
present with a characteristic rash or other agent-
Therefore, the clinician must rely on testing for
specific signs and symptoms (See Figure 10).
A
evidence of infection with tick-borne pathogens.
Major Challenges
and Issues
Serological assays that detect antibodies against
laboratory test cleared by FDA and recommended
B. burgdorferi
are currently the only type of
B
by CDC for diagnosis of Lyme disease. Published
peer-reviewed studies show that serological tests
have technical limitations, such as cross-reactivity
between tests for Lyme disease and those for
have biological limitations related to how the
other infectious diseases. Serological tests also
C
human immune system reacts to infection with
B. burgdorferi.
Antibodies may not be produced
by the immune system early enough or in high
enough quantities to meet the detection limit
of the test. These limitations make it difficult for
health care professionals to determine whether
their patient has Lyme disease. Similar limitations
are found with tests for other tick-borne diseases
D
and coinfections.
The skin lesion of Lyme disease can take on
many appearances and does not always have
the stereotyped bull’s eye appearance
(panel
A).
Most of the time the skin lesion is uniformly
red
(panel B)
or reddish blue
(panel C)
and
does not have the ring-within-a-ring bull’s
eye appearance. Multiple skin lesions can
occur when the
Borrelia burgdorferi
bacteria
spread through the bloodstream to other areas
(panel D).
The rash may not always be seen
or recognized especially when in hard-to-see
places or on dark-skinned individuals
(panel E).
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DIAGNOSIS
Research focusing specifically on the performance
of serological tests for tick-borne disease
diagnosis demonstrates that
need to know the status of the infection (that is,
whether or not it is active) to make an informed
decision about whether or not antibiotic
treatment should be initiated or continued.
Serology, however, remains the most commonly
ordered test for tick-borne diseases in the United
States. The greatest threat of not addressing the
•
Test results can be inconsistent among
different laboratories or with different test
kits;
Serological assays for tick-borne diseases
can be negative during the first several
days to weeks of infection; (See Figure 11)
Serology may not detect all cases of tick-
borne disease, particularly in persons
who do not produce detectable levels of
antibodies in response to infection, and in
patients who were treated with antibiotics
at the beginning of the infection.
•
•
shortcomings in laboratory testing for tick-borne
diseases and coinfections is that a significant
proportion of patients in the United States
who are newly infected with one or more tick-
borne pathogens will not be diagnosed with
the appropriate disease, and will not receive
prompt or proper treatment for a disease with the
potential to cause disabling illness or even death.
The limitations of many currently available
diagnostic tests for tick-borne diseases impact
their clinical performance and interpretation,
which highlights the need for improved
approaches to detecting tick-borne diseases
and coinfections. The consequences of those
limitations include missed and/or incorrect
diagnoses, no treatment or inappropriate
treatment, increased health care costs, and poorer
clinical outcomes.
Also, many previous evaluations of Lyme disease
tests have focused on patients with EM lesions
and, as such, the tests may perform less effectively
than expected when applied to patients without
EM lesions.
Serological tests for tick-borne diseases measure
a person’s past or present immune response
to infection and, thus, do not indicate whether
the infection is active. Health care professionals
Figure 10: Skin Rashes of Tick-Borne Diseases
A
B
C
D
38
Different tick-borne diseases cause different skin rashes. Tularemia may present with ulcerative lesions
(panel A).
Spotted fever rickettsioses, such as Rocky Mountain spotted fever and
Rickettsia parkeri,
may, respectively, have red
spots on the extremities (panel
B)
or an eschar scab-like lesion (panel
C).
Borrelia mayonii
often presents with round
rashes similar to disseminated Lyme disease
(panel D).
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Informed by convergent data from expert presentations, review of peer-reviewed publications, and
multiple patient stories shared during public comment, the Working Group has also identified the
need to include special populations (especially children) in the evaluation of new technology or
approaches for the diagnosis of Lyme disease, other tick-borne diseases, and coinfections. In endemic
areas, Lyme disease cases among children may exceed the number of Lyme disease cases among
adults. This statistic highlights the need to include children in scientific studies of Lyme disease
and other tick-borne diseases. Equally important is the need to include patients from additional
populations, including pregnant women, as some tick-borne infections pose a risk of maternal-fetal
transmission. Populations that were previously under-represented in tick-borne disease studies may
hold clues to special risk factors that could help reduce the number of tick-borne disease cases and the
resulting burden on the health care system.
Figure 11: Immune Response in Rickettsial Infection
The model of rickettsial disease is representative of many tick-borne diseases such as Lyme disease where there is a
delay in the appearance of the antibodies that are used for diagnosis. This “seronegative” window, shown in green,
limits the use of antibody based serologic tests in the first few weeks of infection, which is when the skin findings (eshar
in ricketsial disease and erythema migrans rash in Lyme diseases) are often present and the patient is ill with fever or
other symptoms. Emerging technologies such as detection of pathogen DNA through PCR testing show promise for
improved early detection.
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DIAGNOSIS
Recommendations
The Working Group recommends increased
Federal investment in the following initiatives.
Recommendation 5.1:
Evaluate new
technology or approaches for the diagnosis
of Lyme disease and other tick-borne
diseases.
Opportunities for the Development of
New Technology or Approaches
The United States is well-positioned to markedly
change tick-borne disease diagnosis for
the better. A Federal response that includes
diagnostic test development and implementation
would decrease the number of missed diagnoses
of Lyme disease and other tick-borne infections,
thereby reducing the number of people who have
short- and long-term negative health effects due
to untreated infections. Additionally, improved
tests for tick-borne diseases would reduce the
likelihood of false positive and false negative
results. Also, current diagnostic measurements
do not reliably change with treatment, so there is
essentially no “test for cure.” Improved tests for
tick-borne infections could decrease the societal
burden of Lyme disease and other tick-borne
diseases and associated costs to public health
care systems. A strong Federal response and
immediate investment would help enable rapid
improvements.
However, recent research has helped us
make progress in improving current testing
methodologies and also developing new
technologies or repurposing existing
technologies. Many new tests for infectious
diseases have the potential to be diagnostically
useful for Lyme disease. Improved serological
tests are being developed that target multiple
and more specific components from
Borrelia
or simultaneously detect all tick-borne
infections. Metagenomic sequencing of DNA/
RNA and proteomics can be used to identify
tick-borne pathogens in clinical samples.
Transcriptomics and metabolomics are methods
of comprehensively assessing a patient’s host
response during all stages of infection and can
be potentially leveraged for use as a method
of staging disease. Emerging technologies and
diagnostic platforms—including microfluidics,
affinity capture technology, cytokine release
assays, and nanopore sequencing—are being
repurposed for Lyme disease and other tick-borne
infections.
populations, especially children, in Lyme
disease and other tick-borne diseases
diagnostic studies.
Recommendation 5.2:
Include special
Opportunities to Include Special
Populations in Studies of New
Diagnostics
Of the approximately 300,000 new cases of
Lyme disease occurring each year (Hinckley et
al., 2014; Nelson et al., 2015), more than half
occur in children. However, to date, the majority
of studies evaluating Lyme disease diagnostics
have included few, if any, pediatric patients.
Unique challenges in diagnosing Lyme disease
in children abound. Those challenges include
differences in clinical presentation and a reliance
on caregivers to recognize illness and seek care
for pediatric patients. Additionally, many health
care professionals lack the knowledge that would
enable them to suspect possible Lyme disease
based on presenting signs and symptoms.
In addition to children, there are other patient
populations who have been under-represented in
studies evaluating tick-borne disease diagnostics.
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Those populations include
Possible Actions
Congress can increase appropriations to NIH and
other Federal organizations to fund research that
will advance the ability of health care professionals
to accurately diagnose and effectively treat
patients with tick-borne disease. NIH and other
Federal organizations may then take advantage
of current and existing peer-review processes to
evaluate the feasibility and impact of proposed
research projects, including projects that will
•
•
•
•
•
Under-represented minorities;
Patients from geographic areas with a low
reported prevalence of Lyme disease;
Immunocompromised patients;
Pregnant women; and
Neonates born to women who were
infected during pregnancy.
Recognition of the classic skin findings in
individuals with dark skin pigmentation may
be challenging, resulting in delays or even
failure to diagnose Lyme disease and other tick-
borne diseases. Clinicians who care for patients
residing in geographic areas with a low reported
prevalence of tick-borne infections require
additional education to appropriately suspect
Lyme disease, other tick-borne infections, and
coinfections in patients with appropriate signs
and symptoms
and
to be cognizant of potential
false positives and false negatives. Patients with
suppressed immune systems may not mount a
reliable antibody response to infection; in such
cases, reliance on currently available serological
tests may not be appropriate. Moreover,
hormonal changes during pregnancy can lead to
changes in immune function that may affect the
detection of clinical or laboratory findings.
Clinician awareness and recognition of the
possibility of Lyme disease and other tick-borne
diseases is an important component of the
diagnostic process. Most health care professionals
have received little or no specific training on
the recognition, appropriate evaluation, and
interpretation of testing for tick-borne diseases.
Clinician and patient education and training
should include consideration of additional
diagnostic issues pertinent to the above-
mentioned special populations.
•
•
•
Support translational research leading to
the development of diagnostic tests;
Rapidly translate new diagnostics into
test platforms that can be submitted for
clearance or approval; and
Encourage scientists to repurpose existing
technologies available for the diagnosis of
other diseases, such as cancer and non-tick-
borne infectious diseases.
Other ideas to explore include funding to
develop new, or enhance existing, repositories
of biological samples for basic research and test
validation; private-public partnerships; open
source data-sharing; and cash-based prizes for
the development and validation of diagnostic
technologies.
Additionally, the Working Group has identified
three potential actions that the Federal
Government could take to improve testing
and diagnosis of Lyme disease and tick-
borne infections in children and other special
populations. Those actions are to
•
Encourage the inclusion of special
populations in future Federally funded
research on Lyme disease, other tick-borne
infections, and coinfections;
Provide Federal funds for the development
of high-quality tick-borne infection biobanks
that include special populations; and
Develop and disseminate high-quality
online clinician education modules that
address the diagnosis of tick-borne
infections generally, and special populations
more specifically.
•
•
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DIAGNOSIS
Minority Response
This Minority Response was generated to address the Working Group’s recommendation to
evaluate new technology or approaches for the diagnosis of Lyme disease and other tick-borne
diseases. The recommendation is positive but long range and does not address the immediate
problem facing patients who are unable to get diagnosed using the current two-tiered Lyme
disease testing system.
The two-tiered system was adopted at the 1994 Dearborn, Michigan, meeting, which was co-
sponsored by FDA, NIH, CSTE, the National Committee for Clinical Laboratory Standards (NCCLS), and
sponsored by laboratory directors, the state health department, and CDC. It was announced at the
meeting that the two-tiered testing system would be part of the surveillance case definition for Lyme
disease. A number of experts at the meeting disagreed with the decision because they felt the narrow
definition would miss many patients, especially with the unexpected exclusion of some specific bands
from the Lyme disease western blot test, bands most likely related to the development of a Lyme
disease vaccine.
Health care professionals soon began using the two-tiered surveillance testing criteria in the clinical
setting to diagnose patients. Laboratories only reported the CDC-recommended bands of the western
blot test, leaving doctors without key information that might have helped them diagnose patients. As
a result, more and more patients missed the window of early diagnosis, allowing their conditions to
become chronic and challenging to treat, if they were able to get treatment.
A 2005 survey of patients by the California Lyme Disease Association revealed that 73% were denied
a diagnosis for Lyme disease at least once due to a negative ELISA test result by CDC criteria, and 31%
of those were denied access to a western blot test by their physicians due to a negative ELISA result.
The survey also showed that 61% of respondents were denied a diagnosis of Lyme disease at least
once due to a negative western blot test result by CDC surveillance band criteria. The survey authors
concluded that widespread misuse of the CDC surveillance criteria for diagnostic purposes resulted
in significant diagnostic delays and chronic and debilitating illness for patients nationwide (Johnson &
Denham, 2005). Band exclusion played a significant role in that scenario. Exacerbating the problem,
the Infectious Diseases Society of America (IDSA) incorporated the two-tiered testing criteria into
its 2006 Lyme disease treatment guidelines, formally transforming a testing protocol intended for
surveillance into a diagnostic protocol for use in the clinical setting, complete with the band exclusions.
If laboratories were required to report out all the bands in the current Lyme disease western blot
test, including those that were excluded based on a decision made in 1994, physicians would have
to be developed, and that a meeting should be held involving all relevant stakeholders, including
treating physicians, patients, family members, and advocates, to review all interpretive criteria for Lyme
disease testing using the newest diagnostic methodologies, techniques, and technologies. Meanwhile,
the missing bands need to be restored to the Lyme disease western blot test.
access to a valuable tool to help diagnose patients and facilitate treatment, perhaps preventing the
development of chronic disease. There is general agreement that tests using newer technologies need
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References
Johnson, L., & Denham, T. (2005). CALDA CDC survey preliminary results.
Lyme Times,
41(Spring Issue),
36-37. Retrieved from
https://www.lymedisease.org/members/lyme-times/archive/2005-spring-
toc/
Emerging technologies and diagnostic approaches,
especially those that directly detect active infection, are
research priorities. This will give physicians better tools
for diagnosis and management of Lyme disease and other
tick-borne infections.
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Patient
Stories
In May of 2010, I was a healthy 43-year-old businessman living
with my family in New York City. One morning, I awoke with
symptoms consistent with a sinus infection that evolved into
what felt like the flu. A week later, I visited my internist, who
told me I had a viral infection. I mentioned that I had been
in areas endemic for Lyme disease, but my doctor did not
consider nor test for the illness.
My symptoms worsened in the following weeks. I experienced
stomach pain that migrated throughout my body, involuntary
twitches in my limbs, joint and tendon pain, difficulty
concentrating and memory loss, shortness of breath, difficulty
speaking, and insomnia. I revisited my doctor who once again
told me it was a virus. This time I requested a Lyme disease
test, but the result was negative. As my condition worsened,
with new symptoms piling onto the old ones, I saw six more
doctors, but none mentioned Lyme disease.
Four months into my illness, I went to a doctor who considered
my symptoms and suspected Lyme disease. He ordered a
David Roth
western blot test (my third), and the result showed all three
Retired, Senior Managing Director
IgM bands and four of the ten IgG bands. I also sought a
Finance Industry
second opinion from a “Lyme-literate doctor,” who treated
New York, NY
me for Lyme disease and later clinically diagnosed me with
babesiosis. With extensive, prolonged treatment for the illness
and its myriad symptoms, I slowly recovered to where I am now, about 85 percent of the person I was
before I became sick.
During 2010 and 2011, I was tested several more times for Lyme disease. One test came back positive,
several equivocal (negative by CDC standards but showing multiple bands), and one indicated I
had never been exposed to Lyme disease. I have since learned that the diagnostics used today were
developed before most modern technology.
My experience demonstrates that tick-borne diseases are not properly diagnosed and treated in the
United States. We need better diagnostics, better treatments, safe and effective vaccines, as well as
better medical training and public awareness to combat tick-borne diseases.
David Roth
44
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Chapter 6
Treatment
Recommendations at a Glance: Treatment
Recommendation 6.1:
Prioritize research into the potential pathogenic mechanisms
(such as immune response, cross-reactivity, autoimmunity, bacterial persistence,
coinfections, and other mechanisms) of persistent symptoms in patients who have
received standard treatment regimens for tick-borne diseases, including Lyme disease.
Recommendation 6.2:
Promote research on animal models of
Borrelia burgdorferi
infection (that is, Lyme disease) and the mechanisms of disease processes in
humans with an emphasis on pathologies that are currently lacking, for example,
neuroborreliosis.
Recommendation 6.3:
Improve the education and research on transmission (including
transmission via the blood supply and pregnancy) and treatment of other tick-borne
diseases and coinfections.
Recommendation 6.4:
Conduct additional clinical trials appropriate to the target
populations where gaps may exist.
Recommendation 6.5:
Improve the education and research on the pathogenesis of
alpha-gal allergy, also known as the tick-caused “meat allergy.”
Background
Tick-borne diseases occur in all regions of the United States and are the cause of an increasing burden
of disease.
Ixodes
species alone can transmit multiple human pathogens, including
B. burgdorferi,
the
as the American dog, Rocky Mountain wood, and brown dog ticks (Dermacentor
and
Rhipicephalus
causative agent for Lyme disease. Other tick species such as the lone star tick (A.
americanum),
as well
species) also transmit serious diseases such as Rocky Mountain spotted fever and ehrlichiosis, which
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can be fatal if not treated promptly. In addition,
coinfection by ticks carrying human and animal
pathogens is more widespread than is commonly
majority of the known tick-borne disease burden
in humans.
The estimate of annually occurring new cases of
(Hinckley et al., 2014; Nelson et al., 2015).
recognized by both medical professionals and
the general public. The importance of newly
recognized agents of disease (for example,
A.
Lyme disease in the U.S. is approximately 300,000
The costs associated with both antimicrobial
phagocytophilum, B. miyamotoi,
and Powassan
human host are not yet fully understood
virus) and how they interact with each other in the
(See Figure 12).
and palliative therapies are high. Patients with
manifestations may experience short- and
longstanding untreated disease or with ongoing
long-term disabilities, some approximating the
disability experienced with congestive heart
burden can be substantial.
failure, and the attendant financial and societal
Most individuals who present with symptoms
The fundamental goal of most treatment for
Lyme disease and other tick-borne diseases is
to restore health by treating the disease-causing
parasitic, or viral. While bacterial and parasitic
pathogens. Tick-borne diseases can be bacterial,
diseases are treated by antimicrobials, tick-
with supportive care. Some tick-borne viral
of early Lyme disease, for example EM lesions
borne viral diseases are usually treated solely
infections, such as the Powassan virus, can lead
to permanent neurological symptoms; and no
effective treatment exists for severe Powassan
accompanied by flu-like illness, will recover with
a sufficient course of antibiotics. However, not
all infected humans develop an EM rash, and the
EM may not be noticed or correctly identified in
difficulties in diagnosis, as “flu-like” symptoms
some patients. The absence of an EM rash creates
virus encephalitis, which has a 10% mortality rate.
and infections, Lyme disease still accounts for the
While there are many different tick-borne diseases
are a non-specific finding seen in Lyme disease
ignored by patients or clinicians.
and associated tick-borne diseases, and might be
Figure 12: Types of Organisms That Cause Tick-Borne Diseases
A
B
C
Ticks transmit a range of infections and pathogens, which may be caused by viruses (panel
A),
parasites (panel
B),
and bacteria (panel
C).
Tick-borne diseases may occur either alone or in
combination, which is called a coinfection.
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involving the nervous system, heart, and/or
musculoskeletal tissues. Treatment at this later
stage of infection can be successful but may result
in delayed recovery. Patients may also develop
chronic illness, especially those with central
nervous system and peripheral nervous system
manifestations. Some doctors may choose to treat
these patients with additional antibiotics.
The underlying cause(s) of ongoing disease after
initial antibiotic therapy has been debated in
the medical community and remains a subject
of intense discussion. It is imperative to perform
further basic research to understand these
mechanisms of disease manifestations both
before and after treatment, and then use this
knowledge to identify and test highly effective
therapies to shorten the duration of illness and
minimize the number of people who remain ill
following treatment.
Patients may be misdiagnosed early in infection
because of insufficiently accurate diagnostics and
confusing disease presentations. Unless treated
within the first few weeks of infection, patients
with Lyme disease may develop a multisystemic
illness with clinical inflammatory conditions
the most accurate systems to identify bacterial
factors necessary for infection, to explain host
mechanisms involved, with bacterial clearance or
tolerance, and to determine whether a therapy
can cure infection. Most of what we know about
infection comes from these animal models,
including the study of infection in the white-
footed mouse (Peromyscus
leucopus),
the natural
reservoir species in much of the United States.
However, infection manifestations can vary from
species to species. Therefore, care must be taken
when interpreting these results and their potential
applicability to human disease, particularly when
comparing immunologic responses in a natural
host with those of other mammalian species.
Initially, during a bite from an infected tick,
B.
burgdorferi
is passed through the skin into the
bloodstream and then throughout the body (See
Figure 13). In humans,
B. burgdorferi
disseminates
widely via hematogenous, lymphatic, and tissue
routes. Common dissemination sites include the
musculoskeletal system, skin, nervous system, and
heart. Even before
B. burgdorferi
can travel from
the tick to the vertebrate, tick salivary proteins are
injected through the bite and begin the process
of altering the immune system to allow for
infection to be established.
B. burgdorferi
first comes into contact with
The Immune System and
B. burgdorferi
A hallmark of the Lyme disease-causing
bacterium,
B. burgdorferi,
is its ability to efficiently
transmit from feeding
Ixodes
species ticks to
vertebrates, disseminate throughout the body,
and establish long-term, persistent infection in
the absence, and sometimes in spite of, antibiotic
treatment. This persistent infection is maintained
even when the infected mammal has a complete,
functional immune system.
There is strong evidence that
B. burgdorferi
manipulates its host’s immune system to
enable its persistence. Studying infection in
animal models is important because they are
the innate immune system, including the
complement cascade. This cascade is key in
the rapid, initial host defense and detects and
clears foreign invaders.
B. burgdorferi
infection
in mice is known to resist all three pathways of
complement cascade activation (classical, lectin,
and alternative).
In the second phase of the host response to
B. burgdorferi
infection, adaptive immunity
develops. The antibodies of mice are effective
in clearing a large number of spirochetes, but
not all of the bacteria are eliminated. In mice,
B. burgdorferi
both cloaks itself in host proteins
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TREATMENT
to “hide” from the immune system and rapidly
changes the proteins on its outer surface. By
the adaptive immune response’s ability to
match the antigens being produced.
performing this antigenic variation, it can outrun
produce specific neutralizing antibodies that
Antibiotic-treated humans who have recovered
Potential reasons for this reinfection include
suboptimal immunologic memory, and/or
from infection are susceptible to reinfection.
continue to experience symptoms that can persist
for six months or longer. Patients who remain
symptomatic are objectively ill as measured by
instruments that have been well validated for
measuring symptoms and health-related quality
these patients remain ill following a standard
course of antibiotics.
The spectrum of disease manifestations in
of life. We currently do not fully understand why
as demonstrated in several case reports. Recent
infection by different strains of
B. burgdorferi,
untreated and PTLDS patients is quite broad.
of PTLDS constitute a subset of patients who
In cases where symptoms and signs of Lyme
disease continue following initial treatment,
immune dysfunction, persistent infection by
the bacteria or its parts, complications from
coinfections, and/or a combination of these
it is difficult to know if they are caused by
(Note: Patients who meet the research definition
studies in mice showed a lack of memory B cells
and long-lived plasma cell induction following
B.
burgdorferi
infection that correlated with a rapid
collapse of the lymph nodes usually responsible
immunologic memory has not been demonstrated
for immunological memory. This lack of
have been diagnosed with chronic Lyme disease.)
in humans.
The reduction in immune response effectiveness
were vaccinated with another pathogen, in this
was also seen when
B. burgdorferi-infected
mice
tick-borne pathogens, including
B. burgdorferi,
and different components of the mammalian
leaving many gaps in our understanding of
and other pathologies. The interaction between
generalized alteration of the immune system
in mice during
B. burgdorferi
infections. The
case influenza, providing evidence for a more
immune system has not been fully investigated,
disease pathogenesis. While studies have shown
the ability of
B. burgdorferi
to survive antibiotic
therapy
in vitro,
the pathogenesis of persistent
symptoms in animals and humans is not fully
mechanism by which this immune alteration is
achieved is unknown and merits further study
in other mammalian species that are not natural
hosts for
B. burgdorferi.
of Lyme disease and other tick-borne diseases in
not been developed to gain a full understanding
humans.
understood, and sufficient animal models have
Major Challenges and Issues
While most Lyme disease patients who are
diagnosed with early acute disease have
symptom resolution when treated with
Establishing highly successful treatment regimens
for some Lyme disease presentations and other
researchers, clinicians, and patients. Current
tick-borne diseases is an ongoing challenge for
appropriate courses of antimicrobial therapy,
data for post-treatment Lyme disease (PTLDS)—
10-20% of the patients—based on available
guidelines for recommended treatment may have
recent clinical trials being funded despite growing
been in place for a decade or more, with few
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Figure 13:
Borrelia burgdorferi
Causes Lyme Disease
transmitted by ticks and accounts for 82% of all U.S. tick-borne disease cases.
B. burgdorferi,
the bacterial agent of Lyme disease, is the most common infection
knowledge about diversity and severity of disease
manifestations, including fatal cases of Lyme
carditis. Although some clinical studies in North
America support current antibiotic treatment
regimens for Lyme disease, these studies are
limited in size and scope, and the endpoints
potentially important variant species in humans
(that is,
B. mayonii
in the Midwest; other
B.
burgdorferi sensu lato
species,
B. miyamotoi),
In addition, the discovery of uncommon but
and regionally variant diversity of
B. burgdorferi
Coast) have received little research focus to
used were not developed in consultation with
in ticks (especially in the Southeast and the West
date. Some of these
Borrelia
species may not be
of Lyme disease (for example, neuroborreliosis,
PTLDS, and Lyme carditis) are also insufficient.
Recent evaluations by Cochrane (treatment of
treatment guidelines and evidence review in
patients. Treatment trials for other presentations
disease, may persist following standard anti-
detected by standard two-tiered testing for Lyme
neurologic Lyme disease) and NICE (Lyme disease
the United Kingdom) found that there is poor
infective therapies, and may result in increased
such as the longhorned tick (Haemaphysalis
morbidity and mortality. New, exotic Asian ticks
evidence based on comparative antibiotic trials
disease manifestations, including early disease
also noted weaknesses in study design and
outcome assessment.
longicornis)
have recently been discovered in
associated with the virus that causes severe
to determine the best treatment regimen in Lyme
and late Lyme neuroborreliosis. The evaluations
multiple U.S. states. This tick species has been
fever with thrombocytopenia syndrome (SFTS),
China, as well as the alpha-gal allergy in other
parts of the world. Resources, therefore, need
an emerging hemorrhagic fever discovered in
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TREATMENT
to be allocated to enhance surveillance, to
tick populations have increased, and their ranges
on Ecology and Epidemiology). This expansion
investigate pathogenesis, and to determine how
organisms.
to treat diseases associated with these emerging
Infections caused by bacteria of the genus
have expanded across the country (see chapter 3
brings tick-borne diseases and infections to
regions where the need for tick-borne disease
nor the curriculum developed.
Bartonella
complicate tick-borne infections in
humans.
Bartonella
species are responsible
for some emerging and re-emerging diseases
education programs is not yet fully appreciated
from benign and self-limited diseases to severe
of
Bartonella
is the cat flea, and other known
worldwide and can present with illnesses ranging
Recommendations
The Working Group has identified five initiatives
that the Federal Government could invest in to
improve the treatment of tick-borne diseases
and life-threatening illnesses. The primary vector
vectors include sand flies, the chiefly European
castor bean tick (Ixodes
ricinus),
and body lice.
and
Bartonella
can be detected in the tick
Tick transmission has been confirmed in dogs,
first three are interrelated and dependent on one
together as follows.
and significantly improve patient outcomes. The
another for success; they are, therefore, presented
microbiome. While many patients with tick-borne
diseases present with symptoms consistent with
Bartonella
infection, laboratory diagnosis can
be inaccurate, making confirmation difficult.
Irrespective of vector,
Bartonella
infections may
play a significant role in tick-borne disease
infections, based on case reports and patient
registries. Supporting
Bartonella
research is vital
regimens and to confirm vector competency for
North American
Ixodes
tick species.
Lack of scientific understanding of disease
to determine the most appropriate therapeutic
into the pathogenesis (such as, immune
response, cross-reactivity, autoimmunity,
bacterial persistence, coinfections, and
other mechanisms) of persistent symptoms
in patients who have received standard
treatment regimens for tick-borne diseases,
including Lyme disease.
Recommendation 6.1:
Prioritize research
Recommendation 6.2:
Promote research
on animal models of
Borrelia burgdorferi
infection (that is, Lyme disease) and the
mechanisms of disease processes in
humans with an emphasis on pathologies
that are currently lacking, for example,
neuroborreliosis.
and physicians. Patients may not recall having
with symptoms until months or years after the
mechanisms leads to confusion for both patients
a tick bite-caused EM rash and may not present
onset of the infection. Disease manifestations are
numerous and span most major body systems,
and patients with these diseases can present
to many different primary care and specialist
clinicians in both outpatient and inpatient
settings. In addition,
Ixodes
and
Ambylomma
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education and research on transmission
(including transmission via the blood supply
and pregnancy) and treatment of other tick-
borne diseases and coinfections.
Our limited knowledge of how tick-borne
infections cause human diseases hampers our
ability to successfully identify patients and
treat them appropriately. These persistent
manifestations in patients may be due to multiple
overlapping etiologies increasing an inflammatory
process. Possible etiologies include immune
dysregulation, such as autoimmunity or cross-
reactivity, bacterial persistence of the spirochete
Recommendation 6.3:
Improve the
Lyme disease, there is currently no representative
animal model to mimic the disease course of
Lyme neuroborreliosis. We similarly lack a full
understanding of the role of other tick-borne
infections and how they may be contributing
to neurological symptoms in those with Lyme
disease. Development of a representative animal
model to explore the disease course and long-
term consequences of neuroborreliosis and other
tick-borne infections should be a priority.
or its parts, or coinfection with additional
pathogens such as
Anaplasma, Babesia,
and
B.
miyamotoi
(relapsing fever). Research on the
pathogenic mechanisms of human diseases
induced by
B. burgdorferi
and other tick-borne
infections has been sparse and should be
prioritized and funded in the future.
processes, including
Borrelia’s
ability to evade
the immune system and its ability, in laboratory
studies, to form “persister” cells that enable its
survival despite antibiotic treatment.
One important tool in understanding disease
mechanisms in humans are animal models, but
each animal model has unique advantages and
disadvantages for understanding human disease.
Several different animal models have contributed
substantially to our knowledge of the bacteria’s
ability to cause human disease; however, there
are many gaps. Studies using these models can
contribute to a deeper understanding of disease
Another potential pathogenic mechanism that
requires additional study is potential immune
suppression by tick-borne pathogens. For
example,
Anaplasma
may lead to immune
suppression;
Babesia
can worsen clinical
manifestations of Lyme disease while leading
to impaired clearance of other parasites; and
Bartonella
can act as a stealth pathogen, evading
both the cellular and humoral immune response.
As shown in recent mouse models,
B. burgdorferi
seems to hamper the production of high-quality,
long-lasting antibodies that can control
B.
burgdorferi
infection levels, but cannot clear the
infection. These studies also suggest that the
inhibition of strong adaptive immunity during
B. burgdorferi
infection extends to responses to
other pathogens, such as influenza. Whether or
not this more general immune suppression occurs
in humans should be further studied, as it may
have diagnostic and treatment implications for
patients who are simultaneously or sequentially
infected with more than one tick-borne pathogen.
Once a better understanding of underlying
causes and mechanisms (that is, disease etiology)
in individual patients has been developed,
new therapeutic strategies for PTLDS, chronic
Lyme disease, and complex conditions could be
priority.
initiated. This development should be an area of
In patients with late Lyme neuroborreliosis,
neurological manifestation of infection can cause
significant morbidity. Patients with neurological
disease are more likely to remain ill despite initial
antibiotic treatment. While there have been
studies on the effects of neurological infection in
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TREATMENT
It is also important to conduct animal model
clinically than previously recognized. Molecular
cause disease are poorly understood. Animal
models of the different infections are lacking
are imperfect replications of human disease.
research on modes of transmission (for example,
maternal fetal transmission, transplant/blood
banking) for all tick-borne diseases.
B. miyamotoi
has been shown to be able to survive in human
blood components, and other tick-borne
mechanisms of how these tick-borne pathogens
in many cases; when they do exist, the models
Simultaneous or sequential coinfections with
infections such as
Babesia, Bartonella, Anaplasma,
be transmitted by blood transfusion, and in some
cases by organ transplantation. More education
about the potential risk of contracting tick-borne
diseases after transfusion and/or transplantation
is needed so patients can be monitored for tick-
borne diseases after these procedures.
Ehrlichia,
and
Rickettsia
have been reported to
more than one tick-borne pathogen may also
complicate disease manifestations, diagnosis, and
into the pathogenesis of the different interactions
between these pathogens is crucial to improving
treatment and patient care and should be a
priority for funding.
appropriate treatment regimens. More research
Whether persistence exists after an acute infection
with the deer tick virus/Powassan virus is an
important question, as this has been established
Recommendation 6.4:
Conduct
additional clinical trials appropriate to the
target populations where gaps may exist.
regimens for many tick-borne disease
Establishing highly successful treatment
virus. Presently there is no effective treatment
for other flaviviruses like Zika and West Nile
for neurological complications of Powassan virus
in Lyme disease-endemic areas, the numbers of
infection, and serological studies have shown that
individuals exposed are increasing (Knox et al.,
presentations, including but not limited to, Lyme
2018). Treatment regimens for different infection
stages and the impact of delay in diagnosis must
that studies the effect of simultaneous infection
with multiple tick-borne pathogens in humans
of human tissue—specifically, surgical, biopsy,
and post-mortem tissue—are
also critical to
be evaluated. It is imperative to support research
Recent information has emerged about the
challenge for researchers, clinicians, and patients.
recognized tick-borne diseases, is an ongoing
neuroborreliosis, PTLDS, coinfections, and newly
breadth of diversity of tick-borne disease clinical
presentations and infections in the United States.
Clinical trials for treatment of some aspects of
in order to improve treatment. Research studies
disseminated or late Lyme disease and other tick-
borne diseases are limited in size and scope.
While treatment of patients with early Lyme
disease can be successful with two or three
weeks of antibiotics, clinical trials of more
the pathophysiology of this infection and how
advancing the scientific understanding regarding
changed to more appropriately treat patients with
Lyme disease.
Tick-borne infections are more numerous than
previously known, and more complicated
diagnostic and treatment paradigms might be
serious manifestations have not established
whether this should be the optimum duration
treatment have been in place for a decade or
of therapy. Guidelines outlining recommended
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lack of broad-based human trial data hampers
our ability to identify optimal treatment strategies
for the different stages and manifestations of
Lyme disease and tick-borne disease infections in
patients.
Recognizing the constraints of traditional
research and the opportunities afforded by new
technological advances, government institutions
are adopting big data, patient-centered research,
and personalized medicine initiatives. Examples
include patient-powered research networks,
patient-powered registries, the National Patient-
Centered Clinical Research Network (PCORnet),
FDA’s Patient-Focused Drug Development
program, VA’s Million Veteran Program, and the
NIH Collaboratory. These 21st-century data tools
more, but few recent clinical trials have been
funded despite growing knowledge about
diversity and severity of disease manifestations,
including fatal cases of Lyme carditis. In more
serious manifestations of the disease, such as
Lyme carditis or neuroborreliosis, the evidence
for optimal treatment derived from robust clinical
trials in North America is also insufficient. This
•
the human fetus has been recognized for
Pregnancy:
Transplacental infection of
relapsing fever borreliosis, as well as Lyme
borne flaviviruses. Pregnancy poses
disease, babesiosis, and certain arthropod-
particular challenges for treatment because
few antimicrobials have been approved
and are safe to use during pregnancy.
Additional research into appropriate
treatment options are needed.
•
Other tick-borne pathogens:
The
importance of supporting research into
treatment outcomes for other tick-borne
infections as well as coinfected patients
cannot be understated.
◊
The best treatment regimens
for two emerging pathogens,
A. phagocytophilum
and
B.
miyamotoi,
are currently unknown
and have not been studied in any
clinical trials. Presently there is no
effective treatment for neurological
complications of Powassan virus
infection, which can be fatal. In
addition, resistance to standard
medications for treating babesiosis
has been reported in the scientific
literature. Newer, more effective
treatment regimens targeting these
pathogens are needed.
◊
The understanding of the regionality
of strains and species continues to
evolve. Other
B. burgdorferi sensu
lato
species (B.
mayonii, B. bissettii)
are now known to infect humans in
North America.
◊
There is little understanding if
different treatments are necessary
when multiple pathogens coexist in
the same patients, and if multiple
simultaneous coinfections change
the accuracy of diagnostics for
one or both of these infections.
Peer-reviewed literature suggests
be further evaluated in clinical trials for patients
with persistent disease symptoms after treatment.
In addition to trials to evaluate treatments for
patients who remain ill after initial treatment, gaps
in other patient populations exist.
registry has enrolled over 10,000 patients, and
data from this registry could identify regimens to
could hold enormous potential for tick-borne
disease research. For example, an existing patient
•
Pediatric population:
Comprehensive
studies of children with tick-borne
disease—both
cross-sectional and
prospective—are needed to better
understand potential manifestations in
the patients who continue to be ill despite
antibiotic treatment.
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TREATMENT
coinfection of a patient with
Babesia
and
Borrelia
or with
Ehrlichia,
Anaplasma,
and
Borrelia
result in
increased symptoms and a longer
duration of illness. Knowledge of
how simultaneous coinfections may
affect morbidity and mortality is
crucial to improving treatment.
To enhance our ability to perform clinical
trials more efficiently, a national consortium of
investigators and physicians to facilitate Lyme
disease clinical trials should be constructed. This
antibody immunoglobulin (Ig) E against the
carbohydrate oligosaccharide galactose-alpha-
1,3-galactose (alpha-gal), which has been found
of tick. In patients with convincing evidence
in the gastrointestinal tract of at least one species
of IgE-mediated alpha-gal allergy, the allergic
be delayed three to six hours after ingestion of
meat. It can present with rash-like (urticarial),
reaction can begin within several minutes or can
gastrointestinal symptoms, and airway obstruction
(angioedema). Fatalities are rarely seen, but it
can be life-threatening with anaphylaxis. Patients
mammalian meats, gelatin (highly sensitive
consortium should conduct multi-regional trials
simultaneously, investigating various agents and
treatment durations, using a core set of patient-
centered outcomes.
Despite the large number of patients being
react to a carbohydrate antigen in all non-primate
individuals may react to bovine serum albumin
dairy. Personal care products, certain medical
in a drink or gelatin in a capsule), or very rarely,
products, and nutritional supplements are not
anecdotal cases have been discussed.
diagnosed each year, we do not fully understand
how best to treat patients with Lyme disease and
that include patient and physician perspectives
equip clinicians in treating the many different
other tick-borne diseases. Additional clinical trials
on appropriate endpoints are required to better
presentations of Lyme disease and other tick-
costs and decrease human suffering.
typically implicated in alpha-gal allergy, although
The magnitude of the problem and the true
number of cases of alpha-gal allergy is unknown.
and it is not a reportable disease. Endemic
borne diseases in order to reduce health care
There is very little awareness of alpha-gal allergy,
regions in the United States correspond with the
distribution of lone star ticks, which range from
education and research on the pathogenesis
of alpha-gal allergy, also known as the tick-
caused “meat allergy.”
In addition to infections and diseases, tick bites
can also cause other life-threatening allergic
reactions such as alpha-gal allergy. In the United
States, alpha-gal allergy occurs in individuals
who have experienced prior bites from the lone
Recommendation 6.5:
Improve the
Long Island to the Southeastern states, although
its range has expanded rapidly and extensively
across much of the Eastern and Midwestern
United States during the last 50 years. Some
authorities have suggested that the number
of cases of alpha-gal allergy may be as high
as the number of other tick-borne infections.
geographic range of lone star ticks expands.
The number of cases is likely to increase as the
Increased awareness and public health education
programs targeting both the general public and
clinicians in endemic areas are, therefore, needed.
star tick (A.
americanum).
Unlike other tick-borne
diseases, this illness is not thought to be caused
by an infection, but by the development of the
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In addition, raising pre-diagnosis awareness
and providing counseling and education after
diagnosis on how to prevent exposure to the
allergen will help to improve the care of those
the medical community that misdiagnosis due
to inaccurate diagnostic tests for tick-borne
disease may lead to unnecessary therapies,
especially when symptoms persist after standard
real-world evidence, including basic research
treatment. A comprehensive review of all current,
suffering with this potentially life-threatening
illness.
Education: Signs,
Symptoms, and Treatment
There is an urgent need to educate health care
of these tick-borne infections and tick-caused
providers on the signs, symptoms, and treatment
allergic reactions. Recent published reports of
disease specialists, for diagnosis and treatment
general public should, therefore, be undertaken.
Additional comprehensive clinician education
should highlight diverse symptomology,
expanding geography of vector ticks, and
of tick-borne disease for clinicians and the
evidence and clinical evidence from tick-borne
limitations of current testing and treatment
several deaths caused by undiagnosed cases of
as well as the rising cases of alpha-gal allergy,
protocols. The content must be developed with
input from research scientists, physicians, and
patients to provide broad but rigorous content to
Lyme carditis and Rocky Mountain spotted fever,
illustrate the vital importance of comprehensive
well as tick-caused allergies and conditions.
Manifestations of tick-borne infections are
medical providers and the general public.
medical education for all tick-borne diseases, as
Because of the diverse and migrating clinical
numerous and span most major body systems.
symptomology, patients with tick-borne disease
can present to many different primary care and
specialist clinicians in outpatient or inpatient
pediatrics, emergency medicine, cardiology,
settings, for example, internal/family medicine,
rheumatology, neurology, and psychiatry.
Working Group, multisystemic manifestations of
tick-borne disorders combined with inaccurate
diagnostics and lack of effective treatment
protocols result in misdiagnoses, increased
According to patient testimonies given to the
suffering and disability, as well as increased out-
of-pocket health care expenses. On the other
hand, there is substantial concern in some of
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TREATMENT
Minority Response
While submitted as a Minority Response, the author believes that the essence of this content
reflects a point of view shared by a broad community of clinicians and researchers. All authors
of the Treatment chapter agree on the general recommendations presented in this chapter. We
also agree on the importance of enhanced research into the pathogenesis of PTLDS and other
situations associated with persistent symptoms after antibiotic treatment, as well as the need for
increased support for research into different aspects of the treatment of Lyme disease and of tick-
borne diseases in general. However, as a fusion of work of several subcommittees, the chapter
posed challenges for the authors to integrate differences in emphasis and priority, as well as the
interpretation of the existing science. The following comments regarding gaps and priorities
differ in some respects from those presented in the Treatment chapter.
Additional Research Gaps in the Treatment of Lyme Disease
At least nine randomized clinical trials of antibiotic treatment of early Lyme disease have been
heterogeneous in the choice of antibiotics compared and in study design, these studies are consistent
in 1) their demonstration of the effectiveness of standard treatment strategies, and 2) treatment
recommendations. In addition to the clinical studies mentioned above, a large retrospective two-
conducted in North America, and several additional studies have been conducted in Europe. While
year study reviewed the outcomes of standard antibiotic regimens in more than 600 patients with
early Lyme disease. Results of the study demonstrated that subsequent reinfection (4% of the cases)
measures for those at risk (Kowalski, Tata, Berth, Mathiason, & Agger, 2010).
was more common than treatment failure, which underscores the importance of ongoing preventive
This is not to imply that additional research cannot lead to improvements in these treatment strategies
for early Lyme disease, but rather that research priorities may be best focused on the refinement of
available treatment options for the most problematic, yet less completely studied, manifestations
of Lyme disease, such as neurologic complications of Lyme disease or persistent Lyme arthritis. In
candidate biomarkers to gain insights into pathogenesis and to evaluate post-treatment effects.
addition to comprehensive clinical measurements, future treatment trials, ideally, should also assess
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Research Gaps in Treatment of Other Tick-Borne Infections
While at least five different antibiotic agents of several classes are effective in the treatment of Lyme
tick-borne diseases (that is, anaplasmosis, ehrlichiosis, and rickettsial diseases), and that antibiotic
class carries a contraindication to its use during pregnancy. In regions of the United States where
disease, currently only one available antibiotic class has been proven to be effective for several serious
Lyme disease is infrequently transmitted, ehrlichiosis and/or other rickettsial infections may cause the
transfusion, is on the rise in a wider geographic area and can cause an acutely life-threatening infection
in persons with immune compromise. Currently available treatment options are usually effective,
but limited. All of these tick-borne diseases cause human illness primarily as sole infections, though
greatest burden of tick-borne disease. Babesiosis, transmitted by black-legged ticks and through blood
coinfections can occur with more than one pathogen, if the pathogens are transmissible by the same
tick species.
In determination of the priority of research focus, it is important to discern the regional differences in
tick-borne microbial pathogens and the overlap in some of their clinical presentations.
diseases transmitted and their impact. Scientific and clinical precision is required given the diversity of
References
Kowalski, T. J., Tata, S., Berth, W., Mathiason, M. A., & Agger, W. A. (2010). Antibiotic treatment duration
area.
Clin Infect Dis, 50(4),
512-520. doi:10.1086/649920
and long-term outcomes of patients with early lyme disease from a lyme disease-hyperendemic
The lack of understanding and agreement on the
cause and treatment of patients with chronic
symptoms after treatment of tick-borne diseases
has left patients in a divided world of controversy
without adequate access to affordable care.
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Patient
Stories
Nicole Malachowski
My name is Nicole Malachowski. I am a mother, wife, and retired U.S.
Air Force (USAF) colonel and F-15 fighter pilot; and I have neurological
tick-borne disease.
In the summer of 2012, while still serving in the Air Force, I went to
see a doctor about a growing rash on my right hip and was given
10 days of doxycycline and a topical cream. However, my condition
worsened despite the treatment. Within a month, I began experiencing
fevers, malaise, and burning sensations. A few months later, I began
experiencing neurological symptoms. One day while leading a
formation of F-15E fighter aircraft back from a training mission, I was
overcome by an overwhelming sense that my aircraft was turning left,
though it was not; and I could not get my hands to activate the switch
that I had activated thousands of times. After I finally managed to
activate the switch, I realized that I could not speak. Fortunately, my
experienced wingman led us home, and the instructor pilot in my jet
performed backseat landing.
However, that day marked the beginning of my medical odyssey.
In the following four years, I saw more than twenty doctors across
Colonel Nicole Malachowski
eight specialties. My neurological symptoms continued to worsen,
but none of the doctors knew why and some suggested it was all in
(USAF, Ret.)
my head. I was suffering from intensifying fatigue, joint and muscle
Career Officer, Leader, Fighter Pilot
pain, vestibular issues, ocular manifestations, sensory problems,
First Woman Pilot, USAF Air Demonstration
cognitive dysfunction, and the list goes on. I was misdiagnosed with
Squadron ("Thunderbirds")
everything from possible multiple sclerosis, to autoimmune disease,
Springfield, VA
to fibromyalgia. Eventually I could no longer work in the military as a
fighter pilot, and the military began steps to medically retire me. At
the age of 43, I was permanently, medically retired from the career I loved, after having served in the military for
more than 21 years.
By August 2016, my condition had deteriorated so much that I was having extreme difficulty with speech and
memory, and I could barely walk. Determined to find out the cause of my medical issues, my husband and
I poured through my medical records, and all signs pointed to the rash from 2012 and a tick bite I got the
following year while I was stationed in Rhode Island.
Out of sheer desperation, I reached out to a group of doctors specializing in tick-borne disease in Boston.
They ordered tests that confirmed neuroborreliosis (Borrelia
hermsii),
neurobartonellosis, babesiosis, and
anaplasmosis, confirming severe neurological tick-borne disease. The doctors immediately started treating me
with IV antibiotics. Within 10 days, my daily fevers, chills, sweats, and sleep disturbances were gone. Within a
few weeks, my ability to find words improved, and I could communicate again. However, I was not able to speak
fluently for several more months.
Because my illness went undiagnosed for so long, it is challenging to say how long I will need treatment and
how long my recovery will last. But I can tell you this: I went from someone who literally could not get out of
bed to someone who can take her seven-year-old twins to their soccer games. While I have not recovered
completely, I now have a life worth living. I would never have gotten to this point without the accurate diagnosis
made by competent, experienced physicians who knew how to recognize and treat the devastating tick-borne
illness that so many other doctors missed.
ervices
•
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Chapter 7
Access to Care,
Patient Outcomes
Recommendations at a Glance: Access to Care,
Patient Outcomes
Recommendation 7.1:
Create a Federal repository for information on Lyme disease and
other tick-borne diseases.
Recommendation 7.2:
Allocate increased funding for tick-borne disease in the areas of
research, treatment, and prevention proportional to the burden of illness and need.
Recommendations:
Ensure the rights of those dealing with Lyme disease and tick-borne
diseases and conditions by reducing the burden of the processes under which patients
are currently diagnosed and treated and by which they access care. Basic protections
must include, but not necessarily be limited to, those that:
Recommendation 7.3:
Protect patients from employment discrimination.
Recommendation 7.4:
Protect students of all ages from discrimination.
Recommendation 7.5:
Protect patients from health care and disability
insurance coverage and reimbursement policies that are unduly
burdensome.
Recommendation 7.6:
Protect the rights of licensed and qualified clinicians
to use individual clinical judgment, as well as recognized guidelines, to
diagnose and treat patients in accordance with the needs and goals of
each individual patient.
Major Issue 7.7:
Testing and Diagnostic Bands: How They Are Used Today and What That
Is Doing to Patients
•
•
•
Empower patients with data
Engage diverse stakeholders
Relay information as a neutral knowledge broker
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Background
The majority of people diagnosed with early,
acute Lyme disease or other tick-borne disease
are properly treated and make a full recovery; yet
many others are not so fortunate. This chapter
focuses on the patients in the latter category
and the challenges they face in the United States
today. Their numbers and the full scale of the
problem are unknown.
In a 2009–2010 survey of nearly 2,500 chronic
Lyme disease patients in the United States
with positive laboratory testing and chronic
symptoms, 49.5% of respondents reported
traveling 51 miles or more to see a treating
doctor (Johnson, Aylward, & Stricker, 2011).
Half of the respondents reported seeing at
least seven physicians before the diagnosis
of chronic Lyme disease was made. And most
respondents experienced symptoms lasting six
months or more despite receiving at least 21
days of antibiotic treatment. The follow-up survey
in 2013 indicated that chronic Lyme disease
patients made an average of 19.4 doctor visits
per year, compared to the general population,
which makes on average 3.7 visits (Johnson,
Wilcox, Mankoff, & Stricker, 2014). As evidenced
by the survey results, those who currently have
chronic tick-borne disease in the United States are
unlikely to receive a proper diagnosis from the
first provider they see.
Patients and caregivers who are new to tick-borne
diseases and unfamiliar with the past and present
science and politics surrounding them are often
surprised to discover that the path to diagnosis,
treatment, and long-term support for their illness
is fraught with obstacles and misinformation.
Nevertheless, they must navigate the road to
wellness despite high personal and out-of-pocket
costs as they strive for a return to optimal health.
The recommendations in this chapter are geared
toward finding creative ways to help tick-borne
disease patients and their families, friends, and
caregivers overcome the significant and often
unnecessary burdens they must endure by
eliminating recognized barriers to affordable,
appropriate, and patient-centered diagnosis,
treatment, and care. In co-creating these
solutions, a diversity of voices and opinions must
be heard, valued, and considered along with the
scientific evidence. Patient and caregiver voices
Figure 14: Health Insurance Claims
Health insurance claim denials and the resulting
financial challenges are obstacles for patients seeking
treatment for tick-borne diseases, especially for
complex cases.
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are, after all, data and should be included in
the scientific process. Moreover, the individual
patients and their needs and experiences must
be at the center of this effort to prevent further
suffering and ensure the health of the nation.
Major Challenges and Issues
As they struggle to access care, tick-borne
disease patients and their caregivers experience
myriad stressors, including the loss of the role
they play in their communities, at school, at work,
and within their families. Many withdraw from
social activities, abandon career or school plans,
eliminate hobbies, and place other relationships
on hold to become caregivers, advocates, case
managers, negotiators, researchers, transporters,
record keepers, emotional supporters, and
errand-doers. Finances become strained as family
members and patients consider selling or taking
out loans against their homes, reducing the family
to one car, giving up their jobs or interrupting
their careers, and abandoning planning of all
kinds so that they can tend to the unpredictable
day-to-day needs and condition of the patient.
Figure 15: Extensive Medical Records
One patient’s set of medical records from dozens of doctors
and medical visits for tick-borne disease.
Tick-borne disease patients and their caregivers
also report significant strain on their relationships.
Spouses become caregivers. Divorces occur,
with children and their treatment protocols
levels of depression as well as immune system
compromise years after the care giving has
ceased (Vitaliano, Young, & Zhang, 2004). This
marginalized and risk developing behavioral
issues. Friends retreat. And isolation, which is
sometimes used as collateral in divorce and
custody proceedings. Healthy siblings feel
contributes to the onset of chronic illness and the
resulting costs. Other challenges include job loss,
inability to prepare for retirement, and depletion
of educational accounts. Providing support to
already a substantial public health issue, becomes
a significant contributing factor that adversely
affects the overall quality of life and well-being of
the individual, the family, and the entire support
network.
The health impact on caregivers is also well
documented. Research demonstrates higher
caregivers is imperative, not only to relieve their
burden, but also to reduce the full cost to society
as a whole.
Patients report significant and repeated
experiences with medical staff who are
disrespectful and confrontational. Patients talk
about the stress of needing to obtain medical
care from providers who do not believe them,
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Figure 16: Patient-Provider Relationship
Knowledgeable and compassionate health care providers are important to treatment success in patients
with chronic conditions related to tick-borne disease. These patient-practitioner relationships often involve
shared decision-making to evaluate treatment options, potential risks, and potential benefits depending
on the unique situation.
do not see their suffering as real, and who hold
all of the power in terms of access to medical
care. These adverse experiences with the health
by geography or their health maintenance
care system can exacerbate distress, resulting in
avoidance, anxiety, intrusive memories, intense
emotions or numbing, and hyper-vigilance, and
impact the patients’ sense of safety and optimism
for treatment. Children are more vulnerable to
the impact of disbelief by health care personnel;
and parents report stress and anxiety as they
struggle to maintain employment and parent
their other children while simultaneously
advocating for services and trying to protect
their child from systems and experiences that
threaten further harm.
Patients whose functioning is dramatically
compromised or whose choices are dictated
one. The illness itself can prevent self-advocacy,
given the association of tick-borne disease with
chronic pain, fatigue, and resultant cognitive
impairment. Individuals who do not have a family
member or friend to assist with coordination
of care, research, and advocacy are severely
limited in their ability to secure appropriate
medical intervention, which may lead to a sense
of hopelessness and desperation, followed
by depression and even suicide. Patients who
experience plummeting financial security and
lost earning potential are also vulnerable
to homelessness.
organization (HMO) are not often able to leave
one provider to find another more responsive
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Systemic Barriers
The most avoidable and detrimental limitations to
patient access to appropriate and affordable care
much of the other negative consequences and
suffering described previously.
are interdependent systemic barriers, which cause
of thought, each described in a set of guidelines:
(IDSA) and other medical societies, and (2) the
International Lyme and Associated Diseases
Society (ILADS). The IDSA guidelines promote the
diagnosis of Lyme disease through recognition
(1) the Infectious Diseases Society of America
CDC Surveillance Criteria
As detailed in chapter 3 on epidemiology and
ecology, the inappropriate use of the CDC
surveillance criteria for Lyme disease diagnosis
states where Lyme disease is considered to be
disease and confirm the diagnosis by two-tiered
Lyme disease with the erythema migrans rash,
guidelines usually recommend 10 to 21 days
serological testing, except in cases of early
of more specific objective manifestations of
which constitutes a clinical diagnosis. The IDSA
of antibiotic treatment, except in cases of late
is of particular concern to patients, especially in
“low incidence” despite significant evidence to
arthritis where it may be longer. In contrast, the
ILADS guidelines promote the use of clinical
symptoms of disease when diagnosing and
the long-term use of antibiotics.
judgment with an emphasis on both signs and
treating tick-borne diseases and do not restrict
Despite the existence of two peer-reviewed,
the contrary. Medical providers in low-incidence
regions frequently do not consider Lyme disease
and other tick-borne diseases in their differential
diagnoses. As a result, their patients are not
diagnosed early, are at risk for developing chronic
to seek treatment.
disease, and must travel to “high incidence” states
Compounding the problem, insurance companies
as the recognized clinical criteria for diagnosis
coverage and treatment reimbursement for
routinely use the CDC surveillance case definition
evidence-based treatment guidelines, there is an
apparent governmental and insurance industry
bias for use of the IDSA standards and guidelines
the ILADS guidelines are often criticized by
exclusively. Physicians who choose to follow
and subsequent treatment. They, therefore, deny
patients who do not meet the criteria. When these
other physicians and penalized by state medical
chronically ill patients.
boards, causing many providers to avoid treating
patients find themselves without options, they are
vulnerable to the exploitation of unscrupulous
practitioners offering costly and ineffective
treatments.
Managed Care and HMOs
Another obstacle to affordable care is the
managed care and HMO system. The majority
IDSA and ILADS Guidelines
Clinicians encounter systemic barriers as well.
The medical opinion on diagnosis and treatment
of doctors referred to as “Lyme-literate” are
typically not part of managed care systems due
to imposed compliance with insurance guidelines
for care and low levels of reimbursement for the
largely inaccessible to patients who must obtain
time spent with patients. Those clinicians are
of tick-borne diseases is divided into two schools
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care within their provider group. Patients with
resources to seek care outside their HMO, or
who are covered by preferred provider medical
literate doctor. However, those doctors most
Institutional Discrimination
Another major concern for patients, their families,
friends, and caregivers, and patient advocacy
discrimination, including conscious and
groups is the presence of underlying institutional
unconscious biases against treating late-stage
insurance plans, may seek treatment from a Lyme-
often do not directly bill insurance companies,
incur higher co-pays, and submit claims to the
insurance companies for reimbursement.
leaving the patient to pay for care out of pocket,
and chronic Lyme disease and complex cases of
tick-borne disease. Institutions designed many
decades ago are ill-equipped today to deal with
Attempts to claim reimbursement for services are
fraught with detours and often fail. Initial rejection
of claims is common, followed by long hold times
on the telephone trying to get assistance from the
the complexities of tick-borne disease. This results
in both the employment and educational arenas.
Such bias and discrimination further exacerbate
today’s challenges and negatively impact health
quality of life for patients and their loved ones.
in systemic failures and institutional discrimination
insurance carrier, cumbersome documentation,
and required resubmission of claims. When
patients are severely ill, some with neurological
issues, managing the reimbursement, claims,
outcomes, socioeconomic status, and the overall
sustained tenacity, tracking and recordkeeping,
and potential additional costs are often not
symptoms, which may include neurological
possible for people facing a multitude of
and appeal processes is grueling. The necessary
Recommendations
The Working Group identified the following
recommendations that the Federal Government
could initiate to significantly improve patient
access to care and health outcomes.
processing deficits and exhaustion. Without an
sometimes report “giving up,” feeling that they
advocate or family member to assist, patients
are not capable of fighting for reimbursement
contributes to their financial vulnerability and
recommended treatment.
while also fighting for their health. This further
may obstruct their ability to obtain the doctor-
Those patients who are not rejected outright are
still faced with long authorization periods for
treatment and specialized medications not on
the general formulary. This delay in treatment can
have a detrimental impact on the healing process
of the patient.
Recommendation 7.1:
Create a Federal
repository for information on Lyme disease
and other tick-borne diseases.
Education is a vital first step in the prevention
Patient advocacy groups play a major role in
of Lyme disease and other tick-borne diseases.
educating the public, patients, and providers
and devote significant resources to this effort.
However, their services vary widely from state
to state, leaving those in non-endemic areas
in particular without valuable information and
by state agencies is equally inconsistent.
educational opportunities. Information provided
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Thus, a Federal repository for accurate, up-to-
date information on Lyme disease and other
the dissemination of consistent messaging
throughout the United States.
tick-borne diseases is warranted to allow for
•
•
•
The challenges associated with testing;
What test(s) to ask for and what treatment
options exist;
How to find help when faced with various
forms of discrimination due to tick-borne
diseases; and
Public Education
Public education requires circulation of
information through numerous channels. Many
patient advocacy websites provide free access
to up-to-date curriculum for teachers, outdoor
educators, science teachers, health educators,
organizations also host local community
students, and parents. Advocacy groups and
•
How to obtain accurate, up-to-date
disease.
knowledge in dealing with a tick-borne
According to CDC, children ages five to 14 are
a high-risk population. Children require age-
appropriate materials to protect themselves from
ticks and tick-borne disease. School educators
and nurses need more in-depth education
on prevention, recognition of symptoms, and
education events and conferences with speakers
and exhibitors. They organize workshops and
continuing medical education conferences for
to help bring awareness of tick-borne disease
awareness of exposure. Some states considered
endemic have developed educational curricula
on tick-borne diseases. For example, New
medical providers and mental health clinicians
up-to-date. Many of these organizations are the
mouthpieces for research, publicly sharing the
latest diagnostic tools and treatment options
Jersey encourages districts to adopt their state-
for teachers who instruct students with Lyme
disease. These could be adapted for school
developed curricula and requires annual training
along with information about newly discovered
strains of tick- and vector-borne diseases, while
and other tick-borne diseases.
systems in other regions all across the United
some also directly fund research on Lyme disease
Educating the public is multifaceted and includes
individual education, as well as how to translate
what works for individuals into community
Lyme disease among at-risk school children have
had little attention and warrant further research,
program can improve knowledge, attitude, and
risk children (Shadick et al., 2016).
one study found that a short in-class educational
self-reported precautionary behavior among at-
States. While educational interventions to reduce
solutions at the local, regional, state, and national
scales. The public needs information about
What symptoms to look for;
The positives and negatives of sending
ticks for testing and where to send them;
•
•
•
Patient Education
Through education and greater awareness,
patients and the community at large can be
How and where to seek a medical provider
who is knowledgeable about tick-borne
diseases;
taught the differences between the various tick-
borne diseases and where they occur; which
diseases different ticks are known to carry; and
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how to recognize signs and symptoms. Many
physical symptoms. In addition, mental health
public health offices disseminate information
about ticks and prevention; however, the breadth
and depth of this information, if any at all, varies
from state to state. Most primary care providers
do not customarily offer information about
providers have varying degrees of comfort and
of chronic pain and associated physical
symptoms associated with tick-borne diseases.
While mental health professionals might assist
patients in strengthening their ability to cope
associated psychological disorders through
competency with assessment and management
support group meetings and resources to Lyme
disease and tick-borne disease patients like they
would for cancer or diabetes patients. Advocacy
groups and organizations are the frontrunners in
the public.
with the distress of their disease, as well as any
sharing this information directly with patients and
infectious illness.
interventions, these will not treat the underlying
pharmacotherapy, psychotherapy, and behavioral
Clinician Education
The complexity and controversy of tick-borne
disease(s) discourages many health care
providers and clinicians from even attempting to
treat patients with Lyme disease and other tick-
care providers who are willing and sufficiently
some educational programs and authoritative
borne diseases. This results in a shortage of health
Both medical and mental health professionals
patients who suffer from infection-induced
symptoms, working together in a coordinated,
neuropsychiatric and neuropsychological
need to be better trained to understand
multidisciplinary, treatment-team approach that
fields. Failure to identify a covert medical illness
utilizes the relevant expertise of these respective
trained to treat patients. Compounding the issue,
sources disseminate inaccurate information, which
is easily shared on the Internet. Moreover, many
practitioners are unable to recognize and then
distinguish tick-borne diseases in their various
stages (Hirsch et al., 2018).
Clinician education in the U.S. medical system
is further complicated by a divide between
pthe physical health and mental health systems.
Tick-borne diseases can have neuropsychiatric
mental health providers who have not yet
manifestations and may result in referrals to
such as a tick-borne disease inadvertently delays
which can have dire consequences.
the patient’s diagnosis and subsequent treatment,
Physician and clinician training for tick-borne
avenues:
diseases may be improved through two primary
1.
Curricula taught and tested in medical
schools, in teaching hospitals, and by
the United States Medical Licensing
Examination to earn a U.S. license; and
2.
Continuing medical education (CME)
credits that physicians must annually
licenses.
Some medical associations and advocacy
organizations host scientific conferences where
physicians can earn CME credits. Still, more
complete in order to maintain their U.S.
absence of a positive and trusting relationship
patients may experience a referral to mental
health as diminishing the legitimacy of their
learned to consider tick-borne disease. In the
with their provider as well as health education,
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educational programs are needed for tick-borne
disease, especially high-quality and rigorous
programs that are
Underrepresented and High-Risk
Populations
Certain segments of the population are
particularly vulnerable to tick-borne disease for
a variety of reasons. They should be of special
treatment, and prevention.
Children
Children are one of the highest-risk groups for
consideration when allocating funds for research,
•
•
•
•
Frequently updated with the latest science
and emerging technologies;
Peer-reviewed to satisfy the highest
medical and scientific standards;
Free of charge; and
Openly available online or otherwise,
so that educational materials are easily
by all stakeholders.
discoverable, accessible, and free for use
Some organizations provide grants and funding
for educational programs offered by hospitals,
provide an opportunity for researchers to
universities, and other institutions. These venues
report latest discoveries, exchange hypotheses,
and form research collaborations. Patients
sometimes also attend these conferences, which
offer opportunities to network and learn about
providers, testing, treatment options, and cutting-
edge science that can benefit clinicians and other
stakeholders.
contracting tick-borne diseases. Families may be
especially hard hit when more than one child is
ill because they face higher medical costs and
time lost at work for caregiving. In addition to the
need for financial resources, there is tremendous
need for enlightened academic services and
accommodations for children in schools.
Students with tick-borne diseases often
experience severe disruption in their education
(D.T. Dennis, personal communication, September
2, 1992). Frequent non-specific symptoms, such
as forgetfulness and difficulty concentrating,
can result in academic problems such as falling
averages, as well as social consequences, such
as loss of friends and isolation from peers. The
to more than one-half of the school year. And
in many cases, the time is broken up, so that
multiple years.
behind in schoolwork and declining grade point
funding for tick-borne disease in the areas
of research, treatment, and prevention
proportional to the burden of illness and
need.
Lyme disease and other tick-borne diseases
receive significantly less funding than other
major illnesses that pose a similar level of risk
Recommendation 7.2:
Allocate increased
median duration of school absence is equivalent
disruptions occur throughout a school year or
When the underlying infectious illness is
and burden to the American public. Therefore, an
increase in funding for research, treatment, and
tick-borne illness.
prevention is warranted to match the burden of
unrecognized or poorly understood, students are
at risk for misdiagnosis with a primary psychiatric
deficit disorder, school or social phobia, and
disorder or learning disability, including attention
oppositional defiant disorder. These misdiagnoses
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overlook or ignore critical symptoms such as pain,
fatigue, sleep deprivation, sensory sensitivities,
and processing issues, each of which may impair
attention and impede academic progress. The
unpredictable course of the illness, including day-
to-day fluctuations in its symptoms, challenge the
typical service plans in place for students with
learning disabilities or with illnesses that have a
more predictable course or defined endpoint.
School field trips into Lyme disease-endemic
areas and playgrounds place children at risk
for contracting Lyme disease. Prevention and
Patients who experience Lyme disease and
tick-borne disease-induced neuropsychiatric
symptoms are at risk for misdiagnoses with
primary psychiatric disorders. Given the
5 on diagnosis), physicians sometimes fail to
identify a medical explanation for a patient’s
challenges with diagnostic testing (See chapter
physical symptoms and erroneously attribute
or depression. This results in inadequate
medical treatment and also adds to the
patient’s distress and despair. Many of these
patients bounce between hospitalizations in
psychiatric and medical facilities and receive
them to emotional factors, such as anxiety
awareness measures must be implemented in
these situations, including, but not limited to,
appropriate notification and balanced information
regarding risk and prevention provided to parents
and supervising staff members.
Pregnant Women
Gestational tick-borne disease can be transmitted
to unborn children
in utero
and has the potential
to cause premature labor and fetal death.
One priority research area involves the risks of
little appreciation for the infectious etiology of
continuity of care and results in a fragmented
their neuropsychiatric symptoms. This disrupts
approach to complex, multisystemic illnesses.
There is a need for dual-diagnosis inpatient units
neuropsychiatric symptoms.
equipped to treat patients with infection-induced
maternal-fetal transmission for various tick-borne
diseases, as well as how to treat this population
if exposed during pregnancy and needing
treatment while pregnant.
Behavioral Health Patients
Thousands of articles show associations between
infections and neuropsychiatric manifestation
of illness. At least 400 articles support the
association between tick-borne disease and
neuropsychiatric disorders, which includes, but
is not limited to, depression, anxiety, bipolar
disorder, cognitive impairments, and psychosis.
Other research has addressed the immunological
and neurological mechanisms by which the
Lyme disease bacteria,
B. burgdorferi,
may cause
American Indians and Alaska Natives
The Indian Health Service (IHS), an agency of
HHS, is primarily responsible for providing health
services to American Indians and Alaska Natives.
IHS is chronically underfunded and often not
able to provide all health services available to the
general populations. Moreover, the health care
facilities that could provide the needed services
are located in rural and remote areas and often
hours away from patients by car.
IHS alignment with recommendations in
this report for VA, CMS, and DoD (see
Recommendation 8.3, page 77) would improve
care to American Indians and Alaska Natives
for tick-borne disease. IHS opportunities exist
education through interoperable diagnostic
neuropsychiatric symptoms.
to upgrade processes and improve employee
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codes, standardized medical coverage, and
reimbursement policies for tick-borne disease.
IHS systems with health records that interface
seamlessly with other Federal agencies would
improve care and coverage on tribal lands,
ensuring consistent medical care and coverage
for everyone.
Military Servicemembers, Military
Families, and Veterans
Continuity of care is vital to accurately diagnosing
and adequately treating chronic Lyme disease
and tick-borne diseases. Because the military is
Hispanic or Latino Populations
According to the U.S. Department of Labor,
Hispanic or Latino populations comprise 43.1%
of grounds maintenance workers and 44.3% of
workers in farming, forestry, and fishing industries,
leading to higher rates of exposure to ticks and
potentially tick-borne diseases (“Labor Force
Statistics from the Current Population Survey,”
2017). One study showed that, compared to
other populations, Hispanics or Latinos displayed
signs of disseminated infection and symptoms
onset during the fall at a significantly higher rate.
Placing this group at further risk, only 58.5% were
reported as having health insurance during the
2009 to 2013 period compared to 84.9% of non-
Hispanic or Latino whites. Moreover, 15.5% of the
Hispanics or Latinos studied reported delaying or
not seeking medical intervention (Nelson, Starr,
Kugeler, & Mead, 2016).
Military medicine is well-suited for acute, easy-
consistent care over time with the same provider.
Servicemembers and their families do not receive
under-resourced and understaffed, many military
to-diagnose illnesses, injuries, and infections. It is
not well-suited for chronic or complex conditions
because both families and medical providers
locations.
Military Servicemembers, their families, and
are regularly deployed and moved to different
Migrant Workers
Due to outdoor working habits, migrant workers
Veterans are a high-risk population because of
exposure to global species and strains of tick-
may be medically separated or retired with
borne disease. In the case of Veterans, they
diseases. With limited or no health care, they
proper treatment.
Hunters, Hikers, Golfers, and Outdoor
Enthusiasts
are at high risk for exposure to tick-borne
often lack the means for adequate diagnosis and
undiagnosed or misdiagnosed diseases. For
examples of such scenarios, see the patient
profiles of Veteran Ruben Lee Sims (page 8) and
Those with outdoor occupations or avocations are
increase exposure to ticks and risk for tick-borne
at increased risk. A healthy outdoor lifestyle can
medically retired Colonel Nicole Malachowski
(page 58). Unless Veterans reach the 20-year
pension mark, which allows them more choice
in medical providers, Veterans are dependent
on the VA’s health care system. As such, they are
disease, especially without proper precautions in
and ecology and chapter 4 on prevention).
This high-risk population includes hunters,
high-risk regions (see chapter 3 on epidemiology
subjected to the same Federally endorsed criteria
and guidelines for diagnosing and treating Lyme
disease and other tick-borne diseases that are
being called into question in this report.
hikers, golfers, anglers, park rangers, campers,
landscapers, and others who spend significant
time outdoors.
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ACCESS TO CARE, PATIENT OUTCOMES
Recommendations:
Ensure the rights
infection…All four plaintiffs were assigned
to work in tick-infested areas…and within
weeks or months…manifested symptoms
diagnosed as having Lyme disease. The
of Lyme disease. All were subsequently
of those dealing with Lyme disease and
tick-borne diseases and conditions by
reducing the burden of the processes under
which patients are currently diagnosed and
treated and by which they access care. Basic
protections must include, but not necessarily
be limited to, those that:
Lyme disease contracted by all four plaintiffs
was caused by their working in unsafe areas
where they were doing their jobs, as they
employment by defendant LIRR.
were required to do, in connection with their
7.3:
Protect patients from employment
discrimination.
The highest risk of exposure to Lyme disease and
other tick-borne diseases falls on people who
work outside in regions where ticks are known
to occur. Those individuals make up the majority
of workers who file compensation claims for tick-
borne disease contracted on the job; however,
even employees who work in urban areas, far
from tick habitats, occasionally file tick-borne
disease compensation claims as well (Cohen,
2004).
As demonstrated by this case, the Federal
Government should ensure that existing workers’
compensation laws protect workers who have
denial of insurance compensation claims. In
accommodations under the
Americans with
contracted tick-borne disease on the job from
addition, existing laws that provide for reasonable
Disabilities Act
(ADA) must be enforced for those
tick-borne diseases.
workers who are ill due to Lyme disease and other
sites over a two-year period. The court ultimately
decided in favor of the plaintiffs, ruling that the
LIRR was in breach of the Federal Employer’s
Liability Act requirement for employers to
The case of Grano v. Long Island R. Co. (1993)
serves as an example of an attempt by an
employer to deny its employees compensation
for disability resulting from job-related tick-borne
disease. In this case, four workers brought an
action against their employer, the Long Island
Railroad Company (LIRR), claiming that they had
developed Lyme disease after encountering
ticks at various Suffolk County, New York, work
7.4:
Protect students of all ages from
discrimination.
Students with Lyme disease all too often face the
added burden of needing to convince school
authorities of the reality and credibility of their
ongoing illness. They require flexible attendance
policies without fear of truancy charges. Existing
models of accommodations provided in 504
plans and individualized education programs
(Cohen, 2004). The judge on the case (“Grano
Long Island R. Co., 818 F. Supp. 613 (S.D.N.Y.
1993),” 1993) stated:
of the tick infestations and of the risk of
maintain and inspect work areas and “provide
workers with a reasonably safe workplace”
(IEPs) are often not suited for children with tick-
borne disease. Current educational systems often
present the options of either school attendance or
home instruction. However, hybrid and creatively
designed plans are necessary to provide
opportunities for the richest and most “normal”
growth and development for children who live
with myriad symptoms that wax and wane, even
over the course of a day, and compromise their
ability to fully engage in mainstream education.
The railroad knew or should have known…
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Socialization is an essential part of child
development. Children who have not attended
school are sometimes faced with punitive
measures, such as exclusion from after-school
activities. Preventing them from engaging in
meaningful socialization with their peers is
companies cannot be required to cover Lyme
disease and other tick-borne diseases. In the
interim, the Federal Government is urged to
change its own systems and lead by example.
punishing and isolating, and intensifies the
emotional pain and loss of normalcy. Further,
the longer a young person is at home and outside
the peer environment, the more difficult it may
be to reenter. This isolation may result in
long-term unintended social and emotional
consequences that compound the challenges
the young person faces.
The Department of Education (DoED) should
examine its policies and procedures to ensure
that individuals with Lyme disease and other tick-
borne diseases are protected from discrimination
in schools, especially in the area of 504
compliance and IEPs. This involves protecting and
enforcing the rights of these students under the
ADA. DoED should investigate to determine if all
such policies and procedures are being adhered
to throughout the United States and needs to
Health Care, Health Insurance, and
Disability Coverage
insurance—beginning with VA, CMS, and
Federal providers of health care and health
DoD—need to standardize and streamline
reimbursement policies for tick-borne disease.
Diagnostic coding should be standardized
across all Federal systems, so that patient records
and reimbursement processes are more easily
navigable and consistent for everyone, including
Servicemembers, Veterans, and civilians.
Federal benefits for people with disabilities
should be similarly streamlined and improved,
so that claims are consistently processed without
unduly burdening those disabled by tick-borne
disease. The Federal Government can achieve
this by, first, recognizing the severity of tick-borne
disease and, second, mapping the disabling
consequences of tick-borne disease to DoD,
proactively communicate that Lyme disease and
tick-borne diseases fall under anti-discrimination
laws, such as existing laws that guarantee a free
and appropriate education for students with
tick-borne diseases under the Individuals with
Disabilities Education Act.
VA, and U.S. Social Security Disability Insurance
diseases can disable some—with measurable
programs. Institutional recognition that tick-borne
criteria and codes for disabilities related to tick-
borne disease—will expedite processing and, for
those who qualify, receipt of earned benefits.
7.5:
Protect patients from health care
and disability insurance coverage and
reimbursement policies that are unduly
burdensome.
Shared Medical Decision-Making and
Patient-Centered Care
Beyond Federal health care and insurance
programs, the Federal Government can lead
As detailed in the Systemic Barriers section,
insurance companies regularly deny medical care
to tick-borne disease patients who do not meet
the CDC surveillance criteria for Lyme disease.
Until new laws are passed, private insurance
by example with patient-centered care. This
approach focuses on shared medical decision-
making, which takes into account the individual
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ACCESS TO CARE, PATIENT OUTCOMES
circumstances and values of the patient. It is
Federal momentum already exists to empower
patients to share in their own health care
decisions. CMS, in conjunction with the White
House Office of American Innovation and
VA, has implemented MyHealthEData, which
particularly important when the evidence base
is uncertain. Patient involvement is also critical
to making the “right choice” when different
combinations of treatment options, uncertain
outcomes, and implicit trade-offs exist. Under
shared medical decision-making, clinicians are
are the experts in what matters most to them.
No single diagnostic and treatment program
for Lyme disease is universally successful or
allows patients to choose the provider that best
secure access to their data, leading to greater
meets their needs and then give that provider
viewed as experts in the evidence, and patients
competition and reduced costs. Through
MyHealthEData, patients receive an electronic
share at their own discretion. Patient-centered
own unique health care needs, have a better
copy of their entire health record, which they can
tools such as this allow patients to address their
accepted, causing significant uncertainty. When
more than one set of guidelines exists (ILADS
and IDSA), the question then becomes who
decides the appropriate course of treatment for
the patient. Under the medical ethical principle of
autonomy, the treatment decision belongs to the
patient in consultation with his or her provider.
disease, and make more informed decisions
about their care.
understanding of their overall health, prevent
Thus, the American Medical Association requires
that the physician disclose and discuss with the
patient the risks and benefits of the proposed
treatment and also the risks and benefits of
7.6:
Protect the rights of licensed and
available alternative treatments.
qualified clinicians to use individual clinical
judgment, as well as recognized guidelines,
to diagnose and treat patients in accordance
with the needs and goals of each individual
patient.
The legal doctrine of informed consent requires
options, their probable outcomes, and the risks
who may be too ill to work or attend school,
physicians to inform patients of existing treatment
and benefits associated with each. For a patient
In endemic states, many providers who treat
diseases with long-term antibiotics risk their
livelihoods and reputations to do so. Other
clinicians accuse them of compromising the
persistent Lyme disease and other tick-borne
the potential benefits of treatment may well
be provided the right of informed consent,
outweigh the risks. It is essential that patients
including information on the limitations of current
prosecute them for operating outside the IDSA
to feel hesitant about handling chronic or
health of the patient, and state medical boards
guidelines. These prosecutions have led doctors
recurrent cases, forcing patients in some instances
to seek treatment beyond their home states.
diagnostics, and the authority to decide which
follow.
of the available treatment options they wish to
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The IDSA guidelines for treating Lyme disease
following statements:
(Wormser et al., 2006) contain a footnote with the
It is important to realize that guidelines
cannot always account for individual
variation among patients. They are not
Bands: How They Are Used Today and What
That Is Doing to Patients
Major Issue 7.7:
Testing and Diagnostic
Empower Patients with Data
As previously discussed in chapter 5 on diagnosis,
the western blot test results and reporting for
Lyme disease can be problematic for patients
western blot bands used in CDC surveillance
intended to supplant physician judgment
with respect to particular patients or special
Society of America considers adherence
to these guidelines to be voluntary, with
clinical situations. The Infectious Diseases
and clinicians because laboratories report only
criteria. Most laboratories will not report the other
bands, such as the 31 and 34kDa positions, which
could potentially reveal diagnostic information
to clinicians, especially to those who have
the ultimate determination regarding their
application to be made by the physician
in the light of each patient’s individual
circumstances.
patients with equivocal western blot test results.
Laboratories have latitude on how to display
results, and some claim that Federal regulations
results. Congress and the HHS Secretary could
subject medical providers to disciplinary action
Despite the footnote, state licensing boards
and fines for choosing to determine the direction
judgment, other recognized diagnostic and
restrict them from releasing all western blot test
direct FDA to update and clarify its requirements
on western blot tests for Lyme disease, explicitly
allowing patients to access their own health
data, including their own laboratory results. This
of their patients’ treatments based on their clinical
treatment guidelines, individual circumstances,
and previous treatment responses. Therefore,
it falls on each state to produce legislation or
policy solutions to promote public awareness and
protection for patients and providers. Advocates
have successfully achieved those solutions
in several states to date, although legislative
solutions should be a last resort, since once
passed, they are seldom repealed.
direction aligns with societal and government-
control, share, and use their own medical
wide initiatives to empower patients to access,
records and health care information. Data-driven
decisions are key to improving their health
outcomes.
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ACCESS TO CARE, PATIENT OUTCOMES
Engage Diverse Stakeholders—Update
the CSTE Surveillance Case Definition
with 21st-Century Evidence
Data collection and scientific understanding
have evolved since the 1994 Dearborn
conference (see chapter 5 on diagnosis), yet
Lyme disease diagnostics and surveillance
criteria remain unchanged. It is time to revisit the
Dearborn conference outcomes by convening a
government scientists, academic researchers,
industry leaders, treating clinicians, patients,
meeting of all relevant stakeholders—including
Relay Information as a Neutral
Knowledge Broker
of treatment guidelines over another, yet it can
clarify the intended purpose of its surveillance
The Federal Government cannot endorse one set
that meet pre-defined standards and criteria.
criteria and recognize all third-party guidelines
evidence-based clinical practice guidelines and
related documents. Historically, the National
Guideline Clearinghouse (NGC) served this
Agencies act as a neutral knowledge broker of
family members, and advocates—to review the
purpose by providing one government website
with free online access to all guidelines that
meet pre-defined standards for treating tick-
evidence and interpretive criteria using all of the
newest diagnostic methodologies, techniques,
technologies, and emerging science. Diverse
borne disease. As of July 2018, however, NGC
no longer available to practitioners and patients.
Science and guidelines have not changed; they
are simply no longer easily accessible from a
funding was discontinued, and this resource is
stakeholders, the Working Group, CDC, NIH, FDA,
and CSTE could examine the science and “real-
world evidence”—including clinician data and
criteria that supersede outdated ones.
patient registries—to co-create new outcomes and
trusted government website. As a result, some
to justify their medical treatments and insurance
reimbursements. This Working Group or other
Federal agency could create a webpage with
physicians and patients face increased difficulty
pre-defined standards for diagnosis of tick-borne
diseases and conditions.
those on the former NGC website) that meet
resources and links to all guidelines (for example,
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Challenges Facing Physicians and Impeding Patient
Access to Care
The scientific unknowns and strongly held, differing views have created an
environment where many physicians are confused and uncertain about how to treat
their patients with chronic symptoms after standard antibiotic treatment of Lyme
disease. For those patients, no uniformly accepted treatments exist. Physicians
others call it post-treatment Lyme disease syndrome; and still others claim the
cannot even agree on what to call the illness: Some call it chronic Lyme disease;
altogether by choosing not to provide continuity of care for such patients. Some
are reticent to speak up about the illness, worrying that they may risk their
medical licenses, career, and credibility for doing so.
illness “is all in their patients’ heads.” Many physicians avoid the controversy
This report does not represent a particular stance on these issues;
rather, it recognizes the legal challenges as a barrier to patients’
access to care. Patients bear the brunt of this situation when their
doctors are caught up in these issues, and they risk losing their
trusted physicians. It is time to reexamine the U.S. system of
care and payment for this vulnerable group of patients.
Patients and the stakeholder community are core to the
Working Group process and essential for its success—
and, most importantly, for improved patient outcomes
with tick-borne disease. Diverse perspectives fuel
scientific breakthroughs, innovation, and collaborations
to co-create solutions.
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Patient
Stories
Julia Bruzzese and Family
Julia Bruzzese was a lively nine-year old when she was bitten by a tick and
contracted Lyme disease, associated coinfections, and other types of tick-
borne diseases (“Lyme”). Although she was brought to the pediatrician
with a bull's eye rash after the tick bite and for many subsequent sick visits,
Julia went undiagnosed for more than two years. She is now 15 years old
and bound to a wheelchair due to her ongoing battle with Lyme. After
Julia received extensive serological workups for every possible diagnosis
on numerous occasions, and despite Julia's suffering from early signs of
Lyme and increasingly worsening symptoms, doctors failed to make an
accurate diagnosis and provide her with timely treatment. Because of a
lack of reliable diagnostic testing, doctors and hospitals did not diagnose
or treat Julia for Lyme disease, and insurance companies refused to pay
for the expenses. As a result, Julia eventually lost her ability to walk,
among many other things, and nearly died at age 11.
While Julia’s health was declining, other members of the Bruzzese family
(Julia’s parents, older brothers, and little sister) realized they were all
suffering from many symptoms similar to Julia’s. However, the family’s
focus and dwindling financial resources were allocated to Julia, the sickest
one. They were determined to save Julia’s life, to get her childhood back,
and to seek an answer and hope.
Hope came after Julia met Pope Francis in 2015. The Papal Blessing drew
international attention and increased awareness. Love and support began
pouring in. Julia was subsequently diagnosed with Lyme, bartonellosis,
and babesiosis. All Bruzzese family members were diagnosed with Lyme as
well.
Julia Bruzzese
High School Sophomore
Pediatric Lyme Disease Patient and
Lyme Disease Advocate
Brooklyn, New York
With the financial support raised by her community and people in other
parts of the world, Julia and her family received treatment from physicians experienced with Lyme disease.
The family saw tremendous improvement after proper treatment, and Julia’s symptoms gradually improved.
Because treatment was delayed for so long, Julia, however, still suffers from the chronic effects of Lyme and
remains in
a wheelchair.
“I
t is not fair that many share my story of suffering and a life being lost. I am determined to bring about change, and
bring hope to those who have forgotten the meaning of the word.
“
- Julia Bruzzese, age 15
come back tomorrow, I feel as though years have gone by. It feels as though
seconds are years at home.
“
- James Bruzzese, brother, age 22
“
My friends don't understand. When I leave school today, by the time I
“
One day, I’ll have my sister back.
“
-Sofia Bruzzese, sister, age 9
76
“
Where medicine fails, love for my children
will prevail.
“
- Josephine Bruzzese, mother
ervices
•
Office of the Assistant Secretary for Health
“
We are all being put to the test, pushed to the limit to reveal how
far we go
.”
- Adam Bruzzese, brother, age 17
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Chapter 8
Looking
Forward
Recommendations at a Glance: Looking Forward
Recommendation 8.1:
NIH: Create an NIH tick-borne disease strategic plan, with public
input during creation and implementation, to address tick-borne diseases, including all
stages of Lyme disease. Include in the strategic plan the coordination of research funding
across NIAID, NINDS, NIAMS, and NIMH to increase knowledge of pathogenesis, improve
diagnosis, and develop and test new therapeutics for tick-borne diseases. Update every
five years.
Recommendation 8.2:
CDC: Dedicate funding within CDC to study—with
performance
indicators—babesiosis
incidence, prevalence, treatment resistance, and prevention,
including maternal-fetal and transplantation/transfusion transmission risk. Consider using
advanced data tools, such as patient registries, to study the potential role of
Babesia
in tick-
borne disease patients with continuing manifestations of disease after initial treatment.
Recommendation 8.3:
DoD: Commence study of tick-borne disease incidence and
prevalence of active duty Servicemembers and their dependents. Compile data on the
impact of tick-borne diseases on military readiness. Create education and preparedness
programs that specifically address the unique risks faced by Servicemembers in training
and on deployment and by their families.
Recommendation 8.4:
VA: Commence study of tick-borne disease incidence and prevalence
of Veterans and eligible family members.
Recommendation 8.5:
Develop and disseminate more comprehensive clinician education
that highlights diverse symptomology, expanding geography of infecting ticks, and
limitations of current testing procedure. In developing the curriculum, include diverse
stakeholder groups, including clinicians, research scientists, and patients who represent the
spectrum of scientific and medical expertise and perspectives on tick-borne disease.
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LOOKING FORWARD
Looking Forward
The challenges posed by Lyme disease and other
tick-borne diseases have been increasing in
scope and complexity in recent years. Problems
a single or narrow approach. Solutions must
It is no easy task to tackle thorny scientific
and political quagmires that have divided
stakeholders for decades. If it were easy, many
of today’s tick-borne disease challenges would
be closer to being solved. Much work remains,
move forward. The American people have
amidst great scientific uncertainty, yet we must
demanded it. The American people deserve it.
caused by these illnesses cannot be solved with
be interdisciplinary, evidence-based, and data-
driven. They require a comprehensive and flexible
institutional boundaries, and conventional norms.
If we are to effectively and efficiently address
tick-borne diseases in the United States, we
public health response—across silos, disciplines,
Now is our time to start fresh by re-charting a new
course in the history of tick-borne diseases where
everyone has easy access to accurate diagnostics
and affordable care that restores health. It is time
for 21st-century solutions to make a difference
through participatory medicine, which aligns
must engage all of the diverse stakeholders and
strategically move forward together. A diversity
of perspectives can help us unlock scientific
clinicians, patients, and researchers to co-create
to getting us closer to this shared vision.
breakthroughs and improve policy by harnessing
the power of emerging technologies, methods,
and insights from seemingly unrelated fields.
It also fuels novel exploration, innovation, and
sharing (for example, open data and open
next-generation solutions. This report is one step
The Working Group of 14 members found
though everyone had different expertise
substantial agreement on key concepts, even
and experiences with tick-borne diseases.
the co-creation of solutions through information
science) and collaboration techniques for open
science, prizes, challenges, and innovative
Commonalities that emerged include the need
for better U.S. surveillance data on where ticks
are spreading, which diseases they carry, and
how this translates into cases of human tick-
innovation (for example, crowdsourcing, citizen
public-private partnerships). All of these must be
undertaken through channels that promote and
safeguard scientific and methodologic rigor.
unanimously and enthusiastically supported
Everyone also agreed that we must better
borne diseases. The Working Group members
As part of an ongoing six-year process, this report
is a first step in transforming the United States
response to tick-borne diseases. Success is not
in this report, but rather by improved patient
outcomes due to concrete actions taken by
improved diagnostic tests for tick-borne diseases.
understand the cause of persistent symptoms
after initial treatment of tick-borne diseases.
We may not have agreed on whether to call it
or “post-treatment Lyme disease syndrome
measured by the number of recommendations
“chronic Lyme disease,” “late-stage Lyme disease,”
(PTLDS),” yet we all agreed that individuals with
Congress, HHS, and other Federal agencies. In
two years, when the next report is due in 2020,
recommendations will have been acted upon.
the Working Group hopes and expects that many
persistent symptoms are legitimately sick and in
Americans with tick-borne disease need greater
need of medical care to alleviate suffering today.
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access to quality, affordable patient care. The
•
activities.
the need for increased education and prevention
Looking to the future, report updates in 2020
surrounding tick-borne diseases. The Working
Group expects that future reports will provide
in-depth examination of priority issues identified
limited to
and 2022 will further investigate U.S. issues
Working Group also found agreement around
A systematic review of unresolved priorities
and questions, including:
◊
Rising healthcare costs in the United
States due to Lyme disease, other
tick-borne diseases, and coinfections
with multiple pathogens.
◊
Nomenclature challenges such as
chronic Lyme disease, neurological
Lyme disease, late-stage Lyme
disease, and PTLDS.
◊
The shortcomings and limitations of
vaccine and diagnostic clinical trials.
during the 2017–2018 process, including but not
Scientific literature reviews on tick-borne
diseases in the United States.
Federal research and activities related to
tick-borne diseases across the Federal
Government. The HHS, DoD, and VA
•
•
inventory of activities from this report will
(if applicable) from additional agencies,
departments, and offices.
be updated and new information included
◊
The inclusion of vulnerable and
high-risk populations in clinical trials,
for example, children, pregnant
women, and individuals with ongoing
symptoms who once had Lyme
disease or other tick-borne diseases
and, therefore, may respond to
treatment differently than “healthy”
adults.
◊
Transmission unknowns.
Incorporation of patient experiences into
the conventional scientific approach,
from patient registries and patient-
powered research.
including the evaluation of information
•
A strategic approach to public-private
partnerships and collaborations, so
that tick-borne diseases as a national
•
priority will not only involve the Federal
Government, but will also harness the
power, resources, commitment, and
academia, non-profit organizations, as well
as local, state, and other governments.
innovation across all sectors—industry,
•
erase past events or rewrite the history
we can acknowledge the past, learn
Trust building. The Working Group cannot
that caused distrust of vaccines. However,
from it, and do better by 1) working in
•
A systematic review of adverse effects
from overdiagnosis and the use of
tick-borne diseases.
unsubstantiated treatment for presumed
collaboration with diverse stakeholders, 2)
increasing transparency, and 3) ensuring
that Federally funded research and
Americans.
activities serve the real-world needs of
•
A systematic review of adverse effects from
underdiagnosis and undertreatment for
tick-borne diseases.
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LOOKING FORWARD
Past differences and divisions in Lyme disease
we can choose to reset and move forward to
achieve one shared vision:
A nation free of
history will not go away overnight, yet together
Recommendation 8.1 – NIH:
Create
tick-borne diseases where new infections are
prevented and patients have access to affordable
care that restores health.
The Working Group’s takeaway message to
Congress is this: Allocate increased funding
for tick-borne diseases in the area of research,
treatment, and prevention that is proportional
to the burden of illness and today’s need. Tick-
an NIH tick-borne disease strategic plan,
with public input during creation and
implementation, to address tick-borne
diseases, including all stages of Lyme
disease. Include in the strategic plan the
coordination of research funding across
NIAID, NINDS, NIAMS, and NIMH to increase
knowledge of pathogenesis, improve
diagnosis, and develop and test new
therapeutics for tick-borne diseases. Update
every five years.
borne diseases—beyond just Lyme disease—are
a serious problem that is under-recognized. As
a result, organizations devoted to tick-borne
diseases are understaffed, and research and
in this report will require significant Federal
activities underfunded. Many recommendations
investment—monetary, in-kind, and leadership
resources—to advance research, policy, and
education for tick-borne diseases commensurate
with the scale and scope of the problem today.
The Executive Branch must strategically prioritize
Dedicate funding within CDC to study—
with performance indicators—babesiosis
incidence, prevalence, treatment resistance,
and prevention, including maternal-fetal and
transplantation/transfusion transmission risk.
Consider using advanced data tools, such as
patient registries, to study the potential role
of
Babesia
in tick-borne disease patients with
continuing manifestations of disease after
initial treatment.
Recommendation 8.2 – CDC:
tick-borne diseases across many agencies and
and next-generation solutions. Given limited
Recommendation 8.3 – DoD:
diverse programs to efficiently catalyze science
resources and high scientific uncertainty, we must
ask:
How can the Federal Government accelerate
science and develop answers as quickly as
possible with the least cost to taxpayers?
In
identified recommendations to four Federal
the complexities of tick-borne diseases and
identifying data-driven solutions.
answer to this question, the Working Group
agencies. Each agency is critical to understanding
Commence study of tick-borne disease
incidence and prevalence of active duty
Servicemembers and their dependents.
Compile data on the impact of tick-borne
diseases on military readiness. Create
education and preparedness programs
that specifically address the unique risks
faced by Servicemembers in training and on
deployment and by their families.
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Recommendation 8.4 – VA:
Commence
study of tick-borne disease incidence and
prevalence of Veterans and eligible family
members.
Many recommendations in this report require
systemic changes and possibly even paradigm
help bring more public awareness to existing
outreach campaigns and prevention education
by agencies. Education will be most effective if
reinforced with consistent messaging across all
levels of government, beginning at the top with
the President, Congress, and the HHS Secretary.
The international community is looking to
the United States for leadership, science,
and innovation on how best to address tick-
borne diseases. The United States is uniquely
positioned to markedly change the course of
shifts, depending on the outcomes of future
scientific research. Other recommendations may
be enacted immediately, without Congressional
mandate, funding, policy action, or new scientific
understanding. Examples include education
and public outreach campaigns, which may be
implemented now. They are critically important
and cost-effective. With greater scientific
knowledge and funding, their effectiveness and
impact will only increase. Yet, we should not wait.
Education on tick-borne diseases must be an
immediate national priority. Diverse stakeholders,
including but not limited to the Federal
Government, can:
Recommendation 8.5:
Develop
and disseminate more comprehensive
clinician education that highlights diverse
symptomology, expanding geography of
infecting ticks, and limitations of current
testing procedure. In developing the
curriculum, include diverse stakeholder
groups, including clinicians, research
scientists, and patients who represent the
spectrum of scientific and medical expertise
and perspectives on tick-borne disease.
tick-borne disease, especially Lyme disease, for
the better. Our American innovation, science,
creativity, and emerging technologies—including
next-generation diagnostic platforms such
as microfluidics, affinity capture technology,
cytokine release assays, and nanopore
sequencing—offer
new hope for patients with
Lyme disease and other tick-borne infections. A
U.S. priority response with top Federal leadership
and immediate investment would catalyze
global attention and much-needed scientific
research and development (R&D). It would also
encourage industry, academia, and public-
private partnerships to prioritize scientific R&D,
education, and activities on tick-borne disease in
order to decrease their societal burden and costs
to public health care systems.
Domestically, Americans need Federal action
now. In accordance with the six-year process
established by the
21st Century Cures Act
of
2016, the Working Group aims to deliver a
educate Americans about tick-borne diseases. For
example, Congress or the President of the United
States (through a Presidential Proclamation) could
officially designate the month of May each year
as Lyme Disease Awareness Month and/or Tick-
Borne Disease Awareness Month. Such leadership
would shine a spotlight on these illnesses and
U.S. leadership at the highest levels can help
The immense challenge of tick-borne disease
requires all hands on deck—all sectors, all
disciplines, all of society—to co-create solutions
as quickly as possible. We must do this together.
And we must not stop working until our Working
Group vision is an everyday reality for tick-borne
disease patients in all 50 states.
pragmatic path forward with recommendations
for Federal actions to address tick-borne diseases.
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LOOKING FORWARD
Core Values to Achieve One Shared Vision
Shared Vision:
A nation free of tick-borne diseases
where new infections ar e prevented and patients have
access to affordable care that restores health.
RESPECT:
Everyone is valued
We respect all people, treating them and their diverse
experiences and perspectives with dignity, courtesy, and
openness, and ask only that those we encounter in this
mission return the same favor to us. Differing viewpoints
are encouraged, always, with the underlying assumption
that inclusivity and diversity of minority views will only
strengthen and improve the quality of our collective efforts
in the long term.
COMPASSION:
Finding solutions to relieve suffering
We listen carefully with compassion and an open heart
in order to find solutions which relieve the suffering of
others. We promise to work tirelessly to serve the greater
good until that goal is achieved.
COLLABORATION:
Work with citizens and patients as partners
The best results and outcomes won’t be created behind
closed doors, but will be co-created in the open with
input of the American public working together with
these core values as our guide. We actively listen to the
patient experiences shared with us, respect the lived
experiences of patients and their advocates, and learn
from their experiences in our pursuit of objective truth.
Across diverse audiences, we communicate effectively
and collaborate extensively to identify shared goals and
leverage resources for maximum public health impact.
paradigm, finding a better way
INNOVATION:
Shifting the
We strive to have an open mind and think out of the box.
We keep what works and change what doesn’t. We will
transform outdated paradigms when necessary, in order to
improve the health and quality of life of every American.
HONESTY & INTEGRITY:
Find the truth, tell the truth
We are honest, civil, and ethical in our conduct, speech,
and interactions with our colleagues and collaborators.
We expect our people to be humble, but not reticent,
and to question the status quo whenever the data and
the evidence support such questions, to not manipulate
facts and data to a particular end or agenda, and to
acknowledge and speak the truth where we find it.
ACCOUNTABILITY:
We, as diligent stewards of the public trust and the funds
provided by our fellow citizens, pledge to be transparent
in all of our proceedings and to honor our commitments
to ourselves and others, while taking full responsibility for
our actions in service to American people.
The buck stops here
EXCELLENCE:
Quality, real-world
evidence underlies decision-making
We seek out rigorous, evidence-based, data-driven, and
human-centered insights and innovations—including
physician and patient experiences—that
we believe are
essential for scientific and medical breakthroughs. We
foster an environment of excellence that strives to achieve
the highest ethical and professional standards, and which
values the development of everyone’s skills, knowledge,
and experience.
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Chapter 9
Conclusion
The Tick-Borne Disease Working Group 2018 report is the product of a diverse group of stakeholders,
officials. The co-creation of this report brought this diverse group together (Appendix A), and they
including patients and patient advocates, government officials, physicians, scientists, and public health
successfully produced the first-ever
21st Century Cures Act
report in the controversial field of Lyme
disease and other tick-borne diseases in the United States.
This is one step in a six-year process, yet a
is perfect, the Working Group sees our work
remarkable feat. Although no process, nor report,
Developing this report required listening and
compromise in many areas with incomplete or
It was a truly collaborative project that built
conflicting science or data and differing opinions.
during 2017-2018 as a major and positive step
report voices concerns from Americans, especially
tick-borne disease patients, who demand change.
It focuses on the key challenges of the emerging
epidemic of Lyme disease and other tick-borne
diseases facing the United States including
to changing today’s status quo for the better. This
networks across silos. These will prove valuable
relationships and strengthened professional
the report and recommendations are updated for
Congress and the HHS Secretary.
Many of the recommendations in this report
and evolve further during the next four years as
•
•
Tick ecology and the epidemiology of tick-
borne infections;
The prevention of tick-borne disease and
borne disease;
passed by unanimous consent. All members of
the Working Group agreed that education is
a priority, and that Americans with tick-borne
a few recommendations that had opposing
the need for new strategies to prevent tick-
diseases need Federal action now. There were
viewpoints. In these cases, minority responses
presented differing viewpoints.
At the highest level, the Working Group
•
•
Diagnostic testing challenges;
Treatment challenges, especially for
initial therapy; and
patients with ongoing symptoms after
focused on the need for substantial increases
•
Challenges to patient access to care and
in resources and funding for the urgent, unmet
outcomes in a field with much controversy.
needs in research and patient care. For decades,
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tick-borne diseases have increased at an alarming rate—much faster than Federal R&D investments.
As a result, the Federal Government today faces significant societal challenges and “research
debt” due to the compounded costs over time that, until now, have been largely ignored without a
its understanding of tick-borne disease, as it does other public health threats like HIV/AIDS, Zika virus,
and cancer—are
substantial. Federal priority and investment must begin now.
comprehensive national response. The investments required now—just to catch up the United States in
The continued spread of ticks, the discovery of new tick-borne pathogens, and the spreading outbreak
response to the public health crisis affecting hundreds of thousands of individuals each year in the
United States.
of human disease is a near certainty. This report lays out an initial analysis and recommendations in
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Appendices
Appendix A. Tick-Borne Disease Working Group
or indirectly contributing to this 2018 report. The Working Group members express their gratitude
to the many members of the public—from
across all sectors—who
shared their expertise, stories,
Dozens of individuals participated in the Tick-Borne Disease Working Group process, either directly
and recommendations to help improve the quality of the report. Additionally, a special thanks to the
subcommittee members of the Tick-Borne Disease Working Group who gave so generously of their
time.
Working Group Members
John N. Aucott, MD (Chair)
Associate Professor, Division of Rheumatology,
Johns Hopkins University School of Medicine;
Director, Johns Hopkins Lyme Disease Clinical
Charles Benjamin (Ben) Beard, PhD
Diseases, Centers for Disease Control and
Deputy Director, Division of Vector-Borne
Prevention, U.S. Department of Health and Human
Services; Associate Editor,
Emerging Infectious
Diseases
Research Center
Captain Scott Cooper, PA, MMS
Senior Technical Advisor and Lead Officer,
Medicare Hospital Health and Safety Regulations,
Centers for Medicare and Medicaid Services, U.S.
Kristen T. Honey, PhD, PMP (Vice-Chair)
U.S. Department of Health & Human Services;
Senior Research Scholar, Stanford University;
Member, Stanford University Lyme Disease
Innovator in Residence, Office of the Secretary,
Department of Health and Human Services
Working Group
Dennis M. Dixon, PhD
National Institute of Allergy and Infectious
Chief, Bacteriology and Mycology Branch,
Wendy A. Adams, MBA
Research Grant Director, Bay Area Lyme
Foundation
Diseases, National Institutes of Health, U.S.
Department of Health and Human Services
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APPENDICES
Richard I. Horowitz, MD
Center
Medical Director, Hudson Valley Healing Arts
Robert Smith, MD, MPH
Maine Medical Center Research Institute; Director,
Center
Division of Infectious Diseases, Maine Medical
Director, Vector-Borne Disease Laboratory,
Captain Estella Jones, DVM
Acting Deputy Director, Office of
Counterterrorism & Emerging Threats, Food and
Drug Administration, U.S. Department of Health
and Human Services
Designated Federal Officers
James J. Berger, MS, MT (ASCP), SBB
(Designated Federal Officer)
Senior Blood and Tissue Policy Advisor, Office of
the Assistant Secretary for Health, Office of the
Lise E. Nigrovic, MD, MPH
Services Research Center, Institutional Centers
Director, Population Health Sciences and Health
HIV/AIDS and Infectious Disease Policy, Office of
Secretary, U.S. Department of Health and Human
for Clinical & Translational Research, Boston
Children’s Hospital; Chair, Pediatric Emergency
Medicine Collaborative Research Committee,
Services
American Academy of Pediatrics
Allen L. Richards, PhD
Director, Rickettsial Diseases Research Program,
of Defense
Naval Medical Research Center, U.S. Department
B. Kaye Hayes, MPA (Alternate
Designated Federal Officer)
Acting Director, Office of HIV/AIDS and
Secretary for Health, Office of the Secretary, U.S.
Department of Health and Human Services
Infectious Disease Policy, Office of the Assistant
Robert Sabatino
Founder and Executive Director, Lyme Society, Inc.
Vanila M. Singh, MD, MACM
Chief Medical Officer, Office of the Assistant
Department of Health and Human Services
Secretary for Health, Office of the Secretary, U.S.
Patricia V. Smith
President, Lyme Disease Association, Inc.
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Appendix B. Acronyms and Abbreviations
Acronym/Abbreviation
B.
CDC
CME
CMS
COI
CSTE
CTF
DFO
DoEd
DoD
E.
ELISA
EM
FACA
FDA
FY
GMO
HHS
HME
HMO
IDSA
IHS
ILADS
LIRR
MMWR
Definition
Borrelia
species
Centers for Disease Control and Prevention
Continuing medical education
Centers for Medicare and Medicaid Services
Cost of illness
Council of State and Territorial Epidemiologists
Colorado tick fever
Designated Federal Officer
United States Department of Education
United States Department of Defense
Ehrlichia
species
Enzyme–Linked Immunosorbent Assay
Erythema migrans
Federal Advisory Committee Act
United States Food and Drug Administration
Fiscal year
Genetically modified organism
United States Department of Health and Human Services
Human monocytic ehrlichiosis
Health maintenance organization
Infectious Diseases Society of America
Indian Health Service
International Lyme and Associated Diseases Society
Long Island Railroad Company
Morbidity and Mortality Weekly Report
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APPENDICES
Definition
National Guideline Clearinghouse
National Institute for Health and Care Excellence
National Institute of Allergy and Infectious Diseases
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
NIH
NIMH
NINDS
OASH
OspA
OspC
PCORnet
PCR
PTLDS
R.
R&D
RMSF
RNAi
SFTS
SME
sp.
SSDI
STARI
TBRF
U.S.
USAF
VA
WNV
National Institutes of Health
National Institute of Mental Health
National Institute of Neurological Disorders and Stroke
HHS Office of the Assistant Secretary for Health
Outer surface protein A
Outer surface protein C
Patient-Centered Clinical Research Network
Polymerase chain reaction
Post-treatment Lyme disease syndrome
Rickettsia
species
Research and development
Rocky Mountain spotted fever
RNA interference
Severe fever with thrombocytopenia syndrome
Subject matter expert
Species
Social Security Disability Insurance
Southern tick-associated rash illness
Tick-borne relapsing fever
United States of America
United States Air Force
U.S. Department of Veterans Affairs
West Nile virus
Acronym/Abbreviation
NGC
NICE
NIAID
NIAMS
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Appendix C.
C.1: U.S. Tick-Borne Diseases and Associated Pathogens
Anaplasmosis*
Babesiosis*
Borrelia miyamotoi
Bourbon virus (presumed to be tick-transmitted)
Colorado tick fever (CTF)
Ehrlichiosis*
E. chaffeensis
E. ewingii
E. muris eauclairensis
Heartland virus
Lyme disease*
B. burgdorferi sensu stricto
B. burgorferi sensu lato
Powassan virus disease*
Spotted fever
rickettsiosis*
R. rickettsii
rickettsiosis (RMSF)
R. parkeri
rickettsiosis
Rickettsia
sp. 364D rickettsiosis
STARI (Southern tick-associated rash illness)
Tick-borne relapsing fever (TBRF) carried by soft
ticks
Tularemia*
*Nationally notifiable to the National Notifiable Diseases
Surveillance System
C.2: Annual Reported Tick-Borne Disease Cases by Year, U.S.: 2004-2016
Nationally Notifiable Diseases Surveillance System: https://wwwn.cdc.gov/nndss/infectious-tables.html
Source: https://www.cdc.gov/mmwr/volumes/67/wr/mm6717e1.htm
Note: Lyme disease estimates are based on case reporting to CDC multiplied by an 8- to 12-fold factor to account
for estimated underreporting.
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APPENDICES
Appendix D. Federal Inventory
Tick-Borne Disease Working Group Inventory Analysis
According to the
21st Century Cures Act,
the Tick-Borne Disease Working Group was created to
1.
Review all efforts within the U.S. Department of Health and Human Services (HHS) related to all
tick-borne diseases;
2.
Ensure interagency coordination and minimize overlap; and
3.
Identify research priorities and gaps.
To achieve these outcomes, the Working Group surveyed the following agencies about their roles and
activities, if any, related to tick-borne diseases.
The Centers for Disease Control and Prevention (CDC)
The National Institutes of Health (NIH)
The U.S. Food and Drug Administration (FDA)
The Centers for Medicare and Medicaid Services (CMS)
The U.S. Department of Defense (DoD)
The U.S. Department of Veterans Affairs (VA)
•
•
•
•
•
•
All of the agencies responded to the inventory. However, CMS and VA did not report any program
funding, research, or activity focused on tick-borne diseases.
Agencies Overview
The Working Group sought to align the tick-borne disease activities within the agencies to the topic
areas of the Working Group’s six subcommittees: 1. Disease Vectors, Surveillance, and Prevention; 2.
Pathogenesis, Transmission, and Treatment; 3. Testing and Diagnostics; 4. Access to Care Services and
Care Services and Support to Patients; meanwhile DoD’s activities align with two subcommittee topic
areas (Disease Vectors and Surveillance and Vaccines and Therapeutics). Though FDA indicated not
having an established program dedicated to tick-borne diseases, they reported some activities that
and NIH projects align with five out of the six subcommittee topic areas with the exception of Access to
Support to Patients; 5. Vaccines and Therapeutics; 6. Other Tick-Borne Diseases and Coinfections. CDC
major activities.
align with all of the six subcommittee topic areas. These activities are carried out within existing FDA
In its survey, the Working Group also inquired about the existence of a strategic plan to address Lyme
disease and other tick-borne diseases. Of the six agencies, only CDC and DoD indicated having a
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readily available plan. CDC and NIH report engaging in both vector and human surveillance while DoD
focuses exclusively on vectors. Following the establishment of Lyme disease as a nationally notifiable
condition in 1991, CDC initiated systematic tracking within 11 participating states in 1992. From 2010
to 2016, between 30,000 to 38,000 cases of Lyme disease were reported to CDC each year. However,
reported cases are known to be an underestimation of diagnosed cases of Lyme disease and other
tick-borne diseases.
With the exception of DoD, which tracks diagnosis of its Servicemembers, no other agency reported
tracking cases or diagnosis in its survey. From October 2009 to September 2017, DoD reported that
708 active duty Servicemembers were diagnosed with Lyme disease or other tick-borne disease. Of
those, 549 were stationed within the United States.
Intramural and Extramural Activities
CDC, NIH, and DoD have managed over 1,500 past and ongoing tick-borne disease projects from
were released by four agencies: CDC-467; NIH-235; DoD-41; FDA-7.
fiscal year 2010 to 2018. During the same timeframe, over 750 tick-borne disease-related publications
Also during that time, approximately $554 million have been invested in tick-borne disease-related
projects, activities, and research by CDC, NIH, FDA, and DoD. For example, DoD’s Tick-Borne Disease
Research Program (TBDRP) was established in 2016 to support innovative and impactful research that
addresses issues and gaps in tick-borne diseases. D.1: Tick-Borne Disease Research Program Funding
Allocations (Department of Defense) outlines the program’s budgetary allocations during its first two
years.
D.1: Tick-Borne Disease Research Program Funding Allocations
(Department of Defense)
Allocation Category
Budget
Number of Awards
Funding of Treatment
Funding of Pathogenesis
Funding of Prevention
Funding of Diagnosis
2016
$4.8 million
7
44%
31%
16%
9%
2017
$4.5 million
6
0%
32%
48%
20%
and Radiological Health (CDRH) oversees approval of diagnostic assays for tick-borne diseases; the
Center for Biologics Evaluation and Research (CBER) manages licenses for blood screening assays
In addition, FDA invests in tick-borne disease activities within its departments. The Center for Devices
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APPENDICES
(for example,
Babesia)
and vaccines for tick-borne diseases; and the Center for Drug Evaluation and
Research (CDER) administers the approval process for drug therapies for tick-borne diseases.
In order to understand the gaps and priorities in tick-borne disease research, the Working Group asked
the agencies to describe any unmet needs identified through their work on tick-borne diseases. Below
is a list of identified priorities and gaps extracted from the survey.
Improve early and accurate diagnosis and treatment.
Strengthen national surveillance.
Understand the immunological mechanism (for example, the pathogen-host interaction) of
immune protection for Lyme disease and other tick-borne diseases.
Develop new rapid and accurate lab tests.
Develop antibiotic combination and/or therapeutic options for treating acute and persistent
illness.
Encourage the development of strategic plans for tick-borne disease Federal investments.
Dedicate funding to tick-borne diseases and evaluate related activities using performance
indicators and clear metrics for success.
Characterize how tick-borne disease affects U.S. national security, military readiness, and the
health and wellness of active duty Servicemembers, Veterans, and their families.
•
•
•
•
•
•
•
•
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Appendix E.
21st Century Cures Act
to comprise Federal and public members with diverse disciplines and views pertaining to tick-borne
on its findings and any recommendations every two years. Working Group responsibilities include a
Tick-Borne Disease Working Group to serve as a Federal Advisory Committee. The Working Group is
The
21st Century Cures Act,
enacted in December 2016, authorizes the HHS Secretary to establish a
diseases. The Act charges the Working Group to provide a report to Congress and the HHS Secretary
review of ongoing research and resulting advances; Federal epidemiological and research efforts;
provided below.
and identification of research gaps. The
21st Century Cures Act,
Section 2062 Tick-Borne Diseases, is
SEC. 2062. Tick-Borne Diseases.
(a) IN GENERAL. The Secretary of Health and Human Services (referred to in this section as ‘‘the
Secretary’’) shall continue to conduct or support epidemiological, basic, translational, and clinical
research related to vector-borne diseases, including tick-borne diseases.
(b) REPORTS. The Secretary shall ensure that each triennial report under section 403 of the Public
Health Service Act (42 U.S.C. 283) (as amended by section 2032) includes information on actions
undertaken by the National Institutes of Health to carry out subsection (a) with respect to tick-borne
diseases.
(c) TICK-BORNE DISEASES WORKING GROUP.
(1)
ESTABLISHMENT. The Secretary shall establish a working group, to be known as the Tick-Borne
Disease Working Group (referred to in this section as the ‘‘Working Group’’), comprised of
representatives of appropriate Federal agencies and other non-Federal entities, to provide
expertise and to review all efforts within the Department of Health and Human Services related
to all tick-borne diseases, to help ensure interagency coordination and minimize overlap, and to
examine research priorities.
(2)
RESPONSIBILITIES. The Working Group shall
(A)
Not later than 2 years after the date of enactment of this Act, develop or update a summary
of
(i)
Ongoing tick-borne disease research, including research related to causes, prevention,
treatment, surveillance, diagnosis, diagnostics, duration of illness, and intervention for
individuals with tick-borne diseases;
(ii)
Advances made pursuant to such research;
(iii)
Federal activities related to tick-borne diseases, including—
(I)
Epidemiological activities related to tick-borne diseases; and
(II)
Basic, clinical, and translational tick-borne disease research related to the
pathogenesis, prevention, diagnosis, and treatment of tick-borne diseases;
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(iv)
Gaps in tick-borne disease research described in clause (iii)(II);
(v)
The Working Group’s meetings required under paragraph (4); and
(vi)
The comments received by the Working Group;
(B)
Make recommendations to the Secretary regarding any appropriate changes or
improvements to such activities and research; and
(C)
Solicit input from States, localities, and nongovernmental entities, including organizations
representing patients, health care providers, researchers, and industry regarding scientific
advances, research questions, surveillance activities, and emerging strains in species of
pathogenic organisms.
(3)
MEMBERSHIP. The members of the Working Group shall represent a diversity of scientific
disciplines and views and shall be composed of the following members:
(A)
FEDERAL MEMBERS. Seven Federal members, consisting of one or more representatives of
each of the following:
(i)
The Office of the Assistant Secretary for Health.
(ii)
The Food and Drug Administration.
(iii)
The Centers for Disease Control and Prevention.
(iv)
The National Institutes of Health.
(v)
Such other agencies and offices of the Department of Health and Human Services as
the Secretary determines appropriate.
(B)
NON–FEDERAL PUBLIC MEMBERS. Seven non–Federal public members, consisting of
representatives of the following categories:
(i)
Physicians and other medical providers with experience in diagnosing and treating
tick-borne diseases.
(ii)
Scientists or researchers with expertise.
(iii)
Patients and their family members.
(iv)
Nonprofit organizations that advocate for patients with respect to tick-borne diseases.
(4)
MEETINGS. The Working Group shall meet not less than twice each year.
(5)
REPORTING. Not later than 2 years after the date of enactment of this Act, and every 2 years
thereafter until termination of the Working Group pursuant to paragraph (7), the Working Group
shall
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(A)
Submit a report on its activities under paragraph (2)(A) and any recommendations under
paragraph (2)(B) to the Secretary, the Committee on Energy and Commerce of the House
of Representatives, and the Committee on Health, Education, Labor, and Pensions of the
Senate; and
(B)
Make such report publicly available on the Internet website of the Department of Health
and Human Services.
(6)
APPLICABILITY OF FACA. The Working Group shall be treated as an advisory committee subject
to the
Federal Advisory Committee Act
(5 U.S.C. App.).
(7)
SUNSET. The Working Group under this section shall terminate 6 years after the date of
enactment of this Act.
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APPENDICES
Appendix F. Working Group Charter
The Charter defines how the Working Group will be structured and will function in response to the
Disease Working Group was approved by the Secretary of Health and Human Services on August 10,
2017. The text of the Charter is provided below.
charge provided by the
21st Century Cures Act
(see Appendix E). The charter for the Tick-Borne
Tick-borne Disease Working Group
Authority
The Tick-Borne Disease Working Group (hereafter referred to as the Working Group) is required under
Federal Advisory Committee Act
(FACA), Public Law 92-463, as amended (5 U.S.C. App), which sets
Section 2062 of the
21st Century Cures Act.
The Working Group is governed by the provisions of the
forth standards for the formation and use of advisory committees.
Objectives and Scope of Activities
The Secretary of Health and Human Services (Secretary) is responsible for ensuring the conduct of or
including tick-borne diseases. The Working Group will provide expertise and review all efforts within
support for epidemiological, basic, translational, and clinical research related to vector-borne diseases,
the Department of Health and Human Services related to all tick-borne diseases, to help ensure
interagency coordination and minimize overlap, and to examine research priorities.
Description of Duties
The Working Group shall have the following responsibilities:
(A)
Not later than two years after the date of enactment of the authorizing legislation, develop or
update a summary of
(1)
Ongoing tick-borne disease research, including research related to causes, prevention,
treatment, surveillance, diagnosis, diagnostics, duration of illness, and intervention for
individuals with tick-borne diseases;
(2)
Advances made pursuant to such research;
(3)
Federal activities related to tick-borne diseases, including:
(a)
Epidemiological activities related to tick-borne diseases; and
(b)
Basic, clinical, and translational tick-borne disease research related to the pathogenesis,
prevention, diagnosis, and treatment of tick-borne diseases.
(4)
Gaps in tick-borne disease research described in clause 3b;
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(5)
The Working Group’s meetings; and the comments received by the Working Group.
(B)
Make recommendations to the Secretary regarding any appropriate changes or improvement to
such activities and research; and
(C)
Solicit input from States, localities, and non-governmental entities, including organizations
representing patients, health care providers, researchers, and industry regarding scientific
advances, research questions, surveillance activities, and emerging strains in species of pathogenic
organisms.
Agency or Official to Whom the
Working Group Reports
The Working Group will provide
recommendations to the Secretary.
Not later than two years after the date of
enactment of the authorizing legislation
(December 13, 2016) and every two years
Estimated Annual Operating Costs
and Staff Years
Estimated annual cost for operating the Working
Group, including compensation and travel
expenses for members, but excluding staff
support, is $349,440. Estimated person years
annual cost of $250,560.
of staff support required is 2.0, at an estimated
thereafter until the Working Group is terminated
pursuant to the stipulations of the authorizing
legislation, the Working Group shall:
Designated Federal Officer (DFO)
The ASH will select the Designated Federal
Officer (DFO) from among full-time or permanent
part-time staff within OASH, who have knowledge
of the subject matter and skills and experience
necessary to manage the Working Group. The
ASH may appoint an Alternate DFO who will carry
out these duties in the event that the appointed
DFO cannot fulfill the assigned responsibilities
for the Working Group. In the absence of the
appointed DFO or Alternate DFO, the ASH will
temporarily appoint one or more permanent full-
time or part-time program staff to carry out the
assigned duties.
(A)
Submit a report on its activities and any
recommendations, as stipulated under the
Description of Duties (A) and (B), to the
Secretary, the Committee on Energy and
Commerce of the House of Representatives,
and the Committee on Health, Education,
Labor, and Pensions of the Senate; and
(B)
Make such report publicly available on the
Internet website of the Department of Health
and Human Services.
Support
Management and support services for the
Working Group’s activities will be provided
by staff from within the Office of the Assistant
Secretary for Health (OASH). OASH is a staff
Department of Health and Human Services.
division within the Office of the Secretary in the
The DFO will schedule and approve all meetings
of the Working Group and any subcommittees
that may be established by the Working Group.
The DFO will prepare and approve all meeting
agendas. The DFO may collaborate with the
Working Group Chair in this activity, and when
deemed appropriate, with chairs of any existing
subcommittees that have been established by
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APPENDICES
the Working Group. The DFO, Alternate DFO, or
designee will attend all meetings of the Working
Group and all meetings of any subcommittees
that have been established to assist the Working
Group. The DFO has authority to adjourn
meetings, when it is determined to be in the
public interest, and the DFO can be directed by
the Secretary or designee to chair meetings of the
Working Group.
Duration
Establishment of the Working Group was
mandated under Section 2602 of the
21st Century
Cures Act.
The Working Group will operate
pursuant to the stipulations in the authorizing
legislation.
Termination
Unless extended by Congress, the Working
Group will be terminated (on December 13,
2022) six years after the date of enactment of
the authorizing legislation. Unless renewed by
appropriate action, the charter for the Working
Group will expire two years from the date it is
filed.
Estimated Number and Frequency
of Meetings
The Working Group will meet not less than
twice a year, and these may be conducted
by teleconference or video conference at the
discretion of the ASH. The meetings will be open
to the public, except as determined otherwise by
the Secretary, or other official to whom authority
has been delegated, in accordance with the
guidelines under
Government in the Sunshine
Act,
5 U.S.C. 552b(c). Notice of all meetings will
be provided to the public in accordance with the
FACA. Meetings will be conducted and records
of the proceedings will be kept, as required by
applicable laws and departmental policies. A
quorum is required for the Working Group to
meet to conduct business. A quorum will consist
of a majority of the Working Group’s voting
members.
Membership and Designation
The Working Group will consist of 14 voting
members, including the Chair, who represent
diverse scientific disciplines and views. The
composition will include seven Federal members
and seven non-Federal public members. The
Federal members will consist of one or more
representatives of each of the following: OASH,
the Food and Drug Administration, the Centers
for Disease Control and Prevention, and the
National Institutes of Health. The non-Federal
public members will consist of representatives
of the following categories: physicians and other
medical providers with experience in diagnosing
and treating tick-borne diseases; scientists or
researchers with expertise; patients and their
family members; nonprofit organizations that
advocate for patients with respect to tick-borne
When the Secretary or designee determines
that a meeting will be closed or partially closed
to the public, in accordance with stipulations of
Government in the Sunshine Act,
5 U.S.C. 552b(c),
then a report will be prepared by the DFO that
includes, at a minimum, a list of members and
their business addresses, the Working Group’s
functions, date and place of the meeting, and a
summary of the Working Group’s activities and
recommendations made during the fiscal year.
A copy of the report will be provided to the
Department Committee Management Officer.
diseases. One or more of the non-Federal public
members will be selected by the Secretary to
serve as the Chair, Vice Chair, and/or Co-Chairs.
Individuals who are appointed to represent
Federal entities will be classified as regular
government employees. The non-Federal public
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members will be classified as special government
employees. Invitations of membership will be
extended to other agencies and offices of the
Department of Health and Human Services
and other individuals as determined by the
Secretary to be appropriate and beneficial to the
functioning of the Working Group.
The Federal members will be appointed to
serve for the duration of time that the Working
Group is authorized to operate. Participation of
the appointed Federal members will be at the
discretion of the respective agency head. The
non-Federal public members will be invited
to serve as special government employees
for overlapping terms of up to four years. Any
non-Federal public member who is appointed
to fill the vacancy of an unexpired term will be
appointed to serve for the remainder of that term.
A non-Federal public member may serve after the
expiration of their term until their successor has
taken office, but no longer than 180 days.
Pursuant to advance written agreement, non-
Federal public members of the Working Group
will receive no stipend for the advisory service
that they render as members of the Working
Secretary or another Federal official unless there
is specific statutory authority for such reporting.
The Department Committee Management Officer
will be notified upon establishment of each
subcommittee, and will be given information
regarding its name, membership, function, cost,
and estimated frequency of meetings.
pertinent to the mission of the Working Group.
The established subcommittee may consider
issues in accordance with the mission of the
Working Group, and will, as appropriate, make
recommendations and/or reports to the Working
Group for consideration. Recommendations
and/or reports of the subcommittee that are
provided to the Working Group will be discussed
at an open public meeting that is held by the
Working Group. No established subcommittee
of the Working Group may report directly to the
Recordkeeping
Records of the Working Group and any
established subcommittees will be handled in
accordance with the General Records Schedule
6.2, Federal Advisory Committee Records, or
other approved agency records disposition
schedule.
Group. However, non-Federal public members
will receive per diem and reimbursement for
travel expenses incurred in relation to performing
duties for the Working Group, as authorized by
law under 5 U.S.C. 5703 for persons who are
employed intermittently to perform services for
the Federal Government and in accordance with
Federal travel regulations.
Applicable records will be made available to the
public for inspection and copying, subject to the
Freedom of Information Act,
5 U.S.C. 552.
Approved:
August 10, 2017
Subcommittees
In carrying out its function, the Working Group
Thomas E. Price
Secretary of Health and Human Services
may establish subcommittees composed of
members of the Working Group, as well as
other individuals who have expertise and
knowledge about the topics and issues that are
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APPENDICES
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APPENDICES
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APPENDICES
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