Searching for Persistence of Infection in Lyme Disease
| Status: | Completed |
|---|---|
| Conditions: | Infectious Disease |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 99 |
| Updated: | 3/24/2019 |
| Start Date: | August 1, 2010 |
| End Date: | December 30, 2014 |
Background:
Lyme disease is an infection caused by Borrelia burgdorferi, a bacteria that is transmitted
to humans by ticks. It can cause many different symptoms including rash, fever, headache,
meningitis (infection of the central nervous system), and arthritis. While most patients
improve after taking antibiotics, some patients continue to have symptoms. It is currently
unknown why some patients continue to have symptoms. One possibility is that the antibiotics
have not successfully gotten rid of all of the bacteria. Current tests for Lyme disease
cannot tell whether the bacteria have been successfully eliminated from the body.
Xenodiagnosis is a way to look for Borrelia bacteria using the animal that usually hosts
them, Ixodes scapularis (also known as the deer tick). This method takes advantage of the
evolution of the bacteria and the insect that transmits the infection, which can make the
insect particularly good at finding the agent. In studies of animals, xenodiagnosis may be
more sensitive than current tests for detecting the presence of the Lyme disease bacteria.
Researchers are interested in using xenodiagnosis to determine whether uninfected ticks that
feed on humans who have been infected with Lyme disease bacteria can detect the continued
presence of live bacteria.
Objectives:
- To determine whether xenodiagnosis can be used to successfully investigate the presence of
Lyme disease bacteria.
Eligibility:
1. Individuals at least 18 years of age who are in one of the following categories:
2. Have had the erythema migrans rash (a symptom of Lyme infection) and received antibiotic
therapy less than 4 months ago (but have not had antibiotics in the previous month).
3. Have the erythema migrans rash and received less than 2 days of antibiotic therapy.
4. Have been diagnosed with early or late Lyme disease, have received antibiotic therapy,
but still have high levels of antibodies against the bacteria at least 6 months after
therapy, and have not received antibiotics in the past 3 months.
5. Have been diagnosed with early or late Lyme disease, have received antibiotic therapy,
and have new complaints of fatigue or other symptoms that are persistent for at least 6
months after completion of antibiotic therapy, and have not received antibiotics in the
past 3 months.
6. Have been diagnosed with Lyme arthritis and have not yet received antibiotic therapy.
7. Healthy volunteers who have not had Lyme disease will also be included in this study.
Design:
- Participants will have an initial visit for a physical examination, medical history, and
blood sample.
- For the first study visit, researchers will place a strip of filter paper or a small
plastic container with 20 to 30 disease-free ticks on the participant s skin. If
possible, the ticks will be placed at the site of a Lyme disease rash or another
suspicious area, or on the nondominant forearm. Participants will be asked to keep the
ticks in place, and will keep a diary card at home to record any symptoms or problems.
- The ticks will be collected 4 to 6 days after placement. At that visit, participants
will have a skin biopsy taken of the area tested, a blood sample will be collected, and
participants will receive a new diary card to keep until the next clinic visit.
- After 1 month, participants will provide a final blood sample, and will receive a
follow-up phone call 2 months afterward.
Lyme disease is an infection caused by Borrelia burgdorferi, a bacteria that is transmitted
to humans by ticks. It can cause many different symptoms including rash, fever, headache,
meningitis (infection of the central nervous system), and arthritis. While most patients
improve after taking antibiotics, some patients continue to have symptoms. It is currently
unknown why some patients continue to have symptoms. One possibility is that the antibiotics
have not successfully gotten rid of all of the bacteria. Current tests for Lyme disease
cannot tell whether the bacteria have been successfully eliminated from the body.
Xenodiagnosis is a way to look for Borrelia bacteria using the animal that usually hosts
them, Ixodes scapularis (also known as the deer tick). This method takes advantage of the
evolution of the bacteria and the insect that transmits the infection, which can make the
insect particularly good at finding the agent. In studies of animals, xenodiagnosis may be
more sensitive than current tests for detecting the presence of the Lyme disease bacteria.
Researchers are interested in using xenodiagnosis to determine whether uninfected ticks that
feed on humans who have been infected with Lyme disease bacteria can detect the continued
presence of live bacteria.
Objectives:
- To determine whether xenodiagnosis can be used to successfully investigate the presence of
Lyme disease bacteria.
Eligibility:
1. Individuals at least 18 years of age who are in one of the following categories:
2. Have had the erythema migrans rash (a symptom of Lyme infection) and received antibiotic
therapy less than 4 months ago (but have not had antibiotics in the previous month).
3. Have the erythema migrans rash and received less than 2 days of antibiotic therapy.
4. Have been diagnosed with early or late Lyme disease, have received antibiotic therapy,
but still have high levels of antibodies against the bacteria at least 6 months after
therapy, and have not received antibiotics in the past 3 months.
5. Have been diagnosed with early or late Lyme disease, have received antibiotic therapy,
and have new complaints of fatigue or other symptoms that are persistent for at least 6
months after completion of antibiotic therapy, and have not received antibiotics in the
past 3 months.
6. Have been diagnosed with Lyme arthritis and have not yet received antibiotic therapy.
7. Healthy volunteers who have not had Lyme disease will also be included in this study.
Design:
- Participants will have an initial visit for a physical examination, medical history, and
blood sample.
- For the first study visit, researchers will place a strip of filter paper or a small
plastic container with 20 to 30 disease-free ticks on the participant s skin. If
possible, the ticks will be placed at the site of a Lyme disease rash or another
suspicious area, or on the nondominant forearm. Participants will be asked to keep the
ticks in place, and will keep a diary card at home to record any symptoms or problems.
- The ticks will be collected 4 to 6 days after placement. At that visit, participants
will have a skin biopsy taken of the area tested, a blood sample will be collected, and
participants will receive a new diary card to keep until the next clinic visit.
- After 1 month, participants will provide a final blood sample, and will receive a
follow-up phone call 2 months afterward.
Lyme disease is the most common vector borne disease in the United States. Although
antibiotic therapy is clinically effective in treating the symptoms of Lyme disease for most
patients early in the course of disease, a significant number of patients who receive therapy
report persistent symptoms. The cause of persistent symptoms after antibiotic therapy for
Lyme disease is an area of great controversy. Recent studies have shown that the organism
(Borrelia burgdorferi) may persist in animals after antibiotic therapy and can be detected by
using the natural tick vector (Ixodes scapularis) to acquire the organism through feeding
(xenodiagnosis). Whether this occurs in humans is unknown. Currently available tests for
human Lyme disease do not allow determination of persistent infection after antibiotic
therapy.
In this proposal, the utility of xenodiagnosis for identifying persistence of B. burgdorferi
in treated human Lyme disease will be tested in up to 120 subjects with various stages of
Lyme disease with 30 healthy adults to serve as controls. Subjects will be followed for
approximately 3 months. In Objective #1, subjects who have the characteristic erythema
migrans (EM) rash and have been treated with antibiotics early (within 3 weeks of infection)
in the course of Lyme disease will be tested. After completion of antibiotic therapy, 25-30
larval Ixodes ticks will be allowed to feed on the subject and biopsies of the EM site will
be performed. Repleted ticks will be collected and tested for the presence of B. burgdorferi.
In Objective #2, similar studies will be performed, but enrollment will target subjects with
elevated C6 (region 6 of the VlsE surface protein of B. burgdorferi) antibody levels. In
Objective #3, patients with persistent symptoms after antibiotic therapy will be evaluated.
As an attempt to increase the chances of a positive xenodiagnosis in humans, patients with EM
who are in the first 2 days of antibiotic therapy and patients with untreated Lyme arthritis
will also be evaluated. Evidence that B. burgdorferi can be recovered by xenodiagnosis after
antibiotic therapy in subjects with continued symptoms would change the current paradigm for
potential mechanisms of disease and provide researchers and clinicians a tool for identifying
patients with persistent infection. In Objective #4 we will assess the safety of the planned
xenodiagnostic procedure in humans. All individuals who underwent xenodiagnosis under the
study will be assessed for adverse events.
antibiotic therapy is clinically effective in treating the symptoms of Lyme disease for most
patients early in the course of disease, a significant number of patients who receive therapy
report persistent symptoms. The cause of persistent symptoms after antibiotic therapy for
Lyme disease is an area of great controversy. Recent studies have shown that the organism
(Borrelia burgdorferi) may persist in animals after antibiotic therapy and can be detected by
using the natural tick vector (Ixodes scapularis) to acquire the organism through feeding
(xenodiagnosis). Whether this occurs in humans is unknown. Currently available tests for
human Lyme disease do not allow determination of persistent infection after antibiotic
therapy.
In this proposal, the utility of xenodiagnosis for identifying persistence of B. burgdorferi
in treated human Lyme disease will be tested in up to 120 subjects with various stages of
Lyme disease with 30 healthy adults to serve as controls. Subjects will be followed for
approximately 3 months. In Objective #1, subjects who have the characteristic erythema
migrans (EM) rash and have been treated with antibiotics early (within 3 weeks of infection)
in the course of Lyme disease will be tested. After completion of antibiotic therapy, 25-30
larval Ixodes ticks will be allowed to feed on the subject and biopsies of the EM site will
be performed. Repleted ticks will be collected and tested for the presence of B. burgdorferi.
In Objective #2, similar studies will be performed, but enrollment will target subjects with
elevated C6 (region 6 of the VlsE surface protein of B. burgdorferi) antibody levels. In
Objective #3, patients with persistent symptoms after antibiotic therapy will be evaluated.
As an attempt to increase the chances of a positive xenodiagnosis in humans, patients with EM
who are in the first 2 days of antibiotic therapy and patients with untreated Lyme arthritis
will also be evaluated. Evidence that B. burgdorferi can be recovered by xenodiagnosis after
antibiotic therapy in subjects with continued symptoms would change the current paradigm for
potential mechanisms of disease and provide researchers and clinicians a tool for identifying
patients with persistent infection. In Objective #4 we will assess the safety of the planned
xenodiagnostic procedure in humans. All individuals who underwent xenodiagnosis under the
study will be assessed for adverse events.
- INCLUSION CRITERIA:
Criteria for the diagnosis of Lyme disease can be found at The clinical assessment,
treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis:
clinical practice guidelines by the Infectious Diseases Society of America (4).
1. Patients With EM (N=35), Post Treatment
- Age 18 or older
- EM diagnosed by the study physician or, with a diagnosis of EM that is thought to
be highly likely by the study physician.
- Treatment with at least 1 course of antibiotics that fulfills the Infectious
Diseases Society of America guidelines for the recommended therapy for Lyme
disease. There must be at least 1 month and up to 4 months between the end of the
therapy and the study procedures.
2. High C6 Antibody Titer (N=35)
- Age 18 or older
- Diagnosed with confirmed or probable early or late Lyme disease as per Centers
for Disease Control and Prevention (CDC) case definition
(http://www.cdc.gov/ncphi/disss.nndss/caseded/lyme disease 2008.htm), have
received recommended antibiotic therapy and have a high C6 ELISA titer (index
above 3) at least 6 months after therapy.
3. Post Lyme disease syndrome (N=20)
- Age 18 or older
- Diagnosed with confirmed or probable early or late Lyme disease fulfilling the
case definition of Lyme disease by the CDC
(http://www.cdc.gov/ncphi/disss.nndss/caseded/lyme disease 2008.htm)
- Received recommended antibiotic therapy, with resolution or stabilization of the
objective manifestation(s) of Lyme disease.
- New complaints of fatigue, paresthesias or dysesthesias, widespread
musculoskeletal pain or cognitive difficulties within 6 months of the diagnosis
of Lyme disease
- Symptoms are persistent or relapsing for at least a 6-month period after
completion of antibiotic therapy, causing reduction in previous levels of
occupational, educational, social, or personal activities.
- No antibiotic therapy active against Lyme disease in the previous 3 months.
4. Patients With EM (N=20), On Treatment
- Age 18 or older
- EM diagnosed by the study physician and receiving antibiotic therapy for less
than 48 hours.
5. Lyme Arthritis (N=10)
- Age 18 or older
- Lyme arthritis and have not received therapy.
6. Healthy Volunteers (N=30)
- Age 18 or older
- No history of Lyme disease
- Negative whole-cell Borrelia ELISA or C6 ELISA
- Living in an endemic area for Lyme disease.
EXCLUSION CRITERIA:
- History of allergy to surgical tape or Nitex nylon mesh
- History of severe reactions to tick bites (granuloma or systemic reactions)
- Inability to maintain the dressing for any reason
- Currently receiving any antibiotic or having received antibiotics in the last month (3
months for patients with post Lyme disease syndrome and high C6 titer) (except
patients with EM on treatment)
- Pregnancy or lactation
- Unwillingness to use an effective method of birth control for 3 months after tick
placement (women of child-bearing potential only)
- Not able to understand all of the requirements of the study or unable to give informed
consent and/or comply with all aspects of the evaluation.
- Investigational therapy during the time of the study and/or in the month prior to
signing the informed consent.
- Active severe skin disease, uncontrolled diabetes, cancer other than non-melanoma skin
cancers, autoimmune disease requiring immunosuppressive therapy, or history of HIV,
chronic viral hepatitis, or syphilis.
- Oral steroids in the previous 2 weeks (nasal steroids and replacement doses of
steroids are not exclusions)
- Any other condition that, in the opinion of the investigator, would make the patient
unsuitable for enrollment or could interfere with the patient participating in and
completing the study.
EXCLUSION FROM SKIN BIOPSY PART OF THE PROTOCOL:
- History of forming large thick scars after skin injuries or surgery
- History of excessive bleeding after cuts or procedures
- Currently taking anticoagulants
- History of allergy to lidocaine
- Biopsies will not be done on face, neck, scalp, or over the tibia
We found this trial at
3
sites
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9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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