A Comprehensive Clinical, Microbiological and Immunological Assessment of Patients With Suspected Post Treatment Lyme Disease Syndrome and Selected Control Populations
A Comprehensive Clinical, Microbiological and Immunological Assessment of Patients With Suspected Post Treatment Lyme Disease Syndrome and Selected Control Populations
This study will determine whether patients who have been infected with the Lyme bacteria,
 Borrelia burgdorferi, and treated with antibiotics still have the bacteria alive inside them
 and whether it is causing their symptoms. The information from this study may serve as a
 basis for developing stringent diagnostic criteria for Lyme disease and the establishment of
 future treatment trials.

 Individuals in the following categories may be eligible for this study: chronic Lyme disease;
 chronic Lyme arthritis; seropositive control (are infected with the bacteria that causes Lyme
 disease but do not have disease symptoms); recovered control (have been sick with Lyme
 disease but were treated successfully and are currently well); control with multiple
 sclerosis (patients with multiple sclerosis); and healthy volunteers. Patients in the chronic
 Lyme disease category must be age 13 and above; all others must be age18 and above.
 Candidates will be screened with blood and urine tests.

 Participants will have a physical examination and the following tests:

 Blood tests Includes HLA-typing, a genetic test of immune system markers;

 Leukapheresis Collection of large numbers of white blood cells Whole blood is collected
 through a needle in an arm vein. The blood circulates through a machine that separates it
 into its components. The white cells are removed and the rest of the blood is returned to the
 body, either through the same needle used to draw the blood or through another needle in the
 other arm. (Alternatively, patients will 100 cc (about 7 tablespoons) of blood drawn.);

 Lumbar puncture (spinal tap) Collection of cerebrospinal fluid (CSF, fluid that bathes the
 brain and spinal cord). A local anesthetic is administered and a needle is inserted in the
 space between the bones in the lower back where the cerebrospinal fluid circulates below the
 spinal cord. A small amount of fluid is collected through the needle;

 Magnetic resonance imaging (MRI) of the brain Imaging of the brain using a strong magnetic
 field and radio waves instead of X-rays. During the scan, the patient lies on a table in a
 narrow cylinder containing a magnetic field. He or she can speak with a staff member via an
 intercom at all times during the procedure;

 Neuropsychologic testing;

 Some participants may also have a hearing test and urine collection.

 Participants whose test results are positive for Borrelia burgdorferi will be followed at NIH
 at intervals of 3 to 6 months until it is determined whether there is infection. Those who
 are infected will be offered treatment with the antibiotic ceftriaxone. Following treatment,
 patients will return to the NIH Clinical Center for follow-up visits 1 week after treatment
 and again at 3, 6 and 12 months. The lumbar puncture, hearing examination, blood and urine
 tests will be repeated at these visits to evaluate the response to treatment, and the
 leukapheresis will be repeated for research purposes. Patients whose MRI was abnormal during
 therapy will have a repeat MRI at the 3-month, 6-month and 1-year visits.

 All participants with chronic Lyme disease, chronic Lyme arthritis, seropositive controls and
 recovered controls may be reevaluated at intervals of 6 to 12 months.
Lyme disease has emerged as the leading vector-borne disease in the United States. Despite
 how much has been learned about Lyme borreliosis in the past decade, there are still many
 remaining areas of uncertainty. One fundamental question is whether persistent signs and
 symptoms of disease, despite the administration of what is currently considered to be
 adequate antibiotic therapy, are due to ongoing active borrelial infection, to a
 post-infectious syndrome, to irreversible sequelae of earlier tissue injury or due to a
 condition unrelated to Lyme disease. Reliable objective markers of infection, of clinical
 status and of host responses to the organism are required to discern the scope and the
 implications of persistent borrelial infection, the effectiveness of current treatment
 options, and the development of new therapeutic approaches. The goal of this study is to
 assemble and follow a well-characterized cohort of patients with post-treatment Lyme disease
 syndrome and relevant controls that will yield a prospective database upon which stringent
 diagnostic criteria can be established and future therapeutic trials can be designed.
-  INCLUSION CRITERIA:

 Screening FOR SUSPECTED PTLDS:

 Age greater than or equal to 13 years old, suspect of suffering from Lyme disease

 Post-Treatment Lyme Disease Syndrome (PTLDS): For the purposes of this study, PTLDS is
 defined as occurring in male or female patients age 13 and above who have been diagnosed
 with confirmed or probable Lyme disease per CDC definition
 (https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/). Studyphysician
 will review history to confirm probable cases. They have received recommended antibiotic
 therapy and have persistent or relapsing symptoms and/or signs for at least six months
 after therapy. They also should have no other documented explanation for their signs and
 symptoms.

 Lyme arthritis controls: For the purposes of this study, Lyme arthritis is defined as
 occurring in an otherwise healthy male or female aged 18 and above who have intermittent
 episodes of arthritis involving one or few joint, without any other cause being documented,
 and have positive serum antibodies to B.burgdorferi confirmed by Western blot according to
 the CDC criteria.

 Recovered Controls: For the purposes of this study, a recovered control is defined as an
 otherwise healthy male or female aged 18 and above who has had Lyme disease, fulfilling the
 CDC Lyme Disease National Surveillance Case Definition and who had received accepted
 antibiotic treatment for Lyme disease (at least 3 months since the end of antibiotic
 therapy before protocol evaluation) and who are currently asymptomatic.

 Seropositive Controls: For the purposes of this study, a serpositive control is defined as
 an otherwise healthy male or female aged 18 and above who has positive serum IgG antibody
 to B.burgdorferi by Western blot according to the CDC criteria and are asymptomatic and who
 recall no episodes of disease compatible with Lyme infection and have not received
 antibiotic therapy for Lyme disease.

 OspA vaccinated control: For the purposes of this study, a OspA vaccinated control is
 defined as an otherwise healthy male or female aged 18 and above who has received at least
 two doses of the OspA vaccine for Lyme disease (Lymerix [R]). These controls may have a
 positive ELISA for B.burgdorferi but a negative (or unreadable) IgG western blot.

 Multiple sclerosis controls: For the purposes of this study, a multiple sclerosis control
 is defined as an otherwise healthy male or female aged 18 and above with
 relapsing-remitting or progressive multiple sclerosis as defined by the Clinical Trial
 Committee of the National Multiple Sclerosis Society and no evidence of prior exposure to
 B.burgdorferi as indicate by negative history for Lyme disease and negative Western blot
 for B.burgdorferi in the serum by the CDC criteria. Patients should have a Kurtzke or
 Expanded Disability Status Scale (EDSS) between 1 to 5.

 Healthy Volunteers: For the purpose of this study, a healthy volunteer is defined as
 healthy male or female, age 18 and above, with no history compatible with Lyme disease and
 negative serological testing to B.burgdorferi by the CDC criteria.

 All study participants must agree to allow their samples to be used for future research.

 EXCLUSION CRITERIA:

 General exclusion criteria:

 Age less than 18 (less than 13 for patients with PTLDS).

 Weight less than 70 Lb (35 kg).

 Pregnancy or lactation.

 Women with childbearing potential who are sexually active with a male partner and unwilling
 to use effective contraception during the evaluation and treatment phases of the protocol.

 Clinically significant laboratory abnormalities including positive test for syphilis (RPR),
 HBsAg, anti-HCV, anti-HIV.

 Chronic medication use will be evaluated in a case-by-case basis.

 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.

 EXCLUSION CRITERIA FOR PTLDS PATIENTS AND LYME ARTHRITIS CONTROLS:

 In addition to the general exclusion criteria, these individuals will be excluded for:

 1. Use of immunosuppressive drugs such as systemic (but not topical or inhalant) steroids
 and cytotoxic agents.

 2. History of any recognized autoimmune disease such as rheumatoid arthritis, vasculitis,
 systemic erythematous lupus, etc.

 3. Serious pre-existing or concurrent chronic medical or psychiatric illnesses other than
 Lyme disease.

 4. Past history of significant head trauma, alcohol or substance abuse in the past 5
 years or other medical illness that might produce neurologic deficit (such as
 cerebrovascular disease).

 5. Use of systemic antibiotics in the previous month.

 6. Use of immunomodulators such as interferons.

 7. Chronic medication use will be evaluated in a case-by-case basis.

 8. Patients will be excluded from this protocol if they are judged by the principal
 investigator as having a significant impairment in their capacity for judgment and
 reasoning that compromise their ability to make decisions in their best interest.

 EXCLUSION CRITERIA FOR RECOVERED, SEROPOSITIVE, OSPA VACCINATED AND HEALTHY VOLUNTEERS
 CONTROLS:

 In addition to the above applicable exclusion criteria (general exclusion criteria and
 exclusion criteria for PTLDS patients and Lyme arthritis controls), these individuals will
 be excluded for:

 1. Pre-existing or concurrent serious chronic medical or psychiatric illness.

 EXCLUSION CRITERIA FOR MULTIPLE SCLEROSIS CONTROLS:

 In addition to the above general exclusion criteria, these individuals will be excluded
 for:

 1. Pre-existing or concurrent serious psychiatric or chronic medical illness besides
 Multiple Sclerosis.

 2. Past history of significant head trauma, alcohol or substance abuse in the past 5
 years or other medical illness, besides Multiple Sclerosis, that might produce
 neurologic deficit (such as cerebrovascular disease).

 3. Previously received total lymphoid irradiation (TLI) or cladribine.

 4. Has used of immunoactive medications (excluding beta-interferon) in the three months
 preceding the study.

 5. In the three months prior to the study initiation, was given such investigational
 treatments as plasmapheresis, hyperbaric oxygen, gangliosides, Copolymer 1, etc.

 ELIGIBILITY OF SPECIAL POPULATIONS:

 Children: Children 13 years and older are eligible to participate in the PTLDS cohort
 because the condition under study can affect children. T, and this age was selected as
 appropriate for the children to provide assent to and comply with the study procedures.
 Children younger than 13 will be excluded from the PTLDS cohort, and no children will be
 enrolled in the other study cohorts.

 Pregnant and lactating women: Pregnant and lactating women are excluded from study
 participation. An enrolled participant who becomes pregnant during the study will be
 withdrawn

 Adults who lack capacity to consent: Adults who lack decision-making capacity to provide
 informed consent are excluded at screening, and enrolled adult participants who permanently
 lose the ability to consent during study participation will be withdrawn.

 NIH staff members: NIH staff may be enrolled if they meet eligibility criteria. Neither
 participation nor refusal to participate as a subject in the research will have an effect,
 either beneficial or adverse, on the participant s employment or position at NIH. Every
 effort will be made to protect participant information, but such information may be
 available in medical records and may be available to authorized users outside of the study
 team in both an identifiable and unidentifiable manner.