Lyme Disease Testing - eviCore

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Lab Management Guidelines                                                      V2.0.2021

                                          Lyme Disease Testing
                                                                      MOL.CS.332.X
                                                                              v2.0.2021
Introduction

Lyme Disease testing is addressed by this guideline.

Procedures Addressed

The inclusion of any procedure code in this table does not imply that the code is under
management or requires prior authorization. Refer to the specific Health Plan's
procedure code list for management requirements.

Procedure addressed by this guideline Procedure code
Borrelia burgdorferi antibody                     86618
Borrelia antibody                                 86619
Borrelia burgdorferi, antibody detection of 0041U
5 recombinant protein groups, by
immunoblot, IgM
Borrelia burgdorferi, antibody detection of 0042U
12 recombinant protein groups, by
immunoblot, IgG
Borrelia burgdorferi antibody, confirmatory 86617
assay
Borrelia burgdorferi, infectious agent            87475
detection by nucleic acid (DNA or RNA);
direct probe technique
Borrelia burgdorferi, Infectious agent            87476
detection by nucleic acid (DNA or RNA),
amplified probe technique
Borrelia group, tick-borne relapsing fever,       0043U
antibody detection to 4 recombinant
protein groups, by immunoblot, IgM
Borrelia group, tick-borne relapsing fever,       0044U
antibody detection to 4 recombinant
protein groups, by immunoblot, IgG

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What Is Lyme Disease
Definition

Lyme disease (borreliosis) is caused by a Borrelia bacterial infection following a tick
bite from the hard-backed Ixodes tick. It was named after the towns Lyme and Old
Lyme in Connecticut after a 1975 investigation of 51 cases with a similar form of
arthritis.1 Borrelia are part of the order spirochaetes, which are spiral-shaped
bacteria. There are several subspecies, including B. burgdorferi, B. afezelii, B. garinii,
B. spielmanii, and B. bavariensis. In the United States, the most common Lyme
disease-causing organism is B. burgdorferi.
Lyme disease incidence is significant, exceeding 30,000 new cases annually in the
United States.2 There are some estimates greater than 300,000 when considering
unreported cases.3 The incidence has increased as the geographic range of the ticks
have expanded across the northeastern and upper mid-western states in the U.S., and
most recently into Canada. It is expected that climate change will result in further
northward expansion of the tick’s range. 4
However, the incidence may be confounded by high rates of misdiagnosis due to the
systemic nature of Lyme Disease, and non-specific symptoms. One study found that
84.1% of a population referred to an Infectious Disease Clinic for Lyme disease were
misdiagnosed.5
Lyme disease has three stages of infection: early localized, early disseminated, and
late disseminated. Disseminated infection can affect multiple organs. While there is a
broad spectrum of symptoms and severity, the first signs of infection are a
characteristic skin rash with a bullseye appearance (called erythema migrans), fever,
and non-specific symptoms like headache and lethargy. 6
There are several manifestations of Lyme disease that can occur through the three

                                                                                                Lyme Disease Testing
phases of infection:
   Neuroborreliosis most commonly manifests with painful meningoradiculitis and
    lymphocytic meningitis. This may also manifest as facial palsy in many cases, as
    well as multiple cranial neuropathies. 7 Neuroborreliosis is more common in Europe
    due to the prevalent Borellia subspecies, B. garinii, which is more frequently
    associated with neuroborreliosis than the other subspecies. 7
   Lyme carditis, which may present as pericarditis, myocarditis, and/or conduction
    abnormalities
   Lyme arthritis manifests as migratory large joint arthritis and is a hallmark of late
    disseminated Lyme disease in the U.S.6
   Fibromyalgia and chronic fatigue syndrome have been associated with chronic
    Lyme disease (CLD) or post-treatment Lyme disease syndrome (PTLDS). These
    conditions are characterized by unexplained subjective complaints with similar
    clinical symptoms as fibromyalgia and chronic fatigue syndrome. 8

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Test Information
Introduction

There are several diagnostic tests available for screening and confirmation of Lyme
disease. They have variable sensitivity, specificity, and performance characteristics
depending on the stage of the infection and testing matrix.
Serologic tests include enzyme-linked immunosorbent assay (ELISA) to detect IgM or
IgG antibodies, immunofluorescence assay (IFA), immunoblot, and confirmatory
western blot. Molecular detection of Borrelia organisms is also available in bacterial
isolates from culture, blood, and tissue biopsies.

Borrelia Burgdorferi IgG or IgM Antibodies and Borrelia IgG or IgM Antibodies

This test is performed by enzyme-linked immunosorbent assay (ELISA) or
immunofluorescence assay (IFA). There are several commercially available kits. The
assays use either whole-cell preparations of B. burgdorferi (for the specific test),
Borrelia species, or recombinant antigens, such as C10 peptide, to bind to antibodies
present in patient serum. Whole-cell sonicate preparations result in higher sensitivity
due to the presence of multiple antigens, but some of the antigens cross-react with
antigens from the host or other pathogens, leading to false positives. Overall, there is
lower sensitivity in early stages of Lyme disease.9

Confirmatory Assay for Borrelia Burgdorferi Antibody

This test is performed by western blot and has higher analytical specificity than ELISA.
Patient serum is introduced in a separation gel or strip that has been prepared with
antigen extracts and/or recombinant antigens native to B. burgdorferi and
electrophoretically separated. Antibodies present in the patient’s serum bind to the

                                                                                              Lyme Disease Testing
corresponding antigen bands. The gel is then incubated with a chromogenic substrate
to visualize the antigen-antibody complexes as “bands”. 9

Infectious Agent Detection by Nucleic Acid (DNA or RNA); Borrelia Burgdorferi,
Direct Probe Technique

In direct probe techniques, nucleic acid is extracted from the specimen (isolate, tissue,
CSF, blood, synovial fluid, etc.) and the target sequence is detected by a reporter
molecule, such as an oligonucleotide, DNA fragment, or plasmid DNA. The reporter
molecule has a label attached to generate a signal when hybridized to the target
sequence in solution or immobilized on solid support. This technique is increasingly
being replaced with amplification methods.

Infectious Agent Detection by Nucleic Acid (DNA or RNA); Borrelia Burgdorferi,
Amplified Probe Technique

In amplified probe techniques, nucleic acid is extracted from the specimen (isolate,
tissue, CSF, blood, synovial fluid, etc.) and then amplified using polymerase chain

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reaction. The specific organisms are differentiated through features of the melting
curve analysis. However, due to the amplification steps, there is a high risk for
exogenous contamination, resulting in false-positive results. Additionally, degradation
of the DNA during sample transport, storage, and processing steps can result in false
negatives.10 Standard PCR methods have demonstrated poor sensitivity in testing
tissue and body fluids because the infectious agent resides in low number. 11

Borrelia Burgdorferi, Antibody Detection of (4,5,12) Recombinant Protein
Groups, by Immunoblot (IgM, IgG)

The methodology is similar to the western blot, but is differentiated by using
recombinant proteins derived from several species of Borrelia to prepare antigen strips,
instead of whole blood lysates.12

Guidelines and Evidence
Borrelia Burgdorferi IgG or IgM (CPT 86618) and Borrelia IgG or IgM (CPT 86619)

The diagnosis of Lyme disease can be made clinically in patients with high pre-test
probability, obviating the need for serologic testing. However, serologic testing takes
on greater importance with later disseminated disease. 13
Testing for IgM antibodies is only recommended in the first 30 days of infection, after
which IgG tests should be used.14 Serology should not be used for monitoring
treatment, as antibodies can persist for several years post-infection. Negative serology
does not rule out early infection within six weeks, as false negatives can occur. 1
In patients with an atypical presentation, or later disseminated disease, a two-tiered
testing approach is recommended. The first tier consists of an ELISA or
immunofluorescence assay, and if positive or equivocal, the same sample is tested by

                                                                                             Lyme Disease Testing
the second-tier western blot.15

Borrelia Burgdorferi Antibody, Confirmatory Assay (CPT 86617)

Western blots require interpretation to determine if there are bands present, which is
accomplished by skilled technologists or software. To avoid false positives due to
variation in band interpretation, the CDC guidelines require that a specific number of
bands be present to classify the result as positive: 6
   “It is imperative to avoid interpreting fewer bands as a positive overall result or
    evidence of infection because antibodies to several antigens are cross-reactive with
    non-Borrelial antigens. For example, the 41-kDa band indicates reactive antibody
    against a B. burgdorferi flagellin protein. However, this antibody cross-reacts with
    other bacterial flagellar proteins and was found in 43% of healthy controls in 1
    study, including many persons with little or no exposure risk for Lyme disease."
   The two-tiered approach to serology testing was recently updated by the CDC to
    allow FDA-approved enzyme immunoassays (EIA) to replace traditional western

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    blot assays as the confirmatory test.16 The two-tiered EIA approach consists of the
    traditional whole-cell sonicate EIA followed by a C6 peptide EIA. Both tiers (ELISA
    and western blot or EIA) must be positive to classify the final result as positive. The
    two-tiered approach maximizes test sensitivity and specificity.

Borrelia burgdorferi; Infectious Agent Detection by Nucleic Acid (DNA or RNA)
(CPT 87475, 87476)

Molecular detection of B. burgdorferi using PCR-based technology can identify the
organism in cases of neuroborreliosis, synovial fluid in cases of Lyme arthritis, and
rarely in skin biopsy specimens.
   Synovial fluid PCR testing for B. burgdorferi DNA is often positive prior to treatment,
    but it is not a reliable marker of spirochetal eradication after antibiotic therapy. 17
    Intrathecal antibody production is more sensitive than PCR-based CSF detection in
    patients with suspected neuroborreliosis.18 However, PCR may be useful in patients
    with short duration of neurological symptoms in the early stage of the infection
    before emergence of detectable levels of antibodies in CSF. 6
    o “Synovial fluid PCR is >75% sensitive for Lyme arthritis and might be useful in
      conjunction with other synovial fluid analyses to differentiate Lyme arthritis from
      other arthritides. Comparatively, PCR of CSF is substantially less sensitive,
      which limits its clinical utility. In 1 US study, PCR testing of CSF yielded positive
      results for only 38% of patients with early neuroborreliosis and was even less
      sensitive for late neuroborreliosis."
   Infectious Diseases Society of America clinical practice guidelines state the
    following regarding testing to be performed on CSF from patients suspected of
    having Lyme neuroborreliosis:19
    o “When assessing patients for possible Lyme neuroborreliosis involving either the

                                                                                               Lyme Disease Testing
      PNS or central nervous system (CNS), we recommend serum antibody testing
      rather than PCR or culture of either cerebrospinal fluid (CSF) or serum (strong
      recommendation, moderate-quality evidence).”
    o “If CSF testing is performed in patients with suspected Lyme neuroborreliosis
      involving the CNS, we (a) recommend obtaining simultaneous samples of CSF
      and serum for determination of the CSF:serum antibody index, carried out by a
      laboratory using validated methodology, (b) recommend against CSF serology
      without measurement of the CSF:serum antibody index, and (c) recommend
      against routine PCR or culture of CSF or serum (strong recommendation,
      moderate-quality evidence)”
    o Regarding diagnostic testing for Lyme arthritis, the guidelines state:

          “When assessing possible Lyme arthritis, we recommend serum antibody
           testing over PCR or culture of blood or synovial fluid/tissue (strong
           recommendation, moderate-quality evidence).”

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          “In seropositive patients for whom the diagnosis of Lyme arthritis is being
           considered but treatment decisions require more definitive information, we
           recommend PCR applied to synovial fluid or tissue rather than Borrelia
           culture of those samples (strong recommendation, moderate-quality
           evidence)."
   A meta-analysis examining the overall accuracy of diagnostic tests for the detection
    of Lyme disease reviewed six studies that analyzed bacterial isolation by culture
    and detection of B. burgdorferi by PCR in blood and tissue biopsies. 1
    o "Overall, the sensitivities of PCR studies conducted in North America were lower
      than those that employed a two-tiered serology diagnostic protocol. Due to the
      above limitations, bacterial isolation and PCR are not routinely used as
      diagnostic tools in clinical practise, although bacterial isolation is considered the
      gold standard to confirm diagnosis."
   A novel B. burgdorferi sensu lato genospecies, B. mayonii, was recently discovered
    using real-time PCR assay that targets the chromosomal oppA1 gene. In the first
    six patients detected with this infection, the two-tier algorithm was only positive in
    one patient. Until more is understood about the differences in detection rates by
    the two-tiered testing approach with this infection, PCR may have a role. 20

    o "An important issue raised by identification of the novel B. burgdorferi sensu lato
      genospecies is whether existing Lyme borreliosis diagnostic tests can detect
      infection with this organism…The clinical range of illness must be better defined
      in additional patients to ensure that physicians can recognise the infection and
      distinguish it from other tick-borne infections. Many tick-borne pathogens have
      global distribution, therefore studies are needed to establish the geographic
      distribution of human beings and ticks infected with the novel B. burgdorferi
      sensu lato genospecies. Finally, clinicians should be aware of the potential role
      of oppA1 PCR for diagnosing infection with this novel pathogen."

                                                                                               Lyme Disease Testing
Borrelia Burgdorferi, Antibody Detection of (4,5,12) Recombinant Protein
Groups, by Immunoblot (IgM, IgG): 0041U, 0042U, 0043U, 0044U

Detection of B. burgdorferi and Tick-born relapsing fever antibodies by immunoblot
using recombinant proteins is the latest addition of Lyme disease serology testing.
There are not any independent studies evaluating the accuracy of this method. 12,21

Criteria
Introduction

This policy addresses laboratory testing for the diagnosis of Lyme disease.

B. Burgdorferi Antibodies and Borrelia Antibodies (First-tier)

Procedure codes: 86618 or 86619
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   Medical Necessity Requirements

   o First-tier Lyme serology testing is indicated when all of the following
     circumstances are met:
          History of travel to, or residence in, a Lyme region, and
          Clinically compatible symptoms such as fever; redness, warmth and swelling
           in one or more joints.
   o Testing is not medically necessary when the classic erythema migrans (EM)
     rash is present.
   o IgM is only indicated for the first 30 days after infection. After 30 days, only IgG
     is indicated.

   Test Frequency
   Lyme serology testing is allowed up to 4 times per year for diagnosis of Lyme
   disease.

   Billing and Reimbursement
   First-tier Lyme serology will be considered medically necessary when billed with an
   ICD code from Table: Lyme Disease Testing Indications. Exceptions will be handled
   on a case-by-case basis.
   Because only IgG or IgM testing is indicated (not both) for initial screening, only one
   unit of CPT 86618 or CPT 86619 will be eligible for first-tier screening on a single
   date of service.

B. Burgdorferi Antibody (Confirmatory, or Second-Tier)

                                                                                                Lyme Disease Testing
Procedure codes: 86617 or 86618

   Medical Necessity Requirements
   The confirmatory or second-tier assay B. burgdorferi antibodies is indicated when
   the first-tier serology test is positive for either IgG or IgM antibodies.
   IgM is only indicated for the first 30 days after infection. After 30 days, only IgG is
   indicated.
   Once Lyme disease is confirmed, no further serology testing is indicated because
   serology should not be used for monitoring treatment as antibodies can persist for
   several years post-infection.

   Test Frequency
   Lyme confirmatory testing is allowed up to 4 times per year for diagnosis of Lyme
   disease.

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   Billing and Reimbursement
   Confirmatory testing (86617 or 86618) will only be reimbursable when first-tier
   Lyme serology testing was medically necessary and reimbursed.
   Because only IgG or IgM testing is indicated (not both) for confirmatory testing, only
   one unit of CPT 86617 or 86618 will be eligible for second-tier confirmation on a
   single date of service.
   As a result, when two-tier Lyme disease testing is medically necessary because
   first-tier testing was positive, no more than one unit of 86617 with 86618 or 86619,
   or two units of 86618 is reimbursable.
   Antibody testing that is not species-specific (billed with 86619) has no role in
   confirmatory testing, and is therefore not reimbursable for this purpose.

B. Burgdorferi, Infectious Agent Detection by Nucleic Acid (DNA or RNA)

Procedure codes: 87475, 87476

   Medical Necessity Requirements
   Nucleic acid detection of B. burgdorferi through direct or amplified methods for the
   diagnosis of Lyme disease has not demonstrated value that exceeds the two-tier
   serology testing strategy, and is therefore determined to be not medically
   necessary.
   Nucleic acid detection of B. burgdorferi performed on synovial fluid to inform
   therapeutic decisions for seropositive patients in whom a diagnosis of Lyme arthritis
   is suspected will be considered for reimbursement on a case-by-case basis.

B. Burgdorferi, Anitbody Detection of (4,5,12) Recombinant Protein Groups, by
Immunoblot (IgM, IgG)

                                                                                              Lyme Disease Testing
Procedure codes: 0041U, 0042U, 0043U, 0044U

   Medical Necessity Requirements
   Antibody detection of B. burgdorferi using recombinant protein groups by
   Immunoblot has not been independently tested and validated for clinical use, and is
   therefore determined to be investigational and/or experimental.

Diagnosis Codes

Diagnosis codes in this section may be used to support or refute medical necessity as
described in the above guidelines.

Table: Lyme Disease Testing Indications

Codes and descriptions

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Code or Range                                     Description
A26.X                                             Erysipeloid
A41.8X                                            Other specified sepsis
A41.9                                             Sepsis, unspecified organism
A68.X                                             Relapsing fever
A69.2X                                            Lyme disease
D69.2                                             Other nonthrombocytopenic purpura
D69.3                                             Immune thrombocytopenic purpura
D69.4X                                            Other primary thrombocytopenia
D69.5X                                            Secondary thrombocytopenia
D69.6X                                            Thrombocytopenia, unspecified
G36.X                                             Other acute disseminated demyelination
G37.X                                             Other demyelinating diseases of the
                                                  central nervous system
G50-G59                                           Nerve, nerve root and plexus disorders
G60-G65                                           Polyneuropathies and other disorders of
                                                  the peripheral nervous system
G72.3                                             Other and unspecified myopathies
G72.4                                             Inflammatory and immune myopathies,
                                                  not elsewhere classified
G72.8                                             Other specified myopathies

                                                                                                   Lyme Disease Testing
G72.9                                             Myopathy, unspecified
G81.X                                             Hemiplegia and hemiparesis
G83.X                                             Other paralytic syndromes
G89-G99.X                                         Other disorders of the nervous system
H02.4X                                            Ptosis of eyelid
H15-H22                                           Disorders of sclera, cornea, iris and ciliary
                                                  body
H30-H36                                           Disorders of choroid and retina
H43-H44.X                                         Disorders of vitreous body and globe
H46-H47.X                                         Disorders of optic nerve and visual
                                                  pathways
H49.X                                             Paralytic strabismus
H53-H54.X                                         Visual disturbances and blindness

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Code or Range                                     Description
H55-H57.X                                         Other disorders of eye and adnexa
H81.X                                             Disorders of vestibular function
H90.X-H94.X                                       Other disorders of ear
I30-I52                                           Other forms of heart disease
L08.X                                             Other local infections of skin and
                                                  subcutaneous tissue
M06.4                                             Inflammatory polyarthropathy
M12.X                                             Other and unspecified arthropathy
M13.X                                             Other arthritis
M14.X                                             Arthropathies in other diseases classified
                                                  elsewhere
M25.4                                             Effusion of joint
M25.5                                             Pain in joint
M79.1X                                            Myalgia
M79.2                                             Neuralgia and neuritis, unspecified
M79.6X                                            Pain in limb, hand, foot, fingers, and toes
M79.7                                             Fibromyalgia
R20.X                                             Disturbances of skin sensation
R21                                               Rash and other nonspecific skin eruption
R25-R29.X                                         Symptoms and signs involving the

                                                                                                   Lyme Disease Testing
                                                  nervous and musculoskeletal system
R41.X                                             Other symptoms and signs involving
                                                  cognitive functions and awareness
R42                                               Dizziness and giddiness
R50.9                                             Fever, unspecified
R51                                               Headache
R52                                               Pain, unspecified
R53.X                                             Malaise and fatigue
R55                                               Syncope and collapse
R90.8X                                            Other abnormal findings on diagnostic
                                                  imaging of central nervous system
R93.0                                             Abnormal findings on dx imaging of skull
                                                  and head, NEC

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Code or Range                                     Description
S00.06X                                           Insect bite (nonvenomous) of scalp
S00.26X                                           Insect bite (nonvenomous) of eyelid and
                                                  periocular area
S00.36X                                           Insect bite (nonvenomous) of nose
S00.46X                                           Insect bite (nonvenomous) of ear
S00.56X                                           Insect bite (nonvenomous) of lip and oral
                                                  cavity
S00.86X                                           Insect bite (nonvenomous) of other part of
                                                  head
S00.96X                                           Insect bite (nonvenomous) of unspecified
                                                  part of head
S10.16X                                           Insect bite (nonvenomous) of throat
S10.86X                                           Insect bite of other specified part of neck
S10.96X                                           Insect bite of unspecified part of neck
S20.16X                                           Insect bite (nonvenomous) of breast
S20.36X                                           Insect bite (nonvenomous) of front wall of
                                                  thorax
S20.46X                                           Insect bite (nonvenomous) of back wall of
                                                  thorax
S20.96X                                           Insect bite (nonvenomous) of unspecified
                                                  parts of thorax
S30.86X                                           Insect bite (nonvenomous) of abdomen,

                                                                                                   Lyme Disease Testing
                                                  lower back, pelvis, and external genitals
S40.86X                                           Insect bite (nonvenomous) of upper arm
S50.86X                                           Insect bite (nonvenomous) of forearm
S60.36X                                           Insect bite (nonvenomous) of thumb
S60.46X                                           Insect bite (nonvenomous) of fingers
S60.56X                                           Insect bite (nonvenomous) of hand
S60.86X                                           Insect bite (nonvenomous) of wrist
S70.26X                                           Insect bite (nonvenomous) of hip
S70.36X                                           Insect bite (nonvenomous) of thigh
S80.26X                                           Insect bite (nonvenomous) of knee
S80.86                                            Insect bite (nonvenomous) of lower leg
S90.46X                                           Insect bite (nonvenomous) of toe

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Code or Range                                     Description
S90.56X                                           Insect bite (nonvenomous) of ankle
S90.86X                                           Insect bite (nonvenomous) of foot
W57.XXXA                                          Bitten or stung by nonvenomous insect
                                                  and other nonvenomous arthropods, initial
                                                  encounter
W57.XXXD                                          Bitten or stung by nonvenomous insect
                                                  and other nonvenomous arthropods,
                                                  subsequent encounter

References
Introduction

These references are cited in this guideline.

1. Waddell LA, Greig J, Mascarenhas M, et al. The accuracy of diagnostic tests for
   Lyme disease in humans, a systematic review and meta-analysis of North
   American research. PLoS one. 2016;3(11):1-23.
2. Clark RP, Hu LT. Prevention of Lyme disease and other tick-borne infections. Infect
   Dis Clin North Am. 2008;22(3):381-96.
3. Hinckley AF, Connally NP, Meek JI, et al. Lyme disease testing by large commercial
   laboratories in the United States. Clin Infect Dis. 2014 Sep 1;59(5):676-81.
4. Brownstein JS, Holford TR, Fish D. Effect of climate change on lyme disease risk
   in North America. Ecohealth. 2005 Mar;2(1):38-46. doi: 10.1007/s10393-004-0139-

                                                                                                  Lyme Disease Testing
   x
5. Kobayashi T, Higgins Y, Samuels R, et al. Misdiagnosis of lyme disease with
   unnecessary antimicrobial treatment characterizes patients referred to an
   academic infectious diseases clinic. Open Forum Infect Dis. 2019 Jul 1;6(7):1-9.
6. Moore A, Nelson C, Molins C, Mead P, Schriefer M. Current guidelines, common
   clinical pitfalls, and future directions for laboratory diagnosis of Lyme disease,
   United States. Emerging Infectious Diseases. 2016 Jul; 22(7):1169-77.
7. Ross Russell AL, Dryden MS, Pinto AA, Lovette JK. Lyme disease: diagnosis and
   management. Pract Neurol. 2018;18:455-464.
8. Van Hout MC. The controversies, challenges and complexities of Lyme Disease: a
   narrative review. J Pharm Pharm Sci. 2018; 21: 429-436.
9. Lindsay LR, Bernat K, Dibernardo A. Laboratory diagnostics for Lyme disease.
   CCDR. 2014;40(11):209-17.
10. Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of Lyme
    Borreliosis. Clin Micro Rev. 2005 Jul; 18(3):484-509.

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11. Schutzer SE, Body BA, Boyle J, et al. Direct diagnostic tests for Lyme
    disease. Clin Infect Dis. 2019; 68(6): 1052-1057.
12. Liu S, Cruz ID, Calalo Ramos C, et al. Pilot Study of Immunoblots with
    Recombinant Borrelia burgdorefi Antigens for Laboratory Diagnosis of Lyme
    Disease. Healthcare. 2018;99(6):1-15.
13. Fallon BA, Pavlicova M, Coffino SW, Brenner C. A comparison of Lyme disease
    serologic test results from 4 laboratories in patients with persistent symptoms after
    antibiotic treatment. Clin Infect Dis. 2014 Dec 15;59(12):1705-10.
14. Centers for Disease Control and Prevention. Two-Tiered Testing for Lyme
    Disease. Available at: https://www.cdc.gov/lyme/healthcare/clinician_twotier.html.
15. Centers for Disease Control and Prevention (CDC). Recommendations for test
    performance and interpretation from the Second National Conference on Serologic
    Diagnosis of Lyme disease. MMWR. 1995 Aug 11;44(31):590-1.
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