Lyme Disease (Borrelia burgdorferi), Molecular Detection, PCR
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Lyme disease is a multisystem and multistage infection caused primarily by 3 species of tick-borne spirochetes in the Borrelia burgdorferi sensu lato genogroup. These spirochetes include Borrelia burgdorferi sensu stricto (North America and Western Europe), Borrelia afzelii (Central and Western Europe and Russia), and Borrelia garinii (Europe, Russia, and northern Asia). Endemic areas for Lyme disease in the United States correspond with the distribution of 2 tick species, Ixodes scapularis (Northeastern and Upper Midwestern US) and Ixodes pacificus (West Coast US). In Europe, Ixodes ricinus transmits the spirochete. Lyme disease is the most commonly reported tick-borne infection in Europe and North America (CDC).
Lyme disease exhibits a variety of symptoms that may be confused with immune and inflammatory disorders. Inflammation around the tick bite causes skin lesions. Erythema (chronicum) migrans (ECM), a unique expanding skin lesion with central clearing that has a ring-like appearance, is typically the first stage of the disease. Arthritis, neurological disease, and cardiac disease may be later stage manifestations.
Serology is currently the diagnostic method of choice for Lyme disease. However, serology may not be positive until 2 to 4 weeks after onset of ECM, and direct detection of Borrelia species. Target DNA using PCR may be a useful adjunct to existing diagnostic tests for acute disease. PCR has shown utility for detection of Borrelia DNA from skin biopsies of ECM lesions, as well as DNA from synovial and cerebrospinal fluid in late-stage disease.(1) Borrelia DNA can also, rarely, be detected from blood, but is not the test of choice from this source.
Lyme PCR may be useful for adjunctive testing to support a serologic diagnosis of Lyme disease, and should be performed in conjunction with FDA-approved serologic tests.
PCR results should be correlated with serologic and epidemiologic data and clinical presentation of the patient.
Confirmation of active Lyme disease
Supporting the diagnosis of Lyme arthritis
Testing of cerebrospinal fluid (CSF) by PCR in patients with suspected Lyme neuroborreliosis should be requested only on patients with positive Borrelia burgdorferi antibody in serum confirmed by Western blot assay LYWB / Lyme Disease Antibody, Immunoblot, Serum and with abnormal CSF findings (elevated protein and WBC >10 cells/high-power field).
A positive result indicates the presence of DNA from Borrelia burgdorferi, the agent of Lyme disease.
A negative result indicates the absence of detectable DNA from Borrelia burgdorferi in the specimen. Due to the clinical sensitivity limitations of the PCR assay, a negative result does not preclude the presence of the organism or active Lyme disease.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A negative result does not rule-out Lyme disease, since inhibitory substances may be present in the specimen and the assay has limited clinical sensitivity when testing certain specimen types (eg, cerebrospinal fluid: CSF). If clinical features of illness are highly indicative of Lyme neuroborreliosis, serologic testing on CSF is warranted. Patients with active infection due to Borrelia afzelii or Borrelia garinii may have positive results from this PCR test, which will be reported as atypical gene sequence and prompt additional testing. PCR test results should be used as an aid in diagnosis and not considered diagnostic by themselves. These results should be correlated with serologic and epidemiologic data and clinical presentation of the patient.
Concurrent infections with multiple tick-borne pathogens, including Ehrlichia chaffeensis/Anaplasma phagocytophilum and Babesia microti have been reported in United States, and consideration should be given to testing for other pathogens if clinically indicated.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Nocton JJ, Bloom BJ, Rutledge BJ, et al: Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid with Lyme neuroborreliosis. J Infect Dis 1996;174:623-627
2. CDC: Recommendation for test performance and interpretation. From second national conference on serological diagnosis of lyme disease. MMWR Morb Mortal Wkly Rep 1996;45:481-484
3. Nocton JJ, Dressler F, Rutledge BJ, et al: Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med 1994;330:229-234
4. Babady NE, Sloan LM, Vetter EA, et al: Percent positive rate of Lyme real-time polymerase chain reaction in blood, cerebrospinal fluid, synovial fluid, and tissue. Diagn Microbiol Infect Dis 2008;62(4):464-466