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Confirmation of active Lyme disease
Lyme disease is a multisystem and multistage tick-transmitted infection caused by spirochetal bacteria in the Borrelia burgdorferi sensu lato (Bbsl) complex.(1) Nearly all human infections are caused by 3 Bbsl species; Borrelia burgdorferi sensu stricto (hereafter referred to as Borrelia burgdorferi) is the primary cause of Lyme disease in North America, while Borrelia afzelii and Borrelia garinii are the primary causes of Lyme disease in Europe. Recently, Candidatus Borrelia mayonii has been identified as a second cause of Lyme disease in the United States.(2) Only 6 cases of Borrelia mayonii infection have been described to date, and all patients reported exposure to ticks in Minnesota or Wisconsin.
Lyme disease is the most commonly reported tick-borne infection in Europe and North America, causing an estimated 300,000 cases in the United States each year, and 85,000 cases in Europe.(3,4) The clinical features of Lyme disease are broad and may be confused with various immune and inflammatory disorders. The classic presenting sign of early localized Lyme disease caused by Borrelia burgdorferi is erythema migrans (EM), which occurs in approximately 80% of individuals. Other early signs and symptoms include malaise, headache, fever, lymphadenopathy, myalgia, and arthralgia. Arthritis, neurological disease, and cardiac disease may be later stage manifestations. The chronic skin condition, acrodermatitis chronicum atrophicans, is also associated with Borrelia afzelii infection.
The presence of EM in the appropriate clinical setting is considered diagnostic for Lyme disease and no confirmatory laboratory testing is needed. In the absence of a characteristic EM lesion, serologic testing is the diagnostic method of choice for Lyme disease.(5) However, serology may not be positive until 2 to 4 weeks after onset of symptoms, and may show decreased sensitivity for detection of infection with Borrelia mayonii. Therefore, detection of Bbsl DNA using PCR may be a useful adjunct to serologic testing for detection of acute disease. PCR has shown utility for detection of Borrelia DNA from skin biopsies of EM lesions, as well as DNA from synovial and cerebrospinal fluid in late-stage disease. Borrelia DNA can also, rarely, be detected from blood.(6) In general, blood is not the preferred source for detection of Bbsl DNA by PCR, although it may have increased utility for detection of Borrelia mayonii, due to the higher levels of observed peripheral spirochetemia with this organism.(2,6) Lyme PCR should always be performed in conjunction with FDA-approved serologic tests, and results should be correlated with serologic and epidemiologic data and clinical presentation of the patient. The Mayo Clinic Lyme PCR test detects and differentiates the causes of Lyme disease in North America (Borrelia burgdorferi and Borrelia mayonii) and Europe (Borrelia afzelii and Borrelia garinii).
A positive result indicates the presence of DNA from Borrelia burgdorferi, Borrelia mayonii, Borrelia afzelii, or Borrelia garinii, the agents of Lyme disease.
A negative result indicates the absence of detectable target DNA in the specimen. Due to the diagnostic sensitivity limitations of the PCR assay, a negative result does not preclude the presence of the organism or active Lyme disease.
Serologic tests are recommended for diagnosis of Lyme disease. PCR may play an adjunctive role, but may not detect Borrelia burgdorferi DNA from blood in cases of active or chronic disease. The presence of inhibitory substances may also cause a false-negative result. 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 muris eauclairensis, Anaplasma phagocytophilum, Babesia microti, and Borrelia miyamotoi (a relapsing-fever Borrelia) have been reported in United States, and consideration should be given to testing for other pathogens if clinically indicated.
This assay detects some members of the Borrelia burgdorferi sensu lato (Bbsl) complex that are not considered to be human pathogens, but may be found in ticks and other animals. Therefore, this assay should not be used to test nonhuman specimens.
The following validation data supports the use of this assay for clinical testing.
Analytical Sensitivity/Limit of Detection (LoD):
The lower LoD is approximately 300 to 1,000 genomic copies/mL in cerebrospinal fluid, tissue, and synovial fluid.
Accuracy/Diagnostic Sensitivity and Specificity:
Spiking studies of whole organism in whole blood (spiked near the approximate limit of detection) showed 100% recovery.
No PCR signal was obtained from the extracts of 22 bacterial, viral, parasitic, and fungal isolates that can cause symptoms similar to Lyme disease including; Rickettsia rickettsii, Rickettsia typhi, Ehrlichia canis, Babesia microti, Plasmodium falciparum, Plasmodium vivax, Bartonella henselae, Bartonella quintana, Herpes simplex virus, and Toxoplasma gondii.
Interassay precision was 100% and intra-assay precision was 100%.
The reference range for this assay is negative. This assay is only to be used for patients with a clinical history and symptoms consistent with Lyme, and must be interpreted in the context of serologic tests, which are the gold standard for diagnosis of Lyme disease. This test should not be used to screen asymptomatic patients.
This is a qualitative assay, and the results are reported as negative or positive for targeted Borrelia burgdorferi.
2. Pritt BS, Mead PS, Johnson, DKH, et al: Identification of a Novel Pathogenic Borrelia Species Causing Lyme Borreliosis with Unusually High Levels of Spirochetemia: A Descriptive Study. Lancet Infectious Diseases 2016;In Press
3. Hinckley AF, Connally NP, Meek JI, et al: Lyme disease testing by large commercial laboratories in the United States. Clin Infect Dis 2014;59(5):676-681
4. Lindgren E, Jaenson TGT: Lyme borreliosis in Europe: influences of climate and climate change, epidemiology, ecology and adaptation measures. Copenhagen, Denmark: World Health Organization; 2006
5. Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 1995;44(31):590-591
6. 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
7. 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