Abstract
Diagnostic testing for Lyme disease in the clinical setting primarily relies on assessment of serologic responses to infection, with the exception of the early localized phase of disease, in which the diagnosis must be made clinically, due to the recognized insensitivity of serologic testing at this phase of disease. For the diagnosis of early disseminated and late disease, the Centers for Disease Control and Prevention (CDC) recommends a two-tiered approach to testing consisting of initial IgM and IgG quantitative enzyme-linked immunosorbent assay (ELISA), followed by confirmation of all indeterminate or positive ELISA tests with separate IgG and IgM Western blots. This critical analysis addresses the sensitivity, specificity, and predictive value of serologic testing for Lyme disease in early localized, early disseminated, and late disease. Other testing modalities currently under evaluation are also discussed, including IgG vlsE C6 peptide ELISA, other two-tiered testing strategies, rapid diagnostics, and PCR. An understanding of the strengths and limitations of currently available testing for Lyme disease is critical for appropriate diagnosis.
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References
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Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089–134. This document should serve as the primary reference for clinicians seeking standardized clinical practice guidelines for diagnosis and treatment of Lyme disease, as well as co-infections.
Shapiro ED. Lyme disease. N Engl J Med. 2014;371(7):684.
Steere AC, Sikand VK. The presenting manifestations of Lyme disease and the outcomes of treatment. N Engl J Med. 2003;348(24):2472–4.
Steere AC, Sikand VK, Schoen RT, Nowakowski J. Asymptomatic infection with Borrelia burgdorferi. Clin Infect Dis. 2003;37(4):528–32.
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 Morb Mortal Wkly Rep. 1995;44(31):590–1.
Halperin JJ, Baker P, Wormser GP. Common misconceptions about Lyme disease. Am J Med. 2013;126(3):264.e1–e7.
Steere AC, McHugh G, Damle N, Sikand VK. Prospective study of serologic tests for Lyme disease. Clin Infect Dis. 2008;47(2):188–95. A rigorous prospective evaluation of the sensitivity of Lyme serologic testing at various clinical stages of disease, with very helpful summary tables.
Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of Lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484–509.
Bunikis J, Barbour AG. Laboratory testing for suspected Lyme disease. Med Clin N Am. 2002;86(2):311–40.
Nelson C, Hojvat S, Johnson B, Petersen J, Schriefer M, Beard CB, et al. Concerns regarding a new culture method for Borrelia burgdorferi not approved for the diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2014;63(15):333.
Spinhirne J. Evaluation of tests for Lyme disease. J Clin Microbiol. 2006;44(4):1616. author reply 1616–7.
Stricker RB, Johnson L. Lyme wars: let’s tackle the testing. BMJ. 2007;335(7628):1008.
Wormser GP, Nadelman RB, Dattwyler RJ, Dennis DT, Shapiro ED, Steere AC, et al. Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Clin Infect Dis. 2000;31 Suppl 1:1–14.
Steere AC. Diagnosis and treatment of Lyme arthritis. Med Clin N Am. 1997;81(1):179–94.
Santino I, Berlutti F, Pantanella F, Sessa R, del Piano M. Detection of Borrelia burgdorferi sensu lato DNA by PCR in serum of patients with clinical symptoms of Lyme borreliosis. FEMS Microbiol Lett. 2008;283(1):30–5.
Branda JA, Aguero-Rosenfeld ME, Ferraro MJ, Johnson BJ, Wormser GP, Steere AC. 2-tiered antibody testing for early and late Lyme disease using only an immunoglobulin G blot with the addition of a VlsE band as the second-tier test. Clin Infect Dis. 2010;50(1):20–6.
Branda JA, Linskey K, Kim YA, Steere AC, Ferraro MJ. Two-tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a whole-cell sonicate enzyme immunoassay followed by a VlsE C6 peptide enzyme immunoassay. Clin Infect Dis. 2011;53(6):541–7.
Porwancher RB, Hagerty CG, Fan J, Landsberg L, Johnson BJ, Kopnitsky M, et al. Multiplex immunoassay for Lyme disease using VlsE1-IgG and pepC10-IgM antibodies: improving test performance through bioinformatics. Clin Vaccine Immunol. 2011;18(5):851–9.
Smit PW, Kurkela S, Kuusi M, Vapalahti O. Evaluation of two commercially available rapid diagnostic tests for Lyme borreliosis. Eur J Clin Microbiol Infect Dis. 2014. http://link.springer.com/article/10.1007%2Fs10096-014-2217-5
Molins CR, Sexton C, Young JW, Ashton LV, Pappert R, Beard CB, et al. Collection and characterization of samples for the establishment of a serum repository for Lyme disease diagnostic test development and evaluation. J Clin Microbiol. 2014; 52(10):3755-62
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DeBiasi, R.L. A Concise Critical Analysis of Serologic Testing for the Diagnosis of Lyme Disease. Curr Infect Dis Rep 16, 450 (2014). https://doi.org/10.1007/s11908-014-0450-9
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DOI: https://doi.org/10.1007/s11908-014-0450-9