Diagnostic challenges in Lyme disease

Diagnostic Challenges in Lyme Disease

0.5 CME. This module presents the most commonly used tests to diagnose Lyme disease, describes their deficiencies, and provides clinicians with important findings regarding the variability in immune responses among infected individuals. How to interpret the two-tier test, especially the western blot, is discussed in detail and in conjunction with the research findings on immune response differences. Finally, the needs and challenges for new diagnostic modalities are considered.

Instructor

Monica E. Embers, PhD
Associate Professor in the Division of Immunology
Director of Vector-borne Disease Research
Tulane National Primate Research Center

Description

This module presents the most commonly used tests to diagnose Lyme disease, describes their deficiencies, and provides clinicians with important findings regarding the variability in immune responses among infected individuals. How to interpret the two-tier test, especially the western blot, is discussed in detail and in conjunction with the research findings on immune response differences. Finally, the needs and challenges for new diagnostic modalities are considered.

Learning objective

Make a fast and accurate diagnosis of Lyme disease

Accreditation Statement

This session, Diagnostic Challenges in Lyme Disease, is approved for 0.5 enduring AAFP Prescribed credits.

The AAFP has reviewed VectorWise CME, and deemed it acceptable for AAFP credit. Term of approval is from 05/15/2025 to 05/14/2026. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AAFP Prescribed credit is accepted by the American Medical Association as equivalent to AMA PRA Category 1 credit(s)™ toward the AMA Physician’s Recognition Award. When applying for the AMA PRA, Prescribed credit earned must be reported as Prescribed, not as Category 1.

Evidence-based bibliography for further study

Mead P, Petersen J, Hinckley A. Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 2019;68:703. https://www.cdc.gov/mmwr/volumes/68/wr/mm6832a4.htm?s_cid=mm6832a4_w
https://ndc.services.cdc.gov/case-definitions/lyme-disease-2022/
Philipp, M. T., A. R. Marques, P. T. Fawcett, L. G. Dally and D. S. Martin (2003). “C6 test as an indicator of therapy outcome for patients with localized or disseminated lyme borreliosis.” Journal of Clinical Microbiology 41(11): 4955-4960.
Philipp, M. T., G. P. Wormser, A. R. Marques, S. Bittker, D. S. Martin, J. Nowakowski and L. G. Dally (2005). “A decline in C6 antibody titer occurs in successfully treated patients with culture-confirmed early localized or early disseminated Lyme Borreliosis.” Clin Diagn Lab Immunol 12(9): 1069-1074.
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 Sep;53(6):541-7. doi: 10.1093/cid/cir464. PMID: 21865190.
Binnicker MJ, Jespersen DJ, Harring JA, Rollins LO, Bryant SC, Beito EM. Evaluation of two commercial systems for automated processing, reading, and interpretation of Lyme borreliosis Western blots. J Clin Microbiol. 2008 Jul;46(7):2216-21. doi: 10.1128/JCM.00200-08. Epub 2008 May 7. PMID: 18463211; PMCID: PMC2446909.
Heikkilä T, Seppälä I, Saxen H, Panelius J, Yrjänäinen H, Lahdenne P. Species-specific serodiagnosis of Lyme arthritis and neuroborreliosis due to Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii by using decorin binding protein A. J Clin Microbiol. 2002 Feb;40(2):453-60. doi: 10.1128/JCM.40.02.453-460.2002. PMID: 11825956; PMCID: PMC153353.
Craft JE, Fischer DK, Shimamoto GT, Steere AC. Antigens of Borrelia burgdorferi recognized during Lyme disease. Appearance of a new immunoglobulin M response and expansion of the immunoglobulin G response late in the illness. J Clin Invest. 1986 Oct;78(4):934-9. doi: 10.1172/JCI112683. PMID: 3531237; PMCID: PMC423723.
Craft JE, Grodzicki RL, Shrestha M, Fischer DK, García-Blanco M, Steere AC. The antibody response in Lyme disease. Yale J Biol Med. 1984 Jul-Aug;57(4):561-5. PMID: 6393607; PMCID: PMC2590019.
Dressler F, Whalen JA, Reinhardt BN, Steere AC. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis. 1993 Feb;167(2):392-400. doi: 10.1093/infdis/167.2.392. PMID: 8380611.
Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of lyme borreliosis. Clin Microbiol Rev. 2005 Jul;18(3):484-509. doi: 10.1128/CMR.18.3.484-509.2005. PMID: 16020686; PMCID: PMC1195970.
Embers ME, Hasenkampf NR, Jacobs MB, Philipp MT. Dynamic longitudinal antibody responses during Borrelia burgdorferi infection and antibiotic treatment of rhesus macaques. Clin Vaccine Immunol. 2012 Aug;19(8):1218-26. doi: 10.1128/CVI.00228-12. Epub 2012 Jun 20. PMID: 22718128; PMCID: PMC3416093.
Aucott, J. N., L. A. Crowder and K. B. Kortte (2013). “Development of a foundation for a case definition of post-treatment Lyme disease syndrome.” International Journal of Infectious Diseases 17(6): e443-e449.
Blum, L. K., J. Z. Adamska, D. S. Martin, A. W. Rebman, S. E. Elliott, R. R. L. Cao, M. E. Embers, J. N. Aucott, M. J. Soloski and W. H. Robinson (2018). “Robust B Cell Responses Predict Rapid Resolution of Lyme Disease.” Front Immunol 9: 1634.

About the Instructor

Monica Embers, PhD

Director of Vector-borne Disease Research, Tulane National Primate Research Center

Dr. Embers is currently an Associate Professor in the Division of Immunology and the Director of Vector-borne Disease Research at the Tulane National Primate Research Center. Her research program regarding Lyme disease and its infectious cause Borrelia burgdorferi specializes in animal models. The research is centered around three major efforts: (1) identifying treatments that can eradicate B. burgdorferi infection; (2) detection of persistent Lyme disease spirochetes in human (autopsy) tissues; and (3) immunodiagnosis for B. burgdorferi infection and cure. By transmitting Lyme disease to mice and nonhuman primates by tick, and studying the natural course of infection, her group aims to attain a better understanding of the clinical quandaries of human Lyme disease, including effective diagnosis and treatment. Due to the many similarities between Bartonellosis and Lyme disease, her team has begun to develop research models for Bartonella infection. The goals of Bartonella research involve developing improved treatment strategies, understanding the pathophysiology of co-infection, and interrogating tick vector transmission of these pathogens.