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Volume 22, Number 7—July 2016
CME ACTIVITY - Synopsis

Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States

Andrew Moore1, Christina A. Nelson1, Claudia Molins, Paul S. Mead, and Martin SchrieferComments to Author 
Author affiliations: University of Virginia School of Medicine, Charlottesville, Virginia, USA (A. Moore); Centers for Disease Control and Prevention, Fort Collins, Colorado, USA (C. Nelson, C. Molins, P. Mead, M. Schriefer)

Main Article

Table

Sensitivity and specificity of serologic tests for patients with Lyme disease, United States*

Variable Standard 2-tiered algorithm with whole-cell sonicate EIA†
Standard 2-tiered algorithm with C6 EIA,‡ Wormser et al. (13) Two-EIA algorithm§
Molins et al. (CDC Lyme Repository) (14) Wormser et al. (15) Branda et al. (12) Branda et al. (12) Wormser et al. (13,15)
% Sensitivity (no. tested)
Early Lyme disease with EM¶
Acute phase 40 (40) 38 (298) 42 (114) 38 (298) 53 (114) 58 (298)
Convalescent phase
61 (38)
27 (105)
57 (63)#
26 (105)
89 (63)#
67 (105)
Noncutaneous manifestations 96 (46) 94 (142) 87 (55) 93 (142) 100 (55) 97 (144)
Early disseminated Lyme disease 88 (17) 80 (20) 73 (26) 80 (20) 100 (26) ND
Late disseminated Lyme disease
100 (29)
96 (122)
100 (29)
95 (122)
100 (29)
ND
% Specificity (no. tested)
Healthy controls
Endemic area 98 (101) 99 (1,329) 99 (1,146) 99 (1,329) 99 (1,146) >99 (1,329)**
Nonendemic area
100 (102)
100 (513)
100 (100)
100 (513)
100 (100)
>99 (513)**
Controls with selected other diseases
Syphilis or RPR positive†† 95 (20) 95 (20) ND 95 (20) ND >95 (20)**
Infectious mononucleosis or EBV/CMV positive†† 90 (30) 100 (40) ND 100 (40) ND 100 (20)
Helicobacter pylori
ND
95 (20)
ND
100 (20)
ND
100 (20)
All nonhealthy controls 97 (144)‡‡ 99 (366)§§ 100 (54)¶¶ 100 (366)§§ 100 (54)¶¶ 100 (366)

*All percentage values were rounded to the nearest whole number. C6, C6 peptide of Borrelia burgdorferi; CDC, Centers for Disease Control and Prevention; CMV, cytomegalovirus; EIA, enzyme immunoassay; EM, erythema migrans; EBV, Epstein-Barr virus; ND, not done; RPR, rapid plasma regain.
†Standard 2-tiered algorithm: whole-cell sonicate EIA, then IgG (+IgM if presenting within 1 month) Western immune blot if positive or equivocal result.
‡C6+ Western immunoblot algorithm: C6 EIA, then IgG (+IgM if presenting within 1 month) Western immunoblot if positive or equivocal result.
§Two-tiered EIA: whole-cell sonicate EIA, then C6 EIA if positive or equivocal result.
¶Patients with EM and epidemiologic risk can be given a diagnosis without serologic analysis (see Figure 3).
#Branda et al. (12) conducted only convalescent-phase serologic analysis on a well-characterized serum set of Lyme disease patients and controls. All other data points from this study include the data from well-characterized serum set and serum samples submitted to Massachusetts General Hospital (Boston, MA, USA) for routine testing.
**Minimum specificity reported by Wormser et al. (13,15).
††Molins et al. (14) tested samples from patients with syphilis or infectious mononucleosis. Wormser et al. (13,15) tested blood samples with positive results for RPR or CMV/EBV.
‡‡In the report by Molins et al. (14), 2-tiered testing had 100% specificity for all other diseases not mentioned above. Other conditions tested include fibromyalgia, severe periodontitis, rheumatoid arthritis, and multiple sclerosis.
§§Among patients tested by Wormser et al. (13,15) there was a single hemolyzed blood sample that showed positive results for all tests. However, both methods of 2-tiered testing had 100% specificity for all other conditions not mentioned above, including Mycoplasma pneumoniae infection; HIV; hepatitis A, B, and C; influenza vaccinations; antinuclear antibodies; lipemia; icterus; systemic lupus erythematosus; rheumatoid arthritis; and positive results for rheumatoid factor.
¶¶Includes 25 patients with chronic fatigue syndrome or fibromyalgia, 14 with rheumatic diseases, 9 with neurologic conditions, 5 with infections, and 1 with T-cell lymphoma.

Main Article

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1These authors contributed equally to this article.

Page created: June 15, 2016
Page updated: November 30, 2016
Page reviewed: November 30, 2016
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