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
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.
References
- Pritt BS, Mead PS, Johnson DK, Neitzel DF, Respicio-Kingry LB, Davis JP, Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochataemia: a descriptive study. Lancet Infect Dis. 2016;Feb 5:pii: S1473-3099(15)00464-8.
- Adams DA, Jajosky RA, Ajani U, Kriseman J, Sharp P, Onwen DH, Summary of notifiable diseases—United States, 2012. MMWR Morb Mortal Wkly Rep. 2014;61:1–121.PubMed
- Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, 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;43:1089–134. DOIPubMed
- 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;44:590–1.PubMed
- Centers for Disease Control and Prevention. Notice to readers: caution regarding testing for Lyme disease. MMWR Morb Mortal Wkly Rep. 2005;54:125 [cited 2016 Mar 14]. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5405a6.htm
- Food and Drug Administration. Database: search on product code LSR [cited 2015 Jul 17]. http://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm
- Bacon RM, Biggerstaff BJ, Schriefer ME, Gilmore RD Jr, Philipp MT, Steere AC, Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates. J Infect Dis. 2003;187:1187–99. .DOIPubMed
- Liang FT, Steere AC, Marques AR, Johnson BJ, Miller JN, Philipp MT. Sensitive and specific serodiagnosis of Lyme disease by enzyme-linked immunosorbent assay with a peptide based on an immunodominant conserved region of Borrelia burgdorferi VlsE. J Clin Microbiol. 1999;37:3990–6.PubMed
- Aguero-Rosenfeld ME, Nowakowski J, Bittker S, Cooper D, Nadelman RB, Wormser GP. Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans. J Clin Microbiol. 1996;34:1–9.PubMed
- Nelson C, Johnson B, Petersen J, Schriefer M, Beard CB, Petersen L, Concerns regarding a new culture method for Borrelia burgdorferi not approved for the diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2014;63:333..PubMed
1These authors contributed equally to this article.