Improved Serodiagnostic Testing for Lyme Disease: Results of a Multicenter Serologic Evaluation

Craven, RB; Tj, Quan; Re, Bailey; Dattwyler, Raymond J.; Ryan, RW; Lh, Sigal; Steere, Allen C.; Sullivan, Bradley J.; Bj, Johnson; Dt, Dennis; Dj, Gubler

doi:10.3201/eid0202.960211

Cited by 39 publications

(25 citation statements)

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“…In a comparison of the serologic results of two EIA methods at CDC and serologic results on the same specimens at five academic centers, the EIA methods employing whole cell sonicate and flagella antigen at CDC were shown to have unacceptably low specificity owing to setting the cutoff threshold too low (15). One academic laboratory had a low sensitivity (49%) and poor precision (79%) for case samples.…”

Section: Diagnostic Serologymentioning

confidence: 99%

Tick-Transmitted Infectious Diseases in the United States

Walker

1998

Annu. Rev. Public Health

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The epidemiologic concept of tick-transmitted diseases has increased in importance with the recognition of the emerging infectious diseases, Lyme borreliosis, human monocytotropic and granulocytotropic ehrlichioses, and three different babesioses. Effective public health control of these diseases would depend upon critical knowledge of the vector biology of the ticks that transmit them. Rocky Mountain spotted fever and the human ehrlichioses are life-threatening yet treatable diseases. A major problem remains establishment of the diagnosis when treatment decisions are being made. Clinical manifestations, other than erythema migrans for Lyme borreliosis, do not provide strong diagnostic clues. Ehrlichiae or babesiae are often not detected in peripheral blood smears. Frequently there are no antibodies to these diverse agents at the time of presentation, and isolation does not yield sensitive and timely results. Polymerase chain reaction, still a research tool, promises the greatest sensitivity, specificity, and timeliness. Prevention by vaccines is not yet a reality, although OspA-based vaccines offer hope for the prevention of Lyme disease.

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Section: Diagnostic Serologymentioning

confidence: 99%

Tick-Transmitted Infectious Diseases in the United States

Walker

1998

Annu. Rev. Public Health

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“…We thank the commercial laboratories responding to our quesDue to the large number of EIAs ordered by practicing physi- and its specificity was 82% [5] and there were 300 cases of LD each year (estimate on the basis of official reported cases…”

Section: Acknowledgmentsmentioning

confidence: 99%

Utilization and Cost of Serologic Tests for Lyme Disease in Maryland

et al. 1997

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To ascertain use of serologic tests for Lyme disease (LD) in Maryland, all laboratories registered with the State Health Department were surveyed. Results show that from 1992 to 1995, 17 laboratories performed 100,000 serologic tests costing $7.1 million on Maryland residents; 90% of these tests were EIAs. The proportion of positive EIAs increased from 3.4% in 1992 to Ç7.0% in 1994 and 1995, and the percentage of positive second tests (Western blot, WB) fell from 7.9% to 5.0% -5.5%. The large number of EIAs performed in comparison with the low incidence of LD in the state results in a low predictive value of a positive EIA test. Therefore, the WB is indicated to confirm equivocal and positive EIA tests when characteristic clinical findings of LD are not present. The 30,000 tests for LD performed annually on Maryland residents at a cost of over $2 million in direct medical costs must be added to the public health burden of LD in this state.Lyme disease (LD) is the most common vectorborne illness LD were being performed on Maryland residents. Therefore, we surveyed all laboratories performing diagnostic testing for in the United States and is increasing in prevalence and distribution [1]. The hallmark of early infection, the expanding LD on serum from Maryland residents to estimate the number and types of tests performed and their cost. bull's-eye erythema migrans (EM) rash, is absent in 30% -40% of patients meeting the Centers for Disease Control and Prevention's (CDC) surveillance case definition for LD [2]. Rheumatologic, neurologic, and cardiac manifestations suggesMethods tive of late-stage LD require serologic confirmation, since they The most commonly performed test, an EIA, lacks sensitivity a positive test result to the DHMH, were sent a questionnaire in detecting Borrelia burgdorferi antibodies in the earliest with an explanatory cover letter. The questionnaire inquired about stages of the disease. In patients with late-stage LD, crosswhich tests were performed, the number of tests performed per year, the proportion of positive tests, and charges for performing reactivity during testing lowers specificity and causes confusion the tests. Each laboratory was assured of the confidentiality of its with several infectious and autoimmune diseases [4 -6]. The responses and was assigned an identification number so that results current recommendation is to use a two-test approach to serocould not be traced to specific laboratories. logic testing for LD: the more sensitive EIA test followed byThe survey was mailed to the 27 laboratories identified. Those the more specific Western blot (WB) for those with equivocal that failed to return the survey within 2 weeks were called and and positive EIA test results [4 -6].reminded. Two weeks later, the remaining laboratories wereIn 1992, we began collecting and recording data, including phoned and offered the option of having a project investigator diagnostic laboratory tests, on patients with LD reported to the collect the data from their records. Three chose to be site-v...

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“…Unfortunately, current serodiagnostic enzyme-linked immunosorbent assays (ELISAs) are not highly sensitive and selective, hindering detection (1,3,5,8,12,14,29,32,38,41,50,67,70,74). Definitive serological diagnosis depends on a complex, expensive immunoblot analysis (14,16,31,35,38,40,41,51,56,58,72,74).…”

mentioning

confidence: 99%

“…Definitive serological diagnosis depends on a complex, expensive immunoblot analysis (14,16,31,35,38,40,41,51,56,58,72,74).…”

mentioning

confidence: 99%

Identifying Diagnostic Peptides for Lyme Disease through Epitope Discovery

Kouzmitcheva

Petrenko

Smith

2001

Clin Diagn Lab Immunol

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Serum antibodies from patients with Lyme disease (LD) were used to affinity select peptide epitopes from 12 large random peptide libraries in phage display format. The selected peptides were surveyed for reactivity with a panel of positive sera (from LD patients) and negative sera (from subjects without LD), thus identifying 17 peptides with a diagnostically useful binding pattern: reactivity with at least three positive sera and no reactivity with any of the negative sera. The peptides define eight sequence motifs, none of which can be matched convincingly with segments of proteins from Borrelia burgdorferi, the LD pathogen; evidently, then, they are "mimotopes," mimicking natural pathogen epitopes without matching contiguous amino acids of pathogen proteins. Peptides like these could be the basis of a new diagnostic enzyme-linked immunosorbent assay for LD, with sufficient specificity and sensitivity to replace expensive immunoblotting tests that are currently required for definitive serological diagnosis. Moreover, the method used to discover these peptides did not require any knowledge of the pathogen and involved generic procedures that are applicable to almost any infectious disease, including emerging diseases for which no pathogen has yet been identified.

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Improved Serodiagnostic Testing for Lyme Disease: Results of a Multicenter Serologic Evaluation

Cited by 39 publications

References 20 publications

Tick-Transmitted Infectious Diseases in the United States

Tick-Transmitted Infectious Diseases in the United States

Utilization and Cost of Serologic Tests for Lyme Disease in Maryland

Identifying Diagnostic Peptides for Lyme Disease through Epitope Discovery

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