Performance of 45 Laboratories Participating in a Proficiency Testing Program for Lyme Disease Serology

Bakken, Lori L.; Case, Kay L.; Callister, Steven M.; Bourdeau, Napoleon J.; Schell, Ronald F.

doi:10.1001/jama.1992.03490070073045

Cited by 111 publications

(41 citation statements)

References 13 publications

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“…However, because the study laboratory was located in an area endemic for Lyme disease, we assumed that most patients had potential exposure. Fourth, although interpretation of Lyme disease immunoblots can vary between diagnostic laboratories [25], all but 1 were performed in the same laboratory. Next, our asymptomatic control patients were being evaluated clinically for food or environmental allergies, and we cannot exclude the possibility that the frequency of false-positive Lyme disease serologic results might differ in these patients.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the C6 Lyme Enzyme Immunoassay for the Diagnosis of Lyme Disease in Children and Adolescents

Lipsett¹,

Branda

McAdam

et al. 2016

Clin Infect Dis.

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5Pediatric Physicians' Organization at Children's, Brookline, MassachusettsBackground. The commercially-available C6 Lyme enzyme immunoassay (EIA) has been approved to replace the standard whole-cell sonicate EIA as a first-tier test for the diagnosis of Lyme disease and has been suggested as a stand-alone diagnostic. However, the C6 EIA has not been extensively studied in pediatric patients undergoing evaluation for Lyme disease.Methods. We collected discarded serum samples from children and adolescents (aged ≤21 years) undergoing conventional 2-tiered testing for Lyme disease at a single hospital-based clinical laboratory located in an area endemic for Lyme disease. We performed a C6 EIA on all collected specimens, followed by a supplemental immunoblot if the C6 EIA result was positive but the wholecell sonicate EIA result was negative. We defined a case of Lyme disease as either a clinician-diagnosed erythema migrans lesion or a positive standard 2-tiered serologic result in a patient with symptoms compatible with Lyme disease. We then compared the performance of the C6 EIA alone and as a first-tier test followed by immunoblot, with that of standard 2-tiered serology for the diagnosis of Lyme disease.Results. Of the 944 specimens collected, 114 (12%) were from patients with Lyme disease. The C6 EIA alone had sensitivity similar to that of standard 2-tiered testing (79.8% vs 81.6% for standard 2-tiered testing; P = .71) with slightly lower specificity (94.2% vs 98.8% 2; P < .002). Addition of a supplemental immunoblot improved the specificity of the C6 EIA to 98.6%.Conclusions. For children and adolescents undergoing evaluation for Lyme disease, the C6 EIA could guide initial clinical decision making, although a supplemental immunoblot should still be performed.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the C6 Lyme Enzyme Immunoassay for the Diagnosis of Lyme Disease in Children and Adolescents

Lipsett¹,

Branda

McAdam

et al. 2016

Clin Infect Dis.

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“…This approach is laborintensive, time-consuming, and subjective, allowing for potential intra-and interlaboratory variation in WB reading and interpretation. Previous studies analyzing the performance of LB serologic tests among testing laboratories have demonstrated significant variation in results, even for more objective methods, such as enzyme immunoassay (2,3,10). Therefore, given the inherent subjectivity in reading and interpreting WBs for diagnosis of LB (i.e., Lyme WBs), one would expect to observe significant variation in WB results, with potentially adverse effects on the laboratory diagnosis of Lyme disease and subsequent patient management decisions.…”

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confidence: 99%

Evaluation of Two Commercial Systems for Automated Processing, Reading, and Interpretation of Lyme Borreliosis Western Blots

Binnicker¹,

Jespersen²,

Harring³

et al. 2008

J Clin Microbiol

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The diagnosis of Lyme borreliosis (LB) is commonly made by serologic testing with Western blot (WB) analysis serving as an important supplemental assay. Although specific, the interpretation of WBs for diagnosis of LB (i.e., Lyme WBs) is subjective, with considerable variability in results. In addition, the processing, reading, and interpretation of Lyme WBs are laborious and time-consuming procedures. With the need for rapid processing and more objective interpretation of Lyme WBs, we evaluated the performances of two automated interpretive systems, TrinBlot/BLOTrix (Trinity Biotech, Carlsbad, CA) and BeeBlot/ViraScan (Viramed Biotech AG, Munich, Germany), using 518 serum specimens submitted to our laboratory for Lyme WB analysis. (7), confirming that the disease continues to represent a significant public health threat. The clinical manifestations of early localized disease range from nonspecific sequelae, including malaise, myalgia, and lymphadenopathy, to more characteristic findings, such as erythema migrans (EM). In the absence of appropriate therapy, disease progression may lead to significant complications, including rheumatologic, neurologic, or cardiac manifestations (15, 16).The diagnosis of Lyme borreliosis (LB) can be made clinically when patients from regions where the disease is endemic present with EM (5, 8, 18). However, in patients without EM but with objective clinical findings suggestive of disseminated LB, serologic testing is an important diagnostic approach. Appropriate serologic testing should follow the two-tier algorithm recommended by the CDC (6), consisting of initial testing with a sensitive screening assay (e.g., enzyme immunoassay) with positive or equivocal specimens to be tested by Western blot (WB) analysis. Current CDC criteria for WB interpretation recommend that Ն2 bands on the immunoglobulin M (IgM) WB or Ն5 bands on the IgG WB be present for the immunoblot to be considered positive (6, 9). Although WB is considered to be highly specific, current testing protocols in most clinical laboratories rely on visual reading and interpretation of WB strips. These procedures require the laboratory technologist to visually compare band intensities on the patient strip to those of a weakly reactive control. This approach is laborintensive, time-consuming, and subjective, allowing for potential intra-and interlaboratory variation in WB reading and interpretation. Previous studies analyzing the performance of LB serologic tests among testing laboratories have demonstrated significant variation in results, even for more objective methods, such as enzyme immunoassay (2, 3, 10). Therefore, given the inherent subjectivity in reading and interpreting WBs for diagnosis of LB (i.e., Lyme WBs), one would expect to observe significant variation in WB results, with potentially adverse effects on the laboratory diagnosis of Lyme disease and subsequent patient management decisions. Due to the need for more objective and consistent interpretation of Lyme WBs, we undertook a study to evaluate and comp...

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“…Despite FDA clearance of many of these assays, published proficiency testing studies revealed significant result heterogeneity between the different commercially available kits and, perhaps most worrisome, appreciable intralaboratory variability for duplicate samples. One such study demonstrated that, among the 45 participating laboratories, up to 55% failed to detect antibodies to B. burgdorferi in sera from patients with clinically characterized LD who were seropositive according to a reference IFA (8). Precision was likewise shown to be poor; one laboratory documented a coefficient of variation of more than 120% for a sample tested in triplicate, and another proficiency sample tested across the 45 laboratories had a reproducibility rate of only 27%.…”

Section: Serologic Testing For Lyme Disease: a Historical Perspectivementioning

confidence: 99%

The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease

Theel

2016

J Clin Microbiol

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Lyme disease prevails as the most commonly transmitted tick-borne infection in the United States, and serologic evaluation for antibodies to Borrelia burgdorferi remains the recommended modality for diagnosis. This review presents a brief historical perspective on the evolution of serologic assays for Lyme disease and provides a summary of the performance characteristics for the currently recommended two-tiered testing algorithm (TTTA). Additionally, a recently proposed alternative to the traditional TTTA is discussed, and novel methodologies, including immuno-PCR and metabolic profiling for Lyme disease, are outlined.

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Performance of 45 Laboratories Participating in a Proficiency Testing Program for Lyme Disease Serology

Abstract: Our results indicate that there is an urgent need for standardization of current testing methodologies. Until a national commitment is made, serological testing for Lyme disease will be of questionable value for the diagnosis of the disease.

Cited by 111 publications

References 13 publications

Evaluation of the C6 Lyme Enzyme Immunoassay for the Diagnosis of Lyme Disease in Children and Adolescents

Evaluation of the C6 Lyme Enzyme Immunoassay for the Diagnosis of Lyme Disease in Children and Adolescents

Evaluation of Two Commercial Systems for Automated Processing, Reading, and Interpretation of Lyme Borreliosis Western Blots

The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease

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