Advances in Serodiagnostic Testing for Lyme Disease Are at Hand

Branda, John A.; Body, Barbara A.; Boyle, Jeff; Branson, Bernard M.; Dattwyler, Raymond J.; Fikrig, Erol; Gerald, Noel J.; Gomes-Solecki, Maria; Kintrup, Martin; Ledizet, Michel; Levin, Andrew; Lewinski, Michael A.; Liotta, Lance A.; Marques, Adriana; Mead, Paul S.; Mongodin, Emmanuel F.; Pillai, Segaran P.; Rao, P. Appa; Robinson, William H.; Roth, Kristian M.; Schriefer, Martin E.; Slezak, Thomas R.; Snyder, Jessica L.; Steere, Allen C.; Witkowski, Jan; Wong, Susan J.; Schutzer, Steven E.

doi:10.1093/cid/cix943

Cited by 95 publications

(89 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are many advantages to the MTT approach compared to use of STT algorithms, and they are discussed in detail in a report from a conference on diagnostic tests for Lyme disease which was held in 2016 (31). Overall, the MTT approach is more sensitive than the STT algorithm for early disease, has similar sensitivity for later infection, and maintains similar specificity.…”

mentioning

confidence: 99%

Revisiting the Lyme Disease Serodiagnostic Algorithm: the Momentum Gathers

Marques

2018

J Clin Microbiol

View full text Add to dashboard Cite

Lyme disease is a tick-borne illness caused by () , and it is the most common vector-borne disease in the United States, with an estimated incidence of 300,000 cases per year. The currently recommended approach for laboratory support of the diagnosis of Lyme disease is a standard two-tiered (STT) algorithm comprised of an enzyme-linked immunoassay (EIA) or immunofluorescence assay (IFA), followed by Western blotting (WB). The STT algorithm has low sensitivity in early infection, and there are drawbacks associated with the WB use in practice. Modified two-tiered (MTT) algorithms have been shown to improve the sensitivity of the testing in early disease while maintaining high specificity. In this issue of the, A. Pegalajar-Jurado et al. (J Clin Microbiol 56:e01943-17, 2018, https://doi.org/10.1128/JCM.01943-17) report the results of their evaluation of the Liaison VlsE CLIA, the Captia IgG/IgM EIA, and the C6 (Lyme) EIA as MTT algorithms compared with results with the STT algorithm using the same tests as the first-tier test and the ViraStripe IgM and IgG WBs as the second-tier test. The results showed that all MTT algorithms had higher sensitivities than STT algorithms and were highly specific. These results showed that MTT approaches are a valid alternative to the currently recommended STT algorithm for serodiagnosis of Lyme disease, opening the door for the development of rapid diagnostics and point-of-care testing that can provide diagnostic information during the initial patient visit.

show abstract

mentioning

confidence: 99%

Revisiting the Lyme Disease Serodiagnostic Algorithm: the Momentum Gathers

Marques

2018

J Clin Microbiol

View full text Add to dashboard Cite

show abstract

“…Therefore, our findings should not be applied to children with nonspecific constitutional symptoms, a clinical situation in which Lyme disease testing is not routinely recommended (12). Second, we lack a definitive gold standard for the diagnosis of Lyme disease, as the clinical features are not pathognomonic unless a classical bulls-eye skin rash is present, and Lyme disease serology can produce both false-positive and false-negative test results (18,19). We relied on CDC criteria for interpretation of serologic testing.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Modified Two-Tiered Testing Method for Diagnosis of Lyme Disease in Children

2019

View full text Add to dashboard Cite

Conventional two-tiered testing (CTTT) for Lyme disease includes a first-tier enzyme immunoassay (EIA) followed by a supplemental immunoblot, and modified two-tiered testing (MTTT) relies on two different sequential EIAs without the inclusion of an immunoblot. MTTT has shown promising results as an alternative strategy for the diagnosis of Lyme disease in adults but has not yet been evaluated in children. We performed a cross-sectional study of children and adolescents ≤21 years of age undergoing clinical investigation for suspected Lyme disease. Serum specimens were analyzed with both a whole-cell sonicate (WCS) and a C6 EIA, with a supplemental immunoblot if either EIA was positive or equivocal. We compared CTTT (WCS EIA followed by supplemental immunoblot) to MTTT (WCS EIA followed by C6 EIA) using McNemar’s test to evaluate for agreement beyond chance alone. We then used a kappa statistic to measure level of the agreement between testing strategies. We included 1,066 serum specimens, of which 156 (14.6%) had a positive CTTT and 165 (15.5%) had a positive MTTT. There were no significant differences between MTTT and CTTT (P = 0.16). Although the overall agreement between MTTT and CTTT was high (kappa, 0.88; 95% confidence interval, 0.84 to 0.92), 33 children had discordant test results. In a cohort of children and adolescents undergoing investigation for suspected Lyme disease, CTTT and MTTT results agreed in most cases. Since immunoblots are time-consuming, laborious, and challenging to interpret, MTTT provides a promising alternate Lyme disease testing strategy for children.

show abstract

“…The guidelines are geared to assess exposure to B. burgdorferi through the patient's antibody response to infection rather than direct detection of nucleic acid or protein from the microbe. The limitations of serologic testing and advances were recently reported in detail [4].…”

Section: Current Approach To Laboratory Testing For Lyme Diseasementioning

confidence: 99%

“…However, serologic tests have been hampered by technical and biological shortcomings, the greatest being a time lag for the host to make detectable antibody by current tests. The other biologic hurdle is that a single antibody test can only indicate exposure, not active infection [4] or reinfection. The development of sensitive tests capable of directly detecting the organism in body fluids has proven challenging.…”

mentioning

confidence: 99%

“…There was no intent to take a vote, advocate for one test product over another, or reach a consensus during the meeting; rather, there was discussion of research findings that support or challenge particular diagnostic concepts. What emerged was a recognition that improved approaches to serologic testing were now available [4] and that the technology for direct detection of bacterial proteins or DNA has advanced to the point that it is evaluable in Lyme disease. If the technology meets scientific rigor, these tests could become future diagnostic assays.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Direct Diagnostic Tests for Lyme Disease

Schutzer

Body²,

Boyle

et al. 2018

Clinical Infectious Diseases

Self Cite

View full text Add to dashboard Cite

Borrelia burgdorferi was discovered to be the cause of Lyme disease in 1983, leading to seroassays. The 1994 serodiagnostic testing guidelines predated a full understanding of key B. burgdorferi antigens and have a number of shortcomings. These serologic tests cannot distinguish active infection, past infection, or reinfection. Reliable direct-detection methods for active B. burgdorferi infection have been lacking in the past but are needed and appear achievable. New approaches have effectively been applied to other emerging infections and show promise in direct detection of B. burgdorferi infections.

show abstract

Advances in Serodiagnostic Testing for Lyme Disease Are at Hand

Cited by 95 publications

References 36 publications

Revisiting the Lyme Disease Serodiagnostic Algorithm: the Momentum Gathers

Revisiting the Lyme Disease Serodiagnostic Algorithm: the Momentum Gathers

Evaluation of the Modified Two-Tiered Testing Method for Diagnosis of Lyme Disease in Children

Direct Diagnostic Tests for Lyme Disease

Contact Info

Product

Resources

About