Two-tier Lyme disease test results vary based on initial test

Photo of Lise Nigrovic
Lise E. Nigrovic

Two-tier testing for Lyme disease differed in results based on the type of test used in the first tier, according to study results published in Journal of the Pediatric Infectious Diseases Society.

“We found that the results agree in most cases but disagree in a substantial minority of cases,” Lise E. Nigrovic, MD, MPH, senior associate physician in medicine in the division of emergency medicine at Boston Children’s Hospital and associate professor of pediatrics and emergency medicine at Harvard Medical School, told Infectious Diseases in Children.

The CDC currently recommends a two-tier Lyme disease testing algorithm that includes a sensitive first-tier test — either an enzyme immunoassay (EIA) or immunofluorescence assay — followed by a second-tier supplemental immunoblot assay if the first-tier test result is either positive or equivocal.

“However, the specific Lyme disease serologic assay is frequently selected by the laboratory, not the clinician,” Nigrovic said.

Nigrovic and colleagues conducted a prospective cohort study of 1,714 children aged 1 to 21 years who were being evaluated for Lyme disease in the ED of one of six centers where Lyme disease is endemic. The centers were located in Boston; Wilmington, Delaware; Providence, Rhode Island; Milwaukee, Wisconsin; Philadelphia and Pittsburgh.

Initially, the six EDs conducted a clinical first-tier EIA, and the specific test types varied by institution. A positive or equivocal first-tier test resulted in a second-tier supplemental immunoblot test. If the first-tier test was positive or equivocal and the follow-up assay was positive, the researches defined it as a positive clinical two-tier Lyme test.

Using the same serum samples, Nigrovic and colleagues performed a C6 EIA using an FDA-cleared assay (Oxford Immunotec). For any child who had a positive or equivocal C6 EIA result and did not have an immunoblot test during clinical care, the researchers ordered a supplemental immunoblot test. The researchers defined a positive or equivocal C6 EIA result and a supplemental positive immunoblot assay as a positive C6 two-tier test.

According to the researchers, they chose the C6 test because it is a next-generation, FDA-approved EIA that “has equivalent sensitivity and better specificity than the older, whole-cell sonicate EIA.”

Nigrovic and colleagues collected serum samples from 1,584 children (92.4%). Three hundred-sixteen children (19.9%) had positive clinical two-tier EIA results, and 295 children (18.6%) had positive or equivocal C6 two-tier test results.

“The clinical and C6 two-tier test results disagreed more often than they would have by chance alone (P = .002),” the researchers wrote.

They reported that 39 children had either a positive clinical or C6 two-tier test result alone, with two of those children having an erythema migrans lesion and 29 experiencing symptoms that were compatible with early disseminated Lyme disease.

The researchers concluded that their work underscores “the importance of considering Lyme disease in any patient for whom there is a strong clinical suspicion, even after initially negative two-tier test results.”

A recent, separate study in the Journal of Pediatric Infectious Diseases Society found that appropriate antibiotic therapy typically is successful for treating both early- and late-stage Lyme disease, yet recovery varies at different rates. – by Bruce Thiel

References:

Chason ME, et al. J Pediatric Infect Dis Soc. 2018;doi: 10.1093/jpids/piy067.

Maulden AB, et al. J Pediatric Infect Dis Soc. 2019;doi:10.1093/jpids/piy133.

Disclosures: Nigrovic reports being a community member of the federal Tick-Borne Illness Working Group, but the study does not represent the opinion of the committee. Please see the study for all other authors’ relevant financial disclosures.

Photo of Lise Nigrovic
Lise E. Nigrovic

Two-tier testing for Lyme disease differed in results based on the type of test used in the first tier, according to study results published in Journal of the Pediatric Infectious Diseases Society.

“We found that the results agree in most cases but disagree in a substantial minority of cases,” Lise E. Nigrovic, MD, MPH, senior associate physician in medicine in the division of emergency medicine at Boston Children’s Hospital and associate professor of pediatrics and emergency medicine at Harvard Medical School, told Infectious Diseases in Children.

The CDC currently recommends a two-tier Lyme disease testing algorithm that includes a sensitive first-tier test — either an enzyme immunoassay (EIA) or immunofluorescence assay — followed by a second-tier supplemental immunoblot assay if the first-tier test result is either positive or equivocal.

“However, the specific Lyme disease serologic assay is frequently selected by the laboratory, not the clinician,” Nigrovic said.

Nigrovic and colleagues conducted a prospective cohort study of 1,714 children aged 1 to 21 years who were being evaluated for Lyme disease in the ED of one of six centers where Lyme disease is endemic. The centers were located in Boston; Wilmington, Delaware; Providence, Rhode Island; Milwaukee, Wisconsin; Philadelphia and Pittsburgh.

Initially, the six EDs conducted a clinical first-tier EIA, and the specific test types varied by institution. A positive or equivocal first-tier test resulted in a second-tier supplemental immunoblot test. If the first-tier test was positive or equivocal and the follow-up assay was positive, the researches defined it as a positive clinical two-tier Lyme test.

Using the same serum samples, Nigrovic and colleagues performed a C6 EIA using an FDA-cleared assay (Oxford Immunotec). For any child who had a positive or equivocal C6 EIA result and did not have an immunoblot test during clinical care, the researchers ordered a supplemental immunoblot test. The researchers defined a positive or equivocal C6 EIA result and a supplemental positive immunoblot assay as a positive C6 two-tier test.

According to the researchers, they chose the C6 test because it is a next-generation, FDA-approved EIA that “has equivalent sensitivity and better specificity than the older, whole-cell sonicate EIA.”

Nigrovic and colleagues collected serum samples from 1,584 children (92.4%). Three hundred-sixteen children (19.9%) had positive clinical two-tier EIA results, and 295 children (18.6%) had positive or equivocal C6 two-tier test results.

“The clinical and C6 two-tier test results disagreed more often than they would have by chance alone (P = .002),” the researchers wrote.

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They reported that 39 children had either a positive clinical or C6 two-tier test result alone, with two of those children having an erythema migrans lesion and 29 experiencing symptoms that were compatible with early disseminated Lyme disease.

The researchers concluded that their work underscores “the importance of considering Lyme disease in any patient for whom there is a strong clinical suspicion, even after initially negative two-tier test results.”

A recent, separate study in the Journal of Pediatric Infectious Diseases Society found that appropriate antibiotic therapy typically is successful for treating both early- and late-stage Lyme disease, yet recovery varies at different rates. – by Bruce Thiel

References:

Chason ME, et al. J Pediatric Infect Dis Soc. 2018;doi: 10.1093/jpids/piy067.

Maulden AB, et al. J Pediatric Infect Dis Soc. 2019;doi:10.1093/jpids/piy133.

Disclosures: Nigrovic reports being a community member of the federal Tick-Borne Illness Working Group, but the study does not represent the opinion of the committee. Please see the study for all other authors’ relevant financial disclosures.