Study Highlights Low Sensitivity of Current Lyme Tests in Early Infection

Missed detection at this stage can delay evaluation and management and complicate epidemiologic assessment. Clinical laboratories commonly employ standard or modified two-tiered testing algorithms to assess serum from suspected cases. A new study shows these approaches demonstrate low sensitivity in early infection, despite high specificity.

Researchers at the Lyme Disease Biobank in Portland, Oregon, evaluated standard two-tiered testing (STTT) and modified two-tiered testing (MTTT) algorithms in early Lyme disease. These two-tiered serologic workflows were applied to serum, and all configurations assessed were U.S. Food and Drug Administration (FDA)-cleared. The analysis compared four STTT or MTTT algorithms and assessed agreement among methods.

The study used serum from 107 cases of early Lyme disease, 69 of whom also provided a convalescent draw, alongside 144 endemic controls. Performance was evaluated at the initial blood draw and, where available, at convalescence. The investigators also examined algorithm concordance across samples.

Algorithm sensitivity at the initial blood draw ranged from 22% to 36%, while specificity ranged from 98% to 100%. MTTT approaches showed higher sensitivity than STTT overall, with no sensitivity difference observed between the two MTTT algorithms. One STTT algorithm was less sensitive than the other. Discordance was notable: among 45 laboratory-confirmed cases, only 22 were positive across all algorithms tested. In participants with a suspected erythema migrans lesion, the likelihood of a positive two-tiered result increased with longer lesion duration and when one or more constitutional symptom was present.

Findings were published online April 21, 2026, in the Journal of Clinical Microbiology. The work involved the Lyme Disease Biobank and collaborators. The results underscore limitations of current two-tiered diagnostics in early infection and point to a need for improved medical education on test interpretation.