Related Experiment Video
Updated: Oct 18, 2025
Author Spotlight: Expanding the Scope of Multiplex Immunoassays for Lyme Borreliosis Diagnostics and Pathogen Research
Published on: July 14, 2023
Two-Tier Lyme Disease Serology in Children with Previous Lyme Disease
Paul M Lantos1, Frances Balamuth2, Desiree Neville3
1Department of Medicine, Duke University, Durham, North Carolina, USA.
Insights
A prior Lyme disease diagnosis complicates current diagnosis in children. One-third of these children met acute Lyme disease criteria, with rates declining over time, highlighting the need for better diagnostics.
Area of Science:
- Pediatric Infectious Diseases
- Epidemiology of Tick-Borne Illnesses
Background:
- Interpreting Lyme disease serology in children with a prior history of the illness presents diagnostic challenges.
- Previous Lyme disease diagnosis can affect the accuracy of current serological tests for acute infection.
Purpose of the Study:
- To investigate the relationship between a prior Lyme disease diagnosis and the likelihood of meeting current diagnostic criteria in symptomatic children.
- To assess how the time elapsed since a previous Lyme disease diagnosis influences the diagnosis of acute Lyme disease.
Main Methods:
- Prospective enrollment of children evaluated for Lyme disease in emergency departments across eight Pedi Lyme Net centers.
- Defined Lyme disease cases by erythema migrans (EM) lesion or positive two-tier serology with compatible symptoms.
- Utilized generalized estimating equations to analyze the association between time from previous diagnosis and current Lyme disease diagnosis, adjusting for covariates.
Main Results:
- Of 2501 children, 126 (5.0%) had a history of definite or probable Lyme disease.
- Among those with prior Lyme disease, 37.3% met current diagnostic criteria (2 EM lesions, 45 positive serology).
- The likelihood of meeting current diagnostic criteria decreased significantly with increasing time since the previous Lyme disease diagnosis (aOR 0.62).
Conclusions:
- Approximately one-third of children with a history of Lyme disease met criteria for acute infection upon evaluation.
- The rate of meeting acute Lyme disease criteria declined over time from the previous diagnosis.
- Development of novel Lyme disease diagnostics is crucial for differentiating between acute and past infections.
Abstract:
A history of Lyme disease can complicate the interpretation of Lyme disease serology in acutely symptomatic patients. We prospectively enrolled children undergoing evaluation for Lyme disease in the emergency department of one of eight participating Pedi Lyme Net centers. We selected symptomatic children with a Lyme disease history (definite, probable, or none) as well as an available research biosample. We defined a Lyme disease case with either an erythema migrans (EM) lesion or positive two-tier serology with compatible symptoms. Using a generalized estimating equation, we examined the relationship between time from previous Lyme disease diagnosis and current Lyme disease after adjustment for patient demographics and symptoms as well as clustering by center. Of 2501 prospectively enrolled study patients, 126 (5.0%) reported a history of definite or probable Lyme disease. Of these children with previous Lyme disease, 47 met diagnostic criteria for Lyme disease at the time of enrollment (37.3%; 95% confidence interval [CI] 29.1-45.7%); 2 had an EM lesion, and 45 had positive two-tier Lyme disease serology. Over time from the previous Lyme disease diagnosis, the less likely the patient met diagnostic criteria for Lyme disease (adjusted odds ratio 0.62 per time period; 95% CI 0.46-0.84). For children with a history of Lyme disease before enrollment, one-third met the diagnostic criteria for acute Lyme disease with a declining rate over time from previous Lyme disease diagnosis. Novel Lyme disease diagnostics are needed to help distinguish acute from previous Lyme disease.
