Recent changes to testing methods and case definitions impact our knowledge of Lyme disease in North Carolina

December 13, 2024

By UNC Institute for Global Health and Infectious Diseases

Many cases of Lyme disease are under-recognized because early symptoms – typically fever, fatigue and achiness, are common in many other illnesses. At the same time, testing is fraught with pitfalls, including poor sensitivity early in the course of disease and complicated algorithms that often are misinterpreted. While historically considered a low-incidence state, North Carolina has reported an increasing number of cases over the past decade, particularly in the Blue Ridge Mountains region, where some northwestern counties are experiencing rates similar to New England states.

A new study from Ross Boyce, MD, assistant professor of infectious diseases and epidemiology, with first author Gayoung Lee, MPH, a recent graduate of the Applied Epidemiology MPH program at the Gillings School of Global Public Health and partners at the North Carolina Division of Public Health, looked at how introduction of a new testing approach – known as the modified two-tier testing (MTTT) – along with updated case definitions, impacted surveillance and reporting of Lyme disease in North Carolina between 2017 and 2023. The findings show that a greater proportion of cases were classified as confirmed – rather than probable, following these changes – published in Clinical Infectious Diseases.

“There’s a lot more confirmed (as opposed to probable) cases, which means we feel more certain about the diagnosis, which could ultimately shift us into the CDC’s ‘high incidence’ category in the coming years,” said Boyce.

Diagnostics have traditionally relied on a series of two blood tests performed sequentially, starting with an enzyme immunosorbent assay (EIA) that looks for antibodies to the bacteria that cause Lyme disease. The Western blot is the second test, which is labor intensive and uses electricity to split certain proteins in the blood into patterns that are compared to the pattern in people known to have Lyme disease. But these are not always dependable, particularly in early disease and not all labs have the same standards.

Changes to Testing Methods

In August 2019, the Centers for Disease Control and Prevention endorsed a MTTT algorithm that replaced the immunoblot with a second EIA, providing comparable or better sensitivity early in the disease course, reducing turnaround time and lowering costs. Then in January 2022, the Council of State and Territorial Epidemiologists (CSTE) – which establishes case definitions for public health reporting – revised the criteria for Lyme disease to include the MTTT as confirmatory laboratory evidence, while also narrowing the clinical criteria used in low-incidence jurisdictions to only patients with objective evidence of infection.

Designing the Study

In response, the team designed a study to evaluate the impact of this alternative diagnosing method and its inclusion in updated Lyme disease case definitions in North Carolina, analyzing surveillance data from 2017–2023. Using Lyme disease cases in North Carolina – reported to the Electronic Disease Surveillance System (EDSS), which are classified as confirmed, probable or suspected cases according to the CSTE case definition –the team examined trends in testing utilization and case classifications.

The team found that from January 2017 to December 2023, a total of 2,861 Lyme disease cases were reported to with relatively stable annual incidence. After revision of the Lyme disease case definition and introduction of  modified testing options, the team observed that a greater proportion of cases were being diagnosed using MTTT, representing more than 70% of cases. This resulted in a significant shift from probable to confirmed classifications in the post-MTTT period.

“After the incorporation of the MTTT into the surveillance system, we observed a significant shift from probable to confirmed cases, demonstrating its effectiveness in Lyme disease surveillance,” said Lee. “This research highlights the reliability and accuracy of the MTTT in capturing emerging trends in Lyme disease in low-incidence states.”

In a low-incidence jurisdiction like North Carolina, where Lyme disease is rapidly emerging, regulatory approval, increased use, and incorporation of MTTT into public health surveillance systems are leading to more cases being classified as confirmed. These changes result in a higher level of confidence in the validity of reporting, with more accurate and reliable estimates of Lyme disease transmission in the state. The shift to a greater proportion of cases being classified as confirmed may also affect how the state is considered for surveillance purposes, given that the CDC distinguishes high-versus low-incidence jurisdictions based on the incidence of confirmed cases over the preceding three years.