Schotthoefer, Anna M.

ABSTRACT Current laboratory testing for Lyme disease (LD) relies on serology. We evaluated the performance of standard two-tiered testing (STTT) and modified two-tiered testing (MTTT) algorithms using samples obtained from well-characterized patients with early LD in the U.S. East Coast and Upper Midwest. Participants with signs and symptoms of early LD (cases) and controls were enrolled by Lyme Disease Biobank. We compared the performance of four FDA-cleared STTT or MTTT algorithms using serum samples from 251 participants (107 cases, 69 with a convalescent draw; 144 endemic controls). At the initial blood draw, algorithm sensitivity ranged from 22% to 36%, with specificity ranging from 98% to 100%. MTTT algorithms showed higher sensitivity compared with STTT algorithms ( P ≤ 0.05). One STTT algorithm was less sensitive than the other ( P = 0.035), and there was no significant difference in sensitivity between MTTT algorithms. There was also discordance between algorithms; only 22 of the 45 samples classified as laboratory confirmed by Lyme Disease Biobank testing were positive using all algorithms evaluated. Likelihood of positive two-tiered serology among cases with a suspected erythema migrans (EM) skin lesion increased with longer lesion duration and/or when presenting with >1 constitutional symptom. Participants with suspected EM without constitutional symptoms were unlikely to test positive by any algorithm evaluated. Testing convalescent samples did not improve LD detection, and seroconversion was rare. While MTTT confirmed more early LD cases than STTT, all two-tiered algorithms evaluated were insensitive in this population. Novel diagnostics that improve laboratory confirmation for early LD are urgently needed. IMPORTANCE This study confirms that two-tiered serologic testing algorithms are insensitive in early Lyme disease, particularly within the first 2 weeks after symptom onset or when erythema migrans is not accompanied by constitutional symptoms. It also demonstrates that seroconversion is rare after antibiotic treatment. These results highlight the need for novel diagnostics for early Lyme disease that do not rely on serologic testing.

Abstract Background Lyme disease, the most common tickborne disease in the United States, may be prevented by taking a single 200-mg dose of oral doxycycline after a high-risk bite from a blacklegged tick. Currently, it is not known how Lyme disease post-exposure prophylaxis (PEP) might vary by region and healthcare system. We identified single-dose doxycycline medication orders in three healthcare systems in states with high incidence of Lyme disease and compared associated patient and provider characteristics. Methods Electronic health record data during 2012 – 2016 were obtained from three healthcare systems: Geisinger (Pennsylvania), Marshfield Clinic (Wisconsin), and Mayo Clinic (Minnesota/Wisconsin). Creation of analytic variables and analysis were harmonized across the three sites. Medication orders for single-dose doxycycline ≤200 mg that were accompanied by specific key words or diagnostic codes (e.g., tick bite; Lyme disease prevention) were considered evidence of PEP. Manual chart review was performed from a random subset to evaluate the algorithms used to identify PEP. Results Among 2,937,585 patients with at least one medication order or clinical encounter during the study period, 14,102 single-dose doxycycline orders for Lyme disease PEP for 13,172 unique patients were identified. The typical patient receiving PEP was older (mean age 51 – 58 years), male (56 – 59%), and non-Hispanic White (81 – 98%). The annual seasonality of medication orders was bimodal, with peaks occurring during April – July and October – November. The most common encounter setting was an outpatient clinic or urgent care center (80 – 91%); medication orders after patient phone calls in the absence of an in-person visit occurred frequently (14 – 19%) in two health systems. Chart abstractions (n=600) revealed instances of PEP prescribed inappropriately (e.g., bite from a non-blacklegged tick; patient with symptoms of acute Lyme disease). Conclusion Lyme disease PEP with a single dose of doxycycline was frequently prescribed in healthcare systems where there is a high incidence of Lyme disease. PEP was most commonly prescribed to non-Hispanic Whites over the age of 50 years. Public health initiatives for tickborne disease prevention should include clinician education on the appropriate use of Lyme disease PEP. Disclosures Anna M. Schotthoefer, PhD, HelixBind (Other Financial or Material Support, salary support) John Zeuli, PharmD, INSMED (Other Financial or Material Support, honoraria for educational speaking)

Lyme disease (LD) is an increasing public health problem. Current laboratory testing is insensitive in early infection, the stage at which appropriate treatment is most effective in preventing disease sequelae. The Lyme Disease Biobank (LDB) collects samples from individuals with symptoms consistent with early LD presenting with or without erythema migrans (EM) or an annular, expanding skin lesion and uninfected individuals from areas of endemicity. Samples were collected from 550 participants (298 cases and 252 controls) according to institutional review board-approved protocols and shipped to a centralized biorepository.