Abstract
The diagnosis of Lyme borreliosis is challenging because of the often non-specific symptoms and persisting antibodies after infection. We investigated the diagnostic characteristics of two enzyme-linked immunosorbent assays (ELISAs) and an immunoblot for the detection of Borrelia-specific serum antibodies using different test strategies in individuals with and without antibiotic treatment for Lyme borreliosis. This retrospective study included healthy individuals, patients with active Lyme neuroborreliosis and patients treated for Lyme neuroborreliosis. Two ELISAs were compared: the C6 ELISA and the SERION ELISA. Equivocal and positive results were confirmed by immunoblot. We included 174 healthy individuals, of whom 27 (15.5%) were treated for Lyme borreliosis in the past, 36 patients were treated for Lyme neuroborreliosis and 27 patients had active Lyme neuroborreliosis. All the active Lyme neuroborreliosis patients were reactive in both ELISAs (100% sensitivity); less reactivity was seen in the other three groups (range 17.7% to 69.4%). The concordance between the ELISA results was high in active Lyme neuroborreliosis patients (26/27; 96.3%) and healthy individuals (131/147; 89.1%), but lower in treated healthy individuals (18/27; 66.7%) and treated Lyme neuroborreliosis patients (18/36; 50.0%) (p ≤ 0.005). This study showed that antibiotic treatment against Lyme borreliosis was strongly associated with discordant ELISA and test strategy results (odds ratio: 10.52; p < 0.001 and 9.98; p = 0.014, respectively) suggesting antibiotic treatment influences the pace at which the various antibodies directed to the different antigens used in both ELISAs wane. Among treated neuroborreliosis patients, the SERION ELISA stayed positive for a longer period after infection compared to the C6 ELISA. This should be taken into consideration when requesting and/or interpreting Lyme serology.
Highlights
The recommended approach for the diagnosis of Lyme borreliosis consists of screening for Borrelia-specific serum antibodies with an enzyme-linked immunosorbent assay (ELISA), followed by immunoblot confirmation of equivocal or positive enzyme-linked immunosorbent assays (ELISAs) results [1]
Patients who had been diagnosed and treated for Lyme neuroborreliosis between February 2004 and September 2012 were enrolled from March 2013 to March 2015; active Lyme neuroborreliosis patients were recruited from December 2010 to December 2015 and were only included if they had not yet started antibiotic treatment for Lyme neuroborreliosis
High concordances between the results of the test strategies were found for healthy individuals and active Lyme neuroborreliosis patients groups; low concordances were observed for Lyme neuroborreliosis patients and healthy individuals who had been treated for Lyme borreliosis in the past
Summary
The recommended approach for the diagnosis of Lyme borreliosis consists of screening for Borrelia-specific serum antibodies with an enzyme-linked immunosorbent assay (ELISA), followed by immunoblot confirmation of equivocal or positive ELISA results [1]. In the Dutch population, the seroprevalence is 4–8%, but is higher in certain risk groups, such as forestry workers (20%) [5, 6] These seropositive cases are usually asymptomatic, suggesting a cleared infection with the persistence of Borrelia-specific serum antibodies. Some assays make use of whole-cell lysates, which are mostly derived from cultured Borrelia burgdorferi sensu stricto, Borrelia afzelii or Borrelia garinii [7, 8] These assays have a potential problem of higher cross-reactivity with common antigens of other micro-organisms [9]. A third test strategy was included and consisted of a more unconventional approach based on the combination of both ELISAs as a screening test and immunoblot confirmation of all results, except concordant negative results
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