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. 2022 Sep;22(9):1388-1396.
doi: 10.1016/S1473-3099(22)00205-5. Epub 2022 Jun 14.

Diagnostic parameters of cellular tests for Lyme borreliosis in Europe (VICTORY study): a case-control study

M E Baarsma  1 , Freek R van de Schoor  2 , Stefanie A Gauw  1 , Hedwig D Vrijmoeth  2 , Jeanine Ursinus  1 , Nienke Goudriaan  1 , Calin D Popa  3 , Hadewych Jm Ter Hofstede  2 , Mariska Mg Leeflang  4 , Kristin Kremer  5 , Cees C van den Wijngaard  6 , Bart-Jan Kullberg  2 , Leo Ab Joosten  2 , Joppe W Hovius  7
Affiliations

Diagnostic parameters of cellular tests for Lyme borreliosis in Europe (VICTORY study): a case-control study

M E Baarsma et al. Lancet Infect Dis. 2022 Sep.

Abstract

Background: Cellular tests for Lyme borreliosis might be able to overcome major shortcomings of serological testing, such as its low sensitivity in early stages of infection. Therefore, we aimed to assess the sensitivity and specificity of three cellular tests.

Methods: This was a nationwide, prospective, multiple-gate case-control study done in the Netherlands. Patients with physician-confirmed Lyme borreliosis, either early localised or disseminated, were consecutively included as cases at the start of antibiotic treatment. Controls were those without Lyme borreliosis from the general population (healthy controls) and those with potentially cross-reactive conditions (eg, autoimmune disease). We used three cellular tests for Lyme borreliosis (Spirofind Revised, iSpot Lyme, and LTT-MELISA) as index tests, and standard two-tier serological testing (STTT) as a comparator. Clinical data from Lyme borreliosis patients were collected at baseline and at 12 weeks after inclusion, and blood samples were obtained at baseline, 6 weeks, and 12 weeks. Control participants underwent clinical and laboratory assessments at baseline only.

Findings: Cases comprised 271 patients with Lyme borreliosis (of whom 245 had early-localised Lyme borreliosis and 26 had disseminated disease) and controls comprised 228 participants without Lyme borreliosis from the general population and 41 participants with potentially cross-reactive conditions. Recruitment occurred between May 14, 2018, and March 16, 2020. The specificity of STTT in healthy controls (216 of 228 samples [94·7%, 95% CI 91·5-97·7]) was higher than that of the cellular tests: Spirofind (140 of 171 [81·9%, 76·1-87·2]), iSpot Lyme (32 of 103 [31·1%, 21·5-40·3]) and LTT-MELISA (100 of 190 [52·6%, 44·9-60·3]). Cellular tests had varying sensitivities: Spirofind (88 of 204 [43·1%, 36·4-50·4]), iSpot Lyme (51 of 94 [54·3%, 44·5-63·7]), and LTT-MELISA (66 of 218 [30·3%, 23·8-36·7]). The Spirofind and iSpot Lyme outperformed STTT for sensitivity, but were similar to the C6-ELISA (C6-ELISA: 135 of 270 [50·0%, 44·5-55·5]; STTT: 76 of 270 [28·1%, 23·0-33·6]).

Interpretation: The cellular tests for Lyme borreliosis used in this study have a low specificity compared with serological tests, which leads to a high number of false-positive test results. We conclude that these cellular tests are unfit for clinical use at this stage.

Funding: Netherlands Organization for Health Research and Development, AMC Foundation (Amsterdam UMC), and Ministry of Health of the Netherlands.

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Conflict of interest statement

Declaration of interests The assays under study were supplied by AID/GenID (Strassberg, Germany), InVitaLab (Neuss, Germany), QIAGEN (Germantown, MD, USA), and Oxford Immunotec (Oxford, UK), either free of charge or at a reduced price; none of the authors have received any direct financial compensation from any of these companies for this project or any other project. MEB and JWH collaborate with Bio-Rad Laboratories, ZEUS Scientific, and Pfizer on unrelated projects on Lyme borreliosis. JWH collaborates with Antigen Discovery on unrelated projects on Lyme borreliosis; JWH has an application for a provisional patent related to Borrelia antigens pending. FRvdS and LABJ collaborate with Hycult Biotech on developing novel diagnostic tests for Lyme borreliosis. B-JK and LABJ are coinventors of the Spirofind, an experimental in-house assay for Lyme borreliosis, which is owned by Radboudumc and was licensed for development to Boulder Diagnostics (Boulder, Colorado, USA) and subsequently Oxford Immunotec (Oxford, UK) until 2018. The other authors report no competing interests.

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