TY - JOUR
T1 - Diagnostic parameters of cellular tests for Lyme borreliosis in Europe (VICTORY study)
T2 - a case-control study
AU - Baarsma, M. E.
AU - van de Schoor, Freek R.
AU - Gauw, Stefanie A.
AU - Vrijmoeth, Hedwig D.
AU - Ursinus, Jeanine
AU - Goudriaan, Nienke
AU - Popa, Calin D.
AU - ter Hofstede, Hadewych J. M.
AU - Leeflang, Mariska M. G.
AU - Kremer, Kristin
AU - van den Wijngaard, Cees C.
AU - Kullberg, Bart-Jan
AU - Joosten, Leo A. B.
AU - Hovius, Joppe W.
N1 - Funding Information: We thank the patient representatives associated with this project: Els Duba, Kees Niks, Gert van Dijk, and Koen van Kempen for their efforts in setting up this study (eg, design and choice of the tests to be studied) and their perspectives as patients during the study and analysis, which were greatly appreciated. We also thank the following colleagues for their valuable assistance in setting up or doing the study: Anna Tulen, Ingrid Friesema, Margriet Harms, Carla Nijhuis, Mark Jonker (National Institute for Public Health and the Environment, Bilthoven, Netherlands); Jasmin Ersöz, Dieuwertje Hoornstra, Marga Goris, Bregtje Lemkes, and Carolien Duetz (Amsterdam UMC, Amsterdam, Netherlands); Michelle Brouwer and Fidel Vos (Radboudumc, Nijmegen, Netherlands); Tizza Zomer, Yolande Vermeeren, Barend van Kooten, and Renske Wieberdink (Gelre Ziekenhuizen, Apeldoorn, Netherlands); and Henry de Vries, Jacqueline Woutersen, and Titia Heijman (GGD Amsterdam, Amsterdam, Netherlands). This study was funded by the Netherlands Organization for Health Research and Development (522050001), and cofunded by the Ministry of Health, Welfare and Sports of the Netherlands and by the charitable contributions raised by Rood voor Altijd and Minke Verstrepen, donated through the AMC Foundation (Amsterdam UMC). Neither the funding organisations or the participating commercial partners had any role in the design of the study, or the analysis and interpretation of data. JWH's work on an unrelated project was supported by a grant from the EU through the European Regional Development Fund and the Interreg North Sea Region Programme 2014–2020 as part of the NorthTick project (38-2-7-19). Funding Information: We thank the patient representatives associated with this project: Els Duba, Kees Niks, Gert van Dijk, and Koen van Kempen for their efforts in setting up this study (eg, design and choice of the tests to be studied) and their perspectives as patients during the study and analysis, which were greatly appreciated. We also thank the following colleagues for their valuable assistance in setting up or doing the study: Anna Tulen, Ingrid Friesema, Margriet Harms, Carla Nijhuis, Mark Jonker (National Institute for Public Health and the Environment, Bilthoven, Netherlands); Jasmin Ersöz, Dieuwertje Hoornstra, Marga Goris, Bregtje Lemkes, and Carolien Duetz (Amsterdam UMC, Amsterdam, Netherlands); Michelle Brouwer and Fidel Vos (Radboudumc, Nijmegen, Netherlands); Tizza Zomer, Yolande Vermeeren, Barend van Kooten, and Renske Wieberdink (Gelre Ziekenhuizen, Apeldoorn, Netherlands); and Henry de Vries, Jacqueline Woutersen, and Titia Heijman (GGD Amsterdam, Amsterdam, Netherlands). This study was funded by the Netherlands Organization for Health Research and Development (522050001), and cofunded by the Ministry of Health, Welfare and Sports of the Netherlands and by the charitable contributions raised by Rood voor Altijd and Minke Verstrepen, donated through the AMC Foundation (Amsterdam UMC). Neither the funding organisations or the participating commercial partners had any role in the design of the study, or the analysis and interpretation of data. JWH's work on an unrelated project was supported by a grant from the EU through the European Regional Development Fund and the Interreg North Sea Region Programme 2014–2020 as part of the NorthTick project (38-2-7-19). Publisher Copyright: © 2022 Elsevier Ltd
PY - 2022/9/1
Y1 - 2022/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85136303151&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S1473-3099(22)00205-5
DO - https://doi.org/10.1016/S1473-3099(22)00205-5
M3 - Article
C2 - 35714662
SN - 1473-3099
VL - 22
SP - 1388
EP - 1396
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 9
ER -