G Dobler1, K Kaier2, P Hehn2, M M Böhmer3, T M Kreusch4, J P Borde5. 1. Bundeswehr Institute of Microbiology, German National Reference Laboratory for TBEV, Munich, Germany. 2. Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Centre - University of Freiburg, Freiburg, Germany. 3. Bavarian Health and Food Safety Authority, Department of Infectious Disease Epidemiology & Taskforce Infectiology/Airport, Oberschleissheim, Germany. 4. Robert Koch Institute, Department of Infectious Disease Epidemiology, Immunization Unit, Berlin, Germany. 5. Division of Infectious Diseases, Department of Medicine II, University of Freiburg Medical Centre and Faculty of Medicine, Freiburg, Germany; Praxis Dr. J. Borde/Gesundheitszentrum Oberkirch, Oberkirch, Germany. Electronic address: johannes.borde@web.de.
Abstract
OBJECTIVES: There are few data available regarding the clinical course of tick-borne encephalitis virus (TBEV) vaccination breakthrough infections. The published studies suggest that vaccination breakthrough infections may have a more severe course than native TBEV infection in unvaccinated individuals-potentially due to antibody-dependent enhancement. Here we report a large analysis of vaccination breakthrough infections. METHODS: This retrospective analysis was based on a national surveillance dataset spanning the years 2001-2018. Variables reflecting disease severity, such as 'CNS symptoms', 'myelitis', 'fatal outcome' and 'hospitalization' were analysed as well as general epidemiological variables. Cases were categorized as 'unvaccinated' or 'ever vaccinated', the latter category including cases with at least one dose of a TBEV vaccine. RESULTS: A total of 6073 notified TBEV infection cases were included in our analysis. Sufficient data on vaccination status were available for 95.1% of patients (5777/6073); of these, 5298 presented with a native infection. A total of (334/5777) cases developed an infection despite having been vaccinated at least once. Comparing unvaccinated patients with those with at least one vaccination, we find an odds ratio (OR) 2.73, (95% confidence interval (CI) 0.79-9.50) regarding the variable fatal outcome that did not reach statistical significance. Analysing the clinical variables 'CNS symptoms' and 'myelitis', there is no difference between these groups (OR 0.86, 95% CI 0.68-1.08; and OR 1.30, 95% CI 0.74-2.27 respectively). Patients who were vaccinated and had an assumed protection at symptom onset (n = 100) had a higher risk for the development of myelitic symptoms (OR 2.21, 95% CI 1.01-4.86]) than unvaccinated patients. CONCLUSION: Our findings could neither verify that vaccination breakthrough infections might cause a more severe disease than native infections nor prove a clear antibody-dependent enhancement phenomenon. It remains unclear whether the increased myelitis risk in a subgroup of vaccinated patients is a true effect or confounded.
OBJECTIVES: There are few data available regarding the clinical course of tick-borne encephalitis virus (TBEV) vaccination breakthrough infections. The published studies suggest that vaccination breakthrough infections may have a more severe course than native TBEVinfection in unvaccinated individuals-potentially due to antibody-dependent enhancement. Here we report a large analysis of vaccination breakthrough infections. METHODS: This retrospective analysis was based on a national surveillance dataset spanning the years 2001-2018. Variables reflecting disease severity, such as 'CNS symptoms', 'myelitis', 'fatal outcome' and 'hospitalization' were analysed as well as general epidemiological variables. Cases were categorized as 'unvaccinated' or 'ever vaccinated', the latter category including cases with at least one dose of a TBEV vaccine. RESULTS: A total of 6073 notified TBEVinfection cases were included in our analysis. Sufficient data on vaccination status were available for 95.1% of patients (5777/6073); of these, 5298 presented with a native infection. A total of (334/5777) cases developed an infection despite having been vaccinated at least once. Comparing unvaccinated patients with those with at least one vaccination, we find an odds ratio (OR) 2.73, (95% confidence interval (CI) 0.79-9.50) regarding the variable fatal outcome that did not reach statistical significance. Analysing the clinical variables 'CNS symptoms' and 'myelitis', there is no difference between these groups (OR 0.86, 95% CI 0.68-1.08; and OR 1.30, 95% CI 0.74-2.27 respectively). Patients who were vaccinated and had an assumed protection at symptom onset (n = 100) had a higher risk for the development of myelitic symptoms (OR 2.21, 95% CI 1.01-4.86]) than unvaccinated patients. CONCLUSION: Our findings could neither verify that vaccination breakthrough infections might cause a more severe disease than native infections nor prove a clear antibody-dependent enhancement phenomenon. It remains unclear whether the increased myelitis risk in a subgroup of vaccinated patients is a true effect or confounded.
Authors: Benno Kohlmaier; Nina A Schweintzger; Manfred G Sagmeister; Vendula Švendová; Daniela S Kohlfürst; Astrid Sonnleitner; Manuel Leitner; Andrea Berghold; Erich Schmiedberger; Franz Fazekas; Alexander Pichler; Jana Rejc-Marko; Daniel Růžek; Lucie Dufková; Darina Čejková; Petr Husa; Martina Pýchová; Lenka Krbková; Václav Chmelík; Věra Štruncová; Dace Zavadska; Guntis Karelis; Aukse Mickiene; Joanna Zajkowska; Petra Bogovič; Franc Strle; Werner Zenz Journal: Microorganisms Date: 2021-06-30