In memory of Christian Kunz (1927 – 2020)

Considered a pioneer of virology in Austria, Christian Kunz’s interest in scientific research awoke in the 1950s and was supported by study visits to the then German strongholds for virology – Freiburg, Tübingen and Marburg. His early publications received international attention and earned him a grant from the Rockefeller Foundation to continue his research at Rockefeller Laboratories in New York. The experiences at research institutes and contacts with outstanding international scientists significantly shaped his further career.

Back in Vienna, he established the Institute of Virology with a research focus on arthropodborne diseases and especially TBE – by far the most common virus-related disease of the central nervous system in endemic areas.

He was engaged intensively in virus diagnostics, basic medical virology, and the life cycle of the TBE virus in nature. Also, TBE-endemic areas throughout Austria were identified. He finally used all his knowledge to develop a highly effective vaccine against TBE, initially in cooperation with an English research institute and later with the Austrian pharmaceutical company IMMUNO.

The vaccine was first licensed in 1976 and ever since, the broad use of the vaccine in Austria has led to an impressive reduction of the TBE burden of disease. Prof. Kunz was a founding member and for many years Chairman of the ‘European Group for Rapid Virus Diagnosis’, which became the ‘European Society for Clinical Virology’ in 1997, an association of leading medical virologists from across Europe, who focussed primarily on the development of new methods for early detection of viral infections.

He was awarded the Loeffler-Frosch-Medal of the International Society of Virology for his outstanding achievements for the development of Virology in German-speaking countries. We deeply appreciate Christian Kunz’s scientific achievements and editors and publisher dedicate the 3rd Edition of “The TBE Book” (2020) to him in commemoration.

Franz X. Heinz,
Center for Virology,
Medical University of Vienna

Content

List of Contributing Authors

Introduction
Gerhard Dobler, Wilhelm Erber, Michael Bröker, Lidia Chitimia-Dobler and Heinz-Josef Schmitt – Editors

Chapter 1: A short history of TBE
Olaf Kahl, Vanda V. Pogodina^†, Tatjana Poponnikova, Jochen Süss and Vladimir I. Zlobin

Chapter 2a: Virology
Daniel Růžek, Kentaro Yoshii, Marshall E. Bloom and Ernest A. Gould

Chapter 2b: The molecular and antigenic structure of TBEV
Franz-Xaver Heinz and Karin Stiasny

Chapter 3: Transmission / natural cycle
Lidia Chitimia-Dobler, Ute Mackenstedt and Olaf Kahl

Chapter 4: Pathogenesis of TBE with a focus on molecular mechanisms
Andrea Kröger and Anna K. Överby

Chapter 5: TBE in adults
Johannes P. Borde and Joanna Zajkowska

Chapter 6: TBE in children
Malin Veje and Mikael Sundin

Chapter 7: TBE in special clinical situations
Gerhard Dobler and Igor Stoma

Chapter 8: TBE in animals
Martin Pfeffer, Hannah M. Schmuck and Michael Leschnik

Chapter 9: Immunology of TBEV infection
Sara Gredmark-Russ and Renata Varnaite

Chapter 10: Diagnosis
Gerhard Dobler

Chapter 11: General epidemiology of TBE
Gerhard Dobler and Sergey Tkachev

Chapter 12a: TBE-epidemiology by country – an overview
Wilhelm Erber, Heinz-Josef Schmitt and Tamara Vuković-Janković

Chapter 12b: TBE by country – country data

Austria: Karin Stiasny and Judith H. Aberle
Belarus: Volha Kniazeva, Wilhelm Erber and Tamara Vuković-Janković
Belgium: Marjan Van Esbroeck, Tinne Lernout, Vanessa Suin and Steven Van Gucht
Bosnia and Herzegovina: Wilhelm Erber and Tamara Vuković-Janković
Bulgaria: Iva Christova
China: Yang Junfeng and Heinz-Josef Schmitt
Croatia: Wilhelm Erber and Tamara Vuković-Janković
Czech Republic: Petr Pazdiora
Denmark: Anders Fomsgaard
Estonia: Kuulo Kutsar
Finland: Anu Jääskeläinen and Heidi Åhman
France: Yves Hansmann and Aurélie Velay
Germany: Gerhard Dobler and Ute Mackenstedt
Hungary: Anna Nagy, Ferenc Schneider, Eszter Mezei and András Lakos
Italy: Valentina Tagliapietra, Flavia Riccardo, Martina Del Manso and Giovanni Rezza
Japan: Kentaro Yoshii
Kazakhstan: Andrey Dmitrovskiy
Kyrgyzstan: Wilhelm Erber
Latvia: Dace Zavadska and Zane Freimane
Lithuania: Auksė Mickienė
Moldova: Wilhelm Erber and Tamara Vuković-Janković
Mongolia: Tserennorov Damdindorj, Uyanga Baasandagva, Uranshagai Narankhuu, Tsogbadrakh Nyamdorj, Burmaajav Badrakh and Burmaa Khoroljav
Netherlands: Johannes H. J. Reimerink, Hein Sprong, Margriet Harms and Chantal B.E.M. Reusken
Norway: Katrine M. Paulsen, Rose Vikse, Arnulf Soleng, Kristin S. Edgar, Heidi E.H. Lindstedt, Dagny C.H. Dorenberg, Berit Sofie Wiklund and Åshild K. Andreassen
Poland: Katarzyna Pancer and Włodzimierz Gut
Romania: Lidia Chitimia-Dobler, Adriana Hristea, Wilhelm Erber and Tamara Vuković-Janković
Russia: Vladimir I. Zlobin, Maria Esyunina and Maria Syrochkina
Serbia: Vladimir Petrović, Elizabeta Ristanović and Aleksandar Potkonjak
Slovakia: Jana Kerlik
Slovenia: Zoran Simonović and Tamara Vuković-Janković
South Korea: Song Joon Young
Sweden: Åke Lundkvist
Switzerland and Liechtenstein: Daniel Desgrandchamps and Klara M. Pósfay-Barbe
Ukraine: Igor Nebogatkin, Olga Onishchuk, Oleksandr Hnatiuk, Wilhelm Erber and Tamara Vuković-Janković
United Kingdom: Maya Holding, Heinz-Josef Schmitt and Gillian Ellsbury

Chapter 12c: Global distribution of the TBEV
Gerhard Dobler, Wilhelm Erber and Heinz-Josef Schmitt

Chapter 13: TBE as a matter of public health
Michael Kunze, Wilhelm Erber and Martin Haditsch

Chapter 14: TBE-Prevention: Vaccines and Immunoglobulins
Eva Maria Pöllabauer and Herwig Kollaritsch

List of contributing authors

(in alphabetical order)

Prof. Dr. Judith H. Aberle,
Center for Virology, Medical University of Vienna, Austria

Dr. Heidi Åhman,
Senior Manager Medical Lead Finland & Baltics, Pfizer Vaccines, Helsinki, Finland

Prof. Dr. Åshild Andreassen,
Norwegian Institute of Public Health, Division for Infection Control and Environmental Health, Oslo, Norway

Dr. Uyanga Baasandagva,
Epidemiologist, National Center for Zoonotic Diseases, Ulaanbaatar, Mongolia

Prof. Dr. Burmaajav Badrakh,
Scientific Secretary of the Mongolian Academy of Medical Sciences and Head of Public Health Department of “Ach” Medical University, Ulaanbaatar, Mongolia

Dr. Marshall E. Bloom,
National Institutes of Health, Laboratory of Virology, Rocky Mountain Laboratories, Hamilton, MT, USA

Priv.-Doz. Dr. Johannes P. Borde,
Praxis Dr. J. Borde, Gesundheitszentrum Oberkirch, Germany
Department of Medicine II, Division of Infectious Diseases, Medical Center – University of Freiburg, Germany

Dr. Michael Bröker,
Editor, Global Health Press, Singapore / Marburg, Germany

Dr. Lidia Chitimia-Dobler,
Bundeswehr Institute of Microbiology, Munich, Germany

Prof. Dr. Iva Christova,
Department of Microbiology, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria

Dr. Tserennorov Damdindorj,
Scientific secretary in National Center for Zoonotic Diseases, Ulaanbaatar, Mongolia

Dr. Martina Del Manso,
Department of Infectious Diseases, Istituto Superiore di Sanità, Roma, Italy

Dr. med. Daniel Desgrandchamps,
Pediatric Infectious Diseases, Scientific Consulting Daniel Desgrandchamps, Rotkreuz, Switzerland

Prof. Andrey Dmitrovskiy,
National Scientific Center for Extremely Dangerous Infections, Almaty, Kazakhstan

Prof. Dr. Gerhard Dobler,
Bundeswehr Institute of Microbiology, Munich, Germany

Dr. Dagny Cathrine Haug Dorenberg,
Norwegian Institute of Public Health, Division for Infection Control and Environmental Health, Oslo, Norway

B.Sc. Kristin Skarsfjord Edgar,
Norwegian Institute of Public Health, Division for Infection Control and Environmental Health, Oslo, Norway

Dr. Gillian Ellsbury,
Medical Director, Vaccines UK & Ireland, Pfizer Vaccines, Tadworth, United Kingdom

Dr. Wilhelm Erber,
Director Medical and Scientific Affairs, Pfizer Vaccines, Vienna, Austria

Dr. Maria Sergeevna Esyunina,
Regional Medical Advisor, Vaccines, Pfizer Innovations LLC, Moscow, Russia

Dr. Anders Fomsgaard,
Virus R&D Laboratory, Statens Serum institute, Copenhagen, Denmark
Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark

Dr. Zane Freimane,
Riga Stradins University, Riga, Latvia

Dr. Ernest A. Gould,
Aix-Marseille Université, Marseille, France

Dr. Sara Gredmark-Russ,
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Prof. Dr. Wlodzimierz Gut,
Department of Virology, National Institute of Public Health-NIH (NIPH-NIH), Warsaw, Poland

Prof. Dr. Dr. Martin Haditsch,
Medical Head, Labor Hannover MVZ, Hannover, Germany; TravelMedCenter Leonding, Austria

Dr. Yves Hansmann,
Infectious Disease Department, Strasbourg University Hospital, Strasbourg, France

M.Sc. Margriet Harms,
National Institute for Public Health and the Environment, Bilthoven, the Netherlands

Prof. Dr. Franz-Xaver Heinz,
Center for Virology, Medical University of Vienna, Austria

Oleksandr Hnatiuk
Epidemiologist, SI Volyn Regional Laboratory Center of the Ministry of Health of Ukraine, Kiev, Ukraine

Dr. Maya Holding,
Virology and Pathogenesis Group, National Infection Service, Public Health England, Porton Down, United Kingdom NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom

Ass. Prof. Adriana Hristea,
National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania

Dr. Anu Jääskeläinen,
Department of Virology, Medicum, University of Helsinki, Helsinki, Finland
Helsinki University Hospital, Laboratory Services (HUSLAB), Department of Clinical Microbiology, Helsinki, Finland

Dr. Olaf Kahl,
tick-radar GmbH, Berlin, Germany

Dr. Jana Kerlik,
Department of Epidemiology, Regional Public Health Authority in Banská Bystrica, Slovakia

Dr. Burmaa Khoroljav,
Department of Epidemiology, National Center for Zoonotic Disease, Ulaanbaatar, Mongolia

Dr. Volha Kniazeva,
Republican Research and Practical Center for Epidemiology and Microbiology. Minsk, Belarus

Prof. Dr. Herwig Kollaritsch,
Institute for Specific Prophylaxis and Tropical Medicine, Medical University Vienna, Austria

Prof. Dr. Andrea Kröger,
Institute of Medical Microbiology, Otto-von-Guericke-University, Magdeburg, Germany

Prof. Dr. Michael Kunze,
Center for Public Health, Institute of Social Medicine, Medical University Vienna, Austria

Dr. Kuulo Kutsar,
Health Board, Tallinn, Estonia

Dr. András Lakos,
Centre for Tick-borne Diseases, Outpatient Service, Budapest, Hungary

Dr. Tinne Lernout,
Epidemiology of Infectious Diseases, Epidemiology and Public Health Directorate, Sciensano, Brussels, Belgium

Priv.-Doz. Dr. Michael Leschnik,
Clinical Unit of Internal Medicine Small Animals, Department and Clinic of Companion Animals and Horses,
University of Veterinary Medicine Vienna, Austria

Heidi Elisabeth H. Lindstedt,
Senior Adviser, Norwegian Institute of Public Health, Division of Infection Control and Environmental Health, Oslo, Norway

Prof. Dr. Åke Lundkvist,
Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden

Prof. Dr. Ute Mackenstedt,
Department of Parasitology, University of Hohenheim, Stuttgart, Germany

MScPH Eszter Mezei,
National Public Health Center, Department of Epidemiology and Infection Control, Budapest, Hungary

Prof. Dr. Auksė Mickienė,
Department of Infectious Diseases, Medical Academy of the Lithuanian University of Health Sciences, Kaunas, Lithuania

Dr. Anna Nagy,
National Reference Laboratory for Viral Zoonoses, National Public Health Center, Budapest, Hungary

Dr. Uranshagai Narankhuu,
Department of Epidemiology, National Center for Zoonotic Disease, Ulaanbaatar, Mongolia

Dr. Igor Nebogatkin,
I.I. Schmalhausen Institute of Zoology of the National Academy of Sciences of Ukraine (NASU), Kiev, Ukraine
SI Public Health Centre of the Ministry of Healthcare of Ukraine, Kiev, Ukraine

Dr. Tsogbadrakh Nyamdorj,
Director, National Center for Zoonotic Diseases, Ulaanbaatar, Mongolia

Assoc. Prof. Dr. Anna K. Överby,
Department of Clinical Microbiology, Virology, Umeå University, Sweden
The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå, Sweden

Olga Onishchuk,
Epidemiologist, Manevychi interdistrict department of the SI Volyn Regional Laboratory Center of the Ministry of Health of Ukraine, Kiev, Ukraine

Dr. Katarzyna Pancer,
Department of Virology, National Institute of Public Health-NIH (NIPH-NIH), Warsaw, Poland

Dr. Katrine M. Paulsen,
Senior Adviser Microbiology, TINE SA, Molde, Møre og Romsdal, Norway

Prof. Dr. Petr Pazdiora,
Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic

Prof. Dr. Vladimir Petrović,
Institute of Public Health of Vojvodina, Novi Sad, Serbia

Prof. Dr. Martin Pfeffer,
Institute of Animal Hygiene and Veterinary Public Health, Center for Veterinary Public Health, Faculty of Veterinary Medicine, University of Leipzig, Germany

Dr. Eva-Maria Pöllabauer,
Institute of Specific Prophylaxis and Tropical Medicine, Medical University Vienna, Austria

Prof. Vanda Vatslavovna Pogodina†,
Ministry of Science and Higher Education of the Russian Federation, Moscow, Russia
Federal State Budgetary Scientific Institution, Moscow, Russia
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow, Russia († passed away in early 2020)

Prof. Tatjana Poponnikova,
Department of Neurology, Neurosurgery and Medical Genetics, Kemerovo State Medical University, Russian Federation

Prof. Dr. Klara M. Pósfay-Barbe,
Department of Pediatrics, Children’s Hospital of Geneva, University Hospitals of Geneva, Switzerland

Prof. Dr. Aleksandar Potkonjak,
Department of Veterinary Medicine, Faculty of Agriculture, University of Novi Sad, Serbia

Bsc. Johannes Hermanus Jozef Reimerink,
National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands

Dr. Chantal B.E.M. Reusken,
National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands

Dr. Giovanni Rezza,
Department of Infectious Diseases, Istituto Superiore di Sanità, Roma, Italy

Dr. Flavia Riccardo,
Department of Infectious Diseases, Istituto Superiore di Sanità, Roma, Italy

Prof. Dr. Elizabeta Ristanović,
Military Medical Academy, Belgrade, Serbia

Assoc. Prof. Dr. Daniel Růžek,
Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, České Budějovice, Czech Republic
Veterinary Research Institute, Brno, Czech Republic

Prof. Dr. Heinz-Josef Schmitt,
Editor-in-Chief, Global Health Press, Singapore
Strategic and Scientific Advisor, “Vaccelerate” European Clinical Trial Consortium, Cologne University, Germany

Ph.D.-student Hannah M. Schmuck,
Institute of Animal Hygiene and Veterinary Public Health, Center for Veterinary Public Health, Faculty of Veterinary Medicine, University of Leipzig, Germany

Dr. Ferenc Schneider,
Department of Infectious Diseases, Markusovszky Teaching Hospital, Szombathely, Hungary

Dr. Zoran Simonović,
National Institute of Public Health, Maribor, Slovenia

Dr. Arnulf Soleng,
Norwegian Institute of Public Health, Division for Infection Control and Environmental Health, Oslo, Norway

Prof. Song Joon Young,
Korea University College of Medicine, Seoul, South Korea

Dr. Hein Sprong,
National Institute for Public Health and the Environment, Bilthoven, the Netherlands

Prof. Dr. Karin Stiasny,
Center for Virology, Medical University of Vienna, Austria

Dr. Igor Stoma,
Belarusian State Medical University, Minsk, Belarus

Dr. Vanessa Suin,
Quality coordinator, Clinique Saint Pierre Ottignies, Ottignies, Belgium

Dr. Mikael Sundin,
Division of Paediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden

Prof. Dr. Jochen Süss,
Tick Information Center, Lippersdorf, Germany

Dr. Maria Syrochkina,
Pfizer Vaccines, Moscow, Russia

Dr. Valentina Tagliapietra,
Research and Innovation Centre, Fondazione Edmund Mach, San Michele all’Adige, Italy

Dr. Sergey E. Tkachev,
Research Center “Regulatory Genomics” of Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia

Dr. Marjan Van Esbroeck,
National Reference Center for Arboviruses, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium

Dr. Steven Van Gucht,
Viral Diseases, Infectious Diseases in Humans Directorate, Sciensano, Brussels, Belgium

M.Sci. Renata Varnaite,
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Dr. Malin Veje,
Department of Infectious Diseases, University of Gothenburg , Sweden

Dr. Aurélie Velay,
Institute of Virology, Strasbourg University Hospital, Strasbourg, France

Dr. Rose Vikse,
Norwegian Institute of Public Health, Division for Infection Control and Environmental Health, Oslo, Norway

Dr. Tamara Vuković-Janković,
Senior Medical Manager, Medical and Scientific Affairs, International Developed Markets Pfizer, Belgrade, Serbia

Mpharm Berit Sofie Wiklund,
Norwegian Institute of Public Health, Division for Infection Control and Environmental Health, Oslo, Norway

Dr. Yang Junfeng,
Medical Affairs, Pfizer Investment Co., Ltd., Beijing, China

Dr. Kentaro Yoshii,
Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan

Prof. Dr. Joanna Zajkowska,
Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, Poland

Assoc. Prof. Dace Zavadska,
Department of Paediatrics, Riga Stradins University, Riga, Latvia
Department of Children Infectious Diseases, Children Clinical University Hospital, Riga, Latvia

Prof. Elyes Zhioua,
Department of Parasitology, Institute Pasteur of Tunisia, Tunis, Tunisia

Prof. Vladimir Igorevich Zlobin,
Irkutsk State Medical University, Ministry of Public Health of Russian Federation, Irkutsk, Russian Federation

Introduction to the 1st edition

Dear Reader,

While the number of vector-borne diseases and their incidence in Europe is much less than in tropical and/or developing countries, there are, nevertheless, a substantial number of such infections in Europe. The most important one is the zoonotic arbovirus infection Tick-Borne Encephalitis (TBE), a virus transmitted to humans by ticks or by consumption of unpasteurized dairy products from infected cows, goats, or sheep.

TBE is endemic in the non-tropical Eurasian forest belt with most cases occurring in Russia and in central and eastern parts of Europe. In endemic areas, TBE is one of the most important causes of viral meningitis/encephalitis and a major public health concern. Moreover, TBE is becoming more and more frequent in Europe due to the appearance of new endemic areas and increasing awareness.

However, it might be difficult to diagnose TBE, because clinical manifestations tend to be relatively nonspecific. Although a standardized case definition across the European Union has existed now for a few years, national implementation of TBE programs, including regular screening and diagnosis, are done in only very few countries. Therefore, wide differences in the intensity and quality of national surveillance of TBE cases still exist, and the true burden of disease and the areas with circulation of the TBE viral subtypes in Europe and Asia are not fully known. Moreover, although safe and effective vaccines are available, vaccination uptake in most endemic countries is too low to reduce the TBE burden significantly.

We therefore have tried to compile in this “working book” the most recent and relevant aspects of TBE. Digital technology allows us to continuously review and update the information in the e-book version almost in real time. Therefore, with the publication of this book, all authors and editors, as well as the publisher will continue to provide the best and latest data and the most current insights pertinent to the field of TBE. With this in mind, we urge all readers to communicate to us any news, comments, or scientific input that may be relevant to patients, their physicians, or decision makers.

The editors thank all authors, Global Health Press (GHP) and Thomas Gegeny (Engage Scientific) for their excellent work, contributions, and input.

Priv.-Doz. Dr. G. Dobler, Dr. W. Erber, Prof. Dr. H.J. Schmitt – Editors

Introduction to the 2nd edition

We thank the publisher, all authors, contributors and readers of the TBE-Book who made this such a big success resulting in the need for a second edition within less than one year! Here we present the new edition with some corrections, modifications, one full new chapter, and relevant updates particularly in the epidemiology chapters as well as an improved printing size which allows using larger fonts for easier readability. As before, the TBE Book is also available online and we encourage our readers to join the “TBE-family” under the link below which gives access to all chapters and all updates, access to the monthly newsletter and the weekly snapshots and which helps to exchange relevant information: https://id-ea.org/tbe

We also welcome Dr. Michael Bröker as the fourth Editor – already known to our online readers as the Editor of our monthly newsletter and weekly snapshot.

The editors thank all authors and Global Health Press (GHP) for their excellent work, contributions and input.

Munich (Germany), Vienna (Austria), Marburg (Germany), Collegeville, PA (USA), April 2019
Priv.-Doz. Dr. Gerhard Dobler, Dr. Wilhelm Erber, Dr. Michael Bröker, Prof. Dr. Heinz-Josef Schmitt

Introduction to the 3rd edition

We are grateful to the publisher and to all authors who support us with this 3rd “online only” edition of THE-TBE-Book. We requested from authors any relevant scientific updates, particularly for chapter 12b (TBE in countries), in order to make the latest number of TBE cases diagnosed publicly available.

Munich (Germany), Vienna (Austria), Marburg (Germany), Collegeville, PA (USA), May 2020
Prof. Dr. Gerhard Dobler, Dr. Wilhelm Erber, Dr. Michael Bröker, Prof. Dr. Heinz-Josef Schmitt

Introduction to the 4th edition

Working in the field of infectious diseases in 2020 meant to devote all available resources to focus on protecting, diagnosing and treating almost 8 billion humans on the globe against COVID19. While many airborne diseases like influenza and RSV-infections as well as travel-related infections virtually disappeared due to various restrictions and hygiene measures, TBE cases increased at least in central Europe. This is now all reflected in this updated edition of THE TBE BOOK.

With all this in mind, we thank all country-authors who worked hard to provide us with the local 2020 TBE case numbers – often against the odds and often by working even more extra-hours. Their efforts are much appreciated! We are also indebted to the wonderful team at Global Health Press who again collected, formatted and put all new data as well as many “small” changes together in a publicly available online-format.

Munich (Germany), Vienna (Austria), Marburg (Germany), Collegeville, PA (USA), May 2021
Prof. Dr. Gerhard Dobler, Dr. Wilhelm Erber, Dr. Michael Bröker, Prof. Dr. Heinz-Josef Schmitt

Introduction to the 5th edition

During this spring of 2022, the reported number of COVID-19 cases has decreased to very low levels. Nevertheless, as pointed out in 2021, many infectious disease specialists, microbiologists and public health experts, are still heavily involved in work related to this pandemic. But even against these odds of limited available capacity by researchers, we again were able to capture the 2021 TBE cases reported from most of the affected countries in Eurasia. New publications on vaccine effectiveness, optimal vaccination schedules and epidemiology have come up, but we will only cover this in the next (6th) edition planned for May 2023, once the full picture has become available.

In this 5th edition, we want to highlight to the readers, particularly travelers and travel medicine advisors:

Each country has different methods of detecting and reporting TBE cases, so the data in Chapter 12 must be interpreted cautiously, as they are minimal numbers only.
No single country reports “true TBE incidence data” as nowhere the completeness of testing has been documented and as the impact of vaccine uptake has never been systematically considered anywhere.
As a result of (first) testing, Tunisia (!) is now on the list of TBE-endemic countries, whereas the situation remains unclear for other Mediterranean countries due to a lack of appropriate surveillance.
The impact of climate change and weather factors remain totally unclear as consistent testing for cases has never been established and as many factors may theoretically influence case numbers, most of which were never captured in a scientifically reproducible manner.

With all this in mind, the Editors are extremely pleased that the labelling of countries as “predisposed” (climate, landscape, ticks, etc., are all there, but evidence for autochthonous TBE does not exist); “imperiled” (TBEV detected, but no case yet reported); “affected” (sporadically autochthonous TBE cases reported) and “endemic” (regular report of cases of several continuous seasons) have been generally accepted – and as long as incidence data are missing, this may best reflect local situation.

Furthermore, we have now aimed at documenting TBE-risk areas (i.e., the risk for TBE is >0) in our Map in Chapter 12c down to the county level for each country. This is a technical masterpiece accomplished by our publisher and the IT team in Singapore, Brian Ong, Muhammad Shaqeez and Augustine Hong, as they managed to technically simplify the highly accurate representation of the maps, which before would have even made the best commercially available computers collapse upon login into the immense map database. Congratulations to our IT-colleagues and – last but not least – a big “thank you” to our publisher, Daniela La Marca who made this all happen again in no time.

May 2022, Munich – Wien – Marburg – Nierstein

Prof. Dr. Gerhard Dobler, Dr. Wilhelm Erber, Dr. Michael Bröker, Prof. Dr. Heinz-Josef Schmitt

Introduction to the 6th edition

The World Health Organization (WHO) just declared the end of the COVID-19 pandemic, which kept and keeps infectious diseases specialists extremely busy with taking care of infected patients. COVID case numbers largely declined, but now long/post COVID and organ, mental, and social complications have become a new clinical and research focus. With this in mind, we are extremely grateful to all country authors for providing us with the 2022 TBE case numbers – despite the little time they have due to the additional work created by the pandemic.

While many infectious diseases – specifically acute respiratory tract infections and travel-related diseases – dramatically decreased during the height of the COVID-19 pandemic, in contrast, TBE cases tended to increase in Central Europe and elsewhere during the same time. Here we provide this important new data to our global readers.

We are pleased with the fact that colleagues from the USA have meanwhile become our major readers, and that the graphs and tables provided in this book have been frequently used in a number of prominent other publications. We specifically are encouraged by the feedback to the changes introduced in the 5th edition in 2022, and we will therefore continue to classify regions and countries as “predisposed”, “imperiled”, “affected” and “endemic” as true incidence data is still largely missing.

Our gratitude goes to our publisher, Daniela La Marca, our language Editor, John Hatley, and our Global Health Press IT team, the latter specifically for creating the TBE world map allowing us to enter data down to the level of single counties (Chapter 12c). Without all the excellent hard work of our colleagues this update would not have been possible.

Singapore, Munich, Vienna, Marburg, Nierstein in May 2023

Prof. Dr. Gerhard Dobler, Dr. Wilhelm Erber, Dr. Michael Bröker, Dr. Lidia Chitimia-Dobler, Prof. Dr. Heinz-Josef Schmitt

Click the image above to enlarge

List of TBE abbreviations

ADE	Antibody mediated disease enhancement
AE	Adverse Event
CMV	Cytomegalovirus
CNS	Central Nervous System
CSF	Cerebrospinal Fluid
CT	Computerized Tomography
DENV	Dengue virus
ECDC	European Center for Disease Prevention and Control
EEG	Electro-Encephalography
EMA	European Medicines Agency
FDA	(usually: The American) Food and Drug Administration
GMT	Geometric Mean Titer
HI	Hemagglutinin Inhibition
IFA	Immuno Fluorescence Assay
JEV	Japanese Encephalitis Virus
KFD	Kyasanur Forest Disease
NIP	National Immunization Program
NT	Neutralization Test
OHFV	Omsk Haemorrhagic Fever Virus
POWV	Powassan Virus
TBEV	Tick-Borne Encephalitis Virus
TBEV-EU	Tick-Borne Encephalitis Virus, European subtype
TBEV-FE	Tick-Borne Encephalitis Virus, Far-Eastern subtype
TBEV-SIB	Tick-Borne Encephalitis Virus, Siberian subtype
TBEV-HIM	Tick-Borne Encephalitis Virus, Himalaya subtype
TBEV-BKL	Tick-Borne Encephalitis Virus, Baikalian subtype
WHO	World Health Organization
WNV	West Nile Virus
YFV	Yellow Fever Virus

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The greatest care has been taken in compiling this book. However, no responsibility can be accepted by the publisher or compilers for the accuracy of the information presented.

Where opinion is expressed it is that of the author and does not necessarily coincide with the editorial views of Global Health Press.

While every effort has been made to contact copyright-holders of material produced or cited in this book, in the case of those it has not been possible to contact successfully, the editors, authors, and the publisher will be glad to make amendments in further editions.

Publication of this book was funded by Pfizer Inc.

ISSN: 2661-3980

Published online on May 16, 2023.