Journal of Vector Borne Diseases

: 2020  |  Volume : 57  |  Issue : 1  |  Page : 14--22

Geographic distribution of Tick-borne encephalitis virus complex

Jae Hyoung Im1, Ji-Hyeon Baek1, Areum Durey2, Hea Yoon Kwon1, Moon-Hyun Chung3, Jin-Soo Lee1,  
1 Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea
2 Department of Emergency Medicine, Inha University School of Medicine, Incheon, Republic of Korea
3 Department of Internal Medicine, Seogwipo Medical Center, Jeju-do, Republic of Korea

Correspondence Address:
Dr Jin-Soo Lee
7-206, Shinheung-Dong, Jung-Gu, Incheon, 400–711
Republic of Korea


A comprehensive understanding of the geographic distribution of the tick-borne encephalitis virus (TBEV) complex is necessary due to increasing transboundary movement and cross-reactivity of serological tests. This review was conducted to identify the geographic distribution of the TBEV complex, including TBE virus, Alkhurma haemorrhagic fever virus, Kyasanur forest disease virus, louping-ill virus, Omsk haemorrhagic fever virus, and Powassan virus. Published reports were identified using PubMed, EMBASE, and the Cochrane library. In addition to TBEV complex case-related studies, seroprevalence studies were also retrieved to assess the risk of TBEV complex infection. Among 1406 search results, 314 articles met the inclusion criteria. The following countries, which are known to TBEV epidemic region, had conducted national surveillance studies: Austria, China, Czech, Denmark, Estonia, Finland, Germany, Hungary, Italy, Latvia, Norway, Poland, Romania, Russia, Switzerland, Sweden, Slovenia, and Slovakia. There were also studies/reports on human TBEV infection from Belarus, Bulgaria, Croatia, France, Japan, Kyrgyzstan, Netherland, and Turkey. Seroprevalence studies were found in some areas far from the TBEV belt, specifically Malaysia, Comoros, Djibouti, and Kenya. Kyasanur forest disease virus was reported in southwestern India and Yunnan of China, the Powassan virus in the United States, Canada, and east Siberia, Alkhurma haemorrhagic fever virus in Saudi Arabia and east Egypt, and Louping-ill virus in the United Kingdom, Ireland, and east Siberia. In some areas, the distribution of the TBEV complex overlaps with that of other viruses, and caution is recommended during serologic diagnosis. The geographic distribution of the TBEV complex appears to be wide and overlap of the TBE virus complex with other viruses was observed in some areas. Knowledge of the geographical distribution of the TBEV complex could help avoid cross-reactivity during the serologic diagnosis of these viruses. Surveillance studies can implement effective control measures according to the distribution pattern of these viruses.

How to cite this article:
Im JH, Baek JH, Durey A, Kwon HY, Chung MH, Lee JS. Geographic distribution of Tick-borne encephalitis virus complex.J Vector Borne Dis 2020;57:14-22

How to cite this URL:
Im JH, Baek JH, Durey A, Kwon HY, Chung MH, Lee JS. Geographic distribution of Tick-borne encephalitis virus complex. J Vector Borne Dis [serial online] 2020 [cited 2021 Apr 18 ];57:14-22
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Full Text


The tick-borne encephalitis virus (TBEV) complex consists of single-stranded RNA viruses and is included in the genus Flavivirus. Many viruses of the mammalian tick-borne flavivirus group are important human pathogens. The TBEV complex includes the following viruses: Alkhurma haemorrhagic fever virus (AHFV), Gadgets Gully virus, Karshi virus, Kyasanur Forest disease virus (KFDV), Langat virus, Louping ill virus (LIV), Omsk haemorrhagic fever virus (OHFV), Powassan virus (POWV), and Royal Farm virus[1]. Despite the high sequence similarity within the group, the viruses cause a wide range of clinical syndromes; TBEV, LIV, and POWV are mainly responsible for encephalitis, while OHFV, KFDV, and AHFV mainly cause haemorrhagic fever in humans. Averagely, on annual basis the TBEV causes 2000–3000 cases in Europe, KFDV causes 400–500 cases in India, and AHFV causes approximately 20 cases in the Middle East[2]. The disease burden of TBEV is considered high due to the relatively high incidence and mortality. However, these viruses could show cross-reactivity, which may cause confusion during serologic diagnosis; hence, understanding the geographical distribution of the TBEV complex is essential for the serologic diagnosis of these viruses.

The TBE occurs across a large area in Europe and Asia. Many European countries have a relatively well-established surveillance system and a high perception of TBE[3],[4],[5],[6],[7],[8],[9],[10],[11]. However, there is relatively little interest in TBE beyond Europe. The LIV (United Kingdom, Ireland), AHFV (Arabia), KFDV (Western India), OHFV (Omsk in Siberia), and POWV (United States and Canada) have relatively few endemic countries, and people outside the endemic area are less concerned with the viruses.

Awareness of the international public health problem posed by TBEV has become more important due to climate change[12]. In addition, as travel and immigration in crease, transboundary movements have become common, making it essential to understand the worldwide distribution of viruses when diagnosing suspicious patients. There are some good review articles and books already published on the TBEV distribution. However, the existing literature has the following limitations: the passage of time, lack of systemic reviews, lack of comprehensive analysis of the entire TBE complex, and lack of analysis in non-endemic areas. To perform a comprehensive analysis and an investigation of formerly unknown endemic areas for the TBEV complex, we conducted a study to evaluate the geographic distribution of the TBEV complex.

Data sources and search strategies

A literature search was conducted using PubMed, EMBASE, and the Cochrane library restricted to English articles and human studies during January 2018. The PubMed search strategy comprised “keywords” related to the TBEV complex AND geographic location. The keywords related to the TBEV complex consisted of MeSH terms and the search terms TBEV, AHFV, KFDV, LIV, OHFV and POWV. The keywords related to geographic location consisted of “geographic location” (MeSH) and all the countries in the latitude 10–80° N to increase sensitivity. Similar strategies were used in EMBASE and the Cochrane library. The detailed search terms and strategy are shown in [Supplementary Table 1] [SUPPORTING:1].

Study selection and data extraction

The search results were classified into case studies (including case reports), seroprevalence studies, and national surveillance studies. For the definition of human cases, we used the 2012 European Union case definition for TBE [Supplementary Table 2] [SUPPORTING:2]. Other TBE complex viruses were also defined by modifying the criteria for TBE. Titles and abstracts were screened for compliance with these inclusion criteria, and then full papers were reviewed. Screening and review were performed by two independent reviewers.

The following six variables were extracted from each included article: (i) name of the author and year of publication; (ii) title; (iii) journal name and volume; (iv) identified virus; (v) nation; (vi) method of laboratory diagnosis; and (vii) study site. A normalized Microsoft Office Access 2013 database was created with the information obtained from the extracted variables.


We marked the locations of TBEV complex patients using Google Fusion Tables™. The geographic data were calculated based on the text location of the patients. If the precise location of the patients was not described, the reference laboratory or hospital was used for mapping. Seroprevalence studies and national surveillance reports without location information were excluded from geo-code mapping.

Each study site location was geo-coded to determine the latitude and longitude using web tools (;, Queries were run in the Microsoft Office Access to retrieve data views for import into Google Fusion Tables™ as sites with identical longitudes and latitudes can be overwritten on a Google Map.

Overview of literature collection

From the results of the literature search, 314 articles that met the study criteria were included [Figure 1]. There were 251 TBEV, 13 AHFV, 16 KFDV, 2 LIV, and 32 POWV articles. There was no article on OHFV. There were 213 case reports/research articles, 71 human seroprevalence studies, and 30 nation-based surveillance studies (including the report of the European Center for Diseases Prevention and Control[13]). [Table 2] shows the characteristics of the included articles.{Figure 1}{Table 1}{Table 2}

Geographic distribution of TBEV

There were 24 national TBEV surveillance reports: Austria, China, Czech, Denmark, Estonia, Finland, Germany, Hungary, Italy, Latvia, Norway, Poland, Romania, Russia, Switzerland, Sweden, Slovenia, and Slovakia. Among them, Estonia, Latvia, Lithuania, and Slovenia showed high incidences of above 10 per100,000 population (in 2007~2017). The TBEV human cases were found in some countries with no national surveillance reports, specifically in Belarus, Bulgaria, Croatia, France, Japan, Kyrgyzstan, Netherland and Turkey [Figure 2]. Despite studies showing human seropositivity, there was no direct evidence of TBEV in the following countries: Afghanistan, Comoros, Djibouti, Greece, Kenya, Malaysia, Portugal and Spain [Figure 3].{Figure 2}{Figure 3}

Geographic distribution of other TBEV-complexes

The search for reports on LIV resulted in two articles from the UK and Ireland (each), while 13 articles were retrieved on AFHV. Though most of the AFHV patients were from Saudi Arabia, there were some reports on AHFV patients from Egypt. The search for articles on the KFDV resulted in 15 reports in India and a case in Yunnan, China. The search for reports on the POWV yielded 26 articles. Though most of these reports were published in the United States and Canada, there was a case report in Siberia. There was no OHFV report that satisfied the inclusion criteria due to language restrictions. [Figure 2] shows the geographic distribution of these viruses.

The TBEV is responsible for thousands of cases of neurologic illness (such as meningitis and encephalitis) annually in humans, with a distribution ranging from Europe to Asia[14]. Ixodes ricinus is a known vector of TBEV mainly in western/central Europe while I. persulcatus is the main vector in eastern Europe and Siberia. Other Ixodid ticks such as I. scapularis, I. pavlovskyi, I. plumbeus, and I. nipponesis can also transmit TBEVs. Dermacentor spp. and Haemaphysalis spp. have also been implicated as vectors in Ixodes-free areas[15].

The TBEV is classified into the following three subtypes, namely Western, Siberian and Far-Eastern. These three TBEV subtypes have overlapping distributions in many areas. In Europe, the central to eastern regions as well as the Scandinavian Peninsula are known as TBEV endemic areas. In this review, human TBE cases were observed in Croatia, France, Netherland, Belgium, and Bulgaria in Europe, regions not formerly recognized as TBE endemic areas. Furthermore, TBEV was isolated from vectors/animals in Liechtenstein, Moldova and South Korea[16],[17],[18], although there have been no reports of human TBEV infections in these countries.

The western margin of TBEV distribution is in the Bordeaux region (France), with no confirmed human cases in the Iberian Peninsula. The southern margin is Italy, and the northern margin is the Scandinavian Peninsula. Although some Balkan countries have been relatively well-researched and reported (Bulgaria, Romania, Slovenia, and Croatia), the southwestern Balkans (Albania, Bosnia and Herzegovina, Macedonia, Montenegro and Serbia) have relatively few studies and reports. There were 98 cases reported from 1983 to 2001 in Albania[19],[20]. Other cases have been reported in north Bosnia[21] and the area near Belgrade and Adria in Serbia, although the reports did not meet the criteria for inclusion in this systemic review[21]. In Greece, 2.06% TBEV seropositivity was reported in 921 healthy people. However, there was no confirmed case with central nervous system infection[22].

The authors had difficulties in clearly identifying the TBEV distribution because several papers published in many countries in Eastern Europe and Central Asia (particularly those belonging to the former Soviet Union) were not written in English. Although not included in this study (due to language restrictions), Ukraine and Kazakhstan were identified as potential endemic areas in a review of former Soviet Union countries[23]. Volynska Oblast in Ukraine is known as a TBEV endemic area[24], along with the east area and Almaty region in Kazakhstan (60 patients in 2004–2006, 22 patients in Almaty from 2004–2006)[21]. In Afghanistan, a study showed 23.4% seroprevalence and 20 cases of IgM positivity[25], although it should be considered a possibility of cross-reaction with Royal Farm virus. In Georgia, 7% of acute febrile patients showed TBEV seropositivity[26].

East Siberia, China and Japan are relatively well-known as TBEV endemic areas in Asia. In Japan, most TBEV cases were reported in Hokkaido. Many reports on TBEV in China were written in Chinese and, therefore, were not included in our systematic review. However, TBEV is known to occur in Inner Mongolia, Daxingan Mountain in Jilin province, and the mountains in Changbai[27]. The virus was also isolated from vectors in South Korea[17],[28]. In Mongolia, TBEV is responsible for approximately 20 human infections annually on the border with Russia[29]. Analysis of this review indicates the occurrence of the following TBEV belts: Central Europe-East Europe-Siberia and Central Asia-China- to Far East Asia.

There were some seroprevalence studies in areas remote from the TBEV belt. However, since the TBEV antibody can cross-react with other arboviruses, positive results should be interpreted with caution, especially in endemic areas for other viruses. A human seroprevalence study in Vietnam[30] showed high seropositivity (47.3%), but Vietnam is an endemic country for dengue fever and Japanese encephalitis, which can cross-react with TBEV. Research in Malaysia is notable. Seropositivity (4.2%) was identified among animal farmworkers after ruling out possible cross-reaction with dengue, West Nile virus, and Japanese encephalitis virus[31]. There is a possibility of seropositivity due to the Langat virus in Malaysia and a Malaysian seroprevalence study showed no TBEV seropositivity in 600 patients with a clinical diagnosis of encephalitis[32]. It is interesting to note that there have been studies reporting TBEV seropositivity in Africa. A study in Djibouti showed 0.1% seropositivity (1/893)[33], while a study in Comoros showed 0.7% seropositivity (3/400) in 75 serum donors with 325 medical conditions[34], while a Kenyan study showed 16% seropositivity[35]. However, these studies may have included other viral infections and further research is needed for confirmation.

The POWV causes encephalitis in humans and leads to long-term neurologic sequelae and death in 10% of cases[36]. The Centers for Disease Control and Prevention in the United States has a good surveillance system for POWV. In the United States, POWV was responsible for 6.8 cases annually[37] from 2006–2015. The I. cookie is one of the main vectors for POWV, which is found in Canada and the United States, and human cases were mainly reported in Eastern Canada and the Eastern United States[38]. However, there is serologic evidence of animals/ vectors in British Columbia, Cranbrook (Canada), California, Alaska, and New Mexico[39], showing the possibility of a wider POWV distribution than expected in North America[40],[41]. Beyond North America, there was a human POWV case reported in East Russia[42].

The LIV shows a high mortality rate with symptoms such as tremors, weakness, and encephalitis in sheep, cattle and small mammals[43]. The first human LIV case was reported in 1934, and 44 human cases were subsequently reported in Scotland, Wales, and Northern England until 2000[44]. The TBEV and LIV have the same vector but different regional distributions. However, unlike TBEV, LIV has been reported in animals in Norway and Spain, although it should be considered a possibility of cross-reaction with Spanish goat virus in Spain[45],[46]. Considering the relationship between the Turkey sheep encephalitis virus and the Greek goat encephalitis virus[47],[48], LIV may have a wider distribution than is currently recognized. Although a low incidence has been reported for the past 20 years, there is a possibility of a resurgence with environmental changes and a vigilant observation is needed[43].

The KFDV is transmitted by Haemaphysalis spinigera, and rodents, shrews, and monkeys are common hosts of the virus. It was identified in 1957 in a sick monkey from the Kyasanur forest in the Karnataka state of India. Since then, 400–500 human cases have been reported in India annually[49],[50],[51],[52]. Southwest India (Karnataka, Tamil Nadu, and Kerala states) is known as an endemic area for KFDV and there has been a human case report in Yunnan, China[53]. The Chinese case report suggests that the distribution of KFDV may be wider than expected.

Although transmission of AHFV is not clearly understood, infection is known to occur through ticks (Ornithodoros savignyi and Hyalomma dromedarii). The AHFV was first reported in Saudi Arabia in 1995 and has been documented in Western Saudi Arabia (Jeddah, Mecca, Jian, and Najran) and Eastern Egypt (El Shalateen), mainly in the spring and summer[54],[55],[56],[57],[58],[59],[60]. Interestingly, the virus was found in tick, in Djibouti[61], far from Saudi Arabia and Egypt. Studies on AHFV have not been conducted in other areas, and the virus was found relatively recently. The distribution and burden of the AHFV may be underestimated and further studies are needed.

The OHFV was first isolated from a patient with haemorrhagic fever in Omsk, Siberia in 1947. The vector for the OHFV is Dermacentor reticularis. It has been found in Omsk, Novosibirsk, Tyumen, and Kurgan in Russia with 0.53.0% mortality[62]. Although many studies were not included in the present systematic review due to linguistic limitations, more than 1000 cases of OHF were diagnosed[63],[64] from 1946–1958. After this period, the incidence of OHF decreased, but there was a resurgence[65] in 1988, leading to 165 OHF patients during 1988–1997.

The distribution of the TBEV and other TBEV complexes shows an overlap (LIV and TBEV in Europe, TBEV, OHFV, LIV and POWV in Siberia). Since the diagnosis of the TBEV complex mostly depends on serology including ELISA, it is necessary to be cautious with diagnosis in these regions. This review also uncovered TBEV complexes in most northern temperate countries, but some Southwest and Southeast Asian regions lack sufficient research and further research is needed.

There were some limitations to the present study. First, we implemented a restriction on language, which could have led to the omission of many reports from Eastern Europe and the former Soviet Union. However, the purpose of this review was not to report the precise location where all cases exist but to present the border of the area where the TBEV complex is possible. We also used further non-systematic search to detect for non-English papers in countries where the TBEV complex could not be confirmed by English papers. Second, there were many cases for which the exact location was not recorded in the literature, making precise geo-coding difficult. However, this limitation caused no issue with creating a global map. Third, our approach underestimates the incidences in countries where research is not active. We once again emphasize that the purpose of this paper was not the endemicity analysis of the TBEV complex but rather the identification of the distribution of the complex. Fourth, our study does not show the potential risk of the TBEV complex based on the distribution of the vector. The presence of the vector implies the possibility of viral influx or spread. Therefore, it is important to keep in mind that these viruses may show influx spread to a broader area than that shown in the present study.


In conclusion, the prevalence of TBEV complex is widespread; TBEVs are prevalent from France to Japan, and POWVs in Canada and the US (Eastern Russia case report), LIVs in the UK (animals in Norway and Spain, variants are found in Greece and Turkey), KFDVs in Southwestern India and Yunnan in China, AHFV in Saudi Arabia and Eastern Egypt (tick in Djibouti), and OHFVs in Omsk, Novosibirsk, Tyumen and Kurgan in Russia. Considering the distribution of serologic studies and the vectors known to date, the TBEV complex is likely to exist over a much larger region. Knowledge of the geographical distribution of the TBEV complex could be helpful in avoiding cross-reactivity during the serologic diagnosis of these viruses. Hence, the surveillance studies can implement better control measures according to the distribution pattern of these viruses.

Ethical statement: Not applicable.

Conflict of interest: None.


This work was supported by a research grant from Inha University.


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