The Emergence and Dynamics of Tick-Borne Encephalitis Virus in a New Endemic Region in Southern Germany

Abstract

Tick-borne encephalitis (TBE) is the most important viral tick-borne infection in Europe and Asia. It is emerging in new areas. The mechanisms of emergence are fairly unknown or speculative. In the Ravensburg district in southern Germany, TBE emerged, mainly over the last five years. Here, we analyzed the underlying epidemiology in humans. The resulting identified natural foci of the causal TBE virus (TBEV) were genetically characterized. We sampled 13 potential infection sites at these foci and detected TBEV in ticks (Ixodes ricinus) at eight sites. Phylogenetic analysis spurred the introduction of at least four distinct TBEV lineages of the European subtype into the Ravensburg district over the last few years. In two instances, a continuous spread of these virus strains over up to 10 km was observed.

Increased Vaccination Diversity Leads to Higher and Less-Variable Neutralization of TBE Viruses of the European Subtype

“…All of the other 14 TBEV-EU strains were grouped into 11 separate phylogenetic clades that were dated as having diverged more than 86 years ago, from either of the two seed viruses ( K23 and Neudörfl ; Figure 1 a). This observation is consistent with our previous description of genotypically divergent, locally restricted TBEV microfoci with limited-to-no gene flow and a low effective population size, due to migration barriers of the endemic vectors [ 18 ]. In this scenario, long-range dispersal dependent on random chance encounters with larger non-host targets, i.e., migratory vertebrates such as deer or humans.…”

“…Both seed–virus strains belong to the European subtype; however, they represent distinct phylogenetic subclades of TBEV-EU. In recent years, it has become more and more apparent that the increase and emergence of human TBE cases is accompanied by an increase in TBEV-EU diversity [ 18 ]. In the light of this development, it is unclear whether these two distinct vaccine strains differ in their capacity to induce neutralizing antibody responses to naturally occurring TBEV-EU strains.…”

“…This effect could be a result of the virus strain used in the vaccine. In contrast to strain Neudörfl , which in our taxon set first diverged from the last common ancestor of TBEV-EU strains, the divergence of K23 , like many of the other strains, falls within the likely early diversification period of TBEV in Central Europe [ 18 ] and, thus, may represent a more derived state. The strain has one amino acid substitution, which was probably acquired during the cultivation process in vaccine seed–virus production and was found in any wild-type strains we studied.…”

“…TBEV-EU represents the prevalent subtype and evolutionary TBEV lineage in Europe, possibly tracing to early 1900 and expanding in effective population sizes from east to west until the 1970s. Extant TBEV-EU genotypes persist endemically in local microfoci that can be traced to specific, older phylogenetic clades and, presumably, to long-range dispersal by random chance encounters with migratory animals and humans [ 18 , 19 ].…”

Tick-borne encephalitis

“…In western Europe, lineages of the European subtype of TBEV have been detected for the first time in the Netherlands [19] and the UK [20]. The expansion of TBEV geographic range has also occurred in France and its neighbouring endemic countries including Germany [21], Switzerland [22] and Italy [23]. The western margin of TBEV in France is bordered to the North-East by the region of Alsace and to the east by the Vosges Mountains.…”