The detection of TBEV in the United Kingdom is important because TBEV can infect humans, causing febrile illness and neurologic complications including encephalitis. This evidence is contrary to earlier predictions based on climate change that did not forecast a spread of TBEV to the United Kingdom. However, in addition to climate change, the spread of the tick vector, TBEV, and associated viruses into new regions can be influenced by a variety of other factors, such as transportation of animals and alterations in land management.
Serologic evidence suggests a high prevalence (47.7%) of exposure of deer to flaviviruses, such as TBEV and LIV, in the Norfolk/Suffolk (Thetford Forest) focal area. This seroprevalence is within the upper levels detected in TBEV risk areas of Europe, where seroprevalence studies in deer rarely exceed 50%.[15,16,28,29] In addition, the detected prevalence of flavivirus RNA in ticks collected from deer of 2.6% within the Thetford Forest area falls within the range of findings from other studies in mainland Europe that tested blood-fed ticks. The deer were culled within a large forest habitat, which aligns closer with ecology required for TBEV, rather than LIV, maintenance. Based on these findings, and the evidence that all rRT-PCR–positive results were for TBEV and not LIV, we propose that TBEV is established and is being maintained through enzootic cycles within the Thetford Forest area, rather than resulting from multiple importation events, which is in line with findings in many endemic focal areas of TBEV. The hypothesis that TBEV infection might be maintained in Thetford Forest is supported by previous work in the United Kingdom that provided evidence of co-feeding between ticks from different life stages on small mammals in a southern English woodland, which is a crucial factor for the maintenance of TBEV.[9,12] In addition, our positive serology data support the concept that the virus is circulating nonviremically in local wildlife and by cycling among the co-feeding nymphs, larvae, and adult ticks, through nonviremic transmission. Good evidence shows that TBEV is maintained in other parts of Europe through nonviremic transmission.
In other study areas, we detected serologic evidence of flavivirus exposure but not viral RNA in ticks. The close homology between LIV and TBEV presents challenges when serologic methods are used alone because the tests cannot distinguish between them. Thus, based on such data, confirming which virus is responsible for the seroreactivity in the areas where LIV has previously been reported is not possible. Previous reports of LIV prevalence are limited; just one study showed up to 15.3% of ticks positive for LIV. However, other researchers have not confirmed these data, and our results indicate a much lower prevalence. Nevertheless, we did not find any published clinical reports of LIV in Hampshire livestock despite our detected seroprevalence of 14.3% by ELISA.[1,3,4] Although additional tick and small mammal ecology studies are needed to build on serologic data, evidence shows the maintenance of TBEV in the identified focal endemic area.
The genomic sequence of TBEV-UK shows close identity to a TBEV-Eu virus isolated in 2009 from questing ticks collected in Norway. This similarity suggests that TBEV-UK might have been brought to the United Kingdom on migratory birds, such as blackbirds (Turdus merula) and redwings (Turdus iliacus), which are known to transport ticks over wide distances.[34–37] The United Kingdom experiences a large influx of migratory birds each autumn from several TBEV-endemic countries in northern Europe, including Norway. During this migration, birds first arrive on the east coast of the United Kingdom, and it is feasible that TBEV-UK could have originated from a tick imported by an autumn migratory bird. We are collecting tick samples from migratory birds to assess the proportion of tick-infested birds arriving in the United Kingdom and testing these imported ticks for TBEV (among other potential pathogens). In addition, because of lower viral RNA levels, we are looking into primer-amplification sequencing approaches to further decipher the virus responsible for the rRT-PCR–positive samples detected from Thetford Forest.
For zoonotic infections, detection of a pathogen in the animal reservoir/host, vector, or both often precedes the emergence of human infection. Such was the case in the Netherlands, where deer serum samples, collected 6 years before the first cases in humans, demonstrated serologic evidence of TBEV infection. Similarly, in Spain, Crimean-Congo hemorrhagic fever virus was first reported in ticks in 2010, before autochthonous infections in humans was identified in 2017. Within the focal TBEV-endemic areas we identified in this study, seroepidemiologic studies should be undertaken, particularly in risk groups that include patients presenting to general practitioners and hospitals with central nervous system symptoms.
Although UK-TBEV has not been linked to human disease, it nevertheless shows close homology to pathogenic isolates of TBEV and should be considered to be a potential public health risk. Thus, clinicians in the United Kingdom should consider the European Union case definition of TBE and include TBE in the differential diagnosis of patients with symptoms of meningoencephalitis, especially if they have been exposed to a tick bite, even if they have not traveled recently to a known TBE-endemic country. The European Union case definition specifies clinical criteria as any person presenting with inflammation of the central nervous system. In addition to meeting clinical criteria, laboratory case confirmation requires ≥1 of the following 5 criteria to be satisfied: 1) detection of TBEV nucleic acid, 2) viral isolation from clinical specimens, 3) TBEV-specific IgM and IgG in blood, 4) TBEV-specific IgM in cerebrospinal fluid, and 5) seroconversion or 4-fold increase of TBEV-specific antibodies in paired serum samples.
Although no autochthonous cases of clinical human disease have been diagnosed in the United Kingdom, up to 60% of encephalitis cases reach no diagnosis. Therefore, our results indicate that TBEV should be considered as a potential cause in encephalitis patients, and the wide distribution of the natural vector in the United Kingdom indicates a need for close monitoring and a potential for geographic spread and expanding risk areas.
We are grateful to the Forestry Commission, British Deer Society, Deer Initiative, and Barry Dowsett for their support and promotion of this study. We thank all of the participating deerstalkers for their support in collecting samples for this study; Dylan Turnbull and Ellie Laming for performing HAI testing; Gillian Slack, John Chamberlain, Emma Kennedy, and Victoria Graham for their help processing samples; Penny Roberts for producing study packs; Hein Sprong for his advice in setting up the study; and Nick Johnson for providing control serum for assay testing.
This research was funded by the Virology & Pathogenesis Group's Arbovirus Programme, Public Health England, and by the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine. M.H. is funded by the National Institute of Health Research Health Protection Research Unit in Emerging and Zoonotic Infections. M.S.R. is funded by the Scottish Government.
Emerging Infectious Diseases. 2020;26(1):90-96. © 2020 Centers for Disease Control and Prevention (CDC)