TBE report on disease occurrence 2017-2019

TBE report on disease occurrence 2017-2019

TBE (tick-borne encephalitis) is not a notifiable disease in Denmark, but the diagnostics are done centrally at the SSI, who therefore occasionally reports TBE occurrence, EPI-NEWS 40/17. This annual report covers the 2017-2019 period.

TBE virus detected in North Zealand for the first time ever

In 2019, for the third time, infection with TBE virus (TBEV), also known as Central European encephalitis, was detected in other Danish areas than Bornholm. For many years, the island of Bornholm was the only known endemic risk area in Denmark. In 2008 and 2009, TBE was detected in two persons who had become infected in Tokkekøb Hegn, EPI-NEWS 35/09, but now that some years have passed, this micro focus seems no longer to exist, EPI-NEWS 40/17. In 2018, TBE was detected in two persons who had become infected in the Faaborg area, and in a not otherwise specified area in Central or South Jutland, EPI-NEWS 12-14/19. Another two persons became infected with TBE on Bornholm in 2018. The four TBE cases in 2018 who had become infected in Denmark are more than the usual 1-2 annual cases observed in the 2013-2017 period. The figures are, however, small, and must therefore be interpreted with caution.

In 2019, from June to September, a total of four persons with great certainty became infected with TBE virus from infected ticks in and around Tisvilde Hegn in North Zealand. The affected persons were three men and one woman aged 39-69 years who either resided close to Tisvilde Hegn or used the woods for recreational purposes. All four patients ran a two-phased disease course presenting with fever, fatigue and influenza-like or gastrointestinal symptoms followed by admission due to a clinical presentation similar to that of meningitis or meningo-encephalitis. Several of the patients have experienced sequelae after their infection.

New micro focus in Tisvilde Hegn

In September 2019, ticks were collected by dragging a white piece of cloth across the forest floor (so-called flagging) in a small area in the northeastern corner of Tisvilde Hegn. The collected ticks were separated into nymphs and adults, and collected in pools each counting approx. 40 ticks. RNA was extracted from pools of ticks and used in a TBEV-specific PCR. In four pools derived from two of the five collection areas, PCR for TBEV was positive. An additional collection of ticks in October 2019 in a more limited part of the area confirmed the findings, and the ticks (nymphs only) in an approx. 20 m broad section along Tisvilde Natural Playground in the northeastern corner of the woods were clearly TBEV positive with an estimated prevalence of 8% (95% confidence interval: 4.0-14.0%) (1 in every 12 tick nymphs contained TBE virus).

Based on these findings, the Ministry of Environment and Food of Denmark and the Municipality of Gribskov in October 2019 decided to put up signs for the users of the natural playground warning them of the risk of tick bites and to remove part of the shrubbery in the area due to the risk of tick-borne TBEV infection.

Through subsequent whole-genome sequencing and phylogenetic analyses, three complete whole-genome sequences of TBE virus were attained. The three sequences were identical and characterised by considerable genetic resemblance to a TBE virus strain from Mandal, Norge, from where the infected ticks have probably been brought to Tisvilde Hegn by migratory birds.
In May 2020, the UC/SSI tested 280 tick nymphs and 36 adult ticks collected in Section 3A and 4A . All were tested in pools. Based on the pooled results, the nymphs had an estimated individual prevalence of 1.5% (95% confidence interval: 0.4-3.9%).

The adult ticks had an estimated individual prevalence of 5.7% (95% confidence interval: 1.0-16.6%, whereas all adult ticks from 2019 were TBE negative. However, only five adult ticks of the 119 tested adult ticks from 2019 had been collected in Section 3A and 4A. The authorities have therefore decided to close the natural playground so that it may be moved to a TBE-free area of Tisvilde Hegn.

TBEV infection in Denmark in the 2017-2019 period

In the 2017-2019 period, Denmark recorded a total of 27 cases of presumed TBE infection (positive IgM and IgG in serum, positive IgM in spinal fluids or positive PCR). The primary country of infection was Sweden (with 11 cases). Furthermore, three had become infected on Bornholm and six patients outside of Scandinavia in known endemic areas like the Baltics, the Czech Republic, Austria and Poland. The remaining seven had become infected in Denmark in other areas than Bornholm. The hot and early summer of 2018 brought a particularly high number of tick-transmitted infections, some of which were observed in new geographical areas across most of Europe. In Denmark alone, 2018 saw a total of nine TBE cases. In 2019, the SSI detected TBEV infection in 13 persons, which is the highest number recorded so far in Denmark, Figure 1 and Table 1.

TBE infection

TBEV infection occurs following tick bites by infected ticks (Ixodes ricinus). The European TBE variant (TBE-eu) typically runs a two-phased clinical course: After an average 7-10-day incubation period (range: 4-28 days) following a tick bite, influenza-like illness develops (“summer influenza”) that lasts for a few days. Subsequently, about 1/3 of patients progress and develop central nervous system symptoms in the form of meningitis, encephalitis, meningo-encephalitis or meningo-radiculitis. This occurs following a symptom-free interval lasting from a few days to a few weeks. However, the infection in most cases goes un-noticed, or it may present directly as symptoms from the central nervous system. About 1/3 of hospitalised TBE patients develop transitory or more persisting neuropsychiatric or neurological sequelae of varying degrees of severity.

Transmission of TBE virus

TBE is caused by a flavivirus (TBEV) and is transmitted within minutes after being bitten by an infected tick. The primary virus hosts are small rodents, but virus is also found in foxes, deer and migratory birds. Woods or meadows with a dense undergrowth and shrubs are associated with a greater risk of infection. TBE is therefore seen mainly in persons who spend time in nature, and who walk beyond established paths. For practical reasons and to eliminate any uncertainty about the place of infection, risk areas may be defined as areas where a minimum of two TBE cases have been detected within a three-year period, corresponding the life span of the tick. The tick season peaks from May to October, which is the period when more people spend time in the woods. Ticks become active and start seeking blood meals when temperatures rise to around 5°C.

Diagnostics

The TBE diagnosis is made by detection of specific TBEV antibodies in blood (IgM and IgG) and/or spinal fluids (IgM) in combination with relevant exposure (tick bite) and relevant symptoms (meningo-encephalitis). Elevated IgM titres tentatively indicate ongoing or recently surpassed infection. Seroconversion with a 4-fold IgG titre increase in two separate blood samples underpins the diagnosis. The first blood sample should be taken as early as possible in the course of the disease the second should be taken a minimum of 1-2 weeks later.

Direct TBEV detection by PCR in spinal fluids, blood or urine is also diagnostic, but as TBEV is only briefly present as free virus in spinal fluids, the chance of detecting virus through a single sample is limited. Urine may remain TBEV-PCR positive for up to 1-2 weeks after onset of neurological symptoms in TBE.

The diagnosis should be considered following stays on Bornholm and also following stays in the detected risk area in and around Tisvilde Hegn and, generally, in cases with a relevant exposure and symptoms.

This report is also described in EPI-NEWS 25/20.