A lethal tick-borne encephalitis from an active endemic area in Slovakia

INTRODUCTION

In Slovakia, tick-borne encephalitis (TBE) is endemic disease. Around 35% of Slovakia’s population lives in areas with high TBE endemicity (> 5 cases/100,000 inhabitants). In 2022, Slovakia reported 215 cases TBE (3.4 cases per 100 000). Most of the cases were autochthonous (N = 211. 98.1%), only 4 cases (1.8%) were travel associated (Austria, Czechia, Germany). Tick bite was reported as the most frequently probable mode of transmission (64.7% cases, N = 139 cases). Consumption of infected milk and dairy products was reported in 10.7% (N = 23) cases, and for 24.6% (N = 53) cases the mode of transmission was not known. A total of 3 cases (1.4%) occurred in vaccinated persons and 1 death was recorded (0.47%). Cases were recorded in every age group except group of 0 years and 1–4 years, with the highest age-specific incidence in the 45–54 years (5.52/100,000) and 15–19 years (4.99/100,000) age groups. The incidence of disease was higher in males (5.00/100 000) compared to females (2.6/100 000). A 74.9% (N = 161) of them were recorded in endemic areas with an incidence rate > 5/100,000. The regions demonstrating the highest levels of endemicity include Region of Trenčín (5.2 cases per 100,000), Region of Žilina (9.4 cases per 100,000) and Region of Banská Bystrica (10.6 cases per 100,000) [1]. The data on the number of cases are considered to be relatively accurate given the forty-years tradition of mandatory reporting of TBE laboratory results supplemented by active epidemiological investigation of cases in infectious disease wards. In contrast, much less is known about number of cases that contract long-term or permanent sequelae including a fatal outcome. The development of a severe course may not always be recorded in the surveillance system due to the time latency from the onset of the disease [2, 3]. More follow-up is necessary to update the data on serious TBE cases, including fatal outcomes.

The potentially severe course of infection and the risk of permanent neurological sequelae make TBE an important health problem in many European countries. Many aspects of this infection are still not fully understood.

Notwithstanding the clinical severity of the disease and the relatively large number of persons at risk of exposure to the causative agent in view of the large endemic areas in our country, the most effective form of prevention by vaccination is used relatively little in Slovakia.

THE COURSE OF THE DISEASE

In June 2021 a 45-year-old male was admitted to the hospital due to a two-day fever, weakness, loss of appetite, and dyskinesia of the limbs. His condition progressed with clinical presentation of consciousness disorders including snoring and occasional agitation. Symptoms such as dysphagia and loss of palatal reflexes, breathing alternating with irregular periods of apnea, severe left-sided hemiparesis, dysarthria and other symptoms characteristic of bulbar palsy with persistent meningeal irritation were observed. During hospitalization, he was intensively treated, rehabilitated, and admitted to the intensive care unit. After the 12-week hospitalisation, he was discharged to a long-term care facility due to his inability to perform self-care activities. The findings were classified as a severe tick-borne meningoencephalitis, initially with a qualitative-quantitative disorder of consciousness and bulbar symptomatology, left-sided hemiparesis accentuated in the left upper limb, an organic psychosyndrome in the foreground with a decrease in memory-cognitive functions with intermittent psychomotor restlessness, hypobulimia, severe depressive syndrome and motoric instability with falls during his hospital stay; the CT brain scan showed no signs of trauma. A tonic-clonic seizure was recorded at the 32nd week after the onset of disease. The seizure was secondary to the resolution of TBE, possibly complicating pharmacotherapy with Elontril. A focal orofacial epiparoxysm was recorded 4 weeks later. The EEG showed no specific epileptiform abnormalities. Laboratory analysis showed only a slight increase in inflammatory parameters, and the brain CT scan was without abnormalities. Three lumbar punctures were performed (weeks 1, 2 and 34 after the onset of symptoms). The cerebrospinal fluid (CSF) showed a slightly elevated cell count, proteins, and lactate with normal glucose levels. The results of serological and RT-PCR tests were negative both in blood and CSF (dif. dg. other viral and bacterial pathogens). The CFS cultures were negative. TBEV RNA detection by RT-PCR was not performed. Serum and CSF were analysed for the presence of specific TBEV antibodies by enzyme-linked immunosorbent assay (EUROIMMUN DYNEX ELISA). TBEV IgG and IgM antibodies were positive in serum, with IgM also in CSF. The TBEV IgM antibody index was 2.93 in the second CSF sample. The albumin quotient was positive in the first and second samples and negative in the third sample. Intrathecal production of IgM antibodies was present in the second and third samples, and intrathecal production of IgG antibodies was present only in the third sample of CSF (Table 1).

Brain MRI at that time showed a non-specific hyperintense white matter lesion on axial FLAIR image in the left cella media without hemosiderin deposition, without acute ischaemic and haemorrhagic changes, and without evidence of focal meningeal thickening in both the native and the post-contrast. This MRI finding persisted on repeat MRI (week 47 after the disease onset). In addition, hyperintense signal changes in the basal ganglia were described bilaterally, which were also vaguely visible on the initial MRI. Empirical antimicrobial therapy with ceftriaxone and acyclovir and symptomatic treatment were initiated. Due to the atient’s deteriorated condition, corticosteriods were added. Epidemiological investigation revealed that the patient had lived for a long time in the Western Carpathian Mountains in the Váh River basin (Trenčín Region), which is one of the most active TBE endemic areas in Slovakia.

The man reported no recent tick bites, no consumption of raw milk products, and no professional exposure. He only mentioned frequent walks with his dog. In the 47th week after the onset of the disease, during a hospital readmission due to choreatic dyskinesia, cardiopulmonary insufficiency occurred, leading to the patient’s death. He had not been vaccinated against TBE. In 2009−2023, 1992 TBE cases were reported in Slovakia; 99,4% (1793/1803) of TBE cases with known vaccination history were unvaccinated. Current legislation regulates TBE vaccination as the recommended vaccination for persons who are occupationally exposed to an increased risk of TBE (primarily occupations in agriculture, forestry, tourism and recreation sectors). Based on an assessment of occupational exposure, the vaccine is reimbursed by the employer. Other citizens may be vaccinated at their own request through self-payment of the vaccine or through health insurance benefits.

Table 1. Main laboratory findings

DISCUSSION

The diagnosis of TBE is based on the detection of specific IgM antibodies in the cerebrospinal fluid. These antibodies develop with a slight delay and may not be detectable at the onset of the disease. This may cause underreporting of TBE compared to the real number of cases. The reasons for the underreporting of TBE in Europe are multifactorial; only 8% of European countries use the current ECDC diagnostic criteria. Other reasons include specific symptoms in paediatric patients, access to diagnostic tests, and suboptimal surveillance systems or passive surveillance [2]. Through active-passive surveillance with the integration of microbiological and epidemiological information systems, we strive to improve the quality of data on acute cases of TBE.