Comparison of Clinical, Laboratory and Immune Characteristics of the Monophasic and Biphasic Course of Tick-Borne Encephalitis

Abstract

The biphasic course of tick-borne encephalitis (TBE) is well described, but information on the monophasic course is limited. We assessed and compared the clinical presentation, laboratory findings, and immune responses in 705 adult TBE patients: 283 with monophasic and 422 with biphasic course. Patients with the monophasic course were significantly (p ≤ 0.002) older (57 vs. 50 years), more often vaccinated against TBE (7.4% vs. 0.9%), more often had comorbidities (52% vs. 37%), and were more often treated in the intensive care unit (12.4% vs. 5.2%). Multivariate logistic regression found strong association between the monophasic TBE course and previous TBE vaccination (OR = 18.45), presence of underlying illness (OR = 1.85), duration of neurologic involvement before cerebrospinal fluid (CSF) examination (OR = 1.39), and patients’ age (OR = 1.02). Furthermore, patients with monophasic TBE had higher CSF levels of immune mediators associated with innate and adaptive (Th1 and B-cell) immune responses, and they had more pronounced disruption of the blood–brain barrier. However, the long-term outcome 2–7 years after TBE was comparable. In summary, the monophasic course is a frequent and distinct presentation of TBE that is associated with more difficult disease course and higher levels of inflammatory mediators in CSF than the biphasic course; however, the long-term outcome is similar.

Complete Genome Sequencing of Tick-Borne Encephalitis Virus Directly from Clinical Samples: Comparison of Shotgun Metagenomic and Targeted Amplicon-Based Sequencing

“…Human infections with TBEV have highly variable courses, including asymptomatic infection, febrile illness without central nervous system (CNS) involvement, or various forms of CNS inflammation (TBE), ranging from a mild uneventful course to a fatal outcome. In patients with TBE, older age is a major risk factor for severe disease [12,13], and other host factors that influence the disease course and outcome are still largely unknown. On the other hand, TBEV subtypes have been associated with various disease courses and mortality rates.…”

“…Neurological symptoms appear in the second phase of the disease, which usually follows a week-long improvement. In addition to acute CNS inflammation, 1.0 to 1.7% of patients infected with the TBEV-Sib subtype could develop a chronic course of the disease, with a fatality rate of 6.0 to 8.0% [13]. The TBEV-FE subtype is associated with the most severe disease, which typically has a monophasic course and a 5.0 to 20.0% fatality rate.…”

A Retrospective Analysis of Tick-borne Encephalitis in Children Treated in Kaunas Hospital During 2012 to 2019

“…Similar results were seen in a pediatric study done in Slovenia and Austria. 12,13 Also, although monophasic disease is associated with more severe forms of TBE 14 and expected to be more common in adults who usually have more severe course, a recent adult study in Northern Italy 15 and a previous Lithuanian adult study 16 revealed that 72% of adults had a biphasic course of the disease which shows no significant difference between children and adults in this matter.…”

Safety and immunogenicity following co-administration of Yellow fever vaccine with Tick-borne encephalitis or Japanese encephalitis vaccines: Results from an open label, non-randomized clinical trial

“…These viruses pose major global health challenges, both for inhabitants in affected areas (around 1/3 of the world’s population) as well as for travelers to these areas [ 1 – 5 ]. Infection with these viruses is associated with significant morbidities, hospitalization costs, sick leave-associated costs, and loss of productivity as well as over 100,000 of fatal outcomes per year [ 2 , 4 , 6 – 9 ]. No specific treatment for these diseases exists, though development of antiviral drug candidates has been initiated [ 10 – 14 ].…”