**8.5. Genetic factors**

Knowledge in the understanding of TBE serology is required also in patients with meningitis or meningoencephalitis or who had been previously vaccinated against TBE. Serological response in patients with TBE vaccination breakthroughs is as a rule distinct from the response in patients who had not been vaccinated; unawareness of the pattern may result in fail to notice vaccination breakthrough cases. Serologic response in these patients is characterized by a delayed development of specific IgM response (during the initial days of the meningoencephalitic phase of TBE, specific IgM antibodies may not be detectable) associated with a high and rapidly increasing levels of specific serum IgG antibodies [63, 64, 67]. For a reliable diagnosis of TBE in persons previously vaccinated against TBE, demonstration of intrathecal

32 Meningoencephalitis - Disease Which Requires Optimal Approach in Emergency Manner

**8. Factors influencing clinical course of acute disease and/or long‐term** 

Subtype of TBEV influences the course of acute TBE as well as its long‐term outcome. The disease caused by the European TBEV subtype usually has a biphasic course, around 10% of adult patients have a severe neurologic deficit, case‐fatality rate is <2% [12, 32]. According to a prospective study the abortive form of TBE is rare—the initial phase most of the time move on to the second phase of the disease [51]. Long‐lasting sequelae are identified in up to 50% of adult patients [103]. The disease is less severe and has a better outcome in children than in

Symptomatic infections with Far Eastern TBEV subtype often cause an illness with a gradual onset, more severe course, higher rates of severe neurologic sequelae, and a fatality rate of 20–40%; the severity and outcome in adults and children are similar. Limited information about the clinical course of the disease is available for Siberian TBEV subtype. The case-fatality rate is 2–3%; some reports from Russia suggest an association with a chronic progressive form

Published data suggest the relationship between age of patients and the severity of TBE and its outcome — the severity of acute illness and the proportion of patients with unfavorable

The disease caused by European subtype of TBEV generally has a milder course and better outcome in children than in adults. The predominant form of TBE in children and adolescents is meningitis. A summary of 8 studies on 1169 children with TBE showed that meningitis was present in 802 (69%), meningoencephalitis in 356 (30%), and meningoencephalomyelitis in 11 (1%) patients. A total of 20 out of 945 patients (2.1%) had long‐term neurologic sequelae [34]. In contrary to children, in adults, and especially in elderly patients with TBE caused by European subtype of TBEV, the most frequent presentation is meningoencephalitis [33, 47].

production of TBEV antibodies is needed [45].

**outcome**

**8.1. Subtype of TBEV**

adults [34, 50, 104, 105].

of TBE [1, 11].

**8.2. Age of patients**

outcome increase with age [33, 47, 50, 106].

Host‐related factors, particularly genetically determined variability of the inflammatory/ immune response, very likely have an important impact on the course and long-term outcome of TBE. In 2008, Kindberg and coworkers published the results of the study carried out on the Lithuanians, showing that a mutation in a chemokine receptor 5 (CCR5) gene increases the risk for the development of TBE after TBEV infection, but not for more severe disease [114]. Three years later the same group reported on an association between the wild-type Toll‐like receptor 3 (TLR3) rs3775291 allele and increased risk of TBE and suggested that a functional TLR3 may be associated with disease severity [115]. Similar findings were also reported by Mickiene et al. [116]. Furthermore, Barkhash and coworkers found an association between polymorphism in the promoter region of CD209 gene and predisposition to severe illness, and a possible association between 5 OAS single nucleotide polymorphisms and the TBEV infection outcome in Russians [117, 118].

In the future we expect new interesting discoveries on the role of host genetic factors in TBEV infections.
