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Chapter 6: TBE in children

More specifically, the reason for this is a biomarkers like hepatocyte growth factor and
differential ability of the 2 vaccines to induce vascular endothelial growth factors were
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neutralizing antibodies as a result of a increased in patients with TBE. The
mutation in the DI-DII hinge region of the E significance of immune reactions in pediatric
protein in the K23 strain. This mutation is not TBE has also been reported by Fowler et al.
present in the Neudörfl strain or in any other They found that development of sequelae in
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known naturally occurring TBEVs. Natural pediatric TBE could be related to the grade of
immunity to TBE has seemed to persist over inflammation (i.e., cytokines) rather than
time and as children age, according to direct neuronal damage. High concentrations
Baldovin et al., but with the reservation that of cytokines (interferon-γ, IL-6, and IL-8) in
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their cohort was small. Truly long-term data cerebrospinal fluid might be associated with a
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on natural immunity (for example, follow-up risk of incomplete recovery.
of now-older adults after TBE in childhood
years) have not yet been reported. To conclude, the available TBE vaccines based
on the Neudörfl and K23 strains, respectively,
The differences in clinical appearance of TBE are safe and provide a protective immunity in
between children and adults could stem from most children. The natural long-term
the immune response to the TBEV. In adults, immunity after childhood TBE must be further
polymorphisms and alterations in immune investigated. Evidence suggests that the
receptor genes (such as CCR5, TLR3, immune reactions to the TBEV serve as a key
and CD209) have been reported to play a role player in the clinical course, including risk for
in predisposing individuals to infection and/or residual symptoms and sequelae, in childhood
severity of TBE. 43-45 However, Engman et al. TBE.
reported that the 32-basepair deletion in the

chemokine receptor 5 gene (CCR5Δ32), which
Concluding remarks
impacts adult TBE, were neither more
frequent in children with TBE nor did it have
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any association with the clinical course. The All children deserve the best chance to reach
their full potential. Such a chance includes a
lack of an effect on clinical TBE course life without TBE-related sequelae. Childhood
by CCR5Δ32 in children was later confirmed by
Mickiene et al. Yet, the later and larger study TBE may be associated with death, with
by Mickiene et al. demonstrated that CCR5Δ32 considerable acute disease severity, prolonged
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predisposed children for TBE. convalescence and residual symptoms, and
long-term residua. Hence, advocating for
In adults, the clinical course of TBE has also immunization against TBE in children, even for
been associated with development of auto- the smallest ones, and proper
antibodies against CNS proteins (i.e., markers neurodevelopmental follow-up after cases of
of brain damage). Such autoantibodies were TBE infection cannot be regarded as
detected in children with TBE at a low controversial. Despite being infrequent,
frequency. The occurrence of these antibodies disabling neurologic injuries exist after
did not contrast to those with neuroborreliosis pediatric TBE and, together with the emerging
and had no association with clinical evidence of altered cognitive functioning,
24 action clearly is required–both from the
course. From a study of both children and
adults, Palus et al. have reported a significant medical community and the health authorities
global pro-inflammatory cytokine balance in in TBE endemic regions.
patients with higher serum interleukin (IL)-
12:IL-4 and IL-12:IL-10 ratios versus controls.
Also, novel and mechanistically interesting Contact: mikael.sundin@ki.se

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