The Detectability of the Viral RNA in Blood and Cerebrospinal Fluid of Patients with Tick-Borne Encephalitis

Grygorczuk, Sambor; Dunaj-Małyszko, Justyna; Czupryna, Piotr; Sulik, Artur; Toczyłowski, Kacper; Siemieniako-Werszko, Agnieszka; Żebrowska, Agnieszka; Pancewicz, Sławomir; Moniuszko‐Malinowska, Anna

doi:10.3390/ijms23169332

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…Despite PCR analysis of TBEV using a duplex TaqMan real-time PCR assay of 600 CSF samples, we could not detect any positive findings, which corroborates previous findings indicating that TBEV is rarely detected in serum or CSF at the time of onset of neurological symptoms [150,151]. Among the six patients with a positive serology for TBEV, two patients were regarded as having an ongoing TBEV infection, according to their symptoms and IgM positivity.…”

Section: Polymerase Chain Reaction Analysessupporting

confidence: 82%

Tick-borne diseases and the central nervous system : clinical and immunological aspects

Gyllemark

2023

Linköping University Medical Dissertations

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Lyme neuroborreliosis (LNB) is the dominating form of disseminated infection by the tick-borne bacteria Borrelia (B.) burgdorferi in Sweden as well as in Europe. The diagnosis of the manifestation is based on typical symptoms, together with elevated mononuclear cell count in the cerebrospinal fluid (CSF) and elevated levels of Borrelia-specific antibodies in the CSF. The diagnostic arsenal has, in recent years, been complemented by analysis of the chemokine CXCL13 in the CSF, with increasing levels in the early phase of the disease, even before antibodies can be detected in the CSF. Most patients recover within a couple of months after antibiotic treatment, but a few can suffer from residual symptoms. The mechanisms behind this are still puzzling, but there are indications that the host´s immune response may play a role. Prognostic markers would be desirable and increased understanding of pathogenetic mechanisms may provide a basis for development of new treatment strategies. Other agents besides B. burgdorferi have, however, also been detected in ticks collected in Sweden, but the knowledge of their impact on human health and their ability to invade the central nervous system (CNS) is limited.The aims of this thesis were to investigate a set of cytokines and chemokines associated with Th1 (CXCL10), Th2 (CCL22), Th17 (IL-17A, CXCL1, CCL20) and B cell (APRIL, BAFF, CXCL13) -related immunity and its association with recovery in patients with LNB included both retrospectively and prospectively. The chemokine CXCL13 was further analysed, comparing the performance of two different diagnostic methods. In a large cohort of patients investigated for LNB we investigated signs of other tick-borne diseases by analysing serum and CSF using both molecular and serological techniques.In the retrospective cytokine/chemokine study, all investigated cytokines and chemokines; namely, APRIL, BAFF, CXCL13, IL-17A, CXCL1, and CCL20 could be detected at elevated levels in patients with LNB compared to controls. Patients with recovery > 3 months had higher levels of APRIL, BAFF, and IL-17A. In the prospective study, patients with short recovery (< 1 month) had lower levels of CCL20 and patients with prolonged recovery (> 6 months) had higher levels of IL-17A. The analysis of the chemokine CXCL13 with both an enzyme-linked immunosorbent assay (ELISA) with a best-performanced cut-off of 56 pg/mL and bead-based (Luminex) method with a best-performance cut-off of 158 pg/mL (both assays with 100% sensitivity and specificity) displayed the importance of different cut-offs depending on which method that is used.In 600 patients, we analysed serum and CSF with PCR for the different tick-borne agents Anaplasma phagocytophilum, B. burgdorfer spp. (including B. miyamotoi), Neoehrlichia (N.) mikurensis, Rickettsia spp., Babesia spp. and tick-borne encephalitis virus. N. mikurensis and B. burgdorferi could be detected by PCR in sera from two patients. Neither PCR, nor serological analysis could detect any potential co-infections.In conclusion, we ca...

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Section: Polymerase Chain Reaction Analysessupporting

confidence: 82%

Tick-borne diseases and the central nervous system : clinical and immunological aspects

Gyllemark

2023

Linköping University Medical Dissertations

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“…He was TBEV-PCR positive in both serum and CSF in the second phase of his disease. Viral persistence in serum and CSF is unusual and might indicate a lack of virus neutralisation during the first peripheral disease phase [ 32 ]. Chemotherapy in relation to hematological cancer treatment has previously been associated with prolonged viremia [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Severe Tick-Borne Encephalitis (TBE) in a Patient with X-Linked Agammaglobulinemia; Treatment with TBE Virus IgG Positive Plasma, Clinical Outcome and T Cell Responses

Hedin,

Bergman,

Akhirunessa

et al. 2024

J Clin Immunol

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Purpose A patient with X-linked agammaglobulinemia (XLA) and severe tick-borne encephalitis (TBE) was treated with TBE virus (TBEV) IgG positive plasma. The patient’s clinical response, humoral and cellular immune responses were characterized pre- and post-infection. Methods ELISA and neutralisation assays were performed on sera and TBEV PCR assay on sera and cerebrospinal fluid. T cell assays were conducted on peripheral blood the patient and five healthy vaccinated controls. Results The patient was admitted to the hospital with headache and fever. He was not vaccinated against TBE but receiving subcutaneous IgG-replacement therapy (IGRT). TBEV IgG antibodies were low-level positive (due to scIGRT), but the TBEV IgM and TBEV neutralisation tests were negative. During hospitalisation his clinical condition deteriorated (Glasgow coma scale 3/15) and he was treated in the ICU with corticosteroids and external ventricular drainage. He was then treated with plasma containing TBEV IgG without apparent side effects. His symptoms improved within a few days and the TBEV neutralisation test converted to positive. Robust CD8+ T cell responses were observed at three and 18-months post-infection, in the absence of B cells. This was confirmed by tetramers specific for TBEV. Conclusion TBEV IgG-positive plasma given to an XLA patient with TBE without evident adverse reactions may have contributed to a positive clinical outcome. Similar approaches could offer a promising foundation for researching therapeutic options for patients with humoral immunodeficiencies. Importantly, a robust CD8+ T cell response was observed after infection despite the lack of B cells and indicates that these patients can clear acute viral infections and could benefit from future vaccination programs.

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“…The diagnosis of TBE is dependent on the stage of the disease in which the patient presents. In the first phase of the disease, characterised by viraemia, serum, and very rarely CSF TBEV reverse transcriptase-polymerase chain reaction (RT-PCR) is positive, in the absence of serology [1,93]. In the setting of immunosuppression, peripheral viraemia may persist for up to 74 days post-infection [93].…”

Section: Diagnosing Tbevmentioning

confidence: 99%

“…In the first phase of the disease, characterised by viraemia, serum, and very rarely CSF TBEV reverse transcriptase-polymerase chain reaction (RT-PCR) is positive, in the absence of serology [1,93]. In the setting of immunosuppression, peripheral viraemia may persist for up to 74 days post-infection [93]. As demonstrated in other orthoflaviviruses, urine can be a potential diagnostic sample.…”

Section: Diagnosing Tbevmentioning

confidence: 99%

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Tick-Borne Encephalitis (TBE): From Tick to Pathology

Worku

2023

JCM

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Tick-borne encephalitis (TBE) is a viral arthropod infection, endemic to large parts of Europe and Asia, and is characterised by neurological involvement, which can range from mild to severe, and in 33–60% of cases, it leads to a post-encephalitis syndrome and long-term morbidity. While TBE virus, now identified as Orthoflavivirus encephalitidis, was originally isolated in 1937, the pathogenesis of TBE is not fully appreciated with the mode of transmission (blood, tick, alimentary), viral strain, host immune response, and age, likely helping to shape the disease phenotype that we explore in this review. Importantly, the incidence of TBE is increasing, and due to global warming, its epidemiology is evolving, with new foci of transmission reported across Europe and in the UK. As such, a better understanding of the symptomatology, diagnostics, treatment, and prevention of TBE is required to inform healthcare professionals going forward, which this review addresses in detail. To this end, the need for robust national surveillance data and randomised control trial data regarding the use of various antivirals (e.g., Galidesivir and 7-deaza-2′-CMA), monoclonal antibodies, and glucocorticoids is required to improve the management and outcomes of TBE.

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The Detectability of the Viral RNA in Blood and Cerebrospinal Fluid of Patients with Tick-Borne Encephalitis

Cited by 9 publications

References 28 publications

Tick-borne diseases and the central nervous system : clinical and immunological aspects

Tick-borne diseases and the central nervous system : clinical and immunological aspects

Severe Tick-Borne Encephalitis (TBE) in a Patient with X-Linked Agammaglobulinemia; Treatment with TBE Virus IgG Positive Plasma, Clinical Outcome and T Cell Responses

Tick-Borne Encephalitis (TBE): From Tick to Pathology

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