Tick-borne encephalitis : clinical and pathogenetic aspects

The aims of this study were to investigate the morbidity associated with tick-borne encephalitis (TBE) in the acute stage and at long-term follow-up, to identify the possible host risk factors for development of clinical TBE with special reference to the role of the genetic polymorphism, and to investigate neurochemical changes in the brain induced by TBE virus (TBEV) and their possible role on severity of TBE with special reference to endogenous kynurenic acid (KYNA). Paper I: Of 250 consecutively admitted patients with central nervous system (CNS) infections treated during a 1-year period, all 133 patients with TBE participated in the prospective follow-up study. TBE presented as mild (meningeal), moderate or severe (encephalitic) forms in 43.6%, 43.6% and 12.8%, respectively. Paralytic disease was observed in 3.8%, and cranial nerve injury in 5.3% of the TBE patients. Permanent CNS dysfunction after 1 year was found in 30.8% of patients; in 8.5% of all TBE cases, severe disabilities required adjustment of daily activities. Cognitive CNS dysfunction was the dominant symptom in patients with more pronounced sequelae. A higher risk for incomplete recovery was seen for the encephalitic form of TBE (odds ratio (OR), 4.066; 95% confidence interval (CI), 1.848–8.947). Papers II and III: A prospectively collected material from patients with TBE (n=129), aseptic meningoencephalitis of non-TBEV aetiology (n=79) and healthy TBEV-naive Lithuanians (n=135) were used in studies on chemokine receptor 5 (CCR5) and Toll-like receptor 3 (TLR3) rs3775291 gene polymorphisms. In addition, children TBE cohort (n=117) and a cohort of adults with severe TBE (n=103) were recruited in Paper III. The prevalence of CCR5Δ32 homozygotes was higher among the adults with TBE (2.3%), among children with TBE (2.5%), among adults with severe TBE (1.9%), and in the overall cohort of TBE patients (2.3%) than in controls (0%) (p<0.05). Hence, the CCR5 polymorphism was identified as a significant risk factor for clinical TBE. The CCR5Δ32 allele prevalence was higher in the combined children and adult TBE cohort compared with TBEV-naive individuals, and suggested CCR5Δ32 allele being a risk factor for clinical TBEV infection (OR 1.672; 95% CI 1.005–2.782). The nonfunctional homozygous TLR3 genotype was less prevalent among the combined TBE cohort (11.5%) than among controls (19.9%) (p = 0.025), but did not differ between children TBE and controls. The genotype and allele prevalence of CCR5 and TLR3 did not differ in children nor adult TBE cohorts stratified by disease severity. In adults with severe TBE, homozygous functional TLR3 genotype and wt allele were less prevalent than in adults with the whole disease severity spectrum (44.4% vs 59.8% p = 0.022 and 65.2% vs 76.4% p = 0.009; respectively). Paper IV has shown that cerebrospinal fluid (CSF) KYNA levels were considerably higher in patients with TBE recruited from Paper I (5.3 nmol L-1) than in control subjects (0.99 nmol L-1) and increased (p<0.05) with severity of TBE. Conclusion: TBE is the main CNS infection in adults in Lithuania, causing a considerable morbidity with long-lasting sequelae in one-third of patients. Cognitive CNS dysfunction dominates and is the major cause of long-lasting impairment of the quality of life. High levels of KYNA in CSF of TBE patients serve as a marker of severity of TBE. Host genetic polymorphism plays a role in the development of clinical TBE and may even be linked to the disease severity

Serum and cerebrospinal fluid brain damage markers neurofilament light and glial fibrillary acidic protein correlate with tick-borne encephalitis disease severity—a multicentre study on Lithuanian and Swedish patients

Background and purpose: Our aim was to examine the correlation between biomarkers of neuronal and glial cell damage and severity of disease in patients with tick-borne encephalitis.// Methods: One hundred and fifteen patients with tick-borne encephalitis diagnosed in Lithuania and Sweden were prospectively included, and cerebrospinal fluid (CSF) and serum samples were obtained shortly after hospitalization. Using pre-defined criteria, cases were classified as mild, moderate or severe tick-borne encephalitis. Additionally, the presence of spinal nerve paralysis (myelitis) and/or cranial nerve affection were noted. Concentrations of the brain cell biomarkers glial fibrillary acidic protein (GFAP), YKL-40, S100B, neurogranin, neurofilament light (NfL) and tau were analysed in CSF and, in addition, NfL, GFAP and S100B levels were measured in serum. The Jonckheere-Terpstra test was used for group comparisons of continuous variables and Spearman's partial correlation test was used to adjust for age.// Results: Cerebrospinal fluid and serum concentrations of GFAP and NfL correlated with disease severity, independent of age, and with the presence of nerve paralysis. The markers neurogranin, YKL-40, tau and S100B in CSF and S100B in serum were detected, but their concentrations did not correlate with disease severity.// Conclusions: Neuronal cell damage and astroglial cell activation with increased NfL and GFAP in CSF and serum were associated with a more severe disease, independent of age. Increased GFAP and NfL concentrations in CSF and NfL in serum were also indicative of spinal and/or cranial nerve damage. NfL and GFAP are promising prognostic biomarkers in tick-borne encephalitis, and future studies should focus on determining the association between these biomarkers and long-term sequelae

Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023

Members of the European Hospital Vaccine Effectiveness Group: Portugal: Ana Paula Rodrigues, Débora Pereira, Susana Costa Maia e Silva, Paula Pinto, Cristina Bárbara, António Pais de Lacerda, Raquel Guiomar and Camila Henriques.The European Medicines Agency (EMA) authorised four adapted bivalent mRNA COVID-19 vaccines for use against COVID-19 in September/October 2022: Comirnaty (BNT162b2; Pfizer-BioNTech) and Spikevax (mRNA-1273; Moderna) Original/Omicron BA.1 and Original/Omicron BA.4–5 [1]. During autumn 2022, all European Union/European Economic Area (EU/EEA) countries had vaccination campaigns in place to administer a booster dose, with several countries using the adapted bivalent vaccines [2]. The Omicron-descendent XBB lineage and XBB.1.5 sub-lineage became variants of interest in March 2023 [3]. We estimated the effectiveness of the COVID-19 bivalent vaccines against hospitalisation with PCR-confirmed SARS-CoV-2 infection among patients aged ≥ 60 years with severe acute respiratory infection (SARI) during the XBB lineage-predominant period.The ‘Vaccine Effectiveness, Burden and Impact Studies studies’ (VEBIS) is a project of the European Centre for Disease Prevention and Control (ECDC) run under the framework con tract No. ECDC/2021/016.info:eu-repo/semantics/publishedVersio

Hospitalized Adult Patients with 2009 Pandemic Influenza A (H1N1) in Kaunas, Lithuania

The objective of this study was to identify case characteristics and clinical course of the disease in patients hospitalized with 2009 pandemic influenza A (H1N1) infection during the first wave of the pandemic and to identify risk factors associated with the complicated course of illness. Material and methods. A retrospective study of adult cases of the laboratory-confirmed 2009 pandemic influenza A (H1N1) virus admitted to three hospitals in Kaunas between November 1, 2009, and March 15, 2010, was carried out. The main outcome measures were clinical characteristics, risk factors for complicated disease, treatment, and clinical course of the disease. Results. The study enrolled 121 of the 125 patients hospitalized due to 2009 pandemic influenza A (H1N1) virus infection. The median age was 31 years (range, 18–83); 5% of the patients were aged more than 65 years. Pregnant and postpartum women comprised 26% of all hospitalized cases. Nearly half (49.5%) of those who underwent chest radiography had findings consistent with pneumonia, which was bilateral in one-third of cases. The risk to have pandemic influenza complicated by pneumonia increased significantly with one-day delay from symptom onset to antiviral treatment (OR, 2.241; 95% CI, 1.354–3.710). More than half (57%) of the patients received antiviral treatment. In 45% of the treated patients, antiviral drugs were administered within 48 hours from symptom onset. Intensive care was required in 7.4% of the cases. The overall mortality was 5% (6/121). The median age of the patients who died was 43.5 years (range, 23–62); 4 patients had been previously healthy, 1 patient suffered from chronic lympholeukemia, and 1 patient was a pregnant woman. Conclusion. The 2009 pandemic influenza A (H1N1) caused considerable morbidity in a significant proportion of hospitalized adults. The main risk factor associated with the complicated course of illness was delayed antiviral treatment

COVID-19 in a Patient with Liver Cirrhosis

The outbreak of coronavirus disease 2019 (COVID-19) has recently become a serious issue affecting thousands of people worldwide. It is known that a substantial proportion of patients infected with COVID-19 have abnormal liver function tests; however, the consequences of this information is still not clear. Here we present the first case report of a patient with liver cirrhosis and COVID-19 in our centre. Resolution of COVID-19 symptoms was observed after six days of fever onset. We observed only slight fluctuations of liver enzymes, bilirubin levels and INR without clinical consequences in our case. We suggest testing for severe acute respiratory syndrome coronavirus on any cirrhotic patient on initial presentation, even without symptoms of COVID-19 in areas where the epidemic was prevalent

Acquired immunodeficiency syndrome and opportunistic infections

This article presents a clinical case of late diagnosis of cerebral toxoplasmosis and cytomegalovirus retinitis of right eye in a 32-year-old patient who was unaware of her HIV status. In addition, this article reviews the literature reflecting clinical, diagnostic, and treatment issues of some opportunistic infections in AIDS

Etiology and epidemiology of tick-borne encephalitis. A review

Šiame straipsnyje pateikiama literatūros apžvalga apie erkinio encefalito virusą bei erkinio encefalito epidemiologiją. Erkinio encefalito virusas (EEV) priklauso flavivirusų šeimai. Svarbiausia viruso dalis yra apvalkalo baltymas E, kuris indukuoja apsauginį imunitetą, dalyvauja jungiantis su ląstelės receptoriais, nuo jo priklauso viruso virulentiškumas. EEV skirstomas į tris potipius − Europos, Tolimųjų Rytų ir Sibiro. Nepaisant labai panašios skirtingų potipių antigeninės struktūros, jų virulentiškumas skiriasi. Pagrindiniai viruso pernešėjai yra Ixodidae šeimos erkės. Jos EEV užsikrečia vireminiu, nevireminiu, transovariniu ir transstadijiniu būdu. Nevireminis EEV perdavimas yra svarbiausias viruso persistavimui ir plitimui gamtiniame židinyje. Endeminėse teritorijose 0,1−26,6 proc. erkių yra infekuotos EEV. Erkių šeimininkais gamtoje gali būti daugiau nei šimto rūšių gyvūnai – žinduoliai, paukščiai, ropliai. Jie skirstomi į rezervuarinius, indikatorinius ir atsitiktinius. Svarbiausi rezervuariniai viruso šeimininkai yra smulkieji gaužikai. Jų infekuotumas EEV yra 15−47,9 proc. Paukščiai nėra reikšminga EEV rezervuarinė gyvūnų grupė, tačiau migruojantys paukščiai sąlygoja viruso išplitimą naujuose regionuose. Per pastaruosius tris dešimtmečius sergamumas erkiniu encefalitu (EE) Europoje padidėjo keturis kartus. Kadangi ši liga yra zoonozė, sergamumo didėjimo priežastys yra kompleksinės, susijusios su nuolat didėjančiu rezervuarinių šeimininkų ir ligos pernešėjų paplitimu ir gausa, sąlygotų globalinio klimato atšilimo. Kitos sergamumo didėjimo priežastys yra socialinės, ekonominės arba sąlygotos žmonių veiklos. Didėjantis dėmesys erkių pernešamoms ligoms, dažniau tikslingai taikoma EE diagnostika ir gerėjanti ligų registracija taip pat sąlygoja didesnį nustatomų susirgimų skaičiųBiologijos katedraVytauto Didžiojo universiteta

Effects of Combined Treatment with Sodium Dichloroacetate and Sodium Valproate on the Genes in Inflammation- and Immune-Related Pathways in T Lymphocytes from Patients with SARS-CoV-2 Infection with Pneumonia: Sex-Related Differences

The study presents data on the anti-inflammatory effects of a combination of sodium dichloroacetate and sodium valproate (DCA–VPA) on the expression of inflammation- and immune response-related genes in T lymphocytes of SARS-CoV-2 patients. The study aimed to assess the effects of DCA–VPA on the genes of cytokine activity, chemokine-mediated signaling, neutrophil chemotaxis, lymphocyte chemotaxis, T-cell chemotaxis, and regulation of T-cell proliferation pathways. The study included 21 patients with SARS-CoV-2 infection and pneumonia: 9 male patients with a mean age of 68.44 ± 15.32 years and 12 female patients with a mean age of 65.42 ± 15.74 years. They were hospitalized between December 2022 and March 2023. At the time of testing, over 90% of sequences analyzed in Lithuania were found to be of the omicron variant of SARS-CoV-2. The T lymphocytes from patients were treated with 5 mmol DCA and 2 mmol VPA for 24 h in vitro. The effect of the DCA–VPA treatment on gene expression in T lymphocytes was analyzed via gene sequencing. The study shows that DCA–VPA has significant anti-inflammatory effects and apparent sex-related differences. The effect is more potent in T cells from male patients with SARS-CoV-2 infection and pneumonia than in females

Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza in 2015–2016: a hospital-based testnegative case–control study in Lithuania

Objective A case–control study was conducted to assess seasonal influenza vaccine effectiveness (SIVE) during the 2015–2016 influenza season. Methods A study was performed in three departments in Lithuania between 1 December 2015 and 1 May 2016. Data on demographic and clinical characteristics including influenza vaccination status were collected from the patients recommended to receive the seasonal influenza vaccine. Influenza virus infection was confirmed by multiplex reverse transcription polymerase chain reaction (RT-PCR) . Results Ninety-one (56.4%) of the 163 included subjects were ≥65 years old. Fifteen (9.2%) subjects were vaccinated against influenza at least 2 weeks before the onset of influenza symptoms, 12 of them were ≥65 years old. Of the 72 (44.2%) influenza virus positive cases, 65 (39.9%) were confirmed with influenza A (including 50 cases of influenza A(H1N1)pdm09), eight (4.9%) were confirmed with influenza B and one was a co-infection. Unadjusted SIVE against any influenza, influenza type A and influenza A(H1N1)pdm09 was 57% (95% CI −41% to 87%), 52% (95% CI −57% to 85%) and 70% (95% CI −43% to 94%) respectively. Conclusion Although SIVE estimates were not statistically significant the point estimates suggest moderate effectiveness against influenza type A