Tick-borne encephalitis immunoglobulin human solution for injection 5ml vials

• Tick-borne encephalitis is an emerging arboviral disease in Europe, particularly in France. • TBEV is transmitted not only by tick bites, but also by ingestion of contaminated raw dairy products. • While in 30% of cases TBEV-Eu infections are symptomatic with mild symptoms, some patients develop meningitis or meningoencephalitis, and post-infectious sequelae may occur. • This review provides an up-to-date overview of the latest data concerning TBE, focusing on the epidemiology and clinical, diagnostic, and therapeutic aspects of this emerging infection. Tick-borne encephalitis (TBE), which is caused by the tick-borne encephalitis virus (TBEV), is primarily transmitted to humans through Ixodes bites of infected ticks of the genus Ixodes and, more rarely, by the consumption of contaminated dairy products. TBEV encompasses three main subtypes with distinct degrees of severity and clinical courses: European (TBEV-Eu), Siberian (TBEV-Sib), and Far Eastern (TBEV-FE). Over the past decade, TBE epidemiology has significantly changed in Europe, with increasing incidence in endemic countries and the discovery of new human case foci and areas of virus circulation. This emergence involves many factors of which the impacts are not easily determined. While most TBEV-Eu infections are asymptomatic, some patients develop signs of central nervous system involvement that can be severe (meningitis, encephalitis). While the mortality rate in humans is low (< 2 %), post-infectious sequelae (cognitive and/or motor) can occur in up to 40 % of cases. While TBE treatment is symptomatic, several antiviral treatments are under study. The emergence of TBEV in Europe, particularly in France, represents a significant public health issue. This review provides an up-to-date overview of the latest data concerning TBE, focusing on the epidemiology and clinical, diagnostic, and therapeutic aspects of this emerging infection.

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INTRODUCTION . Pharmaceutical production uses reference standards as an integral part of metrological support for analytical methods. A systematic literature analysis on standardisa­tion of human immunoglobulin preparations, particularly specific and special-purpose ones, will allow evaluating the metrological support in the Russian Federation and identifying new approaches to obtaining and using reference standards to assess specific potency. AIM . This study aimed to analyse published data on the range of reference standards used to evaluate potency of human immunoglobulins in the Russian Federation and abroad. DISCUSSION . PubMed, eLIBRARY.RU, and ConsultantPlus® legal research system showed that the list of international reference standards includes Rh 0 (D), hepatitis B, tetanus, staphylococcal and cytomegalovirus infections, rabies, and smallpox human immunoglobulins. No reference standard is available for human immunoglobulin against tick-borne encephalitis, since no specific human immunoglobulin is produced in the European Union. There is an absolute dependence on the import of international reference standards for assessing the potency of human hepatitis B, cytomegalovirus, and rabies immunoglobulins. Reference standards are typically obtained from ready-to-use batches of medicinal products and then stabilised, bottled under sterile conditions, and lyophilised. The Register of the State Pharmacopoeia of the Russian Federation includes reference standards for Rh 0 (D), anti-tetanus serum, and staphylococcal immunoglobulin. Unlike international reference standards, pharmacopoeial standards are produced as solutions, thus significantly reducing antibody stability. For pharmacopoeial reference standards, statistical uncertainty of the certified value is established in the Russian Federation; however, while certifying international reference standards, their certification is not obligatory. According to literature analysis, the key requirements for reference standards are stability and composition / properties similar to standardised preparations. Russian and foreign certification requirements of reference standards have certain differences. The number of Russian reference standards based on human immunoglobulin G is limited, since they are mostly obtained from horse blood serum. CONCLUSIONS . Russian pharmaceutical industry shows a deficit of national reference standards used for assessing specific potency of human immunoglobulins and donor plasma for their production. Thus, such reference standards should be released as lyophilisates and certified in international units, with an evaluation of statistical uncertainty of the antibody content.

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Tick-borne encephalitis (TBE) is a viral disease endemic in Eurasia. The virus is mainly transmitted to humans via ticks and occasionally via the consumption of unpasteurized milk products. The European Centre for Disease Prevention and Control reported an increase in TBE incidence over the past years in Europe as well as the emergence of the disease in new areas. To better understand this phenomenon, we investigated the drivers of TBE emergence and increase in incidence in humans through an expert knowledge elicitation. We listed 59 possible drivers grouped in eight domains and elicited forty European experts to: (i) allocate a score per driver, (ii) weight this score within each domain, and (iii) weight the different domains and attribute an uncertainty level per domain. An overall weighted score per driver was calculated, and drivers with comparable scores were grouped into three terminal nodes using a regression tree analysis. The drivers with the highest scores were: (i) changes in human behavior/activities; (ii) changes in eating habits or consumer demand; (iii) changes in the landscape; (iv) influence of humidity on the survival and transmission of the pathogen; (v) difficulty to control reservoir(s) and/or vector(s); (vi) influence of temperature on virus survival and transmission; (vii) number of wildlife compartments/groups acting as reservoirs or amplifying hosts; (viii) increase of autochthonous wild mammals; and (ix) number of tick species vectors and their distribution. Our results support researchers in prioritizing studies targeting the most relevant drivers of emergence and increasing TBE incidence.

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Background.In the face of ongoing climate warming, vector-borne diseases are expected to increase in Europe, including tick-borne diseases (TBD).The most abundant tick-borne diseases in Germany are Tick-Borne Encephalitis (TBE) and Lyme Borreliosis (LB), with Ixodes ricinus as the main vector.Methods.In this study, we display and compare the spatial and temporal patterns of reported cases of human TBE and LB in relation to some associated factors.The comparison may help iwith the interpretation of observed spatial and temporal patterns.Results.The spatial patterns of reported TBE cases show a clear and consistent pattern over the years, with many cases in the south and only few and isolated cases in the north of Germany.The identification of spatial patterns of LB disease cases is more difficult due to the different reporting practices in the individual federal states.Temporal patterns strongly fluctuate between years, and are relatively synchronized between both diseases, suggesting common driving factors.Based on our results we found no evidence that weather conditions affect the prevalence of both diseases.Both diseases show a gender bias with LB bing more commonly diagnosed in females, contrary to TBE being more commonly diagnosed in males. Conclusion.For a further investigation of of the underlying driving factors and their interrelations , longer time series as well as standardised reporting and surveillance system would be required.

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BackgroundTick-borne encephalitis virus (TBEV) is a flavivirus spread by ticks and can cause tick-borne encephalitis (TBE) in humans. Previously, TBE has been reported in returning travellers in the United Kingdom (UK), but in 2019 and 2020, two probable cases of TBE acquired in the UK were identified.AimThe aim of this study was to investigate TBE cases in the UK between 2015 and 2023, describing the incidence, place and mode of acquisition and diagnostic process.MethodsA retrospective review of possible, probable and confirmed cases of TBE diagnosed by the Rare and Imported Pathogens Laboratory (RIPL) between January 2015 and December 2023 was performed. For cases identified in 2022 and 2023, clinical data were collected for enhanced surveillance using structured case record forms. Laboratory diagnosis is reviewed and described.ResultsWe identified 21 cases: three possible, seven probable and 11 confirmed cases. Of these, 12 were between January 2022 and December 2023: three possible, three probable and six confirmed cases. Two confirmed TBE cases had definite or highly probable acquisition in the UK, in June and August 2022, respectively. One of the possible cases had definite UK acquisition. Cases typically have a biphasic presentation, with encephalitis in the second phase.ConclusionClinicians should be aware of the possibility of TBE when the cause for encephalitis is not identified, even in the absence of travel to previously identified endemic regions.

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Abstract Incidence of tick-borne encephalitis (TBE) has increased during the last years in Scandinavia, but the underlying mechanism is not understood. TBE human case data reported between 2010 and 2021 were aggregated into postal codes within Örebro County, south-central Sweden, along with tick abundance and environmental data to analyse spatial patterns and identify drivers of TBE. We identified a substantial and continuing increase of TBE incidence in Örebro County during the study period. Spatial cluster analyses showed significant hotspots (higher number of cases than expected) in the southern and northern parts of Örebro County, whereas a cold spot (lower number of cases than expected) was found in the central part comprising Örebro municipality. Generalised linear models showed that the risk of acquiring TBE increased by 12.5% and 72.3% for every percent increase in relative humidity and proportion of wetland forest, respectively, whereas the risk decreased by 52.8% for every degree Celsius increase in annual temperature range. However, models had relatively low goodness of fit (R 2 &lt; 0.27). Results suggest that TBE in Örebro County is spatially clustered, however variables used in this study, i.e., climatic variables, forest cover, water, tick abundance, sheep as indicator species, alone do not explain this pattern.

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BACKGROUND: Ticks are vectors of various pathogens, including tick-borne encephalitis virus causing TBE and bacteria such as Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum causing e.g. viral-bacterial co-infections (TBE + LB/HGA), which pose diagnostic and therapeutic problems. Since these infections are usually accompanied by inflammation and oxidative stress causing metabolic modifications, including phospholipids, the aim of the study was to assess the level of polyunsaturated fatty acids and their metabolism (ROS- and enzyme-dependent) products in the blood plasma of patients with TBE and TBE + LB/HGA before and after pharmacotherapy. METHODS: The total antioxidant status was determined using 2,20-azino-bis-3-ethylbenzothiazolin-6-sulfonic acid. The phospholipid and free fatty acids were analysed by gas chromatography. Lipid peroxidation was estimated by measuring small molecular weight reactive aldehyde, malondialdehyde and neuroprostanes. The reactive aldehyde was determined using gas chromatography coupled with mass spectrometry. The activity of enzymes was examined spectrophotometrically. An analysis of endocannabinoids and eicosanoids was performed using a Shimadzu UPLC system coupled with an electrospray ionization source to a Shimadzu 8060 Triple Quadrupole system. Receptor expression was measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The reduced antioxidant status as a result of infection was accompanied by a decrease in the level of phospholipid arachidonic acid (AA) and docosahexaenoic acid (DHA) in TBE, an increase in DHA in co-infection and in free DHA in TBE with an increase in the level of lipid peroxidation products. The enhanced activity of enzymes metabolizing phospholipids and free PUFAs increased the level of endocannabinoids and eicosanoids, while decreased 15-PGJ2 and PGE2 was accompanied by activation of granulocyte receptors before pharmacotherapy and only tending to normalize after treatment. CONCLUSION: Since classical pharmacotherapy does not prevent disorders of phospholipid metabolism, the need to support treatment with antioxidants may be suggested.

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