The tick-borne pathogen Powassan virus is a rare cause of encephalitis in North America and the Russian Far East. The number of documented cases described since the discovery of Powassan virus in ...1958 may be <150, although detection of cases has increased over the past decade. In the United States, the incidence of Powassan virus infections expanded from the estimated 1 case per year prior to 2005 to 10 cases per year during the subsequent decade. The increased detection rate may be associated with several factors, including enhanced surveillance, the availability of improved laboratory diagnostic methods, the expansion of the vector population, and, perhaps, altered human activities that lead to more exposure. Nonetheless, it remains unclear whether Powassan virus is indeed an emerging threat or if enzootic cycles in nature remain more-or-less stable with periodic fluctuations of host and vector population sizes. Despite the low disease incidence, the approximately 10% to 15% case fatality rate of neuroinvasive Powassan virus infection and the temporary or prolonged sequelae in >50% of survivors make Powassan virus a medical concern requiring the attention of public health authorities and clinicians. The medical importance of Powassan virus justifies more research on developing specific and effective treatments and prevention and control measures.
Tick-borne encephalitis (TBE) is an illness caused by tick-borne encephalitis virus (TBEV) infection which is often limited to a febrile illness, but may lead to very aggressive downstream ...neurological manifestations. The disease is prevalent in forested areas of Europe and northeastern Asia, and is typically caused by infection involving one of three TBEV subtypes, namely the European (TBEV-Eu), the Siberian (TBEV-Sib), or the Far Eastern (TBEV-FE) subtypes. In addition to the three main TBEV subtypes, two other subtypes; i.e., the Baikalian (TBEV-Bkl) and the Himalayan subtype (TBEV-Him), have been described recently. In Europe, TBEV-Eu infection usually results in only mild TBE associated with a mortality rate of <2%. TBEV-Sib infection also results in a generally mild TBE associated with a non-paralytic febrile form of encephalitis, although there is a tendency towards persistent TBE caused by chronic viral infection. TBE-FE infection is considered to induce the most severe forms of TBE. Importantly though, viral subtype is not the sole determinant of TBE severity; both mild and severe cases of TBE are in fact associated with infection by any of the subtypes. In keeping with this observation, the overall TBE mortality rate in Russia is ∼2%, in spite of the fact that TBEV-Sib and TBEV-FE subtypes appear to be inducers of more severe TBE than TBEV-Eu. On the other hand, TBEV-Sib and TBEV-FE subtype infections in Russia are associated with essentially unique forms of TBE rarely seen elsewhere if at all, such as the hemorrhagic and chronic (progressive) forms of the disease. For post-exposure prophylaxis and TBE treatment in Russia and Kazakhstan, a specific anti-TBEV immunoglobulin is currently used with well-documented efficacy, but the use of specific TBEV immunoglobulins has been discontinued in Europe due to concerns regarding antibody-enhanced disease in naïve individuals. Therefore, new treatments are essential. This review summarizes available data on the pathogenesis and clinical features of TBE, plus different vaccine preparations available in Europe and Russia. In addition, new treatment possibilities, including small molecule drugs and experimental immunotherapies are reviewed. The authors caution that their descriptions of approved or experimental therapies should not be considered to be recommendations for patient care.
•Tick-borne encephalitis (TBE) is an acute febrile viral illness with neurological manifestations.•No specific antivirals are approved for TBE therapy.•A number of nucleoside or non-nucleoside antivirals exhibit anti-TBE virus (TBEV) activity in vitro and in vivo.•Specific anti-TBEV immunoglobulin is used for post-exposure prophylaxis and TBE treatment in Russia but not in Europe.•TBE is preventable by effective vaccines but vaccination coverage remains low in many endemic countries.
Tick-borne encephalitis in Europe, 2012 to 2016 Beauté, Julien; Spiteri, Gianfranco; Warns-Petit, Eva ...
Euro surveillance : bulletin européen sur les maladies transmissibles,
11/2018, Letnik:
23, Številka:
45
Journal Article
Recenzirano
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Since 2012, tick-borne encephalitis (TBE) is a notifiable in the European Union. The European Centre for Disease Prevention and Control annually collects data from 28 countries plus Iceland and ...Norway, based on the EU case definition. Between 2012 and 2016, 23 countries reported 12,500 TBE cases (Ireland and Spain reported none), of which 11,623 (93.0%) were confirmed cases and 878 (7.0%) probable cases. Two countries (Czech Republic and Lithuania) accounted for 38.6% of all reported cases, although their combined population represented only 2.7% of the population under surveillance. The annual notification rate fluctuated between 0.41 cases per 100,000 population in 2015 and 0.65 in 2013 with no significant trend over the period. Lithuania, Latvia and Estonia had the highest notification rates with 15.6, 9.5 and 8.7 cases per 100,000 population, respectively. At the subnational level, six regions had mean annual notification rates above 15 cases per 100,000 population, of which five were in the Baltic countries. Approximately 95% of cases were hospitalised and the overall case fatality ratio was 0.5%. Of the 11,663 cases reported with information on importation status, 156 (1.3%) were reported as imported. Less than 2% of cases had received two or more doses of TBE vaccine.
Background. Powassan virus (POWV) is a rarely diagnosed cause of encephalitis in the United States. In the Northeast, it is transmitted by Ixodes scapularis, the same vector that transmits Lyme ...disease. The prevalence of POWV among animal hosts and vectors has been increasing. We present 8 cases of POWV encephalitis from Massachusetts and New Hampshire in 2013–2015. Methods. We abstracted clinical and epidemiological information for patients with POWV encephalitis diagnosed at 2 hospitals in Massachusetts from 2013 to 2015. We compared their brain imaging with those in published findings from Powassan and other viral encephalitides. Results. The patients ranged in age from 21 to 82 years, were, for the most part, previously healthy, and presented with syndromes of fever, headache, and altered consciousness. Infections occurred from May to September and were often associated with known tick exposures. In all patients, cerebrospinal fluid analyses showed pleocytosis with elevated protein. In 7 of 8 patients, brain magnetic resonance imaging demonstrated deep foci of increased T2/fluid-attenuation inversion recovery signal intensity. Conclusions. We describe 8 cases of POWV encephalitis in Massachusetts and New Hampshire in 2013–2015. Prior to this, there had been only 2 cases of POWV encephalitis identified in Massachusetts. These cases may represent emergence of this virus in a region where its vector, I. scapularis, is known to be prevalent or may represent the emerging diagnosis of an underappreciated pathogen. We recommend testing for POWV in patients who present with encephalitis in the spring to fall in New England.
During the last 30 years, there has been a continued increase in human cases of tick-borne encephalitis (TBE) in Europe, a disease caused by tick-borne encephalitis virus (TBEV). TBEV is endemic in ...an area ranging from northern China and Japan, through far-eastern Russia to Europe, and is maintained in cycles involving Ixodid ticks (Ixodes ricinus and Ixodes persulcatus) and wild vertebrate hosts. The virus causes a potentially fatal neurological infection, with thousands of cases reported annually throughout Europe. TBE has a significant mortality rate depending upon the strain of virus or may cause long-term neurological/neuropsychiatric sequelae in people affected. In this review, we comprehensively reviewed TBEV, its epidemiology and pathogenesis, the clinical manifestations of TBE, along with vaccination and prevention. We also discuss the factors which may have influenced an apparent increase in the number of reported human cases each year, despite the availability of effective vaccines.
Powassan virus (POWV) is an encephalitic tick-borne flavivirus which can result in serious neuroinvasive disease with up to a 10% case fatality rate. The study objective was to determine whether the ...salivary gland extract (SGE) from Ixodes scapularis ticks facilitates the transmission and dissemination of POWV in a process known as saliva-activated transmission. Groups of BALB/c mice were footpad inoculated with either a high dose of POWV with and without SGE or a low dose of POWV with and without SGE. Mice from each group were sacrificed daily. Organ viral loads and gene expression profiles were evaluated by quantitative real-time PCR. Both groups of mice infected with high-dose POWV showed severe neurological signs of disease preceding death. The presence of SGE did not affect POWV transmission or disease outcome for mice infected with the high dose of POWV. Neuroinvasion, paralysis, and death occurred for all mice infected with the low dose of POWV plus SGE; however, for mice infected with the low dose of POWV in the absence of SGE, there were no clinical signs of infection and no mice succumbed to disease. Although this group displayed low-level viremias, all mice were completely healthy, and it was the only group in which POWV was cleared from the lymph nodes. We conclude that saliva-activated transmission occurs in mice infected with a low dose of POWV. Our study is the first to demonstrate virus dose-dependent saliva-activated transmission, warranting further investigation of the specific salivary factors responsible for enhancing POWV transmission.
Powassan virus (POWV) is a tick-borne flavivirus that continues to emerge in the United States, as is evident by the surge in number and expanding geographic range of confirmed cases in the past decade. This neuroinvasive virus is transmitted to humans by infected tick bites. Successful tick feeding is facilitated by a collection of pharmacologically active factors in tick saliva. In a process known as saliva-activated transmission, tick bioactive salivary molecules are thought to modulate the host environment, making it more favorable for the transmission and establishment of a pathogen. This phenomenon has been demonstrated for several tick-borne pathogens; however, a systematic investigation of the role of tick saliva on dissemination and pathogenesis of a tick-borne viral disease has never been attempted before. This study will fill that gap by systematically examining whether the presence of tick saliva contributes to the transmission and dissemination of POWV in mice.
Lyme borreliosis (LB) and other Ixodes ricinus-borne diseases (TBDs) are diseases that emerge from interactions of humans and domestic animals with infected ticks in nature. Nature, environmental and ...health policies at (inter)national and local levels affect the risk, disease burden and costs of TBDs. Knowledge on ticks, their pathogens and the diseases they cause have been increasing, and resulted in the discovery of a diversity of control options, which often are not highly effective on their own. Control strategies involving concerted actions from human and animal health sectors as well as from nature managers have not been formulated, let alone implemented. Control of TBDs asks for a "health in all policies" approach, both at the (inter)national level, but also at local levels. For example, wildlife protection and creating urban green spaces are important for animal and human well-being, but may increase the risk of TBDs. In contrast, culling or fencing out deer decreases the risk for TBDs under specific conditions, but may have adverse effects on biodiversity or may be societally unacceptable. Therefore, in the end, nature and health workers together must carry out tailor-made control options for the control of TBDs for humans and animals, with minimal effects on the environment. In that regard, multidisciplinary approaches in environmental, but also medical settings are needed. To facilitate this, communication and collaboration between experts from different fields, which may include patient representatives, should be promoted.
Tick-borne encephalitis (TBE) is a substantial public health problem in many parts of Europe and Asia. To assess the effect of increasing TBE vaccination coverage in Austria, we compared incidence ...rates over 40 years for highly TBE-endemic countries of central Europe (Czech Republic, Slovenia, and Austria). For all 3 countries we found extensive annual and longer range fluctuations and shifts in distribution of patient ages, suggesting major variations in the complex interplay of factors influencing risk for exposure to TBE virus. The most distinctive effect was found for Austria, where mass vaccination decreased incidence to ≈16% of that of the prevaccination era. Incidence rates remained high for the nonvaccinated population. The vaccine was effective for persons in all age groups. During 2000-2011 in Austria, ≈4,000 cases of TBE were prevented by vaccination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tick-borne encephalitis virus (TBEV), of the genus
, is a causative agent of severe encephalitis in regions of endemicity of northern Asia and central and northern Europe. Interferon-induced ...transmembrane proteins (IFITMs) are restriction factors that inhibit the replication cycles of numerous viruses, including flaviviruses such as West Nile virus, dengue virus, and Zika virus. Here, we demonstrate the role of IFITM1, IFITM2, and IFITM3 in the inhibition of TBEV infection and in protection against virus-induced cell death. We show that the most significant role is that of IFITM3, including the dissection of its functional motifs by mutagenesis. Furthermore, through the use of CRISPR-Cas9-generated IFITM1/3-knockout monoclonal cell lines, we confirm the role and additive action of endogenous IFITMs in TBEV suppression. However, the results of coculture assays suggest that TBEV might partially escape interferon- and IFITM-mediated suppression during high-density coculture infection when the virus enters naive cells directly from infected donor cells. Thus, cell-to-cell spread may constitute a strategy for virus escape from innate host defenses.
TBEV infection may result in encephalitis, chronic illness, or death. TBEV is endemic in northern Asia and Europe; however, due to climate change, new centers of endemicity have arisen. Although effective TBEV vaccines have been approved, vaccination coverage is low, and due to the lack of specific therapeutics, infected individuals depend on their immune responses to control the infection. IFITM proteins are components of the innate antiviral defenses that suppress cell entry of many viral pathogens. However, no studies on the role of IFITM proteins in TBEV infection have been published thus far. Understanding antiviral innate immune responses is crucial for the future development of antiviral strategies. Here, we show the important role of IFITM proteins in the inhibition of TBEV infection and virus-mediated cell death. However, our data suggest that TBEV cell-to-cell spread may be less prone to both interferon- and IFITM-mediated suppression, potentially facilitating escape from IFITM-mediated immunity.
Tick-borne encephalitis virus (TBEV) causes serious the neurological disease, tick-borne encephalitis (TBE). TBEV can be transmitted to humans by ticks as well as by the alimentary route, which is ...mediated through the consumption of raw milk products from infected ruminants such as sheep, goats, and cows. The alimentary route of TBEV was recognized in the early 1950s and many important experimental studies were performed shortly thereafter. Nowadays, alimentary TBEV infections are recognized as a relevant factor contributing to the overall increase in TBE incidences in Europe. This review aims to summarize the history and current extent of alimentary TBEV infections across Europe, to analyze experimental data on virus secretion in milk, and to review possible alimentary infection preventive measures.