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usutu virus: an emerging flavivirus in europe.usutu virus (usuv) is an african mosquito-borne flavivirus belonging to the japanese encephalitis virus serocomplex. usuv is closely related to murray valley encephalitis virus, japanese encephalitis virus, and west nile virus. usuv was discovered in south africa in 1959. in europe, the first true demonstration of circulation of usuv was reported in austria in 2001 with a significant die-off of eurasian blackbirds. in the subsequent years, usuv expanded to neighboring countries, including italy, ...201525606971
ixodes scapularis and ixodes ricinus tick cell lines respond to infection with tick-borne encephalitis virus: transcriptomic and proteomic analysis.ixodid ticks are important vectors of a wide variety of viral, bacterial and protozoan pathogens of medical and veterinary importance. although several studies have elucidated tick responses to bacteria, little is known about the tick response to viruses. to gain insight into the response of tick cells to flavivirus infection, the transcriptomes and proteomes of two ixodes spp cell lines infected with the flavivirus tick-borne encephalitis virus (tbev) were analysed.201526582129
a multiplex pcr/ldr assay for the simultaneous identification of category a infectious pathogens: agents of viral hemorrhagic fever and variola virus.cdc designated category a infectious agents pose a major risk to national security and require special action for public health preparedness. they include viruses that cause viral hemorrhagic fever (vhf) syndrome as well as variola virus, the agent of smallpox. vhf is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in ...201526381398
development of a model system for tick-borne flavivirus persistence in hek 293t cells.we devised a model system to study persistent infection by the tick-borne flavivirus langat virus (lgtv) in 293t cells. infection with a molecularly cloned lgtv strain produced an acute lytic crisis that left few surviving cells. the culture was repopulated by cells that were ~90% positive for lgtv e protein, thus initiating a persistent infection that was maintained for at least 35 weeks without additional lytic crises. staining of cells for viral proteins and ultrastructural analysis revealed ...201526045539
emerging horizons for tick-borne pathogens: from the 'one pathogen-one disease' vision to the pathobiome paradigm.ticks, as vectors of several notorious zoonotic pathogens, represent an important and increasing threat for human and animal health in europe. recent applications of new technology revealed the complexity of the tick microbiome, which may affect its vectorial capacity. appreciation of these complex systems is expanding our understanding of tick-borne pathogens, leading us to evolve a more integrated view that embraces the 'pathobiome'; the pathogenic agent integrated within its abiotic and bioti ...201526610021
human coinfection with borrelia burgdorferi and babesia microti in the united states.borrelia burgdorferi, the causative agent of lyme disease, and babesia microti, a causative agent of babesiosis, are increasingly implicated in the growing tick-borne disease burden in the northeastern united states. these pathogens are transmitted via the bite of an infected tick vector, ixodes scapularis, which is capable of harboring and inoculating a host with multiple pathogens simultaneously. clinical presentation of the diseases is heterogeneous and ranges from mild flu-like symptoms to n ...201526697208
coinfection by ixodes tick-borne pathogens: ecological, epidemiological, and clinical consequences.ixodes ticks maintain a large and diverse array of human pathogens in the enzootic cycle, including borrelia burgdorferi and babesia microti. despite the poor ecological fitness of b. microti, babesiosis has recently emerged in areas endemic for lyme disease. studies in ticks, reservoir hosts, and humans indicate that coinfection with b. burgdorferi and b. microti is common, promotes transmission and emergence of b. microti in the enzootic cycle, and causes greater disease severity and duration ...201526613664
ticknet-a collaborative public health approach to tickborne disease surveillance and research.ticknet, a public health network, was created in 2007 to foster greater collaboration between state health departments, academic centers, and the centers for disease control and prevention on surveillance and prevention of tickborne diseases. research activities are conducted through the emerging infections program and include laboratory surveys, high-quality prevention trials, and pathogen discovery.201526291549
experimental transmission of karshi (mammalian tick-borne flavivirus group) virus by ornithodoros ticks >2,900 days after initial virus exposure supports the role of soft ticks as a long-term maintenance mechanism for certain flaviviruses.members of the mammalian tick-borne flavivirus group, including tick-borne encephalitis virus, are responsible for at least 10,000 clinical cases of tick-borne encephalitis each year. to attempt to explain the long-term maintenance of members of this group, we followed ornithodoros parkeri, o. sonrai, and o. tartakovskyi for >2,900 days after they had been exposed to karshi virus, a member of the mammalian tick-borne flavivirus group.201526285211
major emerging vector-borne zoonotic diseases of public health importance in canada.in canada, the emergence of vector-borne diseases may occur via international movement and subsequent establishment of vectors and pathogens, or via northward spread from endemic areas in the usa. re-emergence of endemic vector-borne diseases may occur due to climate-driven changes to their geographic range and ecology. lyme disease, west nile virus (wnv), and other vector-borne diseases were identified as priority emerging non-enteric zoonoses in canada in a prioritization exercise conducted by ...201526954882
whole genome capture of vector-borne pathogens from mixed dna samples: a case study of borrelia burgdorferi.rapid and accurate retrieval of whole genome sequences of human pathogens from disease vectors or animal reservoirs will enable fine-resolution studies of pathogen epidemiological and evolutionary dynamics. however, next generation sequencing technologies have not yet been fully harnessed for the study of vector-borne and zoonotic pathogens, due to the difficulty of obtaining high-quality pathogen sequence data directly from field specimens with a high ratio of host to pathogen dna.201526048573
babesiosis.babesiosis is caused by intraerythrocytic protozoan parasites that are transmitted by ticks, or less commonly through blood transfusion or transplacentally. human babesiosis was first recognized in a splenectomized patient in europe but most cases have been reported from the northeastern and upper midwestern united states in people with an intact spleen and no history of immune impairment. cases are reported in asia, africa, australia, europe, and south america. babesiosis shares many clinical f ...201525999229
human granulocytic anaplasmosis.human granulocytic anaplasmosis, a deer tick-transmitted rickettsial infection caused by anaplasma phagocytophilum, is a common cause of undifferentiated fever in the northeast and upper midwest united states. patients are often initially diagnosed with a mild viral infection, and illness readily resolves in most cases. however, as many as 3% develop life-threatening complications and nearly 1% die from the infection. although coinfections with borrelia burgdorferi and babesia microti occur, the ...201525999228
climate change and ixodes tick-borne diseases of humans.the evidence that climate warming is changing the distribution of ixodes ticks and the pathogens they transmit is reviewed and evaluated. the primary approaches are either phenomenological, which typically assume that climate alone limits current and future distributions, or mechanistic, asking which tick-demographic parameters are affected by specific abiotic conditions. both approaches have promise but are severely limited when applied separately. for instance, phenomenological approaches (e.g ...201525688022
accelerated phenology of blacklegged ticks under climate warming.the phenology of tick emergence has important implications for the transmission of tick-borne pathogens. a long lag between the emergence of tick nymphs in spring and larvae in summer should increase transmission of persistent pathogens by allowing infected nymphs to inoculate the population of naive hosts that can subsequently transmit the pathogen to larvae to complete the transmission cycle. in contrast, greater synchrony between nymphs and larvae should facilitate transmission of pathogens t ...201525688016
identification of 24h ixodes scapularis immunogenic tick saliva proteins.ixodes scapularis is arguably the most medically important tick species in the united states. this tick transmits 5 of the 14 human tick-borne disease (tbd) agents in the usa: borrelia burgdorferi, anaplasma phagocytophilum, b. miyamotoi, babesia microti, and powassan virus disease. except for the powassan virus disease, i. scapularis-vectored tbd agents require more than 24h post attachment to be transmitted. this study describes identification of 24h immunogenic i. scapularis tick saliva prote ...201525825233
insect-specific flaviviruses: a systematic review of their discovery, host range, mode of transmission, superinfection exclusion potential and genomic organization.there has been a dramatic increase in the number of insect-specific flaviviruses (isfs) discovered in the last decade. historically, these viruses have generated limited interest due to their inability to infect vertebrate cells. this viewpoint has changed in recent years because some isfs have been shown to enhance or suppress the replication of medically important flaviviruses in co-infected mosquito cells. additionally, comparative studies between isfs and medically important flaviviruses can ...201525866904
encephalitis surveillance through the emerging infections program, 1997-2010.encephalitis is a devastating illness that commonly causes neurologic disability and has a case fatality rate >5% in the united states. an etiologic agent is identified in <50% of cases, making diagnosis challenging. the centers for disease control and prevention emerging infections program (eip) encephalitis project established syndromic surveillance for encephalitis in new york, california, and tennessee, with the primary goal of increased identification of causative agents and secondary goals ...201526295485
tick saliva enhances powassan virus transmission to the host, influencing its dissemination and the course of disease.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 witho ...201525995246
borrelia burgdorferi promotes the establishment of babesia microti in the northeastern united states.babesia microti and borrelia burgdorferi, the respective causative agents of human babesiosis and lyme disease, are maintained in their enzootic cycles by the blacklegged tick (ixodes scapularis) and use the white-footed mouse (peromyscus leucopus) as primary reservoir host. the geographic range of both pathogens has expanded in the united states, but the spread of babesiosis has lagged behind that of lyme disease. several studies have estimated the basic reproduction number (r0) for b. microti ...201425545393
lyme borreliosis: a review of data on transmission time after tick attachment.lyme borreliosis is increasing rapidly in many parts of the world and is the most commonly occurring vector-borne disease in europe and the usa. the disease is transmitted by ticks of the genus ixodes. they require a blood meal at each stage of their life cycle and feed on a wide variety of wild and domestic animals as well as birds and reptiles. transmission to humans is incidental and can occur during visits to a vector habitat, when host mammals and their associated ticks migrate into the urb ...201425565881
borrelia burgdorferi (lyme disease). 201425452659
genetic variation in the mitochondrial 16s ribosomal rna gene of ixodes scapularis (acari: ixodidae).ixodes scapularis is a vector of several human pathogens in the united states, and there is geographical variation in the relative number of persons infected with these pathogens. geographically isolated populations of i. scapularis have established or are in the process of establishing in southern canada. knowledge of the genetic variation within and among these populations may provide insight into their geographical origins in the united states and the potential risk of exposure of canadians t ...201425430547
emerging and reemerging neurologic infections.the list of emerging and reemerging pathogens that cause neurologic disease is expanding. various factors, including population growth and a rise in international travel, have contributed to the spread of pathogens to previously nonendemic regions. recent advances in diagnostic methods have led to the identification of novel pathogens responsible for infections of the central nervous system. furthermore, new issues have arisen surrounding established infections, particularly in an increasingly i ...201425360203
virome analysis of amblyomma americanum, dermacentor variabilis, and ixodes scapularis ticks reveals novel highly divergent vertebrate and invertebrate viruses.a wide range of bacterial pathogens have been identified in ticks, yet the diversity of viruses in ticks is largely unexplored. in the united states, amblyomma americanum, dermacentor variabilis, and ixodes scapularis are among the principal tick species associated with pathogen transmission. we used high-throughput sequencing to characterize the viromes of these tick species and identified the presence of powassan virus and eight novel viruses. these included the most divergent nairovirus descr ...201425056893
lyme disease. 201425119621
population and demographic structure of ixodes scapularis say in the eastern united states.the most significant vector of tick-borne pathogens in the united states is ixodes scapularis say (the blacklegged tick). previous studies have identified significant genetic, behavioral and morphological differences between northern vs. southern populations of this tick. because tick-borne pathogens are dependent on their vectors for transmission, a baseline understanding of the vector population structure is crucial to determining the risks and epidemiology of pathogen transmission.201425025532
borrelia miyamotoi sensu lato seroreactivity and seroprevalence in the northeastern united states.borrelia miyamotoi sensu lato, a relapsing fever borrelia sp., is transmitted by the same ticks that transmit b. burgdorferi (the lyme disease pathogen) and occurs in all lyme disease-endemic areas of the united states. to determine the seroprevalence of igg against b. miyamotoi sensu lato in the northeastern united states and assess whether serum from b. miyamotoi sensu lato-infected persons is reactive to b. burgdorferi antigens, we tested archived serum samples from area residents during 1991 ...201424960072
chronic coinfections in patients diagnosed with chronic lyme disease: a systematic review.often, the controversial diagnosis of chronic lyme disease is given to patients with prolonged, medically unexplained physical symptoms. many such patients also are treated for chronic coinfections with babesia, anaplasma, or bartonella in the absence of typical presentations, objective clinical findings, or laboratory confirmation of active infection. we have undertaken a systematic review of the literature to evaluate several aspects of this practice.201424929022
clinical practice. lyme disease. 201424785207
the prevalence of borrelia miyamotoi infection, and co-infections with other borrelia spp. in ixodes scapularis ticks collected in canada.blacklegged ticks, ixodes scapularis are vectors of the tick-borne pathogens borrelia burgdorferi, anaplasma phagocytophilum and babesia microti. recently, the i. scapularis-borne bacterium borrelia miyamotoi has been linked to human illness in north america. the range of this tick is expanding in canada which may increase the potential for human exposure to these agents.201424731287
the prevalence of zoonotic tick-borne pathogens in ixodes scapularis collected in the hudson valley, new york state.ixodes scapularis, the blacklegged tick, is capable of transmitting the pathogens that cause lyme disease (borrelia burgdorferi), babesiosis (babesia microti), anaplasmosis (anaplasma phagocytophilum), and to a lesser extent powassan encephalitis (deer tick virus [dtv]). these pathogens represent significant public health problems, but little is known about the occurrence and co-infection prevalence of these pathogens in i. scapularis. here, we used standard pcr and pathogen-specific primers to ...201424689680
monitoring human babesiosis emergence through vector surveillance new england, usa.human babesiosis is an emerging tick-borne disease caused by the intraerythrocytic protozoan babesia microti. its geographic distribution is more limited than that of lyme disease, despite sharing the same tick vector and reservoir hosts. the geographic range of babesiosis is expanding, but knowledge of its range is incomplete and relies exclusively on reports of human cases. we evaluated the utility of tick-based surveillance for monitoring disease expansion by comparing the ratios of the 2 inf ...201424447577
laboratory identification of arthropod ectoparasites.the collection, handling, identification, and reporting of ectoparasitic arthropods in clinical and reference diagnostic laboratories are discussed in this review. included are data on ticks, mites, lice, fleas, myiasis-causing flies, and bed bugs. the public health importance of these organisms is briefly discussed. the focus is on the morphological identification and proper handling and reporting of cases involving arthropod ectoparasites, particularly those encountered in the united states. o ...201424396136
kyasanur forest disease virus infection in mice is associated with higher morbidity and mortality than infection with the closely related alkhurma hemorrhagic fever virus.kyasanur forest disease virus (kfdv) and alkhurma hemorrhagic fever virus (ahfv) are closely related members of the flavivirus genus and are important causes of human disease in india and the arabian peninsula, respectively. despite high genetic similarity, the viruses have distinctly different host ranges and ecologies. human cases of kfdv or ahfv develop a spectrum of disease syndromes ranging from liver pathology to neurologic disease. case reports suggest kfdv is more commonly associated wit ...201424950196
inhibitors of the tick-borne, hemorrhagic fever-associated flaviviruses.no antiviral therapies are available for the tick-borne flaviviruses associated with hemorrhagic fevers: kyasanur forest disease virus (kfdv), both classical and the alkhurma hemorrhagic fever virus (ahfv) subtype, and omsk hemorrhagic fever virus (ohfv). we tested compounds reported to have antiviral activity against members of the flaviviridae family for their ability to inhibit ahfv replication. 6-azauridine (6-azau), 2'-c-methylcytidine (2'-cmc), and interferon alpha 2a (ifn-α2a) inhibited t ...201424663025
the role of viral persistence in flavivirus biology.in nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine. these viruses account for considerable human morbidity and mortality worldwide. increasing and substantial evidence of viral persistence in humans, which includes the isolation of rna by rt-pcr and infectious virus by culture, continues to be reported. viral persistence can also be established in vitro in various human, animal, arachnid, an ...201424737600
tick-borne encephalitis virus (tbev) - findings on cross reactivity and longevity of tbev antibodies in animal sera.by using animal sera as sentinels, natural tbev foci could be identified and further analyses including investigations of ticks could be initiated. however, antibody response against tbev-related flaviviruses might adversely affect the readout of such a monitoring. therefore, the cross-reactivity of the applied tbev serology test systems - enzyme linked immunosorbent assay (elisa) and virus neutralization test (vnt) - as well as the longevity of tbev antibody titres in sheep and goats were inves ...201424690234
molecular archaeology of flaviviridae untranslated regions: duplicated rna structures in the replication enhancer of flaviviruses and pestiviruses emerged via convergent evolution.rna secondary structures in the 3'untranslated regions (3'utr) of the viruses of the family flaviviridae, previously identified as essential (promoters) or beneficial (enhancers) for replication, have been analysed. duplicated enhancer elements are revealed as a global feature in the evolution of the 3'utr of distantly related viruses within the genera flavivirus and pestivirus. for the flaviviruses, duplicated structures occur in the 3'utr of all four distantly related ecological virus subgroup ...201424647143
biologically hazardous agents at work and efforts to protect workers' health: a review of recent reports.because information on biological agents in the workplace is lacking, biological hazard analyses at the workplace to securely recognize the harmful factors with biological basis are desperately needed. this review concentrates on literatures published after 2010 that attempted to detect biological hazards to humans, especially workers, and the efforts to protect them against these factors. it is important to improve the current understanding of the health hazards caused by biological factors at ...201425180133
arboviral bottlenecks and challenges to maintaining diversity and fitness during mosquito transmission.the term arbovirus denotes viruses that are transmitted by arthropods, such as ticks, mosquitoes, and other biting arthropods. the infection of these vectors produces a certain set of evolutionary pressures on the virus; involving migration from the midgut, where the blood meal containing the virus is processed, to the salivary glands, in order to transmit the virus to the next host. during this process the virus is subject to numerous bottlenecks, stochastic events that significantly reduce the ...201425341663
development of an algorithm for production of inactivated arbovirus antigens in cell culture.arboviruses are medically important pathogens that cause human disease ranging from a mild fever to encephalitis. laboratory diagnosis is essential to differentiate arbovirus infections from other pathogens with similar clinical manifestations. the arboviral diseases branch (adb) reference laboratory at the cdc division of vector-borne diseases (dvbd) produces reference antigens used in serological assays such as the virus-specific immunoglobulin m antibody-capture enzyme-linked immunosorbent as ...201425102428
characterization of a novel insect-specific flavivirus from brazil: potential for inhibition of infection of arthropod cells with medically important flaviviruses.in the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. we recently described the isolation of a novel flavivirus (tentatively designated 'nhumirim virus'; nhuv) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. we characterized the in vitro growth p ...201425146007
the relationship between the structure of the tick-borne encephalitis virus strains and their pathogenic properties.tick-borne encephalitis virus (tbev) is transmitted to vertebrates by taiga or forest ticks through bites, inducing disease of variable severity. the reasons underlying these differences in the severity of the disease are unknown. in order to identify genetic factors affecting the pathogenicity of virus strains, we have sequenced and compared the complete genomes of 34 far-eastern subtype (fe) tbev strains isolated from patients with different disease severity (primorye, the russian far east). w ...201424740396
substitution of the premembrane and envelope protein genes of modoc virus with the homologous sequences of west nile virus generates a chimeric virus that replicates in vertebrate but not mosquito cells.most known flaviviruses, including west nile virus (wnv), are maintained in natural transmission cycles between hematophagous arthropods and vertebrate hosts. other flaviviruses such as modoc virus (modv) and culex flavivirus (cxfv) have host ranges restricted to vertebrates and insects, respectively. the genetic elements that modulate the differential host ranges and transmission cycles of these viruses have not been identified.201425151534
tick-borne encephalitis virus subtypes emerged through rapid vector switches rather than gradual evolution.tick-borne encephalitis is the most important human arthropod-borne virus disease in europe and russia, with an annual incidence of about 13 thousand people. tick-borne encephalitis virus (tbev) is distributed in the natural foci of forest and taiga zones of eurasia, from the pacific to the atlantic coast. currently, there are three mutually exclusive hypotheses about the origin and distribution of tbev subtypes, although they are based on the same assumption of gradual evolution. recently, we h ...201425540692
transcriptome of the female synganglion of the black-legged tick ixodes scapularis (acari: ixodidae) with comparison between illumina and 454 systems.illumina and 454 pyrosequencing were used to characterize genes from the synganglion of female ixodes scapularis. go term searching success for biological processes was similar for samples sequenced by both methods. however, for molecular processes, it was more successful for the illumina samples than for 454 samples. functional assignments of transcripts predicting neuropeptides, neuropeptide receptors, neurotransmitter receptors and other genes of interest was done, supported by strong e-value ...201425075967
tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance.the increased distribution of the tick-borne encephalitis virus (tbev) in scandinavia highlights the importance of characterizing novel sequences within the natural foci. in this study, two tbev strains: the norwegian mandal 2009 (questing nymphs pool) and the swedish saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. interestingly, the sequence of mandal 2009 revealed the shorter form of the tbev genome, similar to the highly virulent hypr strain, within the 3' no ...201425058476
comparative pathogenesis of alkhumra hemorrhagic fever and kyasanur forest disease viruses in a mouse model.kyasanur forest disease virus (kfdv) and alkhumra hemorrhagic fever virus (ahfv) are genetically closely-related, tick-borne flaviviruses that cause severe, often fatal disease in humans. flaviviruses in the tick-borne encephalitis (tbe) complex typically cause neurological disease in humans whereas patients infected with kfdv and ahfv predominately present with hemorrhagic fever. a small animal model for kfdv and ahfv to study the pathogenesis and evaluate countermeasures has been lacking mostl ...201424922308
detection of rickettsia amblyommii in ticks collected from missouri, usa. 201426038740
proinflammatory cytokines and chemokines at the skin interface during powassan virus transmission. 201424658509
a blood meal-induced ixodes scapularis tick saliva serpin inhibits trypsin and thrombin, and interferes with platelet aggregation and blood clotting.ixodes scapularis is a medically important tick species that transmits causative agents of important human tick-borne diseases including borreliosis, anaplasmosis and babesiosis. an understanding of how this tick feeds is needed prior to the development of novel methods to protect the human population against tick-borne disease infections. this study characterizes a blood meal-induced i. scapularis (ixsc) tick saliva serine protease inhibitor (serpin (s)), in-house referred to as ixscs-1e1. the ...201424583183
detection of quang binh virus from mosquitoes in china.flaviviruses present a wide range of genetic diversity and exhibit diverse host relationships. mosquito-borne flaviviruses have recently been isolated and characterized worldwide. yunnan province of china is one of the richest areas of species diversity and is the center of multi-species evolution in mainland asia, which supports the circulation of numerous arthropod-borne viruses (arboviruses). in a screening program of arboviruses, mosquitoes were collected during the mosquito activity season ...201424342141
interaction of flaviviruses with reproduction inhibitors binding in β-og pocket: insights from molecular dynamics simulations.flaviviral diseases, including dengue fever, west nile fever, yellow fever, tick-borne encephalitis, omsk haemorrhagic fever, and powassan encephalitis, threaten human health all over the world. lack of effective antivirals targeting replication cycle of flaviviruses makes the search of such compounds a challenging task. recently we have identified a reproduction inhibitor effective against tick-borne encephalitis virus and powassan virus (powv) (acs med. chem. lett., 2013, 4, 869-874). to enabl ...201427485304
dating the origin of the genus flavivirus in the light of beringian biogeography.the genus flavivirus includes some of the most important human viral pathogens, and its members are found in all parts of the populated world. the temporal origin of diversification of the genus has long been debated due to the inherent problems with dating deep rna virus evolution. a generally accepted hypothesis suggests that flavivirus emerged within the last 10 000 years. however, it has been argued that the tick-borne powassan flavivirus was introduced into north america some time between t ...201424914065
[genetic characterisation of powassan virus (powv) isolated from haemophysalis longicornis ticks in primorye and two strains of tick-borne encephalitis virus (tbev) (flaviviridae, flavivirus): alma-arasan virus (aav) isolated from ixodes persulcatus ticks in kazakhstan and malyshevo virus isolated from aedes vexans nipponii mosquitoes in khabarovsk kray].the complete genomes of the three tick-borne flaviviruses (genus flavivirus, fam. bunyaviridae) were sequenced: povassan virus (powv, strain leiv-3070prm, isolated from haemophysalis logicornis in primorsky krai, russia in 1977), alma-arasan virus (aav, strain leiv-1380kaz, isolated from ixodes persulcatus ticks in kazakhstan in 1977) and malyshevo virus (isolated from a pool of aedes vexans nipponii mosquitoes, in the khabarovsk krai, russia in 1978). it is shown that aav and malyshevo virus ar ...201425895206
west nile virus and other arboviral diseases - united states, 2013.arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. west nile virus (wnv) is the leading cause of domestically acquired arboviral disease in the united states. however, several other arboviruses also cause sporadic cases and seasonal outbreaks of neuroinvasive disease (i.e., meningitis, encephalitis, and acute flaccid paralysis). this report summarizes surveillance data reported to cdc in 2013 for wnv and other nationally ...201424941331
tick-borne viruses: a review from the perspective of therapeutic approaches.several important human diseases worldwide are caused by tick-borne viruses. these diseases have become important public health concerns in recent years. the tick-borne viruses that cause diseases in humans mainly belong to 3 families: bunyaviridae, flaviviridae, and reoviridae. in this review, we focus on therapeutic approaches for several of the more important tick-borne viruses from these 3 families. these viruses are crimean-congo hemorrhagic fever virus (cchf) and the newly discovered tick- ...201424907187
powassan virus: investigations of possible natural cycles of infection. 201313774094
west nile virus and other arboviral diseases--united states, 2012.arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. west nile virus (wnv) is the leading cause of domestically acquired arboviral disease in the united states. however, several other arboviruses also cause sporadic cases and seasonal outbreaks of neuroinvasive disease (e.g., meningitis, encephalitis, and acute flaccid paralysis). in 2012, cdc received reports of 5,780 nationally notifiable arboviral disease cases (excludin ...201323803959
presence of cross-reactions with other viral encephalitides in the indirect fluorescent-antibody test for diagnosis of rabies.the antemortem diagnosis of rabies in humans employs techniques that require accuracy, speed, and sensitivity. a combination of histochemical analysis, in vitro virus isolation, immunological methods, and molecular amplification procedures are utilized in efforts to diagnose the disease. modern medicine now offers potentially life-saving treatment for a disease that was considered invariably fatal once clinical signs develop. however, medical intervention efforts require a rapid and accurate dia ...201324088851
seroprevalence of powassan virus in new england deer, 1979-2010.powassan virus and its subtype, deer tick virus, are closely related tick-borne flaviviruses that circulate in north america. the incidence of human infection by these agents appears to have increased in recent years. to define exposure patterns among white-tailed deer, potentially useful sentinels that are frequently parasitized by ticks, we screened serum samples collected during 1979-2010 in connecticut, maine, and vermont for neutralizing antibody by using a novel recombinant deer tick virus ...201323568288
examining the differences in format and characteristics of zoonotic virus surveillance data on state agency websites.zoonotic viruses are infectious organisms transmittable between animals and humans. agencies of public health, agriculture, and wildlife conduct surveillance of zoonotic viruses and often report data on their websites. however, the format and characteristics of these data are not known.201323628771
deorphanization and target validation of cross-tick species conserved novel amblyomma americanum tick saliva protein.we previously identified a cross-tick species conserved tick feeding stimuli responsive amblyomma americanum (aam) av422 gene. this study demonstrates that aamav422 belongs to a novel group of arthropod proteins that is characterized by 14 cysteine amino acid residues: c(23)-x7/9-c(33)-x23/24-c(58)-x8-c(67)-x7-c(75)-x23-c(99)-x15-c(115)-x10-c(126)-x24/25/33-c(150)c(151)-x7-c(159)-x8-c(168)-x23/24-c(192)-x9/10-c(202) predicted to form seven disulfide bonds. we show that aamav422 protein is a ubiq ...201323428900
epidemiology of tick-borne encephalitis (tbe) in europe and its prevention by available vaccines.tick-borne encephalitis (tbe), which is caused by a flavivirus, is the most common tick-transmitted disease in central and eastern europe and russia. today, tbe is endemic in 27 european countries, and has become an international public health problem. the epidemiology of tbe is changing owing to various factors, such as improvements in diagnosis and case reporting, increased recreational activities in areas populated by ticks, and changes in climatic conditions affecting tick habitats. vaccinat ...201323377671
west nile virus drug discovery.the outbreak of west nile virus (wnv) in 1999 in the usa, and its continued spread throughout the americas, parts of europe, the middle east and africa, underscored the need for wnv antiviral development. here, we review the current status of wnv drug discovery. a number of approaches have been used to search for inhibitors of wnv, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. th ...201324300672
fatal neurological respiratory insufficiency is common among viral encephalitides.neurological respiratory insufficiency strongly correlates with mortality among rodents infected with west nile virus (wnv), which suggests that this is a primary mechanism of death in rodents and possibly fatal west nile neurological disease in human patients.201323641019
flaviviruses in europe: complex circulation patterns and their consequences for the diagnosis and control of west nile disease.in europe, many flaviviruses are endemic (west nile, usutu, tick-borne encephalitis viruses) or occasionally imported (dengue, yellow fever viruses). due to the temporal and geographical co-circulation of flaviviruses in europe, flavivirus differentiation by diagnostic tests is crucial in the adaptation of surveillance and control efforts. serological diagnosis of flavivirus infections is complicated by the antigenic similarities among the flavivirus genus. indeed, most flavivirus antibodies are ...201324225644
s-adenosyl-homocysteine is a weakly bound inhibitor for a flaviviral methyltransferase.the methyltransferase enzyme (mtase), which catalyzes the transfer of a methyl group from s-adenosyl-methionine (adomet) to viral rna, and generates s-adenosyl-homocysteine (adohcy) as a by-product, is essential for the life cycle of many significant human pathogen flaviviruses. here we investigated inhibition of the flavivirus mtase by several adohcy-derivatives. unexpectedly we found that adohcy itself barely inhibits the flavivirus mtase activities, even at high concentrations. adohcy was als ...201324130807
a quantitative approach to the prioritization of zoonotic diseases in north america: a health professionals' perspective.currently, zoonoses account for 58% to 61% of all communicable diseases causing illness in humans globally and up to 75% of emerging human pathogens. although the impact of zoonoses on animal health and public health in north america is significant, there has been no published research involving health professionals on the prioritization of zoonoses in this region.201323991057
inhibitors of tick-borne flavivirus reproduction from structure-based virtual screening.flaviviruses form a large family of enveloped viruses affecting millions of people over the world. to date, no specific therapy was suggested for the infected people, making the treatment exclusively symptomatic. several attempts were performed earlier for the design of fusion inhibitors for mosquito-borne flaviviruses, whereas for the tick-borne flaviviruses such design had not been performed. we have constructed homology models of envelope glycoproteins of tick-transmitted flaviviruses with th ...201324900762
ilheus virus isolation in the pantanal, west-central brazil.the wetlands of the brazilian pantanal host large concentrations of diverse wildlife species and hematophagous arthropods, conditions that favor the circulation of zoonotic arboviruses. a recent study from the nhecolândia sub-region of pantanal reported serological evidence of various flaviviruses, including west nile virus and ilheus virus (ilhv). according to the age of seropositive horses, at least three flaviviruses, including ilhv, circulated in the brazilian pantanal between 2005 and 2009. ...201323875051
case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium.encephalitis continues to result in substantial morbidity and mortality worldwide. advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research.201323861361
dose-dependent viremia and the differential immunoglobulin response of hamsters to powassan virus. 20134624393
use of staged molecular analysis to determine causes of unexplained central nervous system infections.no agent is implicated in most central nervous system (cns) infections. to investigate cerebrospinal fluid samples from patients with cns infections of unknown cause in 1 hospital in taiwan, we used a staged molecular approach, incorporating techniques including multiplex masstag pcr, 16s rrna pcr, dna microarray, and high-throughput pyrosequencing. we determined the infectious agent for 31 (24%) of 131 previously negative samples. candidate pathogens were identified for 25 (27%) of 94 unexplain ...201323965845
possible future monoclonal antibody (mab)-based therapy against arbovirus infections.more than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. on the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particula ...201324058915
west nile virus in the united states - a historical perspective.prior to 1999, west nile virus (wnv) was a bit player in the screenplay of global vector-borne viral diseases. first discovered in the west nile district of uganda in 1937, this culex sp.-transmitted virus was known for causing small human febrile outbreaks in africa and the middle east. prior to 1995, the last major human wnv outbreak was in the 1950s in israel. the epidemiology and ecology of wnv began to change in the mid-1990s when an epidemic of human encephalitis occurred in romania. the i ...201324335779
sensitive multiplex pcr assay to differentiate lyme spirochetes and emerging pathogens anaplasma phagocytophilum and babesia microti.the infection with borrelia burgdorferi can result in acute to chronic lyme disease. in addition, coinfection with tick-borne pathogens, babesia species and anaplasma phagocytophilum has been increasing in endemic regions of the usa and europe. the currently used serological diagnostic tests are often difficult to interpret and, moreover, antibodies against the pathogens persist for a long time making it difficult to confirm the cure of the disease. in addition, these tests cannot be used for di ...201324359556
potential role of deer tick virus in powassan encephalitis cases in lyme disease-endemic areas of new york, u.s.a.powassan virus, a member of the tick-borne encephalitis group of flaviviruses, encompasses 2 lineages with separate enzootic cycles. the prototype lineage of powassan virus (powv) is principally maintained between ixodes cookei ticks and the groundhog (marmota momax) or striped skunk (mephitis mephitis), whereas the deer tick virus (dtv) lineage is believed to be maintained between ixodes scapularis ticks and the white-footed mouse (peromyscus leucopus). we report 14 cases of powassan encephalit ...201324274334
isolation of deer tick virus (powassan virus, lineage ii) from ixodes scapularis and detection of antibody in vertebrate hosts sampled in the hudson valley, new york state.deer tick virus, dtv, is a genetically and ecologically distinct lineage of powassan virus (powv) also known as lineage ii powv. human incidence of pow encephalitis has increased in the last 15 years potentially due to the emergence of dtv, particularly in the hudson valley of new york state. we initiated an extensive sampling campaign to determine whether powv was extant throughout the hudson valley in tick vectors and/or vertebrate hosts.201324016533
expression profiling of lymph node cells from deer mice infected with andes virus.deer mice (peromyscus maniculatus) are the principal reservoir hosts of sin nombre virus (snv), the cause of the great majority of hantavirus cardiopulmonary syndrome (hcps) cases in north america. snv, like all hantaviruses with their reservoirs, causes persistent infection without pathology in deer mice and appear to elicit a regulatory t cell response. deer mice are also susceptible to andes virus (andv), which causes the great majority of hcps cases in south america, but they clear infection ...201323570545
what is the risk for exposure to vector-borne pathogens in united states national parks?united states national parks attract > 275 million visitors annually and collectively present risk of exposure for staff and visitors to a wide range of arthropod vector species (most notably fleas, mosquitoes, and ticks) and their associated bacterial, protozoan, or viral pathogens. we assessed the current state of knowledge for risk of exposure to vector-borne pathogens in national parks through a review of relevant literature, including internal national park service documents and organismal ...201323540107
detection of human bacterial pathogens in ticks collected from louisiana black bears (ursus americanus luteolus).there are 4 major human-biting tick species in the northeastern united states, which include: amblyomma americanum, amblyomma maculatum, dermacentor variabilis, and ixodes scapularis. the black bear is a large mammal that has been shown to be parasitized by all the aforementioned ticks. we investigated the bacterial infections in ticks collected from louisiana black bears (ursus americanus subspecies luteolus). eighty-six ticks were collected from 17 black bears in louisiana from june 2010 to ma ...201323415850
vaccination against lyme disease: past, present, and future.lyme borreliosis is a zoonotic disease caused by borrelia burgdorferi sensu lato bacteria transmitted to humans and domestic animals by the bite of an ixodes spp. tick (deer tick). despite improvements in diagnostic tests and public awareness of lyme disease, the reported cases have increased over the past decade to approximately 30,000 per year. limitations and failed public acceptance of a human vaccine, comprised of the outer surface a (ospa) lipoprotein of b. burgdorferi, led to its demise, ...201323407755
structure of the st. louis encephalitis virus postfusion envelope trimer.st. louis encephalitis virus (slev) is a mosquito-borne flavivirus responsible for several human encephalitis outbreaks over the last 80 years. mature flavivirus virions are coated with dimeric envelope (e) proteins that mediate attachment and fusion with host cells. e is a class ii fusion protein, the hallmark of which is a distinct dimer-to-trimer rearrangement that occurs upon endosomal acidification and insertion of hydrophobic fusion peptides into the endosomal membrane. herein, we report t ...201223115296
rapid molecular detection methods for arboviruses of livestock of importance to northern europe.arthropod-borne viruses (arboviruses) have been responsible for some of the most explosive epidemics of emerging infectious diseases over the past decade. their impact on both human and livestock populations has been dramatic. the early detection either through surveillance or diagnosis of virus will be a critical feature in responding and resolving the emergence of such epidemics in the future. although some of the most important emerging arboviruses are human pathogens, this paper aims to high ...201222219660
bioinformatics and expression analyses of the ixodes scapularis tick cystatin family.the cystatins are inhibitors of papain- and legumain-like cysteine proteinases, classified in merops subfamilies i25a-i25c. this study shows that 84 % (42/50) of tick cystatins are putatively extracellular in subfamily i25b and the rest are putatively intracellular in subfamily i25a. on the neighbor joining phylogeny guide tree, subfamily i25a members cluster together, while subfamily i25b cystatins segregate among prostriata or metastriata ticks. two ixodes scapularis cystatins, aay66864 and is ...201223053911
powassan virus encephalitis, minnesota, usa.powassan virus (powv) is a rare tick-borne agent of encephalitis in north america. historically, confirmed cases occurred mainly in the northeastern united states. since 2008, confirmed cases in minnesota and wisconsin have increased. we report a fatal case of powv encephalitis in minnesota. powv infection should be suspected in tick-exposed patients with viral encephalitis.201223017222
revisiting the clinal concept of evolution and dispersal for the tick-borne flaviviruses by using phylogenetic and biogeographic analyses.tick-borne flaviviruses (tbf) are widely dispersed across africa, europe, asia, oceania, and north america, and some present a significant threat to human health. seminal studies on tick-borne encephalitis viruses (tbev), based on partial envelope gene sequences, predicted a westward clinal pattern of evolution and dispersal across northern eurasia, terminating in the british isles. we tested this hypothesis using all available full-length open reading frame (orf) tbf sequences. phylogenetic ana ...201222674986
direct molecular detection and genotyping of borrelia burgdorferi from whole blood of patients with early lyme disease.direct molecular tests in blood for early lyme disease can be insensitive due to low amount of circulating borrelia burgdorferi dna. to address this challenge, we have developed a sensitive strategy to both detect and genotype b. burgdorferi directly from whole blood collected during the initial patient visit. this strategy improved sensitivity by employing 1.25 ml of whole blood, a novel pre-enrichment of the entire specimen extract for borrelia dna prior to a multi-locus pcr and electrospray i ...201222590620
differential salivary gland transcript expression profile in ixodes scapularis nymphs upon feeding or flavivirus infection.ixodid ticks are vectors of human diseases such as lyme disease, babesiosis, anaplasmosis, and tick-borne encephalitis. these diseases cause significant morbidity and mortality worldwide and are transmitted to humans during tick feeding. the tick-host-pathogen interface is a complex environment where host responses are modulated by the molecules in tick saliva to enable the acquisition of a blood meal. disruption of host responses at the site of the tick bite may also provide an advantage for pa ...201222309855
experimental therapies for yellow fever.a number of viruses in the family flaviviridae are the focus of efforts to develop effective antiviral therapies. success has been achieved with inhibitors for the treatment of hepatitis c, and there is interest in clinical trials of drugs against dengue fever. antiviral therapies have also been evaluated in patients with japanese encephalitis and west nile encephalitis. however, no treatment has been developed against the prototype flavivirus, yellow fever virus (yfv). despite the availability ...201223237991
a quantitative and novel approach to the prioritization of zoonotic diseases in north america: a public perspective.zoonoses account for over half of all communicable diseases causing illness in humans. as there are limited resources available for the control and prevention of zoonotic diseases, a framework for their prioritization is necessary to ensure resources are directed into those of highest importance. although zoonotic outbreaks are a significant burden of disease in north america, the systematic prioritization of zoonoses in this region has not been previously evaluated.201223133639
kyasanur forest disease.in the spring of 1957, an outbreak of severe disease was documented in people living near the kyasanur forest in karnataka state, india, which also affected wild nonhuman primates. collection of samples from dead animals and the use of classical virological techniques led to the isolation of a previously unrecognized virus, named kyasanur forest disease virus (kfdv), which was found to be related to the russian spring-summer encephalitis (rsse) complex of tick-borne viruses. further evaluation f ...201223110991
the contribution of rodent models to the pathological assessment of flaviviral infections of the central nervous system.members of the genus flavivirus are responsible for a spectrum of important neurological syndromes in humans and animals. rodent models have been used extensively to model flavivirus neurological disease, to discover host-pathogen interactions that influence disease outcome, and as surrogates to determine the efficacy and safety of vaccines and therapeutics. in this review, we discuss the current understanding of flavivirus neuroinvasive disease and outline the host, viral and experimental facto ...201222592957
prevalence and genetic characterization of powassan virus strains infecting ixodes scapularis in connecticut.a total of 30 powassan virus (powv) isolates from ixodes scapularis collected from bridgeport and north branford, ct in 2008, 2010, 2011, and 2012 and one earlier isolate from ixodes cookei collected in old lyme, ct in 1978 were characterized by phylogenetic analysis of their envelope gene sequences. powassan virus sequences segregated into two major groups termed the deer tick virus (dtv) and powassan (pow) lineages. the lineage from i. cookei was pow. the remaining viruses from i. scapularis g ...201222890037
first dating of a recombination event in mammalian tick-borne flaviviruses.the mammalian tick-borne flavivirus group (mtbfg) contains viruses associated with important human and animal diseases such as encephalitis and hemorrhagic fever. in contrast to mosquito-borne flaviviruses where recombination events are frequent, the evolutionary dynamic within the mtbfg was believed to be essentially clonal. this assumption was challenged with the recent report of several homologous recombinations within the tick-borne encephalitis virus (tbev). we performed a thorough analysis ...201222384119
powassan virus infection: case series and literature review from a single institution.powassan virus is a flavivirus related to eastern hemisphere's tick-borne encephalitis viruses. it can cause a rare but potentially life-threatening disease including encephalitis.201223111001
tick-borne diseases in minnesota: an update.tick-borne diseases endemic to minnesota include lyme disease, babesiosis, anaplasmosis/ehrlichiosis, powassan virus illness and rocky mountain spotted fever. physicians need to be aware of these diseases and be vigilant about testing for them when patients present with acute febrile illness or rash within one month of potential tick exposure. in addition, they need to educate patients about these diseases and encourage prevention measures, especially use of tick repellents. this article reviews ...201222953474
west nile virus disease and other arboviral diseases - united states, 2011.arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. symptomatic infections most often manifest as a systemic febrile illness and, less commonly, as neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis). west nile virus (wnv) is the leading cause of domestically acquired arboviral disease in the united states. however, several other arboviruses also cause seasonal outbreaks and sporadic cases. in ...201222785342
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