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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
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
established population of blacklegged ticks with high infection prevalence for the lyme disease bacterium, borrelia burgdorferi sensu lato, on corkscrew island, kenora district, ontario.we document an established population of blacklegged ticks, ixodes scapularis, on corkscrew island, kenora district, ontario, canada. primers of the outer surface protein a (ospa) gene, the flagellin (fla) gene, and the flagellin b (flab) gene were used in the pcr assays to detect borrelia burgdorferi sensu lato (s.l.), the lyme disease bacterium. in all, 60 (73%) of 82 adult i. scapularis, were infected with b. burgdorferi s.l. as well, 6 (43%) of 14 unfed i. scapularis nymphs were positive for ...201627877080
bunyaviruses are common in male and female ixodes scapularis ticks in central pennsylvania.the blacklegged tick ixodes scapularis is widely distributed in the united states and transmits multiple pathogens to humans, wildlife and domestic animals. recently, several novel viruses in the family bunyaviridae (south bay virus (sbv) and blacklegged tick phlebovirus (btpv)) were identified infecting female i. scapularis ticks collected in new york state. we used metagenomic sequencing to investigate the distribution of viruses infecting male and female i. scapularis ticks collected in centr ...201627602290
human pathogens associated with the blacklegged tick ixodes scapularis: a systematic review.the blacklegged tick ixodes scapularis transmits borrelia burgdorferi (sensu stricto) in eastern north america; however, the agent of lyme disease is not the sole pathogen harbored by the blacklegged tick. the blacklegged tick is expanding its range into areas of southern canada such as ontario, an area where exposure to blacklegged tick bites and tick-borne pathogens is increasing. we performed a systematic review to evaluate the public health risks posed by expanding blacklegged tick populatio ...201627151067
prevalence of the lyme disease spirochete, borrelia burgdorferi, in blacklegged ticks, ixodes scapularis at hamilton-wentworth, ontario.lyme disease has emerged as a major health concern in canada, where the etiological agent, borrelia burgdorferi sensu lato (s.l.), a spirochetal bacterium, is typically spread by the bite of certain ticks. this study explores the presence of b. burgdorferi s.l. in blacklegged ticks, ixodes scapularis, collected at dundas, ontario (a locality within the region of hamilton-wentworth). using passive surveillance, veterinarians and pet groomers were asked to collect blacklegged ticks from dogs and c ...201627226771
ixodes scapularis tick saliva proteins sequentially secreted every 24 h during blood feeding.ixodes scapularis is the most medically important tick species and transmits five of the 14 reportable human tick borne disease (tbd) agents in the usa. this study describes lc-ms/ms identification of 582 tick- and 83 rabbit proteins in saliva of i. scapularis ticks that fed for 24, 48, 72, 96, and 120 h, as well as engorged but not detached (bd), and spontaneously detached (sd). the 582 tick proteins include proteases (5.7%), protease inhibitors (7.4%), unknown function proteins (22%), immunity ...201626751078
lyme disease risk in southern california: abiotic and environmental drivers of ixodes pacificus (acari: ixodidae) density and infection prevalence with borrelia burgdorferi.tick-borne diseases, particularly lyme disease, are emerging across the northern hemisphere. in order to manage emerging diseases and predict where emergence will likely occur, it is necessary to understand the factors influencing the distribution, abundance and infection prevalence of vector species. in north america, lyme disease is the most common vector-borne disease and is transmitted by blacklegged ticks. this study aimed to explore the abiotic and environmental drivers of density and infe ...201728057067
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
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
phidias: a pathogen-host interaction data integration and analysis system.the pathogen-host interaction data integration and analysis system (phidias) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (phis) for pathogen species designated as high priority agents for public health and biological security. in addition, phidias allows submission, search and analysis of phi genes and molecular networks curated fro ...200717663773
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
viral meningitis. 199820401229
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
arbovirosis and potential transmission blocking vaccines.infectious diseases caused by arboviruses (viruses transmitted by arthropods) are undergoing unprecedented epidemic activity and geographic expansion. with the recent introduction of west nile virus (1999), chikungunya virus (2013) and zika virus (2015) to the americas, stopping or even preventing the expansion of viruses into susceptible populations is an increasing concern. with a few exceptions, available vaccines protecting against arboviral infections are nonexistent and current disease pre ...201627664127
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
molecular detection of flaviviruses and alphaviruses in mosquitoes (diptera: culicidae) from coastal ecosystems in the colombian caribbean.arboviruses belonging to the genera flavivirus and alphavirus were detected in mosquitoes in a rural area of san bernardo del viento (córdoba, colombia). a total of 22,180 mosquitoes were collected, sorted into 2,102 pools, and tested by generic/nested reverse transcription-polymerase chain reaction. venezuelan equine encephalitis virus, dengue virus, west nile virus, st. louis encephalitis virus, yellow fever virus, and culex flavivirus were detected and identified by sequencing. the detection ...201627706377
arbovirus infections.arbovirus (arthropod-borne virus) infections are increasingly important causes of neurologic disease in the united states through both endemic transmission and travel-associated infections. this article reviews the major arbovirus infections that can cause neurologic disease likely to be encountered in the united states.026633778
powassan meningoencephalitis, new york, new york, usa.disease caused by powassan virus (powv), a tick-borne flavivirus, ranges from asymptomatic to severe neurologic compromise and death. two cases of powv meningoencephalitis in new york, usa, highlight diagnostic techniques, neurologic outcomes, and the effect of powv on communities to which it is endemic.023969017
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
biological transmission of arboviruses: reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends.among animal viruses, arboviruses are unique in that they depend on arthropod vectors for transmission. field research and laboratory investigations related to the three components of this unique mode of transmission, virus, vector, and vertebrate host, have produced an enormous amount of valuable information that may be found in numerous publications. however, despite many reviews on specific viruses, diseases, or interests, a systematic approach to organizing the available information on all f ...016223950
imported arbovirus infections in canada 1974-89.from 1974 to 1989, sera from symptomatic patients with histories of recent travel outside canada were tested for antibodies to several arboviruses, principally of the alphavirus and flavivirus families. diagnostic seroconversions were documented in 84 individuals from six provinces, including one alphavirus (chikungunya) and 83 flavivirus seroconvertors. dengue 1 virus was isolated from the blood of one patient. most flavivirus seroconvertors were likely infected with dengue virus, but infection ...022529717
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
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
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
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
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
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
underreporting of viral encephalitis and viral meningitis, ireland, 2005-2008.viral encephalitis (ve) and viral meningitis (vm) have been notifiable infectious diseases under surveillance in the republic of ireland since 1981. laboratories have reported confirmed cases by detection of viral nucleic acid in cerebrospinal fluid since 2004. to determine the prevalence of these diseases in ireland during 2005-2008, we analyzed 3 data sources: hospital in-patient enquiry data (from hospitalized following patients discharge) accessed through health intelligence ireland, laborat ...023965781
discovery of dengue virus ns4b inhibitors.the four serotypes of dengue virus (denv-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. no clinically approved vaccine or antiviral is currently available for denv. here we report a spiropyrazolopyridone compound that potently inhibits denv both in vitro and in vivo. the inhibitor was identified through screening of a 1.8-million-compound library by using a denv-2 replicon assay. the compound selectively inhibits denv-2 and -3 (50% effective concentration [ec50], ...026018165
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
ecuador paraiso escondido virus, a new flavivirus isolated from new world sand flies in ecuador, is the first representative of a novel clade in the genus flavivirus.a new flavivirus, ecuador paraiso escondido virus (epev), named after the village where it was discovered, was isolated from sand flies (psathyromyia abonnenci, formerly lutzomyia abonnenci) that are unique to the new world. this represents the first sand fly-borne flavivirus identified in the new world. epev exhibited a typical flavivirus genome organization. nevertheless, the maximum pairwise amino acid sequence identity with currently recognized flaviviruses was 52.8%. phylogenetic analysis o ...201526355096
new insights into flavivirus evolution, taxonomy and biogeographic history, extended by analysis of canonical and alternative coding sequences.to generate the most diverse phylogenetic dataset for the flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 flaviviruses, of which 10 are primarily associated with culex spp. mosquitoes. we analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth. based on the presumed introduction of yellow fever virus into the americ ...201525719412
identification of a flavivirus sequence in a marine arthropod.phylogenetic analysis has yet to uncover the early origins of flaviviruses. in this study, i mined a database of expressed sequence tags in order to discover novel flavivirus sequences. flavivirus sequences were identified in a pool of mrna extracted from the sea spider endeis spinosa (pycnogonida, pantopoda). reconstruction of the translated sequences and blast analysis matched the sequence to the flavivirus ns5 gene. additional sequences corresponding to envelope and the ns5 mtase domain were ...201526717191
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
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
transcriptome analysis reveals a signature profile for tick-borne flavivirus persistence in hek 293t cells.tick-borne flaviviruses (tbfvs) cause febrile illnesses, which may progress to severe encephalitis and/or death in humans globally. most people who recover from severe acute disease suffer from debilitating neurological sequelae, which may be due to viral persistence, infection-induced neurological cell damage, host response, or some combination of these. acute tbfv infection of human embryonic kidney (hek) 293t cells in vitro results in the death of >95% of infected cells by day 5. however, rep ...201627222466
recovery of west nile virus envelope protein domain iii chimeras with altered antigenicity and mouse virulence.flaviviruses are positive-sense, single-stranded rna viruses responsible for millions of human infections annually. the envelope (e) protein of flaviviruses comprises three structural domains, of which domain iii (eiii) represents a discrete subunit. the eiii gene sequence typically encodes epitopes recognized by virus-specific, potently neutralizing antibodies, and eiii is believed to play a major role in receptor binding. in order to assess potential interactions between eiii and the remainder ...201626912625
a preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for japanese encephalitis in nepal.japanese encephalitis (je) virus (jev) is a mosquito-borne flavivirus found across asia that is closely related to west nile virus. there is no known antiviral treatment for any flavivirus. results from in vitro studies and animal models suggest intravenous immunoglobulin (ivig) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. ivig's anti-inflammatory properties may also be beneficial.201525886645
factors responsible for the emergence of arboviruses; strategies, challenges and limitations for their control.slave trading of africans to the americas, during the 16th to the 19th century was responsible for the first recorded emergence in the new world of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. many other arboviruses have since emerged from their sylvatic reservoirs and dispersed globally due to evolving factors that include anthropological behaviour, commercial transportation and land-remediation. here, we outline some characteristics of these highly divergent ...201526038768
state health department perceived utility of and satisfaction with arbonet, the u.s. national arboviral surveillance system.we assessed the perceived utility of data collected through arbonet, the national arboviral surveillance system, and evaluated state health department user satisfaction with system function.022753981
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
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
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
the tortoise or the hare? impacts of within-host dynamics on transmission success of arthropod-borne viruses.arthropod-borne viruses (arboviruses) are maintained in a cycle of alternating transmission between vertebrate hosts and arthropod vectors. arboviruses possess rna genomes capable of rapid diversification and adaptation, and the between-host trade-offs inherent to host alternation impose well-documented constraints on arbovirus evolution. here, we investigate the less well-studied within-host trade-offs that shape arbovirus replication dynamics and transmission. arboviruses generally establish l ...026150665
assessment of arbovirus surveillance 13 years after introduction of west nile virus, united states.before 1999, the united states had no appropriated funding for arboviral surveillance, and many states conducted no such surveillance. after emergence of west nile virus (wnv), federal funding was distributed to state and selected local health departments to build wnv surveillance systems. the council of state and territorial epidemiologists conducted assessments of surveillance capacity of resulting systems in 2004 and in 2012; the assessment in 2012 was conducted after a 61% decrease in federa ...026079471
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
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
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
viruses infecting reptiles.a large number of viruses have been described in many different reptiles. these viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. the imp ...201122163336
changes in the proteome of langat-infected ixodes scapularis ise6 cells: metabolic pathways associated with flavivirus infection.ticks (family ixodidae) transmit a variety of disease causing agents to humans and animals. the tick-borne flaviviruses (tbfs; family flaviviridae) are a complex of viruses, many of which cause encephalitis and hemorrhagic fever, and represent global threats to human health and biosecurity. pathogenesis has been well studied in human and animal disease models. equivalent analyses of tick-flavivirus interactions are limited and represent an area of study that could reveal novel approaches for tbf ...201626859745
zika virus on a spreading spree: what we now know that was unknown in the 1950's.zika virus (zikv) is a mosquito-borne flavivirus that is transmitted through the bite of aedes spp mosquitoes and less predominantly, through sexual intercourse. prior to 2007, zikv was associated with only sporadic human infections with minimal or no clinical manifestations. recently the virus has caused disease outbreaks from the pacific islands, the americas, and off the coast of west africa with approximately 1.62 million people suspected to be infected in more than 60 countries around the g ...201627716242
flavidb: a data mining system for knowledge discovery in flaviviruses with direct applications in immunology and vaccinology.the flavivirus genus is unusually large, comprising more than 70 species, of which more than half are known human pathogens. it includes a set of clinically relevant infectious agents such as dengue, west nile, yellow fever, and japanese encephalitis viruses. although these pathogens have been studied extensively, safe and efficient vaccines lack for the majority of the flaviviruses.025544857
flavivirus ns1: a multifaceted enigmatic viral protein.flaviviruses are emerging arthropod-borne viruses representing an immense global health problem. the prominent viruses of this group include dengue virus, yellow fever virus, japanese encephalitis virus, west nile virus tick borne encephalitis virus and zika virus. these are endemic in many parts of the world. they are responsible for the illness ranging from mild flu like symptoms to severe hemorrhagic, neurologic and cognitive manifestations leading to death. ns1 is a highly conserved non-stru ...201627473856
murine efficacy and pharmacokinetic evaluation of the flaviviral ns5 capping enzyme 2-thioxothiazolidin-4-one inhibitor bg-323.arthropod-borne flavivirus infection continues to cause significant morbidity and mortality worldwide. identification of drug targets and novel antiflaviviral compounds to treat these diseases has become a global health imperative. a previous screen of 235,456 commercially available small molecules identified the 2-thioxothiazolidin-4-one family of compounds as inhibitors of the flaviviral ns5 capping enzyme, a promising target for antiviral drug development. rational drug design methodologies e ...201526075394
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
transmission bottlenecks and rnai collectively influence tick-borne flavivirus evolution.arthropod-borne rna viruses exist within hosts as heterogeneous populations of viral variants and, as a result, possess great genetic plasticity. understanding the micro-evolutionary forces shaping these viruses can provide insights into how they emerge, adapt, and persist in new and changing ecological niches. while considerable attention has been directed toward studying the population dynamics of mosquito-borne viruses, little is known about tick-borne virus populations. therefore, using a mo ...201628058113
aedes aegypti d7 saliva protein inhibits dengue virus infection.aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (denv) types 1-4. ae. aegypti transmits denv by inoculating virus-infected saliva into host skin during probing and feeding. ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. previously, we showed that ae. aegypti salivary gland extracts (sges) enhanced dissemination of denv to draining lymph nodes. in con ...201627632170
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
spinal cord ventral horns and lymphoid organ involvement in powassan virus infection in a mouse model.powassan virus (powv) belongs to the family flaviviridae and is a member of the tick-borne encephalitis serogroup. transmission of powv from infected ticks to humans has been documented in the usa, canada, and russia, causing fatal encephalitis in 10% of human cases and significant neurological sequelae in survivors. we used c57bl/6 mice to investigate powv infection and pathogenesis. after footpad inoculation, infected animals exhibited rapid disease progression and 100% mortality. immunohistoc ...201627529273
in vitro antiviral activity of adenosine analog nitd008 against tick-borne flaviviruses.there are currently no antiviral therapies 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). in this brief study, we describe the in vitro antiviral activity of adenosine analog nitd008 against kfdv, ahfv, ohfv, as well as tick-borne encephalitis virus (tbev). alongside the well-established activity of nitd008 against m ...201627016316
kissing-loop interaction between 5' and 3' ends of tick-borne langat virus genome 'bridges the gap' between mosquito- and tick-borne flaviviruses in mechanisms of viral rna cyclization: applications for virus attenuation and vaccine development.insertion of microrna target sequences into the flavivirus genome results in selective tissue-specific attenuation and host-range restriction of live attenuated vaccine viruses. however, previous strategies for mirna-targeting did not incorporate a mechanism to prevent target elimination under mirna-mediated selective pressure, restricting their use in vaccine development. to overcome this limitation, we developed a new approach for mirna-targeting of tick-borne flavivirus (langat virus, lgtv) i ...201626850640
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
analysis of the langat virus genome in persistent infection of an ixodes scapularis cell line.tick-borne flaviviruses (tbfvs) cause a broad spectrum of disease manifestations ranging from asymptomatic to mild febrile illness and life threatening encephalitis. these single-stranded positive-sense (ss(+)) rna viruses are naturally maintained in a persistent infection of ixodid ticks and small-medium sized mammals. the development of cell lines from the ixodid ticks has provided a valuable surrogate system for studying the biology of tbfvs in vitro. when we infected ise6 cells, an ixodes sc ...201627626437
first evidence of established populations of the taiga tick ixodes persulcatus (acari: ixodidae) in sweden.the tick species ixodes ricinus and i. persulcatus are of exceptional medical importance in the western and eastern parts, respectively, of the palaearctic region. in russia and finland the range of i. persulcatus has recently increased. in finland the first records of i. persulcatus are from 2004. the apparent expansion of its range in finland prompted us to investigate if i. persulcatus also occurs in sweden.201627370406
immune cell targets of infection at the tick-skin interface during powassan virus transmission.powassan virus (powv) is a tick-borne flavivirus that can result in a severe neuroinvasive disease with 50% of survivors displaying long-term neurological sequelae. human powv cases have been documented in canada, the united states, and russia. although the number of reported powv human cases has increased in the past fifteen years, powv remains one of the less studied human pathogenic flaviviruses. ixodes ticks are the vectors for powv, and the virus is transmitted to a host's skin very early d ...201627203436
stability of a tick-borne flavivirus in milk.the tick-borne flaviviruses (tbfv) occur worldwide and the tick-borne encephalitis virus (tbev) members of the group often cause severe, debilitating neurological disease in humans. although the primary route of infection is through the bite of an infected tick, alimentary infection through the consumption of tbev-contaminated dairy products is also well-documented and is responsible for some disease in endemic areas. experimental infection of goats, cattle, and sheep with tbev shows that the vi ...201627243000
diversity of viruses in ixodes ricinus, and characterization of a neurotropic strain of eyach virus.ticks transmit more pathogens-including bacteria, parasites and viruses-than any other arthropod vector. although the epidemiological status of many tick-borne bacteria is very well characterized, tick-borne viruses are still relatively under-studied. recently, several novel tick-borne viruses have been isolated from human febrile illnesses following tick bites, indicating the existence of other potential new and unknown tick-borne viruses. we used high-throughput sequencing to analyse the virom ...201627158509
four emerging arboviral diseases in north america: jamestown canyon, powassan, chikungunya, and zika virus diseases.arthropod-borne viruses, or arboviruses, are viruses that are transmitted through the bites of mosquitoes, ticks, or sandflies. there are numerous arboviruses throughout the world capable of causing human disease spanning different viral families and genera. recently, jamestown canyon, powassan, chikungunya, and zika viruses have emerged as increasingly important arboviruses that can cause human disease in north america. unfortunately, there are currently no proven disease-modifying therapies fo ...201626903031
detection of langat virus by taqman real-time one-step qrt-pcr method.langat virus (lgtv), one of the members of the tick-borne encephalitis virus (tbev) complex, was firstly isolated from ixodes granulatus ticks in malaysia. however, the prevalence of lgtv in ticks in the region remains unknown. surveillance for lgtv is therefore important and thus a tool for specific detection of lgtv is needed. in the present study, we developed a real-time quantitative reverse-transcription-polymerase chain reaction (qrt-pcr) for rapid detection of lgtv. our findings showed th ...201526360297
to beat or not to beat a tick: comparison of dna extraction methods for ticks (ixodes scapularis).background. blacklegged ticks (ixodes scapularis) are important disease vectors in the united states, known to transmit a variety of pathogens to humans, including bacteria, protozoa, and viruses. their importance as a disease vector necessitates reliable and comparable methods for extracting microbial dna from ticks. furthermore, to explore the population genetics or genomics of this tick, appropriate dna extraction techniques are needed for both the vector and its microbes. although a few stud ...201526290800
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
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