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1.
Emerg Infect Dis ; 30(2): 396-398, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38270166

RESUMEN

We report fatal West Nile virus (WNV) infection in a 7-year-old mare returning to the United Kingdom from Spain. Case timeline and clustering of virus sequence with recent WNV isolates suggest that transmission occurred in Andalusía, Spain. Our findings highlight the importance of vaccination for horses traveling to WNV-endemic regions.


Asunto(s)
Fiebre del Nilo Occidental , Animales , Femenino , Análisis por Conglomerados , Caballos , España/epidemiología , Reino Unido/epidemiología , Fiebre del Nilo Occidental/diagnóstico , Fiebre del Nilo Occidental/veterinaria
2.
J Virol ; 97(12): e0118323, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-37991381

RESUMEN

IMPORTANCE: Central nervous system infection by flaviviruses such as Japanese encephalitis virus, Dengue virus, and West Nile virus results in neuroinflammation and neuronal damage. However, little is known about the role of long non-coding RNAs (lncRNAs) in flavivirus-induced neuroinflammation and neuronal cell death. Here, we characterized the role of a flavivirus-induced lncRNA named JINR1 during the infection of neuronal cells. Depletion of JINR1 during virus infection reduces viral replication and cell death. An increase in GRP78 expression by JINR1 is responsible for promoting virus replication. Flavivirus infection induces the expression of a cellular protein RBM10, which interacts with JINR1. RBM10 and JINR1 promote the proinflammatory transcription factor NF-κB activity, which is detrimental to cell survival.


Asunto(s)
Muerte Celular , Virus de la Encefalitis Japonesa (Especie) , FN-kappa B , Neuronas , ARN Largo no Codificante , Proteínas de Unión al ARN , Humanos , Virus de la Encefalitis Japonesa (Especie)/crecimiento & desarrollo , Virus de la Encefalitis Japonesa (Especie)/patogenicidad , Enfermedades Neuroinflamatorias/patología , Enfermedades Neuroinflamatorias/virología , FN-kappa B/metabolismo , ARN Largo no Codificante/genética , Proteínas de Unión al ARN/metabolismo , Neuronas/patología , Neuronas/virología , Replicación Viral
3.
J Gen Virol ; 104(7)2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37432877

RESUMEN

The 2',5'- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL activity in infected cells. We aimed to investigate PDE12 as a potential pan-RNA virus antiviral drug target and develop PDE12 inhibitors that elicit antiviral activity against a range of viruses. A library of 18 000 small molecules was screened for PDE12 inhibitor activity using a fluorescent probe specific for PDE12. The lead compounds (CO-17 or CO-63) were tested in cell-based antiviral assays using encephalomyocarditis virus (EMCV), hepatitis C virus (HCV), dengue virus (DENV), West Nile virus (WNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in vitro. Cross reactivity of PDE12 inhibitors with other PDEs and in vivo toxicity were measured. In EMCV assays, CO-17 potentiated the effect of IFNα by 3 log10. The compounds were selective for PDE12 when tested against a panel of other PDEs and non-toxic at up to 42 mg kg-1 in rats in vivo. Thus, we have identified PDE12 inhibitors (CO-17 and CO-63), and established the principle that inhibitors of PDE12 have antiviral properties. Early studies suggest these PDE12 inhibitors are well tolerated at the therapeutic range, and reduce viral load in studies of DENV, HCV, WNV and SARS-CoV-2 in human cells and WNV in a mouse model.


Asunto(s)
COVID-19 , Virus ARN , Humanos , Ratones , Animales , Ratas , Antivirales/farmacología , SARS-CoV-2 , Interferón-alfa , Virus de la Encefalomiocarditis , Hidrolasas Diéster Fosfóricas
4.
Cytokine ; 172: 156383, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37801852

RESUMEN

BACKGROUND: Japanese Encephalitis Virus (JEV) and West Nile Viruses (WNV) are neurotropic flaviviruses which cause neuronal death and exaggerated glial activation in the central nervous system. Role of host long non coding RNAs in shaping microglial inflammation upon flavivirus infections has been unexplored. This study attempted to decipher the role of lncRNA Gm20559 in regulating microglial inflammatory response in context of flaviviruses. METHODS: Antisense oligonucleotide LNA Gapmers designed against lncRNA Gm20559 and non-specific site (negative control) were used for Gm20559 knockdown in JEV and WNV-infected N9 microglial cells. Upon establishing successful Gm20559 knockdown, expression of various proinflammatory cytokines, chemokines, interferon-stimulated genes (ISGs) and RIG-I were checked by qRT-PCR and cytometric bead array. Western Blotting was done to analyse the phosphorylation level of various inflammatory markers and viral non-structural protein expression. Plaque Assays were employed to quantify viral titres in microglial supernatant upon knocking down Gm20559. Effect of microglial supernatant on HT22 neuronal cells was assessed by checking expression of apoptotic protein and viral non-structural protein by Western Blotting. RESULTS: Upregulation in Gm20559 expression was observed in BALB/c pup brains, primary microglia as well as N9 microglia cell line upon both JEV and WNV infection. Knockdown of Gm20559 in JEV and WNV-infected N9 cell led to the reduction of major proinflammatory cytokines - IL-1ß, IL-6, IP-10 and IFN-ß. Inhibition of Gm20559 upon JEV infection in N9 microglia also led to downregulation of RIG-I and OAS-2, which was not the case in WNV-infected N9 microglia. Phosphorylation level of P38 MAPK was reduced in case of JEV-infected N9 microglia and not WNV-infected N9 microglia. Whereas phosphorylation of NF-κB pathway was unchanged upon Gm20559 knockdown in both JEV and WNV-infected N9 microglia. However, treating HT22 cells with JEV and WNV-infected microglial supernatant with and without Gm20559 could not trigger cell death or influence viral replication. CONCLUSION: Knockdown studies on lncRNA Gm20559 suggests its pivotal role in maintaining the inflammatory milieu of microglia in flaviviral infection by modulating the expression of various pro-inflammatory cytokines. However, Gm20559-induced increased microglial proinflammatory response upon flavivirus infection fails to trigger neuronal death.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Flavivirus , ARN Largo no Codificante , Virus del Nilo Occidental , Humanos , Microglía/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Virus de la Encefalitis Japonesa (Especie)/genética , Encefalitis Japonesa/genética , Inflamación/genética , Inflamación/metabolismo , Citocinas/metabolismo , Virus del Nilo Occidental/genética , Virus del Nilo Occidental/metabolismo
5.
Int J Neurosci ; 133(6): 660-671, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34347576

RESUMEN

Neurological infections are often devastating in their clinical presentation. Although significant advances have made in neuroimaging techniques and molecular tools for diagnosis, as well as in anti-infective therapy, these diseases always difficult to diagnose and treat. Neuroparasitic infections and virus infections lead to neurological infections. In the nervous system, various cytokines and chemokines act as neuroinflammatory agents, neuromodulators, regulate neurodevelopment, and synaptic transmission. Among the most important cytokines, interleukins (ILs) are a large group of immunomodulatory proteins that elicit a wide variety of responses in cells and tissues. These ILs are involved in pro and anti-inflammatory effects, systemic inflammation, immune system modulation and play crucial roles in fighting cancer, infectious disease, and neurological disorders. Interleukin-34 (IL-34) identified by screening a comprehensive human protein library containing ∼3400 secreted and extracellular domain proteins in a human monocyte viability assay. Recent evidence has disclosed the crucial roles of IL-34 in the proliferation and differentiation of mononuclear phagocyte lineage cells, osteoclastogenesis, and inflammation. Additionally, IL-34 plays an important role in development, homeostasis, and disease. Dysregulation in IL-34 function can lead to various inflammatory and infectious diseases (e.g. Inflammatory bowel disease, liver fibrosis, Systemic Lupus erythematosus, rheumatoid arthritis), neurological disorders (e.g. Alzheimer disease) and neurological infectious disease (e.g. West Nile virus disease). In this review, we explore the biological role of IL-34 in addition to various impairments caused by dysregulation in IL-34 and discuss their potential links that may lead to important therapeutic and/or preventive strategies for these disorders.


Asunto(s)
Enfermedades Transmisibles , Enfermedades del Sistema Nervioso , Humanos , Interleucinas/metabolismo , Citocinas , Inflamación
6.
J Virol ; 95(22): e0104021, 2021 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-34495694

RESUMEN

We previously identified a subset of interferon-stimulated genes (ISGs) upregulated by West Nile virus (WNV) infection in wild-type mouse embryo fibroblasts (MEFs) after viral proteins had inhibited type I interferon (IFN)-mediated JAK-STAT signaling and also in WNV-infected RIG-I-/-, MDA5-/-, STAT1-/-, STAT2-/-, IFNAR-/-, IRF3-/-, IRF7-/-, and IRF3/7-/- MEFs. In this study, ISG upregulation by WNV infection in IFNAR-/- MEFs was confirmed by transcriptome sequencing (RNA-seq). ISG upregulation by WNV infection was inhibited in RIG-I/MDA5-/- MEFs. ISGs were upregulated in IRF1-/- and IRF5-/- MEFs but only minimally upregulated in IRF3/5/7-/- MEFs, suggesting redundant IRF involvement. We previously showed that a single proximal interferon-stimulated response element (ISRE) in the Oas1a and Oas1b promoters bound the ISGF3 complex after type I IFN treatment. In this study, we used wild-type and mutant promoter luciferase reporter constructs to identify critical regions in the Oas1b and Ifit1 promoters for gene activation in infected IFNAR-/- MEFs. Two ISREs were required in both promoters. Mutation of these ISREs in an Ifit1 promoter DNA probe reduced in vitro complex formation with infected nuclear extracts. An NF-κB inhibitor decreased Ifit1 promoter activity in cells and in vitro complex formation. IRF3 and p50 promoter binding was detected by chromatin immunoprecipitation (ChIP) for upregulated ISGs with two proximal ISREs. The data indicate that ISREs function cooperatively to upregulate the expression of some ISGs when type I IFN signaling is absent, with the binding complex consisting of IRF3, IRF5, and/or IRF7 and an NF-κB component(s) as well as other, as-yet-unknown factors. IMPORTANCE Type I IFN signaling in mammalian cells induces formation of the ISGF3 transcription factor complex, which binds to interferon stimulated response elements (ISREs) in the promoters of interferon-stimulated genes (ISGs) in the cell nucleus. Flavivirus proteins counteract type I IFN signaling by preventing either the formation or nuclear localization of ISGF3. A subset of ISRE-regulated ISGs was still induced in West Nile virus (WNV)-infected mouse embryo fibroblasts (MEFs), indicating that cells have an alternative mechanism for activating these ISGs. In this study, cellular components involved in this ISG upregulation mechanism were identified using gene knockout MEFs and ChIP, and critical promoter regions for gene activation were mapped using reporter assays. The data indicate a cooperative function between two ISREs and required binding of IRF3, IRF5, and/or IRF7 and an NF-κB component(s). Moreover, type I IFN signaling-independent ISG activation requires different additional promoter activation regions than type I IFN-dependent activation.


Asunto(s)
Fibroblastos , Regulación de la Expresión Génica/inmunología , Interferón Tipo I/inmunología , Fiebre del Nilo Occidental/inmunología , Virus del Nilo Occidental/inmunología , Animales , Fibroblastos/inmunología , Fibroblastos/virología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Elementos de Respuesta/inmunología
7.
J Appl Microbiol ; 133(6): 3512-3522, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36007965

RESUMEN

AIM: West Nile encephalitis caused by infection with the West Nile virus (WNV) is endemic in many regions of the world and is a global public health threat. The aim of this report was to develop a method using colorimetry-based reverse-transcription loop-mediated isothermal amplification (cRT-LAMP) and RT-LAMP combined with lateral-flow dipstick (LFD) for rapidly detecting WNV in low-infrastructure settings. METHODS AND RESULTS: The primers for the cRT-LAMP and RT-LAMP-LFD assays were designed based on env gene of the WNV. Primers concentration, temperature and time were optimized for cRT-LAMP and RT-LAMP-LFD. The diagnostic performance of the cRT-LAMP and RT-LAMP-LFD assays was evaluated using human serum samples from 110 patients who were clinically suspected to be infected with WNV. The RT-LAMP was performed in a heating block at 63°C for 40 min. The LAMP amplicons were visible in the lateral-flow dipstick within 5 min. The detection limit of the developed cRT-LAMP and RT-LAMP-LFD assays was 10 copies and this assay showed a high degree of specificity for WNV. Compared with quantitative real-time RT-PCR assay, the kappa value of cRT-LAMP and RT-LAMP-LFD were 0.970. CONCLUSIONS: These results showed that the newly developed WNV-specific cRT-LAMP and RT-LAMP-LFD assays can be employed as an alternative method for screening of WN-suspected human samples. The results revealed that the assay could potentially identify the virus without interference from human serum samples. Collectively, all results revealed that cRT-LAMP and RT-LAMP-LFD assays offer a suitable field-based diagnosis of WNV. SIGNIFICANCE AND IMPACT OF THE STUDY: The cRT-LAMP and LAMP-LFD platform for the detection of WNV is rapid, accurate and simple-to-perform. Our present method has not only a short turnaround time but also avoided cross-contamination problem. Moreover, the use of simple lateral flow dipsticks broadens its application potential for the point-of-care use in resource-limited settings during outbreak situations. To the best of our knowledge, this is the first report for the development of cRT-LAMP and LAMP-LFD assays for rapid, simple, specific and sensitive detection of WNV using human clinical samples and EvaGreen dye.


Asunto(s)
Virus del Nilo Occidental , Humanos , Virus del Nilo Occidental/genética , Sensibilidad y Especificidad , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Diagnóstico Molecular , Cartilla de ADN/genética
8.
Int J Mol Sci ; 23(15)2022 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-35955738

RESUMEN

Viruses rely on the cellular machinery of host cells to synthesize their proteins, and have developed different mechanisms enabling them to compete with cellular mRNAs for access to it. The genus Flavivirus is a large group of positive, single-stranded RNA viruses that includes several important human pathogens, such as West Nile, Dengue and Zika virus. The genome of flaviviruses bears a type 1 cap structure at its 5' end, needed for the main translation initiation mechanism. Several members of the genus also use a cap-independent translation mechanism. The present work provides evidence that the WNV 5' end also promotes a cap-independent translation initiation mechanism in mammalian and insect cells, reinforcing the hypothesis that this might be a general strategy of flaviviruses. In agreement with previous reports, we show that this mechanism depends on the presence of the viral genomic 3' UTR. The results also show that the 3' UTR of the WNV genome enhances translation of the cap-dependent mechanism. Interestingly, WNV 3' UTR can be replaced by the 3' UTR of other flaviviruses and the translation enhancing effect is maintained, suggesting a molecular mechanism that does not involve direct RNA-RNA interactions to be at work. In addition, the deletion of specific structural elements of the WNV 3' UTR leads to increased cap-dependent and cap-independent translation. These findings suggest the 3' UTR to be involved in a fine-tuned translation regulation mechanism.


Asunto(s)
Flavivirus , Infección por el Virus Zika , Virus Zika , Regiones no Traducidas 3' , Animales , Línea Celular , Flavivirus/genética , Genómica , Humanos , Mamíferos/genética , Virus Zika/genética
9.
Int J Mol Sci ; 23(14)2022 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35887069

RESUMEN

Flaviviruses are single-stranded RNA viruses that have emerged in recent decades and infect up to 400 million people annually, causing a variety of potentially severe pathophysiological processes including hepatitis, encephalitis, hemorrhagic fever, tissues and capillaries damage. The Flaviviridae family is represented by four genera comprising 89 known virus species. There are no effective therapies available against many pathogenic flaviviruses. One of the promising strategies for flavivirus infections prevention and therapy is the use of neutralizing antibodies (NAb) that can disable the virus particles from infecting the host cells. The envelope protein (E protein) of flaviviruses is a three-domain structure that mediates the fusion of viral and host membranes delivering the infectious material. We previously developed and characterized 10H10 mAb which interacts with the E protein of the tick-borne encephalitis virus (TBEV) and many other flaviviruses' E proteins. The aim of this work was to analyze the structure of E protein binding sites recognized by the 10H10 antibody, which is reactive with different flavivirus species. Here, we present experimental data and 3D modeling indicating that the 10H10 antibody recognizes the amino acid sequence between the two cysteines C92-C116 of the fusion loop (FL) region of flaviviruses' E proteins. Overall, our results indicate that the antibody-antigen complex can form a rigid or dynamic structure that provides antibody cross reactivity and efficient interaction with the fusion loop of E protein.


Asunto(s)
Virus de la Encefalitis Transmitidos por Garrapatas , Infecciones por Flavivirus , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Reacciones Cruzadas , Humanos
10.
J Avian Med Surg ; 36(1): 85-91, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35526169

RESUMEN

West Nile virus (WNV) has had a significant effect on avian populations in the United States since being first identified in 1999. Avian species in WNV endemic areas do not suffer the same level of mortality that has been reported in birds within the United States since the virus was first identified in North America. Because of their unique susceptibility, American crows (Corvus brachyrhynchos) are often used to monitor the spread and severity of WNV in North America. American crows with WNV infections are received and treated at the Janet L. Swanson Wildlife Hospital (Cornell University, Ithaca, NY, USA) on a regular basis during the summer and fall and have historically had a 100% mortality rate. This report describes WNV-positive American crows that were treated, recovered from the infection, and were subsequently released. The 5 American crows in this case series were tested, when possible, by polymerase chain reaction (PCR) and plaque reduction neutralization on admission and monitored with both PCR and plaque reduction neutralization throughout their rehabilitation process. Four of the 5 birds had a negative PCR test before release, and 1 bird had a "suspect" positive PCR test result before release. One of the crows was confirmed to have survived for at least 2.5 years after release. Viral shedding was documented up to 93 days after initial hospitalization, which is longer than any previous report of WNV shedding in an American crow.


Asunto(s)
Enfermedades de las Aves , Cuervos , Fiebre del Nilo Occidental , Virus del Nilo Occidental , Animales , Animales Salvajes , Enfermedades de las Aves/epidemiología , Humanos , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/veterinaria
11.
BMC Immunol ; 22(1): 5, 2021 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-33421988

RESUMEN

BACKGROUND: Recent outbreaks of Zika Virus (ZIKV) infection and associated microcephaly has raised multiple scientific questions. The close antigenic relatedness between flaviviruses makes diagnosis of specific infection difficult. This relatedness also raises the potential of Antibody Dependent Enhancement (ADE) via cross reactive antibodies to flaviviruses like West Nile Virus (WNV) and Dengue Virus (DENV). Asymptomatic WNV infections are endemic throughout the US creating a large proportion of the population that is seropositive for WNV antibodies. Whether these sero-positive individuals potentially carry ZIKV enhancing antibodies remains unknown. RESULTS: Serum samples obtained from human subjects with symptomatic or asymptomatic WNV infection from a WNV endemic region in Texas were tested for their ability to enhance or neutralize ZIKV infection. Sero-surveillance data demonstrated a ~ 7% prevalence for WNV antibodies in the population. Sera from both symptomatic and asymptomatic WNV seropositive donors effectively neutralized WNV and to some extent DENV infection. Interestingly, WNV+ sera failed to inhibit ZIKV while significantly enhancing infection. Conversely, ZIKV specific sera effectively neutralized ZIKV, with ADE only evident at lower concentrations. The enhancement of ZIKV via WNV antibody positive sera was likely due to non-neutralizing Envelope (E) antibodies as seen with monoclonal ZIKV E antibodies. CONCLUSIONS: Overall, our findings suggest that WNV antibodies in the sera significantly enhance ZIKV infection in Fc receptor positive cells with limited neutralization activity. Further studies in more relevant models of ADE will be needed to confirm the relevance of these findings in vivo.


Asunto(s)
Anticuerpos Antivirales/inmunología , Acrecentamiento Dependiente de Anticuerpo , Virus del Nilo Occidental/inmunología , Virus Zika/inmunología , Anticuerpos Neutralizantes/inmunología , Reacciones Cruzadas , Virus del Dengue/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Texas/epidemiología , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/inmunología , Infección por el Virus Zika/inmunología
12.
Euro Surveill ; 26(19)2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33988123

RESUMEN

Cases of West Nile neuroinvasive disease (WNND) in Spain increased in summer 2020. Here we report on this increase and the local, regional and national public health measures taken in response. We analysed data from regional surveillance networks and the National Epidemiological Surveillance Network, both for human and animal West Nile virus (WNV) infection. During the 2020 season, a total of 77 human cases of WNV infection (median age 65 years; 60% males) were detected in the south-west of Spain; 72 (94%) of these cases developed WNND, presenting as meningoencephalitis, seven of which were fatal. In the previous two decades, only six human cases of WNND were detected in Spain. Reduced activities for vector control this season, together with other factors, might have contributed to the massive increase. Public health measures including vector control, campaigns to raise awareness among physicians and the general population, and interventions to ensure the safety of donations of blood products, organs, cells and tissues were effective to reduce transmission. Going forward, maintenance of vector control activities and an update of the vector-borne diseases response plan in Spain is needed.


Asunto(s)
Meningoencefalitis , Fiebre del Nilo Occidental , Virus del Nilo Occidental , Anciano , Animales , Femenino , Humanos , Masculino , Estaciones del Año , España/epidemiología , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/prevención & control
13.
J Neurovirol ; 26(2): 281-283, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31713053

RESUMEN

West Nile virus (WNV) is an RNA flavivirus transmitted through a mosquito vector. In 2018 Nebraska reported 242 cases, the highest incidence of WNV since 2003. This included 119 neuroinvasive cases (49%) and 11 deaths (4.5%) (DHHS 2018). Clinical presentation ranges from uncomplicated symptoms including fever, headache, and myalgias to neuroinvasive disease characterized by meningoencephalitis, flaccid paralysis, and other neurologic manifestations. Neuroinvasive WNV usually occurs in elderly and immunocompromised individuals, and ocular involvement is often not detected until later in the disease course. We describe a case of neuroinvasive WNV presenting with uveomeningitis in a young and otherwise healthy patient.


Asunto(s)
Coriorretinitis/virología , Fiebre del Nilo Occidental/complicaciones , Adulto , Coriorretinitis/patología , Humanos , Masculino , Síndrome
14.
J Math Biol ; 80(3): 809-834, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31654120

RESUMEN

In this paper a mathematical model is formulated to study transmission dynamics of West Nile virus (WNv), which incorporates mosquito demographics including pair formation, metamorphic stages and intraspecific competition. The global behaviors of the model are obtained from a geometric approach and theory of monotone dynamics, even though bistability is present due to backward bifurcation. It turns out that the model can be investigated through two auxiliary subsystem, which are cooperative and K-competitive, respectively. Together with implement of compound matrices and Poincaré-Bendixson theorem, a thorough classification of dynamics of the full model is characterized by mosquito reproduction number [Formula: see text], WNv reproduction number [Formula: see text] and a bistability subthreshold [Formula: see text]. The theoretical results show that if [Formula: see text] is not greater than 1, mosquitoes will not survive, and the WNv will die out; if [Formula: see text] is greater than 1, then mosquitoes will persist, and disease may prevail or vanish depending on basin of attraction of the local attractors which are singletons. Our method in this paper can be applied to other mosquito-borne diseases such as malaria, dengue fever which have a similar monotonicity.


Asunto(s)
Culicidae/crecimiento & desarrollo , Culicidae/virología , Modelos Biológicos , Fiebre del Nilo Occidental/transmisión , Virus del Nilo Occidental/fisiología , Animales , Femenino , Estadios del Ciclo de Vida , Población , Conducta Sexual Animal
15.
Euro Surveill ; 25(46)2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33213688

RESUMEN

BackgroundClimate is a major factor in the epidemiology of West Nile virus (WNV), a pathogen increasingly pervasive worldwide. Cases increased during 2018 in Israel, the United States and Europe.AimWe set to retrospectively understand the spatial and temporal determinants of WNV transmission in Israel, as a case study for the possible effects of climate on virus spread.MethodsWe employed a suitability index to WNV, parameterising it with prior knowledge pertaining to a bird reservoir and Culex species, using local time series of temperature and humidity as inputs. The predicted suitability index was compared with confirmed WNV cases in Israel (2016-2018).ResultsThe suitability index was highly associated with WNV cases in Israel, with correlation coefficients of 0.91 (p value = 4 × 10- 5), 0.68 (p = 0.016) and 0.9 (p = 2 × 10- 4) in 2016, 2017 and 2018, respectively. The fluctuations in the number of WNV cases between the years were explained by higher area under the index curve. A new WNV seasonal mode was identified in the south-east of Israel, along the Great Rift Valley, characterised by two yearly peaks (spring and autumn), distinct from the already known single summer peak in the rest of Israel.ConclusionsBy producing a detailed geotemporal estimate of transmission potential and its determinants in Israel, our study promotes a better understanding of WNV epidemiology and has the potential to inform future public health responses. The proposed approach further provides opportunities for retrospective and prospective mechanistic modelling of WNV epidemiology and its associated climatic drivers.


Asunto(s)
Fiebre del Nilo Occidental , Humanos , Israel/epidemiología , Estudios Retrospectivos , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/transmisión
16.
Emerg Infect Dis ; 25(12): 2290-2294, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31742510

RESUMEN

West Nile virus (WNV) lineage 2 is associated with neurologic disease in horses and humans in South Africa. Surveillance in wildlife and nonequine domestic species during 2010-2018 identified WNV in 11 (1.8%) of 608 animals with severe neurologic and fatal infections, highlighting susceptible hosts and risk for WNV epizootics in Africa.


Asunto(s)
Enfermedades de los Animales/epidemiología , Enfermedades de los Animales/virología , Animales Domésticos , Animales Salvajes , Fiebre del Nilo Occidental/veterinaria , Virus del Nilo Occidental , Enfermedades de los Animales/historia , Animales , Geografía Médica , Historia del Siglo XXI , Filogenia , Vigilancia en Salud Pública , Sudáfrica/epidemiología , Proteínas no Estructurales Virales/genética , Virus del Nilo Occidental/clasificación , Virus del Nilo Occidental/genética
17.
Emerg Infect Dis ; 25(10): 1943-1950, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31538563

RESUMEN

The economic burden of West Nile virus (WNV) infection is not known for Canada. We sought to describe the direct and indirect costs of WNV infection in the province of Quebec, Canada, up to 2 years after onset of signs and symptoms. We conducted a retrospective cohort study that included WNV cases reported during 2012 and 2013. For 90 persons infected with WNV, persons with encephalitis accounted for the largest proportion of total cost: a median cost of $21,332 per patient compared with $8,124 for West Nile meningitis (p = 0.0004) and $192 for West Nile fever (p<0.0001). When results were extrapolated to all reported WNV patients, the estimated total cost for 124 symptomatic cases was ≈$1.7 million for 2012 and that for 31 symptomatic cases was ≈$430,000 for 2013. Our study provides information for the government to make informed decisions regarding public health policies and infectious diseases prevention and control programs.


Asunto(s)
Costo de Enfermedad , Costos y Análisis de Costo/estadística & datos numéricos , Fiebre del Nilo Occidental/economía , Anciano , Femenino , Costos de la Atención en Salud/estadística & datos numéricos , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Quebec/epidemiología , Estudios Retrospectivos , Encuestas y Cuestionarios , Fiebre del Nilo Occidental/epidemiología
18.
Emerg Infect Dis ; 25(11): 2064-2073, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31625835

RESUMEN

West Nile Virus (WNV) can result in clinically severe neurologic disease. There is no treatment for WNV infection, but administration of anti-WNV polyclonal human antibody has demonstrated efficacy in animal models. We compared Omr-IgG-am, an immunoglobulin product with high titers of anti-WNV antibody, with intravenous immunoglobulin (IVIG) and normal saline to assess safety and efficacy in patients with WNV neuroinvasive disease as part of a phase I/II, randomized, double-blind, multicenter study in North America. During 2003-2006, a total of 62 hospitalized patients were randomized to receive Omr-IgG-am, standard IVIG, or normal saline (3:1:1). The primary endpoint was medication safety. Secondary endpoints were morbidity and mortality, measured using 4 standardized assessments of cognitive and functional status. The death rate in the study population was 12.9%. No significant differences were found between groups receiving Omr-IgG-am compared with IVIG or saline for either the safety or efficacy endpoints.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades Virales del Sistema Nervioso Central/virología , Inmunoglobulina G/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Fiebre del Nilo Occidental/tratamiento farmacológico , Fiebre del Nilo Occidental/virología , Virus del Nilo Occidental , Adulto , Anciano , Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/administración & dosificación , Anticuerpos Antivirales/inmunología , Enfermedades Virales del Sistema Nervioso Central/inmunología , Femenino , Humanos , Inmunoglobulina G/administración & dosificación , Inmunoglobulinas Intravenosas/administración & dosificación , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Fiebre del Nilo Occidental/inmunología , Virus del Nilo Occidental/inmunología
19.
Emerg Infect Dis ; 25(2)2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30667356

RESUMEN

Infection with West Nile virus (WNV) has a well-characterized acute disease process. However, long-term consequences are less understood. We searched death records for 4,142 residents of Texas, USA, infected with WNV during 2002-2012 and identified 557 (13%) deaths. We analyzed all-cause and cause-specific deaths after WNV infection by calculating standardized mortality ratios and using statewide mortality data. Acute-phase deaths (<90 days after symptom onset) occurred in 289 (7%) of case-patients; of those deaths, 289 (92%) were cases of West Nile neuroinvasive disease (WNND). Convalescent-phase deaths (>90 days after symptom onset) occurred in 268 (7%) of the remaining 3,853 case-patients; 210 (78%) of these deaths occurred in patients with WNND. Convalescent-phase WNND case-patients showed excess deaths from infectious and renal causes; case-patients <60 years of age had increased risk for all-cause death, specifically from renal, infectious, digestive, and circulatory causes. We provide population-level evidence of increased risk for death after WNV infection resulting in WNND.


Asunto(s)
Fiebre del Nilo Occidental/mortalidad , Virus del Nilo Occidental , Edad de Inicio , Anciano , Anciano de 80 o más Años , Causas de Muerte , Femenino , Historia del Siglo XXI , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Vigilancia en Salud Pública , Texas/epidemiología , Factores de Tiempo , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/historia , Fiebre del Nilo Occidental/virología
20.
J Theor Biol ; 463: 22-46, 2019 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-30550862

RESUMEN

This paper proposes a model of West Nile Virus (WNV) including threshold control policies concerning the culling of mosquitoes and birds under different conditions. Two thresholds are introduced to estimate whether and which control strategy should be implemented. For each mosquito threshold level [Formula: see text] the dynamical behaviour of the proposed non-smooth system is investigated as the bird threshold level [Formula: see text] varies, focusing on the existence of sliding domains, the existence of pseudo-equilibria, real or virtual of the endemic equilibria, global stability of these steady states, and the most interesting case of the occurrence of a novel globally asymptotically stable pseudo-attractor. The model solutions ultimately converge to a real equilibrium or a pseudo-equilibrium (if it exists), or a pseudo-attractor if no equilibrium is real and no pseudo-equilibrium exists. Here within, we show that the free system has a single stable endemic equilibrium under biologically reasonable assumptions, and show that when the control system has: (1) a bird-culling threshold that is above the bird equilibrium, culling has no advantage; (2) a bird-culling threshold that is below the bird equilibrium, but a mosquito-culling threshold that lies above the mosquito equilibrium, the infected bird population can be reduced but the infected mosquito population will remain the same; (3) a bird-culling threshold and a mosquito-culling threshold that both lie below their respective equilibrium values of the free system, then both the infected bird and mosquito populations can be reduced to lower levels. The results suggest that preset levels of the number of infected birds and infected mosquitoes can be maintained simultaneously when threshold values are chosen properly, which provides a possible control strategy when an emergent infectious disease cannot be eradicated immediately.


Asunto(s)
Sacrificio de Animales/métodos , Aves/virología , Modelos Biológicos , Fiebre del Nilo Occidental/transmisión , Virus del Nilo Occidental , Animales , Culicidae/virología , Enfermedades Endémicas/prevención & control , Humanos , Fiebre del Nilo Occidental/prevención & control
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