MATHEMATICAL ANALYSIS OF WEST NILE VIRUS MODEL WITH DISCRETE DELAYS

The paper presents the basic model for the transmission dynamics of West Nile virus （WNV）. The model, which consists of seven mutually-exclusive compartments representing the birds and vector dynamics, has a locally-asymptotically stable disease- free equilibrium whenever the associated reproduction number （R0） is less than unity. As reveal in [3, 20], the analyses of the model show the existence of the phenomenon of backward bifurcation （where the stable disease-free equilibrium of the model co-exists with a stable endemic equilibrium when the reproduction number of the disease is less than unity）. It is shown, that the backward bifurcation phenomenon can be removed by substituting the associated standard incidence function with a mass action incidence. Analysis of the reproduction number of the model shows that, the disease will persist, whenever R0 〉 1, and increase in the length of incubation period can help reduce WNV burden in the community if a certain threshold quantities, denoted by △b and △v are negative. On the other hand, increasing the length of the incubation period increases disease burden if △b 〉 0 and △v 〉 0. Furthermore, it is shown that adding time delay to the corresponding autonomous model with standard incidence （considered in [2]） does not alter the qualitative dynamics of the autonomous ：system （with respect to the elimination or persistence of the disease）.

Cauda equina arachnoiditis–a rare manifestation of West Nile virus neuroinvasive disease:A case report

BACKGROUND Data regarding the neuroradiology features of the West Nile virus neuroinvasive disease(WNV NID)is rather scarce.To contribute to the knowledge of the WNV NID,we present a patient with a combination of encephalitis and acute flaccid paresis,with cauda equina arachnoiditis as the main magnetic resonance(MR)finding.CASE SUMMARY A 72-year-old female patient was admitted due to fever,headache and gait instability.During the first several days she developed somnolence,aphasia,urinary incontinence,constipation,and asymmetric lower extremities weakness.Cerebrospinal fluid analysis indicated encephalitis.Native brain computed tomography and MR were unremarkable,while spinal MR demonstrated cauda equina enhancement without cord lesions.Virology testing revealed WNV IgM and IgG antibodies in serum and cerebrospinal fluid,which confirmed acute WNV NID.The treatment was supportive.After two months only a slight improvement was noticed but cognitive impairment,loss of sphincter control and asymmetric inferior extremities weakness remained.The patient died after a month on chronic rehabilitation.CONCLUSION Cauda equina arachnoiditis is a rare,but possible neuroradiological feature in acute flaccid paresis form of WNV NID.

Using a Collateral Damage Model to Explain Survival Data in West Nile Virus Infections

Simulation code for a model of the adaptive immune response seen in flavivirus infections is used to explain the immunopathological consequences seen in West Nile Virus virus (WNV) infections. We use a model that specifically handles the differences in how the virus infects resting cells, the G0 state, versus dividing cells, the G1 state, which includes vastly increased MHC-I upregulation for resting cells over dividing cells. The simulation suggests how the infection progresses in a one host model and the results shed insight into the unusual survival curve data obtained for this infection: there is an increase in health even though viral load has increased.

Isolated Hyperacute T-Waves in West Nile Encephalitis Indicating Atypical Variant of Stress-Induced Cardiomyopathy

Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.

The recombinant truncated envelope protein of West Nile virus adjuvanted with Alum/CpG induces potent humoral and T cell immunity in mice

West Nile virus(WNV)is a mosquito-transmitted flavivirus distributed globally for decades and can cause disease in humans and animals.So far,no WNV vaccine has been licensed for human use.Therefore,the development of novel candidate vaccines and the improvement of vaccination strategies is imperative.As the WNV envelope(E)glycoprotein plays an important role in mediating viral binding to cellular receptors and virus-cell membrane fusion,it is a critical target for the host humoral response.Here,we prepared a recombinant truncated envelope protein of WNV(rWNV-80E)and developed a WNV subunit vaccine formulation with a combination of aluminum hydroxide(alum)and a synthetic oligonucleotide CpG as adjuvants.C57BL/6 mice were immunized twice intramuscularly at 28-day intervals with 5μg purified rWNV-80E adjuvanted with Alum/CpG.WNV E-specific IgG was detected by enzyme-linked immunosorbent assay and neutralizing antibodies(nAbs)was detected using single-round infectious particles of WNV.Furthermore,T cell immunity was detected by enzyme-linked immunospot assay and intracellular cytokine staining assay.Notably,rWNV-80E was highly immunogenic and elicited potent humoral and cell immunity,as evidenced by significant levels of IFN-γ and TNF-αsecretion in the T cells of mice.In summary,the Alum/CpG-adjuvanted rWNV-80E subunit vaccine elicited potent and balanced B-and T-cell immunity in mice,and therefore it is a promising candidate vaccine that warrants further investigation for use in human or veterinary applications.

Development and evaluation of neutralizing antibodies for cross-protection against West Nile virus and Japanese encephalitis virus

Background:West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses,and is fatal for birds,chickens and other poultry.With no specific drugs or vaccines available,antibody-based therapy is a promising treatment.This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus.Methods:Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology.The therapeutic efficacy of these antibodies was evaluated using a mouse model,and a humanized version of the monoclonal antibody was generated for potential human application.Results:In this study,we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV.Their therapeutic effects against WNV were validated both in vivo and in vitro.Among these antibodies,C9-G11-F3 also exhibited cross-protective activity against JEV.We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans.Conclusion:This study highlights the importance of neutralizing antibodies as a promising approach for pro-tection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.

West Nile virus:North American experience

West Nile virus,a mosquito-vectored flavivirus of the Japanese encephalitis serogroup,was first detected in North America following an epizootic in the New York City area in 1999.In the intervening 11 years since the arrival of the virus in North America,it has crossed the contiguous USA,entered the Canadian provinces bordering the USA,and has been reported in the Caribbean islands,Mexico,Central America and,more recently,South America.West Nile virus has been reported in over 300 species of birds in the USA and has caused the deaths of thousands of birds,local population declines of some avian species,the clinical illness and deaths of thousands of domestic horses,and the clinical disease in over 30000 Americans and the deaths of over 1000.Prior to the emergence of West Nile virus in North America,St.Louis encephalitis virus and Dengue virus were the only other known mosquito-transmitted flaviviruses in North America capable of causing human disease.This review will discuss the North American experience with mosquito-borne flavivirus prior to the arrival of West Nile virus,the entry and spread of West Nile virus in North America,effects on wild bird populations,genetic changes in the virus,and the current state of West Nile virus transmission.

The diffusive model for West Nile virus with advection and expanding fronts in a heterogeneous environment

In this paper,we investigate a reaction-diffusion-advection model with expanding fronts,which models the spatial transmission of West Nile virus(WNv)in a heterogeneous environment.A free boundary problem is formulated and the global existence and uniqueness of the solution is presented.In addition to a classical basic reproduction number,the spatial-temporal basic reproduction number for the model with null Dirichlet boundary condition is introduced and the risk index associated with the virus in spatial setting is defined,and their properties are discussed.Sufficient conditions for the WNv to vanish or spread are given,and the asymptotic behavior of the solution to the free boundary problem when the spreading occurs is established.Our results show that the initial number of infected populations and the expanding capability of the expanding fronts exhibit important impacts on the extinction or persistence of the virus.

Adjusting Second Moment Bias in Eigenspace Using Bayesian Empirical Estimators, Dirichlet Tessellations and Worldview I Data for Predicting Culex Quinquefasciatus Habitats in Trinidad

Temporally weighted regression models with a spatial autoregressive component may estimate nonlinearities in spatiotemporal-sampled data of Culex quinquefasciatus, a major vector of West Nile Virus (WNV) which can help implement control strategies by determining optimal predictors associated to prolific habitats. The design of this kind of mixed model can specifically incorporate spatial autocorrelation whilst including the influence of other aspatial predictor variables. Currently, the lack of an estimation theory that allows for het- eroscedasticity and corresponding joint hypothesis testing in the presence of spatial dependence in georefer- enced Cx. quinquefasciatus habitat data is a serious shortcoming in WNV research. In this paper we used spatially lagged and simultaneous autoregressive models based on multiple predictor variables of immature Cx. quinquefasciatus and Worldview 1 (WV-1) data to help implant a remote habitat-based surveillance sys- tem in Trinidad. Initially, we used Geomatica Ortho Engine? v. 10.2 for extracting a Digital Elevation Model (DEM) from the WV-1 raw imagery. Results of the DEM analyses indicated a statistically significant inverse linear relationship between total sampled Cx. quinquefasciatus data and elevation (m) (R2 = -0.439;p < 0.0001), with a standard deviation of 10.41. Additional field-sampled information was derived using data from an or-thogonal grid-matrix constructed in an ArcInfo 9.3? and overlaid onto the WV-1 data. A unique identifier was placed in the centroid of each grid cell. Univariate statistics and Poisson regression models were then generated using the georeferenced covariates in SAS/GIS?. Coefficient estimates were also used to define expectations for prior distributions in a Bayesian estimation matrix using Markov Chain Monte Carlo (MCMC) specifications. A spatial residual trend analyses was then performed using autocorrelation indices which linked tabular data in SAS PROCLMIXED? with the egg-raft count data in ArcInfo?. The estimation matrix identified prolific habitats based on the covariate distance to the nearest house. An Ordinary kriged-based interpolator was then constructed in Geostatistical Analyst Extension of ArcGIS 9.3? based on the adjusted Bayesian estimates. For total Cx. quinquefasciatus egg-raft count, first order trend was fitted to the semivariogram at a partial sill of 5.931 km, nugget of 6.374 km, lag size of 7.184 km, and a range of 31.02 km using 12 lags. We assessed the performance accuracy of the interpolation procedures based on the magnitude and distribution of errors between observed and model-predicted values using Voroni tessella- tions. These residuals divided the space between the individual georeferenced Cx. quinquefasciatus habitats by XY coordinates in 2-dimenisional space which revealed that the geophysical parameter error residuals in the interpolation model were within normal statistical limitations. Newer GIS software and WV-1 data can generate highly accurate predictive Cx. quinquefasciatus habitat distribution models which can target prolific habitats of based on field-sampled count data. Our results suggest it may be unnecessary to manage all Cx. quinquefasciatus habitats to obtain significant reductions in incidence and prevalence of WNV in Trinidad.

Arbovirus and seizures

The high prevalence and spread of arthropod-borne viruses(arboviruses)make them an important cause of viral encephalitis in humans.Most epidemic viral encephalitides have an etiology associated with arboviruses.Among various arboviruses,the Japanese encephalitis virus,West Nile virus,Zika virus,Dengue virus and Chikungunya virus can induce seizures.Arboviruses of the genus Flavivirus are usually transmitted by mosquitoes and other host animals.These vector-borne pathogens can cause epidemic viral encephalitis.Seizures may not be the major manifestation in these viral encephalitides,but may predict a poor prognosis.In this article,we discuss the relationships between these viruses and seizures from perspectives of clinical characteristics,pathogenesis,prognosis and treatments of each.

Reproduction numbers of infectious disease models

This primer article focuses on the basic reproduction number,ℛ0,for infectious diseases,and other reproduction numbers related toℛ0 that are useful in guiding control strategies.Beginning with a simple population model,the concept is developed for a threshold value ofℛ0 determining whether or not the disease dies out.The next generation matrix method of calculatingℛ0 in a compartmental model is described and illustrated.To address control strategies,type and target reproduction numbers are defined,as well as sensitivity and elasticity indices.These theoretical ideas are then applied to models that are formulated for West Nile virus in birds(a vector-borne disease),cholera in humans(a disease with two transmission pathways),anthrax in animals(a disease that can be spread by dead carcasses and spores),and Zika in humans(spread by mosquitoes and sexual contacts).Some parameter values from literature data are used to illustrate the results.Finally,references for other ways to calculateℛ0 are given.These are useful for more complicated models that,for example,take account of variations in environmental fluctuation or stochasticity.