Dengue Disease Model Research Articles

Optimal control strategies and global dynamics for a dengue disease model with waning vaccine-induced immunity and incubation delay

Optimal control strategies and global dynamics for a dengue disease model with waning vaccine-induced immunity and incubation delay

A NUMERICAL STUDY ON THE DYNAMICS OF DENGUE DISEASE MODEL WITH FRACTIONAL PIECEWISE DERIVATIVE

The aim of this paper is to study the dynamics of Dengue disease model using a novel piecewise derivative approach in the sense of singular and non-singular kernels. The singular kernel operator is in the sense of Caputo, whereas the non-singular kernel operator is the Atangana–Baleanu Caputo operator. The existence and uniqueness of a solution with piecewise derivative are examined for the aforementioned problem. The suggested problem’s approximate solution was found using the piecewise numerical iterative Newton polynomial approach. In terms of singular and non-singular kernels, a numerical scheme for piecewise derivatives has been established. The numerical simulation for the piecewise derivable problem under consideration is drawn using data for various fractional orders. This work makes the idea of piecewise derivatives and the dynamics of the crossover problem clearer.

Liver transcriptomics reveals features of the host response in a mouse model of dengue virus infection.

BackgroundDengue virus (DENV) infection induces various clinical manifestations and even causes organ injuries, leading to severe dengue haemorrhagic fever and dengue shock syndrome. Hepatic dysfunction was identified as a risk predictor of progression to severe disease during the febrile phase of dengue. However, the underlying mechanisms of hepatic injury remain unclear.MethodsA model of dengue disease was established in IFNAR −/− C57BL/6 mice by challenge with DENV-2. Body weight, symptoms, haematological parameters and liver pathological observations in mice were used to determine the effects of DENV infection. Liver transcriptome sequencing was performed to evaluate the features of the host response in IFNAR −/− mice challenged with DENV. Functional enrichment analysis and analysis of significantly differentially expressed genes (DEGs) were used to determine the critical molecular mechanism of hepatic injury.ResultsWe observed haemoconcentration, leukopenia and liver pathologies in mice, consistent with findings in clinical dengue patients. Some differences in gene expression and biological processes were identified in this study. Transcriptional patterns in the liver indicated that antiviral responses to DENV and tissue damage via abnormal expression of proinflammatory cytokines were induced. Further analysis showed that the upregulated DEGs were significantly enriched in the leukocyte transendothelial migration, complement and coagulation cascades, and cytokine-cytokine receptor interactions signalling pathways, which are considered to be closely associated with the pathogenic mechanism of dengue. IL6, IL 10, ICAM-1, VCAM-1, MMP9 and NLRP3 were identified as biomarkers of progression to severe disease.ConclusionsThe interactions of these cytokines, which activate inflammatory signalling, may lead to organ injury and haemoconcentration and even to vascular leakage in tissues, including the mouse liver. Our study identifies candidate host targets that could be used for further functional verification.

Flavivirus NS1: Structure and Function of an Enigmatic Virulence Factor

Viruses employ a variety of molecular strategies to carve out an existence in their host and to thwart host defenses. Crystal structures of viral proteins and of the host proteins deployed as molecular weapons contribute enormously to our understanding of viral pathogenesis and our efforts to combat viral infection. Mosquito‐borne flaviviruses, including the dengue, Zika, yellow fever, Japanese encephalitis and West Nile viruses, cause serious human diseases in much of the world. A growing number of diverse functions has been discovered for the enigmatic virulence factor known as NS1: it is an essential cofactor in viral genome replication, a mediator of the host immune response, and a trigger of host vascular leakage. NS1 lacks precedent in the structure and sequence databases, so an accurate 3D structure was key to understanding the basis for its various functions. A high‐throughput survey of expression conditions in baculovirus‐infected insect cells was essential to identifying conditions for production of recombinant NS1 in its natural glycosylated, disulfide‐linked form. We solved a crystal structure of West Nile virus NS1 from the anomalous scattering of the native sulfur atoms using an 18‐crystal data set [1,2]. The structure revealed a previously unknown protein fold with a fundamentally dimeric architecture, and led to assigned functions for two of the three NS1 structural domains. Subsequent structures of NS1 from dengue virus and Zika viruses established the basis for its membrane association in cells and its lipid encapsidation when secreted [3]. Recently discovered functions of this remarkable virulence factor emerged in follow‐up studies that built upon the crystal structures. Prime among these is the discovery that the NS1 protein, in a mouse model of dengue disease and in absence of virus, can induce the vascular leak that is a hallmark of severe dengue disease [4,5]. Clues to the molecular mechanism of NS1‐induced endothelial dysfunction emerged from a study of the protection afforded by a monoclonal antibody and the structure of the Fab fragment bound to the NS1 epitope [6].[1] Akey DL et al. & Smith JL (2014) Science 343, 881‐885.[2] Akey DL et al. & Smith JL (2014) Acta Crystallogr D70, 2719‐2729.[3] Brown WC et al. & Smith JL (2016) Nature Struct Molec Biol 23, 856‐867.[4] Beatty PR et al. & Harris E (2015) Science Trans Med 7, 304ra141.[5] Modhiran N et al. & Young PR (2015) Science Trans Med 7, 304ra142.[6] Biering SB, Akey DL et al. Smith JL & Harris E (2021) Science 371, 194‐200.

Analysis of a host–vector dynamics of a dengue disease model with optimal vector control strategy

Dengue is a mosquito-borne viral disease where the species Aedes aegypti acts as the vector. In this work, we have proposed a biologically well-posed epidemic model to study the dynamics of dengue strain. It is observed that people infected with severe dengue are more infectious than people with mild symptoms in terms of disease transmission. Also, continuous removal of mosquitoes decreases the chances of becoming infected with Dengue significantly. In the later part, an optimal control problem is formulated where a lesser number of people become infected due to time-dependent people’s awareness regarding taking precaution and mosquito removal measures. The numerical simulation shows that the transmission of the virus among mosquitoes becomes lowest when both the control policies are implemented. So, from the overall analysis, it is observed that maintaining effective non-pharmaceutical precautions at an early stage and removing mosquitoes from the system at certain time intervals decrease the infection level significantly in the environment by reducing the probability of becoming infected.

Dynamics of a dengue disease transmission model with two-stage structure in the human population.

Age as a risk factor is common in vector-borne infectious diseases. This is partly because children depend on adults to take preventative measures, and adults are less susceptible to mosquito bites because they generally spend less time outdoors than children. We propose a dengue disease model that considers the human population as divided into two subpopulations: children and adults. This is in order to take into consideration that children are more likely than adults to be bitten by mosquitoes. We calculated the basic reproductive number of dengue, using the next-generation operator method. We determined the local and global stability of the disease-free equilibrium. We obtained sufficient conditions for the global asymptotic stability of the endemic equilibrium using the Lyapunov functional method. When the infected periods in children and adults are the same, we that the endemic equilibrium is globally asymptotically stable in the interior of the feasible region when the threshold quantity $ R_0 > 1 $. Additionally, we performed a numerical simulation using parameter values obtained from the literature. Finally, a local sensitivity analysis was performed to identify the parameters that have the greatest influence on changes in $ (R_0) $, and thereby obtain a better biological interpretation of the results.

Three-dimensional spread analysis of a Dengue disease model with numerical season control

Dengue is among the most important infectious diseases in the world. The main contribution of our paper is to present a mixed system of partial and ordinary differential equations. This combined model is a generalization of the two presented mathematical models (A. L. de Araujo, J. L. Boldrini and B. M. Calsavara, An analysis of a mathematical model describing the geographic spread of dengue disease, J. Math. Anal. Appl. 444 (2016) 298–325) and (L. Cai, X. Li, N. Tuncer, M. Martcheva and A. A. Lashari, Optimal control of a malaria model with asymptomatic class and superinfection, Math. Biosci. 288 (2017) 94–108), describing the geographic spread of dengue disease. Our model has the ability to consider the possibility of asymptomatic infection, which leads to investigate the effect of dengue asymptomatic individuals on disease dynamics and to go into the possibility of superinfection of asymptomatic individuals. In the light of considering these factors, as well as the movements of human and mature female mosquitoes, more realistic modeling of dengue disease can be achieved. We present a mathematical analysis and show the global existence of a unique non-negative solution to this model and then establish ways to control dengue disease using numerical simulations and sensitivity analysis of model parameters (which are related to the contact rates and death rate of winged mosquitoes). To show different biological behaviors, we provide several numerical results, showing the role of parameters in controlling dengue disease transmission. From our numerical simulations, it can also be concluded that local control of dengue transmission can be done at a lower cost.

Analysis for transmission of dengue disease with different class of human population

Abstract Objectives: Vector-borne diseases speedily infest the human population. The control techniques must be applied to such ailment and work swiftly. We proposed a compartmental model of dengue disease by incorporating the standard incidence relation between susceptible vectors and infected humans to see the effect of manageable parameters of the model on the basic reproduction number. Methods: We compute the basic reproduction number by using the next -generation matrix method to study the local and global stability of disease free and endemic equilibrium points along with sensitivity analysis of the model. Results: Numerical results are explored the global behaviourism of disease-free/endemic state for a choice of arbitrary initial conditions. Also, the biting rate of vector population has more influence on the basic reproduction number as compared the other parameters. Conclusion: In this paper, shows that controlling the route of transmission of this disease is very important if we plan to restrict the transmission potential.

Increased serum sialic acid is associated with morbidity and mortality in a murine model of dengue disease.

Dengue virus (DENV) causes the most prevalent arboviral infection of humans, resulting in a spectrum of outcomes, ranging from asymptomatic infection to dengue fever to severe dengue characterized by vascular leakage and shock. Previously, we determined that DENV nonstructural protein 1 (NS1) induces endothelial hyperpermeability, disrupts the endothelial glycocalyx layer (EGL) in vitro and triggers shedding of structural components, including sialic acid (Sia) and heparan sulfate. Here, using a murine model of dengue disease disease, we found high levels of Sia and NS1 circulating in mice with DENV-induced morbidity and lethal DENV infection. Further, we developed a liquid chromatography/mass spectrometry-based method for quantifying free Sia in serum and determined that the levels of free N-glycolylneuraminic acid were significantly higher in DENV-infected mice than in uninfected controls. These data provide additional evidence that DENV infection disrupts EGL components in vivo and warrant further research assessing Sia as a biomarker of severe dengue disease.

Stochastic Optimal Control Model of Dengue Disease

In this research article, an optimal control model of dengue disease with standard incidence rate is proposed. Maximum Principle was employed to derive the necessary conditions for the existence of optimal control. Stochastic version of the model is derived by introducing a random perturbation in the main parameters of the model equations. Numerical solution of the optimality was derived and computed to investigate the optimum control strategy that would be efficacious to be implemented in reducing the number of exposed and infected humans as well as illustrating the explicit differences in the dynamics of the models

The mathematical modelling of the SIR-SI contagion model of dengue disease which considers the blood type O factor human compartment : A theoretical simulation

One of the congenital factors that affect the transmission of dengue disease is blood type. This study mainly aims to consider blood type O in humans and uses a differential equations system formulation to analyse the dynamical system. The basic reproduction number is determined as the threshold for dengue disease transmission model. This model has been applied to the data from weekly data dengue cases occurring in Bandung in the year 2013. When it is supported by actual data which provides the parameters and values for the variables, this model can be implemented and thus used to describe the dynamical system of dengue disease transmission with respect to O blood type in humans. It can be concluded that blood type O is an important factor to be considered when formulating strategies for prevention and treatment. This study provides a significant improvement to the knowledge of dengue transmission dynamics and should be beneficial in aiding control of the transmission of dengue disease.

Effect of freeze-dried Carica papaya leaf juice on inflammatory cytokines production during dengue virus infection in AG129 mice

BackgroundCarica papaya leaves have been used for traditional treatment of dengue fever and have been reported to exhibit an immunomodulatory activity by affecting the level of cytokine production in vitro and in vivo. Due to the lack of adequate in vivo evidence in dengue disease model, the present study was initiated to screen and identify the cytokines affected by freeze-dried C. papaya leaf juice (FCPLJ) treatment in AG129 mice infected with DEN-2 dengue virus.MethodsThe AG129 mice were fed orally with FCPLJ for 3 consecutive days after 24 h of dengue virus inoculation. Plasma cytokines were screened by using ProcartaPlex immunoassay. The gene expression in the liver was analyzed by using RT2 Profiler PCR Array.ResultsThe results showed that FCPLJ treatment has increased the plasma CCL2/MCP-1 level during peak of viremia. Gene expression study has identified 8 inflammatory cytokine genes which were downregulated in the liver of infected AG129 mice treated with FCPLJ. The downregulated inflammatory cytokine genes were CCL6/MRP-1, CCL8/MCP-2, CCL12/MCP-5, CCL17/TARC, IL1R1, IL1RN/IL1Ra, NAMPT/PBEF1 and PF4/CXCL4.ConclusionThe findings indicated the possible immunomodulatory role of FCPLJ during dengue virus infection in AG129 mice.

The SEIR Dynamical Transmission Model of Dengue Disease with and Without the Vertical Transmission of the Virus

The transmission of dengue disease when there is a possibility of Vertical Transmission (VT) is studied using mathematical modeling. In the normal case, the mosquito is infected by the dengue virus when it bites an infectious human being. Evidence is gathering that the mosquitoes can also be infected through sexual contact with infected male mosquito. To see the possible consequence of having this addition mode of transmission, a SEIR, Susceptible-Exposed-Infected-Recovery, model is constructed. The Routh – Hurwitz criteria are applied to the model in order to establish the stability of the infection. It is seen that the model without the VT model has 2 equilibrium points, a disease free equilibrium point and an endemic equilibrium point, while the model with the VT has only an endemic equilibrium point. The numerical solutions of differential equations of the model without the VT mode exhibit dynamical behaviors that converges to the disease free equilibrium state when basic reproduction time R0 is less than 1 and converges to endemic equilibrium state when R0>1. The trajectories of the numerical solutions for all possibilities (with and without VT mode) projected onto various 2D planes and 3D spaces are presented.

Optimal bed net use for a dengue disease model with mosquito seasonal pattern

Controversial results concerning the effectiveness of bed net in reducing dengue fever transmission make further research necessary in this direction. At this aim, we consider a mathematical model of dengue transmission where the use by individuals of insecticide‐treated bed nets is taken into account, combined or not with insecticide spraying. Furthermore, as climatic factors play a key role in mosquito‐borne diseases, we model the effect of seasonality through a periodic mosquito birth rate. We numerically investigate some specific scenarios according to different rainfall and mean temperature values. We set an optimal control problem to minimize the number of human infections and the cost of efforts placed into bed net adoption and maintenance and insecticide spraying. To assess the most appropriate strategy to eliminate dengue with minimum costs, we perform a comparative cost‐effectiveness analysis, which also shows how the cost‐benefit of intervention efforts is affected by changes in the amplitude of seasonal variation. One general result is that in any case the combination of bed net use and insecticide spraying produces the highest ratio of infections averted, whereas in terms of cost‐benefit only spraying campaigns should be implemented in control programs for regions with no large seasonality.

Mathematical Modeling of Dengue Disease under Random Effects

In this study, the deterministic mathematical model of Dengue disease is examined under Laplacian random effects. Random variables with Laplace distribution are used for randomizing the deterministic parameters. Simulations of the numerical results of the equation system are made with Monte-Carlo methods and the results are used for commenting on the disease. Comments are made on the random behavior of the components of the model after the calculation of their numerical characteristics like the expected value, variance, standard deviation, confidence interval and moments along with the coefficients of skewness and kurtosis from the results of the simulations. Results from the deterministic model are compared with the results from the random model to point out the possible contribution of random modeling to mathematical analysis studies on the disease.

Hierarchical Cluster Analysis of Three-Dimensional Reconstructions of Unbiased Sampled Microglia Shows not Continuous Morphological Changes from Stage 1 to 2 after Multiple Dengue Infections in Callithrix penicillata.

It is known that microglial morphology and function are related, but few studies have explored the subtleties of microglial morphological changes in response to specific pathogens. In the present report we quantitated microglia morphological changes in a monkey model of dengue disease with virus CNS invasion. To mimic multiple infections that usually occur in endemic areas, where higher dengue infection incidence and abundant mosquito vectors carrying different serotypes coexist, subjects received once a week subcutaneous injections of DENV3 (genotype III)-infected culture supernatant followed 24 h later by an injection of anti-DENV2 antibody. Control animals received either weekly anti-DENV2 antibodies, or no injections. Brain sections were immunolabeled for DENV3 antigens and IBA-1. Random and systematic microglial samples were taken from the polymorphic layer of dentate gyrus for 3-D reconstructions, where we found intense immunostaining for TNFα and DENV3 virus antigens. We submitted all bi- or multimodal morphological parameters of microglia to hierarchical cluster analysis and found two major morphological phenotypes designated types I and II. Compared to type I (stage 1), type II microglia were more complex; displaying higher number of nodes, processes and trees and larger surface area and volumes (stage 2). Type II microglia were found only in infected monkeys, whereas type I microglia was found in both control and infected subjects. Hierarchical cluster analysis of morphological parameters of 3-D reconstructions of random and systematic selected samples in control and ADE dengue infected monkeys suggests that microglia morphological changes from stage 1 to stage 2 may not be continuous.

A diffusive dengue disease model with nonlocal delayed transmission

In this paper, we derive a nonlocal delayed and diffusive dengue transmission model with a spatial domain being bounded as well as unbounded. We first address the well-posedness to the initial-value problem for the model. In the case of a bounded spatial domain, we establish the threshold dynamics for the spatially heterogeneous system in terms of the basic reproduction number R0. Also, a set of sufficient conditions is further obtained for the global attractivity of the endemic steady state where all the parameters are spatially independent. In the case of an unbounded spatial domain, and when the coefficients are all constants, we show that there exist traveling wave solutions of the model. Numerical simulations are performed to illustrate our main analytic results.

Global dynamics of multi‐group dengue disease model with latency distributions

In this paper, by incorporating latencies for both human beings and female mosquitoes to the mosquito‐borne diseases model, we investigate a class of multi‐group dengue disease model and study the impacts of heterogeneity and latencies on the spread of infectious disease. Dynamical properties of the multi‐group model with distributed delays are established. The results showthat the global asymptotic stability of the disease‐free equilibrium and the endemic equilibrium depends only on the basic reproduction number. Our proofs for global stability of equilibria use the classical method of Lyapunov functions and the graph‐theoretic approach for large‐scale delay systems. Copyright © 2014 John Wiley & Sons, Ltd.

Dengue human infection model: introduction.

Dengue human infection model: introduction.

Infant mouse brain passaged Dengue serotype 2 virus induces non-neurological disease with inflammatory spleen collapse in AG129 mice after splenic adaptation

AG129 mice are known to be permissive to infection by multiple serotypes of Dengue virus (DENV). There exists a concern that mouse passaged strains of the virus may induce neurological complications rather than increased vascular permeability in these mice, hence the use of human clinical isolates of the virus to develop the AG129 mouse model of Dengue disease with increased vascular permeability. The present study evaluated four mouse brain passaged DENV strains, each belonging to a different serotype and three of them having an original isolation history in India, for their suitability to serve as candidates to induce rapid lethal disease in AG129 mice. While all the viruses were able to establish a productive infection in the spleen, none of them induced paralysis despite their mouse brain passage history. Only the type-2 virus acquired the ability to induce a lethal disease after a single round of spleen to spleen passage, and became highly virulent after five more rounds. This apparently non-neurological lethal disease was characterized by high viral burden, elevated vascular permeability, serum TNF-α surge immediately before moribund stage, transient leukocytosis followed by severe leukopenia, lymphopenia throughout the course of the infection, and transient thrombocytopenia. The disease was also characterized by inflammatory splenic collapse during moribund stage, reminiscent of spontaneous splenic rupture reported in rare cases of severe Dengue in humans.