Epidemic Transmission Research Articles

Queueing Based Compartmental Models for Ebola Virus Disease Analysis

Ebola Virus Disease (EVD) is a complex and unprecedented epidemic killer disease. Recently, the disease has caused serious loss of life, waste of economic and material resources in West African nations. The most prevalent countries are Guinea, Liberia and Sierra Leone. Compartmental models are traditional epidemiological mdels that try to explain epidemic problems through the use of specific compartments that are subsets of a given population. Analysis using the developed queueing based compartmental models for Ebola Virus Disease (EVD) resulted in estimates of R0= (2.2550, 3.5264, 2.2325) for Guinea, Liberia and Sierra Leone. R0 > 1 for each of the countries, implying that the transmission and control of the epidemic was unstable and needed urgent intervention. The developed SEILICDR model outperformed the existing SEIR model by 13.10%, 91.76%, and 83.14%, respectively on the basis of their RMSE. Finally, analysis using queueing in SEILICDR compartmental models led to the discovery that, at a probability of 0.4 in each compartment, the transmission of EVD can be controlled.

Harnessing the power of crowdsourcing and Internet of Things in disaster response

Crowdsourcing and Internet of Things (IoT) are gaining more and more attention both in industry and academia in order to explore their effects on disaster relief. The current state of the literature shows a clear focus on the extent to which crowdsourcing on one hand, or IoT on the other hand, can individually make a difference regarding disaster response, but very few studies have considered the integration of both crowdsourcing and internet of things in order to link them with disaster response. Accordingly, in this paper, the authors have attempted to develop a crowdsourcing and IoT integration model which could help improving disaster response by using important value derived from using both social media and RFID technology. Furthermore, despite the fact that disaster relief offers similarities with epidemic transmission, (especially the SIR model), the application of SIR model in disaster relief still remains unexplored, which has led the authors to conduct a series of SIR model-based simulations to investigate the extent to which such integration model helps improving disaster response.

Epidemicity thresholds for water-borne and water-related diseases

Determining the conditions that favor pathogen establishment in a host community is key to disease control and eradication. However, focusing on long-term dynamics alone may lead to an underestimation of the threats imposed by outbreaks triggered by short-term transient phenomena. Achieving an effective epidemiological response thus requires to look at different timescales, each of which may be endowed with specific management objectives. In this work we aim to determine epidemicity thresholds for some prototypical examples of water-borne and water-related diseases, a diverse family of infections transmitted either directly through water infested with pathogens or by vectors whose lifecycles are closely associated with water. From a technical perspective, while conditions for endemicity are determined via stability analysis, epidemicity thresholds are defined through generalized reactivity analysis, a recently proposed method that allows the study of the short-term instability properties of ecological systems. Understanding the drivers of water-borne and water-related disease dynamics over timescales that may be relevant to epidemic and/or endemic transmission is a challenge of the utmost importance, as large portions of the developing world are still struggling with the burden imposed by these infections.

The full life cycle of Leptosphaeria maculans completed on inoculated oilseed rape incubated under controlled conditions

Because epidemics of successive cropping seasons are not independent, epidemiological studies need to encompass the processes occurring during the transmission of epidemics from one season to the next. With Leptosphaeria maculans, infected stubble allows carry‐over of the fungus. Generation experiments using recurrent selection on field plots are a useful means of comparing the effects of selection pressures. However, the full life cycle of the fungus, from plant infection to the next generation of ascospores, has not yet been achieved under controlled conditions. Studies were undertaken to achieve an experimental set‐up with sexual reproduction under controlled conditions. Cankered oilseed rape stems were produced under controlled conditions, after inoculation with a mixture of 12 isolates across both mating types. Stems were cut longitudinally and attached to styropore plates. Stem halves were incubated outside or in climate chambers regularly soaked in tap water to ensure maturation. Incubation was stopped when mature pseudothecia were observed. In all three independent experiments, more stem halves had pseudothecia when incubated under controlled conditions (30–100%) than incubated outside (0–80%). To the authors’ knowledge, this is the first study achieving the full life cycle of the fungus under controlled conditions, from infection of the plant to mature pseudothecia. This opens up the prospect of running experiments year‐round to better understand inoculum production, to compare fungal fitness, or to run generation experiments with exotic pathogen populations.

Feeder density enhances house finch disease transmission in experimental epidemics.

Anthropogenic food provisioning of wildlife can alter the frequency of contacts among hosts and between hosts and environmental sources of pathogens. Despite the popularity of garden bird feeding, few studies have addressed how feeders influence host contact rates and disease dynamics. We experimentally manipulated feeder density in replicate aviaries containing captive, pathogen-naive, groups of house finches (Haemorhous mexicanus) and continuously tracked behaviours at feeders using radio-frequency identification devices. We then inoculated one bird per group with Mycoplasma gallisepticum (Mg), a common bacterial pathogen for which feeders are fomites of transmission, and assessed effects of feeder density on house finch behaviour and pathogen transmission. We found that pathogen transmission was significantly higher in groups with the highest density of bird feeders, despite a significantly lower rate of intraspecific aggressive interactions relative to the low feeder density groups. Conversely, among naive group members that never showed signs of disease, we saw significantly higher concentrations of Mg-specific antibodies in low feeder density groups, suggesting that birds in low feeder density treatments had exposure to subclinical doses of Mg. We discuss ways in which the density of garden bird feeders could play an important role in mediating the intensity of Mg epidemics.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.

Evaluation of epidemiological, clinical, and laboratory features and mortality of 144 HIV/AIDS cases in Turkey

BackgroundThe number of HIV/AIDS cases in Turkey is increasing rapidly, as is the number of cases worldwide. The aim of this study is to evaluate the characteristics of the clinical and laboratory findings and epidemiological features of HIV/AIDS patients to obtain useful data on the epidemic type and transmission routes associated with Turkey and to identify risk factors for mortality.MethodsThe patient records of 144 HIV-infected patients who were admitted to our clinic between 2000 and 2015 were analyzed retrospectively.ResultsMost of the cases (55%) were diagnosed due to the detection of anti-HIV-positive individuals without clinical symptoms. The mean CD4 + lymphocyte count on first admission was 108 cells/μL for those admitted before 2009 and 265 cells/μL for those admitted after 2009 (p = 0.003). When the pre- and post-2009 groups were compared for the status of the disease, 55.6 and 44.4% of patients were in the AIDS stage, respectively (p = 0.04). The most noted opportunistic infection was mycobacterial, and throughout the follow-up, 31.2% of the cases were fatal.ConclusionsEarly diagnosis of HIV infection can have a direct impact on prognosis and survival. Therefore, screening laboratory investigations should be extended, particularly in high-risk groups.

A model of an epidemic mapping

We propose a model consisting in a nonlinear parabolic equation for simulating an epidemic transmission, quantified by some coefficients in the equation, in the perspective of their calibration on the basis of real observations collected during an epidemic outbreak. This model is intended to serve for tracking the epidemic by illustrating a map of the infected population spread. In this paper we discuss the well-posedness of this model by a semigroup technique.

Socio-economic, Knowledge Attitude Practices (KAP), household related and demographic based appearance of non-dengue infected individuals in high dengue risk areas of Kandy District, Sri Lanka

BackgroundSocio-economic, demographic factors and Knowledge Attitude Practices (KAPs) have been recognized as critical factors that influence the incidence and transmission of dengue epidemics. However, studies that characterize above features of a risk free or low risk population are rare. Therefore, the present study was conducted to characterize the household related, demographic, socio-economic factors and KAPs status of five selected dengue free communities.MethodAn analytical cross-sectional survey was conducted on selected demographic, socio-economic, household related and KAPs in five selected dengue free communities living in dengue risk areas within Kandy District, Central Province, Sri Lanka. Household heads of 1000 randomly selected houses were interviewed in this study. Chi-square test for independence, cluster analysis and Principal Coordinates (PCO) analysis were used for data analysis.ResultsKnowledge and awareness regarding dengue, (prevention of the vector breeding, bites of mosquitoes, disease symptoms and waste management) and attitudes of the community (towards home gardening, composting, waste management and maintenance of a clean and dengue free environment) are associated with the dengue free status of the study populations.ConclusionsThe vector controlling authorities should focus on socio-economic, demographic and KAPs in stimulating the community to cooperate in the integrated vector management strategies to improve vector control and reduce transmission of dengue within Kandy District.

Identifiability analysis and parameter estimation of a chikungunya model in a spatially continuous domain

We investigate the identifiability and estimation of parameters of a chikungunya epidemic transmission model. As a novelty, this model incorporates the spatial mobility of humans described as Brownian random motion. Indeed, it is a factor that has influenced the re-emergence of several epidemic diseases. The displacement of mosquitoes is omitted since it is limited to a few meters. This model couples a mosquito dynamics model and a transmission virus model between humans and mosquitoes populations. The mosquito larvae and the human population are supposed to be observed. The complete model is then composed of a reaction–diffusion system coupled with ordinary differential equations (ODEs). The diffusion is assumed to be local. For such a model, the identifiability analysis is studied at first to ensure that the parameters can be uniquely identified. From the identifiability study, we propose a numerical procedure for obtaining a first estimate of the parameters of the transmission virus model without any knowledge of them.

The Analysis of SEIRS-SEI Epidemic Models on Malaria with Regard to Human Recovery Rate

This article discusses SEIRS-SEI epidemic models on malaria with regard to human recovery rate. SEIRS-SEI in this model is an abbreviation of the population class used in the model, ie Susceptible, Exposed, Infected, and Recovered populations in humans and Susceptible, Exposed, and Infected populations in mosquito. These epidemic models belong to mathematical models which clarify a phenomenon of epidemic transmission of malaria by observing the human recovery rate after being infected and susceptible. Human population falls into four classes, namely susceptible humans, exposed humans, infected humans, and recovered humans. Meanwhile, mosquito population serving as vectors of the disease is divided into three classes, including susceptible mosquitoes, exposed mosquitoes, and infected mosquitoes. Such models are termed SEIRS-SEI epidemic models. Analytical discussion covers model formation, existence and stability of equilibrium points, as well as numerical simulation to find out the influence of human recovery rate on population dynamics of both species. The results show that the fixed point without disease ( ) is stable in condition and unstable in condition . The simulation results show that the given treatment has an influence on the dynamics of the human population and mosquitoes. If the human recovery rate from the infected state becomes susceptible to increased, then the number of infected populations of both species will decrease. As a result, the disease will not spread and within a certain time will disappear from the population.

Generalized reproduction numbers, sensitivity analysis and critical immunity levels of an SEQIJR disease model with immunization and varying total population size

An SEQIJR model of epidemic disease transmission which includes immunization and a varying population size is studied. The model includes immunization of susceptible people (S), quarantine (Q) of exposed people (E), isolation (J) of infectious people (I), a recovered population (R), and variation in population size due to natural births and deaths and deaths of infected people. It is shown analytically that the model has a disease-free equilibrium state which always exists and an endemic equilibrium state which exists if and only if the disease-free state is unstable. A simple formula is obtained for a generalized reproduction number Rg where, for any given initial population, Rg<1 means that the initial population is locally asymptotically stable and Rg>1 means that the initial population is unstable. As special cases, simple formulas are given for the basic reproduction number R0, a disease-free reproduction number Rdf, and an endemic reproduction number Ren. Formulas are derived for the sensitivity indices for variations in model parameters of the disease-free reproduction number Rdf and for the infected populations in the endemic equilibrium state. A simple formula in terms of the basic reproduction number R0 is derived for the critical immunization level required to prevent the spread of disease in an initially disease-free population. Numerical simulations are carried out using the Matlab program for parameters corresponding to the outbreaks of severe acute respiratory syndrome (SARS) in Beijing, Hong Kong, Canada and Singapore in 2002 and 2003. From the sensitivity analyses for these four regions, the parameters are identified that are the most important for preventing the spread of disease in a disease-free population or for reducing infection in an infected population. The results support the importance of isolating infectious individuals in an epidemic and in maintaining a critical level of immunity in a population to prevent a disease from occurring.

Definitive tests for dengue fever: when and which should I use?

Dengue is a mosquito-borne viral disease that has established itself globally in both endemic and epidemic transmission cycles. While diagnostic decision-making for dengue is often guided by clinical judgement, definitive laboratory tests, including rapid point-of-care tests, have many advantages in the primary care setting. These include providing epidemiological data and diagnostic clarity for atypical cases, as well as contributing to patient education and compliance. This article discussed the types of diagnostic methods for dengue, when to use them and the appropriateness of each test. Viral detection diagnostic methods such as NS1 antigen assays are generally used within the first week of illness onset, whereas dengue serology testing is most appropriate after that time frame. Locally available rapid point-of-care tests, which include both assays in one convenient test kit, can enhance dengue diagnosis in an endemic setting.

Edge-based epidemic dynamics with multiple routes of transmission on random networks

This paper concerns the SIR dynamics with two types of spreading mechanism, i.e., local spreading through network contacts and global spreading through casual contacts. A low-dimensional edge-based model of ordinary differential equations incorporating arbitrary heterogeneous number of individual contacts is formulated. The basic reproduction number $$R_{0}$$ is obtained, and on networks of Poisson type, it is the sum of the basic reproduction numbers for global and local spreading pathways; however, on networks of other type, it is a nonlinear function of the basic reproduction numbers for global and local spreading pathways. To measure the control efforts imposed on one specific transmission pathway, type reproduction numbers for global and local transmission pathways are calculated, respectively. Equations of the final epidemic size are analytically derived. Finally, the numerical solutions to our model are compared with the ensemble averages of the stochastic simulations. Simulations have shown that casual contacts in the population may trigger large stochastic fluctuations, which may cause huge variances around their mean; thus, in this scenario the ensemble mean is not a good representation of the behavior of the stochastic epidemic process. However, increasing the local infection rate or the connectedness of networks yields better predictions. The results presented provide insights in setting a framework for the analysis and containment of multiple routes of epidemic transmission in reality.

Evolutionary structure of Plasmodium falciparum major variant surface antigen genes in South America: Implications for epidemic transmission and surveillance.

Strong founder effects resulting from human migration out of Africa have led to geographic variation in single nucleotide polymorphisms (SNPs) and microsatellites (MS) of the malaria parasite, Plasmodium falciparum. This is particularly striking in South America where two major founder populations of P. falciparum have been identified that are presumed to have arisen from the transatlantic slave trade. Given the importance of the major variant surface antigen of the blood stages of P. falciparum as both a virulence factor and target of immunity, we decided to investigate the population genetics of the genes encoding “Plasmodium falciparum Erythrocyte Membrane Protein 1” (Pf EMP1) among several countries in South America, in order to evaluate the transmission patterns of malaria in this continent. Deep sequencing of the DBLα domain of var genes from 128 P. falciparum isolates from five locations in South America was completed using a 454 high throughput sequencing protocol. Striking geographic variation in var DBLα sequences, similar to that seen for SNPs and MS markers, was observed. Colombia and French Guiana had distinct var DBLα sequences, whereas Peru and Venezuela showed an admixture. The importance of such geographic variation to herd immunity and malaria vaccination is discussed.

A meta-modeling framework in public health emergency management

Epidemic transmission is a common type of public health emergency that is difficult to forecast and often causes substantial harm. Artificial societal models provide a novel approach to the study of public health problems. However, public health emergency management (PHEM) always involves multi-disciplinary and multi-hierarchical models that complicate the work of modeling. Models are also made more complex by the consideration of new requirements and interactions. Therefore, we propose a domain-specific methodology to guide the modeling process in PHEM. By analyzing domain characteristics and modeling requirements, a meta-modeling framework can be constructed, containing the basic elements with which to construct an artificial society to study epidemic transmission. In this paper, the designs of meta-models are discussed in detail, and domain models are implemented by code generation, which enables the support of large-scale, agent-based computational experiments on the KD-ACP platform. Case studies of Ebola are outlined, emergency scenarios are reconstructed based on pre-designed meta-models, and “scenario-response” experiments are presented. This study provides a valuable framework and methodology with which to study complex social problems in PHEM. The proposed method has been verified effectively and efficiently.

Deep coal mining and meningococcal meningitis in England and Wales, 1931–38: Ecological study, with implications for deep shaft mining activities worldwide

The hypothesized role of deep coal mining in the development of community-based outbreaks of meningococcal meningitis has gone largely unexplored. Taking the coalfields of Britain as a historical testbed, techniques of linear and binomial logistic regression were used to assess the association between meningococcal meningitis rates and male occupation rates for coal mining in England and Wales during the national epidemic of 1931–32 and in its aftermath. Adjusting for the epidemiological effects of age, residential density, recent changes in the number of families, housing stock and low social class, the analysis yielded evidence of a significant and positive association between coal mining occupation rates and notified levels of meningitis activity in the epidemic period. Communities in areas of the world that currently maintain substantial deep coal extraction industries may be at increased risk for the epidemic transmission of meningococcal meningitis.

Hepatitis A virus strains circulating during 1997-2015 in Campania, a Southern Italy region with periodic outbreaks.

In Italy, the incidence of hepatitis A has progressively declined over the last 30 years, though not homogeneously throughout the country. In Campania, Southern Italy, high annual incidence rates have been reported and several periodic outbreaks have occurred. To investigate the phylogenetic and epidemiologic relationships among HAV strains circulating in Campania over the period 1997-2015, 87 hepatitis A cases were investigated. The most frequent risk factor was the consumption of raw/undercooked shellfish (75/87, 86.2%). During 1997-2002 most viral strains were subtype IA (16/23, 70%); the phylogenetic pattern suggests that the incidence peaks observed in 2000-2001 had likely been caused by multiple strains. During a large 2004 outbreak, almost all viral variants were subtype IB (38/41, 93%); most of them (22/38, 58%) were recognized to be one of two main strains (differing for just a single nucleotide), the remaining sequences were strictly related variants. In 2014/2015, only IA strains were observed; two phylogenetically related but distinct strains were responsible, respectively, for a small cluster in 2014 and an outbreak in 2015. In each outbreak, several strains unrelated to those responsible for most cases were detected in a minority of patients, documenting a background of sporadic cases occurring even in the course of outbreaks; some of them proved to be identical to strains detected 11-14 years previously. Overall, the data suggest that several related and unrelated HAV strains have endemically circulated over the last 15 years in Campania, with some strains gaining epidemic transmission likely because of a local combination of multiple factors, including inadequate waste water purification and dietary habits.

A class of epidemic virus transmission population dynamic system

A class of epidemic virus transmission population dynamic system is considered. Firstly, using the functional homotopic analysis method, an initial approximate function is selected. Then, the arbitrary order approximate analytic solutions are obtained successively. Finally, the accuracy of the obtained approximate analytic solutions is described. The influence of the various physical parameters for the epidemic virus transmission population dynamic system is discussed.

The Product of the Herpes Simplex Virus 2 UL16 Gene Is Critical for the Egress of Capsids from the Nuclei of Infected Cells.

The herpes simplex virus (HSV) UL16 gene is conserved throughout the Herpesviridae and encodes a poorly understood tegument protein. The HSV-1 UL16 protein forms complexes with several viral proteins, including UL11, gE, VP22, and UL21. We previously demonstrated that HSV-2 UL21 was essential for virus propagation due to the failure of DNA-containing capsids (C capsids) to exit the nucleus. We hypothesized that if a UL16/UL21 complex was required for nuclear egress, HSV-2 lacking UL16 would have a phenotype similar to that of HSV-2 lacking UL21. Deletion of HSV-2 UL16 (Δ16) resulted in a 950-fold reduction in virus propagation in mouse L cell fibroblasts and a 200-fold reduction in virus propagation in Vero cells that was fully reversed upon the repair of Δ16 (Δ16R) and partially reversed by infecting UL16-expressing cells with Δ16. The kinetics of viral gene expression in cells infected with Δ16 were indistinguishable from those of cells infected with Δ16R or the parental virus. Additionally, similar numbers of capsids were isolated from the nuclei of cells infected with Δ16 and the parental virus. However, transmission electron microscopy, fluorescence in situ hybridization experiments, and fluorescent capsid localization assays all indicated a reduction in the ability of Δ16 C capsids to exit the nucleus of infected cells. Taken together, these data indicate that, like UL21, UL16 is critical for HSV-2 propagation and suggest that the UL16 and UL21 proteins may function together to facilitate the nuclear egress of capsids.IMPORTANCE HSV-2 is a highly prevalent sexually transmitted human pathogen that is the main cause of genital herpes infections and is fueling the epidemic transmission of HIV in sub-Saharan Africa. Despite important differences in the pathological features of HSV-1 and HSV-2 infections, HSV-2 is understudied compared to HSV-1. Here we demonstrate that a deletion of the HSV-2 UL16 gene results in a substantial inhibition of virus replication due to a reduction in the ability of DNA-containing capsids to exit the nucleus of infected cells. The phenotype of this UL16 mutant resembles that of an HSV-2 UL21 mutant described previously by our laboratory. Because UL16 and UL21 interact, these findings suggest that a complex containing both proteins may function together in nuclear egress.

A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models.

Zika virus (ZIKV) infection of pregnant women can cause a wide range of congenital abnormalities, including microcephaly, in the infant, a condition now collectively known as congenital ZIKV syndrome. A vaccine to prevent or significantly attenuate viremia in pregnant women who are residents of or travelers to epidemic or endemic regions is needed to avert congenital ZIKV syndrome, and might also help to suppress epidemic transmission. Here we report on a live-attenuated vaccine candidate that contains a 10-nucleotide deletion in the 3' untranslated region of the ZIKV genome (10-del ZIKV). The 10-del ZIKV is highly attenuated, immunogenic, and protective in type 1 interferon receptor-deficient A129 mice. Crucially, a single dose of 10-del ZIKV induced sterilizing immunity with a saturated neutralizing antibody titer, which no longer increased after challenge with an epidemic ZIKV, and completely prevented viremia. The immunized mice also developed a robust T cell response. Intracranial inoculation of 1-d-old immunocompetent CD-1 mice with 1 × 104 infectious focus units (IFU) of 10-del ZIKV caused no mortality, whereas infections with 10 IFU of wild-type ZIKV were lethal. Mechanistically, the attenuated virulence of 10-del ZIKV may be due to decreased viral RNA synthesis and increased sensitivity to type-1-interferon inhibition. The attenuated 10-del ZIKV was incapable of infecting mosquitoes after oral feeding of spiked-blood meals, representing an additional safety feature. Collectively, the safety and efficacy results suggest that further development of this promising, live-attenuated ZIKV vaccine candidate is warranted.