Dengue is a serious health problem in the Philippines. In 2016, the Department of Health of the country launched a dengue vaccination campaign using Dengvaxia. However, the campaign was mired with controversy and the use of Dengvaxia was banned in the country. This study proposes a mathematical model that represents the dynamics of the transmission of dengue with its four strains. Considering that the Dengvaxia vaccine was intended to be given only to people aging from 9 to 45 years old, the human population is divided into two age groups: from 9-45 years old and the rest of the population. Using this model and optimal control theory we simulate what could have been the effect of Dengvaxia in the number of dengue cases and then compare this with the other usual dengue intervention strategies. Results show that the best implementation of the usual strategies is better than that of Dengvaxia.
We propose an SEIR model for the populations and an SEI model for the vector to describe the transmission dynamics of a four-strain model with both primary and secondary dengue infections. In order to accomplish this, we propose and obtain an analytic solution of a system of 47 coupled differential equations. This would be the most complete epidemic model proposed to describe the dengue epidemic.
Infection by distinct Dengue virus serotypes and host immunity are intricately linked. In particular, certain levels of cross-reactive antibodies in the host may actually enhance infection severity leading to Dengue hemorrhagic fever (DHF). The coupled immunological and epidemiological dynamics of Dengue calls for a multi-scale modeling approach. In this work, we formulate a within-host model which mechanistically recapitulates characteristics of antibody dependent enhancement (ADE) in Dengue infection. The within-host scale is then linked to epidemiological spread by a vector-host partial dif…
Different extensions of the classical single-strain SIR model for the host population, motivated by modeling dengue fever epidemiology, have reported a rich dynamic structure including deterministic chaos which was able to explain the large fluctuations of disease incidences. A comparison between the basic two-strain dengue model, which already captures differences between primary and secondary infections, with the four-strain dengue model, that introduces the idea of competition of multiple strains in dengue epidemics shows that the difference between first and secondary infections drives the…
An epidemic multi-strain model with temporary cross-immunity shows chaos, even in a previously unexpected parameter region. Especially dengue fever models with strong enhanced infectivity on secondary infection have previously shown deterministic chaos motivated by experimental findings of antibody-dependent-enhancement (ADE). Including temporary cross-immunity in such models, which is common knowledge among field researchers in dengue, we find a deterministically chaotic attractor in the more realistic parameter region of reduced infectivity on secondary infection (''inverse ADE'' parameter r…
We analyse an epidemiological model of competing strains of pathogens and hence differences in transmission for first versus secondary infection due to interaction of the strains with previously aquired immunities, as has been described for dengue fever (in dengue known as antibody dependent enhancement, ADE). Such models show a rich variety of dynamics through bifurcations up to deterministic chaos. Including temporary cross-immunity even enlarges the parameter range of such chaotic attractors, and also gives rise to various coexisting attractors, which are difficult to identify by standard n…
Transmission rates are key in understanding the spread of infectious diseases. Using the framework of compartmental models, we introduce a simple method that enables us to reconstruct time series of transmission rates directly from incidence or disease-related mortality data. The reconstruction exploits differential equations, which model the time evolution of infective stages and strains. Being sensitive to initial values, the method produces asymptotically correct solutions. The computations are fast, with time complexity being quadratic. We apply the reconstruction to data of measles (Engla…
According to the World Health Organization the global incidence rate of dengue infections have risen drastically in recent years. It is estimated that globally the number of new infections is in the range of $100$ to $400$ million per annum. At the same time a number of recent studies reported the existence of Wolbachia strains, which inhibit dengue virus replication in mosquito species that are primary vectors for dengue transmission. In this study we focus on the impact of Wolbachia on dengue transmission dynamics in an age-structured human population. We introduce a mathematical model, whic…
Dengue and Zika incidence data and the latest research have raised questions about how dengue vaccine strategies might be impacted by the emergence of Zika virus. Existing antibodies to one virus might temporarily protect or promote infection by the other through antibody-dependent enhancement (ADE). With this condition, understanding the dynamics of propagation of these two viruses is of great importance when implementing vaccines. In this work, we analyze the effect of vaccination against one strain, in a two-strain model that accounts for cross-immunity and ADE. Using basic and invasion rep…
We construct an epidemic model for the transmission of dengue fever with an early-life stage in the vector dynamics and age-structure within hosts. The early-life stage of the vector is modeled via a general function that supports multiple vector densities. The {\it basic reproductive number} and {\it vector demographic threshold} are computed to study the local and global stability of the infection-free state. A numerical framework is implemented and simulations are performed.
Medical statistics reveal a significant dependence of hospitalized dengue patient on the patient's age. To incorporate an age-dependence into a mathematical model, we extend the classical ODE system of disease dynamics to a PDE system. The equilibrium distribution is then determined by the fixed points of resulting integro-differential equations. In this paper we use an extension of the concept of the basic reproductive number to characterize parameter regimes, where either only the disease-free or an endemic equilibrium exists. Using rather general and minimal assumptions on the population di…
Metapopulation (multipatch) models are widely used to study the patterns of spatial spread of epidemics. In this paper we study the impact of inter-patch connection weights on the predictions of these models. We contrast arbitrary, uniform link weights with link weights predicted using a gravity model based on patch populations and distance. In a synthetic system with one large driver city and many small follower cities, we show that under uniform link weights, epidemics in the follower regions are perfectly synchronized. In contrast, gravity-based links allow a more realistic, less synchroniz…
Quantifying the attack ratio of disease is key to epidemiological inference and Public Health planning. For multi-serotype pathogens, however, different levels of serotype-specific immunity make it difficult to assess the population at risk. In this paper we propose a Bayesian method for estimation of the attack ratio of an epidemic and the initial fraction of susceptibles using aggregated incidence data. We derive the probability distribution of the effective reproductive number, R t , and use MCMC to obtain posterior distributions of the parameters of a single-strain SIR transmission model w…
According to the World Health Organization, dengue fever is the most important mosquito-borne disease of humans, and it is currently estimated that there may be 50 - 100 million yearly dengue infections worldwide. For the purpose to provide new techniques to public health policies in course, we introduce a predictive non-linear population dynamics model to describe the population size of four stages of the development of \emph{Aedes aegypti}, having the coefficients set to be dependent on the rainfall index data. In spite of the population dynamics of the \emph{Ae. aegypti} be mainly ruled by …
The June software package is an open-source framework for the detailed simulation of epidemics based on social interactions in a virtual population reflecting age, gender, ethnicity, and socio-economic indicators in England. In this paper, we present a new version of the framework specifically adapted for Germany, which allows the simulation of the entire German population using publicly available information on households, schools, universities, workplaces, and mobility data for Germany. Moreover, JuneGermany incorporates testing and vaccination strategies within the population as well as the…
We consider a general mathematical model of a within-host viral infection with $n$ virus strains and explicit age-since-infection structure for infected cells. In the model, multiple virus strains compete for a population of target cells. Cells infected with virus strain $i\in\left\{1,...,n\right\}$ die at per-capita rate $δ_i(a)$ and produce virions at per-capita rate $p_i(a)$, where $δ_i(a)$ and $p_i(a)$ are functions of the age-since-infection of the cell. Viral strain $i$ has a basic reproduction number, $\mathcal{R}_i$, and a corresponding positive single strain equilibrium, $E_i$, when $…
A simple, but ``classical``, stochastic model for epidemic spread in a finite, but large, population is studied. The progress of the epidemic can be divided into three different phases that requires different tools to analyse. Initially the process is approximated by a branching process. It is discussed for how long time this approximation is valid. When a non-negligible proportion of the population is already infected the process can be studied using differential equations. In a final phase the spread will fade out. The results are used to investigate what happens if two strains of infectious…
Arboviral infections, especially dengue, continue to cause significant health burden in their endemic regions. One of the strategies to tackle these infections is to replace the main vector agent, Ae. aegypti, with the ones incapable of transmitting the virus. Wolbachia, an intracellular bacterium, has shown promise in achieving this goal. However, key factors such as imperfect maternal transmission, loss of Wolbachia infection, reduced reproductive capacity and shortened life-span affect the dynamics of Wolbachia in different forms in the Ae. aegypti population. In this study, we developed a …
We introduce and investigate a series of models for an infection of a diplodiploid host species by the bacterial endosymbiont \textit{Wolbachia}. The continuous models are characterized by partial vertical transmission, cytoplasmic incompatibility and fitness costs associated with the infection. A particular aspect of interest is competitions between mutually incompatible strains. We further introduce an age-structured model that takes into account different fertility and mortality rates at different stages of the life cycle of the individuals. With only a few parameters, the ordinary differen…
Interactions among multiple infectious agents are increasingly recognized as a fundamental issue in the understanding of key questions in public health, regarding pathogen emergence, maintenance, and evolution. The full description of host-multipathogen systems is however challenged by the multiplicity of factors affecting the interaction dynamics and the resulting competition that may occur at different scales, from the within-host scale to the spatial structure and mobility of the host population. Here we study the dynamics of two competing pathogens in a structured host population and asses…
There are economic and physical limitations when applying prevention and control strategies for urban vector borne diseases. Consequently, there are increasing concerns and interest in designing efficient strategies and regulations that health agencies can follow in order to reduce the imminent impact of viruses like Dengue, Zika and Chikungunya. That includes fumigation, abatization, reducing the hatcheries, picking up trash, information campaigns. A basic question that arise when designing control strategies is about which and where these ones should focus. In other words, one would like to …
