A hybrid Lagrangian-Eulerian model for vector-borne diseases.

In this paper, a multi-patch and multi-group vector-borne disease model is proposed to study the effects of host commuting (Lagrangian approach) and/or vector migration (Eulerian approach) on disease spread. We first define the basic reproduction number of the model, R 0 , which completely determines the global dynamics of the model system. Namely, if R 0 ≤ 1 , then the disease-free equilibrium is globally asymptotically stable, and if R 0 > 1 , then there exists a unique endemic equilibrium which is globally asymptotically stable. Then, we show that the basic reproduction number has lower and upper bounds which are independent of the host residence times matrix and the vector migration matrix. In particular, nonhomogeneous mixing of hosts and vectors in a homogeneous environment generally increases disease persistence and the basic reproduction number of the model attains its minimum when the distributions of hosts and vectors are proportional. Moreover, R 0 can also be estimated by the basic reproduction numbers of disconnected patches if the environment is homogeneous. The optimal vector control strategy is obtained for a special scenario. In the two-patch and two-group case, we numerically analyze the dependence of the basic reproduction number and the total number of infected people on the host residence times matrix and illustrate the optimal vector control strategy in homogeneous and heterogeneous environments.

Analysis of the COVID-19 model with self-protection and isolation measures affected by the environment.

Since the global outbreak of COVID-19, the virus has continuously mutated and can survive in the air for long periods of time. This paper establishes and analyzes a model of COVID-19 with self-protection and quarantine measures affected by viruses in the environment to investigate the influence of viruses in the environment on the spread of the outbreak, as well as to develop a rational prevention and control measure to control the spread of the outbreak. The basic reproduction number was calculated and Lyapunov functions were constructed to discuss the stability of the model equilibrium points. The disease-free equilibrium point was proven to be globally asymptotically stable when $ R_0 < 1 $, and the endemic equilibrium point was globally asymptotically stable when $ R_0 > 1 $. The model was fitted using data from COVID-19 cases in Chongqing between November 1 to November 25, 2022. Based on the numerical analysis, the following conclusion was obtained: clearing the virus in the environment and strengthening the isolation measures for infected people can control the epidemic to a certain extent, but enhancing the self-protection of individuals can be more effective in reducing the risk of being infected and controlling the transmission of the epidemic, which is more conducive to the practical application.

A deterministic transmission model for analytics-driven optimization of COVID-19 post-pandemic vaccination and quarantine strategies.

This study developed a deterministic transmission model for the coronavirus disease of 2019 (COVID-19), considering various factors such as vaccination, awareness, quarantine, and treatment resource limitations for infected individuals in quarantine facilities. The proposed model comprised five compartments: susceptible, vaccinated, quarantined, infected, and recovery. It also considered awareness and limited resources by using a saturated function. Dynamic analyses, including equilibrium points, control reproduction numbers, and bifurcation analyses, were conducted in this research, employing analytics to derive insights. Our results indicated the possibility of an endemic equilibrium even if the reproduction number for control was less than one. Using incidence data from West Java, Indonesia, we estimated our model parameter values to calibrate them with the real situation in the field. Elasticity analysis highlighted the crucial role of contact restrictions in reducing the spread of COVID-19, especially when combined with community awareness. This emphasized the analytics-driven nature of our approach. We transformed our model into an optimal control framework due to budget constraints. Leveraging Pontriagin's maximum principle, we meticulously formulated and solved our optimal control problem using the forward-backward sweep method. Our experiments underscored the pivotal role of vaccination in infection containment. Vaccination effectively reduces the risk of infection among vaccinated individuals, leading to a lower overall infection rate. However, combining vaccination and quarantine measures yields even more promising results than vaccination alone. A second crucial finding emphasized the need for early intervention during outbreaks rather than delayed responses. Early interventions significantly reduce the number of preventable infections, underscoring their importance.

Modeling different infectious phases of hepatitis B with generalized saturated incidence: An analysis and control.

Hepatitis B is one of the global health issues caused by the hepatitis B virus (HBV), producing 1.1 million deaths yearly. The acute and chronic phases of HBV are significant because worldwide, approximately 250 million people are infected by chronic hepatitis B. The chronic stage is a long-term, persistent infection that can cause liver damage and increase the risk of liver cancer. In the case of multiple phases of infection, a generalized saturated incidence rate model is more reasonable than a simply saturated incidence because it captures the complex dynamics of the different infection phases. In contrast, a simple saturated incidence rate model assumes a fixed shape for the incidence rate curve, which may not accurately reflect the dynamics of multiple infection phases. Considering HBV and its various phases, we constructed a model to present the dynamics and control strategies using the generalized saturated incidence. First, we proved that the model is well-posed. We then found the reproduction quantity and model equilibria to discuss the time dynamics of the model and investigate the conditions for stabilities. We also examined a control mechanism by introducing various controls to the model with the aim to increase the population of those recovered and minimize the infected people. We performed numerical experiments to check the biological significance and control implementation.

Approximating reproduction numbers: a general numerical method for age-structured models.

In this paper, we introduce a general numerical method to approximate the reproduction numbers of a large class of multi-group, age-structured, population models with a finite age span. To provide complete flexibility in the definition of the birth and transition processes, we propose an equivalent formulation for the age-integrated state within the extended space framework. Then, we discretize the birth and transition operators via pseudospectral collocation. We discuss applications to epidemic models with continuous and piecewise continuous rates, with different interpretations of the age variable (e.g., demographic age, infection age and disease age) and the transmission terms (e.g., horizontal and vertical transmission). The tests illustrate that the method can compute different reproduction numbers, including the basic and type reproduction numbers as special cases.

An SIS epidemic model with individual variation.

We study an extension of the stochastic SIS (Susceptible-Infectious-Susceptible) model in continuous time that accounts for variation amongst individuals. By examining its limiting behaviour as the population size grows we are able to exhibit conditions for the infection to become endemic.

A novel within-host model of HIV and nutrition.

In this paper we develop a four compartment within-host model of nutrition and HIV. We show that the model has two equilibria: an infection-free equilibrium and infection equilibrium. The infection free equilibrium is locally asymptotically stable when the basic reproduction number $ \mathcal{R}_0 < 1 $, and unstable when $ \mathcal{R}_0 > 1 $. The infection equilibrium is locally asymptotically stable if $ \mathcal{R}_0 > 1 $ and an additional condition holds. We show that the within-host model of HIV and nutrition is structured to reveal its parameters from the observations of viral load, CD4 cell count and total protein data. We then estimate the model parameters for these 3 data sets. We have also studied the practical identifiability of the model parameters by performing Monte Carlo simulations, and found that the rate of clearance of the virus by immunoglobulins is practically unidentifiable, and that the rest of the model parameters are only weakly identifiable given the experimental data. Furthermore, we have studied how the data frequency impacts the practical identifiability of model parameters.

Threshold dynamics of a switching diffusion SIR model with logistic growth and healthcare resources.

In this article, we have constructed a stochastic SIR model with healthcare resources and logistic growth, aiming to explore the effect of random environment and healthcare resources on disease transmission dynamics. We have showed that under mild extra conditions, there exists a critical parameter, i.e., the basic reproduction number $ R_0/ $, which completely determines the dynamics of disease: when $ R_0/ < 1 $, the disease is eradicated; while when $ R_0/ > 1 $, the disease is persistent. To validate our theoretical findings, we conducted some numerical simulations using actual parameter values of COVID-19. Both our theoretical and simulation results indicated that (1) the white noise can significantly affect the dynamics of a disease, and importantly, it can shift the stability of the disease-free equilibrium; (2) infectious disease resurgence may be caused by random switching of the environment; and (3) it is vital to maintain adequate healthcare resources to control the spread of disease.

The impact of temperature, humidity and closing school on the mumps epidemic: a case study in the mainland of China.

BACKGROUND: To control resurging infectious diseases like mumps, it is necessary to resort to effective control and preventive measures. These measures include increasing vaccine coverage, providing the community with advice on how to reduce exposure, and closing schools. To justify such intervention, it is important to understand how well each of these measures helps to limit transmission. METHODS: In this paper, we propose a simple SEILR (susceptible-exposed-symptomatically infectious-asymptomatically infectious-recovered) model by using a novel transmission rate function to incorporate temperature, humidity, and closing school factors. This new transmission rate function allows us to verify the impact of each factor either separately or combined. Using reported mumps cases from 2004 to 2018 in the mainland of China, we perform data fitting and parameter estimation to evaluate the basic reproduction number  R 0 . As a wide range of one-dose measles, mumps, and rubella (MMR) vaccine programs in China started only in 2008, we use different vaccination proportions for the first Stage I period (from 2004 to 2008) and the second Stage II period (from 2009 to 2018). This allows us to verify the importance of higher vaccine coverage with a possible second dose of MMR vaccine. RESULTS: We find that the basic reproduction number  R 0  is generally between 1 and 3. We then use the Akaike Information Criteria to assess the extent to which each of the three factors contributed to the spread of mumps. The findings suggest that the impact of all three factors is substantial, with temperature having the most significant impact, followed by school opening and closing, and finally humidity. CONCLUSION: We conclude that the strategy of increasing vaccine coverage, changing micro-climate (temperature and humidity), and closing schools can greatly reduce mumps transmission.

Modelling the impact of precaution on disease dynamics and its evolution.

In this paper, we introduce the notion of practically susceptible population, which is a fraction of the biologically susceptible population. Assuming that the fraction depends on the severity of the epidemic and the public's level of precaution (as a response of the public to the epidemic), we propose a general framework model with the response level evolving with the epidemic. We firstly verify the well-posedness and confirm the disease's eventual vanishing for the framework model under the assumption that the basic reproduction number R 0 < 1 . For R 0 > 1 , we study how the behavioural response evolves with epidemics and how such an evolution impacts the disease dynamics. More specifically, when the precaution level is taken to be the instantaneous best response function in literature, we show that the endemic dynamic is convergence to the endemic equilibrium; while when the precaution level is the delayed best response, the endemic dynamic can be either convergence to the endemic equilibrium, or convergence to a positive periodic solution. Our derivation offers a justification/explanation for the best response used in some literature. By replacing "adopting the best response" with "adapting toward the best response", we also explore the adaptive long-term dynamics.

A mathematical model for HIV dynamics with multiple infections: implications for immune escape.

Multiple infections enable the recombination of different strains, which may contribute to viral diversity. How multiple infections affect the competition dynamics between the two types of strains, the wild and the immune escape mutant, remains poorly understood. This study develops a novel mathematical model that includes the two strains, two modes of viral infection, and multiple infections. For the representative double-infection case, the reproductive numbers are derived and global stabilities of equilibria are obtained via the Lyapunov direct method and theory of limiting systems. Numerical simulations indicate similar viral dynamics regardless of multiplicities of infections though the competition between the two strains would be the fiercest in the case of quadruple infections. Through sensitivity analysis, we evaluate the effect of parameters on the set-point viral loads in the presence and absence of multiple infections. The model with multiple infections predict that there exists a threshold for cytotoxic T lymphocytes (CTLs) to minimize the overall viral load. Weak or strong CTLs immune response can result in high overall viral load. If the strength of CTLs maintains at an intermediate level, the fitness cost of the mutant is likely to have a significant impact on the evolutionary dynamics of mutant viruses. We further investigate how multiple infections alter the viral dynamics during the combination antiretroviral therapy (cART). The results show that viral loads may be underestimated during cART if multiple-infection is not taken into account.

Threshold dynamics of a reaction-advection-diffusion schistosomiasis epidemic model with seasonality and spatial heterogeneity.

Most water-borne disease models ignore the advection of water flows in order to simplify the mathematical analysis and numerical computation. However, advection can play an important role in determining the disease transmission dynamics. In this paper, we investigate the long-term dynamics of a periodic reaction-advection-diffusion schistosomiasis model and explore the joint impact of advection, seasonality and spatial heterogeneity on the transmission of the disease. We derive the basic reproduction number R 0 and show that the disease-free periodic solution is globally attractive when R 0 < 1 whereas there is a positive endemic periodic solution and the system is uniformly persistent in a special case when R 0 > 1 . Moreover, we find that R 0 is a decreasing function of the advection coefficients which offers insights into why schistosomiasis is more serious in regions with slow water flows.

Modelling phytoplankton-virus interactions: phytoplankton blooms and lytic virus transmission.

A dynamic reaction-diffusion model of four variables is proposed to describe the spread of lytic viruses among phytoplankton in a poorly mixed aquatic environment. The basic ecological reproductive index for phytoplankton invasion and the basic reproduction number for virus transmission are derived to characterize the phytoplankton growth and virus transmission dynamics. The theoretical and numerical results from the model show that the spread of lytic viruses effectively controls phytoplankton blooms. This validates the observations and experimental results of Emiliana huxleyi-lytic virus interactions. The studies also indicate that the lytic virus transmission cannot occur in a low-light or oligotrophic aquatic environment.

Effects of fish-human transmission and different life stages of fish on Clonorchiasis: A novel mathematical model.

Clonorchiasis is a zoonotic disease mainly caused by eating raw fish and shrimp, and there is no vaccine to prevent it. More than 30 million people are infected worldwide, of which China alone accounts for about half, and is one of the countries most seriously affected by Clonorchiasis. In this work, we formulate a novel Ordinary Differential Equation (ODE) model to discuss the biological attributes of fish within authentic ecosystems and the complex lifecycle of Clonorchis sinensis. This model includes larval fish, adult fish, infected fish, humans, and cercariae. We derive the basic reproduction number and perform a rigorous stability analysis of the proposed model. Numerically, we use data from 2016 to 2021 in Guangxi, China, to discuss outbreaks of Clonorchiasis and obtain the basic reproduction number R0=1.4764. The fitted curve appropriately reflects the overall trend and replicates a low peak in the case number of Clonorchiasis. By reducing the release rate of cercariae in 2018, the fitted values of Clonorchiasis cases dropped rapidly and almost disappeared. If we decrease the transmission rate from infected fish to humans, Clonorchiasis can be controlled. Our studies also suggest that strengthening publicity education and cleaning water quality can effectively control the transmission of Clonorchiasis in Guangxi, China.

A simulation-based approach for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data.

Tracking pathogen transmissibility during infectious disease outbreaks is essential for assessing the effectiveness of public health measures and planning future control strategies. A key measure of transmissibility is the time-dependent reproduction number, which has been estimated in real-time during outbreaks of a range of pathogens from disease incidence time series data. While commonly used approaches for estimating the time-dependent reproduction number can be reliable when disease incidence is recorded frequently, such incidence data are often aggregated temporally (for example, numbers of cases may be reported weekly rather than daily). As we show, commonly used methods for estimating transmissibility can be unreliable when the timescale of transmission is shorter than the timescale of data recording. To address this, here we develop a simulation-based approach involving Approximate Bayesian Computation for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data. We first use a simulated dataset representative of a situation in which daily disease incidence data are unavailable and only weekly summary values are reported, demonstrating that our method provides accurate estimates of the time-dependent reproduction number under such circumstances. We then apply our method to two outbreak datasets consisting of weekly influenza case numbers in 2019-20 and 2022-23 in Wales (in the United Kingdom). Our simple-to-use approach will allow accurate estimates of time-dependent reproduction numbers to be obtained from temporally aggregated data during future infectious disease outbreaks.

An Efficient Approach to Nowcasting the Time-varying Reproduction Number.

Estimating the instantaneous reproduction number ( ) in near real time is crucial for monitoring and responding to epidemic outbreaks on a daily basis. However, such estimates often suffer from bias due to reporting delays inherent in surveillance systems. We propose a fast and flexible Bayesian methodology to overcome this challenge by estimating while taking into account reporting delays. Furthermore, the method naturally takes into account the uncertainty associated with the nowcasting of cases to get a valid uncertainty estimation of the nowcasted reproduction number. We evaluate the proposed methodology through a simulation study and apply it to COVID-19 incidence data in Belgium.

Markovian Approach for Exploring Competitive Diseases with Heterogeneity-Evidence from COVID-19 and Influenza in China.

Due to the complex interactions between multiple infectious diseases, the spreading of diseases in human bodies can vary when people are exposed to multiple sources of infection at the same time. Typically, there is heterogeneity in individuals' responses to diseases, and the transmission routes of different diseases also vary. Therefore, this paper proposes an SIS disease spreading model with individual heterogeneity and transmission route heterogeneity under the simultaneous action of two competitive infectious diseases. We derive the theoretical epidemic spreading threshold using quenched mean-field theory and perform numerical analysis under the Markovian method. Numerical results confirm the reliability of the theoretical threshold and show the inhibitory effect of the proportion of fully competitive individuals on epidemic spreading. The results also show that the diversity of disease transmission routes promotes disease spreading, and this effect gradually weakens when the epidemic spreading rate is high enough. Finally, we find a negative correlation between the theoretical spreading threshold and the average degree of the network. We demonstrate the practical application of the model by comparing simulation outputs to temporal trends of two competitive infectious diseases, COVID-19 and seasonal influenza in China.

Linking Spontaneous Behavioral Changes to Disease Transmission Dynamics: Behavior Change Includes Periodic Oscillation.

Behavior change significantly influences the transmission of diseases during outbreaks. To incorporate spontaneous preventive measures, we propose a model that integrates behavior change with disease transmission. The model represents behavior change through an imitation process, wherein players exclusively adopt the behavior associated with higher payoff. We find that relying solely on spontaneous behavior change is insufficient for eradicating the disease. The dynamics of behavior change are contingent on the basic reproduction number R a corresponding to the scenario where all players adopt non-pharmaceutical interventions (NPIs). When R a < 1 , partial adherence to NPIs remains consistently feasible. We can ensure that the disease stays at a low level or maintains minor fluctuations around a lower value by increasing sensitivity to perceived infection. In cases where oscillations occur, a further reduction in the maximum prevalence of infection over a cycle can be achieved by increasing the rate of behavior change. When R a > 1 , almost all players consistently adopt NPIs if they are highly sensitive to perceived infection. Further consideration of saturated recovery leads to saddle-node homoclinic and Bogdanov-Takens bifurcations, emphasizing the adverse impact of limited medical resources on controlling the scale of infection. Finally, we parameterize our model with COVID-19 data and Tokyo subway ridership, enabling us to illustrate the disease spread co-evolving with behavior change dynamics. We further demonstrate that an increase in sensitivity to perceived infection can accelerate the peak time and reduce the peak size of infection prevalence in the initial wave.

Generative Bayesian modeling to nowcast the effective reproduction number from line list data with missing symptom onset dates.

The time-varying effective reproduction number Rt is a widely used indicator of transmission dynamics during infectious disease outbreaks. Timely estimates of Rt can be obtained from reported cases counted by their date of symptom onset, which is generally closer to the time of infection than the date of report. Case counts by date of symptom onset are typically obtained from line list data, however these data can have missing information and are subject to right truncation. Previous methods have addressed these problems independently by first imputing missing onset dates, then adjusting truncated case counts, and finally estimating the effective reproduction number. This stepwise approach makes it difficult to propagate uncertainty and can introduce subtle biases during real-time estimation due to the continued impact of assumptions made in previous steps. In this work, we integrate imputation, truncation adjustment, and Rt estimation into a single generative Bayesian model, allowing direct joint inference of case counts and Rt from line list data with missing symptom onset dates. We then use this framework to compare the performance of nowcasting approaches with different stepwise and generative components on synthetic line list data for multiple outbreak scenarios and across different epidemic phases. We find that under reporting delays realistic for hospitalization data (50% of reports delayed by more than a week), intermediate smoothing, as is common practice in stepwise approaches, can bias nowcasts of case counts and Rt, which is avoided in a joint generative approach due to shared regularization of all model components. On incomplete line list data, a fully generative approach enables the quantification of uncertainty due to missing onset dates without the need for an initial multiple imputation step. In a real-world comparison using hospitalization line list data from the COVID-19 pandemic in Switzerland, we observe the same qualitative differences between approaches. The generative modeling components developed in this work have been integrated and further extended in the R package epinowcast, providing a flexible and interpretable tool for real-time surveillance.

Transmission dynamics of a reaction-advection-diffusion dengue fever model with seasonal developmental durations and intrinsic incubation periods.

In this paper, we propose a reaction-advection-diffusion dengue fever model with seasonal developmental durations and intrinsic incubation periods. Firstly, we establish the well-posedness of the model. Secondly, we define the basic reproduction number ℜ 0 for this model and show that ℜ 0 is a threshold parameter: if ℜ 0 < 1 , then the disease-free periodic solution is globally attractive; if ℜ 0 > 1 , the system is uniformly persistent. Thirdly, we study the global attractivity of the positive steady state when the spatial environment is homogeneous and the advection of mosquitoes is ignored. As an example, we use the model to investigate the dengue fever transmission case in Guangdong Province, China, and explore the impact of model parameters on ℜ 0 . Our findings indicate that ignoring seasonality may underestimate ℜ 0 . Additionally, the spatial heterogeneity of transmission may increase the risk of disease transmission, while the increase of seasonal developmental durations, intrinsic incubation periods and advection rates can all reduce the risk of disease transmission.