Investigating the impact of multiple feeding attempts on mosquito dynamics via mathematical models.

A deterministic differential equation model for the dynamics of terrestrial forms of mosquito populations is studied. The model assesses the impact of multiple probing attempts by mosquitoes that quest for blood within human populations by including a waiting class for mosquitoes that failed a blood feeding attempt. The equations are derived based on the idea that the reproductive cycle of the mosquito can be viewed as a set of alternating egg laying and blood feeding outcomes realised on a directed path called the gonotrophic cycle pathway. There exists a threshold parameter, the basic offspring number for mosquitoes, whose nature is affected by the way we interpret the transitions involving the different classes on the gonotrophic cycle path. The trivial steady state for the system, which always exists, can be globally asymptomatically stable whenever the threshold parameter is less than unity. The non-trivial steady state, when it exists, is stable for a range of values of the threshold parameter but can also be driven to instability via a Hopf bifurcation. The model's output reveals that the waiting class mosquitoes do contribute positively to sustain mosquito populations as well as increase their interactions with humans via increased frequency and initial amplitude of oscillations. We conclude that to understand human-mosquito interactions, it is informative to consider multiple probing attempts; known to occur when mosquitoes quest for blood meals within human populations.

Toward Achieving a Vaccine-Derived Herd Immunity Threshold for COVID-19 in the U.S.

A novel coronavirus emerged in December of 2019 (COVID-19), causing a pandemic that inflicted unprecedented public health and economic burden in all nooks and corners of the world. Although the control of COVID-19 largely focused on the use of basic public health measures (primarily based on using non-pharmaceutical interventions, such as quarantine, isolation, social-distancing, face mask usage, and community lockdowns) initially, three safe and highly-effective vaccines (by AstraZeneca Inc., Moderna Inc., and Pfizer Inc.), were approved for use in humans in December 2020. We present a new mathematical model for assessing the population-level impact of these vaccines on curtailing the burden of COVID-19. The model stratifies the total population into two subgroups, based on whether or not they habitually wear face mask in public. The resulting multigroup model, which takes the form of a deterministic system of nonlinear differential equations, is fitted and parameterized using COVID-19 cumulative mortality data for the third wave of the COVID-19 pandemic in the United States. Conditions for the asymptotic stability of the associated disease-free equilibrium, as well as an expression for the vaccine-derived herd immunity threshold, are rigorously derived. Numerical simulations of the model show that the size of the initial proportion of individuals in the mask-wearing group, together with positive change in behavior from the non-mask wearing group (as well as those in the mask-wearing group, who do not abandon their mask-wearing habit) play a crucial role in effectively curtailing the COVID-19 pandemic in the United States. This study further shows that the prospect of achieving vaccine-derived herd immunity (required for COVID-19 elimination) in the U.S., using the Pfizer or Moderna vaccine, is quite promising. In particular, our study shows that herd immunity can be achieved in the U.S. if at least 60% of the population are fully vaccinated. Furthermore, the prospect of eliminating the pandemic in the U.S. in the year 2021 is significantly enhanced if the vaccination program is complemented with non-pharmaceutical interventions at moderate increased levels of compliance (in relation to their baseline compliance). The study further suggests that, while the waning of natural and vaccine-derived immunity against COVID-19 induces only a marginal increase in the burden and projected time-to-elimination of the pandemic, adding the impacts of therapeutic benefits of the vaccines into the model resulted in a dramatic reduction in the burden and time-to-elimination of the pandemic.

Mathematical assessment of the impact of human-antibodies on sporogony during the within-mosquito dynamics of Plasmodium falciparum parasites.

We develop and analyze a deterministic ordinary differential equation mathematical model for the within-mosquito dynamics of the Plasmodium falciparum malaria parasite. Our model takes into account the action and effect of blood resident human-antibodies, ingested by the mosquito during a blood meal from humans, in inhibiting gamete fertilization. The model also captures subsequent developmental processes that lead to the different forms of the parasite within the mosquito. Continuous functions are used to model the switching transition from oocyst to sporozoites as well as human antibody density variations within the mosquito gut are proposed and used. In sum, our model integrates the developmental stages of the parasite within the mosquito such as gametogenesis, fertilization and sporogenesis culminating in the formation of sporozoites. Quantitative and qualitative analyses including a sensitivity analysis for influential parameters are performed. We quantify the average sporozoite load produced at the end of the within-mosquito malaria parasite's developmental stages. Our analysis shows that an increase in the efficiency of the ingested human antibodies in inhibiting fertilization within the mosquito's gut results in lowering the density of oocysts and hence sporozoites that are eventually produced by each mosquito vector. So, it is possible to control and limit oocysts development and hence sporozoites development within a mosquito by boosting the efficiency of antibodies as a pathway to the development of transmission-blocking vaccines which could potentially reduce oocysts prevalence among mosquitoes and hence reduce the transmission potential from mosquitoes to human.

The COVID-19 pandemic preparedness simulation tool: CovidSIM.

BACKGROUND: Efficient control and management in the ongoing COVID-19 pandemic needs to carefully balance economical and realizable interventions. Simulation models can play a cardinal role in forecasting possible scenarios to sustain decision support. METHODS: We present a sophisticated extension of a classical SEIR model. The simulation tool CovidSIM Version 1.0 is an openly accessible web interface to interactively conduct simulations of this model. The simulation tool is used to assess the effects of various interventions, assuming parameters that reflect the situation in Austria as an example. RESULTS: Strict contact reduction including isolation of infected persons in quarantine wards and at home can substantially delay the peak of the epidemic. Home isolation of infected individuals effectively reduces the height of the peak. Contact reduction by social distancing, e.g., by curfews, sanitary behavior, etc. are also effective in delaying the epidemic peak. CONCLUSIONS: Contact-reducing mechanisms are efficient to delay the peak of the epidemic. They might also be effective in decreasing the peak number of infections depending on seasonal fluctuations in the transmissibility of the disease.

On a three-stage structured model for the dynamics of malaria transmission with human treatment, adult vector demographics and one aquatic stage.

A modelling framework that describes the dynamics of populations of the female Anopheles sp mosquitoes is used to develop and analyse a deterministic ordinary differential equation model for dynamics and transmission of malaria amongst humans and varying mosquito populations. The framework includes a characterization of the gonotrophic cycle of the female mosquito. The epidemiological model also captures a novel feature whereby treated human's blood can become mosquitocidal to the questing mosquitoes upon the successful ingestion of the treated human's blood. Analysis of the disease free system, that is the model in the absence of infection in the human and mosquito populations, reveals the presence of a basic offspring number, N, whose size determines the existence and stability of a thriving mosquito population in the sense that when N≤1 we have only the mosquito extinction steady state which is globally asymptotically stable, while for N > 1 we have the persistent mosquito population steady state which is also globally asymptotically stable for these range of values of N. In the presence of disease, N still strongly affects the properties of the epidemiological model in the sense that for N≤1 the only steady state for the system is the mosquito extinction steady state, which is globally and asymptotically stable. As N increases beyond unity in the epidemiological model, we obtained the epidemiological basic reproduction number, R0. For R0 < 1, the disease free equilibrium, with both healthy thriving susceptible human and mosquito populations, is globally asymptotically stable. Both N and R0 are studied for control purposes and our study highlights that multiple control schemes would have a stronger impact on reducing both N and R0 to values small enough for a possible disease vector control and disease eradication. Our model further illustrates that newly emerged mosquitoes that are infected with the malaria parasite during their first blood meal play an important and strong role in the malaria disease dynamics. Additionally, mosquitoes at later gonotrophic cycle stages also impact the dynamics but their contributions to the total mosquito population size decreases with increasing number of gonotrophic cycles. The size of the contribution into the young mosquito population is also dependent on the length of the gonotrophic cycles, an important bionomic parameter, as well as on how the mosquitoes at the final gonotrophic cycles are incorporated into the modelling scheme.

The Impact of Recruitment on the Dynamics of an Immune-Suppressed Within-Human-Host Model of the Plasmodium falciparum Parasite.

A model is developed and used to study within-human malaria parasite dynamics. The model integrates actors involved in the development-progression of parasitemia, gametocytogenesis and mechanisms for immune response activation. Model analyses under immune suppression reveal different dynamical behaviours for different healthy red blood cell (HRBC) generation functions. Existence of a threshold parameter determines conditions for HRBCs depletion. Oscillatory dynamics reminiscent of malaria parasitemia are obtained. A dependence exists on the type of recruitment function used to generate HRBCs, with complexities observed for a more nonlinear function. An upper bound that delimits the size of feasible parasitized steady-state solution exists for a logistic function but not a constant function. The upper bound is completely characterized and is affected by parameters associated with HRBCs recruitment, parasitized red blood cells generation and the release and time-to-release of free merozoites. A stable density size for mature gametocytes, the bridge to invertebrate hosts, is derived.

A Mathematical Model with Quarantine States for the Dynamics of Ebola Virus Disease in Human Populations.

A deterministic ordinary differential equation model for the dynamics and spread of Ebola Virus Disease is derived and studied. The model contains quarantine and nonquarantine states and can be used to evaluate transmission both in treatment centres and in the community. Possible sources of exposure to infection, including cadavers of Ebola Virus victims, are included in the model derivation and analysis. Our model's results show that there exists a threshold parameter, R 0, with the property that when its value is above unity, an endemic equilibrium exists whose value and size are determined by the size of this threshold parameter, and when its value is less than unity, the infection does not spread into the community. The equilibrium state, when it exists, is locally and asymptotically stable with oscillatory returns to the equilibrium point. The basic reproduction number, R 0, is shown to be strongly dependent on the initial response of the emergency services to suspected cases of Ebola infection. When intervention measures such as quarantining are instituted fully at the beginning, the value of the reproduction number reduces and any further infections can only occur at the treatment centres. Effective control measures, to reduce R 0 to values below unity, are discussed.

Persistent oscillations and backward bifurcation in a malaria model with varying human and mosquito populations: implications for control.

We derive and study a deterministic compartmental model for malaria transmission with varying human and mosquito populations. Our model considers disease-related deaths, asymptomatic immune humans who are also infectious, as well as mosquito demography, reproduction and feeding habits. Analysis of the model reveals the existence of a backward bifurcation and persistent limit cycles whose period and size is determined by two threshold parameters: the vectorial basic reproduction number Rm, and the disease basic reproduction number R0, whose size can be reduced by reducing Rm. We conclude that malaria dynamics are indeed oscillatory when the methodology of explicitly incorporating the mosquito's demography, feeding and reproductive patterns is considered in modeling the mosquito population dynamics. A sensitivity analysis reveals important control parameters that can affect the magnitudes of Rm and R0, threshold quantities to be taken into consideration when designing control strategies. Both Rm and the intrinsic period of oscillation are shown to be highly sensitive to the mosquito's birth constant λm and the mosquito's feeding success probability pw. Control of λm can be achieved by spraying, eliminating breeding sites or moving them away from human habitats, while pw can be controlled via the use of mosquito repellant and insecticide-treated bed-nets. The disease threshold parameter R0 is shown to be highly sensitive to pw, and the intrinsic period of oscillation is also sensitive to the rate at which reproducing mosquitoes return to breeding sites. A global sensitivity and uncertainty analysis reveals that the ability of the mosquito to reproduce and uncertainties in the estimations of the rates at which exposed humans become infectious and infectious humans recover from malaria are critical in generating uncertainties in the disease classes.

On a reproductive stage-structured model for the population dynamics of the malaria vector.

A reproductive stage-structured deterministic differential equation model for the population dynamics of the human malaria vector is derived and analysed. The model captures the gonotrophic and behavioural life characteristics of the female Anopheles sp. mosquito and takes into consideration the fact that for the purposes of reproduction, the female Anopheles sp. mosquito must visit and bite humans (or animals) to harvest necessary proteins from blood that it needs for the development of its eggs. Focusing on mosquitoes that feed exclusively on humans, our results indicate the existence of a threshold parameter, the vectorial reproduction number, whose size increases with increasing number of gonotrophic cycles, and is also affected by the female mosquito's birth rate, its attraction and visitation rate to human residences, and its contact rate with humans. A stability analysis of the model indicates that the mosquito can establish itself in the environment if and only if the value of the vectorial reproduction number exceeds unity and that mosquito eradication is possible if the vectorial reproduction number is less than unity, since, then, the trivial steady state which always exist is unique and is globally and asymptotically stable. When a persistent vector population steady state exists, it is locally and asymptotically stable for a range of reproduction numbers, but can also be driven to instability via a Hopf bifurcation as the reproduction number increases further away from unity. The model derivation identifies and characterizes control parameters relating to activities such as human-mosquito contact and the mosquito's survival chances between blood meals and egg laying. Our results show that the total mosquito population size increases with increasing number of gonotrophic cycles. Therefore understanding the fundamental aspects of the mosquito's behaviour provides a pathway for the study of human-mosquito contact and mosquito population control. Control of the mosquito population densities would ultimately lead to malaria control.

Periodic oscillations and backward bifurcation in a model for the dynamics of malaria transmission.

A deterministic ordinary differential equation model for the dynamics of malaria transmission that explicitly integrates the demography and life style of the malaria vector and its interaction with the human population is developed and analyzed. The model is different from standard malaria transmission models in that the vectors involved in disease transmission are those that are questing for human blood. Model results indicate the existence of nontrivial disease free and endemic steady states, which can be driven to instability via a Hopf bifurcation as a parameter is varied in parameter space. Our model therefore captures oscillations that are known to exist in the dynamics of malaria transmission without recourse to external seasonal forcing. Additionally, our model exhibits the phenomenon of backward bifurcation. Two threshold parameters that can be used for purposes of control are identified and studied, and possible reasons why it has been difficult to eradicate malaria are advanced.

On the population dynamics of the malaria vector.

A deterministic differential equation model for the population dynamics of the human malaria vector is derived and studied. Conditions for the existence and stability of a non-zero steady state vector population density are derived. These reveal that a threshold parameter, the vectorial basic reproduction number, exist and the vector can established itself in the community if and only if this parameter exceeds unity. When a non-zero steady state population density exists, it can be stable but it can also be driven to instability via a Hopf Bifurcation to periodic solutions, as a parameter is varied in parameter space. By considering a special case, an asymptotic perturbation analysis is used to derive the amplitude of the oscillating solutions for the full non-linear system. The present modelling exercise and results show that it is possible to study the population dynamics of disease vectors, and hence oscillatory behaviour as it is often observed in most indirectly transmitted infectious diseases of humans, without recourse to external seasonal forcing.