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We consider the dynamics of a virus spreading through a population that produces a mutant strain with the ability to infect individuals that were infected with the established strain. Temporary cross-immunity is included using a time delay, but is found to be a harmless delay. We provide some sufficient conditions that guarantee local and global asymptotic stability of the disease-free equilibrium and the two boundary equilibria when the two strains outcompete one another. It is shown that, due to the immune evasion of the emerging strain, the reproduction number of the emerging strain must be significantly lower than that of the established strain for the local stability of the established-strain-only boundary equilibrium. To analyze the unique coexistence equilibrium we apply a quasi steady-state argument to reduce the full model to a two-dimensional one that exhibits a global asymptotically stable established-strain-only equilibrium or global asymptotically stable coexistence equilibrium. Our results indicate that the basic reproduction numbers of both strains govern the overall dynamics, but in nontrivial ways due to the inclusion of cross-immunity. The model is applied to study the emergence of the SARS-CoV-2 Delta variant in the presence of the Alpha variant using wastewater surveillance data from the Deer Island Treatment Plant in Massachusetts, USA.
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COVID-19 , Ciervos , Humanos , Animales , Aguas Residuales , Monitoreo Epidemiológico Basado en Aguas Residuales , COVID-19/epidemiología , SARS-CoV-2/genéticaRESUMEN
Wastewater-based surveillance (WBS) has been widely used as a public health tool to monitor SARS-CoV-2 transmission. However, epidemiological inference from WBS data remains understudied and limits its application. In this study, we have established a quantitative framework to estimate COVID-19 prevalence and predict SARS-CoV-2 transmission through integrating WBS data into an SEIR-V model. We conceptually divide the individual-level viral shedding course into exposed, infectious, and recovery phases as an analogy to the compartments in a population-level SEIR model. We demonstrated that the effect of temperature on viral losses in the sewer can be straightforwardly incorporated in our framework. Using WBS data from the second wave of the pandemic (Oct 02, 2020-Jan 25, 2021) in the Greater Boston area, we showed that the SEIR-V model successfully recapitulates the temporal dynamics of viral load in wastewater and predicts the true number of cases peaked earlier and higher than the number of reported cases by 6-16 days and 8.3-10.2 folds (R = 0.93). This work showcases a simple yet effective method to bridge WBS and quantitative epidemiological modeling to estimate the prevalence and transmission of SARS-CoV-2 in the sewershed, which could facilitate the application of wastewater surveillance of infectious diseases for epidemiological inference and inform public health actions.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Aguas Residuales , Prevalencia , Monitoreo Epidemiológico Basado en Aguas ResidualesRESUMEN
Wastewater surveillance has been widely used to track and estimate SARS-CoV-2 incidence. While both infectious and recovered individuals shed virus into wastewater, epidemiological inferences using wastewater often only consider the viral contribution from the former group. Yet, the persistent shedding in the latter group could confound wastewater-based epidemiological inference, especially during the late stage of an outbreak when the recovered population outnumbers the infectious population. To determine the impact of recovered individuals' viral shedding on the utility of wastewater surveillance, we develop a quantitative framework that incorporates population-level viral shedding dynamics, measured viral RNA in wastewater, and an epidemic dynamic model. We find that the viral shedding from the recovered population can become higher than the infectious population after the transmission peak, which leads to a decrease in the correlation between wastewater viral RNA and case report data. Furthermore, the inclusion of recovered individuals' viral shedding into the model predicts earlier transmission dynamics and slower decreasing trends in wastewater viral RNA. The prolonged viral shedding also induces a potential delay in the detection of new variants due to the time needed to generate enough new cases for a significant viral signal in an environment dominated by virus shed by the recovered population. This effect is most prominent toward the end of an outbreak and is greatly affected by both the recovered individuals' shedding rate and shedding duration. Our results suggest that the inclusion of viral shedding from non-infectious recovered individuals into wastewater surveillance research is important for precision epidemiology.
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Wastewater surveillance has proved to be a valuable tool to track the COVID-19 pandemic. However, most studies using wastewater surveillance data revolve around establishing correlations and lead time relative to reported case data. In this perspective, we advocate for the integration of wastewater surveillance data with dynamic within-host and between-host models to better understand, monitor, and predict viral disease outbreaks. Dynamic models overcome emblematic difficulties of using wastewater surveillance data such as establishing the temporal viral shedding profile. Complementarily, wastewater surveillance data bypasses the issues of time lag and underreporting in clinical case report data, thus enhancing the utility and applicability of dynamic models. The integration of wastewater surveillance data with dynamic models can enhance real-time tracking and prevalence estimation, forecast viral transmission and intervention effectiveness, and most importantly, provide a mechanistic understanding of infectious disease dynamics and the driving factors. Dynamic modeling of wastewater surveillance data will advance the development of a predictive and responsive monitoring system to improve pandemic preparedness and population health.
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COVID-19 , Humanos , Pandemias , Aguas Residuales , Monitoreo Epidemiológico Basado en Aguas Residuales , Brotes de Enfermedades , ARN ViralRESUMEN
This study presents a genetic-ecology modeling framework for assessing the combined impacts of insecticide resistance, temperature variability, and insecticide-based interventions on the population abundance and control of malaria mosquitoes by genotype. Rigorous analyses of the model we developed reveal that the boundary equilibrium with only mosquitoes of homozygous sensitive (resistant) genotype is locally-asymptotically stable whenever a certain ecological threshold, denoted by R 0 S S ( R 0 R R ) , is less than one. Furthermore, genotype i drives genotype j to extinction whenever R 0 j > 1 and R 0 i < 1 (where i, j = SS or RR, with i ≠ j). The model exhibits the phenomenon of bistability when both thresholds are less than one. In such a bistable situation, convergence to any of the two boundary equilibria depends on the initial allele distribution in the state variables of the model. Furthermore, in this bistable case, where max { R 0 S S , R 0 R R } < 1 , the basin of attraction of the boundary equilibrium of the mosquito genotype with lower value of the ecological threshold is larger. Specifically, the basin of attraction of the boundary equilibrium for genotype i is larger than that of genotype j if R 0 i < R 0 j < 1 . When both ecological thresholds exceed one ( m i n { R 0 S S , R 0 R R } > 1 ) , the two boundary equilibria lose their stability, and a coexistence equilibrium (where all three mosquito genotypes coexist) becomes locally-asymptotically stable. Global sensitivity analysis shows that the key parameters that greatly influence the dynamics and population abundance of resistant mosquitoes include the proportion of new adult mosquitoes that are females, the insecticide-induced mortality rate of adult female mosquitoes, the coverage level and efficacy of adulticides used in the community, the oviposition rates for eggs of heterozygous and homozygous resistant genotypes, and the modification parameter accounting for the reduction in insecticide-induced mortality due to resistance. Numerical simulations show that the adult mosquito population increases with increasing temperature until a peak is reached at 31 °C, and declines thereafter. Simulating the model for moderate and high adulticide coverage, together with varying fitness costs of resistance, shows a switch in the dominant genotype at equilibrium as temperature is varied. In other words, this study shows that, for certain combinations of adulticide coverage and fitness costs of insecticide resistance, increases in temperature could result in effective management of resistance (by causing the switch from a stable resistant-only boundary equilibrium (at 18 °C) to a stable sensitive-only boundary equilibrium (at 25 °C)). Finally, this study shows that, for moderate fitness costs of resistance, density-dependent larval mortality suppresses the total population of adult mosquitoes with the resistant allele for all temperature values in the range [18 °C-36 °C].
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Wastewater-based surveillance (WBS) has been widely used as a public health tool to monitor SARS-CoV-2 transmission. However, epidemiological inference from WBS data remains understudied and limits its application. In this study, we have established a quantitative framework to estimate COVID-19 prevalence and predict SARS-CoV-2 transmission through integrating WBS data into an SEIR-V model. We conceptually divide the individual-level viral shedding course into exposed, infectious, and recovery phases as an analogy to the compartments in population-level SEIR model. We demonstrated that the temperature effect on viral losses in the sewer can be straightforwardly incorporated in our framework. Using WBS data from the second wave of the pandemic (Oct 02, 2020 â" Jan 25, 2021) in the Great Boston area, we showed that the SEIR-V model successfully recapitulates the temporal dynamics of viral load in wastewater and predicts the true number of cases peaked earlier and higher than the number of reported cases by 16 days and 8.6 folds ( R = 0.93), respectively. This work showcases a simple, yet effective method to bridge WBS and quantitative epidemiological modeling to estimate the prevalence and transmission of SARS-CoV-2 in the sewershed, which could facilitate the application of wastewater surveillance of infectious diseases for epidemiological inference and inform public health actions.
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India has been the latest global epicenter for COVID-19, a novel coronavirus disease that emerged in China in late 2019. We present a base mathematical model for the transmission dynamics of COVID-19 in India and its neighbor, Pakistan. The base model was rigorously analyzed and parameterized using cumulative COVID-19 mortality data from each of the two countries. The model was used to assess the population-level impact of the control and mitigation strategies implemented in the two countries (notably non-pharmaceutical interventions). Numerical simulations of the basic model indicate that, based on the current baseline levels of the control and mitigation strategies implemented, the pandemic trajectory in India is on a downward trend. This downward trend will be reversed, and India will be recording mild outbreaks, if the control and mitigation strategies are relaxed from their current levels. By early September 2021, our simulations suggest that India could record up to 460,000 cumulative deaths under baseline levels of the implemented control strategies, while Pakistan (where the pandemic is comparatively milder) could see over 24,000 cumulative deaths at current mitigation levels. The basic model was extended to assess the impact of back-and-forth mobility between the two countries. Simulations of the resulting metapopulation model show that the burden of the COVID-19 pandemic in Pakistan increases with increasing values of the average time residents of India spend in Pakistan, with daily mortality in Pakistan peaking in mid-August to mid-September of 2021. Under the respective baseline control scenarios, our simulations show that the back-and-forth mobility between India and Pakistan could delay the time-to-elimination of the COVID-19 pandemic in India and Pakistan to November 2022 and July 2022, respectively.
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In Appalachia, La Crosse virus (LACV) is a leading pediatric arbovirus and public health concern for children under 16 years. LACV is transmitted via the bite of an infected Aedes mosquito. Thus, it is imperative to understand the dynamics of the local vector population in order to assess risk and transmission. Using entomological data collected from Knox County, Tennessee in 2013, we formulate an environmentally-driven system of ordinary differential equations to model mosquito population dynamics over a single season. Further, we include infected compartments to represent LACV transmission within the mosquito population. Findings suggest that the model, with dependence on degree days and accumulated precipitation, can closely describe field data. This model confirms the need to include these environmental variables when planning control strategies.