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Kim, Jaehee (Ed.)Bacteriophage (phage) cocktail therapy has been relied upon more and more to treat antibiotic-resistant infections. Understanding of the complex kinetics between phages, target bacteria, and the emergence of phage resistance remain hurdles to successful clinical outcomes. Building upon previous mathematical concepts, we develop biologically-motivated nonlinear ordinary differential equation models to explore single, cocktail, and sequential phage treatment modalities. While the optimal pairwise phage treatment strategy was the double simultaneous administration of two highly potent and asymmetrically binding phage strains, it appears unable to prevent the evolution of resistance. This treatment regimen did have a greater lysis efficiency, promoted higher phage population sizes, reduced bacterial density the most, and suppressed the evolution of resistance the longest compared to all other treatments strategies tested. Conversely, the combination of phages with polar potencies allows the more efficiently replicating phages to monopolize susceptible host cells, thereby quickly negating the intended compounding effect of cocktails. Together, we demonstrate that a biologically-motivated modeling-based framework can be leveraged to quantify the effects of each phage’s properties to more precisely predict treatment responses.more » « lessFree, publicly-accessible full text available November 5, 2025
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We propose a modified population-based susceptible-exposed-infectious-recovered (SEIR) compartmental model for a retrospective study of the COVID-19 transmission dynamics in India during the first wave. We extend the conventional SEIR methodology to account for the complexities of COVID-19 infection, its multiple symptoms, and transmission pathways. In particular, we consider a time-dependent transmission rate to account for governmental controls (e.g., national lockdown) and individual behavioral factors (e.g., social distancing, mask-wearing, personal hygiene, and self-quarantine). An essential feature of COVID-19 that is different from other infections is the significant contribution of asymptomatic and pre-symptomatic cases to the transmission cycle. A Bayesian method is used to calibrate the proposed SEIR model using publicly available data (daily new tested positive, death, and recovery cases) from several Indian states. The uncertainty of the parameters is naturally expressed as the posterior probability distribution. The calibrated model is used to estimate undetected cases and study different initial intervention policies, screening rates, and public behavior factors, that can potentially strike a balance between disease control and the humanitarian crisis caused by a sudden strict lockdown.more » « less
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The ongoing COVID-19 pandemic has created major public health and socio-economic challenges across the United States. Among them are challenges to the educational system where college administrators are struggling with the questions of how to mitigate the risk and spread of diseases on their college campus. To help address this challenge, we developed a flexible computational framework to model the spread and control of COVID-19 on a residential college campus. The modeling framework accounts for heterogeneity in social interactions, activities, environmental and behavioral risk factors, disease progression, and control interventions. The contribution of mitigation strategies to disease transmission was explored without and with interventions such as vaccination, quarantine of symptomatic cases, and testing. We show that even with high vaccination coverage (90%) college campuses may still experience sizable outbreaks. The size of the outbreaks varies with the underlying environmental and socio-behavioral risk factors. Complementing vaccination with quarantine and mass testing was shown to be paramount for preventing or mitigating outbreaks. Though our quantitative results are likely provisional on our model assumptions, sensitivity analysis confirms the robustness of their qualitative nature.more » « less
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null (Ed.)Development of strategies for mitigating the severity of COVID-19 is now a top public health priority. We sought to assess strategies for mitigating the COVID-19 outbreak in a hospital setting via the use of non-pharmaceutical interventions. We developed an individual-based model for COVID-19 transmission in a hospital setting. We calibrated the model using data of a COVID-19 outbreak in a hospital unit in Wuhan. The calibrated model was used to simulate different intervention scenarios and estimate the impact of different interventions on outbreak size and workday loss. The use of high-efficacy facial masks was shown to be able to reduce infection cases and workday loss by 80% (90% credible interval (CrI): 73.1–85.7%) and 87% (CrI: 80.0–92.5%), respectively. The use of social distancing alone, through reduced contacts between healthcare workers, had a marginal impact on the outbreak. Our results also indicated that a quarantine policy should be coupled with other interventions to achieve its effect. The effectiveness of all these interventions was shown to increase with their early implementation. Our analysis shows that a COVID-19 outbreak in a hospital's non-COVID-19 unit can be controlled or mitigated by the use of existing non-pharmaceutical measures.more » « less
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