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  1. Kolawole, Olatunji Matthew (Ed.)

    Persons living with human immunodeficiency virus (HIV) have a disproportionately higher burden of human papillomavirus infection (HPV)-related cancers. Causal factors include both behavioral and biological. While pharmaceutical and care support interventions help address biological risk of coinfection, as social conditions are common drivers of behaviors, structural interventions are key part of behavioral interventions. Our objective is to develop a joint HIV-HPV model to evaluate the contribution of each factor, to subsequently inform intervention analyses. While compartmental modeling is sufficient for faster spreading HPV, network modeling is suitable for slower spreading HIV. However, using network modeling for jointly modeling HIV and HPV can generate computational complexities given their vastly varying disease epidemiology and disease burden across sub-population groups. We applied a recently developed mixed agent-based compartmental (MAC) simulation technique, which simulates persons with at least one slower spreading disease and their immediate contacts as agents in a network, and all other persons including those with faster spreading diseases in a compartmental model, with an evolving contact network algorithm maintaining the dynamics between the two models. We simulated HIV and HPV in the U.S. among heterosexual female, heterosexual male, and men who have sex with men (men only and men and women) (MSM), sub-populations that mix but have varying HIV burden, and cervical cancer among women. We conducted numerical analyses to evaluate the contribution of behavioral and biological factors to risk of cervical cancer among women with HIV. The model outputs for HIV, HPV, and cervical cancer compared well with surveillance estimates. Model estimates for relative prevalence of HPV (1.67 times) and relative incidence of cervical cancer (3.6 times), among women with HIV compared to women without, were also similar to that reported in observational studies in the literature. The fraction attributed to biological factors ranged from 22–38% for increased HPV prevalence and 80% for increased cervical cancer incidence, the remaining attributed to behavioral. The attribution of both behavioral and biological factors to increased HPV prevalence and cervical cancer incidence suggest the need for behavioral, structural, and pharmaceutical interventions. Validity of model results related to both individual and joint disease metrics serves as proof-of-concept of the MAC simulation technique. Understanding the contribution of behavioral and biological factors of risk helps inform interventions. Future work can expand the model to simulate sexual and care behaviors as functions of social conditions to jointly evaluate behavioral, structural, and pharmaceutical interventions for HIV and cervical cancer prevention.

     
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    Free, publicly-accessible full text available November 3, 2024
  2. In the absence of pharmaceutical interventions, social distancing and lockdown have been key options for controlling new or reemerging respiratory infectious disease outbreaks. The timely implementation of these interventions is vital for effectively controlling and safeguarding the economy.Motivated by the COVID-19 pandemic, we evaluated whether, when, and to what level lockdowns are necessary to minimize epidemic and economic burdens of new disease outbreaks. We formulated the question as a sequential decision-making Markov Decision Process and solved it using deep Q-network algorithm. We evaluated the question under two objective functions: a 2-objective function to minimize economic burden and hospital capacity violations, suitable for diseases with severe health risks but with minimal death, and a 3-objective function that additionally minimizes the number of deaths, suitable for diseases that have high risk of mortality.A key feature of the model is that we evaluated the above questions in the context of two-geographical jurisdictions that interact through travel but make autonomous and independent decisions, evaluating under cross-jurisdictional cooperation and non-cooperation. In the 2-objective function under cross-jurisdictional cooperation, the optimal policy was to aim for shutdowns at 50 and 25% per day. Though this policy avoided hospital capacity violations, the shutdowns extended until a large proportion of the population reached herd immunity. Delays in initiating this optimal policy or non-cooperation from an outside jurisdiction required shutdowns at a higher level of 75% per day, thus adding to economic burdens. In the 3-objective function, the optimal policy under cross-jurisdictional cooperation was to aim for shutdowns of up to 75% per day to prevent deaths by reducing infected cases. This optimal policy continued for the entire duration of the simulation, suggesting that, until pharmaceutical interventions such as treatment or vaccines become available, contact reductions through physical distancing would be necessary to minimize deaths. Deviating from this policy increased the number of shutdowns and led to several deaths.In summary, we present a decision-analytic methodology for identifying optimal lockdown strategy under the context of interactions between jurisdictions that make autonomous and independent decisions. The numerical analysis outcomes are intuitive and, as expected, serve as proof of the feasibility of such a model. Our sensitivity analysis demonstrates that the optimal policy exhibits robustness to minor alterations in the transmission rate, yet shows sensitivity to more substantial deviations. This finding underscores the dynamic nature of epidemic parameters, thereby emphasizing the necessity for models trained across a diverse range of values to ensure effective policy-making. 
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    Free, publicly-accessible full text available June 29, 2024
  3. Eksin, Ceyhun (Ed.)
    We simulated epidemic projections of a potential COVID-19 outbreak in a residential university population in the United States under varying combinations of asymptomatic tests (5% to 33% per day), transmission rates (2.5% to 14%), and contact rates (1 to 25), to identify the contact rate threshold that, if exceeded, would lead to exponential growth in infections. Using this, we extracted contact rate thresholds among non-essential workers, population size thresholds in the absence of vaccines, and vaccine coverage thresholds. We further stream-lined our analyses to transmission rates of 5 to 8%, to correspond to the reported levels of face-mask-use/physical-distancing during the 2020 pandemic. Our results suggest that, in the absence of vaccines, testing alone without reducing population size would not be sufficient to control an outbreak. If the population size is lowered to 34% (or 44%) of the actual population size to maintain contact rates at 4 (or 7) among non-essential workers, mass tests at 25% (or 33%) per day would help control an outbreak. With the availability of vaccines, the campus can be kept at full population provided at least 95% are vaccinated. If vaccines are partially available such that the coverage is lower than 95%, keeping at full population would require asymptomatic testing, either mass tests at 25% per day if vaccine coverage is at 63–79%, or mass tests at 33% per day if vaccine coverage is at 53–68%. If vaccine coverage is below 53%, to control an outbreak, in addition to mass tests at 33% per day, it would also require lowering the population size to 90%, 75%, and 60%, if vaccine coverage is at 38–53%, 23–38%, and below 23%, respectively. Threshold estimates from this study, interpolated over the range of transmission rates, can collectively help inform campus level preparedness plans for adoption of face mask/physical-distancing, testing, remote instructions, and personnel scheduling, during non-availability or partial-availability of vaccines, in the event of SARS-Cov2-type disease outbreaks. 
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