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Lessler, J.

Publications and source records attributed to Lessler, J..

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Perfect Counterfactuals for Epidemic Simulations

Simulation studies are often used to predict the expected impact of control measures in infectious disease outbreaks. Typically, two independent sets of simulations are conducted, one with the intervetnion, and one without, and epidemic sizes (or some related metric) are compared to estimate the effect of the intervention. Since it is possible that controlled epidemics are larger than uncontrolled ones if there is substantial stochastic variation between epidemics, uncertainty intervals from this approach can include a negative effect even for an effective intervention. To more precisely estimate the number of cases an intervention will prevent within a single epidemic, here we develop a single world approach to matching simulations of controlled epidemics to their exact uncontrolled counterfac-tual. Our method borrows concepts from percolation approaches prune out possible epidemic histories and create potential epidemic graph that can be realized to create perfectly matched controlled and uncontrolled epidemics. We present an implementation of this method for a common class of compartmental models, and its application in a simple SIR model. Results illustrate how, at the cost of some computation time, this method substantially narrows confidence intervals and avoids non-sensical inferences.

epidemiology

Differential human mobility and local variation in human infection attack rate

Infectious disease transmission in animals is an inherently spatial process in which a hosts home location and their social mixing patterns are important, with the mixing of infectious individuals often different to that of susceptible individuals. Although incidence data for humans have traditionally been aggregated into low-resolution data sets, modern representative surveillance systems such as electronic hospital records generate high volume case data with precise home locations. Here, we use a high resolution gridded spatial transmission model of arbitrary resolution to investigate the theoretical relationship between population density, differential population movement and local variability in incidence. We show analytically that uniform local attack rate is only possible for individual pixels in the grid if susceptible and infectious individuals move in the same way. Using a population in Guangdong, China, for which a robust quantitative description of movement is available (a movement kernel), and a natural history consistent with pandemic influenza; we show that for the estimated kernel, local cumulative incidence is positively correlated with population density when susceptible individuals are more connected in space than infectious individuals. Conversely, when infectious individuals are more connected, local cumulative incidence is negatively correlated with population density. The amplitude of correlation is substantial for the estimated kernel. However, the strength and direction of correlation changes sign for other kernel parameter values. These results describe a precise relationship between the spatio-social mixing of infectious and susceptible individuals and local variability in attack rates, and suggest a plausible mechanism for the counter-intuitive scenario in which local incidence is lower on average in less dense populations. Also, these results suggest that if spatial transmission models are implemented at high resolution to investigate local disease dynamics, including micro-tuning of interventions, the underlying detailed assumptions about the mechanisms of transmission become more important than when similar studies are conducted at larger spatial scales.\n\nAuthor SummaryWe know that some places have higher rates of infectious disease than others. However, at the moment, we usually only measure these differences for large towns and cities. With modern data, such as those we can get from mobile phones, we can measure rates of infection at much smaller scales. In this paper, we used a computer simulation of an epidemic to propose ways that rates of incidence in small local areas might be related to population density. We found that if infectious people are better connected than non-infectious people, perhaps because they receive visitors, then, on average, higher density areas would have lower rates of infection. If infectious people were less connected than non-infectious people then higher density areas would have higher rates of infection. As data get more accurate, this type of analysis will allow us to propose and test ways to optimize interventions such as the delivery of vaccines and antivirals during a pandemic.

epidemiology

Micro-hotspots of Risk in Urban Cholera Epidemics

Targeted interventions have been delivered to neighbors of cholera cases in epidemic responses in Haiti and Africa despite little evidence supporting impact. Using data from urban epidemics in Chad and D.R. Congo we estimate the size and extent of spatiotemporal zones of increased cholera risk around cases. In both cities, we found zones of increased risk of at least 200-meters during the 5-days immediately following case presentation to a clinic. Risk was highest for those living closest to cases and diminished in time and space similarly across settings. These results provide a rational basis for targeting interventions, if delivered rapidly.

epidemiology

Simulations for Designing and Interpreting Intervention Trials in Infectious Diseases

Here we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly in emerging infectious disease, that more accurately reflects the dynamics of the transmission process. Interventions in infectious diseases can have indirect effects on those not receiving the intervention as well as direct effects on those receiving the intervention. Combinations of interventions can have complex interactions at the population level. These often cannot be adequately addressed with standard study designs and analytic methods. Simulations can help to accurately represent transmission dynamics in an increasingly complex world which is critical for proper trial design and interpretation. Some ethical aspects of a trial can also be quantified using simulations. After a trial has been conducted, simulations can be used to explore possible explanations for the observed effects. A great deal is to be gained through a multidisciplinary approach that builds collaborations among experts in infectious disease dynamics, epidemiology, statistical science, economics, simulation methods and the conduct of clinical trials.

epidemiology

Preliminary results of models to predict areas in the Americas with increased likelihood of Zika virus transmission in 2017.

Numerous Zika virus vaccines are being developed. However, identifying sites to evaluate the efficacy of a Zika virus vaccine is challenging due to the general decrease in Zika virus activity. We compare results from three different modeling approaches to estimate areas that may have increased relative risk of Zika virus transmission during 2017. The analysis focused on eight priority countries (i.e., Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru). The models projected low incidence rates during 2017 for all locations in the priority countries but identified several subnational areas that may have increased relative risk of Zika virus transmission in 2017. Given the projected low incidence of disease, the total number of participants, number of study sites, or duration of study follow-up may need to be increased to meet the efficacy study endpoints.

epidemiology

Quantifying the Risk and Cost of Active Monitoring for Infectious Diseases

During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and bioterror threats (e.g., smallpox), actively monitoring potentially infected individuals aims to limit disease transmission and morbidity. Guidance issued by CDC on active monitoring was a cornerstone of its response to the West Africa Ebola outbreak. There are limited data on how to balance the costs and performance of this important public health activity. We present a framework that estimates the risks and costs of specific durations of active monitoring for pathogens of significant public health concern. We analyze data from New York Citys Ebola active monitoring program over a 16-month period in 2014-2016. For monitored individuals, we identified unique durations of active monitoring that minimize expected costs for those at \"low (but not zero) risk\" and \"some or high risk\": 21 and 31 days, respectively. Extending our analysis to smallpox and MERS-CoV, we found that the optimal length of active monitoring relative to the median incubation period was reduced compared to Ebola due to less variable incubation periods. Active monitoring can save lives but is expensive. Resources can be most effectively allocated by using exposure-risk categories to modify the duration or intensity of active monitoring.

epidemiology