A pinboard by
Bruce Pell

Visiting Assistant Professor, St. Olaf College


We forecast the trajectory of an infectious disease epidemic.

Mathematical models have proven to be a useful tool in understanding and predicting natural phenomena for centuries. Yet, besides significant increases in computing power, our efforts are constrained by the lack of detailed epidemic data about the transmission characteristics and theories that are required for pushing the frontier of understanding epidemics and how to control them. In addition, understanding the early growth of an infectious disease epidemic is crucial in assessing the potential disease burden inflicted upon the susceptible population.

The research I’m involved in uses mathematical models to investigate the early growth dynamics of epidemics. We then incorporate the validated concepts and mechanisms into more complex models that are used to estimate the final epidemic size, peak timing and other important epidemiological quantities. Lastly, once calibrated, these mathematical models can be used to see what protocols are most significant in controlling an epidemic.


Perspectives on model forecasts of the 2014-2015 Ebola epidemic in West Africa: lessons and the way forward.

Abstract: The unprecedented impact and modeling efforts associated with the 2014-2015 Ebola epidemic in West Africa provides a unique opportunity to document the performances and caveats of forecasting approaches used in near-real time for generating evidence and to guide policy. A number of international academic groups have developed and parameterized mathematical models of disease spread to forecast the trajectory of the outbreak. These modeling efforts often relied on limited epidemiological data to derive key transmission and severity parameters, which are needed to calibrate mechanistic models. Here, we provide a perspective on some of the challenges and lessons drawn from these efforts, focusing on (1) data availability and accuracy of early forecasts; (2) the ability of different models to capture the profile of early growth dynamics in local outbreaks and the importance of reactive behavior changes and case clustering; (3) challenges in forecasting the long-term epidemic impact very early in the outbreak; and (4) ways to move forward. We conclude that rapid availability of aggregated population-level data and detailed information on a subset of transmission chains is crucial to characterize transmission patterns, while ensemble-forecasting approaches could limit the uncertainty of any individual model. We believe that coordinated forecasting efforts, combined with rapid dissemination of disease predictions and underlying epidemiological data in shared online platforms, will be critical in optimizing the response to current and future infectious disease emergencies.

Pub.: 02 Mar '17, Pinned: 16 Jun '17

Modeling the Impact of Interventions on an Epidemic of Ebola in Sierra Leone and Liberia

Abstract: An Ebola outbreak of unparalleled size is currently affecting several countries in West Africa, and international efforts to control the outbreak are underway. However, the efficacy of these interventions, and their likely impact on an Ebola epidemic of this size, is unknown. Forecasting and simulation of these interventions may inform public health efforts. We use existing data from Liberia and Sierra Leone to parameterize a mathematical model of Ebola and use this model to forecast the progression of the epidemic, as well as the efficacy of several interventions, including increased contact tracing, improved infection control practices, the use of a hypothetical pharmaceutical intervention to improve survival in hospitalized patients. Model forecasts until Dec. 31, 2014 show an increasingly severe epidemic with no sign of having reached a peak. Modeling results suggest that increased contact tracing, improved infection control, or a combination of the two can have a substantial impact on the number of Ebola cases, but these interventions are not sufficient to halt the progress of the epidemic. The hypothetical pharmaceutical intervention, while impacting mortality, had a smaller effect on the forecasted trajectory of the epidemic. Near-term, practical interventions to address the ongoing Ebola epidemic may have a beneficial impact on public health, but they will not result in the immediate halting, or even obvious slowing of the epidemic. A long-term commitment of resources and support will be necessary to address the outbreak.

Pub.: 19 Sep '14, Pinned: 16 Jun '17

Characterizing the reproduction number of epidemics with early sub-exponential growth dynamics

Abstract: The reproduction number is a central parameter in epidemiology used to quantify the average number of secondary cases generated by a primary infectious individual during the early epidemic growth phase. Existing methods to estimate the reproduction number generally assume early exponential epidemic growth, but do not account for the possibility of early sub-exponential (i.e., polynomial) growth. Here, we introduce a novel method for estimating the reproduction number without making explicit assumptions about the early epidemic growth profile. We demonstrate our methods using both synthetic and real epidemic datasets. Our results indicate that the effective reproduction number for epidemics characterized by early sub-exponential growth exhibits a natural downward trend over time approaching unity, even in the absence of control interventions, or depletion of susceptibles. This pattern is in stark contrast with the invariant reproduction number predicted for epidemics with an initial exponential growth phase. Our findings provide a compelling argument for understanding the early extinction of some emerging disease outbreaks during the early ascending phase of sub-exponential growth. A reliable data-driven characterization of the early epidemic phase is crucial for estimating the reproduction number, forecasting disease dynamics, and guiding public health intervention strategies.

Pub.: 04 May '16, Pinned: 16 Jun '17

A generalized-growth model to characterize the early ascending phase of infectious disease outbreaks.

Abstract: A better characterization of the early growth dynamics of an epidemic is needed to dissect the important drivers of disease transmission, refine existing transmission models, and improve disease forecasts.We introduce a 2-parameter generalized-growth model to characterize the ascending phase of an outbreak and capture epidemic profiles ranging from sub-exponential to exponential growth. We test the model against empirical outbreak data representing a variety of viral pathogens in historic and contemporary populations, and provide simulations highlighting the importance of sub-exponential growth for forecasting purposes.We applied the generalized-growth model to 20 infectious disease outbreaks representing a range of transmission routes. We uncovered epidemic profiles ranging from very slow growth (p=0.14 for the Ebola outbreak in Bomi, Liberia (2014)) to near exponential (p>0.9 for the smallpox outbreak in Khulna (1972), and the 1918 pandemic influenza in San Francisco). The foot-and-mouth disease outbreak in Uruguay displayed a profile of slower growth while the growth pattern of the HIV/AIDS epidemic in Japan was approximately linear. The West African Ebola epidemic provided a unique opportunity to explore how growth profiles vary by geography; analysis of the largest district-level outbreaks revealed substantial growth variations (mean p=0.59, range: 0.14-0.97). The districts of Margibi in Liberia and Bombali and Bo in Sierra Leone had near-exponential growth, while the districts of Bomi in Liberia and Kenema in Sierra Leone displayed near constant incidences.Our findings reveal significant variation in epidemic growth patterns across different infectious disease outbreaks and highlights that sub-exponential growth is a common phenomenon, especially for pathogens that are not airborne. Sub-exponential growth profiles may result from heterogeneity in contact structures or risk groups, reactive behavior changes, or the early onset of interventions strategies, and consideration of "deceleration parameters" may be useful to refine existing mathematical transmission models and improve disease forecasts.

Pub.: 09 Jun '16, Pinned: 16 Jun '17

Using Phenomenological Models to Characterize Transmissibility and Forecast Patterns and Final Burden of Zika Epidemics.

Abstract: The World Health Organization declared the ongoing Zika virus (ZIKV) epidemic in the Americas a Public Health Emergency of International Concern on February 1, 2016. ZIKV disease in humans is characterized by a "dengue-like" syndrome including febrile illness and rash. However, ZIKV infection in early pregnancy has been associated with severe birth defects, including microcephaly and other developmental issues. Mechanistic models of disease transmission can be used to forecast trajectories and likely disease burden but are currently hampered by substantial uncertainty on the epidemiology of the disease (e.g., the role of asymptomatic transmission, generation interval, incubation period, and key drivers). When insight is limited, phenomenological models provide a starting point for estimation of key transmission parameters, such as the reproduction number, and forecasts of epidemic impact.We obtained daily counts of suspected Zika cases by date of symptoms onset from the Secretary of Health of Antioquia, Colombia during January-April 2016. We calibrated the generalized Richards model, a phenomenological model that accommodates a variety of early exponential and sub-exponential growth kinetics, against the early epidemic trajectory and generated predictions of epidemic size. The reproduction number was estimated by applying the renewal equation to incident cases simulated from the fitted generalized-growth model and assuming gamma or exponentially-distributed generation intervals derived from the literature. We estimated the reproduction number for an increasing duration of the epidemic growth phase.The reproduction number rapidly declined from 10.3 (95% CI: 8.3, 12.4) in the first disease generation to 2.2 (95% CI: 1.9, 2.8) in the second disease generation, assuming a gamma-distributed generation interval with the mean of 14 days and standard deviation of 2 days. The generalized-Richards model outperformed the logistic growth model and provided forecasts within 22% of the actual epidemic size based on an assessment 30 days into the epidemic, with the epidemic peaking on day 36.Phenomenological models represent promising tools to generate early forecasts of epidemic impact particularly in the context of substantial uncertainty in epidemiological parameters. Our findings underscore the need to treat the reproduction number as a dynamic quantity even during the early growth phase, and emphasize the sensitivity of reproduction number estimates to assumptions on the generation interval distribution.

Pub.: 02 Jul '16, Pinned: 16 Jun '17

Using phenomenological models for forecasting the 2015 Ebola challenge.

Abstract: The rising number of novel pathogens threatening the human population has motivated the application of mathematical modeling for forecasting the trajectory and size of epidemics.We summarize the real-time forecasting results of the logistic equation during the 2015 Ebola challenge focused on predicting synthetic data derived from a detailed individual-based model of Ebola transmission dynamics and control. We also carry out a post-challenge comparison of two simple phenomenological models. In particular, we systematically compare the logistic growth model and a recently introduced generalized Richards model (GRM) that captures a range of early epidemic growth profiles ranging from sub-exponential to exponential growth. Specifically, we assess the performance of each model for estimating the reproduction number, generate short-term forecasts of the epidemic trajectory, and predict the final epidemic size.During the challenge the logistic equation consistently underestimated the final epidemic size, peak timing and the number of cases at peak timing with an average mean absolute percentage error (MAPE) of 0.49, 0.36 and 0.40, respectively. Post-challenge, the GRM which has the flexibility to reproduce a range of epidemic growth profiles ranging from early sub-exponential to exponential growth dynamics outperformed the logistic growth model in ascertaining the final epidemic size as more incidence data was made available, while the logistic model underestimated the final epidemic even with an increasing amount of data of the evolving epidemic. Incidence forecasts provided by the generalized Richards model performed better across all scenarios and time points than the logistic growth model with mean RMS decreasing from 78.00 (logistic) to 60.80 (GRM). Both models provided reasonable predictions of the effective reproduction number, but the GRM slightly outperformed the logistic growth model with a MAPE of 0.08 compared to 0.10, averaged across all scenarios and time points.Our findings further support the consideration of transmission models that incorporate flexible early epidemic growth profiles in the forecasting toolkit. Such models are particularly useful for quickly evaluating a developing infectious disease outbreak using only case incidence time series of the early phase of an infectious disease outbreak.

Pub.: 04 Dec '16, Pinned: 16 Jun '17