Retrospective Parameter Estimation and Forecast of Respiratory Syncytial Virus in the United States

Recent studies have shown that systems combining mathematical modeling and Bayesian inference methods can be used to generate real-time forecasts of future infectious disease incidence. Here we develop such a system to study and forecast respiratory syncytial virus (RSV). RSV is the most common cause of acute lower respiratory infection and bronchiolitis. Advanced warning of the epidemic timing and volume of RSV patient surges has the potential to reduce well-documented delays of treatment in emergency departments. We use a susceptible-infectious-recovered (SIR) model in conjunction with an ensemble adjustment Kalman filter (EAKF) and ten years of regional U.S. specimen data provided by the Centers for Disease Control and Prevention. The data and EAKF are used to optimize the SIR model and i) estimate critical epidemiological parameters over the course of each outbreak and ii) generate retrospective forecasts. The basic reproductive number, R0, is estimated at 3.0 (standard deviation 0.6) across all seasons and locations. The peak magnitude of RSV outbreaks is forecast with nearly 70% accuracy (i.e. nearly 70% of forecasts within 25% of the actual peak), four weeks before the predicted peak. This work represents a first step in the development of a real-time RSV prediction system

Comparison of Filtering Methods for the Modeling and Retrospective Forecasting of Influenza Epidemics

A variety of filtering methods enable the recursive estimation of system state variables and inference of model parameters. These methods have found application in a range of disciplines and settings, including engineering design and forecasting, and, over the last two decades, have been applied to infectious disease epidemiology. For any system of interest, the ideal filter depends on the nonlinearity and complexity of the model to which it is applied, the quality and abundance of observations being entrained, and the ultimate application (e.g. forecast, parameter estimation, etc.). Here, we compare the performance of six state-of-the-art filter methods when used to model and forecast influenza activity. Three particle filters—a basic particle filter (PF) with resampling and regularization, maximum likelihood estimation via iterated filtering (MIF), and particle Markov chain Monte Carlo (pMCMC)—and three ensemble filters—the ensemble Kalman filter (EnKF), the ensemble adjustment Kalman filter (EAKF), and the rank histogram filter (RHF)—were used in conjunction with a humidity-forced susceptible-infectious-recovered-susceptible (SIRS) model and weekly estimates of influenza incidence. The modeling frameworks, first validated with synthetic influenza epidemic data, were then applied to fit and retrospectively forecast the historical incidence time series of seven influenza epidemics during 2003–2012, for 115 cities in the United States. Results suggest that when using the SIRS model the ensemble filters and the basic PF are more capable of faithfully recreating historical influenza incidence time series, while the MIF and pMCMC do not perform as well for multimodal outbreaks. For forecast of the week with the highest influenza activity, the accuracies of the six model-filter frameworks are comparable; the three particle filters perform slightly better predicting peaks 1–5 weeks in the future; the ensemble filters are more accurate predicting peaks in the past

The 1918 influenza pandemic in New York City: age-specific timing, mortality, and transmission dynamics

Background: The 1918 influenza pandemic caused disproportionately high mortality among certain age groups. The mechanisms underlying these differences are not fully understood. Objectives: To explore the dynamics of the 1918 pandemic and to identify potential age-specific transmission patterns. Methods: We examined 1915–1923 daily mortality data in New York City (NYC) and estimated the outbreak duration and initial effective reproductive number (Re) for each 1-year age cohort. Results: Four pandemic waves occurred from February 1918 to April 1920. The fractional mortality increase (i.e. ratio of excess mortality to baseline mortality) was highest among teenagers during the first wave. This peak shifted to 25- to 29-year-olds in subsequent waves. The distribution of age-specific mortality during the last three waves was strongly correlated (r = 0·94 and 0·86). With each wave, the pandemic appeared to spread with a comparable early growth rate but then attenuate with varying rates. For the entire population, Re estimates made assuming 2-day serial interval were 1·74 (1·27), 1·74 (1·43), 1·66 (1·25), and 1·86 (1·37), respectively, during the first week (first 3 weeks) of each wave. Using age-specific mortality, the average Re estimates over the first week of each wave were 1·62 (95% CI: 1·55–1·68), 1·68 (1·65–1·72), 1·67 (1·61–1·73), and 1·69 (1·63–1·74), respectively; Re was not significantly different either among age cohorts or between waves. Conclusions: The pandemic generally caused higher mortality among young adults and might have spread mainly among school-aged children during the first wave. We propose mechanisms to explain the timing and transmission dynamics of the four NYC pandemic waves

Forecasting Influenza Outbreaks in Boroughs and Neighborhoods of New York City

The ideal spatial scale, or granularity, at which infectious disease incidence should be monitored and forecast has been little explored. By identifying the optimal granularity for a given disease and host population, and matching surveillance and prediction efforts to this scale, response to emergent and recurrent outbreaks can be improved. Here we explore how granularity and representation of spatial structure affect influenza forecast accuracy within New York City. We develop network models at the borough and neighborhood levels, and use them in conjunction with surveillance data and a data assimilation method to forecast influenza activity. These forecasts are compared to an alternate system that predicts influenza for each borough or neighborhood in isolation. At the borough scale, influenza epidemics are highly synchronous despite substantial differences in intensity, and inclusion of network connectivity among boroughs generally improves forecast accuracy. At the neighborhood scale, we observe much greater spatial heterogeneity among influenza outbreaks including substantial differences in local outbreak timing and structure; however, inclusion of the network model structure generally degrades forecast accuracy. One notable exception is that local outbreak onset, particularly when signal is modest, is better predicted with the network model. These findings suggest that observation and forecast at sub-municipal scales within New York City provides richer, more discriminant information on influenza incidence, particularly at the neighborhood scale where greater heterogeneity exists, and that the spatial spread of influenza among localities can be forecast

Local environmental and meteorological conditions influencing the invasive mosquito Ae. albopictus and arbovirus transmission risk in New York City

Ae. albopictus, an invasive mosquito vector now endemic to much of the northeastern US, is a significant public health threat both as a nuisance biter and vector of disease (e.g. chikungunya virus). Here, we aim to quantify the relationships between local environmental and meteorological conditions and the abundance of Ae. albopictus mosquitoes in New York City. Using statistical modeling, we create a fine-scale spatially explicit risk map of Ae. albopictus abundance and validate the accuracy of spatiotemporal model predictions using observational data from 2016. We find that the spatial variability of annual Ae. albopictus abundance is greater than its temporal variability in New York City but that both local environmental and meteorological conditions are associated with Ae. albopictus numbers. Specifically, key land use characteristics, including open spaces, residential areas, and vacant lots, and spring and early summer meteorological conditions are associated with annual Ae. albopictus abundance. In addition, we investigate the distribution of imported chikungunya cases during 2014 and use these data to delineate areas with the highest rates of arboviral importation. We show that the spatial distribution of imported arboviral cases has been mostly discordant with mosquito production and thus, to date, has provided a check on local arboviral transmission in New York City. We do, however, find concordant areas where high Ae. albopictus abundance and chikungunya importation co-occur. Public health and vector control officials should prioritize control efforts to these areas and thus more cost effectively reduce the risk of local arboviral transmission. The methods applied here can be used to monitor and identify areas of risk for other imported vector-borne diseases

Investigating associations between COVID-19 mortality and population-level health and socioeconomic indicators in the United States: A modeling study

Background: With the availability of multiple Coronavirus Disease 2019 (COVID-19) vaccines and the predicted shortages in supply for the near future, it is necessary to allocate vaccines in a manner that minimizes severe outcomes, particularly deaths. To date, vaccination strategies in the United States have focused on individual characteristics such as age and occupation. Here, we assess the utility of population-level health and socioeconomic indicators as additional criteria for geographical allocation of vaccines. Methods and findings: County-level estimates of 14 indicators associated with COVID-19 mortality were extracted from public data sources. Effect estimates of the individual indicators were calculated with univariate models. Presence of spatial autocorrelation was established using Moran's I statistic. Spatial simultaneous autoregressive (SAR) models that account for spatial autocorrelation in response and predictors were used to assess (i) the proportion of variance in county-level COVID-19 mortality that can explained by identified health/socioeconomic indicators (R2); and (ii) effect estimates of each predictor. Adjusting for case rates, the selected indicators individually explain 24%-29% of the variability in mortality. Prevalence of chronic kidney disease and proportion of population residing in nursing homes have the highest R2. Mortality is estimated to increase by 43 per thousand residents (95% CI: 37-49; p < 0.001) with a 1% increase in the prevalence of chronic kidney disease and by 39 deaths per thousand (95% CI: 34-44; p < 0.001) with 1% increase in population living in nursing homes. SAR models using multiple health/socioeconomic indicators explain 43% of the variability in COVID-19 mortality in US counties, adjusting for case rates. R2 was found to be not sensitive to the choice of SAR model form. Study limitations include the use of mortality rates that are not age standardized, a spatial adjacency matrix that does not capture human flows among counties, and insufficient accounting for interaction among predictors. Conclusions: Significant spatial autocorrelation exists in COVID-19 mortality in the US, and population health/socioeconomic indicators account for a considerable variability in county-level mortality. In the context of vaccine rollout in the US and globally, national and subnational estimates of burden of disease could inform optimal geographical allocation of vaccines

Near-term forecasts of influenza-like illness: An evaluation of autoregressive time series approaches

Seasonal influenza in the United States is estimated to cause 9-35 million illnesses annually, with resultant economic burden amounting to $47-$150 billion. Reliable real-time forecasts of influenza can help public health agencies better manage these outbreaks. Here, we investigate the feasibility of three autoregressive methods for near-term forecasts: an Autoregressive Integrated Moving Average (ARIMA) model with time-varying order; an ARIMA model fit to seasonally adjusted incidence rates (ARIMA-STL); and a feed-forward autoregressive artificial neural network with a single hidden layer (AR-NN). We generated retrospective forecasts for influenza incidence one to four weeks in the future at US National and 10 regions in the US during 5 influenza seasons. We compared the relative accuracy of the point and probabilistic forecasts of the three models with respect to each other and in relation to two large external validation sets that each comprise at least 20 other models. Both the probabilistic and point forecasts of AR-NN were found to be more accurate than those of the other two models overall. An additional sub-analysis found that the three models benefitted considerably from the use of search trends based 'nowcast' as a proxy for surveillance data, and these three models with use of nowcasts were found to be the highest ranked models in both validation datasets. When the nowcasts were withheld, the three models remained competitive relative to models in the validation sets. The difference in accuracy among the three models, and relative to models of the validation sets, was found to be largely statistically significant. Our results suggest that autoregressive models even when not equipped to capture transmission dynamics can provide reasonably accurate near-term forecasts for influenza. Existing support in open-source libraries make them suitable non-naïve baselines for model comparison studies and for operational forecasts in resource constrained settings where more sophisticated methods may not be feasible

Reappraising the utility of Google Flu Trends

Estimation of influenza-like illness (ILI) using search trends activity was intended to supplement traditional surveillance systems, and was a motivation behind the development of Google Flu Trends (GFT). However, several studies have previously reported large errors in GFT estimates of ILI in the US. Following recent release of time-stamped surveillance data, which better reflects real-time operational scenarios, we reanalyzed GFT errors. Using three data sources—GFT: an archive of weekly ILI estimates from Google Flu Trends; ILIf: fully-observed ILI rates from ILINet; and, ILIp: ILI rates available in real-time based on partial reporting—five influenza seasons were analyzed and mean square errors (MSE) of GFT and ILIp as estimates of ILIf were computed. To correct GFT errors, a random forest regression model was built with ILI and GFT rates from the previous three weeks as predictors. An overall reduction in error of 44% was observed and the errors of the corrected GFT are lower than those of ILIp. An 80% reduction in error during 2012/13, when GFT had large errors, shows that extreme failures of GFT could have been avoided. Using autoregressive integrated moving average (ARIMA) models, one- to four-week ahead forecasts were generated with two separate data streams: ILIp alone, and with both ILIp and corrected GFT. At all forecast targets and seasons, and for all but two regions, inclusion of GFT lowered MSE. Results from two alternative error measures, mean absolute error and mean absolute proportional error, were largely consistent with results from MSE. Taken together these findings provide an error profile of GFT in the US, establish strong evidence for the adoption of search trends based 'nowcasts' in influenza forecast systems, and encourage reevaluation of the utility of this data source in diverse domains

Subregional Nowcasts of Seasonal Influenza Using Search Trends

Background: Limiting the adverse effects of seasonal influenza outbreaks at state or city level requires close monitoring of localized outbreaks and reliable forecasts of their progression. Whereas forecasting models for influenza or influenza-like illness (ILI) are becoming increasingly available, their applicability to localized outbreaks is limited by the nonavailability of real-time observations of the current outbreak state at local scales. Surveillance data collected by various health departments are widely accepted as the reference standard for estimating the state of outbreaks, and in the absence of surveillance data, nowcast proxies built using Web-based activities such as search engine queries, tweets, and access of health-related webpages can be useful. Nowcast estimates of state and municipal ILI were previously published by Google Flu Trends (GFT); however, validations of these estimates were seldom reported. Objective: The aim of this study was to develop and validate models to nowcast ILI at subregional geographic scales. Methods: We built nowcast models based on autoregressive (autoregressive integrated moving average; ARIMA) and supervised regression methods (Random forests) at the US state level using regional weighted ILI and Web-based search activity derived from Google's Extended Trends application programming interface. We validated the performance of these methods using actual surveillance data for the 50 states across six seasons. We also built state-level nowcast models using state-level estimates of ILI and compared the accuracy of these estimates with the estimates of the regional models extrapolated to the state level and with the nowcast estimates published by GFT. Results: Models built using regional ILI extrapolated to state level had a median correlation of 0.84 (interquartile range: 0.74-0.91) and a median root mean square error (RMSE) of 1.01 (IQR: 0.74-1.50), with noticeable variability across seasons and by state population size. Model forms that hypothesize the availability of timely state-level surveillance data show significantly lower errors of 0.83 (0.55-0.23). Compared with GFT, the latter model forms have lower errors but also lower correlation. Conclusions: These results suggest that the proposed methods may be an alternative to the discontinued GFT and that further improvements in the quality of subregional nowcasts may require increased access to more finely resolved surveillance data

Hydrometeorology and flood pulse dynamics drive diarrheal disease outbreaks and increase vulnerability to climate change in surface-water-dependent populations: A retrospective analysis

Background The impacts of climate change on surface water, waterborne disease, and human health remain a growing area of concern, particularly in Africa, where diarrheal disease is one of the most important health threats to children under 5 years of age. Little is known about the role of surface water and annual flood dynamics (flood pulse) on waterborne disease and human health nor about the expected impact of climate change on surface-water-dependent populations. Methods and findings Using the Chobe River in northern Botswana, a flood pulse river—floodplain system, we applied multimodel inference approaches assessing the influence of river height, water quality (bimonthly counts of Escherichia coli and total suspended solids [TSS], 2011–2017), and meteorological variability on weekly diarrheal case reports among children under 5 presenting to health facilities (n = 10 health facilities, January 2007–June 2017). We assessed diarrheal cases by clinical characteristics and season across age groups using monthly outpatient data (January 1998–June 2017). A strong seasonal pattern was identified, with 2 outbreaks occurring regularly in the wet and dry seasons. The timing of outbreaks diverged from that at the level of the country, where surface water is largely absent. Across age groups, the number of diarrheal cases was greater, on average, during the dry season. Demographic and clinical characteristics varied by season, underscoring the importance of environmental drivers. In the wet season, rainfall (8-week lag) had a significant influence on under-5 diarrhea, with a 10-mm increase in rainfall associated with an estimated 6.5% rise in the number of cases. Rainfall, minimum temperature, and river height were predictive of E. coli concentration, and increases in E. coli in the river were positively associated with diarrheal cases. In the dry season, river height (1-week lag) and maximum temperature (1- and 4-week lag) were significantly associated with diarrheal cases. During this period, a 1-meter drop in river height corresponded to an estimated 16.7% and 16.1% increase in reported diarrhea with a 1- and 4-week lag, respectively. In this region, as floodwaters receded from the surrounding floodplains, TSS levels increased and were positively associated with diarrheal cases (0- and 3-week lag). Populations living in this region utilized improved water sources, suggesting that hydrological variability and rapid water quality shifts in surface waters may compromise water treatment processes. Limitations include the potential influence of health beliefs and health seeking behaviors on data obtained through passive surveillance. Conclusions In flood pulse river—floodplain systems, hydrology and water quality dynamics can be highly variable, potentially impacting conventional water treatment facilities and the production of safe drinking water. In Southern Africa, climate change is predicted to intensify hydrological variability and the frequency of extreme weather events, amplifying the public health threat of waterborne disease in surface-water-dependent populations. Water sector development should be prioritized with urgency, incorporating technologies that are robust to local environmental conditions and expected climate-driven impacts. In populations with high HIV burdens, expansion of diarrheal disease surveillance and intervention strategies may also be needed. As annual flood pulse processes are predominantly influenced by climate controls in distant regions, country-level data may be inadequate to refine predictions of climate—health interactions in these systems