Strategic testing approaches for targeted disease monitoring can be used to inform pandemic decision-making.

More than 1.6 million Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) tests were administered daily in the United States at the peak of the epidemic, with a significant focus on individual treatment. Here, we show that objective-driven, strategic sampling designs and analyses can maximize information gain at the population level, which is necessary to increase situational awareness and predict, prepare for, and respond to a pandemic, while also continuing to inform individual treatment. By focusing on specific objectives such as individual treatment or disease prediction and control (e.g., via the collection of population-level statistics to inform lockdown measures or vaccine rollout) and drawing from the literature on capture-recapture methods to deal with nonrandom sampling and testing errors, we illustrate how public health objectives can be achieved even with limited test availability when testing programs are designed a priori to meet those objectives.

Quantifying spatio-temporal variation of invasion spread.

- The spread of invasive species can have far-reaching environmental and ecological consequences. Understanding invasion spread patterns and the underlying process driving invasions are key to predicting and managing invasions. - We combine a set of statistical methods in a novel way to characterize local spread properties and demonstrate their application using simulated and historical data on invasive insects. Our method uses a Gaussian process fit to the surface of waiting times to invasion in order to characterize the vector field of spread. - Using this method, we estimate with statistical uncertainties the speed and direction of spread at each location. Simulations from a stratified diffusion model verify the accuracy of our method. - We show how we may link local rates of spread to environmental covariates for two case studies: the spread of the gypsy moth ( Lymantria dispar), and hemlock woolly adelgid ( Adelges tsugae) in North America. We provide an R-package that automates the calculations for any spatially referenced waiting time data.

An attraction-repulsion point process model for respiratory syncytial virus infections.

How is the progression of a virus influenced by properties intrinsic to individual cells? We address this question by studying the susceptibility of cells infected with two strains of the human respiratory syncytial virus (RSV-A and RSV-B) in an in vitro experiment. Spatial patterns of infected cells give us insight into how local conditions influence susceptibility to the virus. We observe a complicated attraction and repulsion behavior, a tendency for infected cells to lump together or remain apart. We develop a new spatial point process model to describe this behavior. Inference on spatial point processes is difficult because the likelihood functions of these models contain intractable normalizing constants; we adapt an MCMC algorithm called double Metropolis-Hastings to overcome this computational challenge. Our methods are computationally efficient even for large point patterns consisting of over 10,000 points. We illustrate the application of our model and inferential approach to simulated data examples and fit our model to various RSV experiments. Because our model parameters are easy to interpret, we are able to draw meaningful scientific conclusions from the fitted models.

Spatial distribution and determinants of childhood vaccination refusal in the United States.

Parental refusal and delay of childhood vaccination has increased in recent years in the United States. This phenomenon challenges maintenance of herd immunity and increases the risk of outbreaks of vaccine-preventable diseases. We examine US county-level vaccine refusal for patients under five years of age collected during the period 2012-2015 from an administrative healthcare dataset. We model these data with a Bayesian zero-inflated negative binomial regression model to capture social and political processes that are associated with vaccine refusal, as well as factors that affect our measurement of vaccine refusal. Our work highlights fine-scale socio-demographic characteristics associated with vaccine refusal nationally, finds that spatial clustering in refusal can be explained by such factors, and has the potential to aid in the development of targeted public health strategies for optimizing vaccine uptake.

Modeling the Social and Spatial Proximity of Crime: Domestic and Sexual Violence Across Neighborhoods.

OBJECTIVES: Our goal is to understand the social dynamics affecting domestic and sexual violence in urban areas by investigating the role of connections between area nodes, or communities. We use innovative methods adapted from spatial statistics to investigate the importance of social proximity measured based on connectedness pathways between area nodes. In doing so, we seek to extend the standard treatment in the neighborhoods and crime literature of areas like census blocks as independent analytical units or as interdependent primarily due to geographic proximity. METHODS: In this paper, we develop techniques to incorporate two types of proximity, geographic proximity and commuting proximity in spatial generalized linear mixed models (SGLMM) in order to estimate domestic and sexual violence in Detroit, Michigan and Arlington County, Virginia. Analyses are based on three types of CAR models (the Besag, York, and Mollié (BYM), Leroux, and the sparse SGLMM models) and two types of SAR models (the spatial lag and spatial error models) to examine how results vary with different model assumptions. We use data from local and federal sources such as the Police Data Initiative and American Community Survey. RESULTS: Analyses show that incorporating information on commuting ties, a non-spatially bounded form of social proximity, to spatial models contributes to better deviance information criteria (DIC) scores (a metric which explicitly accounts for model fit and complexity) in Arlington for sexual and domestic crime as well as overall crime. In Detroit, the fit is improved only for overall crime. The distinctions in model fit are less pronounced when using cross-validated mean absolute error (MAE) as a comparison criteria. CONCLUSION: Overall, the results indicate variations across crime type, urban contexts, and modeling approaches. Nonetheless, in important contexts, commuting ties among neighborhoods are observed to greatly improve our understanding of urban crime. If such ties contribute to the transfer of norms, social support, resources, and behaviors between places, they may then transfer also the effects of crime prevention efforts.

Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants.

Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections.

An ensemble approach to predicting the impact of vaccination on rotavirus disease in Niger.

Recently developed vaccines provide a new way of controlling rotavirus in sub-Saharan Africa. Models for the transmission dynamics of rotavirus are critical both for estimating current burden from imperfect surveillance and for assessing potential effects of vaccine intervention strategies. We examine rotavirus infection in the Maradi area in southern Niger using hospital surveillance data provided by Epicentre collected over two years. Additionally, a cluster survey of households in the region allows us to estimate the proportion of children with diarrhea who consulted at a health structure. Model fit and future projections are necessarily particular to a given model; thus, where there are competing models for the underlying epidemiology an ensemble approach can account for that uncertainty. We compare our results across several variants of Susceptible-Infectious-Recovered (SIR) compartmental models to quantify the impact of modeling assumptions on our estimates. Model-specific parameters are estimated by Bayesian inference using Markov chain Monte Carlo. We then use Bayesian model averaging to generate ensemble estimates of the current dynamics, including estimates of R0, the burden of infection in the region, as well as the impact of vaccination on both the short-term dynamics and the long-term reduction of rotavirus incidence under varying levels of coverage. The ensemble of models predicts that the current burden of severe rotavirus disease is 2.6-3.7% of the population each year and that a 2-dose vaccine schedule achieving 70% coverage could reduce burden by 39-42%.

Automated Factor Slice Sampling.

Markov chain Monte Carlo (MCMC) algorithms offer a very general approach for sampling from arbitrary distributions. However, designing and tuning MCMC algorithms for each new distribution, can be challenging and time consuming. It is particularly difficult to create an efficient sampler when there is strong dependence among the variables in a multivariate distribution. We describe a two-pronged approach for constructing efficient, automated MCMC algorithms: (1) we propose the "factor slice sampler", a generalization of the univariate slice sampler where we treat the selection of a coordinate basis (factors) as an additional tuning parameter, and (2) we develop an approach for automatically selecting tuning parameters in order to construct an efficient factor slice sampler. In addition to automating the factor slice sampler, our tuning approach also applies to the standard univariate slice samplers. We demonstrate the efficiency and general applicability of our automated MCMC algorithm with a number of illustrative examples.

Social Capital and Human Mortality: Explaining the Rural Paradox with County-Level Mortality Data.

The "rural paradox" refers to standardized mortality rates in rural areas that are unexpectedly low in view of well-known economic and infrastructural disadvantages there. We explore this paradox by incorporating social capital, a promising explanatory factor that has seldom been incorporated into residential mortality research. We do so while being attentive to spatial dependence, a statistical problem often ignored in mortality research. Analyzing data for counties in the contiguous United States, we find that: (1) the rural paradox is confirmed with both metro/non-metro and rural-urban continuum codes, (2) social capital significantly reduces the impacts of residence on mortality after controlling for race/ethnicity and socioeconomic covariates, (3) this attenuation is greater when a spatial perspective is imposed on the analysis, (4) social capital is negatively associated with mortality at the county level, and (5) spatial dependence is strongly in evidence. A spatial approach is necessary in county-level analyses such as ours to yield unbiased estimates and optimal model fit.