Geospatial joint modeling of vector and parasite serology to microstratify malaria transmission.

The World Health Organization identifies a strong surveillance system for malaria and its mosquito vector as an essential pillar of the malaria elimination agenda. Anopheles salivary antibodies are emerging biomarkers of exposure to mosquito bites that potentially overcome sensitivity and logistical constraints of traditional entomological surveys. Using samples collected by a village health volunteer network in 104 villages in Southeast Myanmar during routine surveillance, the present study employs a Bayesian geostatistical modeling framework, incorporating climatic and environmental variables together with Anopheles salivary antigen serology, to generate spatially continuous predictive maps of Anopheles biting exposure. Our maps quantify fine-scale spatial and temporal heterogeneity in Anopheles salivary antibody seroprevalence (ranging from 9 to 99%) that serves as a proxy of exposure to Anopheles bites and advances current static maps of only Anopheles occurrence. We also developed an innovative framework to perform surveillance of malaria transmission. By incorporating antibodies against the vector and the transmissible form of malaria (sporozoite) in a joint Bayesian geostatistical model, we predict several foci of ongoing transmission. In our study, we demonstrate that antibodies specific for Anopheles salivary and sporozoite antigens are a logistically feasible metric with which to quantify and characterize heterogeneity in exposure to vector bites and malaria transmission. These approaches could readily be scaled up into existing village health volunteer surveillance networks to identify foci of residual malaria transmission, which could be targeted with supplementary interventions to accelerate progress toward elimination.

An introduction to bayesian spatial smoothing methods for disease mapping: modeling county firearm suicide mortality rates.

This article introduces bayesian spatial smoothing models for disease mapping-a specific application of small area estimation where the full universe of data is known-to a wider audience of public health professionals using firearm suicide as a motivating example. Besag, York, and Mollié (BYM) Poisson spatial and space-time smoothing models were fitted to firearm suicide counts for the years 2014-2018. County raw death rates in 2018 ranged from 0 to 24.81 deaths per 10 000 people. However, the highest mortality rate was highly unstable, based on only 2 deaths in a population of approximately 800, and 80.5% of contiguous US counties experienced fewer than 10 firearm suicide deaths and were thus suppressed. Spatially smoothed county firearm suicide mortality estimates ranged from 0.06 to 4.05 deaths per 10 000 people and could be reported for all counties. The space-time smoothing model produced similar estimates with narrower credible intervals as it allowed counties to gain precision from adjacent neighbors and their own counts in adjacent years. bayesian spatial smoothing methods are a useful tool for evaluating spatial health disparities in small geographies where small numbers can result in highly variable rate estimates, and new estimation techniques in R software have made fitting these models more accessible to researchers.

Spatial Difference Boundary Detection for Multiple Outcomes Using Bayesian Disease Mapping.

Regional aggregates of health outcomes over delineated administrative units (e.g., states, counties, and zip codes), or areal units, are widely used by epidemiologists to map mortality or incidence rates and capture geographic variation. To capture health disparities over regions, we seek "difference boundaries" that separate neighboring regions with significantly different spatial effects. Matters are more challenging with multiple outcomes over each unit, where we capture dependence among diseases as well as across the areal units. Here, we address multivariate difference boundary detection for correlated diseases. We formulate the problem in terms of Bayesian pairwise multiple comparisons and seek the posterior probabilities of neighboring spatial effects being different. To achieve this, we endow the spatial random effects with a discrete probability law using a class of multivariate areally referenced Dirichlet process models that accommodate spatial and interdisease dependence. We evaluate our method through simulation studies and detect difference boundaries for multiple cancers using data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.

Computational network analysis of host genetic risk variants of severe COVID-19.

BACKGROUND: Genome-wide association studies have identified numerous human host genetic risk variants that play a substantial role in the host immune response to SARS-CoV-2. Although these genetic risk variants significantly increase the severity of COVID-19, their influence on body systems is poorly understood. Therefore, we aim to interpret the biological mechanisms and pathways associated with the genetic risk factors and immune responses in severe COVID-19. We perform a deep analysis of previously identified risk variants and infer the hidden interactions between their molecular networks through disease mapping and the similarity of the molecular functions between constructed networks. RESULTS: We designed a four-stage computational workflow for systematic genetic analysis of the risk variants. We integrated the molecular profiles of the risk factors with associated diseases, then constructed protein-protein interaction networks. We identified 24 protein-protein interaction networks with 939 interactions derived from 109 filtered risk variants in 60 risk genes and 56 proteins. The majority of molecular functions, interactions and pathways are involved in immune responses; several interactions and pathways are related to the metabolic and cardiovascular systems, which could lead to multi-organ complications and dysfunction. CONCLUSIONS: This study highlights the importance of analyzing molecular interactions and pathways to understand the heterogeneous susceptibility of the host immune response to SARS-CoV-2. We propose new insights into pathogenicity analysis of infections by including genetic risk information as essential factors to predict future complications during and after infection. This approach may assist more precise clinical decisions and accurate treatment plans to reduce COVID-19 complications.

Social inequalities in health within the City of Milan (Lombardy Region, Northern Italy): An ecological assessment.

OBJECTIVES: to document existing geographical inequalities in health in the city of Milan (Lombardy Region, Northern Italy), examining the association between area socioeconomic disadvantage and health outcomes, with the aim to suggest policy action to tackle them. DESIGN: the analysis used an ecological framework; multiple health indicators were considered in the analysis; socioeconomic disadvantage was measured through indicators such as low education, unemployment, immigration status, and housing crowding. For each municipal statistical area, Bayesian Relative Risks of the outcomes (using the Besag-Yorkand-Mollié model) were plotted on the city map. To evaluate the association between social determinants and health outcomes, Spearman correlation coefficients were estimated. SETTING AND PARTICIPANTS: residents in the City of Milan aged between 30 and 75 years who were residing in Milan as of 01.01.2019, grouped in 88 statistical areas. MAIN OUTCOMES MEASURES: all-cause mortality, type-2 diabetes mellitus, hypertension, neoplasms, respiratory diseases, metabolic syndrome, antidepressants use, polypharmacy, and multimorbidity. RESULTS: the results consistently demonstrated a significant association between socioeconomic disadvantage and various health outcomes, with low education exhibiting the strongest correlations. Neoplasms displayed an inverse social gradient, while the relationship with antidepressant use varied. CONCLUSIONS: these findings provide valuable insights into the distribution of health inequalities in Milan and contribute to the existing literature on the social determinants of health. The study highlights the need for targeted interventions to address disparities and promote equitable health outcomes. The results can serve to inform the development of effective public health strategies and policies aimed at reducing health inequalities in the city.

Space-time modelling of monthly malaria incidence for seasonal associated drivers and early epidemic detection in Southern Ethiopia.

BACKGROUND: Although Ethiopia has made great strides in recent years to reduce the threat of malaria, the disease remains a significant issue in most districts of the country. It constantly disappears in parts of the areas before reappearing in others with erratic transmission rates. Thus, developing a malaria epidemic early warning system is important to support the prevention and control of the incidence. METHODS: Space-time malaria risk mapping is essential to monitor and evaluate priority zones, refocus intervention, and enable planning for future health targets. From August 2013 to May 2019, the researcher considered an aggregated count of genus Plasmodium falciparum from 149 districts in Southern Ethiopia. Afterwards, a malaria epidemic early warning system was developed using model-based geostatistics, which helped to chart the disease's spread and future management. RESULTS: Risk factors like precipitation, temperature, humidity, and nighttime light are significantly associated with malaria with different rates across the districts. Districts in the southwest, including Selamago, Bero, and Hamer, had higher rates of malaria risk, whereas in the south and centre like Arbaminch and Hawassa had moderate rates. The distribution is inconsistent and varies across time and space with the seasons. CONCLUSION: Despite the importance of spatial correlation in disease risk mapping, it may occasionally be a good idea to generate epidemic early warning independently in each district to get a quick picture of disease risk. A system like this is essential for spotting numerous inconsistencies in lower administrative levels early enough to take corrective action before outbreaks arise.

Disease mapping for spatially semi-continuous data by estimating equations with application to dengue control.

Disease mapping is a research field to estimate spatial pattern of disease risks so that areas with elevated risk levels can be identified. The motivation of this article is from a study of dengue fever infection, which causes seasonal epidemics in almost every summer in Taiwan. For analysis of zero-inflated data with spatial correlation and covariates, current methods would either cause a computational burden or miss associations between zero and non-zero responses. In this article, we develop estimating equations for a mixture regression model that accommodates spatial dependence and zero inflation for study of disease propagation. Asymptotic properties for the proposed estimates are established. A simulation study is conducted to evaluate performance of the mixture estimating equations; and a dengue dataset from southern Taiwan is used to illustrate the proposed method.

Landscape Epidemiology of Potato Blackleg.

Potato blackleg is a common bacterial disease that causes serious losses in potato (Solanum tuberosum) production worldwide. Despite this, relatively little is known of the landscape epidemiology of this disease. This study provides the first national-scale analysis of spatial and spatiotemporal patterns of blackleg incidence rates and associated risk factors for disease at the landscape scale. This was achieved through a combination of ArcGIS and interpretable machine learning applied to a longitudinal dataset of naturally infected seed potato crops from across Scotland. We found striking differences in long-term disease outcomes across the country and identified that features (variables) related to the health status and management of mother crops (seed stocks), matching features in daughter crops, and the characteristics of surrounding potato crop distributions were the most important predictors of disease, followed by field, bioclimatic, and soil features. Our approach provides a comprehensive overview of potato blackleg at a national scale, new epidemiological insights, and an accurate model that could serve as the basis of a decision support tool for improved blackleg management.

A practical illustration of spatial smoothing methods for disconnected regions with INLA: spatial survey on overweight and obesity in Malaysia.

BACKGROUND: National prevalence could mask subnational heterogeneity in disease occurrence, and disease mapping is an important tool to illustrate the spatial pattern of disease. However, there is limited information on techniques for the specification of conditional autoregressive models in disease mapping involving disconnected regions. This study explores available techniques for producing district-level prevalence estimates for disconnected regions, using as an example childhood overweight in Malaysia, which consists of the Peninsular and Borneo regions separated by the South China Sea. We used data from Malaysia National Health and Morbidity Survey conducted in 2015. We adopted Bayesian hierarchical modelling using the integrated nested Laplace approximation (INLA) program in R-software to model the spatial distribution of overweight among 6301 children aged 5-17 years across 144 districts located in two disconnected regions. We illustrate different types of spatial models for prevalence mapping across disconnected regions, taking into account the survey design and adjusting for district-level demographic and socioeconomic covariates. RESULTS: The spatial model with split random effects and a common intercept has the lowest Deviance and Watanabe Information Criteria. There was evidence of a spatial pattern in the prevalence of childhood overweight across districts. An increasing trend in smoothed prevalence of overweight was observed when moving from the east to the west of the Peninsular and Borneo regions. The proportion of Bumiputera ethnicity in the district had a significant negative association with childhood overweight: the higher the proportion of Bumiputera ethnicity in the district, the lower the prevalence of childhood overweight. CONCLUSION: This study illustrates different available techniques for mapping prevalence across districts in disconnected regions using survey data. These techniques can be utilized to produce reliable subnational estimates for any areas that comprise of disconnected regions. Through the example, we learned that the best-fit model was the one that considered the separate variations of the individual regions. We discovered that the occurrence of childhood overweight in Malaysia followed a spatial pattern with an east-west gradient trend, and we identified districts with high prevalence of overweight. This information could help policy makers in making informed decisions for targeted public health interventions in high-risk areas.

Mapping the prevalence of cancer risk factors at the small area level in Australia.

BACKGROUND: Cancer is a significant health issue globally and it is well known that cancer risk varies geographically. However in many countries there are no small area-level data on cancer risk factors with high resolution and complete reach, which hinders the development of targeted prevention strategies. METHODS: Using Australia as a case study, the 2017-2018 National Health Survey was used to generate prevalence estimates for 2221 small areas across Australia for eight cancer risk factor measures covering smoking, alcohol, physical activity, diet and weight. Utilising a recently developed Bayesian two-stage small area estimation methodology, the model incorporated survey-only covariates, spatial smoothing and hierarchical modelling techniques, along with a vast array of small area-level auxiliary data, including census, remoteness, and socioeconomic data. The models borrowed strength from previously published cancer risk estimates provided by the Social Health Atlases of Australia. Estimates were internally and externally validated. RESULTS: We illustrated that in 2017-2018 health behaviours across Australia exhibited more spatial disparities than previously realised by improving the reach and resolution of formerly published cancer risk factors. The derived estimates revealed higher prevalence of unhealthy behaviours in more remote areas, and areas of lower socioeconomic status; a trend that aligned well with previous work. CONCLUSIONS: Our study addresses the gaps in small area level cancer risk factor estimates in Australia. The new estimates provide improved spatial resolution and reach and will enable more targeted cancer prevention strategies at the small area level. Furthermore, by including the results in the next release of the Australian Cancer Atlas, which currently provides small area level estimates of cancer incidence and relative survival, this work will help to provide a more comprehensive picture of cancer in Australia by supporting policy makers, researchers, and the general public in understanding the spatial distribution of cancer risk factors. The methodology applied in this work is generalisable to other small area estimation applications and has been shown to perform well when the survey data are sparse.

Understanding the spread of infectious diseases in edge areas of hotspots: dengue epidemics in tropical metropolitan regions.

Identifying clusters or hotspots from disease maps is critical in research and practice. Hotspots have been shown to have a higher potential for transmission risk and may be the source of infections, making them a priority for controlling epidemics. However, the role of edge areas of hotspots in disease transmission remains unclear. This study aims to investigate the role of edge areas in disease transmission by examining whether disease incidence rate growth is higher in the edges of disease hotspots during outbreaks. Our data is based on the three most severe dengue epidemic years in Kaohsiung city, Taiwan, from 1998 to 2020. We employed conditional autoregressive (CAR) models and Bayesian areal Wombling methods to identify significant edge areas of hotspots based on the extent of risk difference between adjacent areas. The difference-in-difference (DID) estimator in spatial panel models measures the growth rate of risk by comparing the incidence rate between two groups (hotspots and edge areas) over two time periods. Our results show that in years characterized by exceptionally large-scale outbreaks, the edge areas of hotspots have a more significant increase in disease risk than hotspots, leading to a higher risk of disease transmission and potential disease foci. This finding explains the geographic diffusion mechanism of epidemics, a pattern mixed with expansion and relocation, indicating that the edge areas play an essential role. The study highlights the importance of considering edge areas of hotspots in disease transmission. Furthermore, it provides valuable insights for policymakers and health authorities in designing effective interventions to control large-scale disease outbreaks.

Spatial distribution of hospital admissions for asthma in the central area of Asturias, Northern Spain.

BACKGROUND: Asturias is one of the communities with the highest rates of hospital admission for asthma in Spain. The environmental pollution or people lifestyle are some of the factors that contribute to the appearance or aggravation of this illness. The aim of this study was to show the spatial distribution of asthma admissions risks in the central municipalities of Asturias and to analyze the observed spatial patterns. METHODS: Urgent hospital admissions for asthma and status asthmaticus occurred between 2016 to 2018 on the public hospitals of the central area of Asturias were used. Population data were assigned in 5 age groups. Standardised admission ratio (SAR), smoothed relative risk (SRR) and posterior risk probability (PP) were calculated for each census tract (CT). A spatial trend analysis was run, a spatial autocorrelation index (Morans I) was calculated and a cluster and outlier analysis (Anselin Local Morans I) was finally performed in order to analyze spatial clusters. RESULTS: The total number of hospital urgent asthma admissions during the study period was 2324, 1475 (63.46%) men and 849 (36.56%) women. The municipalities with the highest values of SRR and PP were located on the northwest area: Avilés, Gozón, Carreño, Corvera de Asturias, Castrillón and Illas. A high risk cluster was found for the municipalities of Avilés, Gozón y Corvera de Asturias. CONCLUSIONS: The spatial analysis showed high risk of hospitalization for asthma on the municipalities of the northwest area of the study, which highlight the existence of spatial inequalities on the distribution of urgent hospital admissions.

Spatial distribution of unscheduled hospital admissions for chronic obstructive pulmonary disease in the central area of Asturias, Spain.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the major causes of mortality worldwide and also reports high morbidity rates and the global burden COPD has continued to rise over the last several decades. The best-known COPD risk factors are tobacco smoke and air pollution, but genetics, age, sex, and socioeconomic status are additional factors. This study aimed to assess the spatial distribution of unscheduled COPD hospital admissions of men and women in the central area of Asturias during 2016-2018 and identify trends, spatial patterns, or clusters in the area. METHODS: Unscheduled COPD hospital admissions in the central area of Asturias were registered, geocoded, and grouped by census tracts (CTs), age, and sex. Standardized admission ratio, smoothed relative risk, posterior risk probability, and spatial clusters between relative risks throughout the study area were calculated and mapped. RESULTS: The spatial distribution of COPD hospital admissions differed between men and women. For men, high-risk values were located primarily in the northwestern area of the study, whereas for women the cluster pattern was not as clear and high-risk CTs also reached central and southern areas. In both men and women, the north-northwest area included the majority of CTs with high-risk values. CONCLUSIONS: The present study showed the existence of a spatial distribution pattern of unscheduled COPD hospital admissions in the central area of Asturias that was more pronounced for men than for women. This study could provide a starting point for generating knowledge about COPD epidemiology in Asturias.

A scalable approach for short-term disease forecasting in high spatial resolution areal data.

Short-term disease forecasting at specific discrete spatial resolutions has become a high-impact decision-support tool in health planning. However, when the number of areas is very large obtaining predictions can be computationally intensive or even unfeasible using standard spatiotemporal models. The purpose of this paper is to provide a method for short-term predictions in high-dimensional areal data based on a newly proposed "divide-and-conquer" approach. We assess the predictive performance of this method and other classical spatiotemporal models in a validation study that uses cancer mortality data for the 7907 municipalities of continental Spain. The new proposal outperforms traditional models in terms of mean absolute error, root mean square error, and interval score when forecasting cancer mortality 1, 2, and 3 years ahead. Models are implemented in a fully Bayesian framework using the well-known integrated nested Laplace estimation technique.

Using mortality to predict incidence for rare and lethal cancers in very small areas.

Incidence and mortality figures are needed to get a comprehensive overview of cancer burden. In many countries, cancer mortality figures are routinely recorded by statistical offices, whereas incidence depends on regional cancer registries. However, due to the complexity of updating cancer registries, incidence numbers become available 3 or 4 years later than mortality figures. It is, therefore, necessary to develop reliable procedures to predict cancer incidence at least until the period when mortality data are available. Most of the methods proposed in the literature are designed to predict total cancer (except nonmelanoma skin cancer) or major cancer sites. However, less frequent lethal cancers, such as brain cancer, are generally excluded from predictions because the scarce number of cases makes it difficult to use univariate models. Our proposal comes to fill this gap and consists of modeling jointly incidence and mortality data using spatio-temporal models with spatial and age shared components. This approach allows for predicting lethal cancers improving the performance of individual models when data are scarce by taking advantage of the high correlation between incidence and mortality. A fully Bayesian approach based on integrated nested Laplace approximations is considered for model fitting and inference. A validation process is also conducted to assess the performance of alternative models. We use the new proposals to predict brain cancer incidence rates by gender and age groups in the health units of Navarre and Basque Country (Spain) during the period 2005-2008.

Spatial correlated incidence modeling with zero inflation.

Disease mapping models have been popularly used to model disease incidence with spatial correlation. In disease mapping models, zero inflation is an important issue, which often occurs in disease incidence datasets with high proportions of zero disease count. It is originated from limited survey coverage or unadvanced testing equipment, which makes some regions have no observed patients. Then excessive zeros recorded in the disease incidence dataset would mess up the true distributions of disease incidence and lead to inaccurate estimates. To address this issue, a zero-inflated disease mapping model is developed in this work. In this model, a zero-inflated process using Bernoulli indicators is assumed to characterize whether the zero inflation occurs for each region. For regions without zero inflation, a coherent and generative disease mapping model is applied for mapping the spatially correlated disease incidence. Independent spatial random effects are incorporated in both processes to account for the spatial patterns of zero inflation and disease incidence. External covariates are also considered in both processes to better explain the disease count data. To estimate the model, a Markov chain Monte Carlo algorithm is proposed. We evaluate model performance via a variety of simulation experiments. Finally, a Lyme disease dataset of Virginia is analyzed to illustrate the application of the proposed model.

Causal decomposition maps: An exploratory tool for designing area-level interventions aimed at reducing health disparities.

Methods for decomposition analyses have been developed to partition between-group differences into explained and unexplained portions. In this paper, we introduce the concept of causal decomposition maps, which allow researchers to test the effect of area-level interventions on disease maps before implementation. These maps quantify the impact of interventions that aim to reduce differences in health outcomes between groups and illustrate how the disease map might change under different interventions. We adapt a new causal decomposition analysis method for the disease mapping context. Through the specification of a Bayesian hierarchical outcome model, we obtain counterfactual small area estimates of age-adjusted rates and reliable estimates of decomposition quantities. We present two formulations of the outcome model, with the second allowing for spatial interference of the intervention. Our method is utilized to determine whether the addition of gyms in different sets of rural ZIP codes could reduce any of the rural-urban difference in age-adjusted colorectal cancer incidence rates in Iowa ZIP codes.

A spatial model to jointly analyze self-reported survey data of COVID-19 symptoms and official COVID-19 incidence data.

This work presents a joint spatial modeling framework to improve estimation of the spatial distribution of the latent COVID-19 incidence in Belgium, based on test-confirmed COVID-19 cases and crowd-sourced symptoms data as reported in a large-scale online survey. Correction is envisioned for stochastic dependence between the survey's response rate and spatial COVID-19 incidence, commonly known as preferential sampling, but not found significant. Results show that an online survey can provide valuable auxiliary data to optimize spatial COVID-19 incidence estimation based on confirmed cases in situations with limited testing capacity. Furthermore, it is shown that an online survey on COVID-19 symptoms with a sufficiently large sample size per spatial entity is capable of pinpointing the same locations that appear as test-confirmed clusters, approximately 1 week earlier. We conclude that a large-scale online study provides an inexpensive and flexible method to collect timely information of an epidemic during its early phase, which can be used by policy makers in an early phase of an epidemic and in conjunction with other monitoring systems.

Simultaneous spatial smoothing and outlier detection using penalized regression, with application to childhood obesity surveillance from electronic health records.

Electronic health records (EHRs) have become a platform for data-driven granular-level surveillance in recent years. In this paper, we make use of EHRs for early prevention of childhood obesity. The proposed method simultaneously provides smooth disease mapping and outlier information for obesity prevalence that are useful for raising public awareness and facilitating targeted intervention. More precisely, we consider a penalized multilevel generalized linear model. We decompose regional contribution into smooth and sparse signals, which are automatically identified by a combination of fusion and sparse penalties imposed on the likelihood function. In addition, we weigh the proposed likelihood to account for the missingness and potential nonrepresentativeness arising from the EHR data. We develop a novel alternating minimization algorithm, which is computationally efficient, easy to implement, and guarantees convergence. Simulation studies demonstrate superior performance of the proposed method. Finally, we apply our method to the University of Wisconsin Population Health Information Exchange database.

A simulation study of disaggregation regression for spatial disease mapping.

Disaggregation regression has become an important tool in spatial disease mapping for making fine-scale predictions of disease risk from aggregated response data. By including high resolution covariate information and modeling the data generating process on a fine scale, it is hoped that these models can accurately learn the relationships between covariates and response at a fine spatial scale. However, validating these high resolution predictions can be a challenge, as often there is no data observed at this spatial scale. In this study, disaggregation regression was performed on simulated data in various settings and the resulting fine-scale predictions are compared to the simulated ground truth. Performance was investigated with varying numbers of data points, sizes of aggregated areas and levels of model misspecification. The effectiveness of cross validation on the aggregate level as a measure of fine-scale predictive performance was also investigated. Predictive performance improved as the number of observations increased and as the size of the aggregated areas decreased. When the model was well-specified, fine-scale predictions were accurate even with small numbers of observations and large aggregated areas. Under model misspecification predictive performance was significantly worse for large aggregated areas but remained high when response data was aggregated over smaller regions. Cross-validation correlation on the aggregate level was a moderately good predictor of fine-scale predictive performance. While these simulations are unlikely to capture the nuances of real-life response data, this study gives insight into the effectiveness of disaggregation regression in different contexts.