Landscape Epidemiology and Machine Learning: A Geospatial Approach to Modeling West Nile Virus Risk in the United States

The complex interactions between human health and the physical landscape and environment have been recognized, if not fully understood, since the ancient Greeks. Landscape epidemiology, sometimes called spatial epidemiology, is a sub-discipline of medical geography that uses environmental conditions as explanatory variables in the study of disease or other health phenomena. This theory suggests that pathogenic organisms (whether germs or larger vector and host species) are subject to environmental conditions that can be observed on the landscape, and by identifying where such organisms are likely to exist, areas at greatest risk of the disease can be derived. Machine learning is a sub-discipline of artificial intelligence that can be used to create predictive models from large and complex datasets. West Nile virus (WNV) is a relatively new infectious disease in the United States, and has a fairly well-understood transmission cycle that is believed to be highly dependent on environmental conditions. This study takes a geospatial approach to the study of WNV risk, using both landscape epidemiology and machine learning techniques. A combination of remotely sensed and in situ variables are used to predict WNV incidence with a correlation coefficient as high as 0.86. A novel method of mitigating the small numbers problem is also tested and ultimately discarded. Finally a consistent spatial pattern of model errors is identified, indicating the chosen variables are capable of predicting WNV disease risk across most of the United States, but are inadequate in the northern Great Plains region of the US

THE ECOLOGY AND FUTURE DISTRIBUTION OF WEST NILE VIRUS IN THE CANADIAN PRAIRIE PROVINCES

This thesis describes aspects of the ecology of West Nile virus (WNV) including factors contributing to the distribution of WNV, possible future distribution, and effects of WNV on host abundance in the Canadian prairies provinces: Alberta, Saskatchewan, and Manitoba. Using mosquito surveillance data collected between 2005 and 2008, models integrating abiotic and biotic factors were constructed to predict the weekly and monthly scales of WNV infection rate in Culex tarsalis, which is the primary vector of WNV in the Canadian prairies. At the weekly scale, the WNV infection rate in Cx. tarsalis increased with increasing Cx. tarsalis abundance and mean temperature lagged from 1 to 8 weeks, but decreased with an increasing mean precipitation lagged from 2 to 6 weeks. Furthermore, precipitation was a ‘distorter variable’ which altered the association between Cx. tarsalis abundance and the WNV infection rate. Study at the monthly scale showed that higher mean temperature and time lagged mean temperature elevated were associated with increased numbers of Cx. tarsalis and higher WNV infection rates. However, increasing precipitation was associated with higher abundance of Cx. tarsalis and lower WNV infection rate. In addition, this study found that increased temperature fluctuation and wetland land cover were associated with decreased WNV infection rate in Cx. tarsalis. Climate change could drive dramatic alterations in the spatial and temporal distribution and overall incidence of vector-borne diseases. The constructed models and biological thresholds were used to predict the distribution of Cx. tarsalis and WNV infection rate in the prairie provinces under a range of potential future climate and habitat conditions. In the current endemic regions, the projected WNV infection rate under the median outcome scenario in 2050 was 18 times higher than under current climate conditions. Seasonal occurence of Cx. tarsalis infected with WNV extended from June to August to include May and September. Moreover, models predicted northward range expansion for Cx. tarsalis and WNV. The declines of susceptible bird abundance caused by WNV may further influence the bird community composition and, in turn, affect the incidence of WNV through a dilution effect. The North American Breeding Bird Survey data was used to evaluate the effect of WNV on the abundance of selected birds in the Canadian prairies, as well as the effects of bird community composition on the WNV risk. There was no significant decline in bird abundances of selected birds following the emergence of WNV. These findings suggest that the effect of WNV on selected bird abundance and bird community composition is insignificant. In addition, there is no evidence to support the association between bird community composition and WNV infection rate in Cx.tarsalis in the Canadian prairies. Lastly, findings in this thesis and current knowledge were integrated to create a decision making flowchart for the prevention of WNV infection in the prairie provinces

Transmission Dynamics and Epidemiology of West Nile Virus in Ontario, Canada

The resurgence of West Nile virus (WNV; Family Flaviviridae, genus Flavivirus) in Ontario, Canada in 2012 demonstrated that there is a great need for a reassessment of the local mosquito fauna, estimation of risk of WNV transmission, and the creation of effective arboviral awareness campaigns. A review of the current literature and collection databases revealed that there are 68 mosquito species known from Ontario (Chapter 2). Ten species were added to the list of species including Culex erraticus (Chapter 3) and Aedes albopictus (Chapter 4), both of which are capable of transmitting West Nile virus. Ae. albopictus was repeatedly collected from Windsor, Ontario in 2016 (Chapter 4). Immatures (n=78) were collected from tires, StyrofoamTM containers, and discarded garbage. Adult female (n=17) and male (n=2) specimens were collected from light traps (n=7) and Biogents-Sentinel traps (n=10). Additional specimens were obtained from Franklin County, Ohio. The generated gene tree and Bayesian cluster analysis grouped sequences described from Ohio and Windsor together on the same branches. Together these data suggest that the population in Windsor originated as a founder population of North American origin by means of human-aided dispersal. Mosquito abundance predication surfaces and seasonal distributions were attempted for each vector species to identify where and when vector species are most abundant in southern Ontario (Chapter 5). Spatial prediction surfaces using kriging were created for Aedes vexans, Aedes japonicus, Culex pipiens, Culex restuans, and Ochlerotatus trivittatus. Proximity to landscape variables was observed to improve model prediction. An epidemiological analysis of WNV human case prevalence and mosquito infection was conducted (Chapter 6). A strong quadratic relationship between the number of human cases and positive mosquito pools at the end of each year was observed (R2=0.9783, p < 0.001). Spearman rank correlation tests identified mosquito infection rates as the strongest predictors of human case prevalence at a one-week lag period. Average temperature was a strong predictor of mosquito infection rates. Cumulative positive Culex pools recorded by epidemiological week 34 is a sufficient action threshold for West Nile virus epidemics. These data have the potential to contribute to a more efficient West Nile virus awareness campaign

The epidemiology of La Crosse virus in Tennessee and West Virginia

La Crosse virus (LACV) was first recognized as a cause of pediatric viral encephalitis in the upper-Midwestern United States following its isolation from a fatal case of pediatric encephalitis in 1964. From that time, LACV infections have been reported in 24 states, with the number of reported cases increasing in recent years in the Appalachian region of the United States. Two states in Appalachia, West Virginia and Tennessee have both seen a large rise in the number of reported cases in recent years. To investigate the epidemiology of the LACV infections in the eastern United States, Tennessee, and West Virginia a combination of field and laboratory studies were initiated. These studies investigated the spatial and temporal patterns of disease risk and the biology and ecosystem dynamics of both indigenous and invasive disease vectors.Four distinct regional clusters of LACV infections were detected at the national level, as well as a higher incidence risk and case-fatality rate than previously reported. The exploration into the variations of risk using different at-risk populations and geographic scales revealed the possibility of missing disease clusters resulting from performing incidence risk investigations of focal diseases using inappropriate at-risk populations and/or large geographic scales. South-central West Virginia was found to be a focus of LACV transmission and in addition to having the highest incidence risk and case-fatality rate reported in the United States. In eastern Tennessee, Aedes albopictus was found to be the most abundant mosquito collected at all sites and vegetation types, by both CO2-baited CDC trapping and human landing catches.Results from the use of variable pressure scanning electron microscopy to describe the egg of Aedes japonicus have provided more detailed information on characters of Aedini eggs, while bringing the number of more complete descriptions and micrographs of the micropyle and associated structures of the subgenus Finlaya to three. The results of these studies have provided a more complete understanding of the epidemiology of LACV and its associated vector species at both the national and state levels. These findings will help guide future research and intervention efforts to understand and prevent virus transmission

Understanding and predicting mosquito-borne disease under current and future scenarios of global change

There is a rapidly growing awareness of the influence of global change processes such as land-use, climate change and socioeconomic factors on the burden of mosquito-borne disease (MBD). Although individual effects of different processes on MBD risk have been studied widely, a holistic approach that considers the combined influence of different global change processes has rarely been implemented. Here, I evaluate the effects of different global change processes on MBD risk, both generally, and in a series of modelling studies using the understudied MBD, Japanese encephalitis (JE) as a case study. I integrate different data types and approaches from ecology and epidemiology, with the aim of informing public health decision-makers in the era of accelerating global change. Firstly, I synthesise current knowledge on relative and interacting effects of global change processes on MBD risk and examine how these factors have been incorporated into existing analyses, highlighting how future research could be improved. Secondly, I compile a vector surveillance database for the predominant vector of JE (Culex tritaeniorhynchus). I use a novel approach that leverages information from sparse vector surveillance data to predict seasonal vector abundance over large spatial scales, that has the potential to be used to provide guidance for the targeting of suitable interventions. I use this information in an epidemiological study of JE case surveillance data and show that human JE incidence is associated with climate, land-use and socioeconomic factors, and these factors can be used to predict JE outbreaks in north-eastern India. Thirdly, I examine possible trends in JE epidemiology by projecting into the future under various scenarios of global change to show divergence in JE risk and burden under different socioeconomic and environmental policy scenarios. Finally, I integrate the implications of these results into our understanding of the effects of global change processes on MBD, the epidemiology and control of JE, and a holistic approach to the understanding and prediction of MBD risk

Malar J

BackgroundSpatial determinants of malaria risk within communities are associated with heterogeneity of exposure to vector mosquitoes. The abundance of adult malaria vectors inside people\ue2\u20ac\u2122s houses, where most transmission takes place, should be associated with several factors: proximity of houses to larval habitats, structural characteristics of houses, indoor use of vector control tools containing insecticides, and human behavioural and environmental factors in and near houses. While most previous studies have assessed the association of larval habitat proximity in landscapes with relatively low densities of larval habitats, in this study these relationships were analysed in a region of rural, lowland western Kenya with high larval habitat density.Methods525 houses were sampled for indoor-resting mosquitoes across an 8 by 8\uc2\ua0km study area using the pyrethrum spray catch method. A predictive model of larval habitat location in this landscape, previously verified, provided derivations of indices of larval habitat proximity to houses. Using geostatistical regression models, the association of larval habitat proximity, long-lasting insecticidal nets (LLIN) use, house structural characteristics (wall type, roof type), and peridomestic variables (cooking in the house, cattle near the house, number of people sleeping in the house) with mosquito abundance in houses was quantified.ResultsVector abundance was low (mean, 1.1 adult Anopheles per house). Proximity of larval habitats was a strong predictor of Anopheles abundance. Houses without an LLIN had more female Anopheles gambiae s.s., Anopheles arabiensis and Anopheles funestus than houses where some people used an LLIN (rate ratios, 95% CI 0.87, 0.85\ue2\u20ac\u201c0.89; 0.84, 0.82\ue2\u20ac\u201c0.86; 0.38, 0.37\ue2\u20ac\u201c0.40) and houses where everyone used an LLIN (RR, 95% CI 0.49, 0.48\ue2\u20ac\u201c0.50; 0.39, 0.39\ue2\u20ac\u201c0.40; 0.60, 0.58\ue2\u20ac\u201c0.61). Cooking in the house also reduced Anopheles abundance across all species. The number of people sleeping in the house, presence of cattle near the house, and house structure modulated Anopheles abundance, but the effect varied with Anopheles species and sex.ConclusionsVariation in the abundance of indoor-resting Anopheles in rural houses of western Kenya varies with clearly identifiable factors. Results suggest that LLIN use continues to function in reducing vector abundance, and that larval source management in this region could lead to further reductions in malaria risk by reducing the amount of an obligatory resource for mosquitoes near people\ue2\u20ac\u2122s homes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1938-1) contains supplementary material, which is available to authorized users.2017-07-17T00:00:00Z28716087PMC551448

A Spatial Analysis Evaluation of DeltaGard®20EW Operational Efficacy in Winnipeg, Manitoba for Adult Mosquito Control

Background: Mosquito abatement includes the management and surveillance of nuisance and potential vector mosquitoes. The major nuisance mosquito in Winnipeg, Manitoba is Ae. vexans, a floodwater mosquito. The City of Winnipeg Insect Control Branch uses surveillance, source elimination, larvicide, and adulticide in their mosquito abatement program. Adulticide application is the last resort when the other methods are not sufficient. This study tested DeltaGard®20EW adulticide efficacy operationally on wild mosquitoes in Winnipeg, Manitoba as a replacement for the previously used Malathion 95ULV® while considering the effect of landscape features. Methods: New Jersey Light and Centre for Disease Control mosquito trap data from July 2010 and July 2020 were used to statistically detect changes in adult mosquito activity before and after treatment with Malathion 95®ULV (2010) and DeltaGard®20EW (2020). Landscape features surrounding traps that were frequently mosquito hot spots and traps that were never hot spots were compared by applying spatial analysis tools. Kriging analysis was performed to estimate changes in mosquito activity citywide. Wing lengths were used as a proxy for adult mosquito body size to determine if body size is positively correlated with mosquito longevity. Results: No significant difference was detected when comparing post-spray mosquito trap counts in treated and untreated (experimental control) locations in July 2010 or July 2020. When daily changes in mosquito activity were analyzed in the treatment group, a significant decrease in mosquito activity was detected in the group treated with Malathion 95ULV® the day after treatment with the effect lasting for two days. No significant daily changes in mosquito activity were detected after DeltaGard®20EW application. There were no significant differences between mosquito activity hot spot locations and non-hot spot locations when tree density, proximity to rivers, proximity to parks/open spaces, or parks/opem spaces density were analyzed spatially. However, hot spots were found to have more trees in a 50m radius and to be closer to rivers. A significant positive correlation between longevity and adult mosquito body size (Ae. vexans) was detected. Conclusions: The lack of significance when comparing traps in areas treated with DeltaGard®20EW and untreated areas indicates that changes may be due to natural background fluctuations in mosquito activity and population. Significant daily decreases in mosquito activity in the treatment groups were detected the day following Malathion 95ULV® treatment. The lack of significance in the DeltaGard®20EW trials may be due to issues with modelling like a lack of untreated trap locations for comparison, a starting population that was too low to detect significant changes, a lack of specific knowledge about the cumulative egg bank and Ae. vexans biology, too few trap locations, traps being placed strategically instead of randomly, the challenge of measuring background mosquito activity and population dynamics, and a lack of meteorological and landscape data specific to trap locations. Measuring adulticide efficacy in wild mosquitoes and creating models to analyze changes in their activity is challenging. A significant positive correlation between longevity and adult mosquito body size was detected for Ae. vexans mosquitoes, although further research should track specific cohorts of mosquitoes over time.City of Winnipeg, University of WinnipegMaster of Science in Bioscience, Technology, and Public Polic

Quantitative analyses of human West Nile Virus outbreaks in Greece, Hungary, Italy and Romania, 2010-2015.

West Nile Virus (WNV) is a non-communicable, geographically sparce, mosquito borne disease with considerable consequences for human health both at individual and collective level. Since its first isolation in 1937, several geographically spread sporadic, endemic and epidemic outbreaks of WNV disease have been recorded in every continent, except Antarctica. WNV is now the third most prevalent zoonotic febrile infectious disease in the EU. There is a gap in the literature that of synthesising multifactorial data relevant to successive human outbreaks in Europe. To address this gap, this study explored epidemiological, hydro-climatological and environmental data to make meaningful inferences about the composition of human epidemic outbreaks in Europe between 2010-2015. The analysis was based on secondary data collected from the ECDC (European Centre for Disease Prevention and Control), EUROSTAT and ECMWF (European Centre for Medium-Range Weather Forecasts). ECDC and EUROSTAT data were employed to generate the epidemiological profiles of human WNV outbreaks in Hungary, Italy, Greece and Romania which experienced consecutive outbreaks during the studied period. It showed that the ratio of men contracting WNV infections compared to women was higher across all years and countries (Hungary 1.7 (95% CI:1.1 to 2.5), Greece 4 (95% CI:3.4 to 4.8), Italy 4.7 (95% CI: 3.7 to 5.9) and Romania 1.7 (95% CI:1.29 to 2.4)). WNV occurred mostly in those over 65 years of age apart from Hungary (0.3 CI: 0.2 to 0.5) which reported most of its cases in those between 45-64 years of age. It also explored environmental and landscape factors influencing WNV’s distribution across the four south eastern and southern European countries experiencing recurring epidemics. The results suggest that human West Nile disease transmission between 2010 and 2015 occurred in both coastal and non-coastal areas but 63.7% of cases, across the four countries, were detected in non-coastal areas. This result may have been skewed as Hungary’s geography is land locked and Greece did not report any cases in 2015. The study also explored urban, intermediate and rural areas in relation to human WNV outbreaks and the analysis showed a mixed picture. The rise of infections in intermediate and urban areas may indicate that residential infrastructure or population concentration may generate more larval growth which may have led to the outbreaks, but this assertion requires further investigation. Hydroclimatic data on air temperature, dewpoint temperature, soil temperature, total precipitation, relative humidity, surface pressure, volumetric soil water, wind components U (east facing wind velocity) and V (north facing wind velocity) were extracted from the ECMWF’s Re-Analysis (ERA-Interim) system. A zero inflated mixture framework was employed as a means of assessing the relationship between these hydroclimatic parameters and human WNV incidence for the same countries and years. Three nested models were tested: lag0 (same month as the outbreak), lag1 (a month before the outbreak) and lag2 (2 months before a human WNV outbreak occurred). lag2 was the best fitting model. Apart from soil temperature and the V wind component, all other parameters were significant and highly associated with human WNV disease outbreaks in the best fitting model. Further research is needed on subsequent years to confirm the robustness of these findings

Predicting tick-borne disease risk: improving the distribution mapping of ticks and tick bite risk in Scotland

Maps of Ixodes ricinus distribution and maps depicting tick bite risk are essential for government and health organisations to target prevention and control strategies for tick-borne diseases. However, researchers often lack robust long-term and geographically extensive tick distribution data, and information about human exposure to ticks to measure risk. Citizen science projects, through the collective effort of many volunteers, have the potential to provide valuable data on tick bite risk and tick distribution, but are often based on opportunistic submission of reports. The overarching aim of this study was to assess methodologies to improve public health decision-making through distribution mapping of ticks and tick bite risk for Scotland. Research was undertaken to: compare the quality and robustness of predictive mapping with the three types of tick data most often used for predictive mapping; use statistical approaches to improve the quality of predictions of the distribution of I. ricinus in Scotland, including the predicted uncertainty; assess whether questing tick surveys reflect human-tick encounter risk; and finally, test the feasibility of a new citizen science approach to assess human risk of tick encounters. Analysis of the three existing datasets with I. ricinus distribution in Scotland showed that whereas data from questing tick surveys generate detailed predictive maps at local scale, at the country level, predictions were affected by poor data coverage. Additionally, dissimilarities in the predicted distribution pattern of I. ricinus between data from passive submission and from questing tick surveys were identified. This suggests the need for data from public submissions to gather information on absences and to account for volunteer effort. A predictive map of I. ricinus distribution in Scotland developed with a sophisticated Bayesian statistical technique (the stochastic partial differential equation (SPDE)) which accounted for several sources of variation was successful in improving the predictions in areas with poor data coverage, and the associated uncertainty. The relationship between questing tick surveys and human tick bite rate was then assessed. Questing tick surveys were carried out whilst collecting contemporaneous data on tick encounters from orienteers running the same areas in 11 events at world, national, regional and local orienteering events. This novel approach found that questing tick surveys are a good indicator of tick bite risk. Also, the number of people multiplied by the hours of exposure is the most meaningful denominator for human exposure to tick bites (correlation coefficient with questing tick abundance of 0.8, p=0.0052). From 340 reports from orienteers recorded across all events, a mean incidence of 409 tick bites per 1,000 person-hours exposure was recorded. Significant correlations were found between tick bite rate and temperature on the event day, the proportion of pastures around the track used by orienteers and the start time of the activity. A citizen science project was implemented in Scotland between May and November 2018 and again between March and November 2019. The project used a novel approach that included collection of denominator data (number of people exposed, and time spent) and additionally asked people to report both when they did, and importantly, when they did not encounter ticks. Tick bite and tick encounter rates calculated from participant reports were compared with predictions of questing tick abundance in two study areas, Lochaber and the Cairngorms using data collected from questing tick surveys. A total of 1,914 reports from 65 volunteers were received, with 231 and 118 reports received, respectively, from the Cairngorms and Lochaber areas. On average, the Cairngorms area registered 0.083 tick bites per person per hour of activity and 0.268 tick encounters per person per hour. Lochaber area registered 0.018 tick bites and 0.028 tick encounters per person per hour. Tick bite and tick encounter rates in the Cairngorms correlated better with predicted tick abundance in the area (correlation coefficient of 0.27 and 0.31, respectively) compared to Lochaber (correlation coefficient of 0.15 in both cases). Tick bite and tick encounter rates were found to depend both on questing tick abundance, and on factors related to human activity and behaviour. Type of human activity explained more variation in tick bite rate than questing tick abundance. Tick bite and tick encounter rates were quantified by activity type. These findings are valuable in identifying high risk activities and targeting public health messages. This study resulted in new methodologies to improve predictive mapping of ticks, and better understanding of tick bite risk and the factors that drive it, with the overall aim of improving control and prevention of tick-borne diseases

Epidemiology of dengue, chikungunya and zika in a naïve population in St. Kitts, West Indies

PhD ThesisArboviruses such as dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) are of increasing global health concern and have caused recent rapid outbreaks in the Americas. However, studies focusing on behavioural risk that would assist with the understanding of transmission factors are scarce. This prospective study followed immunologically naïve adults in an arbovirus endemic environment to investigate disease detection, transmission and associated risk factors. University students from non-endemic areas studying in St. Kitts and Nevis were recruited as volunteers in three cohorts of sentinels between September 2014 and May 2015 (n = 224). Plasma was collected at enrolment and every 4 months subsequently until September 2016 and assayed for anti-DENV and anti-CHIKV IgM and IgG ELISA antibodies. Additionally, specimens collected from suspected cases of acute arboviral infection within the wider island population and mosquitoes captured in neighbourhoods were analysed for DENV, CHIKV and ZIKV by RT-PCR. Epidemiological data gathered at each sampling were investigated using mixed effect models, generalised estimating equations, Bayesian techniques and Cox proportional hazards survival analysis. Evidence of dengue infection was found in all (100%) the suspected cases born in St. Kitts but proof of recent infection was elusive. Chikungunya prevalence in sentinels was 12.7% (95% PI: 8.2-18.4%), whereas prevalence in suspected cases born in St. Kitts was 69.6% (95% CI: 47.1-86.8%). Zika prevalence was 39.1% (95% CI: 25.1- 54.6%) and evidence of infection and vertical transmission were also found in Ae. aegypti mosquitoes. Climatic variables were significantly associated with transmission followed by socio-economic conditions, frequency of mosquito bites and exposure to Ae. aegypti. Data suggested that arbovirus transmission in St. Kitts are epidemic and expire when climatic conditions become unfavourable for mosquito transmission or herd immunity reaches a critical threshold. These findings increase the understanding of arboviral transmission in small islands and can assist in more efficient outbreak response