The Aerosphere as a Network Connector of Organisms and Their Diseases

Aeroecological processes, especially powered flight of animals, can rapidly connect biological communities across the globe. This can have profound consequences for evolutionary diversification, energy and nutrient transfers, and the spread of infectious diseases. The latter is of particular consequence for human populations, since migratory birds are known to host diseases which have a history of transmission into domestic poultry or even jumping to human hosts. In this chapter, we present a scenario under which a highly pathogenic avian influenza (HPAI) strain enters North America from East Asia via postmolting waterfowl migration. We use an agent-based model (ABM) to simulate the movement and disease transmission among 106 generalized waterfowl agents originating from ten molting locations in eastern Siberia, with the HPAI seeded in only ~102 agents at one of these locations. Our ABM tracked the disease dynamics across a very large grid of sites as well as individual agents, allowing us to examine the spatiotemporal patterns of change in virulence of the HPAI infection as well as waterfowl host susceptibility to the disease. We concurrently simulated a 12-station disease monitoring network in the northwest USA and Canada in order to assess the potential efficacy of these sites to detect and confirm the arrival of HPAI. Our findings indicated that HPAI spread was initially facilitated but eventually subdued by the migration of host agents. Yet, during the 90-day simulation, selective pressures appeared to have distilled the HPAI strain to its most virulent form (i.e., through natural selection), which was counterbalanced by the host susceptibility being conversely reduced (i.e., through genetic predisposition and acquired immunity). The monitoring network demonstrated wide variation in the utility of sites; some were clearly better at providing early warnings of HPAI arrival, while sites further from the disease origin exposed the selective dynamics which slowed the spread of the disease albeit with the result of passing highly virulent strains into southern wintering locales (where human impacts are more likely). Though the ABM presented had generalized waterfowl migration and HPAI disease dynamics, this exercise demonstrates the power of such simulations to examine the extremely large and complex processes which comprise aeroecology. We offer insights into how such models could be further parameterized to represent HPAI transmission risks as well as how ABMs could be applied to other aeroecological questions pertaining to individual-based connectivity

The Aerosphere as a Network Connector of Organisms and Their Diseases

Aeroecological processes, especially powered flight of animals, can rapidly connect biological communities across the globe. This can have profound consequences for evolutionary diversification, energy and nutrient transfers, and the spread of infectious diseases. The latter is of particular consequence for human populations, since migratory birds are known to host diseases which have a history of transmission into domestic poultry or even jumping to human hosts. In this chapter, we present a scenario under which a highly pathogenic avian influenza (HPAI) strain enters North America from East Asia via postmolting waterfowl migration. We use an agent-based model (ABM) to simulate the movement and disease transmission among 106 generalized waterfowl agents originating from ten molting locations in eastern Siberia, with the HPAI seeded in only ~102 agents at one of these locations. Our ABM tracked the disease dynamics across a very large grid of sites as well as individual agents, allowing us to examine the spatiotemporal patterns of change in virulence of the HPAI infection as well as waterfowl host susceptibility to the disease. We concurrently simulated a 12-station disease monitoring network in the northwest USA and Canada in order to assess the potential efficacy of these sites to detect and confirm the arrival of HPAI. Our findings indicated that HPAI spread was initially facilitated but eventually subdued by the migration of host agents. Yet, during the 90-day simulation, selective pressures appeared to have distilled the HPAI strain to its most virulent form (i.e., through natural selection), which was counterbalanced by the host susceptibility being conversely reduced (i.e., through genetic predisposition and acquired immunity). The monitoring network demonstrated wide variation in the utility of sites; some were clearly better at providing early warnings of HPAI arrival, while sites further from the disease origin exposed the selective dynamics which slowed the spread of the disease albeit with the result of passing highly virulent strains into southern wintering locales (where human impacts are more likely). Though the ABM presented had generalized waterfowl migration and HPAI disease dynamics, this exercise demonstrates the power of such simulations to examine the extremely large and complex processes which comprise aeroecology. We offer insights into how such models could be further parameterized to represent HPAI transmission risks as well as how ABMs could be applied to other aeroecological questions pertaining to individual-based connectivity

Could changes in the agricultural landscape of northeastern China have influenced the long-distance transmission of highly pathogenic avian influenza H5Nx viruses?

In the last few years, several reassortant subtypes of highly pathogenic avian influenza viruses (HPAI H5Nx) have emerged in East Asia. These new viruses, mostly of subtype H5N1, H5N2, H5N6, and H5N8 belonging to clade 2.3.4.4, have been found in several Asian countries and have caused outbreaks in poultry in China, South Korea, and Vietnam. HPAI H5Nx also have spread over considerable distances with the introduction of viruses belonging to the same 2.3.4.4 clade in the U.S. (2014-2015) and in Europe (2014-2015 and 2016-2017). In this paper, we examine the emergence and spread of these new viruses in Asia in relation to published datasets on HPAI H5Nx distribution, movement of migratory waterfowl, avian influenza risk models, and land-use change analyses. More specifically, we show that between 2000 and 2015, vast areas of northeast China have been newly planted with rice paddy fields (3.21 million ha in Heilongjiang, Jilin, and Liaoning) in areas connected to other parts of Asia through migratory pathways of wild waterfowl. We hypothesize that recent land use changes in northeast China have affected the spatial distribution of wild waterfowl, their stopover areas, and the wild-domestic interface, thereby altering transmission dynamics of avian influenza viruses across flyways. Detailed studies of the habitat use by wild migratory birds, of the extent of the wild-domestic interface, and of the circulation of avian influenza viruses in those new planted areas may help to shed more light on this hypothesis, and on the possible impact of those changes on the long-distance patterns of avian influenza transmission

Integrating animal movement with habitat suitability for estimating dynamic landscape connectivity

Context: High-resolution animal movement data are becoming increasingly available, yet having a multitude of trajectories alone does not allow us to easily predict animal movement. To answer ecological and evolutionary questions at a population level, quantitative estimates of a species' potential to act as a link between patches, populations, or ecosystems are of importance. Objectives: We introduce an approach that combines movement-informed simulated trajectories with an environment-informed estimate of their ecological likelihood. With this approach, we estimated connectivity at the landscape level throughout the annual cycle of bar-headed geese (Anser indicus) in its native range. Methods: We used a tracking dataset of bar-headed geese to parameterise a multi-state movement model and to estimate temporally explicit habitat suitability within the species' range. We simulated migratory movements between range fragments, and estimated their ecological likelihood. The results are compared to expectations derived from published literature. Results: Simulated migrations matched empirical trajectories in key characteristics such as stopover duration. The estimated likelihood of simulated migrations was similar to that of empirical trajectories. We found that the predicted connectivity was higher within the breeding than in wintering areas, corresponding to previous findings for this species. Conclusions: We show how empirical tracking data and environmental information can be fused to make meaningful predictions about future animal movements. These are temporally explicit and transferable even outside the spatial range of the available data. Our integrative framework will prove useful for modelling ecological processes facilitated by animal movement, such as seed dispersal or disease ecology

The impact of surveillance and control on highly pathogenic avian influenza outbreaks in poultry in Dhaka division, Bangladesh

In Bangladesh, the poultry industry is an economically and socially important sector, but it is persistently threatened by the effects of H5N1 highly pathogenic avian influenza. Thus, identifying the optimal control policy in response to an emerging disease outbreak is a key challenge for policy-makers. To inform this aim, a common approach is to carry out simulation studies comparing plausible strategies, while accounting for known capacity restrictions. In this study we perform simulations of a previously developed H5N1 influenza transmission model framework, fitted to two separate historical outbreaks, to assess specific control objectives related to the burden or duration of H5N1 outbreaks among poultry farms in the Dhaka division of Bangladesh. In particular, we explore the optimal implementation of ring culling, ring vaccination and active surveillance measures when presuming disease transmission predominately occurs from premises-to-premises, versus a setting requiring the inclusion of external factors. Additionally, we determine the sensitivity of the management actions under consideration to differing levels of capacity constraints and outbreaks with disparate transmission dynamics. While we find that reactive culling and vaccination policies should pay close attention to these factors to ensure intervention targeting is optimised, across multiple settings the top performing control action amongst those under consideration were targeted proactive surveillance schemes. Our findings may advise the type of control measure, plus its intensity, that could potentially be applied in the event of a developing outbreak of H5N1 amongst originally H5N1 virus-free commercially-reared poultry in the Dhaka division of Bangladesh

Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor

Background: Endothelin receptor antagonists inhibit the progression of many cancers, but research into their influence on glioma has been limited. Methods: We treated glioma cell lines, LN-229 and SW1088, and melanoma cell lines, A375 and WM35, with two endothelin receptor type B (ETRB)-specific antagonists, A-192621 and BQ788, and quantified viable cells by the capacity of their intracellular esterases to convert non-fluorescent calcein AM into green-fluorescent calcein. We assessed cell proliferation by labeling cells with carboxyfluorescein diacetate succinimidyl ester and quantifying the fluorescence by FACS analysis. We also examined the cell cycle status using BrdU/propidium iodide double staining and FACS analysis. We evaluated changes in gene expression by microarray analysis following treatment with A-192621 in glioma cells. We examined the role of ETRB by reducing its expression level using small interfering RNA (siRNA). Results: We report that two ETRB-specific antagonists, A-192621 and BQ788, reduce the number of viable cells in two glioma cell lines in a dose- and time-dependent manner. We describe similar results for two melanoma cell lines. The more potent of the two antagonists, A-192621, decreases the mean number of cell divisions at least in part by inducing a G2/M arrest and apoptosis. Microarray analysis of the effects of A-192621 treatment reveals up-regulation of several DNA damage-inducible genes. These results were confirmed by real-time RT-PCR. Importantly, reducing expression of ETRB with siRNAs does not abrogate the effects of either A-192621 or BQ788 in glioma or melanoma cells. Furthermore, BQ123, an endothelin receptor type A (ETRA)-specific antagonist, has no effect on cell viability in any of these cell lines, indicating that the ETRB-independent effects on cell viability exhibited by A-192621 and BQ788 are not a result of ETRA inhibition. Conclusion: While ETRB antagonists reduce the viability of glioma cells in vitro, it appears unlikely that this effect is mediated by ETRB inhibition or cross-reaction with ETRA. Instead, we present evidence that A-192621 affects glioma and melanoma viability by activating stress/DNA damage response pathways, which leads to cell cycle arrest and apoptosis. This is the first evidence linking ETRB antagonist treatment to enhanced expression of DNA damage-inducible genes

Pathways for avian influenza virus spread: GPS reveals wild waterfowl in commercial livestock facilities and connectivity with the natural wetland landscape

Zoonotic diseases are of considerable concern to the human population and viruses such as avian influenza (AIV) threaten food security, wildlife conservation and human health. Wild waterfowl and the natural wetlands they use are known AIV reservoirs, with birds capable of virus transmission to domestic poultry populations. While infection risk models have linked migration routes and AIV outbreaks, there is a limited understanding of wild waterfowl presence on commercial livestock facilities, and movement patterns linked to natural wetlands. We documented 11 wild waterfowl (three Anatidae species) in or near eight commercial livestock facilities in Washington and California with GPS telemetry data. Wild ducks used dairy and beef cattle feed lots and facility retention ponds during both day and night suggesting use for roosting and foraging. Two individuals (single locations) were observed inside poultry facility boundaries while using nearby wetlands. Ducks demonstrated high site fidelity, returning to the same areas of habitats (at livestock facilities and nearby wetlands), across months or years, showed strong connectivity with surrounding wetlands, and arrived from wetlands up to 1251 km away in the week prior. Telemetry data provides substantial advantages over observational data, allowing assessment of individual movement behaviour and wetland connectivity that has significant implications for outbreak management. Telemetry improves our understanding of risk factors for waterfowl–livestock virus transmission and helps identify factors associated with coincident space use at the wild waterfowl–domestic livestock interface. Our research suggests that even relatively small or isolated natural and artificial water or food sources in/near facilities increases the likelihood of attracting waterfowl, which has important consequences for managers attempting to minimize or prevent AIV outbreaks. Use and interpretation of telemetry data, especially in near-real-time, could provide key information for reducing virus transmission risk between waterfowl and livestock, improving protective barriers between wild and domestic species, and abating outbreaks

Flying Over an Infected Landscape: Distribution of Highly Pathogenic Avian Influenza H5N1 Risk in South Asia and Satellite Tracking of Wild Waterfowl

Highly pathogenic avian influenza (HPAI) H5N1 virus persists in Asia, posing a threat to poultry, wild birds, and humans. Previous work in Southeast Asia demonstrated that HPAI H5N1 risk is related to domestic ducks and people. Other studies discussed the role of migratory birds in the long distance spread of HPAI H5N1. However, the interplay between local persistence and long-distance dispersal has never been studied. We expand previous geospatial risk analysis to include South and Southeast Asia, and integrate the analysis with migration data of satellite-tracked wild waterfowl along the Central Asia flyway. We find that the population of domestic duck is the main factor delineating areas at risk of HPAI H5N1 spread in domestic poultry in South Asia, and that other risk factors, such as human population and chicken density, are associated with HPAI H5N1 risk within those areas. We also find that satellite tracked birds (Ruddy Shelduck and two Bar-headed Geese) reveal a direct spatio-temporal link between the HPAI H5N1 hot-spots identified in India and Bangladesh through our risk model, and the wild bird outbreaks in May–June–July 2009 in China (Qinghai Lake), Mongolia, and Russia. This suggests that the continental-scale dynamics of HPAI H5N1 are structured as a number of persistence areas delineated by domestic ducks, connected by rare transmission through migratory waterfowl