Prediction and management of zoonotic spillover requires an understanding of infection dynamics within reservoir host populations. Spillover risk is commonly inferred from infection prevalence based on detection of viral genomic material, yet detection alone does not indicate the presence of infectious virus or a sufficient dose for transmission. We undertook a comprehensive investigation of Hendra virus shedding in its primary reservoir, Pteropus bats, analyzing quantitative PCR with reverse transcription (RT-qPCR) data from 6151 pooled urine samples collected across five sites over 3 years. We assessed longitudinal associations between viral prevalence (proportion of positive pooled urine samples), viral load proxies, and equine spillover, using generalized additive models and a permutation analysis. Peak prevalence periods associated with spillover events (N = 5) had a higher proportion of samples with high viral loads than periods without spillover. Prolonged periods of low viral load and low prevalence likely reflect noninfectious RNA or doses insufficient for cross-species transmission. Incorporating viral load metrics alongside prevalence can improve prediction of spillover risk.

Linking individual-level processes, such as survival and reproduction, to ecosystem dynamics is challenging due to interactions among populations and species. These interactions depend on organism traits, such as age, body size, and mass, and are influenced by fluctuations in population structure. Integral projection models (IPMs) have advanced our understanding of dynamics arising from population structure in continuous traits. Yet, these models have only been applied to relatively simple systems, featuring one or two species and spanning a fraction of the trophic levels observed in natural food webs. We extend these models in four ways. First, we provide a general multi-species IPM where population structure can be included in primary producers and primary and secondary consumers. Second, we link individual-level processes to ecosystem functioning by mapping fluxes of biomass between species to fluxes within individuals, using bioenergetic principles for allocation to maintenance, reproduction, or growth. Third, we introduce a nutrient recycling loop through which decomposers break down organic matter into nutrients that enable plant growth. Finally, we provide an efficient fitting algorithm to calibrate the model with time series of population sizes. We showcase our approach by parameterising and fitting the model to counts of elk, bison, wolves, and cougars in northern Yellowstone National Park to study the impact of predator extirpation and recovery. Our model predicts that bison decrease following predator removal and recover following predator recovery, suggesting a positive contribution of wolves and cougars to the increase of bison in northern Yellowstone. It also reproduces indirect effects of predators on woody deciduous vegetation regeneration. Our approach is suitable for a broad range of ecosystems, with applications for population management and ecological forecasting.

Rodents have co-existed with humans for centuries, and frequently exchange pathogens. Historically, rodent-driven plague outbreaks scoured the Old World, resulting in substantial human mortality. Although such pandemics have not occurred for centuries, serious threats from rodent-borne infections, such as the global emergence of mpox, still exist. Moreover, endemic and emerging rodent infections continue to cause substantial human morbidity and mortality in low-income and middle-income countries. Efforts by the medical community to control rodent-borne zoonoses primarily focus on treating or preventing symptoms in humans using biomedical interventions (eg, vaccination). Such approaches are geared towards preparedness and response but are insufficient for prevention. In this Personal View, we identify three key pillars that drive rodent-borne zoonotic spillover: ecology of rodent infections; use of human habitation by rodents (synanthropy); and the influence of humans on the ecological proliferation of rodents in our landscape (rodentation). The challenge is to leverage these pillars as entry points for interventions, to prevent spillover and reduce disease burden. Given shortcomings of rodent culling, we advocate for integrated countermeasures that are socially and ecologically grounded, apply systems thinking, and leverage emerging technologies to prevent spillover driven by persistent human-rodent interactions and global change.

Changes in the quality and quantity of food consumed can affect the health of hosts, their ability to control infections and potentially shape the likelihood of pathogen spillover. Dietary shifts have been proposed as one of the factors driving spillovers of zoonotic viruses from bats to humans. In this study, we examined how diet composition alters the immune response to viral shedding and the risk of spillover by developing a mechanistic model fitted to experimental data of Jamaican fruit bats infected with influenza A virus H18N11 and fed different diets. The model selected from alternative immune and metabolic relationships showed that the coupled effects of citrulline and tumour necrosis factor alpha (TNF) affected the control of viral shedding with parameters that varied with diet. Bats on the suboptimal fat diet appeared to control shedding more successfully than bats on suboptimal sugar or optimal protein diets. Yet, bats on the optimal diet could potentially cause lower hazard of spillover because of reduced food consumption, suggesting fewer and/or shorter visits at the feeding sites and thus transmission to secondary hosts. This study provides a parsimonious explanation of the barriers that affect viral shedding by reservoir hosts and the consequences for the hazard of spillover.

Background:Brucellosis is a significant but under-reported bacterial zoonosis in Rwanda. Despite recognition as one of Rwanda's top six priority zoonotic diseases in 2019, comprehensive epidemiological data linking human and animal infections remain limited, particularly in high-risk pastoral communities. This study aimed to determine brucellosis seroprevalence and associated risk factors in humans and livestock in Nyagatare District, a major livestock-producing region of Rwanda. Methods:A cross-sectional study was conducted from March to October 2023 across three sectors (Karangazi, Rwempasha, and Rwimiyanga sectors) using stratified random sampling. Blood samples were collected from 886 humans and 930 livestock (637 cattle, 222 goats, 71 sheep) and screened via indirect Enzyme-Linked-Immunosorbent Assay. Risk factor data were collected through structured questionnaires. Multivariable logistic regression identified factors associated with seropositivity, with results expressed as odds ratios (OR) and 95% confidence intervals (CI). Results:The overall seroprevalence was 19.9% (176/886; 95% CI: 17.3-22.6) in humans and 10.9% (101/930; 95% CI: 9.0-13.0) in livestock. Among livestock, seroprevalence was highest in cattle (11.9%, 76/637; 95% CI: 9.4-14.5), followed by goats (11.3%, 25/222; 95% CI: 7.1-15.4), and sheep (1.4%, 1/71; 95% CI: 0.0-4.2). In humans, significant risk factors included male gender (OR = 2.66, 95% CI: 1.57-4.64, p < 0.001), age >55 years (OR = 7.39, 95% CI: 3.82-14.8, p < 0.001), and working as an animal health practitioner (OR = 2.90, 95% CI: 1.38-6.06, p = 0.005). In livestock, key risk factors included retention of aborted animals in herds (OR = 10.0, 95% CI: 2.27-49.2, p = 0.003), improper disposal of aborted fetuses (OR = 3.15, 95% CI: 1.18-7.99, p = 0.018), and shared water sources (OR = 2.49, 95% CI: 1.27-4.93, p = 0.008). Geographic analysis revealed higher seropositivity in the Rwimiyaga sector (OR = 3.06, 95% CI: 1.37-7.45, p = 0.009). Conclusions:This study reveals a high burden of brucellosis in both human and livestock populations in Nyagatare District, with particularly elevated risk among animal health workers and where livestock management practices are poor. Our findings suggest three targeted interventions: (1) Mandatory use of personal protective equipment for animal health workers, (2) Proper disposal of infectious animal materials, and (3) Sector-specific control strategies for high prevalence areas. These results provide critical evidence for developing One-Health interventions to control brucellosis in Rwanda and similar East Africa settings.

Peste des petits ruminants virus (PPRV) is a multi-host pathogen with sheep and goats as main hosts. To investigate the role of cattle in the epidemiology of PPR, we simulated conditions similar to East African zero-grazing husbandry practices in a series of trials with local Zebu cattle (Bos taurus indicus) co-housed with goats (Capra aegagrus hircus). Furthermore, we developed a mathematical model to assess the impact of PPRV-transmission from cattle to goats. Of the 32 cattle intranasally infected with the locally endemic lineage IV strain PPRV/Ethiopia/Habru/2014 none transmitted PPRV to 32 co-housed goats. However, these cattle or cattle co-housed with PPRV-infected goats seroconverted. The results confirm previous studies that cattle currently play a negligible role in PPRV-transmission and small ruminant vaccination is sufficient for eradication. However, the possible emergence of PPRV strains more virulent for cattle may impact eradication. Therefore, continued monitoring of PPRV circulation and evolution is recommended.

Substantial global attention is focused on how to reduce the risk of future pandemics. Reducing this risk requires investment in prevention, preparedness, and response. Although preparedness and response have received significant focus, prevention, especially the prevention of zoonotic spillover, remains largely absent from global conversations. This oversight is due in part to the lack of a clear definition of prevention and lack of guidance on how to achieve it. To address this gap, we elucidate the mechanisms linking environmental change and zoonotic spillover using spillover of viruses from bats as a case study. We identify ecological interventions that can disrupt these spillover mechanisms and propose policy frameworks for their implementation. Recognizing that pandemics originate in ecological systems, we advocate for integrating ecological approaches alongside biomedical approaches in a comprehensive and balanced pandemic prevention strategy.

Nipah virus spillovers via consumption of date palm sap in Bangladesh vary substantially between years and have been associated with lower winter temperatures and precipitation. However, the mechanisms driving the interannual variation and the influence of weather remain unexplained. Here we investigated the hypothesis that weather patterns change human sap consumption and explain interannual variation in observed spillovers. We analyzed responses from a nationally representative survey conducted in Bangladesh in 2013-2016 on household date palm sap consumption and weather data for each division of Bangladesh, using logistic regression to examine whether sap consumption is associated with weather variability. We found significant associations of lower minimum temperatures and precipitation with increased household sap consumption during the sap harvesting season. This relationship was largely similar within all months and divisions, and strong associations of temperature (χ2 (1, n = 5,027) = 7.74, p < 0.01) and, independently, precipitation (χ2 = 8.00, p < 0.01) remained strong after accounting for month, location, and annual sap season. Interannual variation in date palm sap consumption in Bangladesh is likely best explained by temperature and precipitation patterns, where colder, drier winter days pose a higher risk for Nipah virus spillover. The knowledge gained in this study may be valuable for targeting timing of future behavioral interventions against consumption of date palm sap in Bangladesh.

Changes in the quality and quantity of food resources can affect individuals' health, the way they control infections and consequently the likelihood of onward transmission of pathogens. Dietary shifts have been proposed as one of the factors driving spillovers of zoonotic viruses from bats through a bridging host to humans. While there is a general understanding of the relationship between nutrition and infection in model systems, how diet affects pathogen shedding and the risk of spillover from bats is lacking. We used a data-driven mathematical modeling approach to disentangle the relation between diet, immunity, and viral shedding of Jamaican fruit bats infected with H18N11 and fed different dietary regimes. Model selection indicates that the synergistic interaction between the metabolite citrulline and the cytokine TNFα controls viral shedding in a diet-dependent manner. Bats on a sub-optimal fat diet are more successful in terminating shedding than bats on an optimal or sub-optimal sugar diet. However, when bat foraging behavior is considered, bats on the optimal diet show a lower spillover hazard, probably because of a feeding behavior less conducive to transmission. This study provides novel insights into the diet-driven mechanisms of viral shedding and how they can potentially contribute to spillover events.

Health SecurityAhead of Print CommentaryOpen AccessLooking Left: Ecologically Based Biosecurity to Prevent PandemicsJamie K. Reaser, Rohit A. Chitale, Gary M. Tabor, Peter J. Hudson, and Raina K. PlowrightJamie K. ReaserSearch for more papers by this author, Rohit A. ChitaleAddress correspondence to: Rohit A. Chitale, Council on Strategic Risks, 1025 Connecticut Ave NW, Suite 1000, Washington, DC 20036, E-mail Address: [email protected]Search for more papers by this author, Gary M. TaborSearch for more papers by this author, Peter J. HudsonSearch for more papers by this author, and Raina K. PlowrightSearch for more papers by this authorPublished Online:11 Dec 2023https://doi.org/10.1089/hs.2023.0089AboutSectionsPDF/EPUB Permissions & CitationsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail IntroductionEnvironmental conditions and human health are core contributors to national security.1 For decades, governments have been called to take a more comprehensive approach to biosecurity as a component of national security by broadening the concept of biological security to encompass ecological security.2 We define biosecurity, for the purposes of this commentary, as measures aimed at preventing the introduction and spread of biological organisms harmful to human assets, including human lives and livelihoods. In this context, we regard harm as processes that adversely impact the ability of ecological systems to generate ecosystem products (eg, fresh water, food, fuel sources) and services (eg, regulation of pests and disease). Highly influential institutions such as the World Health Organization acknowledge that "human health ultimately depends upon ecosystem products and services which are requisite for good human health and productive livelihoods."3 Such acknowledgments recognize that the protection of human health is a paramount ecological service provided by nature.4-6In the United States, policy actions have become increasingly consistent with the premise that a wide range of biologically based threats place the nation at risk. This is evidenced in recent executive orders and actions, including policies that regard health security and biological preparedness in the national security context7; connect human, animal, and environmental health within the US Global Health Security Strategy8; and frame the invasive species issue as a national security imperative.9 However, despite this policy framework, a review by the Council on Strategic Risks states that "global ecological disruption is arguably the 21st Century's most underappreciated security risk" and that "both climate and broader ecological security risks continue to be underrecognized as issues with present and tangible consequences for safety, security, and US strategic interests."10The COVID-19 pandemic brought biosecurity to the forefront of policymaking worldwide, drawing civil society's attention to the implications of "wildlife diseases" on human populations. As much as 75% of emerging zoonoses, infectious diseases arising from pathogens that spread from animals to humans, were initially detected in wildlife.11 While pathogens are a fundamental aspect of ecological systems, various perturbations can disrupt pathogen-wildlife interactions. Typically, land use change is the primary trigger for the chain of events by which zoonotic pathogens pass from wildlife to humans.12,13 This process includes (1) the presence of microbes that are pathogenic to humans circulating in free-living wildlife populations (pathogen host infection), (2) the infected host shedding viable pathogens into the environment (eg, via feces, urine, saliva), (3) human exposure to the pathogens occurring with subsequent infection (ie, spillover),14 and (4) further spread of the pathogen through the human population.15 We have previously termed this sequence of events the infect-shed-spill-spread cascade and the overall process land use-induced spillover.16 The spread of such pathogens from human to human may result in a small number of cases (clusters) or in regional (epidemic) or global (pandemic) outbreaks.Human consumption of and trade in wildlife are closely tied to land use changes; effects on natural resources may force local people to find alternative ways to sustain themselves, and habitat degradation often enables greater human access to wildlife. Wildlife consumption and commerce must be addressed to reduce the risk of human exposure to zoonotic pathogens.17 However, the most fundamental approach to minimizing pandemic risk is to prevent the ecological conditions that initiate land use-induced spillover.16 This, from our perspective, is where biosecurity should be rooted—in the security of living systems (bio in Greek). Because harm to ecological systems is an integral aspect of our definition of biosecurity, we also view biosecurity as integral to biological conservation. This type of biosecurity could be achieved by (1) fostering landscape immunity, the ecological conditions that, in combination, keep pathogen populations in check and foster the immunological defenses of wildlife within a specific ecosystem; and (2) minimizing the risk of human exposure to zoonotic pathogens, known as managing the dynamics of wildlife-human proximity.18-20Here we build on previous work (cited throughout this commentary) to make the case that ecological countermeasures (defined in the next section) provide a practical approach to achieving biosecurity at the landscape scale. We place ecological countermeasures squarely within the biosecurity context, with emphasis on the environment, defense, and health sectors, and highlight the importance of ecological countermeasures in building a more biologically informed approach to national security.Ecological CountermeasuresEcologically based solutions are needed to counter land use-driven problems. Thus, there is an urgent need to consider how the condition of lands and waters affects global health security, and to recognize that one of our best defenses against future pandemics is ecological protection and restoration—measures that will enable ecological systems to be more resilient to acute and chronic perturbations. This perspective builds on and advances the options to respond to zoonotic outbreaks outlined by Everard et al,21 who made an explicit call to consider the foundational role of ecosystems and their services in zoonotic disease prevention, as well as to regard ecological restoration as a strategic response to zoonotic disease regulation.For the purposes of this commentary, we regard ecological protection (sometimes referred to as environmental protection) as the act of preventing harm to ecosystem structures and functions, including ecological services. Where the protection of human health is a valued ecological service, protecting landscape immunity may be an explicit goal of ecological protection. Ecological restoration, in contrast, is intended to halt ecological harm and institute processes that reverse damage to an area for the purposes of recovering ecological structures and functions. For example, in 2021, we proposed the recovery of landscape immunity as an explicit goal of ecological restoration.20 As a related concept, ecological resilience can be regarded as the capacity of an ecosystem to resist and recover quickly from harm, thereby maintaining its structures and functions. Resilient ecosystems are regarded as "healthy" ecosystems.4 In 2022, we proposed that landscape immunity conveys resilience in ecosystems where zoonotic disease outbreaks are a potential perturbation.19Ecological countermeasures are highly targeted, landscape-based interventions aimed at arresting one or more of the components of land use-induced spillover. Fundamentally, ecological countermeasures are an aspect of ecological restoration intended to achieve resilience to anthropogenic disturbances at the ecosystem scale.19 Ecological countermeasures are therefore biosecurity measures that warrant at least as much research and development investment as other technical approaches to zoonotic disease risk reduction (eg, vaccines, vector biocontrols).22 Without question, spillover prevention—that is, keeping zoonotic pathogens from being transmitted between species—is the most cost-efficient approach to future biosecurity policy development.23Any act of ecological restoration taken to prevent zoonotic spillover by fostering landscape immunity can be considered an ecological countermeasure.19 At the local scale, relatively straightforward activities such as installing nesting boxes to help recover populations of vector-eating birds, or controlling invasive plants that provide ideal microclimates for pathogen vectors, can be conceived of as ecological countermeasures. The need and challenge going forward is to implement ecological countermeasures at ecosystem scale. Here, we briefly summarize 2 large-scale zoonosis-prevention projects, one aquatic and the other terrestrial, that we have conceptualized within an ecological countermeasures framework.Ecological Countermeasures to Prevent ZoonosesSchistosomiasis PreventionSchistosomiasis is an infestation of parasitic flatworms (Schistosoma spp) via aquatic snail hosts (eg, invasive Biomphalaria straminea) that causes life-threatening health conditions (eg, anemia, liver failure, bladder cancer, and lasting cognitive impairment) in more than 250 million people in Africa, Asia, and South America, with nearly 800 million more at risk. In Africa's Senegal River Basin, reintroduction of river prawns indigenous to the west coast of Africa (Macrobrachium vollenhovenii), where dam construction had blocked their annual migration, could offer a sustainable, low-cost form of snail control; when this approach was used in synergy with existing drug distribution campaigns (ie, medical countermeasures), the prawns were able to reduce or locally eliminate the parasite.24,25 Reestablishing trophic structure by restoring river prawns throughout these river ecosystems could serve as a novel ecological countermeasure.Hendra Virus PreventionHendra virus is a fruit bat-borne virus associated with high fatality in horses and humans (with horses acting as a bridging host) in Eastern Australia. The virus was first isolated in 1994, from an outbreak involving 21 horses and 2 humans in the Brisbane suburb of Hendra, Australia.26 Historically, flying foxes (fruit bats; Pteropus spp) were nomadic across vast expanses of their native habitats, moving thousands of kilometers in accordance with tree phenology, often in response to major climatic events. However, winter food shortages due to loss of forests that provide nectar in winter, interacting with moderate to severe climate events, caused these bats to take up residence in human-dominated landscapes where they can access reliable but poor-quality foods, especially from trees planted for decoration, shade, or fruit production.27 The agricultural landscapes the fruit bats now inhabit include horse pastures, and thus create the potential for horses to be exposed to bat excrement near the fruiting trees where the bats feed. Bats from roosts in such pastures are responsible for almost all Hendra virus spillover events in Australia.26,27 However, when remnant winter-flowering forests produce flushes of nectar, the bats leave their agricultural roosting sites en masse, flying long distances to feed in what remains of their traditional forested landscapes. Every time these increasingly rare pulses of winter nectar occur, spillovers are prevented. Thus, reestablishing winter-flowering eucalyptus tree species could enable bats to return to a context that conveys landscape immunity.27 This enhanced winter habitat could change the dynamics of human-bat proximity by reducing bat contact with horses, as well as improve the bats' nutritional status, thereby improving bat immune capacity and decreasing viral shedding of zoonotic viruses (eg, via urination).27 Implementation of this ecological countermeasure is in progress.Ecological Countermeasure Concepts in Interrelated SectorsCountermeasures in DefenseFrom an environmental perspective, countermeasures typically refer to site remediation and restoration activities undertaken to address contaminants.28 However, the ecological countermeasures concept and term itself arose out of a project supported by the US Defense Advanced Research Projects Agency (DARPA), which focused on stopping zoonotic spillover by characterizing the dynamics of henipavirus spillover from flying foxes to humans in Asia, Africa, and Australia. DARPA's support for the project reflected an understanding by the US Department of Defense (DOD) that environmental and human health are irrevocably linked. From a defense perspective, preventing zoonotic diseases reduces the need for military intervention by, for example, preventing forced human migration and conflict over limited resources.29 In addition, military personnel are especially at risk of disease when they occupy degraded environments, and they may place other people at risk by spreading pathogens or their vectors when relocating. DARPA's investment in the henipavirus spillover project also reflects DOD's charge to take the conservation actions necessary to "sustain the long-term ecological integrity of the resource base and the ecosystem services it provides."30Multiple DOD agencies, in addition to DARPA, execute innovative conservation- and human health-relevant research and development via projects facilitated by several grantmaking programs. In 2022, DOD issued a sustainability plan that recognizes that "to successfully execute this mission, the Military Departments must have access to the energy, land, air, water and other natural resources necessary to develop, train, and operate—today, and in the future. The Department recognizes the reality of an emerging climate crisis that is impacting our installations, equipment, and forces."31 The concept and practice of ecological countermeasures is thus consistent with the military mission-space, at least within the United States.The term ecological countermeasure is also in alignment with military linguistic frameworks: DOD defines countermeasure to mean "that form of military science that, by the employment of devices and/or techniques, has as its object the impairment of the operational effectiveness of enemy activity."32 This definition recognizes countermeasures not as single interventions, but as a body of science that applies a diverse array of technical tools and approaches to problem resolution—that is, to impede a potentially harmful agent from becoming harmful. It, therefore, stands to reason that ecological countermeasures, like any other form of countermeasure, should be applied to national security. This can be exemplified by the notion of landscape immunity, an ecological condition that minimizes the risk of zoonotic spillover—with spillover being the "enemy activity" to be prevented.Countermeasures in HealthIn the context of a broad national security agenda that links environmental condition to human wellbeing, it is also important to note that the term countermeasure is already well established in the health sector and is thus a key concept to be integrated into multiple US and global strategic documents, including the US Global Health Security Agenda33 and the US National Health Security Strategy and Implementation Plan.34 Medical countermeasures include lifesaving medicines and medical supplies used to diagnose, prevent, or treat conditions associated with chemical, biological, radiological, or nuclear threats, emerging infectious diseases, or natural disasters.35 The US Centers for Disease Control and Prevention uses the term medical countermeasure (eg, vaccines, antiviral drugs) within their public health and emergency preparedness framework36 to guide their capacity to provide medical interventions when a public health incident occurs. This work is complemented by the US Food and Drug Administration Medical Countermeasures Initiative, which coordinates medical countermeasure development, preparedness, and response.37 The World Health Organization has also adopted the medical understanding of countermeasures; for example, "sufficiency of countermeasures" is one of the primary criteria used to determine if a pathogen is of substantial health risk. Indeed, many zoonotic diseases are considered among the greatest public health threats due to their epidemic potential and countermeasure insufficiencies.38Advancing Ecological Countermeasure ScienceIn 2021, we established a 5-point action plan to address the needs and opportunities to further elucidate land use-induced spillover and establish ecological countermeasures as a component of ecological restoration.20 Given that ecological resilience conveys biosecurity, this proposal is readily applicable to advancing ecological countermeasure science through a biosecurity lens. Here, we succinctly summarize this high-level proposal for advancing ecological countermeasure science: 1.One Health and Planetary Health frameworks are ideal contexts for collaborative, interdisciplinary ecological countermeasure concept development, case study cataloging, and research collaboration.39,40 Although every ecological countermeasure project needs to be fit-to-context in terms of approaches and timelines, a next step in this field of work is to develop risk analysis frameworks that can be used to assess the costs and benefits of interventions, identify opportunities to amplify returns on investment where multiple goals can be achieved simultaneously (eg, conserving biodiversity and protecting public health), and plan for the mitigation of unintended adverse consequences.2.Despite increased investments for zoonotic pathogen discovery in understudied species and regions, there remains a need to educate policymakers, funding agencies, and early-career scientists on these information gaps—with the goal to inspire development of the resources and sizable body of researchers needed to identify and employ ecological countermeasures.3.Untangling the causal relationships between land use change and zoonotic spillover will require the coupling of field-based empirical studies that identify the parsimonious links with large-scale experiments and dynamic mechanistic models. Thus, there is a need for granting agencies to prioritize the funding that makes these complex investigations possible over adequate timescales.4.Readily accessible zoonotic pathogen/host datasets are fundamental to ecological countermeasure development. National governments and multilateral frameworks should therefore set targets that prioritize zoonotic pathogen surveillance and monitoring, especially considering the pending shifts in species' geography due to globalization and climate change.5.Public health interventions often neglect context-specific social, cultural, and historical factors and inadequately engage the people they are designed to benefit. To be effective, ecological countermeasures development and implementation must consider inputs from social science disciplines, as well as the expertise gained by Indigenous and local peoples.Advancing Ecological Countermeasure PolicyIn principle, biosecurity draws from multiple fields, sectors, and agencies, particularly those with missions related to the management of harmful, or potentially harmful, biological organisms (eg, invasive species). One Biosecurity has been proposed as a framework to improve scientific and policy integration across the full spectrum of biosecurity concerns driven by the biological invasion of organisms, including zoonotic pathogens and their hosts.41 We have already addressed countermeasures in environmental, defense, and health sector contexts as historically relevant for the points made and reflecting the current highly fragmented policy paradigm within the United States. In this section, we align with a more comprehensive, integrated approach to biosecurity policy that would include ecological countermeasures as one "tool" in a comprehensive "toolkit."Biosecurity policy development in the United States has lagged behind that of other countries, most notably Australia and New Zealand.42,43 New Zealand was the earliest adopter of a comprehensive approach to biosecurity; its 1993 Biosecurity Act44 provides a rigorous framework for preventing harmful organisms from entering the country. New Zealand's strong commitment to enforcing this legislation, and the nearly 3 decades that its civil society has had to adopt prevention measures as societal norms, undoubtedly played a significant role in the country's ability to rapidly and robustly respond to COVID-19 in the first year of the pandemic, in a manner approachable by few other countries.45We cannot identify a national security issue in the United States in which there is a greater disparity between the scale of effect and the scale of response than biological invasions, of which nonnative zoonotic pathogens are a major component. At the level of the US Executive Office of the President, the call for greater comprehensive attention to biosecurity has existed since the Carter-era executive order on exotic organisms,46 and has since been repeated in 2 executive orders on invasive species, in which the National Invasive Species Council (NISC) was established and then expanded to institute a cost-efficient, cooperative leadership.9,47 NISC now includes the secretaries of DOD and the US Department of Health and Human Services, as well as the senior-most political appointees of 10 other agencies and 4 components of the Executive Office of the President (ie, The White House).NISC management plans and other guidance documents48 place a strong emphasis on prevention measures, but almost exclusively from the border control perspective. Recently, a more holistic vision was reflected in a special issue of Biological Invasions that responds to NISC's 2016-2018 management plan.49 For example, Burgos-Rodríguez and Burgiel50 reviewed the patchwork of US authorities that unevenly address various aspects of the federal government's legislative capacity to rapidly detect and respond to infectious pathogens, nonnative pathogen hosts, and all other invasive species, with a view toward addressing framework gaps. After considering the recommendations arising out of all of the articles in the special issue, Reaser51 drafted a blueprint that outlines policies, goals, and actions to be taken by relevant Executive Branch agencies and components of the Executive Office of the President to institute a national biosecurity program that engages agencies with missions ranging from border control and defense to human health and conservation. (The role of land management agencies in biosecurity should be readily apparent.) We also believe that ecological countermeasures must be a core component of this framework; reestablishing landscape immunity following environmental perturbations and managing wildlife-human dynamics of proximity will minimize the risk of biological invasion by all nonnative taxa. This is critically important given the role that a wide range of invasive plants, insects, arthropods, and vertebrates play in amplifying zoonotic disease risks.52From its outset in 2021, the Biden administration has voiced an intent to address pandemic risks and interrelated national security agendas, including by prioritizing an update to the National Biodefense Strategy.53 The president stated thatit is essential that we refresh and reinvigorate our national science and technology strategy to set us on a strong course for the next 75 years, so that our children and grandchildren may inhabit a healthier, safer, more just, peaceful, and prosperous world. This effort will require us to bring together our brightest minds across academia, medicine, industry, and government—breaking down the barriers that too often limit our vision and our progress, and prioritizing the needs, interests, fears, and aspirations of the American people.54While biosecurity is now unusually high on the US national security agenda, there is yet good reason to draw attention to what remains lacking; an ecological approach to addressing zoonotic disease is still largely absent from these policy constructs. For example, the National Strategy for the COVID-19 Response and Pandemic Preparedness55 is focused on medical countermeasures and safeguarding the economy. Although it does include a goal to restore US leadership and build better preparedness for future threats, measures to safeguard ecological resilience (eg, via landscape immunity) are noticeably absent from a list of measures to "build better biopreparedness and expand resilience for biological threats"—a list that includes monitoring current and emerging biological threats, securing funding to improve biopreparedness, establishing the Center for Forecasting and Outbreak Analytics at the US Centers for Disease Control and Prevention, and developing a sustainable US infrastructure for biological and pandemic events. Neither the executive order to mobilize the US response to COVID-19 and provide leadership on global health security56 nor the executive order to protect public health and the environment, as well as restore science to tackle the climate crisis,57 point to the critical role of ecological systems in addressing these issues or direct agencies to take supportive, ecologically based actions. Even within an executive order focused on the climate crises,58 the only explicit directive focused on ecological resilience is an echoing of the widely popularized "30 by 30" goal, which calls for saving at least 30% of US land and water by 2030.59 Across the full suite of pandemic-related executive actions, we also note the tendency to place agencies such as the Department of the Interior, which has a mission to conserve and manage the nation's natural resources, at the leadership periphery.An understanding of land use-induced spillover and the deployment of ecological countermeasures is crucial to future biosecurity policy development. Protection of ecological systems goes far beyond values in aesthetics, outdoor recreation, and long-term access to the natural resources that support the human enterprise. The protection of human health is an ecological service, and COVID-19 has aptly demonstrated that site-specific measures to maintain and restore landscape immunity should be regarded as biosecurity measures of national priority and global-scale importance. Our assertion here is consistent with the "8 pillars of action" that the Council on Strategic Risks proposes to address the security implications of ecological disruption—particularly Pillar 2 to "promote methods that protect and expand critical systems and services," Pillar 5 to "reduce pandemic risk at point of origin," Pillar 6 to "amplify ecological and national security issues in the US government," and Pillar 7 to "initiate an ecological security research agenda."10 It is our hope that future actions spurred by the council's findings and recommendations will explicitly incorporate ecological countermeasures in policy and practice.This commentary focuses on US biosecurity because that is the context in which we have explicit expertise. However, the overarching message that biosecurity should include landscape-based interventions—ecological countermeasures—to prevent the emergence and movement of zoonotic pathogens clearly has global relevance. In the modern age, the implications of landscape decisions made at the local level can transcend ecological and jurisdictional boundaries via trade and transportation pathways. The biosecurity principles and practices presented in this commentary need to be taken up by, among others, the International Zoonoses Community of Experts, convened by the Group of 7 ministers responsible for climate and the environment to facilitate scientific and technological collaboration,60 as well as the international partnership initiatives prompted by the COVID-19 pandemic, such as PREZODE (Preventing Zoonotic Disease Emergence)61 and the Preventing Pandemics at the Source coalition.62 Readers interested in advancing the science of ecological countermeasures to better inform policy can find the basis for a One Health research agenda in articles that informed this commentary.16,19ConclusionThe large-scale protection and restoration of natural systems affords adaptation and resilience capacity—which is what literally enables Earth to sustain humans and all other species. A resilient biosphere is generative in the face of tremendous pressures, including crises that facilitate human conflicts. All the options and opportunities that humans will have available to them as the world changes in unpredictable and unprecedented ways are ecologically based. In the context of zoonotic disease outbreaks, ecological countermeasures should be considered fundamental components of the national security agenda. Performance metrics for ecological countermeasures, guided by the outputs of the action plan developed by us in 2021,20 could serve as land management standards worldwide.We therefore emphasize the importance of using the concept and term ecological countermeasures to help normalize zoonotic disease risk management as a core component of national security and to emphasize the importance of prioritizing ecologically oriented concerns and solutions among competing policy issues. Furthermore, it is our hope that frameworks and terms that explicitly make the connection between national security and its ecological foundations will help government administrations, in the United States and elsewhere, increase their support for senior-level representatives from the life sciences within national security bodies and as external advisor

Prediction and management of zoonotic pathogen spillover requires an understanding of infection dynamics within reservoir host populations. Transmission risk is often assessed using prevalence of infected hosts, with infection status based on the presence of genomic material. However, detection of viral genomic material alone does not necessarily indicate the presence of infectious virus, which could decouple prevalence from transmission risk. We undertook a multi-faceted investigation of Hendra virus shedding in Pteropus bats, combining insights from virus isolation, viral load proxies, viral prevalence, and longitudinal patterns of shedding, from 6,151 samples. In addition to seasonal and interannual fluctuation in prevalence, we found evidence for periodic shifts in the distribution of viral loads. The proportion of bats shedding high viral loads was higher during peak prevalence periods during which spillover events were observed, and lower during non-peak periods when there were no spillovers. We suggest that prolonged periods of low viral load and low prevalence reflect prolonged shedding of non-infectious RNA, or viral loads that are insufficient or unlikely to overcome dose barriers to spillover infection. These findings show that incorporating viral load (or proxies of viral load) into longitudinal studies of virus excretion will better inform predictions of spillover risk than prevalence alone. Significance statement We present a comprehensive analysis of a high-profile bat-virus system (Hendra virus in Australian flying-foxes) to demonstrate that both prevalence and viral loads can shift systematically over time, resulting in concentrated periods of increased spillover risk when prevalence and viral loads are high. We further suggest that prolonged periods of low-prevalence, low-load shedding may not reflect excretion of infectious virus, resolving the outstanding puzzle of why spillovers have not been observed during periods of low off-season prevalence in subtropical Australia, or more frequently in tropical Australia despite consistent low-prevalence shedding. The consideration of viral loads (or proxies of viral load) along with prevalence may improve risk inference from longitudinal surveys of zoonotic viruses across wildlife reservoir hosts.

A central debate in ecology has been the long-running discussion on the role of apex predators in affecting the abundance and dynamics of their prey. In terrestrial systems, research has primarily relied on correlational approaches, due to the challenge of implementing robust experiments with replication and appropriate controls. A consequence of this is that we largely suffer from a lack of mechanistic understanding of the population dynamics of interacting species, which can be surprisingly complex. Mechanistic models offer an opportunity to examine the causes and consequences of some of this complexity. We present a bioenergetic mechanistic model of a tritrophic system where the primary vegetation resource follows a seasonal growth function, and the herbivore and carnivore species are modeled using two integral projection models (IPMs) with body mass as the phenotypic trait. Within each IPM, the demographic functions are structured according to bioenergetic principles, describing how animals acquire and transform resources into body mass, energy reserves, and breeding potential. We parameterize this model to reproduce the population dynamics of grass, elk, and wolves in northern Yellowstone National Park (USA) and investigate the impact of wolf reintroduction on the system. Our model generated predictions that closely matched the observed population sizes of elk and wolf in Yellowstone prior to and following wolf reintroduction. The introduction of wolves into our basal grass-elk bioenergetic model resulted in a population of 99 wolves and a reduction in elk numbers by 61% (from 14,948 to 5823) at equilibrium. In turn, vegetation biomass increased by approximately 25% in the growing season and more than threefold in the nongrowing season. The addition of wolves to the model caused the elk population to switch from being food-limited to being predator-limited and had a stabilizing effect on elk numbers across different years. Wolf predation also led to a shift in the phenotypic composition of the elk population via a small increase in elk average body mass. Our model represents a novel approach to the study of predator-prey interactions, and demonstrates that explicitly considering and linking bioenergetics, population demography and body mass phenotypes can provide novel insights into the mechanisms behind complex ecosystem processes.

Abstract Anthropogenic land use change is a major driver of zoonotic pathogen spillover from wildlife to humans. According to the land use‐induced spillover model, land use change alters environmental conditions that in turn alter the dynamics between zoonotic pathogens and their wildlife hosts. Thus, in response to the global spread of the SARS‐CoV‐2 virus (the agent of COVID‐19 disease), there have been renewed calls for landscape conservation as a disease preventive measure, including by the G7 Ministers responsible for Climate and the Environment. Landscape immunity, as a new construct, points to four paradigm shifts the world must favor to effectively mitigate pandemic risks. We provide a landscape immunity primer for policy makers and make the case for “world views” that place Homo sapiens within ecological systems, regard human health as an ecological service, prioritize investments in prevention, and apply ecological restoration to human health goals. Crisis is a conversation starter for reimagining and recommitting ourselves to what is most vital and generative. We urge world leaders to make the move to a nature‐positive world.

Many animal species are susceptible to SARS-CoV-2 and could potentially act as reservoirs, yet transmission of the virus in non-human free-living animals has not been documented. White-tailed deer (Odocoileus virginianus), the predominant cervid in North America, are susceptible to SARS-CoV-2 infection, and experimentally infected fawns can transmit the virus. To test the hypothesis that SARS-CoV-2 may be circulating in deer, we tested 283 retropharyngeal lymph node (RPLN) samples collected from 151 free-living and 132 captive deer in Iowa from April 2020 through December of 2020 for the presence of SARS-CoV-2 RNA. Ninety-four of the 283 deer (33.2%; 95% CI: 28, 38.9) samples were positive for SARS-CoV-2 RNA as assessed by RT-PCR. Notably, between November 23, 2020 and January 10, 2021, 80 of 97 (82.5%; 95% CI 73.7, 88.8) RPLN samples had detectable SARS-CoV-2 RNA by RT-PCR. Whole genome sequencing of the 94 positive RPLN samples identified 12 SARS-CoV-2 lineages, with B.1.2 (n = 51; 54.5%), and B.1.311 (n = 19; 20%) accounting for ~75% of all samples. The geographic distribution and nesting of clusters of deer and human lineages strongly suggest multiple zooanthroponotic spillover events and deer-to-deer transmission. The discovery of sylvatic and enzootic SARS-CoV-2 transmission in deer has important implications for the ecology and long-term persistence, as well as the potential for spillover to other animals and spillback into humans. These findings highlight an urgent need for a robust and proactive “One Health” approach to obtaining a better understanding of the ecology and evolution of SARS-CoV-2. One-Sentence Summary SARS-CoV-2 was detected in one-third of sampled white-tailed deer in Iowa between September 2020 and January of 2021 that likely resulted from multiple human-to-deer spillover and deer-to-deer transmission events.

Helminth infections are cryptic and can be difficult to study in wildlife species. Helminth research in wildlife hosts has historically required invasive animal handling and necropsy, while results from noninvasive parasite research, like scat analysis, may not be possible at the helminth species or individual host levels. To increase the utility of noninvasive sampling, individual hosts can be identified by applying molecular methods. This allows for longitudinal sampling of known hosts and can be paired with individual-level covariates. Here we evaluate a combination of methods and existing long-term monitoring data to identify patterns of cestode infections in gray wolves in Yellowstone National Park. Our goals were: (1) Identify the species and apparent prevalence of cestodes infecting Yellowstone wolves; (2) Assess the relationships between wolf biological and social characteristics and cestode infections; (3) Examine how wolf samples were affected by environmental conditions with respect to the success of individual genotyping. We collected over 200 wolf scats from 2018-2020 and conducted laboratory analyses including individual wolf genotyping, sex identification, cestode identification, and fecal glucocorticoid measurements. Wolf genotyping success rate was 45%, which was higher in the winter but decreased with higher precipitation and as more time elapsed between scat deposit and collection. One cestode species was detected in 28% of all fecal samples, and 38% of known individuals. The most common infection was Echinococcus granulosus sensu lato (primarily E. canadensis). Adult wolves had 4x greater odds of having a cestode infection than pups, as well as wolves sampled in the winter. Our methods provide an alternative approach to estimate cestode prevalence and to linking parasites to known individuals in a wild host system, but may be most useful when employed in existing study systems and when field collections are designed to minimize the time between fecal deposition and collection.

There is mounting evidence of SARS-CoV-2 spillover from humans into many domestic, companion, and wild animal species. Research indicates that humans have infected white-tailed deer, and that deer-to-deer transmission has occurred, indicating that deer could be a wildlife reservoir and a source of novel SARS-CoV-2 variants. We examined the hypothesis that the Omicron variant is actively and asymptomatically infecting the free-ranging deer of New York City. Between December 2021 and February 2022, 155 deer on Staten Island, New York, were anesthetized and examined for gross abnormalities and illnesses. Paired nasopharyngeal swabs and blood samples were collected and analyzed for the presence of SARS-CoV-2 RNA and antibodies. Of 135 serum samples, 19 (14.1%) indicated SARS-CoV-2 exposure, and 11 reacted most strongly to the wild-type B.1 lineage. Of the 71 swabs, 8 were positive for SARS-CoV-2 RNA (4 Omicron and 4 Delta). Two of the animals had active infections and robust neutralizing antibodies, revealing evidence of reinfection or early seroconversion in deer. Variants of concern continue to circulate among and may reinfect US deer populations, and establish enzootic transmission cycles in the wild: this warrants a coordinated One Health response, to proactively surveil, identify, and curtail variants of concern before they can spill back into humans.

During recent decades, pathogens that originated in bats have become an increasing public health concern. A major challenge is to identify how those pathogens spill over into human populations to generate a pandemic threat1. Many correlational studies associate spillover with changes in land use or other anthropogenic stressors2,3, although the mechanisms underlying the observed correlations have not been identified4. One limitation is the lack of spatially and temporally explicit data on multiple spillovers, and on the connections among spillovers, reservoir host ecology and behaviour and viral dynamics. We present 25 years of data on land-use change, bat behaviour and spillover of Hendra virus from Pteropodid bats to horses in subtropical Australia. These data show that bats are responding to environmental change by persistently adopting behaviours that were previously transient responses to nutritional stress. Interactions between land-use change and climate now lead to persistent bat residency in agricultural areas, where periodic food shortages drive clusters of spillovers. Pulses of winter flowering of trees in remnant forests appeared to prevent spillover. We developed integrative Bayesian network models based on these phenomena that accurately predicted the presence or absence of clusters of spillovers in each of the 25 years. Our long-term study identifies the mechanistic connections between habitat loss, climate and increased spillover risk. It provides a framework for examining causes of bat virus spillover and for developing ecological countermeasures to prevent pandemics.

Body size variation is an enigma. We do not understand why species achieve the sizes they do, and this means we also do not understand the circumstances under which gigantism or dwarfism is selected. We develop size-structured integral projection models to explore evolution of body size and life history speed. We make few assumptions and keep models simple: all functions remain constant across models except for the one that describes development of body size with age. We set sexual maturity to occur when size attains 80% of the asymptotic size, which is typical of a large mammal, and allow negative density dependence to only affect either reproduction or juvenile survival. Fitness – the quantity that is maximized by adaptive evolution – is carrying capacity in our models, and we are consequently interested in how it changes with size at sexual maturity, and how this association varies with development rate. The simple models generate complex dynamics while providing insight into the circumstances when extremes of body size evolve. The direction of selection leading to either gigantism or dwarfism crucially depends on the proportion of the population that is sexually mature, which in turn depends on how the development function determines the survivorship schedule. The developmental trajectories consequently interact with size-specific survival or reproductive rates to determine the best life history and the optimal body size emerges from that interaction. These dynamics result in trade-offs between different components of the life history, with the form of the trade-off that emerges depending upon where in the life history density dependence operates most strongly. Empirical application of the approach we develop has potential to help explain the enigma of body size variation across the tree of life.

A central debate in ecology has been the long running discussion on the role of apex predators in affecting the abundance and dynamics of their prey. In terrestrial systems, research has primarily relied on correlational approaches, due to the challenge of implementing robust experiments with replication and appropriate controls. A consequence of this is that we largely suffer from a lack of mechanistic understanding of the population dynamics of interacting species that can be surprisingly complex. Mechanistic models offer an opportunity to examine the causes and consequences of some of this complexity. We present a bioenergetic mechanistic model of a tri-trophic system where the primary vegetation resource follows a seasonal growth function, and the herbivore and carnivore species are modelled using two integral projection models (IPMs) with body mass as the phenotypic trait. Within each IPM, the demographic functions are structured according to bioenergetic principles, describing how animals acquire and transform resources into body mass, energy reserves and breeding potential. We parameterise this model to reproduce the population dynamics of grass, elk and wolves in northern Yellowstone (USA), and investigate the impact of wolf reintroduction on the system. Our model generated predictions that closely matched the observed population sizes of elk and wolf in Yellowstone prior to and post wolf reintroduction. The introduction of wolves into our basal grass-elk bioenergetic model resulted in a population of 99 wolves, and a reduction in elk numbers by 61% (from 14,948 to 5,823) at equilibrium. In turn, vegetation biomass increased by approximately 25% in the growing season and more than 3-fold in the non-growing season. The addition of wolves to the model caused the elk population to shift from being food-limited to being predator-limited, and had a stabilising effect on elk numbers across different years. Wolf predation also led to a shift in the phenotypic composition of the elk population, via a small increase in elk average body mass. Our model represents a novel approach to the study of predator-prey interactions. Explicitly considering and linking bioenergetics, population demography and body mass phenotypes can provide novel insights into the mechanisms behind complex ecosystem processes.