Ecological and socioeconomic factors associated with the human burden of environmentally mediated pathogens: a global analysis.

BACKGROUND: Billions of people living in poverty are at risk of environmentally mediated infectious diseases-that is, pathogens with environmental reservoirs that affect disease persistence and control and where environmental control of pathogens can reduce human risk. The complex ecology of these diseases creates a global health problem not easily solved with medical treatment alone. METHODS: We quantified the current global disease burden caused by environmentally mediated infectious diseases and used a structural equation model to explore environmental and socioeconomic factors associated with the human burden of environmentally mediated pathogens across all countries. FINDINGS: We found that around 80% (455 of 560) of WHO-tracked pathogen species known to infect humans are environmentally mediated, causing about 40% (129 488 of 359 341 disability-adjusted life years) of contemporary infectious disease burden (global loss of 130 million years of healthy life annually). The majority of this environmentally mediated disease burden occurs in tropical countries, and the poorest countries carry the highest burdens across all latitudes. We found weak associations between disease burden and biodiversity or agricultural land use at the global scale. In contrast, the proportion of people with rural poor livelihoods in a country was a strong proximate indicator of environmentally mediated infectious disease burden. Political stability and wealth were associated with improved sanitation, better health care, and lower proportions of rural poverty, indirectly resulting in lower burdens of environmentally mediated infections. Rarely, environmentally mediated pathogens can evolve into global pandemics (eg, HIV, COVID-19) affecting even the wealthiest communities. INTERPRETATION: The high and uneven burden of environmentally mediated infections highlights the need for innovative social and ecological interventions to complement biomedical advances in the pursuit of global health and sustainability goals. FUNDING: Bill & Melinda Gates Foundation, National Institutes of Health, National Science Foundation, Alfred P. Sloan Foundation, National Institute for Mathematical and Biological Synthesis, Stanford University, and the US Defense Advanced Research Projects Agency.

Evidence gaps and diversity among potential win-win solutions for conservation and human infectious disease control.

As sustainable development practitioners have worked to "ensure healthy lives and promote well-being for all" and "conserve life on land and below water", what progress has been made with win-win interventions that reduce human infectious disease burdens while advancing conservation goals? Using a systematic literature review, we identified 46 proposed solutions, which we then investigated individually using targeted literature reviews. The proposed solutions addressed diverse conservation threats and human infectious diseases, and thus, the proposed interventions varied in scale, costs, and impacts. Some potential solutions had medium-quality to high-quality evidence for previous success in achieving proposed impacts in one or both sectors. However, there were notable evidence gaps within and among solutions, highlighting opportunities for further research and adaptive implementation. Stakeholders seeking win-win interventions can explore this Review and an online database to find and tailor a relevant solution or brainstorm new solutions.

Environmental Persistence of the World's Most Burdensome Infectious and Parasitic Diseases.

Humans live in complex socio-ecological systems where we interact with parasites and pathogens that spend time in abiotic and biotic environmental reservoirs (e.g., water, air, soil, other vertebrate hosts, vectors, intermediate hosts). Through a synthesis of published literature, we reviewed the life cycles and environmental persistence of 150 parasites and pathogens tracked by the World Health Organization's Global Burden of Disease study. We used those data to derive the time spent in each component of a pathogen's life cycle, including total time spent in humans versus all environmental stages. We found that nearly all infectious organisms were "environmentally mediated" to some degree, meaning that they spend time in reservoirs and can be transmitted from those reservoirs to human hosts. Correspondingly, many infectious diseases were primarily controlled through environmental interventions (e.g., vector control, water sanitation), whereas few (14%) were primarily controlled by integrated methods (i.e., combining medical and environmental interventions). Data on critical life history attributes for most of the 150 parasites and pathogens were difficult to find and often uncertain, potentially hampering efforts to predict disease dynamics and model interactions between life cycle time scales and infection control strategies. We hope that this synthetic review and associated database serve as a resource for understanding both common patterns among parasites and pathogens and important variability and uncertainty regarding particular infectious diseases. These insights can be used to improve systems-based approaches for controlling environmentally mediated diseases of humans in an era where the environment is rapidly changing.

Host preferences inhibit transmission from potential superspreader host species.

Host species that are particularly abundant, infectious and/or infected tend to contribute disproportionately to symbiont (parasite or mutualist) maintenance in multi-host systems. Therefore, in a facultative multi-host system where two host species had high densities, high symbiont infestation intensities and high infestation prevalence, we expected interspecific transmission rates to be high. Instead, we found that interspecific symbiont transmission rates to caged sentinel hosts were an order of magnitude lower than intraspecific transmission rates in the wild. Using laboratory experiments to decompose transmission rates, we found that opportunities for interspecific transmission were frequent, where interspecific and intraspecific contact rate functions were statistically indistinguishable. However, most interspecific contacts did not lead to transmission events owing to a previously unrecognized transmission barrier: strong host preferences. During laboratory choice experiments, the symbiont preferred staying on or dispersing to its current host species, even though the oligochaete symbiont is a globally distributed host generalist that can survive and reproduce on many snail host species. These surprising results suggest that when managing symbiont transmission, identifying key host species is still important, but it may be equally important to identify and manage transmission barriers that keep potential superspreader host species in check.

Schistosome infection in Senegal is associated with different spatial extents of risk and ecological drivers for Schistosoma haematobium and S. mansoni.

Schistosome parasites infect more than 200 million people annually, mostly in sub-Saharan Africa, where people may be co-infected with more than one species of the parasite. Infection risk for any single species is determined, in part, by the distribution of its obligate intermediate host snail. As the World Health Organization reprioritizes snail control to reduce the global burden of schistosomiasis, there is renewed importance in knowing when and where to target those efforts, which could vary by schistosome species. This study estimates factors associated with schistosomiasis risk in 16 villages located in the Senegal River Basin, a region hyperendemic for Schistosoma haematobium and S. mansoni. We first analyzed the spatial distributions of the two schistosomes' intermediate host snails (Bulinus spp. and Biomphalaria pfeifferi, respectively) at village water access sites. Then, we separately evaluated the relationships between human S. haematobium and S. mansoni infections and (i) the area of remotely-sensed snail habitat across spatial extents ranging from 1 to 120 m from shorelines, and (ii) water access site size and shape characteristics. We compared the influence of snail habitat across spatial extents because, while snail sampling is traditionally done near shorelines, we hypothesized that snails further from shore also contribute to infection risk. We found that, controlling for demographic variables, human risk for S. haematobium infection was positively correlated with snail habitat when snail habitat was measured over a much greater radius from shore (45 m to 120 m) than usual. S. haematobium risk was also associated with large, open water access sites. However, S. mansoni infection risk was associated with small, sheltered water access sites, and was not positively correlated with snail habitat at any spatial sampling radius. Our findings highlight the need to consider different ecological and environmental factors driving the transmission of each schistosome species in co-endemic landscapes.

Continued preference for suboptimal habitat reduces bat survival with white-nose syndrome.

Habitat alteration can influence suitability, creating ecological traps where habitat preference and fitness are mismatched. Despite their importance, ecological traps are notoriously difficult to identify and their impact on host-pathogen dynamics remains largely unexplored. Here we assess individual bat survival and habitat preferences in the midwestern United States before, during, and after the invasion of the fungal pathogen that causes white-nose syndrome. Despite strong selection pressures, most hosts continued to select habitats where disease severity was highest and survival was lowest, causing continued population declines. However, some individuals used refugia where survival was higher. Over time, a higher proportion of the total population used refugia than before pathogen arrival. Our results demonstrate that host preferences for habitats with high disease-induced mortality can create ecological traps that threaten populations, even in the presence of accessible refugia.

Improving rural health care reduces illegal logging and conserves carbon in a tropical forest.

Tropical forest loss currently exceeds forest gain, leading to a net greenhouse gas emission that exacerbates global climate change. This has sparked scientific debate on how to achieve natural climate solutions. Central to this debate is whether sustainably managing forests and protected areas will deliver global climate mitigation benefits, while ensuring local peoples' health and well-being. Here, we evaluate the 10-y impact of a human-centered solution to achieve natural climate mitigation through reductions in illegal logging in rural Borneo: an intervention aimed at expanding health care access and use for communities living near a national park, with clinic discounts offsetting costs historically met through illegal logging. Conservation, education, and alternative livelihood programs were also offered. We hypothesized that this would lead to improved health and well-being, while also alleviating illegal logging activity within the protected forest. We estimated that 27.4 km2 of deforestation was averted in the national park over a decade (∼70% reduction in deforestation compared to a synthetic control, permuted P = 0.038). Concurrently, the intervention provided health care access to more than 28,400 unique patients, with clinic usage and patient visitation frequency highest in communities participating in the intervention. Finally, we observed a dose-response in forest change rate to intervention engagement (person-contacts with intervention activities) across communities bordering the park: The greatest logging reductions were adjacent to the most highly engaged villages. Results suggest that this community-derived solution simultaneously improved health care access for local and indigenous communities and sustainably conserved carbon stocks in a protected tropical forest.

Handling times and saturating transmission functions in a snail-worm symbiosis.

All dynamic species interaction models contain an assumption that describes how contact rates scale with population density. Choosing an appropriate contact-density function is important, because different functions have different implications for population dynamics and stability. However, this choice can be challenging, because there are many possible functions, and most are phenomenological and thus difficult to relate to underlying ecological processes. Using one such phenomenological function, we described a nonlinear relationship between field transmission rates and host density in a common snail-oligochaete symbiosis. We then used a well-known contact function from predator-prey models, the Holling Type II functional response, to describe and predict host snail contact rates in the laboratory. The Holling Type II functional response accurately described both the nonlinear contact-density relationship and the average contact duration that we observed. Therefore, we suggest that contact rates saturate with host density in this system because each snail contact requires a non-instantaneous handling time, and additional possible contacts do not occur during that handling time. Handling times and nonlinear contact rates might also explain the nonlinear relationship between symbiont transmission and snail density that we observed in the field, which could be confirmed by future work that controls for other potential sources of seasonal variation in transmission rates. Because most animal contacts are not instantaneous, the Holling Type II functional response might be broadly relevant to diverse host-symbiont systems.

Defensive Symbionts Mediate Host-Parasite Interactions at Multiple Scales.

In protection mutualisms, defensive symbionts protect their hosts from natural enemies, including parasites. Protection mutualisms were historically considered rare ecological relationships, but recent examples demonstrate that defensive symbionts are both quite common and diverse. Defensive symbionts can have surprisingly large effects on host and parasite ecology at the individual, population, guild, and community scales. However, the highly context-dependent nature of protection mutualisms makes it difficult to identify and quantify the roles that defensive symbionts play in host-parasite systems. The mutualism-parasitism continuum framework can be used to understand and predict the outcomes of these interactions under variable environmental and ecological contexts. Embracing and expanding this theory will improve future research, and may better prepare us to use defensive symbionts as biocontrol agents.

Dispersal of a defensive symbiont depends on contact between hosts, host health, and host size.

Symbiont dispersal is necessary for the maintenance of defense mutualisms in space and time, and the distribution of symbionts among hosts should be intricately tied to symbiont dispersal behaviors. However, we know surprisingly little about how most defensive symbionts find and choose advantageous hosts or what cues trigger symbionts to disperse from their current hosts. In a series of six experiments, we explored the dispersal ecology of an oligochaete worm (Chaetogaster limnaei) that protects snail hosts from infection by larval trematode parasites. Specifically, we determined the factors that affected net symbiont dispersal from a current "donor" host to a new "receiver" host. Symbionts rarely dispersed unless hosts directly came in contact with one another. However, symbionts overcame their reluctance to disperse across the open environment if the donor host died. When hosts came in direct contact, net symbiont dispersal varied with both host size and trematode infection status, whereas symbiont density did not influence the probability of symbiont dispersal. Together, these experiments show that symbiont dispersal is not a constant, random process, as is often assumed in symbiont dispersal models, but rather the probability of dispersal varies with ecological conditions and among individual hosts. The observed heterogeneity in dispersal rates among hosts may help to explain symbiont aggregation among snail hosts in nature.

Parasite predators exhibit a rapid numerical response to increased parasite abundance and reduce transmission to hosts.

Predators of parasites have recently gained attention as important parts of food webs and ecosystems. In aquatic systems, many taxa consume free-living stages of parasites, and can thus reduce parasite transmission to hosts. However, the importance of the functional and numerical responses of parasite predators to disease dynamics is not well understood. We collected host-parasite-predator cooccurrence data from the field, and then experimentally manipulated predator abundance, parasite abundance, and the presence of alternative prey to determine the consequences for parasite transmission. The parasite predator of interest was a ubiquitous symbiotic oligochaete of mollusks, Chaetogaster limnaei limnaei, which inhabits host shells and consumes larval trematode parasites. Predators exhibited a rapid numerical response, where predator populations increased or decreased by as much as 60% in just 5 days, depending on the parasite:predator ratio. Furthermore, snail infection decreased substantially with increasing parasite predator densities, where the highest predator densities reduced infection by up to 89%. Predators of parasites can play an important role in regulating parasite transmission, even when infection risk is high, and especially when predators can rapidly respond numerically to resource pulses. We suggest that these types of interactions might have cascading effects on entire disease systems, and emphasize the importance of considering disease dynamics at the community level.