A planetary health innovation for disease, food and water challenges in Africa.

Many communities in low- and middle-income countries globally lack sustainable, cost-effective and mutually beneficial solutions for infectious disease, food, water and poverty challenges, despite their inherent interdependence1-7. Here we provide support for the hypothesis that agricultural development and fertilizer use in West Africa increase the burden of the parasitic disease schistosomiasis by fuelling the growth of submerged aquatic vegetation that chokes out water access points and serves as habitat for freshwater snails that transmit Schistosoma parasites to more than 200 million people globally8-10. In a cluster randomized controlled trial (ClinicalTrials.gov: NCT03187366) in which we removed invasive submerged vegetation from water points at 8 of 16 villages (that is, clusters), control sites had 1.46 times higher intestinal Schistosoma infection rates in schoolchildren and lower open water access than removal sites. Vegetation removal did not have any detectable long-term adverse effects on local water quality or freshwater biodiversity. In feeding trials, the removed vegetation was as effective as traditional livestock feed but 41 to 179 times cheaper and converting the vegetation to compost provided private crop production and total (public health plus crop production benefits) benefit-to-cost ratios as high as 4.0 and 8.8, respectively. Thus, the approach yielded an economic incentive-with important public health co-benefits-to maintain cleared waterways and return nutrients captured in aquatic plants back to agriculture with promise of breaking poverty-disease traps. To facilitate targeting and scaling of the intervention, we lay the foundation for using remote sensing technology to detect snail habitats. By offering a rare, profitable, win-win approach to addressing food and water access, poverty alleviation, infectious disease control and environmental sustainability, we hope to inspire the interdisciplinary search for planetary health solutions11 to the many and formidable, co-dependent global grand challenges of the twenty-first century.

Predicting Increased Incidence of Common Antibiotic-Resistant and Antibiotic-Associated Pathogens Using Ensemble Species Distribution Modeling.

The Centers for Disease Control estimates antibiotic-associated pathogens result in 2.8 million infections and 38,000 deaths annually in the United States. This study applies species distribution modeling to elucidate the impact of environmental determinants of human infectious disease in an era of rapid global change. We modeled methicillin-resistant Staphylococcus aureus and Clostridioides difficile using 31 publicly accessible bioclimatic, healthcare, and sociodemographic variables. Ensemble models were created from 8 unique statistical and machine learning algorithms. Using International Classification of Diseases, 10th Edition codes, we identified 305,528 diagnoses of methicillin-resistant S.aureus and 302,001 diagnoses of C.difficile presence. Three environmental factors - average maximum temperature, specific humidity, and agricultural land density - emerged as major predictors of increased methicillin-resistant S.aureus and C.difficile presence; variables representing healthcare availability were less important. Species distribution modeling may be a powerful tool for identifying areas at increased risk for disease presence and have important implications for disease surveillance systems.

Reframing Optimal Control Problems for Infectious Disease Management in Low-Income Countries.

Optimal control theory can be a useful tool to identify the best strategies for the management of infectious diseases. In most of the applications to disease control with ordinary differential equations, the objective functional to be optimized is formulated in monetary terms as the sum of intervention costs and the cost associated with the burden of disease. We present alternate formulations that express epidemiological outcomes via health metrics and reframe the problem to include features such as budget constraints and epidemiological targets. These alternate formulations are illustrated with a compartmental cholera model. The alternate formulations permit us to better explore the sensitivity of the optimal control solutions to changes in available budget or the desired epidemiological target. We also discuss some limitations of comprehensive cost assessment in epidemiology.

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.

Direct oral anticoagulants in patients with nonvalvular atrial fibrillation and extreme body weight.

BACKGROUND: Limited clinical data exist describing the use of direct oral anticoagulants (DOACs) in patient with extreme body weight. Thus, the International Society of Thrombosis and Haemostasis (ISTH) recommends avoiding DOACs in patients with weight >120 Kg, and on the contrary, no restrictions exist for underweight patients. OBJECTIVE: To evaluate the effects of extreme body weight on DOAC activity and to compare the clinical outcomes of patients with an extreme body weight versus patients with a normal weight (61-119 Kg) treated with DOACs. METHODS: Single tertiary care Italian centre multidisciplinary registry including nonvalvular atrial fibrillation (NVAF) patients treated with DOACs. Based on weight, three subcohorts were defined: (i) underweight patients (≤60 Kg); (ii) patients with a normal weight (61-119 Kg, as control group); and (iii) overweight patients (≥120 Kg). Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. RESULTS: 812 NVAF patients were included, 108 patients weighed ≤60 Kg (13%, underweight), 688 weighed between 61 and 119 Kg (85%, normal weight), and 16 weighed ≥120 Kg (2%, overweight). In particular, among underweight patients, dabigatran was prescribed in 26% patients, apixaban in 27%, rivaroxaban in 28% and edoxaban in 22% ones. Instead, among overweight patients, 44% were treated with dabigatran, 25% with apixaban, 25% with rivaroxaban and 4% with edoxaban. Underweight patients were older, more frequently women, with lower creatinine clearance and a history of previous strokes, resulting in higher CHA2DS2-VASc score than in both remaining groups. Up to 2 years, no statistically significant difference was observed between the three groups of weight for thromboembolic events (P = .765) and for overall bleeding (P = .125), but a trend towards decreased overall bleeding rates was noticed as weight increased (24.1% vs 16.7% vs 12.5%, respectively). CONCLUSION: In this tertiary care centre registry, 15% of patients treated with DOACs presented an extreme weight. Compared to patients with a normal weight, no significant rates of thromboembolic events were observed for underweight or overweight patients. A trend towards decreased overall bleeding frequency as weight increased was highlighted up to 2 years. The present results should be considered as preliminary and hypothesis generating.

Development, environmental degradation, and disease spread in the Brazilian Amazon.

The Amazon is Brazil's greatest natural resource and invaluable to the rest of the world as a buffer against climate change. The recent election of Brazil's president brought disputes over development plans for the region back into the spotlight. Historically, the development model for the Amazon has focused on exploitation of natural resources, resulting in environmental degradation, particularly deforestation. Although considerable attention has focused on the long-term global cost of "losing the Amazon," too little attention has focused on the emergence and reemergence of vector-borne diseases that directly impact the local population, with spillover effects to other neighboring areas. We discuss the impact of Amazon development models on human health, with a focus on vector-borne disease risk. We outline policy actions that could mitigate these negative impacts while creating opportunities for environmentally sensitive economic activities.

Precision mapping of snail habitat provides a powerful indicator of human schistosomiasis transmission.

Recently, the World Health Organization recognized that efforts to interrupt schistosomiasis transmission through mass drug administration have been ineffective in some regions; one of their new recommended strategies for global schistosomiasis control emphasizes targeting the freshwater snails that transmit schistosome parasites. We sought to identify robust indicators that would enable precision targeting of these snails. At the site of the world's largest recorded schistosomiasis epidemic-the Lower Senegal River Basin in Senegal-intensive sampling revealed positive relationships between intermediate host snails (abundance, density, and prevalence) and human urogenital schistosomiasis reinfection (prevalence and intensity in schoolchildren after drug administration). However, we also found that snail distributions were so patchy in space and time that obtaining useful data required effort that exceeds what is feasible in standard monitoring and control campaigns. Instead, we identified several environmental proxies that were more effective than snail variables for predicting human infection: the area covered by suitable snail habitat (i.e., floating, nonemergent vegetation), the percent cover by suitable snail habitat, and size of the water contact area. Unlike snail surveys, which require hundreds of person-hours per site to conduct, habitat coverage and site area can be quickly estimated with drone or satellite imagery. This, in turn, makes possible large-scale, high-resolution estimation of human urogenital schistosomiasis risk to support targeting of both mass drug administration and snail control efforts.

The influence of vector-borne disease on human history: socio-ecological mechanisms.

Vector-borne diseases (VBDs) are embedded within complex socio-ecological systems. While research has traditionally focused on the direct effects of VBDs on human morbidity and mortality, it is increasingly clear that their impacts are much more pervasive. VBDs are dynamically linked to feedbacks between environmental conditions, vector ecology, disease burden, and societal responses that drive transmission. As a result, VBDs have had profound influence on human history. Mechanisms include: (1) killing or debilitating large numbers of people, with demographic and population-level impacts; (2) differentially affecting populations based on prior history of disease exposure, immunity, and resistance; (3) being weaponised to promote or justify hierarchies of power, colonialism, racism, classism and sexism; (4) catalysing changes in ideas, institutions, infrastructure, technologies and social practices in efforts to control disease outbreaks; and (5) changing human relationships with the land and environment. We use historical and archaeological evidence interpreted through an ecological lens to illustrate how VBDs have shaped society and culture, focusing on case studies from four pertinent VBDs: plague, malaria, yellow fever and trypanosomiasis. By comparing across diseases, time periods and geographies, we highlight the enormous scope and variety of mechanisms by which VBDs have influenced human history.

Cost-effectiveness of combining drug and environmental treatments for environmentally transmitted diseases.

Control of neglected tropical diseases (NTDs) via mass drug administration (MDA) has increased considerably over the past decade, but strategies focused exclusively on human treatment show limited efficacy. This paper investigated trade-offs between drug and environmental treatments in the fight against NTDs by using schistosomiasis as a case study. We use optimal control techniques where the planner's objective is to treat the disease over a time horizon at the lowest possible total cost, where the total costs include treatment, transportation and damages (reduction in human health). We show that combining environmental treatments and drug treatments reduces the dependency on MDAs and that this reduction increases when the planners take a longer-run perspective on the fight to reduce NTDs. Our results suggest that NTDs with environmental reservoirs require moving away from a reliance solely on MDA to integrated treatment involving investment in both drug and environmental controls.

Tracking the response of industrial fishing fleets to large marine protected areas in the Pacific Ocean.

Large marine protected areas (MPAs) of unprecedented size have recently been established across the global oceans, yet their ability to meet conservation objectives is debated. Key areas of debate include uncertainty over nations' abilities to enforce fishing bans across vast, remote regions and the intensity of human impacts before and after MPA implementation. We used a recently developed vessel tracking data set (produced using Automatic Identification System detections) to quantify the response of industrial fishing fleets to 5 of the largest MPAs established in the Pacific Ocean since 2013. After their implementation, all 5 MPAs successfully kept industrial fishing effort exceptionally low. Detected fishing effort was already low in 4 of the 5 large MPAs prior to MPA implementation, particularly relative to nearby regions that did not receive formal protection. Our results suggest that these large MPAs may present major conservation opportunities in relatively intact ecosystems with low immediate impact to industrial fisheries, but the large MPAs we considered often did not significantly reduce fishing effort because baseline fishing was typically low. It is yet to be determined how large MPAs may shape global ocean conservation in the future if the footprint of human influence continues to expand. Continued improvement in understanding of how large MPAs interact with industrial fisheries is a crucial step toward defining their role in global ocean management.

Seguimiento a la Respuesta de las Flotillas de Pesca Industrial a las Grandes Áreas Marinas Protegidas Extensas Resumen Recientemente se han establecido grandes áreas marinas protegidas (AMPs) de tamaños nunca vistos en todos los océanos del mundo; sin embargo, se sigue debatiendo su habilidad para lograr los objetivos de conservación. El debate se centra en los siguientes temas importantes: la incertidumbre por la capacidad de las naciones para hacer cumplir las vedas de pesca en regiones vastas y remotas y la intensidad del impacto humano antes y después de la implementación de una AMP. Usamos un conjunto de datos de rastreo de navíos recientemente desarrollado (producido usando detecciones mediante el Sistema Automático de Identificación) para cuantificar la respuesta de las flotillas de pesca industrial ante cinco de las AMPs más grandes establecidas en el océano Pacífico desde 2013. Después de su implementación, las cinco AMPs mantuvieron exitosamente los esfuerzos de pesca industrial a niveles excepcionalmente bajos. El esfuerzo de pesca detectado ya se encontraba bajo en cuatro de las cinco grandes AMPs previo a la implementación, particularmente en relación con las regiones próximas que no reciben protección formal. Nuestros resultados sugieren que estas grandes AMPs pueden presentar oportunidades importantes de conservación en ecosistemas relativamente intactos con un impacto inmediato bajo para las pesquerías industriales, pero las grandes AMPs que consideramos con frecuencia no redujeron significativamente el esfuerzo de pesca porque la línea base de la pesca con frecuencia ya era baja. Todavía se debe determinar cómo las grandes AMPs pueden moldear la conservación mundial de los océanos en el futuro si la huella de la influencia humana continúa expandiéndose. La mejoría continua del entendimiento de cómo las grandes AMPs interactúan con las pesquerías industriales es un paso importante hacia la definición de su papel en el manejo mundial de los océanos.

Catastrophic Mortality, Allee Effects, and Marine Protected Areas.

For many species, reproductive failure may occur if abundance drops below critical Allee thresholds for successful breeding, in some cases impeding recovery. At the same time, extreme environmental events can cause catastrophic collapse in otherwise healthy populations. Understanding what natural processes and management strategies may allow for persistence and recovery of natural populations is critical in the face of expected climate change scenarios of increased environmental variability. Using a spatially explicit continuous-size fishery model with stochastic dispersal parameterized for abalone-a harvested species with sedentary adults and a dispersing larval phase-we investigated whether the establishment of a system of marine protected areas (MPAs) can prevent population collapse, compared with nonspatial management when populations are affected by mass mortality from environmental shocks and subject to Allee effects. We found that MPA networks dramatically reduced the risk of collapse following catastrophic events (75%-90% mortality), while populations often continued to decline in the absence of spatial protection. Similar resilience could be achieved by closing the fishery immediately following mass mortalities but would necessitate long periods without catch and therefore economic income. For species with Allee effects, the use of protected areas can ensure persistence following mass mortality events while maintaining ecosystem services during the recovery period.

The Potential Role of Direct and Indirect Contacts on Infection Spread in Dairy Farm Networks.

Animals' exchanges are considered the most effective route of between-farm infectious disease transmission. However, despite being often overlooked, the infection spread due to contaminated equipment, vehicles, or personnel proved to be important for several livestock epidemics. This study investigated the role of indirect contacts in a potential infection spread in the dairy farm network of the Province of Parma (Northern Italy). We built between-farm contact networks using data on cattle exchange (direct contacts), and on-farm visits by veterinarians (indirect contacts). We compared the features of the contact structures by using measures on static and temporal networks. We assessed the disease spreading potential of the direct and indirect network structures in the farm system by using data on the infection state of farms by paratuberculosis. Direct and indirect networks showed non-trivial differences with respect to connectivity, contact distribution, and super-spreaders identification. Furthermore, our analyses on paratuberculosis data suggested that the contributions of direct and indirect contacts on diseases spread are apparent at different spatial scales. Our results highlighted the potential role of indirect contacts in between-farm disease spread and underlined the need for a deeper understanding of these contacts to develop better strategies for prevention of livestock epidemics.

Reduced transmission of human schistosomiasis after restoration of a native river prawn that preys on the snail intermediate host.

Eliminating human parasitic disease often requires interrupting complex transmission pathways. Even when drugs to treat people are available, disease control can be difficult if the parasite can persist in nonhuman hosts. Here, we show that restoration of a natural predator of a parasite's intermediate hosts may enhance drug-based schistosomiasis control. Our study site was the Senegal River Basin, where villagers suffered a massive outbreak and persistent epidemic after the 1986 completion of the Diama Dam. The dam blocked the annual migration of native river prawns (Macrobrachium vollenhoveni) that are voracious predators of the snail intermediate hosts for schistosomiasis. We tested schistosomiasis control by reintroduced river prawns in a before-after-control-impact field experiment that tracked parasitism in snails and people at two matched villages after prawns were stocked at one village's river access point. The abundance of infected snails was 80% lower at that village, presumably because prawn predation reduced the abundance and average life span of latently infected snails. As expected from a reduction in infected snails, human schistosomiasis prevalence was 18 ± 5% lower and egg burden was 50 ± 8% lower at the prawn-stocking village compared with the control village. In a mathematical model of the system, stocking prawns, coupled with infrequent mass drug treatment, eliminates schistosomiasis from high-transmission sites. We conclude that restoring river prawns could be a novel contribution to controlling, or eliminating, schistosomiasis.

Heterogeneity in schistosomiasis transmission dynamics.

Simple models of disease propagation often disregard the effects of transmission heterogeneity on the ecological and epidemiological dynamics associated with host-parasite interactions. However, for some diseases like schistosomiasis, a widespread parasitic infection caused by Schistosoma worms, accounting for heterogeneity is crucial to both characterize long-term dynamics and evaluate opportunities for disease control. Elaborating on the classic Macdonald model for macroparasite transmission, we analyze families of models including explicit descriptions of heterogeneity related to differential transmission risk within a community, water contact patterns, the distribution of the snail host population, human mobility, and the seasonal fluctuations of the environment. Through simple numerical examples, we show that heterogeneous multigroup communities may be more prone to schistosomiasis than homogeneous ones, that the availability of multiple water sources can hinder parasite transmission, and that both spatial and temporal heterogeneities may have nontrivial implications for disease endemicity. Finally, we discuss the implications of heterogeneity for disease control. Although focused on schistosomiasis, results from this study may apply as well to other parasitic infections with complex transmission cycles, such as cysticercosis, dracunculiasis and fasciolosis.

The spatial spread of schistosomiasis: A multidimensional network model applied to Saint-Louis region, Senegal.

Schistosomiasis is a parasitic, water-related disease that is prevalent in tropical and subtropical areas of the world, causing severe and chronic consequences especially among children. Here we study the spatial spread of this disease within a network of connected villages in the endemic region of the Lower Basin of the Senegal River, in Senegal. The analysis is performed by means of a spatially explicit metapopulation model that couples local-scale eco-epidemiological dynamics with spatial mechanisms related to human mobility (estimated from anonymized mobile phone records), snail dispersal and hydrological transport of schistosome larvae along the main water bodies of the region. Results show that the model produces epidemiological patterns consistent with field observations, and point out the key role of spatial connectivity on the spread of the disease. These findings underline the importance of considering different transport pathways in order to elaborate disease control strategies that can be effective within a network of connected populations.

Body size and meta-community structure: the allometric scaling of parasitic worm communities in their mammalian hosts.

In this paper we derive from first principles the expected body sizes of the parasite communities that can coexist in a mammal of given body size. We use a mixture of mathematical models and known allometric relationships to examine whether host and parasite life histories constrain the diversity of parasite species that can coexist in the population of any host species. The model consists of one differential equation for each parasite species and a single density-dependent nonlinear equation for the affected host under the assumption of exploitation competition. We derive threshold conditions for the coexistence and competitive exclusion of parasite species using invasion criteria and stability analysis of the resulting equilibria. These results are then used to evaluate the range of parasites species that can invade and establish in a target host and identify the 'optimal' size of a parasite species for a host of a given body size; 'optimal' is defined as the body size of a parasite species that cannot be outcompeted by any other parasite species. The expected distributions of parasites body sizes in hosts of different sizes are then compared with those observed in empirical studies. Our analysis predicts the relative abundance of parasites of different size that establish in the host and suggests that increasing the ratio of parasite body size to host body size above a minimum threshold increases the persistence of the parasite population.

A global viability assessment of the European eel.

The global European eel (Anguilla anguilla) stock is critically endangered according to the IUCN, and the European Commission has urged the development of conservation plans aimed to ensure its viability. However, the complex life cycle of this panmictic species, which reproduces in the open ocean but spends most of its prereproductive life in continental waters (thus embracing a huge geographic range and a variety of habitat types), makes it difficult to assess the long-term effectiveness of conservation measures. The interplay between local and global stressors raises intriguing cross-scale conservation challenges that require a comprehensive modelling approach to be addressed. We developed a full life cycle model of the global European eel stock, encompassing both the oceanic and the continental phases of eel's life, and explicitly allowing for spatial heterogeneity in vital rates, availability of suitable habitat and settlement potential via a metapopulation approach. We calibrated the model against a long-term time series of global European eel catches and used it to hindcast the dynamics of the stock in the past and project it over the 21st century under different management scenarios. Although our analysis relies on a number of inevitable simplifying assumptions and on data that may not embrace the whole range of variation in population dynamics at the small spatiotemporal scale, our hindcast is consistent with the general pattern of decline of the stock over recent decades. The results of our projections suggest that (i) habitat loss played a major role in the European eel decline; (ii) the viability of the global stock is at risk if appropriate protection measures are not implemented; (iii) the recovery of spawner escapement requires that fishing mortality is significantly reduced; and (iv) the recovery of recruitment might not be feasible if reproductive output is not enhanced.

Infection with schistosome parasites in snails leads to increased predation by prawns: implications for human schistosomiasis control.

Schistosomiasis - a parasitic disease that affects over 200 million people across the globe - is primarily transmitted between human definitive hosts and snail intermediate hosts. To reduce schistosomiasis transmission, some have advocated disrupting the schistosome life cycle through biological control of snails, achieved by boosting the abundance of snails' natural predators. But little is known about the effect of parasitic infection on predator-prey interactions, especially in the case of schistosomiasis. Here, we present the results of laboratory experiments performed on Bulinus truncatus and Biomphalaria glabrata snails to investigate: (i) rates of predation on schistosome-infected versus uninfected snails by a sympatric native river prawn, Macrobrachium vollenhovenii, and (ii) differences in snail behavior (including movement, refuge-seeking and anti-predator behavior) between infected and uninfected snails. In predation trials, prawns showed a preference for consuming snails infected with schistosome larvae. In behavioral trials, infected snails moved less quickly and less often than uninfected snails, and were less likely to avoid predation by exiting the water or hiding under substrate. Although the mechanism by which the parasite alters snail behavior remains unknown, these results provide insight into the effects of parasitic infection on predator-prey dynamics and suggest that boosting natural rates of predation on snails may be a useful strategy for reducing transmission in schistosomiasis hotspots.

React or wait: which optimal culling strategy to control infectious diseases in wildlife.

We applied optimal control theory to an SI epidemic model to identify optimal culling strategies for diseases management in wildlife. We focused on different forms of the objective function, including linear control, quadratic control, and control with limited amount of resources. Moreover, we identified optimal solutions under different assumptions on disease-free host dynamics, namely: self-regulating logistic growth, Malthusian growth, and the case of negligible demography. We showed that the correct characterization of the disease-free host growth is crucial for defining optimal disease control strategies. By analytical investigations of the model with negligible demography, we demonstrated that the optimal strategy for the linear control can be either to cull at the maximum rate at the very beginning of the epidemic (reactive culling) when the culling cost is low, or never to cull, when culling cost is high. On the other hand, in the cases of quadratic control or limited resources, we demonstrated that the optimal strategy is always reactive. Numerical analyses for hosts with logistic growth showed that, in the case of linear control, the optimal strategy is always reactive when culling cost is low. In contrast, if the culling cost is high, the optimal strategy is to delay control, i.e. not to cull at the onset of the epidemic. Finally, we showed that for diseases with the same basic reproduction number delayed control can be optimal for acute infections, i.e. characterized by high disease-induced mortality and fast dynamics, while reactive control can be optimal for chronic ones.