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.

Pyrethroid insecticides pose greater risk than organophosphate insecticides to biocontrol agents for human schistosomiasis.

Use of agrochemicals, including insecticides, is vital to food production and predicted to increase 2-5 fold by 2050. Previous studies have shown a positive association between agriculture and the human infectious disease schistosomiasis, which is problematic as this parasitic disease infects approximately 250 million people worldwide. Certain insecticides might runoff fields and be highly toxic to invertebrates, such as prawns in the genus Macrobrachium, that are biocontrol agents for snails that transmit the parasites causing schistosomiasis. We used a laboratory dose-response experiment and an observational field study to determine the relative toxicities of three pyrethroid (esfenvalerate, λ-cyhalothrin, and permethrin) and three organophosphate (chlorpyrifos, malathion, and terbufos) insecticides to Macrobrachium prawns. In the lab, pyrethroids were consistently several orders of magnitude more toxic than organophosphate insecticides, and more likely to runoff fields at lethal levels according to modeling data. At 31 water contact sites in the lower basin of the Senegal River where schistosomiasis is endemic, we found that Macrobrachium prawn survival was associated with pyrethroid but not organophosphate application rates to nearby crop fields after controlling for abiotic and prawn-level factors. Our laboratory and field results suggest that widely used pyrethroid insecticides can have strong non-target effects on Macrobrachium prawns that are biocontrol agents where 400 million people are at risk of human schistosomiasis. Understanding the ecotoxicology of high-risk insecticides may help improve human health in schistosomiasis-endemic regions undergoing agricultural expansion.

Exposure, hazard, and vulnerability all contribute to Schistosoma haematobium re-infection in northern Senegal.

BACKGROUND: Infectious disease risk is driven by three interrelated components: exposure, hazard, and vulnerability. For schistosomiasis, exposure occurs through contact with water, which is often tied to daily activities. Water contact, however, does not imply risk unless the environmental hazard of snails and parasites is also present in the water. By increasing reliance on hazardous activities and environments, socio-economic vulnerability can hinder reductions in exposure to a hazard. We aimed to quantify the contributions of exposure, hazard, and vulnerability to the presence and intensity of Schistosoma haematobium re-infection. METHODOLOGY/PRINCIPAL FINDINGS: In 13 villages along the Senegal River, we collected parasitological data from 821 school-aged children, survey data from 411 households where those children resided, and ecological data from all 24 village water access sites. We fit mixed-effects logistic and negative binomial regressions with indices of exposure, hazard, and vulnerability as explanatory variables of Schistosoma haematobium presence and intensity, respectively, controlling for demographic variables. Using multi-model inference to calculate the relative importance of each component of risk, we found that hazard (Æ©wi = 0.95) was the most important component of S. haematobium presence, followed by vulnerability (Æ©wi = 0.91). Exposure (Æ©wi = 1.00) was the most important component of S. haematobium intensity, followed by hazard (Æ©wi = 0.77). Model averaging quantified associations between each infection outcome and indices of exposure, hazard, and vulnerability, revealing a positive association between hazard and infection presence (OR = 1.49, 95% CI 1.12, 1.97), and a positive association between exposure and infection intensity (RR 2.59-3.86, depending on the category; all 95% CIs above 1). CONCLUSIONS/SIGNIFICANCE: Our findings underscore the linkages between social (exposure and vulnerability) and environmental (hazard) processes in the acquisition and accumulation of S. haematobium infection. This approach highlights the importance of implementing both social and environmental interventions to complement mass drug administration.

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.

Identification of Snails and Schistosoma of Medical Importance via Convolutional Neural Networks: A Proof-of-Concept Application for Human Schistosomiasis.

In recent decades, computer vision has proven remarkably effective in addressing diverse issues in public health, from determining the diagnosis, prognosis, and treatment of diseases in humans to predicting infectious disease outbreaks. Here, we investigate whether convolutional neural networks (CNNs) can also demonstrate effectiveness in classifying the environmental stages of parasites of public health importance and their invertebrate hosts. We used schistosomiasis as a reference model. Schistosomiasis is a debilitating parasitic disease transmitted to humans via snail intermediate hosts. The parasite affects more than 200 million people in tropical and subtropical regions. We trained our CNN, a feed-forward neural network, on a limited dataset of 5,500 images of snails and 5,100 images of cercariae obtained from schistosomiasis transmission sites in the Senegal River Basin, a region in western Africa that is hyper-endemic for the disease. The image set included both images of two snail genera that are relevant to schistosomiasis transmission - that is, Bulinus spp. and Biomphalaria pfeifferi - as well as snail images that are non-component hosts for human schistosomiasis. Cercariae shed from Bi. pfeifferi and Bulinus spp. snails were classified into 11 categories, of which only two, S. haematobium and S. mansoni, are major etiological agents of human schistosomiasis. The algorithms, trained on 80% of the snail and parasite dataset, achieved 99% and 91% accuracy for snail and parasite classification, respectively, when used on the hold-out validation dataset - a performance comparable to that of experienced parasitologists. The promising results of this proof-of-concept study suggests that this CNN model, and potentially similar replicable models, have the potential to support the classification of snails and parasite of medical importance. In remote field settings where machine learning algorithms can be deployed on cost-effective and widely used mobile devices, such as smartphones, these models can be a valuable complement to laboratory identification by trained technicians. Future efforts must be dedicated to increasing dataset sizes for model training and validation, as well as testing these algorithms in diverse transmission settings and geographies.

Land use impacts on parasitic infection: a cross-sectional epidemiological study on the role of irrigated agriculture in schistosome infection in a dammed landscape.

BACKGROUND: Water resources development promotes agricultural expansion and food security. But are these benefits offset by increased infectious disease risk? Dam construction on the Senegal River in 1986 was followed by agricultural expansion and increased transmission of human schistosomes. Yet the mechanisms linking these two processes at the individual and household levels remain unclear. We investigated the association between household land use and schistosome infection in children. METHODS: We analyzed cross-sectional household survey data (n = 655) collected in 16 rural villages in August 2016  across demographic, socio-economic and land use dimensions, which were matched to Schistosoma haematobium (n = 1232) and S. mansoni (n = 1222) infection data collected from school-aged children. Mixed effects regression determined the relationship between irrigated area and schistosome infection presence and intensity. RESULTS: Controlling for socio-economic and demographic risk factors, irrigated area cultivated by a household was associated with an increase in the presence of S. haematobium infection (odds ratio [OR] = 1.14; 95% confidence interval [95% CI]: 1.03-1.28) but not S. mansoni infection (OR = 1.02; 95% CI: 0.93-1.11). Associations between infection intensity and irrigated area were positive but imprecise (S. haematobium: rate ratio [RR] = 1.05; 95% CI: 0.98-1.13, S. mansoni: RR = 1.09; 95% CI: 0.89-1.32). CONCLUSIONS: Household engagement in irrigated agriculture increases individual risk of S. haematobium but not S. mansoni infection. Increased contact with irrigated landscapes likely drives exposure, with greater impacts on households relying on agricultural livelihoods.

Visualization of schistosomiasis snail habitats using light unmanned aerial vehicles.

Schistosomiasis, or "snail fever", is a parasitic disease affecting over 200 million people worldwide. People become infected when exposed to water containing particular species of freshwater snails. Habitats for such snails can be mapped using lightweight, inexpensive and field-deployable consumer-grade Unmanned Aerial Vehicles (UAVs), also known as drones. Drones can obtain imagery in remote areas with poor satellite imagery. An unexpected outcome of using drones is public engagement. Whereas sampling snails exposes field technicians to infection risk and might disturb locals who are also using the water site, drones are novel and fun to watch, attracting crowds that can be educated about the infection risk.

Aquatic macrophytes and macroinvertebrate predators affect densities of snail hosts and local production of schistosome cercariae that cause human schistosomiasis.

BACKGROUND: Schistosomiasis is responsible for the second highest burden of disease among neglected tropical diseases globally, with over 90 percent of cases occurring in African regions where drugs to treat the disease are only sporadically available. Additionally, human re-infection after treatment can be a problem where there are high numbers of infected snails in the environment. Recent experiments indicate that aquatic factors, including plants, nutrients, or predators, can influence snail abundance and parasite production within infected snails, both components of human risk. This study investigated how snail host abundance and release of cercariae (the free swimming stage infective to humans) varies at water access sites in an endemic region in Senegal, a setting where human schistosomiasis prevalence is among the highest globally. METHODS/PRINCIPAL FINDINGS: We collected snail intermediate hosts at 15 random points stratified by three habitat types at 36 water access sites, and counted cercarial production by each snail after transfer to the laboratory on the same day. We found that aquatic vegetation was positively associated with per-capita cercarial release by snails, probably because macrophytes harbor periphyton resources that snails feed upon, and well-fed snails tend to produce more parasites. In contrast, the abundance of aquatic macroinvertebrate snail predators was negatively associated with per-capita cercarial release by snails, probably because of several potential sublethal effects on snails or snail infection, despite a positive association between snail predators and total snail numbers at a site, possibly due to shared habitat usage or prey tracking by the predators. Thus, complex bottom-up and top-down ecological effects in this region plausibly influence the snail shedding rate and thus, total local density of schistosome cercariae. CONCLUSIONS/SIGNIFICANCE: Our study suggests that aquatic macrophytes and snail predators can influence per-capita cercarial production and total abundance of snails. Thus, snail control efforts might benefit by targeting specific snail habitats where parasite production is greatest. In conclusion, a better understanding of top-down and bottom-up ecological factors that regulate densities of cercarial release by snails, rather than solely snail densities or snail infection prevalence, might facilitate improved schistosomiasis control.

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.

Unavoidable Risks: Local Perspectives on Water Contact Behavior and Implications for Schistosomiasis Control in an Agricultural Region of Northern Senegal.

Human schistosomiasis is a snail-borne parasitic disease affecting more than 200 million people worldwide. Direct contact with snail-infested freshwater is the primary route of exposure. Water management infrastructure, including dams and irrigation schemes, expands snail habitat, increasing the risk across the landscape. The Diama Dam, built on the lower basin of the Senegal River to prevent saltwater intrusion and promote year-round agriculture in the drought-prone Sahel, is a paradigmatic case. Since dam completion in 1986, the rural population-whose livelihoods rely mostly on agriculture-has suffered high rates of schistosome infection. The region remains one of the most hyperendemic regions in the world. Because of the convergence between livelihoods and environmental conditions favorable to transmission, schistosomiasis is considered an illustrative case of a disease-driven poverty trap (DDPT). The literature to date on the topic, however, remains largely theoretical. With qualitative data generated from 12 focus groups in four villages, we conducted team-based theme analysis to investigate how perception of schistosomiasis risk and reported preventive behaviors may suggest the presence of a DDPT. Our analysis reveals three key findings: 1) rural villagers understand schistosomiasis risk (i.e., where and when infections occur), 2) accordingly, they adopt some preventive behaviors, but ultimately, 3) exposure persists, because of circumstances characteristic of rural livelihoods. These findings highlight the capacity of local populations to participate actively in schistosomiasis control programs and the limitations of widespread drug treatment campaigns. Interventions that target the environmental reservoir of disease may provide opportunities to reduce exposure while maintaining resource-dependent livelihoods.

Potential Biological Control of Schistosomiasis by Fishes in the Lower Senegal River Basin.

More than 200 million people in sub-Saharan Africa are infected with schistosome parasites. Transmission of schistosomiasis occurs when people come into contact with larval schistosomes emitted from freshwater snails in the aquatic environment. Thus, controlling snails through augmenting or restoring their natural enemies, such as native predators and competitors, could offer sustainable control for this human disease. Fishes may reduce schistosomiasis transmission directly, by preying on snails or parasites, or indirectly, by competing with snails for food or by reducing availability of macrophyte habitat (i.e., aquatic plants) where snails feed and reproduce. To identify fishes that might serve as native biological control agents for schistosomiasis in the lower Senegal River basin-one of the highest transmission areas for human schistosomiasis globally-we surveyed the freshwater fish that inhabit shallow, nearshore habitats and conducted multivariate analyses with quantitative diet data for each of the fish species encountered. Ten of the 16 fish species we encountered exhibited diets that may result in direct (predation) and/or indirect (food competition and habitat removal) control of snails. Fish abundance was low, suggesting limited effects on schistosomiasis transmission by the contemporary fish community in the lower Senegal River basin in the wild. Here, we highlight some native species-such as tilapia, West African lungfish, and freshwater prawns-that could be aquacultured for local-scale biological control of schistosomiasis transmission.

Emerging human infectious diseases and the links to global food production.

Infectious diseases are emerging globally at an unprecedented rate while global food demand is projected to increase sharply by 2100. Here, we synthesize the pathways by which projected agricultural expansion and intensification will influence human infectious diseases and how human infectious diseases might likewise affect food production and distribution. Feeding 11 billion people will require substantial increases in crop and animal production that will expand agricultural use of antibiotics, water, pesticides and fertilizer, and contact rates between humans and both wild and domestic animals, all with consequences for the emergence and spread of infectious agents. Indeed, our synthesis of the literature suggests that, since 1940, agricultural drivers were associated with >25% of all - and >50% of zoonotic - infectious diseases that emerged in humans, proportions that will likely increase as agriculture expands and intensifies. We identify agricultural and disease management and policy actions, and additional research, needed to address the public health challenge posed by feeding 11 billion people.

Agrochemicals increase risk of human schistosomiasis by supporting higher densities of intermediate hosts.

Schistosomiasis is a snail-borne parasitic disease that ranks among the most important water-based diseases of humans in developing countries. Increased prevalence and spread of human schistosomiasis to non-endemic areas has been consistently linked with water resource management related to agricultural expansion. However, the role of agrochemical pollution in human schistosome transmission remains unexplored, despite strong evidence of agrochemicals increasing snail-borne diseases of wildlife and a projected 2- to 5-fold increase in global agrochemical use by 2050. Using a field mesocosm experiment, we show that environmentally relevant concentrations of fertilizer, a herbicide, and an insecticide, individually and as mixtures, increase densities of schistosome-infected snails by increasing the algae snails eat and decreasing densities of snail predators. Epidemiological models indicate that these agrochemical effects can increase transmission of schistosomes. Identifying agricultural practices or agrochemicals that minimize disease risk will be critical to meeting growing food demands while improving human wellbeing.

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.

The prawn Macrobrachium vollenhovenii in the Senegal River basin: towards sustainable restocking of all-male populations for biological control of schistosomiasis.

Early malacological literature suggests that the outbreak of schistosomiasis, a parasitic disease transmitted by aquatic snails, in the Senegal River basin occurred due to ecological changes resulting from the construction of the Diama dam. The common treatment, the drug praziquantel, does not protect from the high risk of re-infection due to human contact with infested water on a daily basis. The construction of the dam interfered with the life cycle of the prawn Macrobrachium vollenhovenii by blocking its access to breeding grounds in the estuary. These prawns were demonstrated to be potential biological control agents, being effective predators of Schistosoma-susceptible snails. Here, we propose a responsible restocking strategy using all-male prawn populations which could provide sustainable disease control. Male prawns reach a larger size and have a lower tendency to migrate than females. We, therefore, expect that periodic restocking of all-male juveniles will decrease the prevalence of schistosomiasis and increase villagers' welfare. In this interdisciplinary study, we examined current prawn abundance along the river basin, complemented with a retrospective questionnaire completed by local fishermen. We revealed the current absence of prawns upriver and thus demonstrated the need for restocking. Since male prawns are suggested to be preferable for bio-control, we laid the molecular foundation for production of all-male M. vollenhovenii through a complete sequencing of the insulin-like androgenic gland-encoding gene (IAG), which is responsible for sexual differentiation in crustaceans. We also conducted bioinformatics and immunohistochemistry analyses to demonstrate the similarity of this sequence to the IAG of another Macrobrachium species in which neo-females are produced and their progeny are 100% males. At least 100 million people at risk of schistosomiasis are residents of areas that experienced water management manipulations. Our suggested non-breeding sustainable model of control-if proven successful-could prevent re-infections and thus prove useful throughout the world.

[Evaluation of the Kato-Katz technique for monitoring Schistosoma mansoni infestation in endemic areas]. / Évaluation de la technique de Kato-Katz pour la surveillance des infestations à Schistosoma mansoni en zone d'endémie.

The Kato-Katz technique has become the gold standard for all studies on intestinal schistosomiasis. Though repeatability and reproducibility can be disappointing and the sensitivity is low, it remains easy, inexpensive, and fast and as such, is perfectly suited for epidemiological surveys or to monitor the effectiveness of mass treatment. For optimal interpretation of the Kato-Katz results in a recent study of three endemic villages in the Senegal River basin, a study of the measurement uncertainties of this analysis was conducted according to Cofrac and ISO 15189 guidelines. Repeat examinations of stool smears from the same individual, taken a few days apart, can significantly increase the sensitivity of the Kato-Katz test, which allows its use as a technique in clinical biology.