Re-assessing thermal response of schistosomiasis transmission risk: Evidence for a higher thermal optimum than previously predicted.

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3°C and 23.6-27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

Re-assessing thermal response of schistosomiasis transmission risk: evidence for a higher thermal optimum than previously predicted.

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7 °C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3 °C and 23.6-27.9 °C (95 % CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

Helminth ecological requirements shape the impact of climate change on the hazard of infection.

Outbreaks and spread of infectious diseases are often associated with seasonality and environmental changes, including global warming. Free-living stages of soil-transmitted helminths are highly susceptible to climatic drivers; however, how multiple climatic variables affect helminth species, and the long-term consequences of these interactions, is poorly understood. We used experiments on nine trichostrongylid species of herbivores to develop a temperature- and humidity-dependent model of infection hazard, which was then implemented at the European scale under climate change scenarios. Intestinal and stomach helminths exhibited contrasting climatic responses, with the former group strongly affected by temperature while the latter primarily impacted by humidity. Among the demographic traits, larval survival heavily modulated the infection hazard. According to the specific climatic responses of the two groups, climate change is expected to generate differences in the seasonal and spatial shifts of the infection hazard and group co-circulation. In the future, an intensification of these trends could create new opportunities for species range expansion and co-occurrence at European central-northern latitudes.

Spatially explicit effective reproduction numbers from incidence and mobility data.

Current methods for near real-time estimation of effective reproduction numbers from surveillance data overlook mobility fluxes of infectors and susceptible individuals within a spatially connected network (the metapopulation). Exchanges of infections among different communities may thus be misrepresented unless explicitly measured and accounted for in the renewal equations. Here, we first derive the equations that include spatially explicit effective reproduction numbers, ℛk(t), in an arbitrary community k. These equations embed a suitable connection matrix blending mobility among connected communities and mobility-related containment measures. Then, we propose a tool to estimate, in a Bayesian framework involving particle filtering, the values of ℛk(t) maximizing a suitable likelihood function reproducing observed patterns of infections in space and time. We validate our tools against synthetic data and apply them to real COVID-19 epidemiological records in a severely affected and carefully monitored Italian region. Differences arising between connected and disconnected reproduction numbers (the latter being calculated with existing methods, to which our formulation reduces by setting mobility to zero) suggest that current standards may be improved in their estimation of disease transmission over time.

Modeling the contribution of antibody attack rates to single and dual helminth infections in a natural system.

Within-host models of infection can provide important insights into the processes that affect parasite spread and persistence in host populations. However, modeling can be limited by the availability of empirical data, a problem commonly encountered in natural systems. Here, we used six years of immune-infection observations of two gastrointestinal helminths (Trichostrongylus retortaeformis and Graphidium strigosum) from a population of European rabbits (Oryctolagus cuniculus) to develop an age-dependent, mathematical model that explicitly included species-specific and cross-reacting antibody (IgA and IgG) responses to each helminth in hosts with single or dual infections. Different models of single infection were formally compared to test alternative mechanisms of parasite regulation. The two models that best described single infections of each helminth species were then coupled through antibody cross-immunity to examine how the presence of one species could alter the host immune response to, and the within-host dynamics of, the other species. For both single infections, model selection suggested that either IgA or IgG responses could equally explain the observed parasite intensities by host age. However, the antibody attack rate and affinity level changed between the two helminths, it was stronger against T. retortaeformis than against G. strigosum and caused contrasting age-intensity profiles. When the two helminths coinfect the same host, we found variation of the species-specific antibody response to both species together with an asymmetric cross-immune response driven by IgG. Lower attack rate and affinity of antibodies in dual than single infections contributed to the significant increase of both helminth intensities. By combining mathematical modeling with immuno-infection data, our work provides a tractable model framework for disentangling some of the complexities generated by host-parasite and parasite-parasite interactions in natural 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.

The enemy of my enemy is my friend: Immune-mediated facilitation contributes to fitness of co-infecting helminths.

The conceptual understanding of immune-mediated interactions between parasites is rooted in the theory of community ecology. One of the limitations of this approach is that most of the theory and empirical evidence has focused on resource or immune-mediated competition between parasites and yet there is ample evidence of positive interactions that could be generated by immune-mediated facilitation. We developed an immuno-epidemiological model and applied it to long-term data of two gastrointestinal helminths in two rabbit populations to investigate, through model testing, how immune-mediated mechanisms of parasite regulation could explain the higher intensities of both helminths in rabbits with dual than single infections. The model framework was selected and calibrated on rabbit population A and then validated on the nearby rabbit population B to confirm the consistency of the findings and the generality of the mechanisms. Simulations suggested that the higher intensities in rabbits with dual infections could be explained by a weakened or low species-specific IgA response and an asymmetric IgA cross-reaction. Simulations also indicated that rabbits with dual infections shed more free-living stages that survived for longer in the environment, implying greater transmission than stages from hosts with single infections. Temperature and humidity selectively affected the free-living stages of the two helminths. These patterns were comparable in the two rabbit populations and support the hypothesis that immune-mediated facilitation can contribute to greater parasite fitness and local persistence.

Across the deserts and sea: inter-individual variation in migration routes of south-central European barn swallows (Hirundo rustica).

BACKGROUND: The spatiotemporal organization of migratory routes of long-distance migrants results from trade-offs between minimizing the journey length and en route risk of migration-related mortality, which may be reduced by avoiding crossing inhospitable ecological barriers. Despite flourishing avian migration research in recent decades, little is still known about inter-individual variability in migratory routes, as well as the carry-over effects of spatial and temporal features of migration on subsequent migration stages. METHODS: We reconstructed post- and pre-breeding migration routes, barrier crossing behaviour and non-breeding movements of the largest sample (N = 85) analysed to date of individual barn swallows breeding in south-central Europe, which were tracked using light-level geolocators. RESULTS: Most birds spent their non-breeding period in the Congo basin in a single stationary area, but a small fraction of itinerant individuals reaching South Africa was also observed. Birds generally followed a 'clockwise loop migration pattern', moving through the central Mediterranean and the Sahara Desert during post-breeding (north to south) migration yet switching to a more western route, along the Atlantic coast of Africa, Iberia and western Mediterranean during the pre-breeding (south to north) migration. Southward migration was straighter and less variable, while northward migration was significantly faster despite the broader detour along the Atlantic coast and Iberia. These patterns showed limited sex-related variability. The timing of different circannual events was tightly linked with previous migration stages, considerably affecting migration route and speed of subsequent movements. Indeed, individuals departing late from Africa performed straighter and faster pre-breeding migrations, partly compensating for the initial departure delays, but likely at the cost of performing riskier movements across ecological barriers. CONCLUSIONS: Different spatiotemporal migration strategies during post- and pre-breeding migration suggest that conditions en route may differ seasonally and allow for more efficient travelling along different migration corridors in either season. While highlighting patterns of inter-individual variability, our results support increasing evidence for widespread loop migration patterns among Afro-Palearctic avian migrants. Also, they suggest that carry-over effects acting across different phases of the annual cycle of migratory species can have major impacts on evolutionary processes.

Optimal control of the spatial allocation of COVID-19 vaccines: Italy as a case study.

While campaigns of vaccination against SARS-CoV-2 are underway across the world, communities face the challenge of a fair and effective distribution of a limited supply of doses. Current vaccine allocation strategies are based on criteria such as age or risk. In the light of strong spatial heterogeneities in disease history and transmission, we explore spatial allocation strategies as a complement to existing approaches. Given the practical constraints and complex epidemiological dynamics, designing effective vaccination strategies at a country scale is an intricate task. We propose a novel optimal control framework to derive the best possible vaccine allocation for given disease transmission projections and constraints on vaccine supply and distribution logistics. As a proof-of-concept, we couple our framework with an existing spatially explicit compartmental COVID-19 model tailored to the Italian geographic and epidemiological context. We optimize the vaccine allocation on scenarios of unfolding disease transmission across the 107 provinces of Italy, from January to April 2021. For each scenario, the optimal solution significantly outperforms alternative strategies that prioritize provinces based on incidence, population distribution, or prevalence of susceptibles. Our results suggest that the complex interplay between the mobility network and the spatial heterogeneities implies highly non-trivial prioritization strategies for effective vaccination campaigns. Our work demonstrates the potential of optimal control for complex and heterogeneous epidemiological landscapes at country, and possibly global, scales.

Data-driven analysis of amino acid change dynamics timely reveals SARS-CoV-2 variant emergence.

Since its emergence in late 2019, the diffusion of SARS-CoV-2 is associated with the evolution of its viral genome. The co-occurrence of specific amino acid changes, collectively named 'virus variant', requires scrutiny (as variants may hugely impact the agent's transmission, pathogenesis, or antigenicity); variant evolution is studied using phylogenetics. Yet, never has this problem been tackled by digging into data with ad hoc analysis techniques. Here we show that the emergence of variants can in fact be traced through data-driven methods, further capitalizing on the value of large collections of SARS-CoV-2 sequences. For all countries with sufficient data, we compute weekly counts of amino acid changes, unveil time-varying clusters of changes with similar-rapidly growing-dynamics, and then follow their evolution. Our method succeeds in timely associating clusters to variants of interest/concern, provided their change composition is well characterized. This allows us to detect variants' emergence, rise, peak, and eventual decline under competitive pressure of another variant. Our early warning system, exclusively relying on deposited sequences, shows the power of big data in this context, and concurs to calling for the wide spreading of public SARS-CoV-2 genome sequencing for improved surveillance and control of the COVID-19 pandemic.

The epidemicity index of recurrent SARS-CoV-2 infections.

Several indices can predict the long-term fate of emerging infectious diseases and the effect of their containment measures, including a variety of reproduction numbers (e.g. [Formula: see text]). Other indices evaluate the potential for transient increases of epidemics eventually doomed to disappearance, based on generalized reactivity analysis. They identify conditions for perturbations to a stable disease-free equilibrium ([Formula: see text]) to grow, possibly causing significant damage. Here, we introduce the epidemicity index e0, a threshold-type indicator: if e0 > 0, initial foci may cause infection peaks even if [Formula: see text]. Therefore, effective containment measures should achieve a negative epidemicity index. We use spatially explicit models to rank containment measures for projected evolutions of the ongoing pandemic in Italy. There, we show that, while the effective reproduction number was below one for a sizable timespan, epidemicity remained positive, allowing recurrent infection flare-ups well before the major epidemic rebounding observed in the fall.

A parsimonious mechanistic model of reproductive and vegetative growth in fruit trees predicts consequences of fruit thinning and branch pruning.

Productivity of fruit tree crops depends on the interaction between plant physiology, environmental conditions and agricultural practices. We develop a mechanistic model of fruit tree crops that reliable simulates the dynamics of variables of interest for growers and consequences of agricultural practices while relying on a minimal number of inputs and parameters. The temporal dynamics of carbon content in the different organs (i.e., shoots-S, roots-R and fruits-F) are the result of photosynthesis by S, nutrient supply by R, respiration by S, R and F, competition among different organs, photoperiod and initial system conditions partially controlled by cultural practices. We calibrate model parameters and evaluate model predictions using unpublished data from a peach (Prunus persica) experimental orchard with trees subjected to different levels of branch pruning and fruit thinning. Fiinally, we evaluate the consequences of different combinations of pruning and thinning intensities within a multi-criteria analysis. The predictions are in good agreement with the experimental measurements and for the different conditions (pruning and thinning). Our simulations indicate that thinning and pruning practices actually used by growers provide the best compromise between total shoot production, which impacts next year's abundance of shoots and fruits, and current year's fruit production in terms of quantity (yield) and quality (average fruit size). This suggests that growers are not only interested in maximizing current year's yield but also in its quality and its durability. The present work provides for modelers a system of equations based on acknowledged principles of plant science easily modifiable for different purposes. For horticulturists, it gives insights on the potentialities of pruning and thinning. For ecologists, it provides a transparent quantitative framework that can be coupled with biotic and abiotic stressors.

The dynamics of microplastics and associated contaminants: Data-driven Lagrangian and Eulerian modelling approaches in the Mediterranean Sea.

Plastic pollution is widespread in the global oceans, but at the same time several other types of hydrophobic pollutants contaminate the marine environment. As more and more evidence highlights, microplastics and polluting chemicals are intertwined via adsorption/desorption processes. A thorough assessment of their total impact on marine ecosystems thus requires that these two kinds of pollution are not considered separately. Here we compare the outcomes of two complementary, data-driven modelling approaches for microplastic dispersal and for Plastic-Related Organic Pollutants (PROPs) in the marine environment. Focusing on the Mediterranean Sea, we simulate two years of Lagrangian particle tracking to map microplastic dispersion from the most impacting sources of pollution (i.e. coastal areas, the watersheds of major rivers, and fishing activities). Our particle sources are data-informed by national census data, hydrological regimes, and vessel tracking data to account for spatial and temporal variability of mismanaged plastic waste generation. These particle-based simulations are complemented with a simulation of the dynamics of primary pollutants in the sea, obtained via an advection-diffusion Eulerian model. While providing further understanding of the spatiotemporal distribution of microplastics and the dynamics of PROPs at a Mediterranean-wide scale, our results call for the development of novel integrated modelling approaches aimed at coupling the dynamics of microplastics with the chemical exchanges occurring through them, thus promoting a holistic description of marine plastic pollution.

Modelled effects of prawn aquaculture on poverty alleviation and schistosomiasis control.

Recent evidence suggests that snail predators may aid efforts to control the human parasitic disease schistosomiasis by eating aquatic snail species that serve as intermediate hosts of the parasite. Potential synergies between schistosomiasis control and aquaculture of giant prawns are evaluated using an integrated bio-economic-epidemiologic model. Combinations of stocking density and aquaculture cycle length that maximize cumulative, discounted profit are identified for two prawn species in sub-Saharan Africa: the endemic, non-domesticated Macrobrachium vollenhovenii, and the non-native, domesticated Macrobrachium rosenbergii. At profit maximizing densities, both M. rosenbergii and M. vollenhovenii may substantially reduce intermediate host snail populations and aid schistosomiasis control efforts. Control strategies drawing on both prawn aquaculture to reduce intermediate host snail populations and mass drug administration to treat infected individuals are found to be superior to either strategy alone. Integrated aquaculture-based interventions can be a win-win strategy in terms of health and sustainable development in schistosomiasis endemic regions of the world.

Within-host mechanisms of immune regulation explain the contrasting dynamics of two helminth species in both single and dual infections.

Variation in the intensity and duration of infections is often driven by variation in the network and strength of host immune responses. While many of the immune mechanisms and components are known for parasitic helminths, how these relationships change from single to multiple infections and impact helminth dynamics remains largely unclear. Here, we used laboratory data from a rabbit-helminth system and developed a within-host model of infection to investigate different scenarios of immune regulation in rabbits infected with one or two helminth species. Model selection suggests that the immunological pathways activated against Trichostrongylus retortaeformis and Graphidium strigosum are similar. However, differences in the strength of these immune signals lead to the contrasting dynamics of infections, where the first parasite is rapidly cleared and the latter persists with high intensities. In addition to the reactions identified in single infections, rabbits with both helminths also activate new pathways that asymmetrically affect the dynamics of the two species. These new signals alter the intensities but not the general trend of the infections. The type of interactions described can be expected in many other host-helminth systems. Our immune framework is flexible enough to capture different mechanisms and their complexity, and provides essential insights to the understanding of multi-helminth infections.

The geography of COVID-19 spread in Italy and implications for the relaxation of confinement measures.

The pressing need to restart socioeconomic activities locked-down to control the spread of SARS-CoV-2 in Italy must be coupled with effective methodologies to selectively relax containment measures. Here we employ a spatially explicit model, properly attentive to the role of inapparent infections, capable of: estimating the expected unfolding of the outbreak under continuous lockdown (baseline trajectory); assessing deviations from the baseline, should lockdown relaxations result in increased disease transmission; calculating the isolation effort required to prevent a resurgence of the outbreak. A 40% increase in effective transmission would yield a rebound of infections. A control effort capable of isolating daily  ~5.5% of the exposed and highly infectious individuals proves necessary to maintain the epidemic curve onto the decreasing baseline trajectory. We finally provide an ex-post assessment based on the epidemiological data that became available after the initial analysis and estimate the actual disease transmission that occurred after weakening the lockdown.

Spread and dynamics of the COVID-19 epidemic in Italy: Effects of emergency containment measures.

The spread of coronavirus disease 2019 (COVID-19) in Italy prompted drastic measures for transmission containment. We examine the effects of these interventions, based on modeling of the unfolding epidemic. We test modeling options of the spatially explicit type, suggested by the wave of infections spreading from the initial foci to the rest of Italy. We estimate parameters of a metacommunity Susceptible-Exposed-Infected-Recovered (SEIR)-like transmission model that includes a network of 107 provinces connected by mobility at high resolution, and the critical contribution of presymptomatic and asymptomatic transmission. We estimate a generalized reproduction number ([Formula: see text] = 3.60 [3.49 to 3.84]), the spectral radius of a suitable next-generation matrix that measures the potential spread in the absence of containment interventions. The model includes the implementation of progressive restrictions after the first case confirmed in Italy (February 21, 2020) and runs until March 25, 2020. We account for uncertainty in epidemiological reporting, and time dependence of human mobility matrices and awareness-dependent exposure probabilities. We draw scenarios of different containment measures and their impact. Results suggest that the sequence of restrictions posed to mobility and human-to-human interactions have reduced transmission by 45% (42 to 49%). Averted hospitalizations are measured by running scenarios obtained by selectively relaxing the imposed restrictions and total about 200,000 individuals (as of March 25, 2020). Although a number of assumptions need to be reexamined, like age structure in social mixing patterns and in the distribution of mobility, hospitalization, and fatality, we conclude that verifiable evidence exists to support the planning of emergency measures.

Protection reveals density-dependent dynamics in fish populations: A case study in the central Mediterranean.

Casting light on how the interaction between protection and density dependence affects fish population dynamics is critical for understanding the effectiveness of marine protected areas (MPAs). We developed a framework based on nonparametric statistics, model selection and multi-model inference to contrast alternative hypotheses about the effect of density dependence on demographic dynamics under protected and unprotected conditions. We trialed it using a 12-year long time series of white seabream (Diplodus sargus sargus) population density within the no-take zone of Torre Guaceto MPA (Italy) and at two nearby unprotected locations. Then, we showed how the demographic models obtained can be used to assess the consequences of protection on population viability. Population dynamics were significantly influenced by fish density within the MPA and at one of the unprotected locations, where demography is possibly driven by directional recruitment subsidy from the MPA. The comparison of population growth rates within and outside the MPA suggests that in unprotected conditions the fishery may remove a fraction between 40 and 70% of the population each year. The population viability analysis pointed out that, while the probability that the population becomes depleted (i.e. undergoes a local, temporary quasi-extinction) is high in unprotected locations, it is negligible within the no-take zone of the MPA.

When resolution does matter: Modelling indirect contacts in dairy farms at different levels of detail.

Animal exchanges are considered the major pathway for between-farm transmission of many livestock infectious diseases. Yet, vehicles and operators visiting several farms during routine activities can also contribute to disease spread. Indeed, if contaminated, they can act as mechanical vectors of fomites, generating indirect contacts between visited farms. While data on animal exchanges is often available in national databases, information about the daily itineraries of trucks and operators is rare because difficult to obtain. Thus, some unavoidable approximations have been frequently introduced in the description of indirect contacts in epidemic models. Here, we showed that the level of detail in such description can significantly affect the predictions on disease dynamics. Our analyses focused on the potential spread of a disease in a dairy farm system subject of a comprehensive data collection campaign on calf transportations. We developed two temporal multilayer networks to model between-farm contacts generated by either animal exchanges (direct contacts) and connections operated by trucks moving calves (indirect contacts). The complete model used the full knowledge of the daily trucks' itineraries, while the partial informed one used only a subset of such available information. To account for various conditions of pathogen survival ability and effectiveness of cleaning operations, we performed a sensitivity analysis on trucks' contamination period. An accurate description of indirect contacts was crucial both to correctly predict the final size of epidemics and to identify the seed farms responsible for generating the most severe outbreaks. The importance of detailed information emerged even more clearly in the case of short contamination periods. Our conclusions could be extended to between-farm contacts generated by other vehicles and operators. Overcoming these information gaps would be decisive for a deeper understanding of epidemic spread in livestock and to develop effective control plans.

Reconstruction of long-distance bird migration routes using advanced machine learning techniques on geolocator data.

Geolocators are a well-established technology to reconstruct migration routes of animals that are too small to carry satellite tags (e.g. passerine birds). These devices record environmental light-level data that enable the reconstruction of daily positions from the time of twilight. However, all current methods for analysing geolocator data require manual pre-processing of raw records to eliminate twilight events showing unnatural variation in light levels, a step that is time-consuming and must be accomplished by a trained expert. Here, we propose and implement advanced machine learning techniques to automate this procedure and we apply them to 108 migration tracks of barn swallows ( Hirundo rustica). We show that routes reconstructed from the automated pre-processing are comparable to those obtained from manual selection accomplished by a human expert. This raises the possibility of fully automating light-level geolocator data analysis and possibly analysing the large amount of data already collected on several species.