Drivers and epidemiological patterns of West Nile virus in Serbia

Background: West Nile virus (WNV) is an emerging mosquito-borne pathogen in Serbia, where it has been detected as a cause of infection in humans since 2012. We analyzed and modelled WNV transmission patterns in the country between 2012 and 2023. Methods: We applied a previously developed modelling approach to quantify epidemiological parameters of interest and to identify the most important environmental drivers of the force of infection (FOI) by means of statistical analysis in the human population in the country. Results: During the study period, 1,387 human cases were recorded, with substantial heterogeneity across years. We found that spring temperature is of paramount importance for WNV transmission, as FOI magnitude and peak timing are positively associated with it. Furthermore, FOI is also estimated to be greater in regions with a larger fraction of older adult people, who are at higher risk to develop severe infections. Conclusion: Our results highlight that temperature plays a key role in shaping WNV outbreak magnitude in Serbia, confirming the association between spring climatic conditions and WNV human transmission risk and thus pointing out the importance of this factor as a potential early warning predictor for timely application of preventive and control measure

High habitat richness reduces the risk of tick-borne encephalitis in Europe: a multi-scale study

Background The natural transmission cycle of tick-borne encephalitis (TBE) virus is enhanced by complex interactions between ticks and key hosts strongly connected to habitat characteristics. The diversity of wildlife host species and their relative abundance is known to affect transmission of tick-borne diseases. Therefore, in the current context of global biodiversity loss, we explored the relationship between habitat richness and the pattern of human TBE cases in Europe to assess biodiversity's role in disease risk mitigation. Methods We assessed human TBE case distribution across 879 European regions using official epidemiological data reported to The European Surveillance System (TESSy) between 2017 and 2021 from 15 countries. We explored the relationship between TBE presence and the habitat richness index (HRI1) by means of binomial regression. We validated our findings at local scale using data collected between 2017 and 2021 in 227 municipalities located in Trento and Belluno provinces, two known TBE foci in northern Italy. Findings Our results showed a significant parabolic effect of HRI on the probability of presence of human TBE cases in the European regions included in our dataset, and a significant, negative effect of HRI on the local presence of TBE in northern Italy. At both spatial scales, TBE risk decreases in areas with higher values of HRI. Interpretation To our knowledge, no efforts have yet been made to explore the relationship between biodiversity and TBE risk, probably due to the scarcity of high-resolution, large-scale data about the abundance or density of critical host species. Hence, in this study we considered habitat richness as proxy for vertebrate host diversity. The results suggest that in highly diverse habitats TBE risk decreases. Hence, biodiversity loss could enhance TBE risk for both humans and wildlife. This association is relevant to support the hypothesis that the maintenance of highly diverse ecosystems mitigates disease ris

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Scleritis

Introduction This article points out the design, methods, development and deployment of the international registry promoted by the AutoInflammatory Disease Alliance (AIDA) Network with the aim to define and assess paediatric and adult patients with immune-mediated scleritis. Methods This registry collects both retrospective and prospective real-world data from patients with non-infectious scleritis through the Research Electronic Data Capture (REDCap) tool and aims to promote knowledge and real-life evidence from patients enrolled worldwide; the registry also allows the collection of standardised data, ensuring the highest levels of security and anonymity of patients' data and flexibility to change according to scientific acquisitions over time. The communication with other similar registries has been also ensured in order to pursue the sustainability of the project with respect to the adaptation of collected data to the most diverse research projects. Results Since the launch of the registry, 99 centres have been involved from 20 countries and four continents. Forty-eight of the centres have already obtained a formal approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers); the platform collects baseline and follow-up data using 3683 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger or risk factors, therapies and healthcare utilization. Conclusions The development of the AIDA International Registry for patients with non-infectious scleritis will allow solid research on this rare condition. Real-world evidence resulting from standardised real-life data will lead to the optimisation of routine clinical and therapeutic management, which are currently limited by the rarity of this ocular inflammatory condition

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Uveitis

Introduction: The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU). Methods: This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform. Results: Ninety-five centres have been involved from 19 countries and four continents from 24 March to 16 November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU. Conclusions: The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide

Efficacy of canakinumab in patients with Still's disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still's Disease

Introduction: The effectiveness of canakinumab may change according to the different times it is used after Still's disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment.Methods: Patients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still's disease. Seventy-seven (51 females and 26 males) patients with Still's disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent.Results: No statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment.Conclusion: Canakinumab has proved to be effective in patients with Still's disease, regardless of its line of biologic treatment

Development and Implementation of the AIDA International Registry for Patients With Still's Disease

Objective: Aim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder. Methods: This Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The collection of standardized data is thought to bring knowledge about real-life clinical research and potentially communicate with other existing and future Registries dedicated to Still's disease. Moreover, it has been conceived to be flexible enough to easily change according to future scientific acquisitions. Results: Starting from June 30th to February 7th, 2022, 110 Centers from 23 Countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 4449 fields organized into 14 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access. Conclusions: This international Registry for patients with Still's disease will allow a robust clinical research through collection of standardized data, international consultation, dissemination of knowledge, and implementation of observational studies based on wide cohorts of patients followed-up for very long periods. Solid evidence drawn from "real-life " data represents the ultimate goal of this Registry, which has been implemented to significantly improve the overall management of patients with Still's disease. NCT 05200715 available at

Why account for biodiversity for mitigating tick-borne disease risk? Insights and perspectives from eastern Italian Alps

The biodiversity crisis is one of the most critical environmental issues of our time. Species losses affect ecosystem functioning by depriving those services - such as carbon sequestration, nutrient cycling and resistance to drought - on which also humans rely. Among these, control of infectious diseases is a highly valuable service provided by biodiversity with implications for human health. Habitat degradation and the resulting biodiversity loss, alter the ratio among generalist species and specialist, thus increasing the risk of zoonotic emergence since many generalist species are competent reservoirs. Currently, scientific studies considered either the role of anthropogenic changes (e.g., climate and land-use) on disease emergence or how biodiversity affects dynamics of endemic diseases. Indeed, a multitude of studies performed in the Eastern Italian Alps (Autonomous Province of Trento, Italy) unveiled what are the environmental and climatic factors driving risk of tick-borne zoonoses emergence. In particular, findings from a systematic review evidenced that temperature-dependent variables were negatively associated to the variation of Tick borne encephalitis (TBE) across Europe. Further, habitat diversity seemed to also dilute TBE virus (TBEv) incidence. Conversely, covariates related to the presence of competent hosts (i.e., rodents) and forest cover had a positive role in TBEv circulation, while incompetent hosts (i.e., deer) showed a hump-shaped effect. These patterns were confirmed also through empirical studies. Specifically, a study found that TBEv detection was related with number of co-feeding ticks carried by rodents, which in turn is negatively correlated with autumnal cooling rate and increased with tick burden on rodents, deer and rodent abundance. Therefore, a specific combination of climatic conditions and certain rodent and deer densities resulted the principal determinants of the TBEv incidence. Similarly, another study highlighted the strong relation between TBEv cases and air pollen abundance, a proxy for seed production. This suggested the major role of rodents as amplifying hosts, being favored by the availability of seeds and thus by pollen quantities. Similar insights were observed in experimental research evaluating the role of artificial ungulate feeding sites in disease spreading. Here, food availability promoted the density of mice, while favoring revisitation patterns of roe deer and interspecific competition among rodents’ species. Co-occurrence of roe deer and mice at these sites affected infectious pathogen transmission, with lower prevalence of tick-borne pathogens (Borrelia burgdorferi s.l., Babesia microti, Anaplasma phagocytophylum and Hepatozoon spp.), while the opposite was found for rodent-borne ones (hantaviruses). Beyond hosts, also land-use plays a crucial role in driving disease circulation. In this sense, a study investigating the effects of land-use type on acarological hazard for Ixodes ricinus and on its infection rate found a positive effect of climate on relative abundance of questing nymphs, while no differences were observed among land-use categories. However, when considering the density of infected nymphs (DIN), the effect of land-use emerged with the natural habitats having the highest DIN values for B. burgdorferi s.l., the urban habitats the highest ones for A. phagocytophilum, while for Rickettsia spp., no differences were observed. Overall, this provides evidence for complex ecological factors to consider for predicting microbial hazard. However, so far, few studies have tried to reconcile the relationship between biodiversity, anthropogenic change, circulation of endemic pathogens and risk of disease emergence. By considering the cascading eco-epidemiological processes occurring in ecosystems with different degrees of naturalness we aim to identify the anthropogenic impacts on biodiversity, and the role of the latter in driving infectious disease circulation and emergence

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 longitudinal 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 asymmetrical 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

In vitro percutaneous absorption of silver nanoparticles | [Assorbimento percutaneo di nanoparticelle di argento in un sistema in vitro]

There is a growing interest in the debate on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin lies. This study aims at evaluating in vitro silver nanoparticles skin penetration. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 microg/cm2 of silver nanoparticles dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24h. The receptor fluid measurements were performed by Electro Thermal Atomic Absorption Spectroscopy (ETAAS). Silver concentration of 0.2 microg/L was found in the receiving solutions of two cells, in which damaged skin membranes were set up. In the other tests, we obtained a silver concentration below the limit of detection in the receiving cells. Our experimental data show that silver nanoparticles permeation through intact and damaged skin is negligible. These findings are consistent with previously published results. Further researches are necessary to explore skin absorption of silver nanoparticles