Ecotoxicological Effects of Emerging Contaminants on Aquatic Species.

Emerging contaminants (ECs), also known as contaminants of emerging concern (CECs), are defined as synthetic or naturally occurring chemicals or biological agents that are not commonly monitored in the environment but have the potential to enter the environment and cause known or supposed adverse ecological and human health effects [...].

Assessing the Analgesic Efficacy of Lumbosacral Epidural Morphine in Cats Undergoing Ovariohysterectomy: A Comparative Study of Two Doses.

Opioids are administered epidurally (PV) to provide trans- and postoperative analgesia. Twenty healthy female cats aged between 6 and 24 months and weighing between 2 and 3.7 kg, undergoing elective ovariohysterectomy (OVH), were induced with propofol (8 mg/kg), followed by continuous infusion (0.1-0.4 mg/kg/min). Three groups were defined: CG (0.1 mL/kg of iodinated contrast, n = 6), G0.1 (0.1 mg/kg of morphine, n = 7), and G0.2 (0.2 mg/kg of morphine, n = 7) per VP. All received 0.1 mL/kg of iodinated contrast per VP and injection water to obtain a total of 0.3 mL/kg. Heart rate (HR), systolic blood pressure (SBP), temperature, expired CO2, oxygen saturation, and number of rescue analgesics were monitored. Postoperatively, a multidimensional scale was used to assess acute pain in cats for 12 h. The mean HR and SBP in the CG were higher at the time of maximum noxious stimulation and required fentanyl in all groups. Postoperatively, 83%, 28%, and 7% of the animals in CG, G0.1, and G0.2, respectively, received rescue analgesia. In cats undergoing OVH, epidural morphine at doses of 0.1 and 0.2 mg/kg did not prevent the need for intraoperative rescue analgesia but reduced the postoperative analgesic needed.

Hazardous effects of plastic microfibres from facial masks to aquatic animal health: Insights from zebrafish model.

Facial masks are a source of plastic microfibres (PMFs) in the aquatic environment, an emerging risk factor for aquatic organisms. However, little is known concerning its impact during the early developmental stages of fish. Thus, the current study aimed to evaluate the potential interaction and developmental toxicity of PMFs derived from leachate of surgical masks (SC-Msk) and N-95 facial masks (N95-Msk) using a multi-biomarker approach in developing zebrafish (Danio rerio). PMFs from both facial masks were obtained and characterized by multiple techniques. Zebrafish embryos were exposed to environmentally relevant concentrations of PMFs from both facial masks (1000, 10,000, and 100,000 particle L-1), and the toxicity was analysed in terms of mortality, hatching rate, neurotoxicity, cardiotoxicity, morphological changes, reactive oxygen species (ROS) levels, cell viability, and behavioural impairments. The results showed that both facial masks can release PMFs, but the N95-Msk produced a higher concentration of PMFs than SC-Msk. Both PMFs can interact with zebrafish chorion and don't cause effects on embryo mortality and hatching; however, zebrafish embryos showed cardiotoxic effects, and larvae showed increased agitation, average speed, and distance travelled, indicating the behavioural impairments induced by PMFs derived from facial masks. Overall, results showed the risk of PMFs to the health of freshwater fish, indicating the need for greater attention to the disposal and ecotoxicological effects of facial masks on aquatic organisms.

Visual-Aided Obstacle Climbing by Modular Snake Robot.

Snake robots, also known as apodal robots, are among the most common and versatile modular robots. Primarily due to their ability to move in different patterns, they can evolve in scenarios with several constraints, some of them hardly accessible to other robot configurations. This paper deals with a specific environment constraint where the robot needs to climb a prismatic obstacle, similar to a step. The objective is to carry out simulations of this function, before implementing it in the physical model. To this end, we propose two different algorithms, parameterized by the obstacle dimensions determined by image processing, and both are evaluated in simulated experiments. The results show that both algorithms are viable for testing in real robots, although more complex scenarios still need to be further studied.

Ecotoxicological assessment of UV filters benzophenone-3 and TiO2 nanoparticles, isolated and in a mixture, in developing zebrafish (Danio rerio).

The increasing use of UV filters, such as benzophenone-3 (BP-3) and titanium dioxide nanoparticles (TiO2 NPs), has raised concerns regarding their ecotoxicological effects on the aquatic environment. The aim of the present study was to examine the embryo-larval toxicity attributed to BP-3 or TiO2 NPs, either alone or in a mixture, utilizing zebrafish (Danio rerio) as a model after exposure to environmentally relevant concentrations of these compounds. Zebrafish embryos were exposed to BP-3 (10, 100, or 1000 ng/L) or TiO2 NPs (1000 ng/L) alone or in a mixture (BP-3 10, 100, or 1000 ng/L plus 1000 ng/L of TiO2 NPs) under static conditions for 144 hr. After exposure, BP-3 levels were determined by high-performance liquid chromatography (HPLC). BP-3 levels increased in the presence of TiO2 NPs, indicating that the BP-3 degradation decreased in the presence of the NPs. In addition, in the presence of zebrafish, BP-3 levels in water decreased, indicating that zebrafish embryos and larvae might absorb BP-3. Data demonstrated that, in general, environmentally relevant concentrations of BP-3 and TiO2 NPs, either alone or in a mixture, did not significantly induce changes in heart and spontaneous contractions frequencies, levels of reactive oxygen species (ROS), morphological and morphometric parameters as well as mortality rates during 144 hr exposure. However, the groups exposed to TiO2 NPs alone and in a mixture with BP-3 at 10 ng/L exhibited an earlier significant hatching rate than the controls. Altogether, the data indicates that a potential ecotoxicological impact on the aquatic environment exists.

Tuning Biocompatibility and Bactericidal Efficacy as a Function of Doping of Gold in ZnO Nanocrystals.

Doping nanoparticles represents a strategy for modulating the energy levels and surface states of nanocrystals (NCs), thereby enhancing their efficiency and mitigating toxicity. Thus, we herein focus on the successful synthesis of pure and gold (Au)-doped zinc oxide (ZnO) nanocrystals (NCs), investigating their physical-chemical properties and evaluating their applicability and toxicity through in vitro and in vivo assessments. The optical, structural, and photocatalytic characteristics of these NCs were scrutinized by using optical absorption (OA), X-ray diffraction (XRD), and methylene blue degradation, respectively. The formation and doping of the NCs were corroborated by the XRD and OA results. While the introduction of Au as a dopant did induce changes in the phase and size of ZnO, a high concentration of Au ions in ZnO led to a reduction in their photocatalytic activity. This demonstrated a restricted antibacterial efficacy against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Remarkably, Au-doped counterparts exhibited enhanced biocompatibility in comparison to ZnO, as evidenced in both in vitro (murine macrophage cells) and in vivo (Drosophila melanogaster) studies. Furthermore, confocal microscopy images showed a high luminescence of Au-doped ZnO NCs in vivo. Thus, this study underscores the potential of Au doping of ZnO NCs as a promising technique to enhance material properties and increase biocompatibility.

Multi- and transgenerational effects of environmental chemicals on mollusks: An underexplored experimental design in aquatic (eco)toxicological studies.

(Eco)toxicological studies frequently evaluate the effects of chemicals in one life stage of organisms, but the use of these outcomes can only partially estimate populational effects. In this regard, multi- and/or transgenerational studies should be performed in order to provide information on contaminant effects in a populational functioning context. The present review aimed to summarize and critically evaluate the current knowledge regarding multi- and/or transgenerational effects of traditional and emerging environmental chemicals on mollusks. Results showed that these kinds of studies were performed in aquatic mollusks (bivalve and gastropod), being Gastropoda the mollusk Class most frequently studied. Additionally, freshwater species and multigenerational studies were more common for this class. For the Bivalvia class, only marine species were evaluated, and transgenerational exposure was more commonly assessed. The effects were reported for 15 species, highlighting the marine bivalves Crassostrea gigas and Saccostrea glomerata, and the freshwater gastropod Lymnaea stagnalis. Multi- and transgenerational effects were described for 8 environmental chemical groups, mainly metals, pesticides, and pharmaceuticals. In general, multi- and transgenerational exposure induced biometric, developmental, and reproductive impairments in mollusks, indicating that environmental chemicals might lead to generational impairments, reduced population growth and reproductive capacity, and decreased fitness. The current study indicated that bivalves and gastropods are suitable organism models to assess the multi- and transgenerational adverse effects induced by traditional and emerging environmental chemicals.

Green synthesis of silver nanoparticles using Croton urucurana and their toxicity in freshwater snail species Biomphalaria glabrata.

Green silver nanoparticles (G-Ag NPs) have contributed to the development of ecological technologies with low environmental impact and safer for human health, as well as demonstrating potential for the control of vectors and intermediate hosts. However, knowledge about its toxicity in the early stages of gastropod development remains scarce. Therefore, the current study aimed to investigate the toxicity of G-Ag NPs synthesized from Croton urucurana leaf extracts in snail species Biomphalaria glabrata, which is an intermediate host for Schistosoma mansoni parasite. G-Ag NPs were synthesized using two types of plant extracts (aqueous and hydroethanolic) and characterized using multiple techniques. Bioassays focused on investigating G-Ag NPs and plant extracts were carried out with embryos and newly hatched snails, for 144 h and 96 h, respectively; toxicity was analyzed based on mortality, hatching, development inhibition, and morphological changes. Results have shown that both G-Ag NPs were more toxic to embryos and newly hatched snails than the investigated plant extracts. G-Ag NPs deriving from aqueous extract have higher molluscicidal activity than those deriving from hydroethanolic extract. Both G-Ag NPs induced mortality, hatching delay, development inhibition, and morphological changes (i.e., hydropic embryos), indicating their molluscicidal activities. Moreover, embryos were more sensitive to G-Ag NPs than newly hatched snails. Thus, the toxicity of G-Ag NPs to freshwater snails depends on the type of extracts and the snail's developmental stages. These findings can contribute to the development of green nanobiotechnologies applicable to control snails of medical importance.

Applicability of machine learning algorithm to predict the therapeutic intervention success in Brazilian smokers.

Smoking cessation is an important public health policy worldwide. However, as far as we know, there is a lack of screening of variables related to the success of therapeutic intervention (STI) in Brazilian smokers by machine learning (ML) algorithms. To address this gap in the literature, we evaluated the ability of eight ML algorithms to correctly predict the STI in Brazilian smokers who were treated at a smoking cessation program in Brazil between 2006 and 2017. The dataset was composed of 12 variables and the efficacies of the algorithms were measured by accuracy, sensitivity, specificity, positive predictive value (PPV) and area under the receiver operating characteristic curve. We plotted a decision tree flowchart and also measured the odds ratio (OR) between each independent variable and the outcome, and the importance of the variable for the best model based on PPV. The mean global values for the metrics described above were, respectively, 0.675±0.028, 0.803±0.078, 0.485±0.146, 0.705±0.035 and 0.680±0.033. Supporting vector machines performed the best algorithm with a PPV of 0.726±0.031. Smoking cessation drug use was the roof of decision tree with OR of 4.42 and importance of variable of 100.00. Increase in the number of relapses also promoted a positive outcome, while higher consumption of cigarettes resulted in the opposite. In summary, the best model predicted 72.6% of positive outcomes correctly. Smoking cessation drug use and higher number of relapses contributed to quit smoking, while higher consumption of cigarettes showed the opposite effect. There are important strategies to reduce the number of smokers and increase STI by increasing services and drug treatment for smokers.

Toxicity Assessment of New Ag-ZnO/AgO Nanocomposites: An In Vitro and In Vivo Approach.

Zinc oxide nanoparticles (ZnO NPs) are metal oxide nanomaterials, which are important for several applications: antibacterial, anthelmintic, antiprotozoal and antitumoral, among others. These applications are mainly related to the ability to spontaneously produce and induce the production of reactive oxygen species that are important components for the destruction of pathogens and tumor cells. While trying to potentiate ZnO NPs, studies have associated these NPs with silver oxide (AgO) or silver (Ag) NPs. It has already been reported that this combination (Ag-ZnO/AgO NPs) is able to enhance the microbicidal potential. Although possessing much potential for several purposes, it is important to evaluate whether this association also poses the risk of toxicity to cells and experimental models. Therefore, this work aimed to evaluate the toxicity of various Ag-ZnO/AgO NP nanocomposites, in vitro and in vivo. Accordingly, ZnO nanocrystals and nanocomposites with various concentrations of AgO (ZnO:5Ag, ZnO:9Ag or ZnO:11Ag) were used in different cytotoxicity models: Galleria mellonella (G. mellonella), cell lines (VERO and RAW 264.7) and C57BL/6 mice. In the G. mellonella model, four concentrations were used in a single dose, with subsequent evaluation of mortality. In the case of cells, serial concentrations starting at 125 µg/mL were used, with subsequent cytotoxicity assessment. Based on the safe doses obtained in G. mellonella and cell models, the best doses were used in mice, with subsequent evaluations of weight, biochemistry as also renal and liver histopathology. It was observed that the toxicity, although low, of the nanocomposites was dependent upon the concentration of AgO used in association with ZnO NPs, both in vitro and in vivo.

Biocompatibility of Brazilian native yeast-derived sophorolipids and Trichoderma harzianum as plant-growth promoting bioformulations.

The replacement of agrochemicals by biomolecules is imperative to mitigate soil contamination and inactivation of its core microbiota. Within this context, this study aimed at the interaction between a biological control agent such as Trichoderma harzianum CCT 2160 (BF-Th) and the biosurfactants (BSs) derived from the native Brazilian yeast Starmerella bombicola UFMG-CM-Y6419. Thereafter, their potential in germination of Oryza sativa L. seeds was tested. Both bioproducts were produced on site and characterized according to their chemical composition by HPLC-MS and GC-MS for BSs and SDS-PAGE gel for BF-Th. The BSs were confirmed to be sophorolipids (SLs) which is a well-studied compound with antimicrobial activity. The biocompatibility was examined by cultivating the fungus with SLs supplementation ranging from 0.1 to 2 g/L in solid and submerged fermentation. In solid state fermentation the supplementation of SLs enhanced spore production, conferring the synergy of both bioproducts. For the germination assays, bioformulations composed of SLs, BF-Th and combined (SLT) were applied in the germination of O. sativa L seeds achieving an improvement of up to 30% in morphological aspects such as root and shoot size as well as the presence of lateral roots. It was hypothesized that SLs were able to regulate phytohormones expression such as auxins and gibberellins during early stage of growth, pointing to their novel plant-growth stimulating properties. Thus, this study has pointed to the potential of hybrid bioformulations composed of biosurfactants and active endophytic fungal spores in order to augment the plant fitness and possibly the control of diseases.

Microplastics and TiO2 nanoparticles mixture as an emerging threat to amphibians: A case study on bullfrog embryos.

Emerging contaminants can act as contributing factors to the decline of amphibian populations worldwide. Recently, scientists have drawn attention to the potential ecotoxicity of microplastics and nanomaterials in amphibians, however, their possible effects on embryonic developmental stages are still absent. Thus, the present study analyzed the developmental toxicity of environmentally relevant concentrations of polyethylene microplastics (PE MPs; 60 mg/L) and titanium dioxide nanoparticles (TiO2 NPs; 10 µg/L), isolated or in combination (Mix group) on bullfrog embryos, Aquarana catesbeiana, adapting the Frog Embryo Teratogenesis Assay (FETAX, 96h). Allied to the FETAX protocol, we also analyzed the heart rate and morphometric data. The exposure reduced the survival and hatching rates in groups exposed to TiO2 NPs, and to a lesser extent, also affected the Mix group. TiO2 NPs possibly interacted with the hatching enzymes of the embryos, preventing hatching, and reducing their survival. The reduced effects in the Mix group are due to the agglomeration of both toxicants, making the NPs less available for the embryos. PE MPs got attached to the gelatinous capsule of the chorion (confirmed by fluorescence microscopy), which protected the embryos from eventual direct effects of the microplastics on the hatching and survival rates. Although there were no cardiotoxic effects nor morphometric alterations, there was a significant increase in abdominal edemas in the hatched embryos of the PE MPs group, which indicates that osmoregulation might have been affected by the attachment of the microplastics on the embryos' gelatinous capsule. This study presents the first evidence of developmental toxicity of environmental mixtures of microplastics and nanoparticles on amphibians and reinforces the need for more studies with other amphibian species, especially neotropical specimens that could present bigger sensibility. Our study also highlighted several features of the FETAX protocol as useful tools to evaluate the embryotoxicity of several pollutants on amphibians.

How do microplastics alter molluscicidal activity? Effects of weathered microplastics and niclosamide in developing freshwater snails.

Despite the wide distribution and persistence of microplastics (MPs), their interactive effects with molluscicides are unknown. Schistosomiasis, a neglected tropical disease, affects 236.6 million people worldwide. Niclosamide (NCL) is the only molluscicide recommended by the World Health Organization (WHO) and it is used to control the population of Schistosoma spp.'s intermediate host. Thus, this study aimed to evaluate of the interaction between polyethylene (PE) MPs and NCL, and their associated toxicity in the freshwater snail Biomphalaria glabrata (Say 1818). Weathered PE MPs were characterized and theoretical analysis of NCL-MP adsorption nature was made using quantum mechanical calculations. The toxicity of NCL isolated (0.0265 to 0.0809 mg L-1) and under interaction with PE MPs (3400 µg L-1) in B. glabrata embryos and newly hatched snails was analyzed. In silico analysis confirmed the adsorption mechanisms of NCL into PE MPs. PE MPs decreased the NCL toxicity to both B. glabrata developmental stages, increasing their survival and NCL lethal concentrations, indicating concerns regarding NCL use as molluscicide in aquatic environments polluted by MPs. In conclusion, MPs may change the efficiency of chemicals used in snail control programs.

Pointing out geographic and gender disparities related to productivity indicators among Brazilian ecotoxicologists.

Policies and actions related to diversity, equity, and inclusion have been discussed recently in Brazil, but there is still limited information available for most academic and knowledge fields, including ecotoxicology. This study aimed to describe the profile of Brazilian ecotoxicologists and assess gender and geographical disparities, especially regarding productivity indicators. An ecological study was conducted using data of the researchers registered in the open-access database of the Brazilian Society of Ecotoxicology, along with their respective curriculum data available on the Lattes Platform, which is the main registry portal for Brazilian researchers. The target population of our study was ecotoxicology researchers in academic educational institutions with a focus on human resource training. The data, collected in 2021, led to the inclusion of a total of 177 researchers in this study, with 62 men and 115 women, and 42.37% working in the southeastern region. Female researchers generally showed lower rates of scientific productivity when the analyzed metrics included research productivity scholarships, the number of articles published in scientific journals, and the number of articles published with international collaborations, compared to male researchers. Researchers from the southeastern and southern regions also had higher rates of productivity and human resource training compared to those from other regions of the country. The proportion of funding grants received was significantly higher among men, and this profile was also observed among researchers from the southern and southeastern regions, although with a smaller disparity. This means that there is an uneven distribution of funding grants from funding organizations, which favors men and urban centers. Our findings highlight gender and geographic disparities in the scientific production of ecotoxicologists working in Brazil and reinforce the existence of complex obstacles that need to be addressed and combated within scientific societies. Integr Environ Assess Manag 2024;20:1209-1216. © 2024 SETAC.

Zebrafish neuromast sensory system: Is it an emerging target to assess environmental pollution impacts?

Environmental pollution poses risks to ecosystems. Among these risks, one finds neurotoxicity and damage to the lateral line structures of fish, such as the neuromast and its hair cells. Zebrafish (Danio rerio) is recommended as model species to be used in ecotoxicological studies and environmental biomonitoring programs aimed at assessing several biomarkers, such as ototoxicity. However, little is known about the history of and knowledge gaps on zebrafish ototoxicity. Thus, the aim of the current study is to review data available in the scientific literature about using zebrafish as animal model to assess neuromast toxicity. It must be done by analyzing the history and publication category, world production, experimental design, developmental stages, chemical classes, neuromasts and hair cell visualization methods, and zebrafish strains. Based on the results, number, survival and fluorescence intensity of neuromasts, and their hair cells, were the parameters oftentimes used to assess ototoxicity in zebrafish. The wild AB strain was the most used one, and it was followed by Tübingen and transgenic strains with GFP markers. DASPEI was the fluorescent dye most often applied as method to visualize neuromasts, and it was followed by Yo-Pro-1 and GFP transgenic lines. Antibiotics, antitumorals, metals, nanoparticles and plant extracts were the most frequent classes of chemicals used in the analyzed studies. Overall, pollutants can harm zebrafish's mechanosensory system, as well as affect their behavior and survival. Results have shown that zebrafish is a suitable model system to assess ototoxicity induced by environmental pollution.

2,4-D Herbicide-Induced Hepatotoxicity: Unveiling Disrupted Liver Functions and Associated Biomarkers.

2,4-dichlorophenoxyacetic acid (2,4-D) is a widely used herbicide worldwide and is frequently found in water samples. This knowledge has prompted studies on its effects on non-target organisms, revealing significant alterations to liver structure and function. In this review, we evaluated the literature on the hepatotoxicity of 2,4-D, focusing on morphological damages, toxicity biomarkers and affected liver functions. Searches were conducted on PubMed, Web of Science and Scopus and 83 articles were selected after curation. Among these studies, 72% used in vivo models and 30% used in vitro models. Additionally, 48% used the active ingredient, and 35% used commercial formulations in exposure experiments. The most affected biomarkers were related to a decrease in antioxidant capacity through alterations in the activities of catalase, superoxide dismutase and the levels of malondialdehyde. Changes in energy metabolism, lipids, liver function, and xenobiotic metabolism were also identified. Furthermore, studies about the effects of 2,4-D in mixtures with other pesticides were found, as well as hepatoprotection trials. The reviewed data indicate the essential role of reduction in antioxidant capacity and oxidative stress in 2,4-D-induced hepatotoxicity. However, the mechanism of action of the herbicide is still not fully understood and further research in this area is necessary.

Polystyrene nanoplastics induce developmental impairments and vasotoxicity in zebrafish (Danio rerio).

The exponential use of plastics has significantly increased environmental pollution by nanoplastics (NPs). In the aquatic environment, NPs interact and bioaccumulate in the biota, posing a potential ecotoxicological risk. The present study investigated the developmental toxicity, vasotoxicity, cytotoxicity, ROS induction, and behavioral impairments in zebrafish (Danio rerio) exposed to environmentally relevant polystyrene NPs (PS-NPs) concentrations (0.04, 34 ng L-1, and 34 µg L-1) for 144 h through multiple biomarkers response (mortality, frequency of spontaneous contractions, heart rate, and morphological changes). Furthermore, vasotoxicity (head, yolk sac, tail, and branchial vessels) was evaluated using the transgenic zebrafish tg(Fli1:eGFP). Results showed that PS-NPs interacted mainly with zebrafish chorion, gills, tail, and larvae head. PS-NPs at 34 ng L-1 and 34 µg L-1 induced neurotoxicity (decreased frequency of spontaneous contractions), cardiotoxicity (bradycardia), and morphological changes in the eyes and head, indicating that PS-NPs induce developmental impairments in zebrafish. In addition, cytotoxicity in the caudal region (34 ng L-1), ROS production, decreased mean swimming speed, and distance covered were observed in all tested concentrations. PS-NPs also induced vasotoxicity (yolk sac region) in transgenic zebrafish. Overall, the present study demonstrates the harmful effects of PS-NPs on the early developmental stages of freshwater fish, indicating their environmental risk.

Exposure to microcrystallized cellulose affects the health of tadpoles and sheds light on the threat these materials pose to amphibians.

The increasing use of cellulose-based materials (CBMs) has provided beneficial applications in different sectors. However, its release into environments may represent an ecological risk, therefore demanding that ecotoxicological studies be conducted to understand the risks (current and future) of CBM pollution. Thus, we evaluated the possible effects of microcrystalline cellulose (CMs) in Physalaemus cuvieri tadpoles. After seven days of exposure to CMs (at 58.29 and 100 mg/L), the animals were subjected to behavioral evaluation, and different biomarkers (biometric and biochemical) were evaluated. Although our data do not point to a neurotoxic effect of CMs (inferred by the absence of behavioral changes and changes in AChE and BChE activity), animals exposed to CMs showed differences in body condition. Furthermore, we noticed an increase in the frequency of erythrocyte nuclear abnormalities and DNA damage, which were correlated with the ingestion of CMs. We noticed that the antioxidant activity of tadpoles exposed to CMs (inferred by SOD, CAT, and DPPH radical scavenging activity) was insufficient to control the increase in ROS and MDA production. Furthermore, exposure to CMs induced a predominant Th2-specific immune response, marked by suppressed IFN-γ and increased IL-10 levels, with a consequent reduction in NO levels. Principal component analysis and IBRv-2 indicate, in general, a primarily more toxic response to animals exposed to the highest CM concentration. Therefore, our study evidence that CMs affect the health of P. cuvieri tadpoles and sheds light on the threat these materials pose to amphibians.

Scaling up antivenom for snakebite envenoming in the Brazilian Amazon: a cost-effectiveness analysis.

Background: Snakebite envenoming (SBE) affects nearly three million people yearly, causing up to 180,000 deaths and 400,000 cases of permanent disability. Brazil's state of Amazonas is a global hotspot for SBE, with one of the highest annual incidence rates per 100,000 people, worldwide. Despite this burden, snake antivenom remains inaccessible to a large proportion of SBE victims in Amazonas. This study estimates the costs, and health and economic benefits of scaling up antivenom to community health centers (CHCs) and hospitals in the state. Methods: We built a decision tree model to simulate three different antivenom scale-up scenarios: (1) scale up to 95% of hospitals, (2) scale up to 95% of CHCs, and (3) scale up to 95% of hospitals and 95% of CHCs. We consider each scenario with and without a 10% increase in demand for antivenom among SBE victims. For each scenario, we model the treatment costs averted, deaths averted, and disability-adjusted life years (DALYs) averted from a societal, health system, and patient perspective relative to the status quo and over a time horizon of one year. For each scenario and perspective, we also calculate the incremental cost per DALY averted and per death averted. We use a willingness to pay threshold equal to the 2022 gross domestic product (GDP) per capita of Brazil. Findings: Scaling up antivenom to 95% of hospitals averts up to 2022 DALYs, costs up to USD $460 per DALY averted from a health system perspective, but results in net economic benefits up to USD $4.42 million from a societal perspective. Scaling up antivenom to 95% of CHCs averts up to 3179 DALYs, costs up to USD $308 per DALY averted from a health system perspective, but results in net economic benefits up to USD $7.35 million from a societal perspective. Scaling up antivenom to 95% of hospitals and CHCs averts up to 3922 DALYs, costs up to USD $328 per DALY averted from a health system perspective, but results in net economic benefits up to USD $8.98 million from a societal perspective. Interpretation: All three antivenom scale up scenarios - scale up to 95% of hospitals, scale up to 95% of CHCs, and scale up to 95% of hospitals and 95% of CHCs - avert a substantial proportion of the SBE burden in Amazonas and are cost-saving from a societal perspective and cost-effective from a health system perspective. Funding: W.M. and J.S. were funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq productivity scholarships). W.M. was funded by Fundação de Amparo à Pesquisa do Estado do Amazonas (PRÓ-ESTADO, call n. 011/2021-PCGP/FAPEAM, call n. 010/2021-CT&I ÁREAS PRIORITÁRIAS, call n. 003/2022-PRODOC/FAPEAM, POSGRAD/FAPEAM) and by the Ministry of Health, Brazil (Proposal No. 733781/19-035). Research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health under Award Number R21TW011944. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.