Health Assessment of Free-Ranging Eastern Indigo Snakes (Drymarchon couperi) from Hydrologic Restoration Construction Sites in South Florida, USA.

There is a paucity of information regarding the health status of free-ranging eastern indigo snakes (EIS; Drymarchon couperi) in heavily modified and developing landscapes. As a component of regional Florida Everglades restoration efforts, several areas occupied by EIS are being converted from agricultural lands to reservoirs. From 2020 to 2022, 28 EIS were opportunistically captured at two of these sites and brought into captivity to join a captive breeding colony; however, 11 snakes died within 5 mo of capture. Health assessments were performed on 28 individuals and included hematology and plasma biochemistry analysis, as well as screening for pesticide contaminant levels, parasites, and other pathogens. Overall, the presence of pathogens was relatively high, suggesting immunosuppression secondary to stress: 25/28 (89.4%) Kalicephalus sp.; 12/28 (42.9%) Raillietiella orientalis; 11/28 (39.2%) Ochetosoma validum; 7/28 (25.0%) Cryptosporidium serpentis; 3/28 (10.7%) snake adenovirus 1; and 1/28 (3.6%) Ferlavirus genotype C. Stress may have been caused by physical displacement, habitat modification, and noise pollution. These potential stressors (including the presence of remnant harmful chemicals from previous land use and the impacts on this federally threatened species) should be considered further when making restoration or construction decisions.

Snakebites in Northeastern Brazil: accessing clinical-epidemiological profile as a strategy to deal with Neglected Tropical Diseases.

BACKGROUND: Brazil ranks first in the number of snakebites in South America. A detailed analysis of these cases is required to improve the public health planning. In this study, we retrospectively examined the clinical and epidemiological profiles of snakebites in Maranhão between January 2009 and December 2019. METHODS: Data were obtained from the compulsory notification forms provided by the Health Department of Maranhão. RESULTS: A total of 17,658 cases were recorded during the study period. Most of the bites were from snakes belonging to the genus Bothrops. Medical care was mostly within three hours after the bite. Most cases were classified as mild and most victims recovered; however, 139 deaths were recorded. Most bites occurred among people aged 20-39 years, mainly among rural workers. The most frequent local clinical manifestations were pain, edema, and ecchymosis. The most common systemic clinical manifestations include neuroparalysis, vagal syndrome, and myolysis. Most snakebites occurred between January and March. The municipalities with the highest number of notifications were Buriticupu (936 cases), Arame (705 cases), and Grajaú (627 cases). CONCLUSIONS: The clinical profile of snakebites in Maranhão is similar to that observed in other states of Northeast Brazil. However, we found that some systemic manifestations are not compatible with the etiology of snakebites, which leads us to believe that the problem could be the lack of knowledge of the health professionals at the site of envenomation, who may not be ready for attendance, and an important lack of health centers with snake antivenom to treat snakebites.

Recent advancements in snake antivenom production.

Snakebite envenoming (SBE), a neglected tropical disease, claims lives of about 138,000 people globally, and antivenom is the only approved treatment worldwide. However, this century-old therapy has serious limitations, including limited efficacy and some side effects. Although alternative and adjunct therapies are being developed, their commercialization will take time. Hence, improving existing antivenom therapy is crucial for immediate reduction in the global SBE burden. The neutralization potential and immunogenicity of antivenoms depend primarily on the venom pool used for animal immunization and the production host, along with antivenom purification procedure and quality control. Enhancing antivenom quality and production capacity are also critical actions of the World Health Organization (WHO) roadmap 2021 against SBE. The present review details the latest developments in antivenom production, such as immunogen preparation, production host, antibody purification methods, antivenom testing-including alternative animal models, in vitro assays, and proteomics and in silico methodologies, and storage, reported from 2018 to 2022. Based on these reports, we propose that production of broadly specific, affordable, safe, and effective (BASE) antivenoms is fundamental to realizing the WHO roadmap and reducing the global SBE burden. This concept can also be applied during the designing of alternative antivenoms.

Retrospective assessment of general anesthesia-related challenges, morbidity, and death in snakes: 139 cases (2000-2022).

OBJECTIVE: To summarize the anesthetic events of snakes seen at a large university hospital, identify challenges with record keeping, and assess patient and anesthesia-related morbidity and death. SAMPLE: 139 anesthetic events were performed; only 106 cases had detailed anesthetic reports available for further analyses. PROCEDURES: Medical records of snakes that underwent general anesthesia between October 2000 and January 2022 were retrospectively reviewed. Only cases with complete anesthesia records were used to assess anesthetic parameters. Collected data included general patient details, diagnoses, procedures, premedication, induction, maintenance, monitoring, and recovery. RESULTS: A thorough review of the records identified issues or scenarios that resulted in poor record management as well as highlighted the most frequently used anesthetics in snakes. For premedication this was alfaxalone, butorphanol, and hydromorphone, whereas isoflurane, alfaxalone, or propofol were the most common with induction. Lastly, with maintenance, isoflurane was the most popular choice. Of the 139 cases performed, 127 animals recovered, 8 were euthanatized due to poor prognosis, and 4 failed to recover. All snakes that failed to recover had preexisting disease identified pre-, peri-, or postoperatively at necropsy. CLINICAL RELEVANCE: General anesthesia can be reliably and safely undertaken in snakes without severe preexisting disease. Efforts should be directed at identifying preexisting disease and maintaining and completing anesthesia records, and we recommend an auditing system to identify and correct issues as they arise.

Potential economic and clinical implications of improving access to snake antivenom in five ASEAN countries: A cost-effectiveness analysis.

BACKGROUND: Despite domestic production of antivenoms in the Association of Southeast Asian Nations (ASEAN) countries, not all victims with snakebite envenomings indicated for antivenom received the appropriate or adequate effective dose of antivenom due to insufficient supply and inadequate access to antivenoms. We aimed to conduct a cost-effectiveness analysis to project the potential economic and clinical impact of improving access to antivenoms when all snakebite envenomings in ASEAN countries were hypothetically treated with geographically appropriate antivenoms. METHODOLOGY: Using a decision analytic model with input parameters from published literature, local data, and expert opinion, we projected the impact of "full access" (100%) to antivenom, compared to "current access" in five most impacted ASEAN countries, including Indonesia (10%), Philippines (26%), Vietnam (37%), Lao PDR (4%), and Myanmar (64%), from a societal perspective with a lifetime time horizon. Sensitivity analyses were performed. PRINCIPAL FINDINGS: In base-case analyses, full access compared to current access to snake antivenom in the five countries resulted in a total of 9,362 deaths averted (-59%), 230,075 disability-adjusted life years (DALYs) averted (-59%), and cost savings of 1.3 billion USD (-53%). Incremental cost-effectiveness ratios (ICERs) of improving access to antivenom found higher outcomes but lower costs in all countries. Probabilistic sensitivity analyses of 1,000 iterations found that 98.1-100% of ICERs were cost-saving. CONCLUSION/SIGNIFICANCE: Improving access to snake antivenom will result in cost-saving for ASEAN countries. Our findings emphasized the importance of further strengthening regional cooperation, investment, and funding to improve the situation of snakebite victims in ASEAN countries.

Ontogeny of risk assessment and escape-hatching performance by red-eyed treefrog embryos in two threat contexts.

Arboreal embryos of red-eyed treefrogs, Agalychnis callidryas, hatch prematurely in response to hypoxia when flooded and to mechanosensory cues in snake attacks, but hatching later improves tadpole survival. We studied ontogenetic changes in risk assessment and hatching performance of embryos in response to flooding and physical disturbance. We hypothesized that risk assessment decreases as hatchling survival improves and hatching performance increases as embryos develop. Because snakes eat faster than embryos asphyxiate, we hypothesized that embryos decide to hatch sooner and hatch faster in response to mechanosensory cues. We video-recorded individual embryos hatching in response to each cue type, then compared the incidence and timing of a series of events and behaviors from cue onset to complete hatching across ages and stimuli. Latency from cue to hatching decreased developmentally in both contexts and was shorter with mechanosensory cues, but the elements contributing to those changes differed. Hypoxia assessment involved position changes, which decreased developmentally along with assessment time. Mechanosensory cue assessment occurred more rapidly, without movement, and decreased with age. The first stages of hatching, membrane rupture and head emergence, were surprisingly age independent but faster with mechanosensory cues, congruent with greater effort under more immediate risk. In contrast, body emergence and compression showed ontogenetic improvement consistent with morphological constraints but no cue effect. Both appropriate timing and effective performance of hatching are necessary for continued development. Different stages of the process vary with development and environmental context, suggesting combinations of adaptive context- and stage-dependent behavior, cue-related constraints on information acquisition, and ontogenetic constraints on elements of performance.

Frog embryos use multiple levels of temporal pattern in risk assessment for vibration-cued escape hatching.

Stereotyped signals can be a fast, effective means of communicating danger, but animals assessing predation risk must often use more variable incidental cues. Red eyed-treefrog, Agalychnis callidryas, embryos hatch prematurely to escape from egg predators, cued by vibrations in attacks, but benign rain generates vibrations with overlapping properties. Facing high false-alarm costs, embryos use multiple vibration properties to inform hatching, including temporal pattern elements such as pulse durations and inter-pulse intervals. However, measures of snake and rain vibration as simple pulse-interval patterns are a poor match to embryo behavior. We used vibration playbacks to assess if embryos use a second level of temporal pattern, long gaps within a rhythmic pattern, as indicators of risks. Long vibration-free periods are common during snake attacks but absent from hard rain. Long gaps after a few initial vibrations increase the hatching response to a subsequent vibration series. Moreover, vibration patterns as short as three pulses, separated by long periods of silence, can induce as much hatching as rhythmic pulse series with five times more vibration. Embryos can retain information that increases hatching over at least 45 s of silence. This work highlights that embryo behavior is contextually modulated in complex ways. Identical vibration pulses, pulse groups, and periods of silence can be treated as risk cues in some contexts and not in others. Embryos employ a multi-faceted decision-making process to effectively distinguish between risk cues and benign stimuli.

Energy expenses on prey processing are comparable, but paid at a higher metabolic scope and for a longer time in ambush vs active predators: a multispecies study on snakes.

Snakes are characterized by distinct foraging strategies, from ambush to active hunting, which can be predicted to substantially affect the energy budget as a result of differential activity rates and feeding frequencies. Intense foraging activity and continuously upregulated viscera as a result of frequent feeding leads to a higher standard metabolic rate (SMR) in active than in ambush predators. Conversely, the costs of digestion (Specific Dynamic Action-SDA) are expected to be higher in ambush predators following the substantial remodelling of the gut upon ingestion of a meal after a long fasting period. This prediction was tested on an interspecific scale using a large multispecies dataset (> 40 species) obtained from published sources. I found that the metabolic scope and duration of SDA tended to reach higher values in ambush than in active predators, which probably reflects the greater magnitude of postprandial physiological upregulation in the former. In contrast, the SDA energy expenditure appeared to be unrelated to the foraging mode. The costs of visceral activation conceivably are not negligible, but represent a minor part of the total costs of digestion, possibly not large enough to elicit a foraging-mode driven variation in SDA energy expenditure. Non-mutually exclusive is that the higher costs of structural upregulation in ambush predators are balanced by the improved, thus potentially less expensive, functional performance of the more efficient intestines. I finally suggest that ambush predators may be less susceptible than active predators to the metabolic 'meltdown effect' driven by climate change.

Multiscale assessment of functional connectivity: Landscape genetics of eastern indigo snakes in an anthropogenically fragmented landscape in central Florida.

Landscape features can strongly influence gene flow and the strength and direction of these effects may vary across spatial scales. However, few studies have evaluated methodological approaches for selecting spatial scales in landscape genetics analyses, in part because of computational challenges associated with optimizing landscape resistance surfaces (LRS). We used the federally threatened eastern indigo snake (Drymarchon couperi) in central Florida as a case study with which to compare the importance of landscape features and their scales of effect in influencing gene flow. We used genetic algorithms (ResistanceGA) to empirically optimize LRS using categorical land cover surfaces, multiscale resource selection surfaces (RSS), and four combinations of landscape covariates measured at multiple spatial scales (multisurface multiscale LRS). We compared LRS where scale was selected using pseudo- and full optimization. Multisurface multiscale LRS received more empirical support than LRS optimized from categorical land cover surfaces or RSS. Multiscale LRS with scale selected using full optimization generally outperformed those with scale selected using pseudo-optimization. Multiscale LRS with large spatial scales (1200-1800 m) received the most empirical support. Our results highlight the importance of considering landscape features across multiple spatial scales in landscape genetic analyses, particularly broad scales relative to species movement potential. Different effects of scale on home range-level movements and dispersal could explain weak associations between habitat suitability and gene flow in other studies. Our results also demonstrate the importance of large tracts of undeveloped upland habitat with heterogenous vegetation communities and low urbanization for promoting indigo snake connectivity.

The in vitro laboratory tests and mass spectrometry-assisted quality assessment of commercial polyvalent antivenom raised against the 'Big Four' venomous snakes of India.

India has recorded the maximum snakebite deaths in the world. Intravenous administration of polyvalent antivenom (PAV) raised against the 'Big Four' venomous snakes of India (Naja naja, Daboia russelli, Echis carinatus, and Bungarus caeraleus) is the only choice of treatment. The WHO has recommended the evaluation of quality and safety of commercial antivenom by in vitro laboratory tests prior to their pre-clinical evaluation in animal model and therapeutic use. Therefore, in this study an attempt has been made to evaluate the quality of commercial polyvalent antivenom produced in India by simple, and affordable laboratory tests. Proteomic analysis revealed that PAVs contained 78.7-94.8% IgG/F(ab')2 and small quantities of plasma proteins. The PAVs showed batch-to-batch variations with varying amounts of undigested IgG and its aggregates, and moderate complement activation. However, absence of IgE, negligible endotoxin contamination, and recommended limit of preservative (cresol) in PAVs were observed. The PAVs contain varying proportions and least amount of venom-specific antibodies against venoms of the 'Big Four' snakes from different locales of India, and against eastern India N. kaouthia venom, respectively. The importance of independent in vitro laboratory tests for the quality control and safety assessment for improving the quality of Indian commercial PAV is reinforced.

The cost of travel: How dispersal ability limits local adaptation in host-parasite interactions.

Classical theory suggests that parasites will exhibit higher fitness in sympatric relative to allopatric host populations (local adaptation). However, evidence for local adaptation in natural host-parasite systems is often equivocal, emphasizing the need for infection experiments conducted over realistic geographic scales and comparisons among species with varied life history traits. Here, we used infection experiments to test how two trematode (flatworm) species (Paralechriorchis syntomentera and Ribeiroia ondatrae) with differing dispersal abilities varied in the strength of local adaptation to their amphibian hosts. Both parasites have complex life cycles involving sequential transmission among aquatic snails, larval amphibians and vertebrate definitive hosts that control dispersal across the landscape. By experimentally pairing 26 host-by-parasite population infection combinations from across the western USA with analyses of host and parasite spatial genetic structure, we found that increasing geographic distance-and corresponding increases in host population genetic distance-reduced infection success for P. syntomentera, which is dispersed by snake definitive hosts. For the avian-dispersed R. ondatrae, in contrast, the geographic distance between the parasite and host populations had no influence on infection success. Differences in local adaptation corresponded to parasite genetic structure; although populations of P. syntomentera exhibited ~10% mtDNA sequence divergence, those of R. ondatrae were nearly identical (<0.5%), even across a 900 km range. Taken together, these results offer empirical evidence that high levels of dispersal can limit opportunities for parasites to adapt to local host populations.

Snakebite Envenomation in Rwanda: Patient Demographics, Medical Care, and Antivenom Availability in the Formal Healthcare Sector.

Snakebite envenomation (SBE) is a neglected One Health issue that overwhelmingly affects people living in rural and impoverished regions of Africa and Asia. Information on SBE is scarce in Rwanda; thus, our objectives were to 1) describe the demographics of SBE patients seeking hospital care, 2) evaluate physician adherence to national treatment guidelines, and 3) assess availability of snake antivenom at hospitals in Rwanda. To achieve these goals, we obtained national data on animal bites/stings and visited every district and provincial hospital in Rwanda to obtain physical records of SBE patients treated in 2017 and 2018. Hospital pharmacies were assessed for antivenom availability. We identified snakes as the second leading cause of animal bites, after dogs, among patients who sought hospital care in 2017 and 2018. Of 363 SBE patients, the highest number of cases occurred among children (< 18 years; 32%) and young adults (18-30 years; 33%), females (61%), farmers (82%), and those living in Eastern Province (37%). Overall, physician adherence to treatment guidelines was 63%. Prescriptions of vitamin K and antivenom were low (4% and 13%, respectively), and only 8% of hospital pharmacies had antivenom in stock throughout the study period. The antivenom stocked was an Indian generic suited for Asian snakes. This minimum estimate of hospitalization cases does not include individuals who died in communities or sought care outside the formal sector. Our study highlights the need to map incidence, risk factors, and patient experiences to mitigate human-snake conflicts and improve patient outcomes.

Good management practices of venomous snakes in captivity to produce biological venom-based medicines: achieving replicability and contributing to pharmaceutical industry.

One of the factors responsible for lack of reproducible findings may be attributed to the raw material used. To date, there are no apparent studies examining reproducibility using venoms for the development of new toxin-based drugs with respect to regulatory agencies' policies. For this reason, protocols were implemented to produce animal toxins with quality, traceability, and strict compliance with Good Manufacturing Practices. This required validation of the production chain from the arrival of the animal to the vivarium, followed by handling, housing, as well as compliance with respect to extraction, freeze-drying, and, finally, storage protocols, aimed at generating compounds to serve as candidate molecules applicable in clinical trials. Currently, to produce quality snake venoms to support reproductive studies, the Center for the Study of Venoms and Venomous Animals (CEVAP) from São Paulo State University (UNESP), São Paulo, Brazil has 449 microchipped snakes through rigid and standardized operating procedures for safety, health, and welfare of animals. Snakes were frequently subjected to vet clinical examination, anthelmintic, and antiparasitic treatment. Venom milk used to destroy prey was collected from each animal in individual plastic microtubes to avoid contamination and for traceability. In addition, venoms were submitted to microbiological, and biochemical toxicological analyses. It is noteworthy that investigators are responsible for caring, maintaining, and manipulating snakes and ensuring their health in captivity. This review aimed to contribute to the pharmaceutical industry the experimental experience and entire snake venom production chain required to generate quality products for therapeutic human consumption.

Venomous snakebites: Rapid action saves lives-A multifaceted community education programme increases awareness about snakes and snakebites among the rural population of Tamil Nadu, India.

The lack of public awareness surrounding the dangers of snakebite envenomation (SBE) is one of the most critical factors contributing to SBE-induced complications, and subsequently exacerbating the number of deaths and disabilities resulting from SBE. In this study, we deployed a multifaceted community education programme to educate students, healthcare professionals and members of the public in rural areas of Tamil Nadu, India about the dangers of SBE, appropriate first aid measures and the 'do's and don'ts' following a snakebite. An assessment of prior knowledge within these communities identified several misconceptions concerning snakes and SBE. Using a combination of direct engagement (estimated to reach over 200,000 people), information leaflets (200,000 distributed), posters, video documentaries, media and social media (>2.8 million engagements), over the course of one year (January to December 2019) we reached over 3 million people in rural Tamil Nadu (around 8% of population). Evaluation of community-based assemblies indicated that at least 90% of attendees were able to recall the key messages at the end of the events, and at least 85% were able to recall the key messages even after 12 months. Due to high demand, a one-day symposium was organised to provide clinical knowledge and training on SBE to 250 healthcare professionals in rural Tamil Nadu. Notably, an assessment of patient data (291 victims) collected from a snakebite referral hospital over the same 12-month period (2019) indicated that arrival time at hospital following a snakebite was significantly faster and the effective first aid measures were administered to patients who were aware of our activities compared to those that were not. Overall, our approach provides a framework on how to educate rural communities about the dangers of SBE and thereby, mitigate delayed SBE treatment leading to an overall reduction in SBE-induced mortality, morbidity, treatment costs and other socio-economic ramifications.

Camera-traps are a cost-effective method for surveying terrestrial squamates: A comparison with artificial refuges and pitfall traps.

INTRODUCTION: Fundamental data on the distributions, diversity, and threat status of terrestrial snakes and lizards (hereafter squamates) is limited. This is due to the cryptic nature of species in this faunal group, and to limitations in the effectiveness of the survey methods used to detect these species. Camera-traps are a useful tool for detecting numerous vertebrate species, yet their use for detecting squamates has been limited. Here, we apply recent methodological advancements in camera-trapping and assessed the utility of camera-traps for inventorying a squamate assemblage by comparing camera-trapping survey results with two widely used labour-intensive methods: artificial refuges and pitfall traps. METHODS: We conducted a 74-day survey using camera-traps and, concurrently, four by four-day surveys using labour-intensive methods. Given the duration and three detection methods, we compared seven variants of survey protocol, including using each method alone or all methods simultaneously. We compared both the effectiveness and cost-effectiveness of each survey protocol by estimating the number of species detected at the transect level, and by calculating the costs of conducting those surveys. RESULTS: We found the camera-trapping survey was most cost-effective, costing 687 AUD (CI 534-912) per squamate species detected, compared with the 2975 AUD (CI 2103-4486) per squamate species detected with the labour-intensive methods. Using all methods together was less cost-effective than using camera-traps alone. Additionally, there was a 99% probability that camera-traps would detect more species per transect than the labour-intensive methods examined. DISCUSSION & CONCLUSION: By focusing the analysis at the level of the survey, rather than the level of the device, camera-traps are both a more effective and cost-effective technique for surveying terrestrial squamates. Where circumstances are appropriate, those wildlife researchers and managers currently using camera-traps for non-squamate surveys, can adopt the methods presented to incorporate squamate surveys with little upfront cost. Additionally, researchers currently using traditional techniques can be confident that switching to camera-traps will likely yield improved results. Still, camera-traps are not a panacea and careful consideration into the benefits and usefulness of these techniques in individual circumstances is required.

Snakebite accidents in Rio Grande do Norte state, Brazil: Epidemiology, health management and influence of the environmental scenario.

OBJECTIVES: Brazil is home to large variety of snake species, of which about 17% are venomous. A large proportion of reported snakebite accidents in the country take place in northeast Brazil. We aimed to analyse the epidemiology of snakebites as a public health concern in Rio Grande do Norte state. METHODS: A retrospective epidemiologic analysis was performed using data from the Brazilian Case Registry Database pertaining to the period 2007-2016, and considering environmental climate characteristics as an influential factor. RESULTS: A number of 3909 cases were reported in total. Among those cases, 58% involved venomous species and more than 80% of these were caused by Bothrops species. An association between environmental characteristics and the incidence of reported cases was found. The Borborema Potiguar region was the most affected area. Apart from that, deficiencies in managing the victims were described. CONCLUSION: This study highlights snakebite accidents as a public health concern in Rio Grande do Norte state. Snake bites are most likely being influenced by climate change and human activities. Continuous training of involved medical personnel could help optimise patient care and avoid under reporting in the accident reporting system.

OBJECTIFS: Le Brésil abrite de très nombreuses espèces de serpents, dont environ 17% sont venimeuses. Une grande partie des accidents rapportés de morsures de serpent dans le pays ont lieu dans le nord-est du pays. Notre objectif était d'analyser l'épidémiologie des morsures de serpents en tant que problème de santé publique dans l'Etat du Rio Grande do Norte. MÉTHODES: Une analyse épidémiologique rétrospective a été réalisée à l'aide des données de la Base de Données du Registre Brésilien des cas couvrant la période 2007-2016 et prenant en compte les caractéristiques climatiques de l'environnement comme facteur d'influence. RÉSULTATS: 3.909 cas au total ont été rapportés. 58% concernaient des espèces venimeuses et plus de 80% d'entre elles étaient causées par l'espèce Bothrops. Une association entre les caractéristiques environnementales et l'incidence des cas rapportés a été mise en évidence. La région de Borborema Potiguar était la plus touchée. Outre cela, les déficiences dans la prise en charges des victimes ont été décrites. CONCLUSION: Cette étude souligne que les accidents causés par des morsures de serpent constituent un problème de santé publique dans l'Etat de Rio Grande do Norte. Les morsures de serpents sont très probablement influencées par les changements climatiques et les activités humaines. La formation continue du personnel médical impliqué pourrait aider à optimiser les soins prodigués aux patients et à éviter une sous-notification dans le système de notification des accidents.

Vulnerability to snakebite envenoming: a global mapping of hotspots.

BACKGROUND: Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed. METHODS: We assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but <5 species occurrence records), and group C (EOR map and ≥5 species occurrence records). For group C species, we did a multivariate environmental similarity analysis using the 2008 WHO EOR maps and newly available evidence. Using these data and the EOR maps, we produced contemporary range maps for medically important venomous snake species at a 5 × 5 km resolution. We subsequently triangulated these data with three health system metrics (antivenom availability, accessibility to urban centres, and the Healthcare Access and Quality [HAQ] Index) to identify the populations most vulnerable to snakebite morbidity and mortality. FINDINGS: We provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within the lowest decile are at risk of exposure to any snake for which no effective therapy exists compared with 519·46 million individuals (27·79%) within the highest HAQ Index decile, showing a disproportionate coverage in reported antivenom availability. Antivenoms were available for 119 (43%) of 278 snake species evaluated by WHO, while globally 750·19 million (10·95%) of those living within snake ranges live more than 1 h from population centres. In total, we identify about 92·66 million people living within these vulnerable geographies, including many sub-Saharan countries, Indonesia, and other parts of southeast Asia. INTERPRETATION: Identifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease. FUNDING: Bill & Melinda Gates Foundation.

Toxin-resolved antivenomics-guided assessment of the immunorecognition landscape of antivenoms.

Snakebite envenoming represents a major issue in rural areas of tropical and subtropical regions across sub-Saharan Africa, South to Southeast Asia, Latin America and Oceania. Antivenoms constitute the only scientifically validated therapy for snakebite envenomings, provided they are safe, effective, affordable, accessible and administered appropriately. However, the lack of financial incentives in a technology that has remained relatively unchanged for more than a century, has contributed to some manufacturers leaving the market and others downscaling production or increasing the prices, leading to a decline in the availability and accessibility for these life-saving antidotes to millions of rural poor most at risk from snakebites in low income countries. The shortage of antivenoms can be significantly alleviated by optimizing the use of current antivenoms (through the assessment of their specific and paraspecific efficacy against the different medically relevant homologous and heterologous snake venoms) and by generating novel polyspecific antivenoms exhibiting broad clinical spectrum and wide geographic distribution range. Research on venoms has been continuously enhanced by advances in technology. Particularly, the last decade has witnessed the development of omics strategies for unravelling the toxin composition of venoms ("venomics") and to assess the immunorecognition profile of antivenoms ("antivenomics"). Here, we review recent developments and reflect on near future innovations that promise to revolutionize the mutually enlightening relationship between evolutionary and translational venomics.

Preclinical assessment of the neutralizing efficacy of snake antivenoms in Latin America and the Caribbean: A review.

The preclinical evaluation of the neutralizing efficacy of antivenoms is mandatory before a product is introduced for clinical use. The World Health Organization (WHO) guidelines for antivenoms categorize the tests used in preclinical studies as 'essential assay' (neutralization of lethality) and 'additional recommended assays' (neutralization of other relevant toxic activities). The present review presents an overview of the methodological aspects of snake antivenom preclinical efficacy tests, and summarizes the studies performed in this subject on antivenoms used in Latin America and the Caribbean. General trends emerging from this analysis show that: (a) Bothrops antivenoms have a broad spectrum of neutralizing efficacy against venoms of snakes of the genera Agkistrodon, Atropoides, Bothriechis, Bothrops, Cerrophidion, and Porthidium. (b) Crotalus antivenoms show a dichotomic pattern of efficacy depending on whether the venoms used for immunization are crotoxin-rich or metalloproteinase-rich. (c) A complete neutralization of Lachesis sp venoms is achieved only by antivenoms that include Lachesis sp venoms in the immunizing mixture. (d) Micrurus sp venoms have a high immunological heterogeneity which impacts in the cross-neutralization by available antivenoms. There is a need to further expand the knowledge base of the preclinical efficacy of antivenoms in Latin America and the Caribbean.