Diagnosing snakebite envenoming is a critical aspect of managing this life-threatening condition. Achieving the impacts and clinical applications of the diagnosis of snakebites is important to help clarify the challenges faced in identifying venomous snakebites and implementing effective treatment strategies. The complexity of the envenomation requires a comprehensive diagnostic approach, considering both clinical symptoms and laboratory findings. Despite advances in diagnostic technologies, the lack of standardized tools represents a significant obstacle to obtaining accurate and timely assessments. This paper analyzes the state-of-the-art snakebite diagnosis, emphasizing the need for methodologies for differential diagnosis of snakebites. Furthermore, it investigates the far-reaching consequences of late or incorrect diagnoses, emphasizing their role in the potential development of serious morbidity and even mortality. The discussion extends to the global health burden caused by snakebite envenoming, emphasizing the importance of personalized diagnostic methods in regions with diverse snake species. Furthermore, the review explores recent advances in the global scale diagnosis of snakebite venom. The clinical applications of these innovations are explored, highlighting their potential to revolutionize snakebite management in resource-limited settings. By addressing the multifaceted challenges in snakebite diagnosis, this summary contributes to ongoing efforts to mitigate the global impact of snakebite envenoming by highlighting the critical need for collaborative research, standardization, and accessibility of diagnostic tools.

Every 5 minutes, 50 people are bitten by a snake worldwide; four will be permanently disabled and one will die. Most approaches to treating and diagnosing snake envenomation, a World Health Organization (WHO)-neglected tropical disease, rely on antibody-based solutions derived from animals or cell culture. Here, we present the first proof of concept for a glycopolymer-based ultraviolet-visible (UV-vis) assay to detect snake venom, specifically Western Diamondback Rattlesnake (Crotalus atrox) venom. This was achieved by synthesizing a library of glycan-terminated poly(hydroxyethyl acrylamide) functionalized gold nanoparticles. The library was analyzed using UV-vis spectroscopy and biolayer interferometry, with galactose-terminating systems found to demonstrate specificity for C. atrox venom, versus model lectins and Naja naja venom in UV-vis assays. This corroborates glycan array data in the literature and highlights our glycopolymer systems' potential as a diagnostic tool for snakebite, with the best particle system displaying a limit of detection of ∼20 μg·mL-1.

Mouse lethality assays (MLA) remain the gold standard for evaluating antivenom potency despite ethical concerns regarding animal welfare. This study assessed whether reducing observation periods from 48 to 24 h in MLA for determining median lethal dose (LD50) and median effective dose (ED50) of Bothrops jararaca and Crotalus durissus terrificus venoms and antivenoms maintains scientific validity while improving animal welfare. Through retrospective analysis of 518 quality control assays conducted between 2009-2023 at INCQS, including 334 potency assays and 27 median lethal dose assays for B. jararaca, and 134 ED50 assays and 23 LD50 assays for C. d. terrificus, we found that over 98% of deaths occurred within the first 24 h post-injection for all LD50 determinations on venoms and all ED50 determinations on antivenoms for both species. Statistical analyses demonstrated exceptional agreement between 24-hour and 48-hour endpoints, with concordance correlation coefficients exceeding 0.96 for all assays. Bland-Altman analysis revealed narrow limits of agreement with minimal systematic bias, particularly for antivenom potency measurements. Classification performance metrics showed excellent accuracy (98.5%-100%) in identifying satisfactory antivenoms at 24 h compared to the standard 48-hour protocol, with weighted kappa coefficients exceeding 0.98, indicating near-perfect agreement. For C. d. terrificus antivenom, the 24-hour assay demonstrated 100% concordance with the 48-hour classification, while B. jararaca antivenom showed 98.5% accuracy with only 6 discordant results among 334 assays. Kaplan-Meier survival analysis confirmed statistically equivalent survival probabilities between both time points. These findings provide robust evidence supporting the adoption of a 24-hour observation period as an ethically superior refinement that maintains scientific integrity while significantly reducing animal distress. This refinement aligns with the 3Rs principles and could enhance testing efficiency in antivenom quality control, establishing a precedent for similar refinements in other biological assays and supporting the revision of regulatory guidelines to incorporate more humane testing protocols.

This study focuses on the quaternary structure of the viper-secreted phospholipase A2 (PLA2), a central toxin in viper envenomation. PLA2 enzymes catalyze the hydrolysis of the sn-2 ester bond of membrane phospholipids. Small-molecule inhibitors that act as snakebite antidotes, such as varespladib, are currently in clinical trials. These inhibitors likely bind to the enzyme in the aqueous cytosol prior to membrane-binding. Thus, understanding its controversial solution structure is key for drug design. Crystal structures of PLA2 in the PDB show at least four different dimeric conformations, the most well-known being "extended" and "compact". This variability among enzymes with >50 % sequence identity raises questions about their transferability to aqueous solution. Therefore, we performed extensive molecular dynamics (MD) simulations of several PLA2 enzymes in water to determine their quaternary structure under physiological conditions. The MD simulations strongly indicate that PLA2 enzymes adopt a "semi-compact" conformation in cytosol, a hybrid between extended and compact conformations. To our knowledge, this is the first study that determines the most favorable dimeric conformation of PLA2 enzymes in solution, providing a basis for advancements in snakebite envenoming treatment. Recognizing snakebite envenoming as a neglected tropical disease has driven the search for efficient, affordable alternatives to the current antivenoms. Therefore, understanding the main drug targets within snake venom is crucial to this achievement.

Snakebite envenoming is a neglected public health problem in many tropical countries, resulting in over 100 000 deaths and 400 000 disabilities worldwide each year. In Gabon, where venomous snakes are abundant, studies on the epidemiology and treatment of snakebites are lacking.

Between October 2022 and June 2023, we conducted a cross-sectional community survey in the department of Ogooué et des Lacs in central Gabon to estimate the snakebite incidence, describe clinical presentations and treatment-seeking behaviours, and describe the burden of snakebites to animal populations in rural and urban communities. We also surveyed health facilities in the department to describe treatment practices and the availability of antivenom.

The standardised annual incidence rate was 246 snakebite cases per 100 000 person-years (95% confidence interval (CI) = 138-438). Of the 175 snakebite cases reported in the five years prior to the survey, 18% showed signs of envenomation, predominantly with cytotoxic signs. The mortality among the bitten population was 3%. Snakebite treatment was first sought at a formal health facility in 55% of cases, from traditional healers in 22%, and with self-treatment or no treatment in the remaining 23%. Of snakebite patients treated at a formal health facility in the five years prior to the survey, 81% received antivenom, 41% received antibiotics, and 51% received corticosteroids. Almost one in six households reported animal deaths due to snakebites in the previous 12 months.

This study provides the first robust epidemiological estimates of the burden of snakebites in Gabon and highlights the importance of community-based surveys in accurately assessing this high burden. Training health care workers, developing treatment guidelines, and ensuring the availability of effective and affordable antivenom are important steps to improving the outcome for snakebite victims.

Snakebite envenoming is often discussed in terms of lethality and limb loss, but local tissue injury and coagulotoxic effects of venom are significantly more common acute manifestations of snakebite envenoming (SBE). Local tissue injury and the hemorrhagic and coagulotoxic effects of venom are challenging to study in live animals and can be ethically fraught due to animal welfare concerns such that attention to the 3Rs of animal welfare motivates the development of in vitro techniques in this arena. Herein, we tested the use of a wound-healing study technique known as Electric Cell-Substrate Impedance Sensing (ECIS) to assess populations of cultured cells exposed to venom with or without sPLA2 and/or metalloprotease inhibitors (varespladib and marimastat, respectively). For comparison, the StarMax coagulation analyzer for coagulotoxicity was further used to evaluate the venoms and the neutralizing capabilities of the abovementioned direct toxin inhibitors (DTIs) against the same venoms examined using ECIS. Three viper and three elapid venoms that were examined for their effects on H1975 cells were Agkistrodon contortrix (Eastern Copperhead), Crotalus helleri (Southern Pacific Rattlesnake), and Vipera ammodytes (Horned Viper) and Naja atra (Chinese Cobra), Naja mossambica (Mozambique Spitting Cobra), and Naja nigricollis (Black-necked Spitting Cobra), respectively. The combination of cellular and coagulation techniques appears to usefully discriminate the in vitro capabilities and limitations of specific inhibitors to inhibit specific venom effects. This study suggests that ECIS with or without concomitant coagulation testing is a feasible method to generate reproducible, meaningful preclinical data and could be used with any type of cell line. Importantly, this approach is both quantitative and has the potential of reducing animal use and suffering during the evaluation of potential therapeutics. To further evaluate the potential of this method, rescue studies should be performed.

To investigate the frequency, timing, and characteristics of cardiovascular collapse after snakebite in Australia, and the complications of collapse following envenoming.

Observational study; analysis of prospectively collected demographic and clinical data.

People with confirmed snake envenoming recruited to the Australian Snakebite Project at one of 200 participating Australian hospitals, 1 July 2005 - 30 June 2020.

Time from snakebite to collapse; post-collapse complications (cardiac arrest, seizures, death).

Of 1259 envenomed people, 157 (12%) collapsed within 24 hours of the snakebite; venom-induced consumption coagulopathy (VICC) was determined in all 156 people for whom coagulation testing could be performed. The exact time between bite and collapse was known for 149 people (median, 20 min; interquartile range, 15-30 min; range, 5-115 min); the time exceeded 60 minutes for only two people, each after releasing tight bandages 60 minutes after the bite. The collapse preceded hospital arrival in 132 cases (84%). Brown snake (Pseudonaja spp.) envenoming was the leading cause of collapse (103 cases, 66%). Forty-two collapses (27%) were followed by cardiac arrest, 49 (31%) by seizures (33 without cardiac arrest), and five by apnoea; collapse was associated with hypotension in all 24 people whose blood pressure could be measured at or close to the time of collapse. Twenty-five people who collapsed died (16%), and seven of the envenomed people who did not collapse (0.6%; difference: 15 percentage points; 95% confidence interval, 8-21 percentage points). The deaths of 21 of the 25 people who collapsed were immediately associated with the cardiac arrest that followed the collapse; three people who did not have cardiac arrests died later of intracranial haemorrhage, and one of hyperthermia. The proportion of people who had collapsed before reaching hospital was larger for people who died of post-collapse cardiac arrest (13 of 21, 62%) than for those who survived (6 of 21, 28%).

Collapse after Australian snake envenoming almost always occurred within 60 minutes of the bite, was always accompanied by VICC, and most frequently followed brown snake bites. Poorer outcomes, including cardiac arrest, seizures, and death, were more frequent for people who collapsed than for those who did not. Outcomes for people who collapsed before medical care arrived were poorer than for those who collapsed in hospital or in an ambulance.

The Philippines has a high diversity of venomous snake species, but there is minimal information on their envenomation effects. This is evidenced by the small number of case reports, the poor reporting of envenomation cases, and the absence of specific antivenoms apart from one against the Philippine cobra (Naja philippinensis). This study sought to profile the action of selected Philippine pit viper venoms on blood coagulation and to investigate whether commercially available non-specific antivenoms can provide adequate protection against these venoms. Venom from the pit vipers Trimeresurus flavomaculatus and Trimeresurus mcgregori were subjected to coagulation assays, antivenom cross-neutralization tests, and thromboelastography. Venoms from both species were able to clot human plasma and isolated human fibrinogen. Consistent with pseudo-procoagulant/thrombin-like activity, the resulting fibrin clots were weak and transient, thereby contributing to net anticoagulation through the depletion of fibrinogen levels. Clotting factors fIXa and fXa were also inhibited by the venoms, further contributing to the net anticoagulant activity. Monovalent and polyvalent antivenoms from the Thai Red Cross Society were effective against both venoms, indicating cross-neutralization of venom toxins; the polyvalent antivenom was able to rescue fibrinogen clotting to a greater degree than the monovalent antivenom. Our findings highlight the coagulopathic effects of these pit viper venoms and suggest the utility of procuring the non-specific antivenoms for areas in the Philippines with a high risk for pit viper envenomation.

Snakebite envenomation is a neglected public health issue affecting thousands of victims worldwide. In Brazil, the genus Bothrops is responsible for 88 % of snakebites; bites from the species B. jararacussu present at a high frequency and are associated with high lethality and morbidity rates. B. jararacussu injects a large volume of venom, leading to massive tissue necrosis, hemorrhage, and eventually death. Antivenom is the only available treatment for neutralizing such toxic effects; it effectively prevents death but not the physical sequelae caused by muscle damage. Antivenom has other drawbacks, such as fever and anaphylactic reactions, high production costs, and the need for controlled storage temperatures. Thus, complementary treatments are sought to overcome these disadvantages of antivenoms. Here, we assessed the effects of commercial tannic acid on the major toxic activities of B. jararacussu venom, such as its proteolytic, plasma coagulation, edematogenic, hemorrhagic, and lethal effects. Overall, the incubation of tannic acid with B. jararacussu venom inhibited the venom's in vitro coagulant and proteolytic effects and in vivo hemorrhagic and edematogenic activities; however, it failed to prevent against lethality. Antibothropic serum protected mice from B. jararacussu venom-induced death and inhibited edema by approximately 45 % but did not protect against hemorrhage. In conclusion, tannic acid efficiently neutralized the main toxic activities of B. jararacussu venom, which causes severe envenomation in some South American countries. Thus, tannic acid is a candidate for managing Bothrops snakebites and, alongside antivenom, may hasten and improve victim recovery.

Haemotoxicity is the most common complication of systemic envenoming following snakebite, leading to diverse clinical syndromes ranging from haemorrhagic to prothrombotic manifestations. Key haematological abnormalities include platelet dysfunction, venom-induced consumption coagulopathy, anticoagulant coagulopathy and organ-threatening thrombotic microangiopathy. Diagnostic methods include the bedside whole blood clotting test, laboratory coagulation screening and other advanced methods such as thromboelastogram and clot strength analysis. The primary management strategies are venom neutralisation with antivenom and correction of coagulopathy with blood component transfusions, while options such as plasma exchange are utilised in certain cases. Recent advancements in understanding the pathogenesis of haemotoxicity have facilitated the development of new diagnostic and treatment modalities. This review summarises current knowledge on the pathogenesis, diagnosis, clinical and laboratory manifestations and treatment of the haematological effects of snake envenoming. Furthermore, it highlights important challenges concerning diagnosis and management. Addressing these challenges is crucial for achieving the WHO's goal of reducing deaths and disabilities caused by snakebites by 2030.

Nearly 60 000 Indians die of snakebite envenoming each year. Most deaths occur in rural communities and remote tribal settlements. We describe snakebite-related epidemiology and health-seeking behaviours in a rural (Timiri) and remote tribal block (Jawadhu Hills) in Tamil Nadu, India.

This cross-sectional survey used structured questionnaires for information pertaining to snakebites and their treatment in the preceding year. Treatment-seeking behaviour from the moment reported until recovery was mapped. Traditional healers residing in the two blocks were also surveyed.

Snakebite incidence and mortality were 174/100 000 population and 2.7/100 000 population in Jawadhu Hills and 194/100 000 population and 2.6/100 000 population in Timiri, respectively. More snakebite victims applied tourniquets in Jawadhu Hills (90%) than in Timiri (69%). Traditional healers were the first contact for 64% in Jawadhu Hills. Ambulances and buses were reported as unavailable in Jawadhu Hills. Traditional healers in Jawadhu Hills did not refer snakebite victims to hospitals.

Three challenges to snakebite mitigation in Indian rural and tribal communities highlighted in this study are potentially harmful first aid, a disconnect between traditional healers and the public health system and a lack of emergency transport to health facilities. Addressing these challenges would necessitate community awareness, traditional healer engagement and improved means of public transportation.

Snakes are stimuli inducing an ancestral fear response in humans and other primates. Certain snakes evoke more subjective fear than others. True vipers are high-fear-eliciting snakes for both African and European respondents. This can be explained by the evolutionary experience of human ancestors in Africa. The question arises as to how snakes living in the Americas and Australia, with which humans have no evolutionary experience, will be evaluated. While these snakes belong to broader taxonomic groups that have distant relatives in the Old World, they have evolved independently for tens of millions of years. We prepared a set of 32 pictures depicting eight American pit vipers, eight Australian elapids, eight constrictors, and eight colubrids and asked the respondents to rank these stimuli according to the fear these snakes evoke. Here, we show a high cross-cultural agreement between evaluations by African and European respondents. Snakes characterized by a robust body shape, such as American pit vipers, Australian death adders, pythons, and boas, were the most fear-evoking. The body width was the strongest predictor of evoked fear. The contribution of coloration and pattern of the stimulus to the fear response was not proved. This supports the view that the patterns of fear are not dependent on direct experience, but its underlying mechanisms are shared cross-culturally.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity4. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5-7. Here we used deep learning methods to de novo design proteins to bind short-chain and long-chain α-neurotoxins and cytotoxins from the 3FTx family. With limited experimental screening, we obtained protein designs with remarkable thermal stability, high binding affinity and near-atomic-level agreement with the computational models. The designed proteins effectively neutralized all three 3FTx subfamilies in vitro and protected mice from a lethal neurotoxin challenge. Such potent, stable and readily manufacturable toxin-neutralizing proteins could provide the basis for safer, cost-effective and widely accessible next-generation antivenom therapeutics. Beyond snakebite, our results highlight how computational design could help democratize therapeutic discovery, particularly in resource-limited settings, by substantially reducing costs and resource requirements for the development of therapies for neglected tropical diseases.

India has a high incidence of snakebite-related mortality, making effective snakebite management crucial. This study aimed to explore current practices, challenges, and opportunities for improvement in snakebite management across India.

A cross-sectional survey was conducted among physicians in India covering aspects such as scope of practice, snake identification, first aid measures, institutional management, and specific management practices for hump-nosed pit viper (Hypnale hypnale) bites. The survey included 37 questions across 5 sections, with data collected via emails, professional networks, and online platforms. Statistical analysis was performed using SPSS Statistics 23 (IBM Corp, Armonk, NY), and manual thematic analysis was applied to open-ended responses.

The survey revealed a discrepancy between physicians' confidence and accuracy in snake identification, with some still reporting outdated first aid and treatment practices. Despite recognizing the importance of snake species identification, a significant portion of respondents incorrectly identified the snakes. The study highlighted variability in institutional practices for snakebite management, such as administering prophylactic antibiotics and tetanus prophylaxis and monitoring periods for asymptomatic patients. In managing H hypnale viper bites, a demand for specific guidelines and a monovalent antivenom was evident because the current polyvalent antivenom is ineffective for this species.

The survey emphasizes the need for improved training in snake identification, standardized treatment protocols, and the development of region-specific antivenoms. It emphasizes the necessity of updating guidelines to address the unique challenges of snakebite management in India, particularly for species not covered by existing antivenoms.

There is a lack of objective tools to assess the local changes following snakebite envenomation. We aimed to describe the progression of local changes in envenomed patients using serial infrared thermal imaging.

In a prospective sample of patients with snakebite envenomation, clinical assessment and infrared imaging of local changes were done at enrolment and 6 h and 24 h later, followed by once daily until hospital discharge or day 7, whichever was earlier. Infrared images were interpreted by an investigator masked to clinical findings.

We studied 39 patients with snakebite envenomation. Their mean age was 44.6±12.7 y and 25 (64%) were men. The median time to stability of local changes was 24.6 h (interquartile range [IQR] 17.0-30.1) on clinical examination and 28.0 h (IQR 13.7-55.2) on infrared imaging. At 24 h there was simple agreement between the two methods on whether the local changes were progressing or not in 31 of 39 patients (80%; Cohen's κ=0.59, p<0.001). The maximum proximal extent of local changes assessed using the two methods had a good correlation (Spearman's ρ=0.713, p<0.001). However, the extent of thermal changes on infrared images often exceeded the upper limit of swelling detected clinically.

Infrared imaging could be used to objectively document the local changes caused by snakebite envenomation.

Epidemiological modelling studies in snakebite envenoming research are evolving. Their techniques can be essential in filling the knowledge gap needed to attain the World Health Organization's (WHO) goal of halving the burden of snakebite envenoming by complementing the current data scarcity. Hence, there is a need for a systematic review to summarise epidemiological models used in estimating the burden of snakebite envenoming.

We conducted a systematic review by searching PubMed, EMBASE, and Scopus to identify articles reporting epidemiological models in snakebite envenoming from database inception to 31st December 2023. A narrative synthesis was performed to summarise types of models, methodologies, input parameters, model outputs, and associating factors.

Thirty-nine modelling studies were included from 2426 retrieved articles, comprising statistical models (76.9%) and mathematical models (23.1%). Most of the studies were conducted in South Asia, (35.9%) and Latin America (35.9%), and only a few (5.1%) were a global burden estimation. The eligible studies constructed 42 epidemiological models, of which 33 were statistical models that included regression, (60.6%) geostatistical (21.2%), and time series, (18.2%) while 9 mathematical models comprised compartmental, (44.4%) agent-based, (22.2%) transmission dynamics, (11.1%) network, (11.1%) and a simple mathematical model (11.1%). The outputs of the models varied across the study objectives. Statistical models analysed the relationship between incidence, (83.3%) mortality, (33.3%) morbidity (16.7%) and prevalence (10.0%) and their associating factors (environmental, [80%] socio-demographic [33.3%] and therapeutic [10.0%]). Mathematical models estimated incidence, (100%) mortality (33.3%), and morbidity (22.2%). Five mathematical modelling studies considered associating factors, including environmental (60%) and socio-demographic factors (40%).

Mathematical and statistical models are crucial for estimating the burden of snakebite envenoming, offering insights into risk prediction and resource allocation. Current challenges include low-quality data and methodological heterogeneity. Modelling studies are needed, and their continued improvement is vital for meeting WHO goals. Future research should emphasise standardised methodologies, high-quality community data, and stakeholder engagement to create accurate, applicable models for prevention and resource optimization in high-burden regions, including Africa and Asia.

Snakebite envenoming, classified as a neglected tropical disease, poses a significant threat to life in India, where it is estimated to cause 58 000 fatalities as well as 140 000 morbidities annually. To reduce the occurrence of snakebite, we need a comprehensive understanding of human-snake conflict ecology. Snake rescue networks represent a vital resource for gathering such ecological data.

In this study, we utilised snake rescue data from 520 rescue encounters carried out by a local rescue network in Hooghly, West Bengal, from July 2020 to October 2022, to investigate patterns of human-snake conflict and the influence of climatic factors on these patterns.

The spectacled cobra Naja naja was the most encountered of the five venomous species involved in 365 rescues. Our analysis revealed a significant correlation between rescue location and venomous/non-venomous encounters, with non-venomous encounters being more prevalent inside built-up locations. Rainfall on the previous day significantly increased encounters and influenced the species involved, while daily minimum temperature also influenced encounters with venomous species. We also found that both Bungarus (krait) species present were mostly encountered between 18:00 h and midnight.

This study highlights the multifaceted factors influencing human-snake conflicts in the region, including seasonality, geographic location, rainfall patterns, and temperature dynamics. It underscores the potential of snake rescue data as a valuable resource for deepening our understanding of regional variations in snake-human interactions.

Snakebite is a neglected tropical disease that causes significant morbidity and mortality in India. In this study, we describe the clinical characteristics and outcomes of Echis carinatus sochureki envenoming from Western Rajasthan. We document the clinical ineffectiveness of the currently available Indian polyvalent antivenom in managing E. c. sochureki envenoming.

In this ambispective study, conducted from 14 April 2019 to 15 April 2024, we enrolled all patients presenting to our emergency department at a tertiary care centre in Jodhpur, Rajasthan, with a history of snakebite. After they provided informed consent, the demographic details, bite geo-location, bite-to-antivenom time, antivenom dose, coagulation profile, mortality and duration of hospital stay of those patients with E. c. sochureki envenoming were recorded.

Of 210 patients screened, 105 had E. c. sochureki envenoming, 103 venom-induced consumption coagulopathy, 36 (34.3%) local bleeding and 55 (52.3%) systemic bleeding. The median bite-to-antivenom time was 2 (IQR: 1.13-4.0) h. The median antivenom dose was 22 (IQR: 10-30) vials. Of 92 patients who received antivenom, 63 (68.4%) were unresponsive. Total antivenom dose and geographical location (West zone) were significant predictors of antivenom unresponsiveness. Fifty-three of 70 patients (75.7%) had delayed hypofibrinogenaemia. The mean hospital stay was 8.3±7.1 d with nine (8.6%) mortalities.

Our study highlights the alarming finding of poor antivenom response to E. c. sochureki envenoming, with significant clinical bleeding and delayed coagulopathy. There is an urgent need for region-specific antivenom in Western India.

Snakebite envenomation continues to affect lives globally, with >1.2 million envenomations and approximately 120 000 annual mortalities. Unfortunately, low- and middle-income countries (LMICs) contribute to >80% of these global statistics. With different targets set to minimize the impact of snakebite envenoming, such as halving the envenoming cases by 2030 from the World Health Organization (WHO), multiple initiatives are inevitable. Gender intersectionality and tropical disease research for infectious diseases of poverty, developed by the WHO, has championed the exploration of neglected diseases, stratifying them using gendered domains. However, minimal research using the gender intersectionality framework has been conducted to explore snakebite envenoming, especially among LMICs. Exploring snakebite envenomation through a gendered lens is critical in developing gender-specific interventions for the prevention and treatment of envenomation. This narrative review explores the available literature about snakebite envenomation in LMICs through a gender intersectionality lens. It provides insights into the existing gaps, especially regarding research using intersectionality frameworks and the gendered matrix. It further proposes avenues of research using these domains to understand snakebite envenomation, especially through the intersectionality lens.

A considerable number of patients present to hospitals in Eswatini each year following bites by venomous snakes. Effectively diagnosing and treating patients with snakebite envenoming requires healthcare workers to have a variety of generic and snakebite-specific medical skills. In several countries, however, healthcare workers have been found to have limited skills in managing snakebite patients. We used the Delphi method to adapt the Hennessy-Hicks training needs analysis questionnaire to the context of snakebite envenoming and subsequently used the adapted questionnaire to assess the self-perceived training needs of 90 healthcare workers from ten hospitals in Eswatini. Two-thirds (63%) of participants were nursing staff and one third (34%) medical doctors. Overall, 74% of healthcare workers had previously received training on snakebite. Although a training need was reported for all skills included in the survey, the extent of the training need varied between different skills and groups of healthcare workers. The highest average training need was registered in the domains 'research and audit' and 'clinical tasks' with the latter accounting for nine of the ten skills with the highest training need. Nurses reported a higher training need than doctors, especially for clinical tasks. Receiving snakebite training before as well as after obtaining the primary qualification was associated with the lowest average training need, particularly in clinical skills. Ninety-three percent of interviewed healthcare workers would welcome more frequent training opportunities on the clinical management of snakebite patients. This newly developed snakebite training needs analysis tool can aid in adapting training initiatives to a dynamic and evolving healthcare workforce and it is designed to be transferrable to snakebite endemic settings worldwide.

Envenomation by aquatic species is an under-investigated source of human morbidity and mortality. Increasing population density along marine and freshwater coastlines increases these incidents. Specific occupational groups - including commercial fishery workers, fisherfolk, marine tourism workers, and researchers - rely on aquatic resources for their livelihood. While diverse venomous aquatic species exhibit a broad array of habitats worldwide, they are most abundant in the tropics. Specific tropical regions present historic "hot spot" areas of concern for occupational groups with heightened risk of aquatic envenomation. Towards the overall objective of characterizing the health burden of aquatic envenomations, this review seeks to define (1) vulnerable, high-risk populations and (2) geographic hot-spot regions. To formally assess these metrics, a systematic literature review was performed where inclusion criteria requirements were peer-reviewed, published, epidemiological studies with defined denominators from January 1, 2000, to July 31, 2024, on the topic of human envenomation by aquatic species. Fifty-three articles met the inclusion criteria. Excluded articles were comprised of case reports, news and magazine articles, and those in languages aside from English, French, Portuguese, and Spanish. Most of the included articles examined emergency department and poison-control datasets that reported few overall envenomations (< 1%) from populations with physical and financial access to medical care. In contrast, datasets surveying beachgoers or fisherfolk directly, and life-guard incident reports, demonstrated that aquatic envenomation is an important source of injury for these groups and settings (envenomation frequency mean: 71%, median: 80%). Reports on additional high-risk groups, including marine and aquatic biologists, military personnel etc., and in key high-risk geographic regions including Thailand, Indonesia, and other Indo-Pacific countries were missing from the reviewed literature. Socio-demographic data were also largely missing from the literature. This systematic review highlights critical gaps where further research is needed, especially in under-represented regions and vulnerable populations.

Envenomings from Russell's viper typically result in local tissue damage and bleeding complications, but the bites from common krait and cobra primarily cause neurotoxic effects. While most symptoms can be treated with appropriate antivenom, additional support is necessary for several snakebite victims to tackle a broad range of unusual complications that they develop following bites. Reversible vasoconstriction syndrome (RCVS), characterised by the constriction of cerebral arteries, is a rare but serious issue, presenting with severe headaches and, in extreme cases, haemorrhagic/ischaemic stroke. This report presents three cases of RCVS in snakebite victims following Russell's viper, krait and cobra bites. The patients were admitted to the hospital with neurological and/or haematological complications, and they were treated with polyvalent antivenom. After two days of antivenom treatment, all the patients developed intense headaches that lasted for several hours and failed to respond to commonly used analgesics. While the physical, laboratory and computed tomography examinations were normal, the RCVS was diagnosed with multimodal magnetic resonance angiography. All patients were successfully treated with oral nimodipine, and during their follow-ups, physical and laboratory examinations were unremarkable, and the magnetic resonance imaging confirmed the reversal of RCVS. To achieve positive outcomes in patients, clinicians must swiftly identify such rare complications and make accurate diagnoses to provide prompt treatments. Overall, this report presents an unusual complication of RCVS in snakebite patients and appropriate diagnosis and treatment approaches to tackle this condition.

Snakebite envenoming results in the death of thousands of people each year and has been classified as a neglected tropical disease by the World Health Organization (WHO). The toxins released into the bloodstream of the victim bind to the nicotinic acetylcholine receptor and restrict transmission of nerve impulses leading to paralysis and cardiac arrest. Conventional antibody-based treatments often have adverse side effects or are difficult to perform. Hence, efforts are underway to devise alternative forms of treatment that address these therapeutic shortcomings. Peptide-based inhibitors have recently gained attention due to their high specificity and ease of preparation. Here, we explore the mechanism of a peptide inhibitor of α-cobratoxin using all-atom molecular dynamics (MD) simulations. We also quantify the energetics of the toxin-peptide dissociation process using the non-equilibrium steered MD technique. Our study reveals that the inhibitor migrates close to Loop-II of α-cobratoxin and alters its dimerization tendency. From energy studies, we found that the peptide first binds to one unit of α-cobratoxin in a particular orientation, followed by the binding of a second toxin molecule, which effectively masks the residues that interact with the nicotinic acetylcholine receptor. Our work provides atomic-level insight into the inhibition process that can be utilized in the future design of inhibitors with superior binding capabilities.

The ability to detect threats quickly is crucial for survival. Primates, including humans, have been shown to identify snakes quickly and accurately due to their evolutionary history. However, it is unclear which visual features humans and primates detect as threat targets. Several studies have suggested that snake scales possess potent visual features. My previous study demonstrated that removing snake scales through digital image processing reduces attention directed toward snakes. Here, I conducted a visual search task using luminance- and contrast-adjusted photographs of snakes and salamanders in monkeys that had never seen these real reptiles and amphibians. This study demonstrates that the presence or absence of snake scales is responsible for the rapid detection of target animals. The monkeys quickly detected one snake photograph from the eight salamander photographs than vice versa. However, when the same salamanders were clothed with snake scales using image processing, the difference in detection speed between snakes and salamanders disappeared. These results are consistent with the snake-detection theory that snakes were a strong selective pressure favoring modifications in the primate visual system that allow them to detect snakes more quickly or reliably. This strongly suggests that primates' snake detection depends on the snake-scale shapes, which are both snake-specific and common to all snakes.

Non-front-fanged snakes (NFFS) have long been overlooked by snake venom research, likely due to most of them being considered non-medically relevant for humans. The paucity of information about composition and activities of NFFS venoms and oral secretions makes it difficult to assess whether a given species can inflict medically significant bites. Here, we provide a review of the information currently available about the symptoms/signs elicited by bites from European NFFS, aiming to offer a foundation for understanding the threat they pose in terms of snakebite. Despite an overall limited amount of available data for most of the considered taxa, the genus Malpolon is notable for its capacity to cause local and systemic envenoming, including neurotoxic symptoms. Bites by other genera like, Hemorrhois, Hierophis, Natrix, Platyceps, Telescopus, and Zamenis are mainly associated with local symptoms, but the extent of their medical significance remains unclear. Our findings suggest that, although bites from European NFFS generally cause only mild effects, the potential occurrence of systemic effects from some species cannot be ruled out. Considering the above, any bite by European NFFS should receive professional medical evaluation in order to ensure patient safety and appropriate management, as well as detailed documentation facilitating construction of an accurate medical risk profile for the species.

Envenomation after a North American rattlesnake (Crotalus spp. and Sistrusus spp.) bite is associated with substantial morbidity. Arizona reports the highest number of rattlesnake envenomations annually in the United States. We evaluated the performance of poison and drug information centers for snakebite surveillance, compared with the hospital and emergency department discharge database. We used both datasets to improve the characterization of epidemiology, healthcare costs, and clinical effects of snakebite envenomations in Arizona.

We identified patients with a snakebite during 2017-2021 using Arizona hospital and emergency department discharge data and snakebite consults with two regional Arizona poison centers. Patients were matched using name and birthdate. The performance of poison center data for snakebite surveillance was evaluated using the percentage of snakebite patients in hospital and emergency department discharge data that consulted with poison centers. Patient demographics, healthcare characteristics, clinical effects, and context of snakebite events were described using both datasets.

In total, 1,288 patients with a snakebite were identified using the Arizona hospital and emergency department discharge data, which resulted in 953 (74%) consultations with poison centers. The median age of patients was 48 years (IQR 28-62 years), and they were predominantly male (66%), White (90%), and non-Hispanic (84%). The median billed charges were US$ 84,880 (IQR US$ 13,286-US$ 168,043); the median duration of a healthcare stay was 34 h (IQR 13-48 h), and 29% of patients were transferred between healthcare facilities. Among 953 consulted poison center calls for a snakebite, a median of 14 vials of antivenom was administered per patient; 375 (60%) bites occurred near the home, and 345 (43%) patients were bitten on a lower extremity. One death was identified.

Snakebites in Arizona can cause severe morbidity and require extensive healthcare resources for treatment. Poison centers are valuable for monitoring venomous snakebites in Arizona.

Using hospital and emergency department discharge data with poison center records can improve public health surveillance data regarding snakebite epidemiology and human-snake interaction information and be used to tailor interventions to increase awareness of snake encounters and prevent snakebites.

Background & objectives Snakebite envenoming (SBE) is a major public health concern, with India bearing the highest global burden of SBE-related deaths. SBE is concentrated in rural and tribal regions of India, where the knowledge, attitude and behaviour of the dwelling communities largely influence mortality and morbidity. Understanding these factors is crucial to designing effective SBE prevention and management strategies. The present study's objective was to document the perspectives of community members and practices in selected blocks of Maharashtra and Odisha States regarding SBE prevention, first aid and health-seeking behaviour. Methods Between March and April 2022, 28 focus group discussions (FGDs) were conducted. Study sites included Shahapur block in Thane district, Aheri block in Gadchiroli district of Maharashtra, and Khordha block in Khordha district, Kasipur block in Rayagada district of Odisha. Separate FGDs were held for males (n=14) and females (n=14), involving about 8-16 participants above 18 yr. All discussions were audio recorded, and a grounded theory approach was employed to identify key themes from the translated transcripts. Results The findings of this study revealed a variety of perspectives and practices determining the SBE burden at the study sites. The findings included insufficient knowledge about snake species and their nature of toxicity, use of non-scientific first aid techniques, inaccessible health care and reliance on traditional healers, non-utilization of prevention methods, varied cultural beliefs and practices, and differential treatments based on gender. The findings have been collated in two simplistic frameworks; barriers to effective prevention and barriers to effective management. Interpretation & conclusions SBE burden results from a complex interplay between socioeconomic, cultural, and demographic factors, necessitating a collaborative inter-sectoral effort for adequate control. Through crucial regional inputs and the barriers to prevention and management models, this study provides critical insights and priority intervention areas to strengthen India's upcoming National Action Plan for Prevention and Control of Snakebite Envenoming (NAPSE) in all high-burden States.

Snakebite primarily impacts rural communities of Africa, Asia, and Latin America. The sharp-nosed viper (Deinagkistrodon acutus) is among the snakes of highest medical importance in Asia. Despite various studies on its venom using modern venomics techniques, a comprehensive understanding of composition and function of this species' venom remains lacking. We combined proteogenomics with extensive bioactivity profiling to present the first genome-level catalogue of D. acutus venom proteins and their exochemistry. Our analysis identified an unusually simple venom containing 45 components from 20 distinct protein families. Relative toxin abundances indicate that C-type lectin and C-type lectin-related protein (CTL), snake venom metalloproteinase (svMP), snake venom serine protease (svSP), and phospholipase A2 (PLA2) constitute 90 % of the venom. Bioassays targeting key aspects of viperid envenomation showed considerable concentration-dependent cytotoxicity, particularly in kidney and lung cells, and potent protease and PLA2 activity. Factor Xa and thrombin activities were minor, and no plasmin activity was observed. Effects on haemolysis, intracellular calcium (Ca2+) release, and nitric oxide (NO) synthesis were negligible. Our analysis provides the first holistic genome-based overview of the toxin arsenal of D. acutus, predicting the molecular and functional basis of its life-threatening effects, and opens novel avenues for treating envenomation by this highly dangerous snake.

The 2019 WHO strategy to reduce snakebite burden emphasises the need for fostering research on snakebite treatments. A core outcome set (COS) is a consensus minimal list of outcomes that should be measured in research on a particular condition. We aimed to develop a COS for snakebite research in South Asia, the region with the highest burden.

We used data from a systematic review of outcomes to develop a long list of outcomes which were rated in two rounds of online Delphi survey with healthcare providers, patients and the public, and potential COS users to develop a COS for intervention research on snakebite treatments in South Asia for five intervention groups. Subsequently, meetings, consultations and workshops were organised to reach further consensus. We defined the consensus criteria a priori.

Overall, 72 and 61 people, including patients and the public, participated in round I and round II of the Delphi, respectively. Consensus COSs (including definition and time points) were developed for interventions that prevent adverse reaction to snake antivenom (three outcomes), specifically manage neurotoxic manifestations (five outcomes), specifically manage haematological manifestations (five outcomes) and those that act against snake venom (seven) outcomes. A priori criteria for inclusion in COS were not met for COS on interventions for management of the bitten part.

The COS contributes to improving research efficiency by standardising outcome measurement in South Asia. It also provides methodological insights for future development of COS, beyond snakebite.

Snakebite is a major global health concern, for which antivenom remains the only approved treatment to neutralise the harmful effects of the toxins. However, some medically important toxins are poorly immunogenic, resulting in reduced efficacy of the final product. Boosting the immunogenicity of these toxins in the commercial antivenom immunising mixtures could be an effective strategy to improve the final dose efficacy, and displaying snake antigens on Virus-like particles (VLPs) is one method for this. However, despite some applications in the field of snakebite, VLPs have yet to be explored in methods that could be practical at an antivenom manufacturing scale. Here we describe the utilisation of a "plug and play" VLP system to display immunogenic linear peptide epitopes from three finger toxins (3FTxs) and generate anti-toxin antibodies. Rabbits were immunised with VLPs displaying individual consensus linear epitopes and their antibody responses were characterised by immunoassay. Of the three experimental consensus sequences, two produced antibodies capable of recognising the consensus peptides, whilst only one of these could also recognise native whole toxins. Further characterisation of antibodies raised against this peptide demonstrated a sub-class specific response, and that these were able to elicit partially neutralising antibody responses, resulting in increased survival times in a murine snakebite envenoming model.

Snake venom variations are a crucial factor to understand the consequences of snakebite envenoming worldwide, and therefore it is important to know about toxin composition alterations between taxa. Palearctic vipers of the genera Vipera, Montivipera, Macrovipera, and Daboia have high medical impacts across the Old World. One hotspot for their occurrence and diversity is Türkiye, located on the border between continents, but many of their venoms remain still understudied. Here, we present the venom compositions of seven Turkish viper taxa. By complementary mass spectrometry-based bottom-up and top-down workflows, the venom profiles were investigated on proteomics and peptidomics level. This study includes the first venom descriptions of Vipera berus barani, Vipera darevskii, Montivipera bulgardaghica albizona, and Montivipera xanthina, as well as the first snake venomics profiles of Turkish Macrovipera lebetinus obtusa, and Daboia palaestinae, including an in-depth reanalysis of M. bulgardaghica bulgardaghica venom. Additionally, we identified the modular consensus sequence pEXW(PZ)1-2P(EI)/(KV)PPLE for bradykinin-potentiating peptides in viper venoms. For better insights into variations and potential impacts of medical significance, the venoms were compared against other Palearctic viper proteomes, including the first genus-wide Montivipera venom comparison. This will help the risk assessment of snakebite envenoming by these vipers and aid in predicting the venoms' pathophysiology and clinical treatments.

Snake bites cause considerable morbidity and mortality worldwide, yet evidence from low- and middle-income countries remains fragmented. This is particularly the case in Eastern Mediterranean Region where available data on snake bites is relatively weak. Without reliable data, it is difficult to make the case for greater visibility and investment to address the snakebite burden in this Region. A scoping review was therefore conducted to summarize evidence on snake bites in countries of the Eastern Mediterranean.

The review employed manual and electronic searching methods of four databases plus Google Scholar, ultimately including 196 records from 20 countries published between 2000 and 2023. More than half originated from Iran, Morocco, and Pakistan. Many records lacked information on permanent sequalae, disability, snake species, and types and sources of antivenoms. When identified, offending snakes belonged to 30 species. Use of more than 12 types of antivenoms were described across the Region, and some were not specific to indigenous species.

Despite the relatively large number of publications identified, the data were concentrated in just a few countries in the Region, and there was little or no information available for the remainder. As is the case worldwide, disability associated with snake bites was poorly characterized and quantified across the Region. There is an urgent need for concrete action at national and regional levels to enhance epidemiological surveillance, research, and the collection of clinical, disability and outcomes data to inform policy and public health investment. Greater regional cooperation and collaboration is also crucial for addressing this neglected disease throughout the Region.

To analyze the vulnerability factors of snakebite patients in China.

Multi-stage random sampling was used as the main sampling method and snowball sampling as the auxiliary sampling method. The knowledge, attitude and behavior of snakebite among Chinese residents were investigated. Non-parametric test was used to compare the percentage differences in residents' knowledge, attitude and behavior of snakebite, and generalized linear regression analysis was used to analyze the influencing factors, and the vulnerability factors of snakebite patients were comprehensively analyzed.

A total of 6338 subjects were included in this study, of which 68.4% were males, and 58.6% were farmers, workers and service personnel. The median total score of knowledge, attitude, and behavior was 26 (22,36). The patients who were improperly treated after injury were ligation proximal to the affected area (23.43%), squeezing (21.82%), and oral and suction wounds (8.74%). Did not go to hospital due to poverty (1351 cases) and did not receive antivenom (2068 cases). There were 21.32% and 32.63%, respectively. Among 4270 patients injected with antivenom 30.7% were vaccinated within 2 h. Among the patients who went to the hospital for treatment (4987), 75.0% arrived at the hospital within 6 h; Among the 4,761 patients who made emergency calls, 37.4% were treated within 0.5 h.

Snakebite patients in China have weak knowledge about snakebite, low awareness of medical treatment, lack of correct prevention and emergency treatment measures, dependence on folk remedies, poor housing and so on. In addition, there are low availability of antivenoms and unreasonable distribution of medical resources in some areas of China. Multisectoral and multidisciplinary cooperation should be developed to prevent and control snakebites in order to reduce the burden caused by snakebites.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors (nAChRs) resulting in life-threatening neurotoxicity4. Currently, the only available treatments for snakebite consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5,6,7. Here, we use deep learning methods to de novo design proteins to bind short- and long-chain α-neurotoxins and cytotoxins from the 3FTx family. With limited experimental screening, we obtain protein designs with remarkable thermal stability, high binding affinity, and near-atomic level agreement with the computational models. The designed proteins effectively neutralize all three 3FTx sub-families in vitro and protect mice from a lethal neurotoxin challenge. Such potent, stable, and readily manufacturable toxin-neutralizing proteins could provide the basis for safer, cost-effective, and widely accessible next-generation antivenom therapeutics. Beyond snakebite, our computational design methodology should help democratize therapeutic discovery, particularly in resource-limited settings, by substantially reducing costs and resource requirements for development of therapies to neglected tropical diseases.

Members of the genus Protobothrops are amongst the more than twenty-eight range-restricted Indian pit viper species. Their bites and envenomings are rarely documented from India. Pit viper envenomings can be challenging to treat in the Indian setting, since available antivenoms do not satisfactorily neutralize their venoms. Herein, we present the first Indian reports on bites and envenoming by Protobothrops jerdonii and Protobothrops himalayanus resulting in local effects, coagulopathy and acute kidney injury in the case of the former and possible mild, isolated coagulopathy in the case of the latter; and discuss management-related challenges in the context of absent specific antivenoms.

Globally, snakebites cause an estimated 80 000-140 000 deaths annually. While there are evidence-based recommendations for managing snakebite victims, recommendations on the prevention of snakebites are limited to expert opinions. We conducted a rapid review to summarise evidence from human studies with a control group on preventing snakebites. Searching PubMed, Web of Science, Scopus, CINAHL and EMBASE with inclusive search terms without language or time limits only yielded three eligible studies (one case control study and two prospective controlled clinical studies), highlighting a knowledge gap. Two studies in Nepal by the same group showed that health education of stakeholders and sleeping under a bednet can significantly reduce snakebite incidence (p<0.05), but these observations are not confirmed elsewhere, and because of the high risk of bias the certainty of evidence was low. The third study from Sri Lanka, which assessed if sleeping above ground would prevent snakebites, had inconclusive results. This demonstrates an urgent need for studies with a control group to guide evidence-based recommendations for snakebite prevention. Potential interventions tested can range from low-cost measures such as wearing appropriate footwear in resource-limited settings to testing the efficacy of chemical, biological (e.g. rodent control) or device-based methods and community-supported platforms tracking snakebite sightings with real-time geolocation data in highly resourced settings.

Despite the widespread use of antivenom for the treatment of snakebite envenoming in the Indian subcontinent, the ideal dose of antivenom has been a point of contention. Low-dose regimens can economize on a scarce resource in low- and middle-income countries. This study assessed the effectiveness of a low-dose (10 vials) antivenom regimen compared to the usual 20 vials in patients with krait bite neuroparalysis requiring mechanical ventilation.

This study was a prospective controlled pilot study conducted in a tertiary-care hospital in north India. Participants were eligible if they were ≥12 years old, had krait bite neurotoxicity, showed severe paralysis requiring mechanical ventilation, and had access to antivenom therapy within 24 h of the bite. The primary outcome was the duration of mechanical ventilation, and the secondary outcomes were the length of hospital stay and in-hospital survival.

Fifteen patients received 10 vials of antivenom, and 25 received 20 vials. The two treatment groups had similar baseline demographics, clinical and laboratory features, snakebite severity scores, and median time from snakebite to initiation of antivenom therapy. The low-dose regimen was as effective as the standard dose concerning the median duration of mechanical ventilation (41 h vs. 55 h, P = 0.094), the median length of stay (78 h vs. 85.5 h, P = 0.360), and in-hospital deaths (1 vs. 3, P = 1.000). The incidence of ventilator-associated pneumonia was similar between the two groups (1 vs 3, P = 1.000).

A low dose of antivenom effectively treats patients with severe krait bite neuroparalysis.