Subject(s)
Antivenins , Snake Bites , Snake Bites/drug therapy , Humans , Antivenins/therapeutic use , AnimalsABSTRACT
Background: Snakebite is a global environmental and occupational hazard and a significant public health threat. In rural areas, snakebite cases often go unreported and undocumented due to the lack of access to well-structured healthcare facilities/infrastructure. In some cases, the need for antisnake venom (ASV) far outstrips supply, negatively affecting treatment outcomes. This study, therefore, assessed the epidemiological characteristics of snakebite cases, their management, and how antivenoms are utilised at the selected hospital in the Jasikan District Hospital. Methods: A 6-year retrospective study using secondary data from antivenom return forms (pharmacy records), clinical records (patient folders), the District Health Information Management System-2 (DHIMS-2) database, and consulting room registers was carried out in selected hospitals in the Jasikan District, Oti, Ghana. Results: The predominant symptom of snakebite was localised pain (71.4%). The snakebite commonly occurred at home (19%) and on farms (18%). Of the 98 snakebite cases, ASV was administered to 73 (74.5%) cases. Supportive treatment applied included prophylactic antitetanus immunoglobulin (ATS) (80.6%), prophylactic antibiotics (63%), corticosteroids (80.6%), and analgesics (63%). 95% (n = 94) of complete recoveries were recorded; three were discharged against medical advice, and one was mortality. The supply and use of antivenom were erratic throughout the months of high incidence, partly due to inconsistent availability at the Regional Medical Stores. The average ASV vials and hospital stay duration were 1.23 ± 0.86 vials and 2.67 ± 1.97 days, respectively. Although the peak of snakebites occurs in April, May, and June, the demand for antivenom in April and May exceeded supply. Conclusion: The outcome of most snakebite case management was appropriate, irrespective of inadequate ASV supply in certain months. The erratic antivenom supply should be aligned with seasonal and facility-use patterns to enhance regional snakebite management.
Subject(s)
Antivenins , Snake Bites , Snake Bites/epidemiology , Snake Bites/drug therapy , Humans , Ghana/epidemiology , Antivenins/therapeutic use , Male , Retrospective Studies , Female , Adult , Middle Aged , Adolescent , Young Adult , Child , Aged , Child, Preschool , Snake VenomsABSTRACT
Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to spitting cobra venoms. A large portion of modifying genes that conferred resistance to venom cytotoxicity was found to control proteoglycan biosynthesis, including EXT1, B4GALT7, EXT2, EXTL3, XYLT2, NDST1, and SLC35B2, which we validated independently. This finding suggested heparinoids as possible inhibitors. Heparinoids prevented venom cytotoxicity through binding to three-finger cytotoxins, and the US Food and Drug Administration-approved heparinoid tinzaparin was found to reduce tissue damage in mice when given via a medically relevant route and dose. Overall, our systematic molecular dissection of cobra venom cytotoxicity provides insight into how we can better treat cobra snakebite envenoming.
Subject(s)
Elapid Venoms , Snake Bites , Animals , Humans , Snake Bites/drug therapy , Mice , Antidotes/pharmacologyABSTRACT
Snakebite envenoming is a high-priority neglected tropical disease and antivenom is the cornerstone of treatment. Antivenom is listed among essential medicines and its access must be considered as a human right. Despite resolutions from various international organizations including the WHO, antivenom remains unavailable, unaffordable, and sometimes not targeted against the specific snake involved. Also, despite an expanding global antivenom market, some manufacturers have stopped production due to a lack of profits. However, justice and equitable access to care according to medical needs are among the four pillars of medical ethics. Overall, snakebite envenoming is a typical example of social and ethnic inequity in medicine. It is imperative that this issue be addressed from an ethical standpoint and that government laboratories take the lead in antivenom production.
Subject(s)
Antivenins , Health Services Accessibility , Snake Bites , Snake Bites/therapy , Snake Bites/drug therapy , Antivenins/therapeutic use , Humans , AnimalsABSTRACT
Snakebite envenomation remains an important, yet a neglected public health issue in most tropical and subtropical countries. Underdeveloped medical infrastructure, suboptimal medical services, poor documentation and failure to make snake-related injury a mandatory notifiable disease are important contributing factors. The King Cobra (Ophiophagus hannah) is a medically significant species encountered in Malaysia however, there have been few publications from the clinical perspective. The objectives of this study were to determine the frequency of King Cobra related injuries, geographical distribution, clinical presentation, type and frequency of antivenom utilization and the management outcome. This is a cross-sectional study of confirmed King Cobra related injuries consulted to Remote Envenomation Consultation Services (RECS) from 2015 to 2020. Data were extracted from the RECS database and descriptively analyzed. A total of 32 cases of King Cobra bite were identified. Most cases were from Peninsular Malaysia with the most frequent from the state of Pahang (n = 9, 28.1%). Most patients got bitten while attempting to catch or play with the snake (68.8%). Signs and symptoms of envenomation were documented in 24 (75.0%) cases and the most frequent systemic manifestation was ptosis (n = 13, 40.6%). Tracheal intubation and ventilatory support were required in 13 (40.6%) patients. Antivenom was administered to 22 (68.8%) patients with most (25.0%) receiving 10 vials (1 dose). The commonest antivenom used was monospecific King Cobra antivenom (50.0%) from Thai Red Cross. There was one death documented due to complications from necrotizing fasciitis and septicemia. Public awareness of the dangers and proper handling of King Cobras needs to be emphasised. Timely administration of the appropriate antivenom is the definitive treatment and leads to favorable outcomes.
Subject(s)
Antivenins , Ophiophagus hannah , Snake Bites , Humans , Snake Bites/drug therapy , Snake Bites/therapy , Snake Bites/epidemiology , Antivenins/therapeutic use , Antivenins/administration & dosage , Animals , Malaysia/epidemiology , Male , Female , Cross-Sectional Studies , Adult , Middle Aged , Young Adult , Adolescent , Child , Aged , Treatment Outcome , Elapid Venoms , Child, PreschoolABSTRACT
Introduction: Local tissue destruction following envenomation from North American snakes, particularly those within the Crotalinae subfamily, has the potential to progress to compartment syndrome. The pathophysiology of venom-induced compartment syndrome (VICS) is a debated topic and is distinct from trauma/reperfusion-induced compartment syndrome. Heterogeneity exists in the treatment practices of VICS, particularly regarding the decision to progress to fasciotomy. Associations with functional outcomes and evolution in clinical practice since the introduction of Crotalidae polyvalent immune Fab (FabAV) have not been well defined. Our goal was to identify the potential gaps in the literature regarding this phenomenon, as well as illuminate salient themes in the clinical characteristics and treatment practices of VICS. Methods: We conducted this systematic scoping-style review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Records were included if they contained data surrounding the envenomation and hospital course of one or more patients who were envenomated by a snake species native to North America and were diagnosed with compartment syndrome from 1980-2020. Results: We included 19 papers: 10 single- or two-patient case reports encompassing 12 patients, and nine chart reviews providing summary statistics of the included patients. In case reports, the median compartment pressure when reported was 60 millimeters of mercury (interquartile range 55-68), 66% underwent fasciotomy, and functional outcomes varied. Use of antivenom appeared to be more liberal with FabAV than the earlier antivenin Crotalidae polyvalent. Rapid progression of swelling was the most commonly reported symptom. Among the included retrospective chart reviews, important data such as compartment pressures, consistent laboratory values, and snake species was inconsistently reported. Conclusions: Venom-induced compartment syndrome is relatively rare. Existing papers generally describe good outcomes even in the absence of surgical management. Significant gaps in the literature regarding antivenom dosing practices, serial compartment pressure measurements, and functional outcomes highlight the need for prospective studies and consistent standardized reporting.
Subject(s)
Antivenins , Compartment Syndromes , Snake Bites , Animals , Humans , Antivenins/therapeutic use , Compartment Syndromes/drug therapy , Compartment Syndromes/etiology , Compartment Syndromes/surgery , Fasciotomy , Immunoglobulin Fab Fragments/therapeutic use , Snake Bites/complications , Snake Bites/drug therapy , United States/epidemiologyABSTRACT
Access to antivenoms in cases of snakebite continues to be an important public health issue around the world, especially in rural areas with poorly developed health care systems. This study aims to evaluate therapeutic itineraries and antivenom accessibility following snakebites in the states of Oaxaca and Chiapas in southern Mexico. Employing an intercultural health approach that seeks to understand and bridge allopathic and traditional medical perceptions and practices, we conducted field interviews with 47 snakebite victims, documenting the therapeutic itineraries of 54 separate snakebite incidents that occurred between 1977 and 2023. Most victims used traditional remedies as a first line of treatment, often to withstand the rigors of a long journey to find antivenoms. The main obstacles to antivenom access were distance, poor antivenom availability, and cost. Standard antivenom treatment is highly valued and sought after, even as traditional beliefs and practices persist within a cultural framework known as the "hot-cold" system. The findings are crucial for informing future enhancements to antivenom distribution systems, health education initiatives, and other interventions aimed at mitigating the impact of snakebites in the region.
Subject(s)
Antivenins , Health Services Accessibility , Snake Bites , Snake Bites/therapy , Snake Bites/drug therapy , Snake Bites/epidemiology , Humans , Mexico/epidemiology , Antivenins/therapeutic use , Male , Female , Adult , Middle Aged , Adolescent , Young Adult , AgedABSTRACT
BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.
Subject(s)
Antivenins , Snake Bites , Snakes , Snake Bites/epidemiology , Snake Bites/drug therapy , Antivenins/therapeutic use , Humans , Animals , Antidotes/therapeutic use , Mediterranean Region/epidemiology , Iran/epidemiology , Pakistan/epidemiologyABSTRACT
This retrospective, observational study describes the clinical findings, case management trends, and outcomes of 83 dogs and nine cats exposed to eastern coral snakes in a university teaching hospital setting. The medical records of dogs and cats that received antivenom following coral snake exposure were reviewed. Data collected included signalment, time to antivenom administration, physical and laboratory characteristics at presentation, clinical course during hospitalization, length of hospitalization, and survival to discharge. The mean time from presentation to coral snake antivenom administration was 2.26 ± 1.46 h. Excluding cases where the owner declined in-hospital care, the mean hospitalization time for dogs and cats was 50.8 h and 34 h, respectively. The mean number of antivenom vials was 1.29 (1-4). Gastrointestinal signs (vomiting and ptyalism) occurred in 42.2% (35/83) of dogs and 33.3% (3/9) of cats. Peripheral neurologic system deficits (ataxia, paresis to plegia, absent reflexes, and hypoventilation) were noted in 19.6% (18/92) of dogs and cats. Hemolysis was also common in 37.9% (25/66) of dogs but was not observed in cats. Mechanical ventilation (MV) was indicated in 12% (10/83) of dogs but no cats. Acute kidney injury (AKI), while rare, was a common cause of euthanasia at 20% (2/5) and was the most common complication during MV at 44.4% (4/9). Pigmenturia/hemolysis occurred in 88.9% (8/9) of MV cases and in all cases with AKI. Despite delays in antivenom administration by several hours, dogs and cats with coral snake exposure have low mortality rates (6% of dogs (5/83) and 0% of cats). Gastrointestinal signs were common but were not predictive of progression to neurological signs. Thus, differentiating between coral snake exposure and envenomation before the onset of neurological signs remains challenging.
Subject(s)
Antivenins , Cat Diseases , Coral Snakes , Dog Diseases , Elapid Venoms , Snake Bites , Animals , Dogs , Antivenins/therapeutic use , Retrospective Studies , Cats , Snake Bites/veterinary , Snake Bites/therapy , Snake Bites/drug therapy , Cat Diseases/therapy , Elapid Venoms/toxicity , Male , Female , Treatment Outcome , Venomous SnakesABSTRACT
The genus Vipera encompasses most species of medically significant venomous snakes of Europe, with Italy harbouring four of them. Envenomation by European vipers can result in severe consequences, but underreporting and the absence of standardised clinical protocols hinder effective snakebite management. This study provides an updated, detailed set of guidelines for the management and treatment of Vipera snakebite tailored for Italian clinicians. It includes taxonomic keys for snake identification, insights into viper venom composition, and recommendations for clinical management. Emphasis is placed on quick and reliable identification of medically relevant snake species, along with appropriate first aid measures. Criteria for antivenom administration are outlined, as well as indications on managing potential side effects. While the protocol is specific to Italy, its methodology can potentially be adapted for other European countries, depending on local resources. The promotion of comprehensive data collection and collaboration among Poison Control Centres is advocated to optimise envenomation management protocols and improve the reporting of epidemiological data concerning snakebite at the country level.
Subject(s)
Antivenins , Snake Bites , Viper Venoms , Viperidae , Snake Bites/epidemiology , Snake Bites/therapy , Snake Bites/drug therapy , Snake Bites/diagnosis , Italy , Animals , Antivenins/therapeutic use , Humans , Viper Venoms/toxicity , ViperaABSTRACT
Viper bites pose a significant public health issue in Armenia, even within urban areas, often resulting in clotting disorders, hypofibrinogenemia, and tissue necrosis in humans. This study investigates histopathological changes in various tissues during mice envenomation by West-Asian blunt-nosed viper (Macrovipera lebetina obtusa) venom, as well as the recovery process aided by experimental antivenom derived from sheep. The high venom dose caused substantial damage to the heart, lungs, liver, and kidneys in mice, indicating systemic harm. While antivenom administration can prevent mortality in mice envenomation, it may not fully mitigate histological damage in affected organs. Additionally, the study highlights the importance of timing antivenom administration, as the severity of tissue alterations can vary depending on the duration of envenomation. These findings shed light on antivenom's effects on viper envenomation and stress the need for further research to optimize its timing and dosage for minimizing histological damage and enhancing clinical outcomes.
Subject(s)
Antivenins , Snake Bites , Viper Venoms , Viperidae , Animals , Antivenins/therapeutic use , Antivenins/pharmacology , Mice , Viper Venoms/toxicity , Snake Bites/drug therapy , Sheep , Lung/pathology , Lung/drug effects , Kidney/pathology , Kidney/drug effects , Liver/pathology , Liver/drug effects , MaleABSTRACT
Snakebite envenomation often induces acute kidney injury (AKI) and acute liver injury (ALI), leading to augmented injuries and poor rehabilitation. Phospholipase A2 (PLA2) and metalloproteinase (SVMP) present in venom are responsible for the envenomation-associated events. In this study, mice envenomed with Deinagkistrodon acutus, Naja atra, or Agkistrodon halys pallas venom exhibited typical AKI and ALI symptoms, including significantly increased plasma levels of myoglobin, free hemoglobin, uric acid, aspartate aminotransferase, and alanine aminotransferase and upregulated expression of kidney NGAL and KIM-1. These effects were significantly inhibited when the mice were pretreated with natural inhibitors of PLA2 and SVMP isolated from Sinonatrix annularis (SaPLIγ and SaMPI). The inhibitors protected the physiological structural integrity of the renal tubules and glomeruli, alleviating inflammatory infiltration and diffuse hemorrhage in the liver. Furthermore, the dual therapy alleviated oxidative stress and apoptosis in the kidneys and liver by mitigating mitochondrial damage, thereby effectively reducing the lethal effect of snake venom in the inhibitor-treated mouse model. This study showed that dual therapy with inhibitors of metalloproteinase and phospholipase can effectively prevent ALI and AKI caused by snake bites. Our findings suggest that intrinsic inhibitors present in snakes are prospective therapeutic agents for multi-organ injuries caused by snake envenoming.
Subject(s)
Acute Kidney Injury , Metalloproteases , Snake Bites , Animals , Acute Kidney Injury/drug therapy , Acute Kidney Injury/pathology , Mice , Male , Metalloproteases/antagonists & inhibitors , Metalloproteases/metabolism , Snake Bites/drug therapy , Snake Bites/complications , Phospholipase A2 Inhibitors/pharmacology , Phospholipases A2/metabolism , Liver/drug effects , Liver/pathology , Liver/metabolism , Crotalinae , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/etiology , Oxidative Stress/drug effects , Kidney/drug effects , Kidney/pathology , Crotalid Venoms/toxicity , Snake Venoms , Apoptosis/drug effects , Elapid VenomsABSTRACT
This case report presents an exotic envenomation by a Chinese snake, Protobothrops mangshanensis. Its venom exhibited potent activity against plasma and fibrinogen, among other enzymatic activities. The patient initially presented with edema of the right upper limb, without tissue necrosis. There were no signs of bleeding; however, severe hypofibrinogenemia was observed (nadir value at 0.4 g/L), with a marked increase in fibrinogen degradation products and D-dimers, without any other coagulation disturbances. In the absence of a specific antivenom available against Asian Crotalinae venoms, the patient was treated at the 29th hour after bite with six vials of Antivipmyn™ TRI (Instituto Bioclon, Mexico, Mexico), a Mexican antivenom initially intended for American Crotalinae venoms, i.e., Bothrops asper, Lachesis muta and Crotalus durissus. Fibrinogen began to rise 6 hours after the antivenom infusion and was within the normal range 38 hours later. The report also underscores the utility of ClotPro® (Haemonetics ®USA), a viscoelastic test, for real-time monitoring of the snakebite-related coagulopathy. The clotting time was extended to 188 seconds on the EX-test while the MCF was decreased to 31 mm on the EX-test and the AP-test and was not measurable on the FIB-test, confirming severe hypofibrinogenemia. In order to confirm the paraspecificity of antivenom on the venom of P. mangshanensis, we studied the experimental neutralization of the venom procoagulant effect by Antivipmyn TRI and Green Pit Viper antivenom, which has been used in previous published clinical cases of P. mangshanensis envenomation. Both Antivipmyn™ TRI and Green Pit Viper antivenom corrected the procoagulant effect induced by P. mangshanensis venom. These findings suggest that Antivipmyn™ TRI cross-reacts with Protobothrops mangshanensis venom. In the absence of antivenom covering Asian Crotalinae, Antivipmyn TRI should be considered to treat an envenomation by Protobothrops spp.
Subject(s)
Antivenins , Crotalid Venoms , Snake Bites , Antivenins/therapeutic use , Animals , Snake Bites/drug therapy , Humans , Crotalid Venoms/toxicity , Male , Mexico , France , Crotalinae , Blood Coagulation/drug effects , FibrinogenABSTRACT
Snakebite is a significant health concern in Africa, particularly due to neurotoxic envenomation which can lead to neuromuscular paralysis and respiratory failure. In Nigeria, snakes from the Elapidae family are a notable cause of envenomation cases, though these incidents are underreported. This review examined case reports of neurotoxic envenomation in Africa, highlighting the clinical impacts and the efficacy of available antivenoms. Preclinical studies showed that the polyvalent antivenom from the South African Institute for Medical Research (SAIMR) was highly effective against neurotoxicity with a protective efficacy (R) of 1346.80 mg/mL, while clinical assessment emphasized the need for high-dose antivenom therapy along with supportive measures like mechanical ventilation. Unlike hemorrhagic envenomation, where antivenom promptly resolves bleeding, neurotoxic cases often require additional interventions. The review underscores the necessity for tailored approaches in antivenom therapy to address the complexities of neurotoxic snakebites and reduce their public health burden in Africa.
Subject(s)
Antivenins , Snake Bites , Snake Bites/drug therapy , Snake Bites/therapy , Antivenins/therapeutic use , Humans , Animals , Africa/epidemiology , Neurotoxicity Syndromes/etiologyABSTRACT
Eastern Diamondback Rattlesnake (Crotalus adamanteus) envenomation is a medical emergency encountered in the Southeastern United States. The venom contains a snake venom thrombin-like enzyme (SVTLE) that is defibrinogenating, causing coagulopathy without effects on platelets in humans. This investigation utilized thrombelastographic methods to document this coagulopathy kinetically on the molecular level in a rabbit model of envenomation via the analyses of whole blood samples without and with platelet inhibition. Subsequently, the administration of a novel ruthenium compound containing site-directed antivenom abrogated the coagulopathic effects of envenomation in whole blood without platelet inhibition and significantly diminished loss of coagulation in platelet-inhibited samples. This investigation provides coagulation kinetic insights into the molecular interactions and results of SVTLE on fibrinogen-dependent coagulation and confirmation of the efficacy of a ruthenium antivenom. These results serve as a rationale to investigate the coagulopathic effects of other venoms with this model and assess the efficacy of this site-directed antivenom.
Subject(s)
Antivenins , Blood Coagulation , Crotalid Venoms , Crotalus , Animals , Rabbits , Antivenins/pharmacology , Crotalid Venoms/pharmacology , Crotalid Venoms/antagonists & inhibitors , Blood Coagulation/drug effects , Thrombelastography , Ruthenium/chemistry , Ruthenium/pharmacology , Snake Bites/drug therapy , Male , Venomous SnakesABSTRACT
INTRODUCTION: Antivenom is first line treatment for snake envenomation worldwide, despite few placebo controlled clinical trials demonstrating effectiveness. We aimed to investigate whether early antivenom in red-bellied black snake (Pseudechis porphyriacus) bites would prevent systemic myotoxicity. METHODS: We undertook a multicentre randomized placebo-controlled trial of antivenom for red-bellied black snake bites with patients recruited from the Australian Snakebite Project (July 2014 to June 2020). In addition, we report all patients with red-bellied black snake bites during the same period, comparing the same outcomes. Patients over 2 years of age with definite red-bellied black snake bites and early systemic effects were randomized to receive 50 per cent glucose (placebo) or tiger snake antivenom within 6 hours post-bite, or in the cohort group received antivenom determined by the treating clinician. The primary outcome was the proportion of patients with myotoxicity (peak creatine kinase activity >1,000 U/L). Secondary outcomes were: area under the curve of total creatine kinase elevation over 48 hours, presence of venom post-antivenom, and adverse reactions. We analyzed both the randomized control trial patients and the combination of randomized control trial and cohort patients. RESULTS: Fifteen patients were recruited to the randomized controlled trial, and a cohort of 68 patients who were not randomized were included in the analysis. After treatment, two of seven patients given placebo had a peak creatine kinase activity >1,000 U/L versus none of the eight given antivenom (difference in favour of antivenom; 29 per cent; 95 per cent confidence interval:-18 per cent to +70 per cent; P = 0.2). The median area under the curve of total creatine kinase elevation over 48 hours in patients given placebo was 0 U/L*h (interquartile range: 0-124 U/L*h), which was not significantly different to those given antivenom: 197 U/L*h (interquartile range: 0-66,353 U/L*h; P = 0.26). Venom was not detected post-antivenom in six patients with measured venom concentrations given antivenom. Two patients given antivenom had immediate hypersensitivity reactions, one severe anaphylaxis, and another had serum sickness. Combining randomized and not randomized patients, three of 36 (8 per cent) administered antivenom less than 6 hours post-bite had a peak creatine kinase activity >1,000 U/L versus 17/47 (36 per cent) patients not receiving antivenom less than 6 hours post-bite (difference in favour of antivenom 29 per cent; 95 per cent confidence interval: 8 per cent to 44 per cent; P < 0.004). Overall, 13/36 (36 per cent) patients administered antivenom within 6 hours had hypersensitivity reactions, six severe anaphylaxis (17 per cent). DISCUSSION: We found that early antivenom was effective in red-bellied black snake bites, and only three patients need to be given antivenom within 6 hours to prevent myotoxicity in one (number needed to treat = 3). However, one in three patients administered antivenom developed a hypersensitivity reaction, and one in six had severe anaphylaxis. The major limitation of this study was the small number of patients recruited to the randomized controlled trial. CONCLUSION: Administration of antivenom in red-bellied black snake envenomation within 6 hours post-bite appeared to decrease the proportion of patients with myotoxicity, but a third of patients had adverse reactions.
Subject(s)
Antivenins , Elapid Venoms , Snake Bites , Humans , Snake Bites/drug therapy , Antivenins/therapeutic use , Male , Female , Adult , Prospective Studies , Middle Aged , Animals , Elapid Venoms/antagonists & inhibitors , Myotoxicity/drug therapy , Young Adult , Australia , Elapidae , Adolescent , Treatment Outcome , Creatine Kinase/blood , AgedABSTRACT
Snakebite envenomation is a major public health issue which causes severe morbidity and mortality, affecting millions of people annually. Of a diverse range of clinical manifestations, local and systemic haemorrhage are of particular relevance, as this may result in ischemia, organ failure and even cardiovascular shock. Thus far, in vitro studies have failed to recapitulate the haemorrhagic effects observed in vivo. Here, we present an organ-on-a-chip approach to investigate the effects of four different snake venoms on a perfused microfluidic blood vessel model. We assess the effect of the venoms of four snake species on epithelial barrier function, cell viability, and contraction/delamination. Our findings reveal two different mechanisms by which the microvasculature is being affected, either by disruption of the endothelial cell membrane or by delamination of the endothelial cell monolayer from its matrix. The use of our blood vessel model may shed light on the key mechanisms by which tissue-damaging venoms exert their effects on the capillary vessels, which could be helpful for the development of effective treatments against snakebites.
Subject(s)
Lab-On-A-Chip Devices , Snake Venoms , Animals , Humans , Endothelial Cells/drug effects , Hemorrhage , Cell Survival/drug effects , Snake Bites/drug therapy , Human Umbilical Vein Endothelial Cells/drug effects , Microphysiological SystemsABSTRACT
On the 26 th January 2023, a free to attend, 'improving in vivo snake venom research: a community discussion' meeting was held virtually. This webinar brought together researchers from around the world to discuss current neutralisation of venom lethality mouse assays that are used globally to assess the efficacy of therapies for snakebite envenoming. The assay's strengths and weaknesses were highlighted, and we discussed what improvements could be made to refine and reduce animal testing, whilst supporting preclinical antivenom and drug discovery for snakebite envenoming. This report summarises the issues highlighted, the discussions held, with additional commentary on key perspectives provided by the authors.
Subject(s)
Antivenins , Snake Bites , Snake Venoms , Antivenins/therapeutic use , Animals , Snake Venoms/antagonists & inhibitors , Mice , Snake Bites/drug therapy , HumansABSTRACT
INTRODUCTION: Antivenom is widely accepted as an effective treatment for snake envenomation. This is despite very limited evidence supporting clinical effectiveness for major envenomation syndromes, and is mainly based on pre-clinical studies and observational studies without control groups. EFFECTIVENESS OF EARLY ANTIVENOM: Although antivenom exhibits efficacy by binding to snake toxins and preventing toxic injury in animals if pre-mixed with venom, this efficacy does not always translate to clinical effectiveness. There are many irreversible venom mediated effects that antivenom cannot neutralise or reverse, such as pre-synaptic neurotoxicity and myotoxicity. Fortunately, early antivenom appears to prevent some of these. PRACTICALITIES OF ADMINISTERING ANTIVENOM EARLY: With good evidence that early antivenom prevents some envenomation syndromes, the time between bite and antivenom administration must be reduced. This requires improving the initial assessment of snakebite patients, and improving early decision making based on clinical effects. CONCLUSION: Until there are improved, simplified, easy to use, rapid and inexpensive tests, whether available in the laboratory or preferably at the bedside that identify systemic envenomation, the key to early antivenom administration is early assessment and decision making based on systemic symptoms, including nausea, vomiting, headache and abdominal pain.
Subject(s)
Antivenins , Snake Bites , Animals , Humans , Antivenins/therapeutic use , Antivenins/administration & dosage , Snake Bites/drug therapy , Snake Venoms/antagonists & inhibitors , Time FactorsABSTRACT
Current treatment of snakebite relies on immunoglobulin-rich antivenoms. However, production of these antivenoms is complicated and costly. Aptamers - single-stranded DNAs or RNAs with specific folding structures that bind to specific target molecules - represent excellent alternatives or complements to antibody-based therapeutics. However, no studies have systematically assessed the feasibility of using aptamers to mitigate venom-induced toxicity in vivo. ß-bungarotoxin is the predominant protein responsible for the toxicity of the venom of Bungarus multicinctus, a prominent venomous snake inhabiting Taiwan. In this study, we reported the screening and optimization of a DNA aptamer against ß-bungarotoxin and tested its utility in a mouse model. After 14 rounds of directed evolution of ligands by exponential enrichment, an aptamer, called BB3, displaying remarkable binding affinity and specificity for ß-bungarotoxin was obtained. Following structural prediction and point-modification experiments, BB3 underwent truncation and was modified with 2'-O-methylation and a 3'-inverted dT. This optimized aptamer showed sustained, high-affinity binding for ß-bungarotoxin and exhibited remarkable nuclease resistance in plasma. Importantly, administration of this optimized aptamer extended the survival time of mice treated with a lethal dose of ß-bungarotoxin. Collectively, our data provide a compelling illustration of the potential of aptamers as promising candidates for development of recombinant antivenom therapies.