Snakebite Research Articles

Comprehensive Review of Epidemiology and Treatment of Snakebite Envenomation in West Africa: Case of Benin.

Snakebite envenomation (SBE) constitutes a public health, social, and economic problem affecting poor communities in intertropical and subtropical regions. This review sought to synthesize literature on snakebite envenomation in Benin to highlight research perspectives and strategies for better management of the menace. A literature search performed in multidisciplinary electronic databases showed that the prevalence of SBE is high in Benin, but the incidences, associated morbidities, and mortalities are greatly underestimated. Most snake envenomations are by Echis ocellatus in Northern Benin during the rainy season. Adults involved in agricultural activities are the most affected. The absence of antivenin serum in the most affected areas explains the preference for alternative and traditional medicine as the first-line treatment for SBE in Benin. In conclusion, it would be imperative to revitalize the snakebite reporting system in order to have better epidemiological data and to develop a sustainable national strategy for the control and management of snakebite envenomation.

Development of a membrane-disruption assay using phospholipid vesicles as a proxy for the detection of cellular membrane degradation

Snakebite envenoming is a global health issue that affects millions of people worldwide, and that causes morbidity rates surpassing 450,000 individuals annually. Patients suffering from snakebite morbidities may experience permanent disabilities such as pain, blindness and amputations. The (local) tissue damage that causes these life-long morbidities is the result of cell- and tissue-damaging toxins present in the venoms. These compounds belong to a variety of toxin classes and may affect cells in various ways, for example, by affecting the cell membrane. In this study, we have developed a high-throughput in vitro assay that can be used to study membrane disruption caused by snake venoms using phospholipid vesicles from egg yolk as a substrate. Resuspended chicken egg yolk was used to form these vesicles, which were fluorescently stained to allow monitoring of the degradation of egg yolk vesicles on a plate reader. The assay proved to be suitable for studying phospholipid vesicle degradation of crude venoms and was also tested for its applicability for neutralisation studies of varespladib, which is a PLA2 inhibitor. We additionally made an effort to identify the responsible toxins using liquid chromatography, followed by post-column bioassaying and protein identification using high-throughput venomics. We successfully identified various toxins in the venoms of C. rhodostoma and N. mossambica, which are likely to be involved in the observed vesicle-degrading effect. This indicates that the assay can be used for screening the membrane degrading activity of both crude and fractionated venoms as well as for neutralisation studies.

Snakebite envenoming: A systematic review and meta-analysis of global morbidity and mortality.

Snakebite envenoming represents a significant and often neglected public health challenge, particularly in rural communities across tropical and subtropical regions. An estimated 1.2-5.5 million people are envenomed by snakebites annually. More than 125,000 of these bites are fatal, and 3-4 times as many results in disability/disfigurement. Despite its prevalence, collecting accurate epidemiological data on snakebite is challenging. This systematic review and meta-analysis collates global epidemiology data on snakebite morbidity and mortality. Medline, Embase, Cochrane and CINAHL Plus databases were searched for articles published between 2001-2022. Pooled incidence and mortality were obtained using random effects modelling, heterogeneity (I2) was tested, and sensitivity analyses performed. Newcastle-Ottawa Scale assessed study quality. Out of the four databases, 5,312 articles were found. After removing duplicates, 3,953 articles were screened by title and abstract and 65 articles containing information on snakebite epidemiology, encompassing 663,460 snakebites, were selected for analysis. The people most at risk for snakebite were men (59%), engaged in agricultural labour (27.5%), and residing in rural areas (66.7%). More than half (57%) of the reported bites resulted in envenoming. Incidents occurred frequently in the summer season (38.5%), during daytime (56.7%), and bites were most often to the lower limb (56.4%). Envenoming severity was frequently mild (46.7%), treated in hospital (68.3%), and was treated with anti-venom (64.7%). The pooled global incidence and mortality was 69.4 /100,000 population (95%CI: 36.8 to 101.9) and 0.33/100,000 population (95%CI, 0.14 to 0.52) per year, respectively. Stratified by continents, Asia had the highest incidence of 130.7/100,000 population (95%CI: 48.3 to 213.1) while Europe has the lowest with 0.7/100,000 population (95%CI: -0.2 to 1.5). The highest mortality was reported in Asia at 0.96/100,000 population (95% CI: 0.22 to 1.70), and Africa 0.44/100,000 population (95%CI: -0.03 to 0.84). Incidence was highest among inhabitants of lower-middle-income countries 132.7/100,000 population (95%CI: 55.4 to 209.9) while mortality was highest in low-income countries at 0.85/100,000 population (95% CI: -0.06 to 2.31). Incidence and mortality rates noted here highlight the global impact of snakebite and underscore the critical need to address the burden of snakebite envenoming. It also reveals that while reported snakebite incidence was higher in lower-middle-income countries, the burden of mortality was greatest among inhabitants of low-income countries, again emphasising the need for greater efforts to tackle this neglected tropical disease.

Insuficiencia cardíaca secundaria a mordedura de serpiente. La visión del intensivista: reporte de caso

Background: Ophidic accident is a neglected disease that affects tropical countries. Latin America is the second region after Africa, with the most cases worldwide. Local lesions accompany its clinical course up to systemic affectations such as renal, hematological, and neurological lesions. Cardiac complications are rare, especially in patients who do not have cardiovascular risk factors. There are reports of acute myocardial infarction, but there is little information about heart failure due to Bothrops spp. Case report: We present the case of a 25-year-old man without cardiovascular risk factors who was admitted to the intensive care unit and developed heart failure with cardiogenic shock and multi-organ failure secondary to a snake bite. Conclusions: Although the characteristic clinical course of a bothropic ophidian accident and its systemic manifestations are mainly related to coagulation abnormalities, there are cardiovascular complications within its clinical presentation that, although rare, if not detected promptly and not adequately managed, are associated with high morbidity and mortality.

Biochemical and biological characterization of the venoms of Naja kaouthia and Naja mandalayensis from Myanmar and neutralization effects of BPI cobra antivenom

Snakebite is a neglected public health issue, with many scientific and medical issues to be solved. Cobras are among the most common venomous snakes in Myanmar and are responsible for a considerable number of severe snakebite envenoming. There are three species of cobra (Naja kaouthia, Naja mandalayensis and Ophiophagus hannah) in Myanmar. The study aims to characterize the N. kaouthia and N. mandalayensis venoms and to investigate the efficacy of anti-cobra antivenom (BPI) against the two venoms. Protein components and fibrinogenolytic activity were determined by SDS-PAGE. Enzymatic activities for PLA2, protease and acetylcholinesterase were determined by spectrophotometric method. Anticoagulant activity was determined by recalcification time of citrated human plasma. Myotoxicity, necrotizing activity, median lethal dose (LD50) and median effective dose (ED50) were determined by WHO recommended methods. The SDS-PAGE displayed the proteins and enzymes containing in two venoms were different. N. kaouthia venom exhibited more in PLA2, acetylcholinesterase, anticoagulant, fibrinogenolytic and necrotizing activities than N. mandalayensis venom. N. mandalayensis venom had more protease activity and myotoxicity than N. kaouthia venom. The median lethal dose (LD50) of N. kaouthia and N. mandalayensis venom was 4.33 μg/mouse and 5.04 μg/mouse respectively. Both venoms induced fibrinogen Aα chain degradation in 30 min (N. kaouthia) and in 6 h (N. mandalayensis). The same median effective dose (ED50) (19.56 μg/mouse) showed that anti-NK antivenom can neutralize against lethal effect of N. mandalayensis venom. It can also neutralize the protease activity, anticoagulant activity and fibrinogenolytic activity of both venoms. Immunodiffusion and immunoblotting studies showed that the antivenom recognized its homologous venom (N. kaouthia) and cross-reacted against the heterologous venom (N. mandalayensis). The anti-NK antivenom is suitable to use for N. mandalayensis bite if monospecific antivenom is not available.

The great escape- preserved cilioretinal artery with transient central retinal artery occlusion following snake bite

A 24-year female sustained a snake bite on the lateral side of the left ankle, followed by localized pain and blurring of vision in right eye. Her best corrected visual acuity was 20/20 in the both eyes. Relative afferent pupillary defect was noted in right eye. Fundus examination of right eye showed clear media, normal optic disc and retinal whitening with sparing of small area on macula, temporal to disc with small cilioretinal artery, suggestive of central retinal artery occlusion (CRAO) with presence of cilioretinal artery sparing. Ophthalmic manifestations following a snake bite are uncommon and can arise through diverse mechanism such as hematotoxicity from the snake bite, resulting in CRAO. Although CRAO following snake bite has been reported, we present a very rare case of snake bite induced transient CRAO with presence of spared cilioretinal artery.

IJCM_289A: Determination of factors favouring the snake bite mortality in Himachal Pradesh

Background: Snake bite is an established important cause of morbidity and mortality among the poor and rural population across the world including India. India accounts for the highest number of snakebites and related mortality globally. Objective: Identification of factors favoring the mortality due to snake bite. Methodology: A descriptive cross-sectional study was conducted from April 2022 to March 2023, and deaths due to snake bites reported from different health care facilities and community were included in the study. Results: A case-fatality rate of 5.9% due to snake bite was documented in the study. The factors identified as favorable for mortality were delayed treatment, followed by suboptimal care at primary and secondary health care facilities and traditional beliefs of the community. Conclusion: Provision of emergency service as point of care delivery, focusing on provision of training to strength point of care emergency services, co-ordination and linkages with the community members can strengthen the efforts toward reducing the mortality due to snake bites.

Epidemiological and sociodemographic description of snakebite envenoming cases in Paraguay reported between 2015 and 2021

IntroductionSnakebite envenoming (SBE) is a public health problem in Paraguay where the presence of 15 medically important snake species has been reported. Blessed with large forested areas, its economy largely...

Disability resulting from Delayed treatment after a Copperhead snake bite to the hand

Disability resulting from Delayed treatment after a Copperhead snake bite to the hand

VENOMOUS ENCOUNTER: A CASE REPORT ON SNAKE BITE DURING FULL-TERM GESTATION WITH DELAYED MANIFESTATION

Background: Snake bite is uncommon among pregnant women, that too presentation in third trimester with late presentation, with envenomation is rare. Knowledge about the toxic symptoms and management of snake bite poisoning is very low due the rarity of cases. Case report: Presenting a case of 26 year old female, Primigravida with Premature Rupture of Membranes with Snake bite in Acute Kidney Injury with Disseminate Intravascular Coagulopathy. Appropriate care and management led to the survival of both mother and baby. Discussion: In India, 216 snake species exist, 52 are venomous. Elapids like cobras, kraits, vipers, and sea snakes pose threats. Venom potency varies with seasons and snake color. Envenomation symptoms include local pain, systemic effects, and coagulopathy. Pregnancy complicates management antivenom and careful monitoring are vital. Conclusion: Acute kidney injury with disseminated intravascular coagulopathy arising from systemic poisoning due to snake bite in pregnancy is difficult and challenging. Obstetric and medical line of treatment depends on the severity of envenomation, gestational age at presentation, timing, duration and quality of treatment.

Varespladib mitigates acute liver injury via suppression of excessive mitophagy on Naja atra envenomed mice by inhibiting PLA2

Snakebite envenomation often leads to severe visceral injuries, including acute liver injury (ALI). However, the toxicity mechanism remains unclear. Moreover, varespladib can directly inhibit phospholipase A2 (PLA2) in snake venom, but its protective effect on snakebite-induced ALI and the mechanism have not been clarified. Previous studies have shown that snake venom PLA2 leads to neuron cell death via reactive oxygen species (ROS), one of the initial factors related to the mitophagy pathway. The present study group also found that ROS accumulation occurred after Naja atra envenoming. Hematoxylin and eosin (H/E) staining and immunohistochemistry (IHC) were performed to identify the expression of inflammatory factors in the liver tissue, and flow cytometry and immunofluorescence were used to detect ROS levels and mitochondrial function. Immunofluorescence and western blotting were also used for detecting mitophagy pathway-related proteins. The results showed that N. atra bite induced ALI by activating mitophagy and inducing inflammation and that varespladib had a protective effect. Collectively, these results showed the pathological mechanism of ALI caused by N. atra bite and revealed the protective effect of varespladib.

Momordica dioica: A medicinal plant, its benefits and pharmacological activity

Momordica dioica is a cucurbitaceous climbing creeper (commonly known as kakrol, spiny gourd or teasle gourd). It is native to Asia with widely distributed in India and Bangladesh also. It is used as preventive and curative agent for various diseases. It has also significant nutritional value as vegetable over thousands of years. This review aims to take an attempt to evaluate the pharmacological properties and benefits of Momordica dioica according to the view of traditional medicinal plant based on treatment including. Momordica dioica is considered as an underutilized vegetable, although having significant presence of certain compounds containing higher nutritional value than many frequently consumed vegetables. Different plant parts of Momordica dioica provide a numbers of phyto-constituents like alkaloids, glycosides, steroids, triterpenoids, flavonoids, ursolic acid, vitamins, minerals and rich in fibre. They have potential to cure asthma, excessive salivation and inflammation caused by lizards, snake bite, elephantiasis, fever, mental and digestive disorders. It is used to maintain skin health.

ROLE OF MADANPHALA IN MANAGEMENT OF MUSHIKA VISHA - A REVIEW ARTICLE

An ingredient that is used in various formulations in the treatment of Vishas (poisons). Many formulations for the management of various poisons like snake bite, keetavisha (insect poisons), etc. have been explained in Ayurveda treatise that contains it as an ingredient.in the present article we are discussing regarding the Madanphala and ghrita of Tanduliyaka in management of Mushika visha. Madanphala is having properties of Laghu, Ruksha Guna, Kashaya, Katu, Tikta Rasa and Ushna Veerya. It acts as a Vranashodhan and Ropan properties. Paste of Madanphala applied over skin and wounds helps in Vranashodhan therefore used in the Mushika visha effectively. Tanduliya (Amaranthus spinosus) prepared in the form of Ghrita (Ghee) is said to reduce the bastivedana (pain in urinary system) and anaha (Distension of abdomen due to obstruction to passage of urine and stools) in the complications caused because of visha

A comprehensive review of the botany, phytochemistry, pharmacology, and toxicology of Murrayae Folium et Cacumen.

Ethnopharmacological relevance: Murrayae Folium et Cacumen (MFC) is a plant considered to be a traditional Chinese medicine with culinary value as well. The dry leaves and twigs of Murraya paniculata and M. exotica are used to treat stomach aches, rheumatism, toothaches, swelling, and insect and snake bites. They are also used to prepare spicy chicken dishes. Aim of the review: This review comprehensively summarizes the available information on the botanical characterization, phytochemistry, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC. Methods: Relevant scientific literature up to August 2023 was included in the study. Chinese and English studies on MFC were collected from databases, including PubMed, Elsevier, Web of Science, Springer, Science Direct, Wiley, ACS, and CNKI (Chinese). Doctoral and Master's dissertations were also included. Results: In total, 720 compounds have been identified and reported in the literature, including flavonoids, coumarins, alkaloids, sterols, phenylpropenols, organic acids, spirocyclopentenones, and volatile oils. Flavonoids and coumarins are the two most important bioactive compounds responsible for these pharmacological activities. MFC has anti-inflammatory, anti-bacterial, anti-microbial, anti-diabetic, anti-tumor, anti-oxidant, anti-depressant, potential anti-Alzheimer's disease, chondroprotective, and analgesic properties. The pharmacological effects include interrupting the STAT3/NF-κB/COX-2 and EGFR signaling pathways, downregulating EpCAM expression, inhibiting NF-κB and ERK signals, inhibiting the EP/cAMP/PKA signaling pathway and miR-29a/Wnt/β-catenin signaling activity, and upregulating Foxo3a expression. Conclusion: This review demonstrates that the chemical constituents, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC support its use in traditional Chinese botanical medicines. MFC contains a wide range of chemical compounds. Flavonoids and coumarins promote strong pharmacological activity and, are low-toxicity natural phytomedicines that are widely used in medicine, food, ornamentation, and cosmetics, making MFC a promising compound for development and use in the treatment of several medical conditions.

Landscape of toxin-neutralizing therapeutics for snakebite envenoming (2015-2022): Setting the stage for an R&D agenda.

Progress in snakebite envenoming (SBE) therapeutics has suffered from a critical lack of data on the research and development (R&D) landscape. A database characterising this information would be a powerful tool for coordinating and accelerating SBE R&D. To address this need, we aimed to identify and categorise all active investigational candidates in development for SBE and all available or marketed products. In this landscape study, publicly available data and literature were reviewed to canvas the state of the SBE therapeutics market and research pipeline by identifying, characterising, and validating all investigational drug and biologic candidates with direct action on snake venom toxins, and all products available or marketed from 2015 to 2022. We identified 127 marketed products and 196 candidates in the pipeline, describing a very homogenous market of similar but geographically bespoke products and a diverse but immature pipeline, as most investigational candidates are at an early stage of development, with only eight candidates in clinical development. Further investment and research is needed to address the shortfalls in products already on the market and to accelerate R&D for new therapeutics. This should be accompanied by efforts to converge on shared priorities and reshape the current SBE R&D ecosystem to ensure translation of innovation and access.

Recombinant snake antivenoms get closer to the clinic

Snakebite envenomings kill ~100 000 victims each year and leave many more with permanent sequelae. Antivenoms have been available for more than 125 years but are in need of innovation. A new study by Khalek et al. highlights broadly neutralizing human monoclonal antibodies (mAbs) that might be used to develop recombinant antivenoms with superior therapeutic benefits.

In vitro immunoreactivity and in vivo neutralization of Trimeresurus gracilis venom with antivenoms targeting four pit viper species.

Snakebite envenomation is a significant global health issue that requires specific antivenom treatments. In Taiwan, available antivenoms target a variety of snakes, but none specifically target Trimeresurus gracilis, an endemic and protected species found in the high mountain areas of Taiwan. This study evaluated the effectiveness of existing antivenoms against T. gracilis venom, focusing on a bivalent antivenom developed for Trimeresurus stejnegeri and Protobothrops mucrosquamatus (TsPmAV), as well as monovalent antivenoms for Deinagkistrodon acutus (DaAV) and Gloydius brevicaudus (GbAV). Our research involved in vivo toxicity testing in mice and in vitro immunobinding experiments using (chaotropic) enzyme-linked immunosorbent assays, comparing venoms from four pit viper species (T. gracilis, T. stejnegeri, P. mucrosquamatus, and D. acutus) with three types of antivenoms. These findings indicate that TsPmAV partially neutralized T. gracilis venom, marginally surpassing the efficacy of DaAV. In vitro tests revealed that GbAV displayed higher binding capacities toward T. gracilis venom than TsPmAV or DaAV. Comparisons of electrophoretic profiles also reveal that T. gracilis venom has fewer snake venom C-type lectin like proteins than D. acutus, and has more P-I snake venom metalloproteases or fewer phospholipase A2 than G. brevicaudus, T. stejnegeri, or P. mucrosquamatus. This study highlights the need for antivenoms that specifically target T. gracilis, as current treatments using TsPmAV show limited effectiveness in neutralizing local effects in patients. These findings provide crucial insights into clinical treatment protocols and contribute to the understanding of the evolutionary adaptation of snake venom, aiding in the development of more effective antivenoms for human health.

Use of Thromboelastography in Assessment of Snake Bite Coagulopathy.

Background: Monitoring for envenomation coagulopathy following snake bites has traditionally involved using serial coagulation studies.Purpose: Thromboelastography (TEG), with its real-time assessment, could offer an alternative to standard of care. This study aims to evaluate the use of TEG with traditional coagulation labs in the assessment of snake bite coagulopathy.Research Design: A retrospective review of patients who presented to a level 1 trauma center between 2014 and 2020 with snake bite envenomation was conducted, comparing traditional coagulation studies to TEG plus coagulation studies.Results: The 12 patients who had studies within the stipulations of our review were tracked and subsequently progressed well clinically with no adverse effects and ultimately discharged home with an average hospital stay of 2.2days.Conclusions: Our data suggests that patients can be observed clinically without needing repeat coagulation studies if initial TEG and TCS are within normal limits.

Assessing the Incidence of Snakebites in Rural Gabon-A Community-Based, Cross-Sectional Pilot Survey.

Snakebite envenoming (SBE) is a neglected tropical disease (NTD). Community-based studies from sub-Saharan Africa are urgently required as data on the incidence are scarce. This study aimed to determine the lifetime prevalence of snakebites in rural Gabon by preparing the conduct of a larger regional survey. A cross-sectional community-based epidemiological survey in Sindara, Ngounie province, was conducted. Households were interviewed about the history of snakebites of household members to calculate lifetime prevalence. In addition, the average annual incidence rate per 100,000 over the last 5 years was calculated. A total of 771 inhabitants were enrolled, of which 5 (0.65%; 95% confidence interval (95% CI: 0.2-1.5%)) were victims of snakebites. Over the past 5 years, annual incidence was 77 bites per 100,000 (95% CI: 0-620). This study provides a first rough estimate of the incidence of SBE from rural central Gabon, demonstrating the importance of this NTD. Key Contribution: The estimated annual incidence of snakebites found was 77 per 100,000. Snakebites occurred mainly during agricultural activities.

Snakebites in Cameroon: Tolerance of a Snake Antivenom (Inoserp™ PAN-AFRICA) in Africa in Real-Life Conditions.

Snakebite envenomation (SBE) is a public health issue in sub-Saharan countries. Antivenom is the only etiological treatment. Excellent tolerance is essential in managing SBE successfully. This study aimed to evaluate tolerance of InoserpTM PAN-AFRICA (IPA). It was conducted on fourteen sites across Cameroon. IPA was administered intravenously and repeated at the same dose every two hours if needed. Early and late tolerance was assessed by the onset of clinical signs within two hours and at a visit two weeks or more after the first IPA administration, respectively. Over 20 months, 447 patients presenting with a snakebite were included. One dose of IPA was administered to 361 patients and repeated at least once in 106 patients. No significant difference was shown between the proportion of adverse events in patients who received IPA (266/361, 73.7%) and those who did not (69/85, 81.2%) (p = 0.95). Adverse reactions, probably attributable to IPA, were identified in four (1.1%) patients, including one severe (angioedema) and three mild. All these reactions resolved favorably. None of the serious adverse events observed in twelve patients were attributed to IPA. No signs of late intolerance were observed in 302 patients. Tolerance appears to be satisfactory. The availability of effective and well-tolerated antivenoms would reduce the duration of treatment and prevent most disabilities and/or deaths.