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Toxins
Special Issues
Pre-clinical and Clinical Management of Snakebite Envenomation
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Pre-clinical and Clinical Management of Snakebite Envenomation

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 7938

Special Issue Editors

Prof. Dr. Sakthivel Vaiyapuri

E-Mail Website
Guest Editor
School of Pharmacy, University of Reading, Reading RG6 6UB, UK
Interests: venom research; sequence, structure and functional analysis of venom proteins; development of diagnostic and improved therapeutic strategies for snakebites; the impact of venoms on the cardiovascular system; clinical man-agement of snakebites in patients; policy development for snakebites
Special Issues, Collections and Topics in MDPI journals
Dr. Subramanian Senthilkumaran

E-Mail Website
Guest Editor
Manian Medical Centre, Erode 638001, Tamil Nadu, India
Interests: snakebite envenomation; emergency medicine; toxicology

Special Issue Information

Dear Colleagues,

Snakebites pose a significant public health concern, especially in underdeveloped rural areas with limited access to appropriate medical care. The World Health Organisation (WHO) estimates that about 5 million people worldwide suffer from snakebites each year, with 2.5 million of these resulting in envenoming. The symptoms of snakebite envenoming range from mild local pain and swelling to life-threatening systemic effects such as respiratory failure, kidney damage, and cardiac arrest. Hence, clinical management is essential to prevent morbidity and mortality resulting from envenoming. Prompt and proper treatment can greatly reduce symptom severity and enhance patient outcomes. The initial step in clinical management is to identify the snake species responsible for the bite, as this will determine the type and amount of antivenom required and expected envenomation effects. However, identifying the species can be challenging in regions with several venomous snake species or where the bite happens in the dark. In addition, there are no specific diagnostic tests available for most of the medically important venomous snakes worldwide. Furthermore, antivenom is not without risks and can cause allergic reactions, serum sickness, and anaphylaxis. Therefore, it should only be administered by trained medical professionals in a hospital setting. In addition to antivenom, other supportive measures such as pain relief medication, wound care, and fluid resuscitation may be required to manage symptoms such as pain, necrosis, and bleeding. In severe cases, patients may require mechanical ventilation or other advanced life support measures. Due to these challenges and complications, many rural healthcare practitioners are not confident in treating snakebite victims, leading to referrals to distant hospitals. Therefore, it is vital to consolidate the clinical practices and research on snakebite envenomation worldwide into one source. This will facilitate the adaptation of best practices and improved knowledge using evidence-based research, enhancing the clinical management of snakebites worldwide and saving countless lives from unexpected snakebite envenoming.

In this Special Issue, we invite scientific colleagues, clinicians, and other healthcare professionals to submit different types of articles reporting varying aspects of the pre-clinical and clinical management of snakebites. This may include the pre-clinical assessment of potential therapeutic agents for snakebites, pre-hospital care such as appropriate first aid and field intervention for snakebite victims, and any specific practice that was used to tackle envenomation effects in the hospitals. Please contact the editorial team if you are not sure about the suitability of your article for this Special Issue.

Prof. Dr. Sakthivel Vaiyapuri
Dr. Subramanian Senthilkumaran
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • snakebite envenomation
  • snakes
  • venoms
  • clinical management
  • clinical manifestations
  • diagnosis of envenomation effects
  • treatment for snakebite-induced complications

Published Papers (5 papers)

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Research

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21 pages, 4265 KiB  
Article
Standard Quality Characteristics and Efficacy of a New Third-Generation Antivenom Developed in Colombia Covering Micrurus spp. Venoms
by Santiago Tabares Vélez, Lina María Preciado, Leidy Johana Vargas Muñoz, Carlos Alberto Madrid Bracamonte, Angelica Zuluaga, Jeisson Gómez Robles, Camila Renjifo-Ibañez and Sebastián Estrada-Gómez
Toxins 2024, 16(4), 183; https://doi.org/10.3390/toxins16040183 - 09 Apr 2024
Viewed by 710
Abstract
In Colombia, Micrurus snakebites are classified as severe according to the national clinical care guidelines and must be treated with specific antivenoms. Unfortunately, these types of antivenoms are scarce in certain areas of the country and are currently reported as an unavailable vital [...] Read more.
In Colombia, Micrurus snakebites are classified as severe according to the national clinical care guidelines and must be treated with specific antivenoms. Unfortunately, these types of antivenoms are scarce in certain areas of the country and are currently reported as an unavailable vital medicine. To address this issue, La Universidad de Antioquia, through its spin-off Tech Life Saving, is leading a project to develop third-generation polyvalent freeze-dried antivenom. The goal is to ensure access to this therapy, especially in rural and dispersed areas. This project aims to evaluate the physicochemical and preclinical parameters (standard quality characteristics) of a lab-scale anti-elapid antivenom batch. The antivenom is challenged against the venoms of several Micrurus species, including M. mipartitus, M. dumerilii, M. ancoralis, M. dissoleucus, M. lemniscatus, M. medemi, M. spixii, M. surinamensis, and M. isozonus, following the standard quality characteristics set by the World Health Organization (WHO). The antivenom demonstrates an appearance consistent with standards, 100% solubility within 4 min and 25 s, an extractable volume of 10.39 mL, a pH of 6.04, an albumin concentration of 0.377 mg/mL (equivalent to 1.22% of total protein), and a protein concentration of 30.97 mg/mL. Importantly, it maintains full integrity of its F(ab′)2 fragments and exhibits purity over 98.5%. Furthermore, in mice toxicity evaluations, doses up to 15 mg/mouse show no toxic effects. The antivenom also demonstrates a significant recognition pattern against Micrurus venoms rich in phospholipase A2 (PLA2) content, as observed in M. dumerilii, M. dissoleucus, and M. isozonus. The effective dose 50 (ED50) indicates that a single vial (10 mL) can neutralize 2.33 mg of M. mipartitus venom and 3.99 mg of M. dumerilii venom. This new anti-elapid third-generation polyvalent and freeze-dried antivenom meets the physicochemical parameters set by the WHO and the regulators in Colombia. It demonstrates significant efficacy in neutralizing the venom of the most epidemiologically important Micrurus species in Colombia. Additionally, it recognizes seven other species of Micrurus venom with a higher affinity for venoms exhibiting PLA2 toxins. Fulfilling these parameters represents the first step toward proposing a new pharmacological alternative for treating snakebites in Colombia, particularly in dispersed rural areas, given that this antivenom is formulated as a freeze-dried product. Full article
(This article belongs to the Special Issue Pre-clinical and Clinical Management of Snakebite Envenomation)
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18 pages, 2327 KiB  
Article
A Comparison of the Efficacy of Antivenoms and Varespladib against the In Vitro Pre-Synaptic Neurotoxicity of Thai and Javanese Russell’s Viper (Daboia spp.) Venoms
by Mimi Lay and Wayne C. Hodgson
Toxins 2024, 16(3), 124; https://doi.org/10.3390/toxins16030124 - 01 Mar 2024
Viewed by 1039
Abstract
The heterogeneity in venom composition and potency in disparate Eastern Russell’s viper (Daboia siamensis) populations has repercussions for the efficacy of antivenoms. This is particularly pronounced in geographical areas in which the venom of the local species has not been well [...] Read more.
The heterogeneity in venom composition and potency in disparate Eastern Russell’s viper (Daboia siamensis) populations has repercussions for the efficacy of antivenoms. This is particularly pronounced in geographical areas in which the venom of the local species has not been well studied and locally produced antivenoms are unavailable. In such cases, alternative therapies following envenoming, which are not limited by species specificity, may be employed to complement antivenoms. We studied the neuromuscular activity of D. siamensis venom from Thailand and Java (Indonesia) and the ability of Thai antivenoms and/or Varespladib to prevent or reverse these effects. Both Thai and Javanese D. siamensis venoms displayed potent pre-synaptic neurotoxicity but weak myotoxicity in the chick biventer cervicis nerve–muscle preparation. Whilst the neurotoxicity induced by both venoms was abolished by the prior administration of Thai D. siamensis monovalent antivenom or pre-incubation with Varespladib, Thai neuro-polyvalent antivenom only produced partial protection when added prior to venom. Pre-synaptic neurotoxicity was not reversed by the post-venom addition of either antivenom 30 or 60 min after either venom. Varespladib, when added 60 min after venom, prevented further inhibition of indirect twitches. However, the subsequent addition of additional concentrations of Varespladib did not result in further recovery from neurotoxicity. The combination of Thai monovalent antivenom and Varespladib, added 60 min after venom, resulted in additional recovery of twitches caused by either Thai or Javanese venoms compared with antivenom alone. In conclusion, we have shown that Varespladib can prevent and partially reverse the pre-synaptic neurotoxicity induced by either Thai or Javanese D. siamensis venoms. The efficacy of Thai D. siamensis monovalent antivenom in reversing pre-synaptic neurotoxicity was significantly enhanced by its co-administration with Varespladib. Further work is required to establish the efficacy of Varespladib as a primary or adjunct therapy in human envenoming. Full article
(This article belongs to the Special Issue Pre-clinical and Clinical Management of Snakebite Envenomation)
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14 pages, 2148 KiB  
Article
Development of a Biosensor to Detect Venom of Malayan Krait (Bungarus candidus)
by Kiattawee Choowongkomon, Janeyuth Chaisakul, Supaphorn Seetaha, Taksa Vasaruchapong, Wayne C. Hodgson, Natchaya Rasri, Katechawin Chaeksin, Sattawat Boonchaleaw and Nattapon Sookprasert
Toxins 2024, 16(1), 56; https://doi.org/10.3390/toxins16010056 - 19 Jan 2024
Viewed by 1509
Abstract
Malayan krait (Bungarus candidus) envenoming is a cause of significant morbidity and mortality in many Southeast Asian countries. If intubation and specific antivenom administration are delayed, the most significant life-threatening outcome may be the inhibition of neuromuscular transmission and subsequent respiratory [...] Read more.
Malayan krait (Bungarus candidus) envenoming is a cause of significant morbidity and mortality in many Southeast Asian countries. If intubation and specific antivenom administration are delayed, the most significant life-threatening outcome may be the inhibition of neuromuscular transmission and subsequent respiratory failure. It is recommended that krait-envenomed victims without indications of neurotoxicity, e.g., skeletal muscle weakness or ptosis, immediately receive 10 vials of antivenom. However, the administration of excess antivenom may lead to hypersensitivity or serum sickness. Therefore, monitoring venom concentrations in patients could be used as an indicator for snake antivenom treatment. In this study, we aimed to develop a screen-printed gold electrode (SPGE) biosensor to detect B. candidus venom in experimentally envenomed rats. The gold electrodes were coated with monovalent Malayan krait IgG antivenom and used as venom detection biosensors. Electrochemical impedance spectrometry (EIS) and square wave voltammetry (SWV) measurements were performed to detect the electrical characterization between B. candidus venom and monovalent IgG antivenom in the biosensor. The EIS measurements showed increases in charge transfer resistance (Rct) following IgG immobilization and incubation with B. candidus venom solution (0.1–0.4 mg/mL); thus, the antibody was immobilized on the electrode surface and venom was successfully detected. The lowest current signal was detected by SWV measurement in rat plasma collected 30 min following B. candidus experimental envenoming, indicating the highest level of venom concentration in blood circulation (4.3 ± 0.7 µg/mL). The present study demonstrates the ability of the SPGE biosensor to detect B. candidus venom in plasma from experimentally envenomed rats. The technology obtained in this work may be developed as a detection tool for use along with the standard treatment of Malayan krait envenoming. Full article
(This article belongs to the Special Issue Pre-clinical and Clinical Management of Snakebite Envenomation)
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16 pages, 14537 KiB  
Article
Intramuscular Bleeding and Formation of Microthrombi during Skeletal Muscle Damage Caused by a Snake Venom Metalloprotease and a Cardiotoxin
by Medha Sonavane, José R. Almeida, Elanchezhian Rajan, Harry F. Williams, Felix Townsend, Elizabeth Cornish, Robert D. Mitchell, Ketan Patel and Sakthivel Vaiyapuri
Toxins 2023, 15(9), 530; https://doi.org/10.3390/toxins15090530 - 28 Aug 2023
Cited by 1 | Viewed by 2286
Abstract
The interactions between specific snake venom toxins and muscle constituents are the major cause of severe muscle damage that often result in amputations and subsequent socioeconomic ramifications for snakebite victims and/or their families. Therefore, improving our understanding of venom-induced muscle damage and determining [...] Read more.
The interactions between specific snake venom toxins and muscle constituents are the major cause of severe muscle damage that often result in amputations and subsequent socioeconomic ramifications for snakebite victims and/or their families. Therefore, improving our understanding of venom-induced muscle damage and determining the underlying mechanisms of muscle degeneration/regeneration following snakebites is critical to developing better strategies to tackle this issue. Here, we analysed intramuscular bleeding and thrombosis in muscle injuries induced by two different snake venom toxins (CAMP—Crotalus atrox metalloprotease (a PIII metalloprotease from the venom of this snake) and a three-finger toxin (CTX, a cardiotoxin from the venom of Naja pallida)). Classically, these toxins represent diverse scenarios characterised by persistent muscle damage (CAMP) and successful regeneration (CTX) following acute damage, as normally observed in envenomation by most vipers and some elapid snakes of Asian, Australasian, and African origin, respectively. Our immunohistochemical analysis confirmed that both CAMP and CTX induced extensive muscle destruction on day 5, although the effects of CTX were reversed over time. We identified the presence of fibrinogen and P-selectin exposure inside the damaged muscle sections, suggesting signs of bleeding and the formation of platelet aggregates/microthrombi in tissues, respectively. Intriguingly, CAMP causes integrin shedding but does not affect any blood clotting parameters, whereas CTX significantly extends the clotting time and has no impact on integrin shedding. The rates of fibrinogen clearance and reduction in microthrombi were greater in CTX-treated muscle compared to CAMP-treated muscle. Together, these findings reveal novel aspects of venom-induced muscle damage and highlight the relevance of haemostatic events such as bleeding and thrombosis for muscle regeneration and provide useful mechanistic insights for developing better therapeutic interventions. Full article
(This article belongs to the Special Issue Pre-clinical and Clinical Management of Snakebite Envenomation)
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Review

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14 pages, 500 KiB  
Review
Use of Antibiotics following Snakebite in the Era of Antimicrobial Stewardship
by Helena Brenes-Chacon, José María Gutiérrez and María L. Avila-Aguero
Toxins 2024, 16(1), 37; https://doi.org/10.3390/toxins16010037 - 11 Jan 2024
Viewed by 1718
Abstract
Even though there are guidelines for the management of snakebite envenoming (SBE), the use of antibiotics in this pathology remains controversial. The aim of this study is to provide a narrative review of the literature and recommendations based on the best available evidence [...] Read more.
Even though there are guidelines for the management of snakebite envenoming (SBE), the use of antibiotics in this pathology remains controversial. The aim of this study is to provide a narrative review of the literature and recommendations based on the best available evidence regarding antibiotic use in SBE. We performed a narrative review of relevant literature regarding SBE and antibiotic use as prophylaxis or treatment. A total of 26 articles were included. There is wide use of antibiotics in SBE; nevertheless, infection was not necessarily documented. The antibiotics used varied according to the study, from beta lactams to lincosamide and nitroimidazoles, and from monotherapy to combined antimicrobials. The most common recommendations were to manage skin and soft tissue infections and avoid infectious complications, but these suggestions are not necessarily based on bacteriological findings. Prophylactic use of antibiotics in SBE is discouraged in most studies. Antibiotic prescription in SBE should be based on the susceptibility of microorganisms isolated from the affected tissue or identified in snakes’ oral cavities. Antibiotics should be reserved only for patients with a demonstrated infection, or those at a high risk of developing an infection, i.e., presenting severe local envenoming, local signs of infection, or those with incorrect manipulation of wounds. Prospective studies are needed to correlate microbiological findings at the wound site and the response to antibiotic use. Full article
(This article belongs to the Special Issue Pre-clinical and Clinical Management of Snakebite Envenomation)
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