Use of Antibodies/Antivenom Against Envenoming

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

Deadline for manuscript submissions: closed (15 July 2017) | Viewed by 37156

Special Issue Editors


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Guest Editor
Monash Venom Group, Department of Pharmacology, Monash University, VIC 3800, Australia
Interests: animal venoms & toxins; receptors; pharmacology; antivenoms

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Guest Editor
Clinical Toxicology Research Group, University of Newcastle, Australia, New South Wales, Australia
Interests: clinical toxicology and clinical toxinology: toxins; venoms; antivenom; overdose; antidotes; poisoning

Special Issue Information

Dear Colleagues,

Antivenoms remain the mainstay treatment of systemic envenoming in humans following bites by a range of animals. However, there is still considerable debate about the effectiveness of some antivenoms, the correct dose and frequency of administration of antivenoms to maximise their effectiveness, as well as the ability of antivenoms to cross-neutralise the effects of venom from closely related, or even unrelated, species. There is also a lack of clarity regarding the ability of antivenoms to neutralise different classes of toxins and the timeframe for this neutralisation to occur. This Special Issue of Toxins aims to provide insight into these issues as well as provide the opportunity for exploration of emerging issues in the use and/or development of antivenoms.

Prof. Dr. Wayne Hodgson
Prof. Dr. Geoff Isbister
Guest Editors

Manuscript Submission Information

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Keywords

  • envenoming
  • antivenom
  • toxin
  • antibodies
  • neurotoxicity
  • coagulopathy
  • myotoxicity
  • cross neutralization

Published Papers (4 papers)

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Research

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2352 KiB  
Article
Third Generation Antivenomics: Pushing the Limits of the In Vitro Preclinical Assessment of Antivenoms
by Davinia Pla, Yania Rodríguez and Juan J. Calvete
Toxins 2017, 9(5), 158; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins9050158 - 10 May 2017
Cited by 46 | Viewed by 5478
Abstract
Second generation antivenomics is a translational venomics approach designed to complement in vivo preclinical neutralization assays. It provides qualitative and quantitative information on the set of homologous and heterologous venom proteins presenting antivenom-recognized epitopes and those exhibiting impaired immunoreactivity. In a situation of [...] Read more.
Second generation antivenomics is a translational venomics approach designed to complement in vivo preclinical neutralization assays. It provides qualitative and quantitative information on the set of homologous and heterologous venom proteins presenting antivenom-recognized epitopes and those exhibiting impaired immunoreactivity. In a situation of worrying antivenom shortage in many tropical and sub-tropical regions with high snakebite mortality and morbidity rates, such knowledge has the potential to facilitate the optimal deployment of currently existing antivenoms and to aid in the rational design of novel broad specificity antidotes. The aim of the present work was to expand the analytical capability of the immunoaffinity second-generation antivenomics platform, endowing it with the ability to determine the maximal binding capacity of an antivenom toward the different toxins present in a venom, and to quantify the fraction of venom-specific antibodies present in a given antivenom. The application of this new platform, termed third generation (3G) antivenomics, in the preclinical evaluation of antivenoms is illustrated in this paper for the case of antivenom EchiTAb-Plus-ICP® reactivity towards the toxins of homologous (B. arietans) and heterologous (N. melanoleuca) venoms. Full article
(This article belongs to the Special Issue Use of Antibodies/Antivenom Against Envenoming)
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Review

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1494 KiB  
Review
Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead
by José María Gutiérrez, Gabriela Solano, Davinia Pla, María Herrera, Álvaro Segura, Mariángela Vargas, Mauren Villalta, Andrés Sánchez, Libia Sanz, Bruno Lomonte, Guillermo León and Juan J. Calvete
Toxins 2017, 9(5), 163; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins9050163 - 13 May 2017
Cited by 103 | Viewed by 12642
Abstract
Animal-derived antivenoms constitute the mainstay in the therapy of snakebite envenoming. The efficacy of antivenoms to neutralize toxicity of medically-relevant snake venoms has to be demonstrated through meticulous preclinical testing before their introduction into the clinical setting. The gold standard in the preclinical [...] Read more.
Animal-derived antivenoms constitute the mainstay in the therapy of snakebite envenoming. The efficacy of antivenoms to neutralize toxicity of medically-relevant snake venoms has to be demonstrated through meticulous preclinical testing before their introduction into the clinical setting. The gold standard in the preclinical assessment and quality control of antivenoms is the neutralization of venom-induced lethality. In addition, depending on the pathophysiological profile of snake venoms, the neutralization of other toxic activities has to be evaluated, such as hemorrhagic, myotoxic, edema-forming, dermonecrotic, in vitro coagulant, and defibrinogenating effects. There is a need to develop laboratory assays to evaluate neutralization of other relevant venom activities. The concept of the 3Rs (Replacement, Reduction, and Refinement) in Toxinology is of utmost importance, and some advances have been performed in their implementation. A significant leap forward in the study of the immunological reactivity of antivenoms against venoms has been the development of “antivenomics”, which brings the analytical power of mass spectrometry to the evaluation of antivenoms. International partnerships are required to assess the preclinical efficacy of antivenoms against snake venoms in different regions of the world in order to have a detailed knowledge on the neutralizing profile of these immunotherapeutics. Full article
(This article belongs to the Special Issue Use of Antibodies/Antivenom Against Envenoming)
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762 KiB  
Review
Treatments for Latrodectism—A Systematic Review on Their Clinical Effectiveness
by Nicole M. Ryan, Nicholas A. Buckley and Andis Graudins
Toxins 2017, 9(4), 148; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins9040148 - 21 Apr 2017
Cited by 18 | Viewed by 7822
Abstract
Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results in toxic effects observed in humans. Symptoms may be incapacitating and include severe pain that can persist for days. The management of [...] Read more.
Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results in toxic effects observed in humans. Symptoms may be incapacitating and include severe pain that can persist for days. The management of mild to moderate latrodectism is primarily supportive while severe cases have variously been treated with intravenous calcium, muscle relaxants, widow-spider antivenom and analgesic opioids. The object of this systematic review is to examine the literature on the clinical effectiveness of past and current treatments for latrodectism. MEDLINE, EMBASE and Google Scholar were searched from 1946 to December 2016 to identify clinical studies on the treatment of latrodectism. Studies older than 40 years and not in English were not reviewed. There were only two full-publications and one abstract of placebo-controlled randomised trials on antivenom use for latrodectism. Another two randomised comparative trials compared the route of administration of antivenom for latrodectism. There were fourteen case series (including two abstracts), fourteen case reports and one letter investigating drug treatments for latrodectism with the majority of these also including antivenom for severe latrodectism. Antivenom with opioid analgesia is often the major treatment reported for latrodectism however; recent high quality evidence has cast doubt on the clinical effectiveness of this combination and suggests that other treatments need to be investigated. Full article
(This article belongs to the Special Issue Use of Antibodies/Antivenom Against Envenoming)
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425 KiB  
Review
Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming
by Anjana Silva, Wayne C. Hodgson and Geoffrey K. Isbister
Toxins 2017, 9(4), 143; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins9040143 - 19 Apr 2017
Cited by 36 | Viewed by 10435
Abstract
Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the [...] Read more.
Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information. We searched MEDLINE (from 1946) and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded no randomised placebo-controlled trials of antivenom for neuromuscular dysfunction. There were several randomised and non-randomised comparative trials that compared two or more doses of the same or different antivenom, and numerous cohort studies and case reports. The majority of studies available had deficiencies including poor case definition, poor study design, small sample size or no objective measures of paralysis. A number of studies demonstrated the efficacy of antivenom in human envenoming by clearing circulating venom. Studies of snakes with primarily pre-synaptic neurotoxins, such as kraits (Bungarus spp.) and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species (Naja spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this. Full article
(This article belongs to the Special Issue Use of Antibodies/Antivenom Against Envenoming)
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