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Toxins Sep 2022Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom,... (Review)
Review
Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom, which is composed of immunoglobulins or immunoglobulin fragments obtained from the plasma of animals hyperimmunized with one (monospecific) or several (polyspecific) venoms. In this review, the efforts made in the improvement of the already available antivenoms and the development of new antivenoms, focusing on snakes of medical importance from sub-Saharan Africa and Latin America, are described. Some antivenoms currently used are composed of whole IgGs, whereas others use F(ab')2 fragments. The classic methods of attaining snake antivenoms are presented, in addition to new strategies to improve their effectiveness. Punctual changes in immunization protocols, in addition to the use of cross-reactivity between venoms from different snakes for the manufacture of more potent and widely used antivenoms, are presented. It is known that venoms are a complex mixture of components; however, advances in the field of antivenoms have shown that there are key toxins that, if effectively blocked, are capable of reversing the condition of in vivo envenomation. These studies provide an opportunity for the use of monoclonal antibodies in the development of new-generation antivenoms. Thus, monoclonal antibodies and their fragments are described as a possible alternative for the production of antivenoms, regardless of the venom. This review also highlights the challenges associated with their development.
Topics: Animals; Antibodies, Monoclonal; Antivenins; Humans; Immunoglobulin Fragments; Snake Bites; Snakes
PubMed: 36136544
DOI: 10.3390/toxins14090606 -
Revista Da Sociedade Brasileira de... 2015Scorpion stings are currently the leading cause of venom-related injury to humans in Brazil and are a significant public health problem globally. Only scorpions of the... (Review)
Review
Scorpion stings are currently the leading cause of venom-related injury to humans in Brazil and are a significant public health problem globally. Only scorpions of the Tityus genus are of medical importance in Brazil, and Tityus serrulatus is responsible for the most serious envenomations and deaths. The toxic effects of scorpion envenomation are due to a massive release of sympathetic and parasympathetic neurotransmitters; the severity is related to cardiac and hemodynamic changes, with cardiogenic shock and pulmonary edema contributing to the main causes of death. The pathophysiology of cardiac involvement has been discussed for decades and has been attributed to adrenergic discharge and a possible toxic effect of venom on the myocardium, while acute pulmonary edema may have a cardiogenic and/or non-cardiogenic origin. Currently, the clinical data point to catecholamine excess as the cause for reversible scorpion cardiomyopathy . These data include electrocardiographic changes, profiling of cardiac enzymes and troponin I, echocardiographic data with global or regional left ventricle dysfunction, and myocardial perfusion alterations compatible with spasm in the coronary microcirculation. Furthermore, recent data on cardiac magnetic resonance imaging findings, which are similar to those observed for stress-induced cardiomyopathy, have also been linked to catecholamine excess. The efficiency of antivenom serum treatment is controversial in the literature. Our experience in Brazil is that the management of patients with systemic manifestations of scorpion stings is based on three approaches, all of which are extremely important. These include symptomatic treatment, antivenom serum, and cardiorespiratory support.
Topics: Animals; Antivenins; Brazil; Humans; Prognosis; Scorpion Stings; Scorpion Venoms; Severity of Illness Index
PubMed: 26676487
DOI: 10.1590/0037-8682-0237-2015 -
Toxins Sep 2018Diagnostic tests for arachnid accidents remain unavailable for patients and clinicians. Together with snakes, these accidents are still a global medical concern, and are... (Review)
Review
Diagnostic tests for arachnid accidents remain unavailable for patients and clinicians. Together with snakes, these accidents are still a global medical concern, and are recognized as neglected tropical issues. Due to arachnid toxins' fast mechanism of action, quick detection and quantification of venom is required to accelerate treatment decisions, rationalize therapy, and reduce costs and patient risks. This review aims to understand the current limitations for arachnid venom identification and quantification in biological samples. We benchmarked the already existing initiatives regarding test requirements (sample or biomarkers of choice), performances (time, detection limit, sensitivity and specificity) and their validation (on animal models or on samples from envenomed humans). Our analysis outlines unmet needs for improving diagnosis and consequently treatment of arachnid accidents. Hence, based on lessons from past attempts, we propose a road map for raising best practice guidelines, leading to recommendations for future progress in the development of arachnid diagnostic assays.
Topics: Animals; Antivenins; Biological Assay; Diagnostic Tests, Routine; Humans; Spider Bites; Spider Venoms
PubMed: 30201918
DOI: 10.3390/toxins10090365 -
PLoS Neglected Tropical Diseases Nov 2020Bungarus multicinctus is the most venomous snake distributed in China and neighboring countries of Myanmar, Laos, north Vietnam and Thailand. The high mortality rate of...
Immunoreactivity and neutralization study of Chinese Bungarus multicinctus antivenin and lab-prepared anti-bungarotoxin antisera towards purified bungarotoxins and snake venoms.
Bungarus multicinctus is the most venomous snake distributed in China and neighboring countries of Myanmar, Laos, north Vietnam and Thailand. The high mortality rate of B. multicinctus envenomation is attributed to the lethal components of α-, β-, γ- and κ- bungarotoxins contained in the venom. Although anti-B. multicinctus sera were produced in Shanghai, Taiwan and Vietnam, the most widely clinic used product was term as B. multicinctus antivenin and manufactured by Shanghai Serum Bio-technology Co. Ltd. In the present investigation, high purity α-, β- and γ-bungarotoxins were separately isolated from B. multicinctus crude venom. Rabbit anti- α-, β- and γ-bungarotoxin antisera were prepared by common methods, respectively. LD50 values of α-, β- and γ-bungarotoxins were systematically determined via three administration pathways (intraperitoneal, intramuscular and intravenous injections) in Kunming mice. LD50 values of β-bungarotoxin were closely related with injection routines but those of both α- and γ-bungarotoxins were not dependent on the injection routines. Commercial B. multicinctus antivenin showed strong immunoreaction with high molecular weight fractions of the B. multicinctus but weakly recognized low molecular weight fractions like α- and γ-bungarotoxins. Although B. multicinctus antivenin showed immunoreaction with high molecular weight fractions of Bungarus fasciatus, Naja atra, Ophiophagus hannah venoms but the antivenin only demonstrated animal protection efficacy against O. hannah venom. These results indicated that the high molecular weight fractions of the O. hannah played an important role in venom lethality but those of B. fasciatus and N. atra did not have such a role.
Topics: Animals; Antivenins; Bungarotoxins; Bungarus; China; Elapid Venoms; Immune Sera; Lethal Dose 50; Male; Mice; Neutralization Tests; Ophiophagus hannah; Rabbits
PubMed: 33253321
DOI: 10.1371/journal.pntd.0008873 -
FEBS Letters Jun 2009Venoms comprise mixtures of peptides and proteins tailored by Natural Selection to act on vital systems of the prey or victim. Here we review our proteomic protocols for... (Review)
Review
Venoms comprise mixtures of peptides and proteins tailored by Natural Selection to act on vital systems of the prey or victim. Here we review our proteomic protocols for uncoiling the composition, immunological profile, and evolution of snake venoms. Our long-term goal is to gain a deep insight of all viperid venom proteomes. Knowledge of the inter- and intraspecies ontogenetic, individual, and geographic venom variability has applied importance for the design of immunization protocols aimed at producing more effective polyspecific antivenoms. A practical consequence of assessing the cross-reactivity of heterologous antivenoms is the possibility of circumventing the restricted availability of species-specific antivenoms in some regions. Further, the high degree of target specificity makes toxins valuable scaffolds for drug development.
Topics: Antivenins; Chromatography, High Pressure Liquid; Electrophoresis, Polyacrylamide Gel; Proteomics; Snake Venoms
PubMed: 19303875
DOI: 10.1016/j.febslet.2009.03.029 -
The American Journal of Tropical... May 2024
Topics: Humans; Anti-Bacterial Agents; Snake Bites; Antibiotic Prophylaxis; Animals; Antivenins
PubMed: 38507806
DOI: 10.4269/ajtmh.24-0033 -
Toxins Jun 2023Envenomations induced by animal bites and stings constitute a significant public health burden. Even though a standardized protocol does not exist, parenterally... (Review)
Review
Envenomations induced by animal bites and stings constitute a significant public health burden. Even though a standardized protocol does not exist, parenterally administered polyclonal antivenoms remain the mainstay in snakebite therapy. There is a prevailing opinion that their application by the route has poor efficacy and that administration should preferentially be chosen in order to achieve better accomplishment of the antivenom therapeutic activity. Recently, it has been demonstrated that neutralization not only in the systemic circulation but also in the lymphatic system might be of great importance for the clinical outcome since it represents another relevant body compartment through which the absorption of the venom components occurs. In this review, the present-day and summarized knowledge of the laboratory and clinical findings on the and routes of antivenom administration is provided, with a special emphasis on the contribution of the lymphatic system to the process of venom elimination. Until now, antivenom-mediated neutralization has not yet been discussed in the context of the synergistic action of both blood and lymph. A current viewpoint might help to improve the comprehension of the venom/antivenom pharmacokinetics and the optimal approach for drug application. There is a great need for additional dependable, practical, well-designed studies, as well as more practice-related experience reports. As a result, opportunities for resolving long-standing disputes over choosing one therapeutic principle over another might be created, improving the safety and effectiveness of snakebite management.
Topics: Animals; Antivenins; Snake Bites; Elapid Venoms; Snakes; Snake Venoms
PubMed: 37368699
DOI: 10.3390/toxins15060398 -
Molecules (Basel, Switzerland) Sep 2019Snakebite envenomation is a life-threatening disease that was recently re-included as a neglected tropical disease (NTD), affecting millions of people in tropical and... (Review)
Review
Snakebite envenomation is a life-threatening disease that was recently re-included as a neglected tropical disease (NTD), affecting millions of people in tropical and subtropical areas of the world. Improvement in the therapeutic approaches to envenomation is required to palliate the morbidity and mortality effects of this NTD. The specific therapeutic treatment for this NTD uses snake antivenom immunoglobulins. Unfortunately, access to these vital drugs is limited, principally due to their cost. Different ethnic groups in the affected regions have achieved notable success in treatment for centuries using natural sources, especially plants, to mitigate the effects of snake envenomation. The ethnopharmacological approach is essential to identify the potential metabolites or derivatives needed to treat this important NTD. Here, the authors describe specific therapeutic snakebite envenomation treatments and conduct a review on different strategies to identify the potential agents that can mitigate the effects of the venoms. The study also covers an increased number of literature reports on the ability of natural sources, particularly plants, to treat snakebites, along with their mechanisms, drawbacks and future perspectives.
Topics: Animals; Antivenins; Ethnopharmacology; Humans; Snake Bites; Snake Venoms; Snakes
PubMed: 31505752
DOI: 10.3390/molecules24183276 -
Toxins Apr 2017Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results... (Review)
Review
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.
Topics: Animals; Antivenins; Humans; Spider Bites; Treatment Outcome
PubMed: 28430165
DOI: 10.3390/toxins9040148 -
International Journal of Molecular... Nov 2023In many animals belonging to different taxa, venoms evolved as a means of defense and/or a means of attack/hunting [...].
In many animals belonging to different taxa, venoms evolved as a means of defense and/or a means of attack/hunting [...].
Topics: Animals; Antivenins; Toxins, Biological; Crotalid Venoms
PubMed: 38003582
DOI: 10.3390/ijms242216389