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

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 24882

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Special Issue Editors

Dr. Chih-Chuan Lin

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Guest Editor

Department of Emergency Medicine Chang Gung Memorial Hospital and Chang Gung University Taiwan, Taoyuan, Taiwan
Interests: snakebites; antivenom; snakebite diagnosis and treatment

Dr. Yen-Chia Chen

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Guest Editor

Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
Interests: snakebite; venom; envenoming; antivenom; first aid

Dr. Rittirak Othong

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Guest Editor

Department of Emergency Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
Interests: snakebite; green pit viper envenomation; centipede bite; exotic snakebite; drug induced QT prolongation; drug induced torsade de pointes

Special Issue Information

Dear Colleagues,

Any article regarding snakebite and clinically relevant is welcomed.

Snakebite is a major neglected tropical disease and the global snakebite burden is huge, with the highest rates of snakebite envenomation and death occurring in South Asia, Southeast Asia, and sub-Saharan Africa. For example, India reports 81,000 snake envenomation cases with nearly 11,000 deaths each year. Although antivenoms were developed to treat snakebite patients, mortality or profound morbidity remain an issue. Developing novel strategies for the clinical diagnosis, treatment, or prediction of patients’ prognosis in the event of snakebites may provide better care for snakebite patients.

This Special Issue aims to publish original research articles, reviews, and short communications in the broad area of snakebites and clinical toxicology research. Since Toxins is a well-known journal in this field, we strongly believe that the articles published in this issue will reach a wide audience and aid in the development of better diagnostic and therapeutic strategies for snakebites.

Dr. Chih-Chuan Lin
Dr. Yen-Chia Chen
Dr. Rittirak Othong
Guest Editors

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Keywords

snakebite
snake
venom
diagnostic test for snakebites
antivenom
treatment for snakebite
prognosis

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Published Papers (9 papers)

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Research

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9 pages, 1445 KiB

Open AccessArticle

Comparative Analysis of Alpha-1 Orthosteric-Site Binding by a Clade of Central American Pit Vipers (Genera Atropoides, Cerrophidion, Metlapilcoatlus, and Porthidium)

by Lee Jones, Callum Waite, Edgar Neri-Castro and Bryan G. Fry

Toxins 2023, 15(8), 487; https://doi.org/10.3390/toxins15080487 - 2 Aug 2023

Cited by 1 | Viewed by 1321

Abstract

The distribution and relative potency of post-synaptic neurotoxic activity within Crotalinae venoms has been the subject of less investigation in comparison with Elapidae snake venoms. No previous studies have investigated post-synaptic neurotoxic activity within the Atropoides, Metlapilcoatlus, Cerrophidion, and Porthidium clade. Given the specificity of neurotoxins to relevant prey types, we aimed to uncover any activity present within this clade of snakes that may have been overlooked due to lower potency upon humans and thus not appearing as a clinical feature. Using biolayer interferometry, we assessed the relative binding of crude venoms to amphibian, lizard, bird, rodent and human α-1 nAChR orthosteric sites. We report potent alpha-1 orthosteric site binding in venoms from Atropoides picadoi, Metlapilcoatlus occiduus, M. olmec, M. mexicanus, M. nummifer. Lower levels of binding, but still notable, were evident for Cerrophidion godmani, C. tzotzilorum and C. wilsoni venoms. No activity was observed for Porthidium venoms, which is consistent with significant alpha-1 orthosteric site neurotoxicity being a trait that was amplified in the last common ancestor of Atropoides/Cerrophidion/Metlapilcoatlus subsequent to the split by Porthidium. We also observed potent taxon-selective activity, with strong selection for non-mammalian targets (amphibian, lizard, and bird). As these are poorly studied snakes, much of what is known about them is from clinical reports. The lack of affinity towards mammalian targets may explain the knowledge gap in neurotoxic activity within these species, since symptoms would not appear in bite reports. This study reports novel venom activity, which was previously unreported, indicating toxins that bind to post-synaptic receptors may be more widespread in pit vipers than previously considered. While these effects appear to not be clinically significant due to lineage-specific effects, they are of significant evolutionary novelty and of biodiscovery interest. This work sets the stage for future research directions, such as the use of in vitro and in vivo models to determine whether the alpha-1 orthosteric site binding observed within this study confers neurotoxic venom activity. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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16 pages, 1941 KiB

Open AccessArticle

Children and Snakebite: Snake Venom Effects on Adult and Paediatric Plasma

by Christina N. Zdenek, Caroline F. B. Rodrigues, Lachlan A. Bourke, Anita Mitico Tanaka-Azevedo, Paul Monagle and Bryan G. Fry

Toxins 2023, 15(2), 158; https://doi.org/10.3390/toxins15020158 - 14 Feb 2023

Cited by 6 | Viewed by 3816

Abstract

Snakebite is a globally neglected tropical disease, with coagulation disturbances being the primary pathology of many deadly snake venoms. Age-related differences in human plasma have been abundantly reported, yet the effect that these differences pose regarding snakebite is largely unknown. We tested for differences in coagulotoxic effects (via clotting time) of multiple snake venoms upon healthy human adult (18+) and paediatric (median 3.3 years old) plasma in vivo and compared these effects to the time it takes the plasmas to clot without the addition of venom (the spontaneous clotting time). We tested venoms from 15 medically significant snake species (from 13 genera) from around the world with various mechanisms of coagulotoxic actions, across the three broad categories of procoagulant, pseudo-procoagulant, and anticoagulant, to identify any differences between the two plasmas in their relative pathophysiological vulnerability to snakebite. One procoagulant venom (Daboia russelii, Russell’s Viper) produced significantly greater potency on paediatric plasma compared with adult plasma. In contrast, the two anticoagulant venoms (Pseudechis australis, Mulga Snake; and Bitis cornuta, Many-horned Adder) were significantly more potent on adult plasma. All other procoagulant venoms and all pseudo-procoagulant venoms displayed similar potency across both plasmas. Our preliminary results may inform future studies on the effect of snake venoms upon plasmas from different age demographics and hope to reduce the burden of snakebite upon society. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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13 pages, 1201 KiB

Open AccessArticle

Green Pit Viper Envenomations in Bangkok: A Comparison of Follow-Up Compliance and Clinical Outcomes in Older and Younger Adults

by Rittirak Othong, Thanaphat Eurcherdkul and Prasit Chantawatsharakorn

Toxins 2022, 14(12), 869; https://doi.org/10.3390/toxins14120869 - 10 Dec 2022

Cited by 2 | Viewed by 2496

Abstract

We compared older and younger adults envenomated by the green pit viper (GPV) with regard to the following: follow-up compliance, elapsed time between envenomation and emergency department (ED) visit, and clinical/treatment outcomes. This was a two-site retrospective cohort study. We searched hospital electronic medical databases between January 2011 and December 2021. Patients aged 15 and above were eligible if they had a history of snakebite and had at least two VCT and/or platelet count results in their medical records. After the search, 1550 medical records were reviewed and 760 cases were found to be eligible for analysis. In total, 205 cases (27.0%) were ≥60 years old. The median ages in the younger and older groups were 40 (26–51) and 68 (64–75) years, respectively. The median elapsed times from bite to the ED were 47 (30–118) vs. 69 (35–150) min (p-value = 0.001). Overall, 91.3% of all cases were managed as out-patient cases and were eligible for follow-up appointments. The rate of out-patient follow-up at 72 ± 12 h in the older patients was significantly higher (43.2%) than in the younger adult patients (32.4%) (p-value = 0.01). Regarding the clinical/treatment outcomes, the rates of coagulopathy, antivenom administration, and hospital admission were not statistically different between both groups. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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13 pages, 837 KiB

Open AccessArticle

The Clinical Usefulness of Taiwan Bivalent Freeze-Dried Hemorrhagic Antivenom in Protobothrops mucrosquamatus- and Viridovipera stejnegeri-Envenomed Patients

by Chih-Chuan Lin, Chia-Pang Shih, Chia-Cheng Wang, Chun-Hsiang Ouyang, Chien-Chun Liu, Jau-Song Yu and Chih-Hong Lo

Toxins 2022, 14(11), 794; https://doi.org/10.3390/toxins14110794 - 15 Nov 2022

Cited by 5 | Viewed by 1842

Abstract

Snakebites from Protobothrops mucrosquamatus (Taiwan habus) and Viridovipera stejnegeri (green bamboo vipers) account for the most venomous snakebites in Taiwan. The bivalent freeze-dried hemorrhagic (FH) antivenom is employed to treat these two snakebite patients without a strict clinical trial. We evaluated the clinical usefulness of Taiwan bivalent freeze-dried hemorrhagic (FH) antivenom in Taiwan habu- and green bamboo viper-envenomed patients. We checked ELISA- based serum venom antigen levels before and after FH antivenom to evaluate FH’s ability to neutralize patients’ serum snake venom and its usefulness in reducing limb swelling after snakebites. Patients who had higher serum venom antigen levels had more severe limb swelling. Of the 33 enrolled patients, most of their snake venom antigen levels were undetected after the appliance of antivenom. Most enrolled patients (25/33) had their limb swelling subside within 12 h after antivenom treatment. The failure to reduce limb swelling was probably due to an inadequate antivenom dose applied in more severely envenomated patients. Our data indicate the feasibility of the FH antivenom in effectively eliminating venom and resolving the affected limb swelling caused by Taiwan habu and green bamboo viper bites. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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11 pages, 978 KiB

Open AccessEditor’s ChoiceArticle

Bites by Non-Native Reptiles in France: Species, Circumstances and Outcome

by Gaël Le Roux, Guillaume Grenet, Corinne Schmitt, French Poison Control Centers Research Group, Sébastien Larréché and Alexis Descatha

Toxins 2022, 14(8), 570; https://doi.org/10.3390/toxins14080570 - 20 Aug 2022

Cited by 3 | Viewed by 2118

Abstract

We aimed to make an exhaustive assessment of circumstances of bites by exotic reptiles bred in France. A retrospective observational study was conducted in all the reported cases from 2000 to 2020 in French poison control centers (PCCs). Two hundred and eighteen cases of bites were recorded. The sex ratio (M/F) of the patients was 1.79 and the mean age of the patients was 29.0 ± 15.8 years. Twenty-two cases (10.1%) occurred during the deep night. One hundred and eighty-six bites (85.7%) occurred in a private context; however, there were more cases of high severity when it occurred in a professional setting (60.0% vs. 11.2%, p < 0.01). The feeding/nursing activity accounted for 54.7% cases. Forty-three species of snake were identified; 28 were considered venomous. There were no deaths among the patients in the study. Most of the cases (85.8%) were of mild severity. All of the patients bitten by a venomous reptile were hospitalized: 10 patients received an antivenom; and 2 required surgery. Bites occurred at home and by a small number of popular non-venomous reptile species (pythons and boas, colubrids). These occurred mainly when handling the animals. The rare envenomations were mainly by Asian and American crotalids, followed by elapids. One-third of them were treated with antivenom when available. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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12 pages, 1171 KiB

Open AccessArticle

Fibrinogenolysis in Venom-Induced Consumption Coagulopathy after Viperidae Snakebites: A Pilot Study

by Jiri Valenta, Alzbeta Hlavackova, Zdenek Stach, Jana Stikarova, Marek Havlicek and Pavel Michalek

Toxins 2022, 14(8), 538; https://doi.org/10.3390/toxins14080538 - 6 Aug 2022

Cited by 3 | Viewed by 2386

Abstract

Envenomations that are caused by Viperidae snakebites are mostly accompanied by venom-induced consumption coagulopathy (VICC) with defibrination. The clinical course of VICC is well described; however, reports about its detailed effects in the hemocoagulation systems of patients are sparse. In this pilot study, we prospectively analyzed the changes in plasma fibrinogen that were caused by the envenomation of six patients by five non-European Viperidae snakes. Western blot analysis was employed and fibrinogen fragments were visualized with the use of specific anti-human fibrinogen antibodies. All of the studied subjects experienced hypo- or afibrinogenemia. The western blot analysis demonstrated fibrinogenolysis of the fibrinogen chains in all of the cases. Fibrinogenolysis was considered to be a predominant cause of defibrination in Crotalus, Echis, and Macrovipera envenomation; while, in the cases of VICC that were caused by Atheris and Calloselasma envenomation, the splitting of the fibrinogen chains was present less significantly. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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17 pages, 3256 KiB

Open AccessArticle

Equatorial Spitting Cobra (Naja sumatrana) from Malaysia (Negeri Sembilan and Penang), Southern Thailand, and Sumatra: Comparative Venom Proteomics, Immunoreactivity and Cross-Neutralization by Antivenom

by Choo Hock Tan, Kae Yi Tan, Kin Ying Wong, Nget Hong Tan and Ho Phin Chong

Toxins 2022, 14(8), 522; https://doi.org/10.3390/toxins14080522 - 29 Jul 2022

Cited by 8 | Viewed by 3739

Abstract

The Equatorial Spitting Cobra (Naja sumatrana) is a medically important venomous snake species in Southeast Asia. Its wide geographical distribution implies potential intra-specific venom variation, while there is no species-specific antivenom available to treat its envenoming. Applying a protein-decomplexing proteomic approach, the study showed that three-finger toxins (3FTX), followed by phospholipases A₂ (PLA₂), were the major proteins well-conserved across N. sumatrana venoms of different locales. Variations were noted in the subtypes and relative abundances of venom proteins. Of note, alpha-neurotoxins (belonging to 3FTX) are the least in the Penang specimen (Ns-PG, 5.41% of total venom proteins), compared with geographical specimens from Negeri Sembilan (Ns-NS, 14.84%), southern Thailand (Ns-TH, 16.05%) and Sumatra (Ns-SU, 10.81%). The alpha-neurotoxin abundance, in general, correlates with the venom’s lethal potency. The Thai Naja kaouthia Monovalent Antivenom (NkMAV) was found to be immunoreactive toward the N. sumatrana venoms and is capable of cross-neutralizing N. sumatrana venom lethality to varying degrees (potency = 0.49–0.92 mg/mL, interpreted as the amount of venom completely neutralized per milliliter of antivenom). The potency was lowest against NS-SU venom, implying variable antigenicity of its lethal alpha-neurotoxins. Together, the findings suggest the para-specific and geographical utility of NkMAV as treatment for N. sumatrana envenoming in Southeast Asia. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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13 pages, 2280 KiB

Open AccessEditor’s ChoiceArticle

Development of a Monoclonal scFv against Cytotoxin to Neutralize Cytolytic Activity Induced by Naja atra Venom on Myoblast C2C12 Cells

by Chien-Chun Liu, Cho-Ju Wu, Tsai-Ying Chou, Geng-Wang Liaw, Yung-Chin Hsiao, Lichieh-Julie Chu, Chi-Hsin Lee, Po-Jung Wang, Cheng-Hsien Hsieh, Chun-Kuei Chen and Jau-Song Yu

Toxins 2022, 14(7), 459; https://doi.org/10.3390/toxins14070459 - 4 Jul 2022

Cited by 8 | Viewed by 2182

Abstract

The Taiwanese cobra, Naja atra, is a clinically significant species of snake observed in the wild in Taiwan. Victims bitten by N. atra usually experience severe pain and local tissue necrosis. Although antivenom is available for treatment of cobra envenomation, its neutralization potency against cobra-induced necrosis is weak, with more than 60% of cobra envenoming patients developing tissue necrosis after antivenom administration. The present study found that cytotoxin (CTX) is a key component of N. atra venom responsible for cytotoxicity against myoblast cells. Anti-CTX IgY was generated in hens, and the spleens of these hens were used to construct libraries for the development of single chain variable fragments (scFv). Two anti-CTX scFv, S1 and 2S7, were selected using phage display technology and biopanning. Both polyclonal IgY and monoclonal scFv S1 reacted specifically with CTX in cobra venom. In a cell model assay, the CTX-induced cytolytic effect was inhibited only by monoclonal scFv S1, not by polyclonal IgY. Moreover, the neutralization potency of scFv S1 was about 3.8 mg/mg, approximately three times higher than that of conventional freeze-dried neurotoxic antivenom (FNAV). Collectively, these results suggest that scFv S1 can effectively neutralize CTX-induced cytotoxicity and, when combined with currently available antivenom, can improve the potency of the latter, thereby preventing tissue damage induced by cobra envenoming. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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Review

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13 pages, 856 KiB

Open AccessReview

Antibodies as Snakebite Antivenoms: Past and Future

by Wilmar Dias da Silva, Sonia A. De Andrade, Ângela Alice Amadeu Megale, Daniel Alexandre De Souza, Osvaldo Augusto Sant’Anna, Fábio Carlos Magnoli, Felipe Raimondi Guidolin, Kemily Stephanie Godoi, Lucas Yuri Saladini, Patrick Jack Spencer and Fernanda Calheta Vieira Portaro

Toxins 2022, 14(9), 606; https://doi.org/10.3390/toxins14090606 - 1 Sep 2022

Cited by 13 | Viewed by 3635

Abstract

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. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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