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Toxins Apr 2024Snakebite envenomation (SBE) causes diverse toxic effects in humans, including disability and death. Current antivenom therapies effectively prevent death but fail to...
BACKGROUND
Snakebite envenomation (SBE) causes diverse toxic effects in humans, including disability and death. Current antivenom therapies effectively prevent death but fail to block local tissue damage, leading to an increase in the severity of envenomation; thus, seeking alternative treatments is crucial.
METHODS
This study analyzed the potential of two fucoidan sulfated polysaccharides extracted from brown seaweeds (FVF) and (UPF) against the fibrinogen or plasma coagulation, proteolytic, and phospholipase A (PLA) activities of , , and venom. The toxicity of FVF and UPF was assessed by the hemocompatibility test.
RESULTS
FVF and UPF did not lyse human red blood cells. FVF and UPF inhibited the proteolytic activity of , , and venom by approximately 25%, 50%, and 75%, respectively, while all venoms led to a 20% inhibition of PLA activity. UPF and FVF delayed plasma coagulation caused by the venoms of and but did not affect the activity of venom. FVF and UPF blocked the coagulation of fibrinogen induced by all these Bothropic venoms.
CONCLUSION
FVF and UPF may be of importance as adjuvants for SBE caused by species of , which are the most medically relevant snakebite incidents in South America, especially Brazil.
Topics: Animals; Antivenins; Blood Coagulation; Bothrops; Bothrops jararaca; Crotalid Venoms; Edible Seaweeds; Fucus; Phospholipases A2; Polysaccharides; Proteolysis; Seaweed; Undaria; Venomous Snakes
PubMed: 38668613
DOI: 10.3390/toxins16040188 -
Toxins Apr 2024In Colombia, snakebites are classified as severe according to the national clinical care guidelines and must be treated with specific antivenoms. Unfortunately, these...
In Colombia, 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 species, including , , , , , , , , and , 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') 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 venoms rich in phospholipase A (PLA) content, as observed in , , and . The effective dose 50 (ED) indicates that a single vial (10 mL) can neutralize 2.33 mg of venom and 3.99 mg of 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 species in Colombia. Additionally, it recognizes seven other species of venom with a higher affinity for venoms exhibiting PLA 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.
Topics: Animals; Antivenins; Colombia; Elapid Venoms; Mice; Snake Bites; Coral Snakes; Male
PubMed: 38668608
DOI: 10.3390/toxins16040183 -
Toxins Mar 2024Snakebite envenomation (SBE) is a public health issue in sub-Saharan countries. Antivenom is the only etiological treatment. Excellent tolerance is essential in managing...
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 Inoserp 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%) ( = 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.
Topics: Humans; Snake Bites; Antivenins; Male; Cameroon; Female; Adult; Middle Aged; Adolescent; Young Adult; Child; Aged; Child, Preschool; Aged, 80 and over; Snake Venoms; Animals; Drug Tolerance
PubMed: 38668590
DOI: 10.3390/toxins16040165 -
Toxicon : Official Journal of the... May 2024African spitting cobra, Naja nigricincta nigricincta (Zebra snake), envenomation is an important cause of snakebite morbidity and mortality in Namibia. The snake is...
Naja nigricincta nigricincta venom, a murine model. Evaluation of skeletal and cardio-myonecrosis, kidney injury and inflammatory response along with neutralisation efficacy by the SAIMR/SAVP - And EchiTAb-Plus-ICP polyvalent antivenoms.
African spitting cobra, Naja nigricincta nigricincta (Zebra snake), envenomation is an important cause of snakebite morbidity and mortality in Namibia. The snake is endemic to central and northern Namibia as well as southern Angola. The venom is mainly cytotoxic, resulting in aggressive dermo-necrosis and often accompanied by severe systemic complications. No specific antivenom exists. Rhabdomyolysis, systemic inflammatory response, haemostatic abnormalities, infective necrotising fasciitis as well as acute kidney failure have been documented. Based on murine models, this study assessed SAVP/SAIMR - and EchiTAb-Plus-ICP polyvalent antivenom neutralisation as well as subdermal necrosis. Additional muscle, cardiac, kidney and lung histology, creatine kinase measurements and post-mortems were performed. An intravenous median lethal dose (LD50) of Naja nigricincta nigricincta venom was determined at 18.4 (CI: 16.3; 20.52) μg and a subdermal lethal dose at 15.3(CI: 12.96; 17.74)μg. The SAIMR/SAVP polyvalent antivenom median effective dose (ED50) was 1.2 ml antivenom/1 mg venom equating to a potency (WHO) of 1 ml antivenom neutralising 0.63 mg venom and approximately 240 ml (24 vials) needed for initial treatment. The ED50 of the EchiTAb-Plus-ICP was 1 ml antivenom/1 mg venom and a potency of 65 mg venom/ml antivenom (3.3 x LD), estimating 230 ml (23 vials) for treatment. Histology and serology (creatine kinase) evidenced venom induced skeletal myotoxicity, which was not prevented by the antivenoms tested. Cardiac myonecrosis, an inflammatory response, direct venom kidney tubular necrosis and cardio-pulmonary failure were documented.
Topics: Animals; Antivenins; Mice; Elapid Venoms; Snake Bites; Necrosis; Disease Models, Animal; Muscle, Skeletal; Inflammation; Lethal Dose 50; Naja; Male; Creatine Kinase; Kidney
PubMed: 38631492
DOI: 10.1016/j.toxicon.2024.107719 -
Italian Journal of Pediatrics Apr 2024Bites caused by European vipers are rare medical emergencies but can occasionally cause life-threatening complications. Viper venom causes local symptoms, which can be...
BACKGROUND
Bites caused by European vipers are rare medical emergencies but can occasionally cause life-threatening complications. Viper venom causes local symptoms, which can be accompanied by systemic manifestations in severe cases. The local effects of snakebites include edema and, more rarely, necrosis and compartment syndrome. The consequences of envenomation are often more pronounced in children due to their smaller body size.
CASE PRESENTATION
We present the case of a 6-year-old girl who experienced multiple viper bites in the lower limb in northwest Italy. The girl received supportive care but progressed to develop compartment syndrome that required emergency fasciotomy. The patient's condition improved promptly after surgical decompression and administration of antivenom, but full recovery required prolonged hospitalization and rehabilitation.
CONCLUSIONS
This case highlights the importance of obtaining a timely assessment of the severity of viper envenomation without delaying the administration of antivenom in most serious cases. The presence of multiple bite marks on the patient is one factor that may help to predict the clinical severity of snakebites and anticipate symptom progression.
Topics: Child; Female; Humans; Antivenins; Compartment Syndromes; Fasciotomy; Italy; Snake Bites
PubMed: 38627836
DOI: 10.1186/s13052-024-01638-5 -
Journal of Tropical Medicine 2024Snakebite envenomation (SBE) constitutes a public health, social, and economic problem affecting poor communities in intertropical and subtropical regions. This review... (Review)
Review
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 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.
PubMed: 38623180
DOI: 10.1155/2024/8357312 -
PLoS Neglected Tropical Diseases Apr 2024
Topics: Animals; Antivenins; Bungarus; Snake Bites; Bungarotoxins; Asia, Southeastern
PubMed: 38603643
DOI: 10.1371/journal.pntd.0012079 -
PLoS Neglected Tropical Diseases Apr 2024Snakebite envenoming represents a significant and often neglected public health challenge, particularly in rural communities across tropical and subtropical regions. An... (Meta-Analysis)
Meta-Analysis
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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.
Topics: Male; Humans; Female; Snake Bites; Antivenins; Incidence; Asia; Prevalence
PubMed: 38574167
DOI: 10.1371/journal.pntd.0012080 -
PLoS Neglected Tropical Diseases Apr 2024Intraspecific variations in snake venom composition have been extensively documented, contributing to the diverse clinical effects observed in envenomed patients....
BACKGROUND
Intraspecific variations in snake venom composition have been extensively documented, contributing to the diverse clinical effects observed in envenomed patients. Understanding these variations is essential for developing effective snakebite management strategies and targeted antivenom therapies. We aimed to comprehensively investigate venoms from three distinct populations of N. mossambica from Eswatini, Limpopo, and KwaZulu-Natal regions in Africa in terms of their protein composition and reactivity with three commercial antivenoms (SAIMR polyvalent, EchiTAb+ICP, and Antivipmyn Africa).
METHODOLOGY/PRINCIPAL FINDINGS
Naja mossambica venoms from Eswatini region exhibited the highest content of neurotoxic proteins, constituting 20.70% of all venom proteins, compared to Limpopo (13.91%) and KwaZulu-Natal (12.80%), and was characterized by the highest diversity of neurotoxic proteins, including neurotoxic 3FTxs, Kunitz-type inhibitors, vespryns, and mamba intestinal toxin 1. KwaZulu-Natal population exhibited considerably lower cytotoxic 3FTx, higher PLA2 content, and significant diversity in low-abundant proteins. Conversely, Limpopo venoms demonstrated the least diversity as demonstrated by electrophoretic and mass spectrometry analyses. Immunochemical assessments unveiled differences in venom-antivenom reactivity, particularly concerning low-abundance proteins. EchiTAb+ICP antivenom demonstrated superior reactivity in serial dilution ELISA assays compared to SAIMR polyvalent.
CONCLUSIONS/SIGNIFICANCE
Our findings reveal a substantial presence of neurotoxic proteins in N. mossambica venoms, challenging previous understandings of their composition. Additionally, the detection of numerous peptides aligning to uncharacterized proteins or proteins with unknown functions underscores a critical issue with existing venom protein databases, emphasizing the substantial gaps in our knowledge of snake venom protein components. This underscores the need for enhanced research in this domain. Moreover, our in vitro immunological assays suggest EchiTAb+ICP's potential as an alternative to SAIMR antivenom, requiring confirmation through prospective in vivo neutralization studies.
Topics: Animals; Humans; Antivenins; Naja; Proteomics; Prospective Studies; South Africa; Elapid Venoms; Proteins
PubMed: 38557658
DOI: 10.1371/journal.pntd.0012057 -
Biomolecules Feb 2024Viperid snake venoms induce severe tissue damage, characterized by the direct toxic action of venom components, i.e., phospholipases A (PLAs) and metalloproteinases...
Viperid snake venoms induce severe tissue damage, characterized by the direct toxic action of venom components, i.e., phospholipases A (PLAs) and metalloproteinases (SVMPs), concomitantly with the onset of endogenous inflammatory processes, in an intricate scenario of tissue alterations. Understanding the expression of relevant genes in muscle tissue will provide valuable insights into the undergoing pathological and inflammatory processes. In this study, we have used the Nanostring technology to evaluate the patterns of gene expression in mouse skeletal muscle 1 h, 6 h, and 24 h after injection of the venoms of and , two medically relevant species in Latin America and Asia, respectively, with somewhat different clinical manifestations. The dose of venoms injected (30 µg) induced local pathological effects and inflammation in muscle tissue. We focused our analysis on genes related to extracellular matrix (ECM) metabolism, immune system, programmed cell death, and autophagy. The results revealed a complex pattern of expression of genes. Regarding ECM metabolism and regulation, up-regulated genes included proteinase inhibitor Serpine 1, thrombospondin 1, collagens 1A1 and 4A1 (at 1 h in the case of ), TIMP1, MMP-3 (at 24 h), and lysil oxidase (LOX). In contrast, collagen chains 5A3 and 5A1 were down-regulated, especially at 6 h. Transforming growth factor β (TGF-β) and several genes related to myofibroblast regulation were also up-regulated, which might be related to the development of fibrosis. Several genes related to cytokine and chemokine synthesis and regulation and NFκB signaling were also up-regulated. Our observations show a variable expression of genes associated with programmed cell death and autophagy, thus revealing a hitherto unknown role of autophagy in tissue affected by snake venoms. These results provide clues to understanding the complex pattern of gene expression in tissue affected by viperid snake venoms, which likely impacts the final pathophysiology of damaged tissue in envenomings.
Topics: Animals; Mice; Antivenins; Snake Bites; Snake Venoms; Crotalid Venoms; Muscles; Collagen
PubMed: 38540699
DOI: 10.3390/biom14030278