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Shewale AD, Mishra D, Tiwari S, Nale TN, Kuwatada J, Khandelwal N. Implementing Interventions Under "National Action Plan for Snakebite Envenoming (NAPSE) in India": Challenges, Lessons Learnt and Way Forward for Stakeholders Participatory Approach. Trop Med Infect Dis 2025; 10:132. [PMID: 40423362 DOI: 10.3390/tropicalmed10050132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/15/2025] [Accepted: 04/30/2025] [Indexed: 05/28/2025] Open
Abstract
Snakebite envenoming remains a critical yet underrecognized public health issue, particularly in tropical and subtropical regions, with India bearing nearly half of the global burden of snakebite-related deaths. Despite its significant impact, underreporting, delayed medical intervention, and insufficiently trained healthcare professionals continue to exacerbate the problem. In response, the Government of India launched the National Action Plan for Prevention and Control of Snakebite Envenoming (NAPSE) in March 2024, aiming to halve snakebite-related deaths by 2030. Key challenges during the development and implementation of NAPSE included the limited multisectoral engagement initially, variations in state-level capacities, and logistical barriers in reaching remote populations. Lessons learned include the value of early stakeholder consultations, the importance of inter-ministerial collaboration, and the need for continuous community engagement. This comprehensive strategy emphasizes strengthening surveillance systems, enhancing anti-snake venom (ASV) distribution and quality, improving healthcare infrastructure, and promoting community awareness through a One Health approach. The plan also addresses critical challenges such as inadequate training at primary healthcare levels, inconsistent ASV supply, and inefficient emergency referral systems. By fostering multisectoral collaboration and targeted interventions, such as strengthening Regional Venom Centres and establishing Poison Information Centre, targeted training, and awareness campaigns, NAPSE aims to reduce mortality and disability associated with snakebite envenoming, aligning with global health objectives and setting an example for regional efforts in Southeast Asia.
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Affiliation(s)
- Ajit Dadaji Shewale
- Centre for One Health, National Centre for Disease Control, Ministry of Health & Family Welfare, New Delhi 110074, India
| | - Dipti Mishra
- Centre for One Health, National Centre for Disease Control, Ministry of Health & Family Welfare, New Delhi 110074, India
| | - Simmi Tiwari
- Centre for One Health, National Centre for Disease Control, Ministry of Health & Family Welfare, New Delhi 110074, India
| | - Tushar Nanasaheb Nale
- Centre for One Health, National Centre for Disease Control, Ministry of Health & Family Welfare, New Delhi 110074, India
| | - Jitesh Kuwatada
- Centre for One Health, National Centre for Disease Control, Ministry of Health & Family Welfare, New Delhi 110074, India
| | - Nidhi Khandelwal
- Centre for One Health, National Centre for Disease Control, Ministry of Health & Family Welfare, New Delhi 110074, India
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Talukdar A, Giri S, Doley R. Kraits of Indian subcontinent: Natural history, risks, venom variation, lethality and treatment strategies - A comprehensive review. Toxicon 2025; 262:108406. [PMID: 40374096 DOI: 10.1016/j.toxicon.2025.108406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2025] [Revised: 04/30/2025] [Accepted: 05/11/2025] [Indexed: 05/17/2025]
Abstract
The World Health Organization (WHO) has re-classified "Snakebite" as a Neglected Tropical Disease in 2017, and estimated that as many as 5.4 million people suffer from snakebites every year. Out of this large number of snakebites, envenoming occurs in about 50 % of the cases, and the number of resulting deaths could be as high as 138,000. The genus Bungarus commonly known as kraits are medically important elapid snakes widely distributed in the Indian subcontinent, southern China and the Southeast Asian countries (except Philippines). The Indian subcontinent (India, Bangladesh, Bhutan, Nepal, Pakistan, Sri Lanka and Maldives) is home to 8-9 krait species, among which B. caeruleus and B. niger are highly venomous. This review presents the current state of knowledge on krait bites in the Indian subcontinent. The risk of envenomation by kraits, the venom lethality and krait bite management in the Indian subcontinent have been critically analyzed. Moreover, the issue of dry bites from kraits and their management has also been reviewed. Furthermore, critical aspects, such as knowledge of snakebite management among healthcare workers, clinical symptoms of snakebite patients, and treatment in healthcare facilities including antivenom administration and their clinical efficacy, have helped us in identifying the critical knowledge gaps. Proposed preventive measures will help to reduce krait bite associated mortality and morbidity. Moreover, development and accessibility to affordable treatment options may help in the effective management of krait bites.
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Affiliation(s)
- Amit Talukdar
- Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur, Assam, 784028, India
| | - Surajit Giri
- Demow Rural Government Community Health Centre, Raichai, Konwar Dihingia Gaon, Sivasagar, Assam, India
| | - Robin Doley
- Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur, Assam, 784028, India.
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Pavuluri LA, Bitla AR, Vishnubotla SK, Rapur R. Oxidative Stress, DNA Damage, Inflammation and Endothelial Dysfunction in Snakebite-Induced Acute Kidney Injury. Indian J Nephrol 2025; 35:349-354. [PMID: 40352896 PMCID: PMC12065592 DOI: 10.25259/ijn_545_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/04/2024] [Indexed: 05/14/2025] Open
Abstract
Background Snakebite-induced acute kidney injury (SAKI) is a life-threatening complication. Despite its impact on public health, the understanding of the underlying cellular and molecular mechanisms remains limited. There is a lack of studies investigating the role of oxidative stress, oxidative deoxyribonucleic acid (DNA) damage, inflammation, and endothelial dysfunction in SAKI. This study aims to address this knowledge gap. Materials and Methods Biomarkers of oxidative stress, including oxidative DNA damage, inflammation, and endothelial dysfunction were assessed in 30 patients with SAKI and 30 healthy controls. Malondialdehyde (MDA), protein carbonyl content (PCC), advanced glycation end products (AGEs), 8-hydroxy-2'-deoxyguanosine (8-OHdG), ferric reducing ability of plasma (FRAP), high-sensitivity C-reactive protein (hs-CRP), and nitric oxide (NO) were used as biomarkers. Results We found significantly elevated levels of MDA (2.1590±0.68221 µmol/L vs 0.8769±0.2958 µmol/L, p = <0.001), PCC (0.0905±0.040 nmol/L vs 0.0501±0.024 nmol/L, p = <0.001) and 8-OHdG (47.0757±37.09105 ng/mL vs 18.8450±9.31479 ng/mL, p = <0.001) in SAKI patients compared to controls, indicating increased oxidative damage to lipids, proteins, and DNA respectively. Although AGEs showed higher levels in SAKI patients, the difference was not significant. FRAP levels were significantly reduced [0.214 (0.051-0.489) mmol/L vs 0.470 (0.136-0.564) mmol/L, p = 0.024], indicating compromised antioxidant capacity. Significantly elevated levels of hs-CRP [40.18 (16.96-77.56) mg/L vs 1.44 (0.5-4.45) mg/L, p = <0.001] and NO [25.59 (22.75-28.43) µmol/L vs 14.218 (11.37-16.35) µmol/L, p = <0.001] confirmed the presence of inflammation and endothelial dysfunction in these patients. Conclusion Our study demonstrated oxidative stress, including oxidative DNA damage, inflammation, and endothelial dysfunction, in SAKI patients. Understanding these intricate mechanisms could lead to the development of novel diagnostic tools and therapeutic strategies.
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Affiliation(s)
| | - Aparna R. Bitla
- Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, India
| | - Siva Kumar Vishnubotla
- Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India
| | - Ram Rapur
- Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India
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Abouyannis M, Marriott AE, Stars E, Kitchen DP, Kitchen S, Woods TAL, Kreuels B, Amuasi JH, Monteiro WM, Stienstra Y, Senthilkumaran S, Isbister GK, Lalloo DG, Ainsworth S, Casewell NR. Handheld Point-of-Care Devices for Snakebite Coagulopathy: A Scoping Review. Thromb Haemost 2025; 125:405-420. [PMID: 39214143 PMCID: PMC12040437 DOI: 10.1055/a-2407-1400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 08/17/2024] [Indexed: 09/04/2024]
Abstract
Venom-induced consumption coagulopathy (VICC) is a common complication of snakebite that is associated with hypofibrinogenemia, bleeding, disability, and death. In remote tropical settings, where most snakebites occur, the 20-minute whole blood clotting test is used to diagnose VICC. Point-of-care (POC) coagulation devices could provide an accessible means of detecting VICC that is better standardized, quantifiable, and more accurate. In this scoping review, the mechanistic reasons that previously studied POC devices have failed in VICC are considered, and evidence-based recommendations are made to prioritize certain devices for clinical validation studies. Four small studies have evaluated a POC international normalized ratio (INR) device in patients with Australian Elapid, Daboia russelii, and Echis carinatus envenoming. The devices assessed in these studies either relied on a thrombin substrate endpoint, which is known to underestimate INR in patients with hypofibrinogenemia, have been recalled due to poor accuracy, or have since been discontinued. Sixteen commercially available POC devices for measuring INR, activated clotting time, activated partial thromboplastin time, fibrinogen, D-dimer, and fibrin(ogen) degradation products have been reviewed. POC INR devices that detect fibrin clot formation, as well as a novel POC device that quantifies fibrinogen were identified, which show promise for use in patients with VICC. These devices could support more accurate allocation of antivenom, reduce the time to antivenom administration, and provide improved clinical trial outcome measurement instruments. There is an urgent need for these promising POC coagulation devices to be validated in prospective clinical snakebite studies.
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Affiliation(s)
- Michael Abouyannis
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - Amy E. Marriott
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
- Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Emma Stars
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - Dianne P. Kitchen
- UK National External Quality Assessment Scheme for Blood Coagulation (UK NEQAS BC), Sheffield, United Kingdom
| | - Steve Kitchen
- UK National External Quality Assessment Scheme for Blood Coagulation (UK NEQAS BC), Sheffield, United Kingdom
| | - Tim A. L. Woods
- UK National External Quality Assessment Scheme for Blood Coagulation (UK NEQAS BC), Sheffield, United Kingdom
| | - Benno Kreuels
- Department of Implementation Research, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
| | - John H. Amuasi
- Department of Implementation Research, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
- Department of Global Health, School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Wuelton M. Monteiro
- College of Health Sciences, University of the State of Amazonas, Manaus, Brazil
- Department of Teaching and Research, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil
| | - Ymkje Stienstra
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
- Department of Internal Medicine/Infectious Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Geoff K. Isbister
- Clinical Toxicology Research Group, University of Newcastle, Newcastle, NSW, Australia
| | - David G. Lalloo
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - Stuart Ainsworth
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
- Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Nicholas R. Casewell
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
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Ojha A, Hadimani P, Anthony D, Raj V, Bhasker S, Mishra M, Johri S. Optimizing Anti-Snake Venom Strategies for Hemotoxic Envenomation in Northern India: Clinical Outcomes and Regional Challenge. Cureus 2025; 17:e84090. [PMID: 40519476 PMCID: PMC12164467 DOI: 10.7759/cureus.84090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2025] [Indexed: 06/18/2025] Open
Abstract
Snakebite envenomation, especially from hemotoxic species such as Daboia russelii and Echis carinatus, remains a significant public health challenge in the northern Indian states of Punjab, Haryana, Uttar Pradesh, Uttarakhand, and Himachal Pradesh. Despite the availability of polyvalent anti-snake venom (ASV), inconsistent dosing strategies, delayed administration, and disparities in healthcare contribute to high morbidity and mortality rates. This review examines optimal ASV dosing protocols, clinical outcomes, and host-specific factors that influence the therapeutic efficacy in hemotoxic envenomation. Drawing from regional epidemiological data, toxicological insights, and clinical studies, the review underscores the influence of bite-to-needle intervals, ASV administration routes, and infrastructural readiness on patient survival. Notably, intravenous administration proves superior, while early intervention significantly reduces systemic complications. The study identifies key gaps in national guidelines, particularly the mismatch between regional venom variability and available ASV formulations. It also explores emerging alternatives like Varespladib and monoclonal antivenoms. Methodologically, the review adopts a narrative synthesis of peer-reviewed literature and policy frameworks. It concludes that standardizing ASV treatment based on regional evidence, enhancing healthcare capacity, and integrating public health education are essential to improving outcomes. The findings support the need for locally tailored, patient-centric treatment protocols and stronger public health systems to mitigate snakebite-related burdens.
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Affiliation(s)
- Ashutosh Ojha
- Department of General Medicine, Government Medical College, Maharashtra Post Graduate Institute of Medical Education and Research, Nashik, IND
| | - Prakash Hadimani
- Department of General Medicine, Employees State Insurance Corporation (ESIC) Medical College and Hospital, Kalburagi, IND
| | - Dawn Anthony
- Department of General Medicine, Malankara Orthodox Syrian Church College of Nursing, Kolenchery, IND
| | - Vikas Raj
- Department of Medicine, Pondicherry Institute of Medical Sciences, Kalapet, IND
| | - Sumit Bhasker
- Department of Medicine and Geriatrics, Military Hospital, Jalandhar, IND
| | - Mayank Mishra
- Deparment of General Medicine, Military Hospital, Meerut, IND
| | - Sharat Johri
- Department of Neurology, SRM Institute of Medical Sciences, Bareilly, IND
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Sarangi N, Laxme RRS, Sunagar K. Significant Serpents: Predictive Modelling of Bioclimatic Venom Variation in Russell's Viper. PLoS Negl Trop Dis 2025; 19:e0012949. [PMID: 40208847 PMCID: PMC11984747 DOI: 10.1371/journal.pntd.0012949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 02/24/2025] [Indexed: 04/12/2025] Open
Abstract
BACKGROUND Russell's viper (Daboia russelii) is the clinically most important snake species in the world. Considerable variation has been documented in D. russelii venoms across the Indian subcontinent, which can drive the diverse envenomation profiles in snakebite victims. Therefore, understanding the role of ecological and environmental factors influencing the compositional and functional variation can provide critical insights into the complex evolutionary adaptations of this species and pave the way for the development of targeted therapies. METHODS We examined the influence of bioclimatic factors on D. russelii venom functions by analysing 115 samples sourced from various locations across India. The enzymatic activities of major toxins, such as proteases and phospholipases, were estimated to capture the functional variation in these venoms. Multiple regression models were developed to evaluate the relationship between venom variability and the historical climate data, specifically temperature and precipitation. Furthermore, predictive models were employed to map venom phenotypes across the distribution range of D. russelii. FINDINGS Our findings reveal a collective influence of various temperature and precipitation parameters that partly explain the variability in enzymatic activities of D. russelii venom. Our models effectively captured regional differences in venom composition and linked climatic conditions with functional variations. CONCLUSION This study highlights the significant role of abiotic factors in shaping the venom profiles of Russell's vipers across India. The predictive venom phenotype maps developed from our models can guide the deployment of targeted therapies and treatment protocols across the biogeographically diverse Indian subcontinent and improve clinical treatment outcomes of D. russelii envenoming. This research enhances our understanding of venom phenotype evolution and has practical implications for improving snakebite management.
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Affiliation(s)
- Navaneel Sarangi
- Centre for Ecological Sciences, Indian Institute of Science Bangalore, India
| | - R. R. Senji Laxme
- Centre for Ecological Sciences, Indian Institute of Science Bangalore, India
| | - Kartik Sunagar
- Centre for Ecological Sciences, Indian Institute of Science Bangalore, India
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7
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Barker A, Jones L, Bourke LA, Seneci L, Chowdhury A, Violette A, Fourmy R, Soria R, Aldridge M, Fry BG. Snake Venom Makeover: Age-Dependent Variations in Procoagulant Biochemistry of Egyptian Saw-Scaled Viper ( Echis pyramidum pyramidum) Venom. Toxins (Basel) 2025; 17:149. [PMID: 40137922 PMCID: PMC11946080 DOI: 10.3390/toxins17030149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/12/2025] [Accepted: 03/17/2025] [Indexed: 03/29/2025] Open
Abstract
Echis species (saw-scaled vipers) are WHO Category 1 medically significant venomous snakes with potent procoagulant venoms, which cause lethal venom-induced consumptive coagulopathy in human victims. Despite clinical presentations of bites varying significantly between individuals within the same species, the contribution of age-related changes in the venom biochemistry has not been investigated. This study investigated the ontogenetic changes in Echis pyramidum pyramidum venom and its impact on therapeutic efficacy. The efficacy of various antivenoms (Echitab, Echitab+ ICP, Inosan MENA, Inosan Pan African, and SAVP-Echis) was tested against both venom phenotypes. While both neonate and adult venoms were procoagulant, there were differences in the underlying biochemistry. Neonate venom was found to potently pathophysiologically activate Factor VII and Factor X, and to a lesser degree Factor XII. In contrast, adult venom was a slower clotter, less potent in activating FVII, equipotent with neonate venom on FXII, and inactive on FX. This is the first documentation of FVII and FXII activation for any Echis venom. The significant ontogenetic toxicological variations in Echis species were shown to impact antivenom efficacy. Among the tested antivenoms, SAVP-Echis was the most effective against both venom phenotypes, with adult venom being better neutralized. These findings suggest the need for a reconsideration of venom mixture selection in antivenom production through the inclusion of neonate venom. Additionally, the results indicate differential ontogenetic predatory ecology, providing a foundation for future natural history investigations.
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Affiliation(s)
- Alex Barker
- Adaptive Biotoxicology Lab, School of the Environment, University of Queensland, St Lucia, QLD 4072, Australia; (A.B.); (L.J.); (L.A.B.); (L.S.); (A.C.)
| | - Lee Jones
- Adaptive Biotoxicology Lab, School of the Environment, University of Queensland, St Lucia, QLD 4072, Australia; (A.B.); (L.J.); (L.A.B.); (L.S.); (A.C.)
| | - Lachlan A. Bourke
- Adaptive Biotoxicology Lab, School of the Environment, University of Queensland, St Lucia, QLD 4072, Australia; (A.B.); (L.J.); (L.A.B.); (L.S.); (A.C.)
| | - Lorenzo Seneci
- Adaptive Biotoxicology Lab, School of the Environment, University of Queensland, St Lucia, QLD 4072, Australia; (A.B.); (L.J.); (L.A.B.); (L.S.); (A.C.)
| | - Abhinandan Chowdhury
- Adaptive Biotoxicology Lab, School of the Environment, University of Queensland, St Lucia, QLD 4072, Australia; (A.B.); (L.J.); (L.A.B.); (L.S.); (A.C.)
| | - Aude Violette
- Alphabiotoxine Laboratory srl, Barberie 15, 7911 Montroeul-au-bois, Belgium; (A.V.); (R.F.)
| | - Rudy Fourmy
- Alphabiotoxine Laboratory srl, Barberie 15, 7911 Montroeul-au-bois, Belgium; (A.V.); (R.F.)
| | | | | | - Bryan G. Fry
- Adaptive Biotoxicology Lab, School of the Environment, University of Queensland, St Lucia, QLD 4072, Australia; (A.B.); (L.J.); (L.A.B.); (L.S.); (A.C.)
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Alonso LL, Slagboom J, Casewell NR, Samanipour S, Kool J. Categorization and Characterization of Snake Venom Variability through Intact Toxin Analysis by Mass Spectrometry. J Proteome Res 2025; 24:1329-1341. [PMID: 40009567 PMCID: PMC11894662 DOI: 10.1021/acs.jproteome.4c00923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 01/08/2025] [Accepted: 02/10/2025] [Indexed: 02/28/2025]
Abstract
The variation in venom between and within snake species has significant implications for snakebite treatment. This highlights the critical importance of studying venom composition and its variations, not only for medical purposes but also from an evolutionary perspective. This study explores analytics for characterizing venom variability, focusing on venom toxin accurate masses, and emphasizes how the complexity of studying snake venom variability can be addressed by using liquid chromatography mass spectrometry (LC-MS) analysis with bioinformatics tools. This was demonstrated by investigating LC-MS data obtained from the venoms of 15 true cobras (Naja spp.), 5 mambas (Dendroaspis spp.) and 28 vipers (Crotalus and Bothrops spp.; total of 20 Elapidae and 28 Viperidae venoms), with newly developed bioinformatics tools. The measured LC-MS data was processed in an automated fashion and sorted based on the monoisotopic accurate masses of all toxins found, their peak intensities, and their retention times in LC. The data was then investigated using bioinformatic tools, before the toxin data available in open-source databases was used to predict the class of a toxin by means of its mass. This study highlights the importance of studying venom variability, which is performed by our combinatorial approach of intact-toxin analysis and toxin grouping by accurate mass.
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Affiliation(s)
- Luis L. Alonso
- Division
of BioAnalytical Chemistry, Amsterdam Institute of Molecular and Life
Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081, HV, Amsterdam, The Netherlands
- Centre
for Analytical Sciences Amsterdam (CASA), The Netherlands, 1012 WP, Amsterdam, The Netherlands
| | - Julien Slagboom
- Division
of BioAnalytical Chemistry, Amsterdam Institute of Molecular and Life
Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081, HV, Amsterdam, The Netherlands
- Centre
for Analytical Sciences Amsterdam (CASA), The Netherlands, 1012 WP, Amsterdam, The Netherlands
| | - Nicholas R. Casewell
- Centre
for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, L3 5QA, Pembroke Place, Liverpool, United Kingdom
| | - Saer Samanipour
- Van
‘t Hof Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands
| | - Jeroen Kool
- Division
of BioAnalytical Chemistry, Amsterdam Institute of Molecular and Life
Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081, HV, Amsterdam, The Netherlands
- Centre
for Analytical Sciences Amsterdam (CASA), The Netherlands, 1012 WP, Amsterdam, The Netherlands
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9
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Puzari U, Khan MR, Mukherjee AK. Diagnosis of Indian Big Four and monocled Cobra snakebites in envenomed plasma using smartphone-based digital imaging colourimetry method. PLoS Negl Trop Dis 2025; 19:e0012913. [PMID: 40085527 PMCID: PMC11936222 DOI: 10.1371/journal.pntd.0012913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 03/25/2025] [Accepted: 02/12/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND Venomous or dry bites can result from snake envenomation. Therefore, developing a detection test for venomous snakebites in envenomed patients can prevent from unnecessary antivenom therapy for dry bites, thereby, saving them from adverse effects and cost of antivenom therapy. METHODOLOGY This study demonstrates a method for the diagnosis of medically significant 'Big Four' Indian snake venoms (Naja naja, Bungarus caeruleus, Daboia russelii, Echis carinatus) in the plasma of experimentally envenomed animals (envenomed under laboratory conditions). Rabbit polyclonal antibodies (PAbs) were produced by generating modified bespoke peptides identified by computational analysis from the antigenic sites of the main toxins found in the proteome of India's 'Big Four' venomous snakes. The polyclonal antibody formulation (FPAb) prepared by mixing the five representative PAbs in the ratio of 1:1:1:1:1 demonstrated synergistic immune recognition of the 'Big Four' snakes and Naja kaouthia venoms. The recognition for these venoms under in vitro and in vivo conditions by FPAb was significantly higher (p<0.05) than commercial polyvalent antivenom produced against native venom toxins. The FPAb was tested to detect the venoms in subcutaneously envenomed rat plasmas until 240 minutes post-injection. Fourier-transform infrared spectroscopy, zeta potential, transmission electron microscopy, and atomic force microscopy characterised gold nanoparticles (AuNP) conjugated with FPAb. The FPAb-conjugated AuNP demonstrated aggregation upon interaction with venom toxins, changing the colour from red through burgundy to blue, monitored using a smartphone. From the digital image colourimetry analysis of the images, calibration curves for venoms were obtained, and each venom in the envenomed plasma at different time intervals was quantified using these curves. CONCLUSION A method for detection of venomous snakebites has been reported. The formulation of polyclonal antibodies generated against toxins of 'Big Four' venomous snakes of India immune-recognise venoms of 'Big Four' venomous snakes of India and N. kaouthia venoms under both in vitro and in vivo conditions. The antibody formulation conjugated to AuNP detected the venoms in envenomed plasma. This method of detection has potential to be useful for snakebite management in clinical settings.
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Affiliation(s)
- Upasana Puzari
- Microbial Biotechnology and Protein Research Laboratory, Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur, Assam, India
| | - Mojibur R. Khan
- Division of Life Sciences, Institute of Advanced Study in Science and Technology, Vigyan Path Garchuk, Paschim Boragaon, Guwahati, Assam, India
- Academy of Science and Innovative Research (AcSIR), Ghaziabad, India
| | - Ashis K. Mukherjee
- Microbial Biotechnology and Protein Research Laboratory, Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur, Assam, India
- Division of Life Sciences, Institute of Advanced Study in Science and Technology, Vigyan Path Garchuk, Paschim Boragaon, Guwahati, Assam, India
- Academy of Science and Innovative Research (AcSIR), Ghaziabad, India
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Pandey DP, Adhikari B, Pandey P, Sapkota K, Bhusal MK, Kandel P, Shrestha DL, Shrestha BR. Cost of Snakebite and Its Impact on Household Economy in Southern Nepal. Am J Trop Med Hyg 2025; 112:431-440. [PMID: 39561391 PMCID: PMC11803655 DOI: 10.4269/ajtmh.24-0399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 09/29/2024] [Indexed: 11/21/2024] Open
Abstract
We aimed to estimate the cost of snakebite and its impact on the economy of snakebite-affected households in southern Nepal. We conducted cross-sectional and prospective studies of confirmed snakebite cases at two hospitals in south central and southwestern Nepal during May to October 2020. We estimated the economic impact of snakebite on affected households by evaluating direct and indirect costs for treatments and opportunity costs of patients and attendants (household members or relatives). We included 553 snakebites that caused 185 envenomings (34%), resulting in 15 deaths (case fatality rate, 8%). These occurred across 87 subdistricts, 21 districts, and six provinces (25% rural, 75% urban overall). Median direct, indirect, and opportunity costs of snakebite were US$95.30, US$65.80, and US$4,995.20 for envenomings and US$14.50, US$13.50, and US$10.10 for nonenvenomed snakebites, respectively. The impact of snakebite envenomings on household economy included not only the remarkable out-of-pocket expenditure but also the loss of patients' and visitors' productivity (i.e., daily income/wages while seeking snakebite care in hospitals). Lack of insurance for snakebite treatment increased the psychosocial and economic burden. Deterioration in family economy and psychology was particularly severe when death from snakebite affected breadwinners. Therefore, taking action to minimize the impact of snakebite envenoming becomes a priority for all.
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Affiliation(s)
- Deb Prasad Pandey
- Department of Veterinary Microbiology and Parasitology, Agriculture and Forestry University, Bharatpur Metropolitan City, Nepal
- Institute for Social and Environmental Research–Nepal, Bharatpur Metropolitan City, Nepal
| | - Bhojraj Adhikari
- Department of Medicine, Bharatpur Hospital, Bharatpur Metropolitan City, Nepal
| | - Parash Pandey
- Department of Anesthesiology, Bheri Hospital, Nepalgunj, Nepal
| | - Kalyan Sapkota
- Department of Medicine, Bharatpur Hospital, Bharatpur Metropolitan City, Nepal
| | - Mina Kumari Bhusal
- Bharatpur Hospital Nursing College, Bharatpur Hospital, Bharatpur Metropolitan City, Nepal
| | - Priti Kandel
- Department of Microbiology, Birendra Multiple Campus, Bharatpur Metropolitan City, Nepal
| | | | - Bhola Ram Shrestha
- Department of General Practice and Emergency Medicine, Chitwan Medical College, Bharatpur Metropolitan City, Nepal
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Kadam P, Patel B, Gopalakrishnan M, Sirur FM, Bharti OK, Agrawal A, Yunus M, Majumdar DB, Ainsworth S. Reported snakebite mortality and state compensation payments in Madhya Pradesh, India, from 2020 to 2022. Trans R Soc Trop Med Hyg 2025; 119:158-165. [PMID: 39105603 PMCID: PMC11791426 DOI: 10.1093/trstmh/trae045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 04/19/2024] [Accepted: 07/26/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND India experiences the highest snakebite burden globally, with 58 000 predicted deaths annually. The central Indian state of Madhya Pradesh is thought to have a substantial snakebite burden and provides compensation to families who can demonstrate by postmortem and hospital treatment reports that their relatives have died due to snakebite. This study represents the first report on the frequency of distribution of compensation for snakebite deaths in Madhya Pradesh. METHODS Statewide snakebite death compensation data from 2020-2021 and 2021-2022, provided by the Madhya Pradesh health authorities, were analysed alongside interviews with 15 families that described the events that ultimately led to their compensation claims. RESULTS Compensation was paid to a total of 5728 families, with a total value equating to 22 912 Lakhs (approximately US${\$}$27.94 million). Families described commonly recognised snakebite risk factors and behaviours in the events that resulted in their relatives' deaths. CONCLUSIONS The snakebite burden in Madhya Pradesh is significant, both in terms of mortality and economic expenditure of the state. Sustained investment in preventative interventions, as well as monitoring of the rate of compensation payouts due to snakebite death as a measure of intervention effectiveness, should be considered to substantially reduce snakebite incidence and mortality.
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Affiliation(s)
- Priyanka Kadam
- Snakebite Healing and Education Society, Mumbai 400050, India
| | - Bhupeshwari Patel
- Department of Trauma & Emergency Medicine, All India Institute of Medical Sciences, Bhopal 462026, Madhya Pradesh, India
| | - Maya Gopalakrishnan
- Department of Medicine, All India Institute of Medical Sciences, Jodhpur 342005, Rajasthan, India
| | - Freston M Sirur
- Department of Emergency Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
- Centre for Wilderness Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Omesh K Bharti
- State Institute of Health & Family Welfare, Kasumpti, Shimla 171009, Himachal Pradesh, India
| | - Amit Agrawal
- Department of Neurosurgery, All India Institute of Medical Sciences, Bhopal 462026, Madhya Pradesh, India
| | - Md Yunus
- Department of Trauma & Emergency Medicine, All India Institute of Medical Sciences, Bhopal 462026, Madhya Pradesh, India
| | - Dayal B Majumdar
- Calcutta National Medical College & Hospital, Kolkata 700014, West Bengal, India
| | - Stuart Ainsworth
- Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK
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Sreekumar A, Abraham SV, Rajeev PC, Chanchal A B V, Suseel A, Mathew D, George CR, Palatty BU. Educating healthcare workers in snakebite management: A study to determine the effectiveness of the snake bite life support workshop. Toxicon 2025; 255:108235. [PMID: 39793626 DOI: 10.1016/j.toxicon.2025.108235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/06/2025] [Accepted: 01/07/2025] [Indexed: 01/13/2025]
Abstract
INTRODUCTION Snakebite envenomation is a significant global health issue, with India bearing a substantial burden. Despite the development of guidelines, knowledge gaps and lack of training persist among healthcare workers (HCWs), contributing to high morbidity and mortality. This study aimed to evaluate the impact of the Snake Bite Life Support (SBLS) workshop on HCWs' knowledge, practices, self-efficacy, and advocacy skills in snakebite management. METHODS A pre-post interventional study was conducted during the SBLS workshop at a tertiary care center in May 2024. HCWs' knowledge, practical skills, self-efficacy, and advocacy skills were assessed using standardized questionnaires and a modified General Self-Efficacy (GSE) scale, both before and after the workshop. Data were analyzed using SPSS v25.0, employing paired t-tests and Wilcoxon signed-rank tests for comparison. RESULTS Forty-one HCWs completed the pre- and post-workshop assessments. Significant improvements were observed in knowledge, particularly in avoiding false positive 20-min whole blood clotting test (20WBCT) results (p = 0.020) and premedication for antivenom (p < 0.001). Participants reported a marked increase in self-efficacy across all GSE parameters and demonstrated enhanced advocacy intent in resource management, policy influence, and educational outreach. The workshop influenced practice changes, notably reducing the administration of antivenom in confirmed hump-nosed pit viper bites. CONCLUSION The SBLS workshop effectively enhanced HCWs' knowledge, management practices, self-efficacy, and advocacy intentions, emphasizing the need for integrating such training into healthcare education to drive systemic change in snakebite management and improve patient outcomes. Future studies should focus on long-term impacts and broader implementation.
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Affiliation(s)
- Aravind Sreekumar
- Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India
| | - Siju V Abraham
- Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India.
| | - P C Rajeev
- Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India
| | - Vijay Chanchal A B
- Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India
| | - Appu Suseel
- Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India
| | - Deo Mathew
- Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India
| | - Collin R George
- Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India
| | - Babu U Palatty
- Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India
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Gololo AA, Veettil SK, Anantachoti P, Taychakhoonavudh S, Patikorn C. Epidemiological models to estimate the burden of snakebite envenoming: A systematic review. Trop Med Int Health 2025; 30:71-83. [PMID: 39743841 DOI: 10.1111/tmi.14080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
BACKGROUND Epidemiological modelling studies in snakebite envenoming research are evolving. Their techniques can be essential in filling the knowledge gap needed to attain the World Health Organization's (WHO) goal of halving the burden of snakebite envenoming by complementing the current data scarcity. Hence, there is a need for a systematic review to summarise epidemiological models used in estimating the burden of snakebite envenoming. METHODS We conducted a systematic review by searching PubMed, EMBASE, and Scopus to identify articles reporting epidemiological models in snakebite envenoming from database inception to 31st December 2023. A narrative synthesis was performed to summarise types of models, methodologies, input parameters, model outputs, and associating factors. RESULTS Thirty-nine modelling studies were included from 2426 retrieved articles, comprising statistical models (76.9%) and mathematical models (23.1%). Most of the studies were conducted in South Asia, (35.9%) and Latin America (35.9%), and only a few (5.1%) were a global burden estimation. The eligible studies constructed 42 epidemiological models, of which 33 were statistical models that included regression, (60.6%) geostatistical (21.2%), and time series, (18.2%) while 9 mathematical models comprised compartmental, (44.4%) agent-based, (22.2%) transmission dynamics, (11.1%) network, (11.1%) and a simple mathematical model (11.1%). The outputs of the models varied across the study objectives. Statistical models analysed the relationship between incidence, (83.3%) mortality, (33.3%) morbidity (16.7%) and prevalence (10.0%) and their associating factors (environmental, [80%] socio-demographic [33.3%] and therapeutic [10.0%]). Mathematical models estimated incidence, (100%) mortality (33.3%), and morbidity (22.2%). Five mathematical modelling studies considered associating factors, including environmental (60%) and socio-demographic factors (40%). CONCLUSION Mathematical and statistical models are crucial for estimating the burden of snakebite envenoming, offering insights into risk prediction and resource allocation. Current challenges include low-quality data and methodological heterogeneity. Modelling studies are needed, and their continued improvement is vital for meeting WHO goals. Future research should emphasise standardised methodologies, high-quality community data, and stakeholder engagement to create accurate, applicable models for prevention and resource optimization in high-burden regions, including Africa and Asia.
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Affiliation(s)
- Ahmed Adamu Gololo
- Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Sajesh K Veettil
- Department of Pharmacy Practice, School of Pharmacy, IMU University, Kuala Lumpur, Malaysia
| | - Puree Anantachoti
- Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Suthira Taychakhoonavudh
- Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Chanthawat Patikorn
- Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
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Kaulgud RS, Hasan T, Astagimath M, Vanti GL, Veeresh S, Kurjogi MM, Belur S. Nucleotidase as a Clinical Prognostic Marker in Snakebites: A Prospective Study. Indian J Crit Care Med 2025; 29:125-129. [PMID: 40110145 PMCID: PMC11915441 DOI: 10.5005/jp-journals-10071-24901] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 01/15/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Snakebite envenomation is a critical global health issue, causing substantial mortality and morbidity. Snake venom includes various enzymes, such as nucleotidase, phosphatases, etc. which impact physiological functions. However, research on the role of serum 5'-nucleotidase levels in assessing the severity and outcomes of snakebites is limited. This study aims to measure serum 5'-nucleotidase levels and explore their correlation with the severity of envenomation, to better understand its role in predicting patient prognosis. METHODS This is a single-center, prospective observational analysis involving 82 snakebite patients. Serum 5'-nucleotidase levels were measured using enzyme-linked immunosorbent assay, and clinical severity was evaluated using the snakebite severity score (SSS). Statistical analyses were performed to determine the correlation between 5'-nucleotidase levels and SSS, as well as various complications. RESULTS Among the 82 snakebite patients, 71.9% were male and 28.1% were female. Most bites (62.2%) occurred during the day, and 83% involved the lower limbs. Recovery was high, with 93.9% discharged, 3.7% deceased, and 2.4% lost to follow-up. A positive correlation was observed between 5'-nucleotidase levels and SSS at both 0 and 24 hours, with correlation coefficients of 0.55 and 0.61, respectively (p < 0.001). CONCLUSION Serum 5'-nucleotidase serves as an effective biomarker for assessing the severity of snakebite envenomation and predicting patient outcomes. Its strong correlation with clinical severity scores makes it a valuable tool for improving the prognostication and management of snakebite cases when used in conjunction with clinical assessments. HOW TO CITE THIS ARTICLE Kaulgud RS, Hasan T, Astagimath M, Vanti GL, Veeresh S, Kurjogi MM, et al. Nucleotidase as a Clinical Prognostic Marker in Snakebites: A Prospective Study. Indian J Crit Care Med 2025;29(2):125-129.
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Affiliation(s)
- Ram S Kaulgud
- Department of General Medicine and Multidisciplinary Research Unit, Karnataka Medical College and Research Institute, Hubballi, Karnataka, India
| | - Tousif Hasan
- Department of General Medicine, Karnataka Medical College and Research Institute, Hubballi, Karnataka, India
| | - Muragendraswami Astagimath
- Department of Biochemistry, Karnataka Medical College and Research Institute, Hubballi, Karnataka, India
| | - Gulamnabi L Vanti
- Multidisciplinary Research Unit, Karnataka Medical College and Research Institute, Hubballi; LabCorp Laboratories India Pvt. Ltd., Bengaluru, Karnataka, India
| | - S Veeresh
- Multidisciplinary Research Unit, Karnataka Medical College and Research Institute, Hubballi, Karnataka, India
| | - Mahantesh M Kurjogi
- Multidisciplinary Research Unit, Karnataka Medical College and Research Institute, Hubballi; LabCorp Laboratories India Pvt. Ltd., Bengaluru, Karnataka, India
| | - Shivakumar Belur
- Multidisciplinary Research Unit, Karnataka Medical College and Research Institute, Hubballi, Karnataka, India
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Bala AA, Oukkache N, Sanchez EE, Suntravat M, Galan JA. Venoms and Extracellular Vesicles: A New Frontier in Venom Biology. Toxins (Basel) 2025; 17:36. [PMID: 39852989 PMCID: PMC11769160 DOI: 10.3390/toxins17010036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/19/2024] [Accepted: 12/24/2024] [Indexed: 01/26/2025] Open
Abstract
Extracellular vesicles (EVs) are nanoparticle-sized vesicles secreted by nearly all cell types under normal physiological conditions. In toxicological research, EVs have emerged as a crucial link between public health and multi-omics approaches, offering insights into cellular responses to disease-causing injury agents such as environmental and biological toxins, contaminants, and drugs. Notably, EVs present a unique opportunity to deepen our understanding of the pathophysiology of envenomation by natural toxins. Recent advancements in isolating and purifying EV cargo, mass spectrometry techniques, and bioinformatics have positioned EVs as potential biomarkers that could elucidate biological signaling pathways and provide valuable information on the relationship between venomous toxins, their mechanisms of action, and the effectiveness of antivenoms. Additionally, EVs hold promise as proxies for various aspects of envenomation, including the toxin dosage, biological characterization, injury progression, and prognosis during therapeutic interventions. These aspects can be explored through multi-omics technology applied to EV contents from the plasma, saliva, or urine samples of envenomated individuals, offering a comprehensive integrative approach to understanding and managing envenomation cases.
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Affiliation(s)
- Auwal A. Bala
- Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA;
| | - Naoual Oukkache
- Laboratory of Venoms and Toxins, Pasteur Institute of Morocco, Casablanca 20360, Morocco;
| | - Elda E. Sanchez
- Department of Chemistry and National Natural Toxins Research Center, Texas A&M University-Kingsville, Kingsville, TX 78363, USA; (E.E.S.); (M.S.)
| | - Montamas Suntravat
- Department of Chemistry and National Natural Toxins Research Center, Texas A&M University-Kingsville, Kingsville, TX 78363, USA; (E.E.S.); (M.S.)
| | - Jacob A. Galan
- Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA;
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Gopalakrishnan M, Kumar Ph A, Tanwar D, Bhat Ks S, Choudhary B, Garg MK. Antivenom ineffectiveness in Echis carinatus sochureki envenoming: a five-year, single-centre experience from India. Trans R Soc Trop Med Hyg 2025:trae111. [PMID: 39749523 DOI: 10.1093/trstmh/trae111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 09/10/2024] [Accepted: 10/24/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Snakebite is a neglected tropical disease that causes significant morbidity and mortality in India. In this study, we describe the clinical characteristics and outcomes of Echis carinatus sochureki envenoming from Western Rajasthan. We document the clinical ineffectiveness of the currently available Indian polyvalent antivenom in managing E. c. sochureki envenoming. METHODS In this ambispective study, conducted from 14 April 2019 to 15 April 2024, we enrolled all patients presenting to our emergency department at a tertiary care centre in Jodhpur, Rajasthan, with a history of snakebite. After they provided informed consent, the demographic details, bite geo-location, bite-to-antivenom time, antivenom dose, coagulation profile, mortality and duration of hospital stay of those patients with E. c. sochureki envenoming were recorded. RESULTS Of 210 patients screened, 105 had E. c. sochureki envenoming, 103 venom-induced consumption coagulopathy, 36 (34.3%) local bleeding and 55 (52.3%) systemic bleeding. The median bite-to-antivenom time was 2 (IQR: 1.13-4.0) h. The median antivenom dose was 22 (IQR: 10-30) vials. Of 92 patients who received antivenom, 63 (68.4%) were unresponsive. Total antivenom dose and geographical location (West zone) were significant predictors of antivenom unresponsiveness. Fifty-three of 70 patients (75.7%) had delayed hypofibrinogenaemia. The mean hospital stay was 8.3±7.1 d with nine (8.6%) mortalities. CONCLUSIONS Our study highlights the alarming finding of poor antivenom response to E. c. sochureki envenoming, with significant clinical bleeding and delayed coagulopathy. There is an urgent need for region-specific antivenom in Western India.
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Affiliation(s)
- Maya Gopalakrishnan
- Department of Medicine, All India Institute of Medical Sciences, Jodhpur 342005, India
| | - Akhilesh Kumar Ph
- Department of Medicine, All India Institute of Medical Sciences, Jodhpur 342005, India
- Department of Medicine, Atal Bihari Vajpayee Institute of Medical Sciences and Dr Ram Manohar Lohia Hospital, New Delhi 110001, India
| | - Divya Tanwar
- Department of Medicine, All India Institute of Medical Sciences, Jodhpur 342005, India
| | - Samarth Bhat Ks
- Department of Medicine, All India Institute of Medical Sciences, Jodhpur 342005, India
| | - Bharat Choudhary
- Department of Trauma and Emergency Medicine (Paediatrics), All India Institute of Medical Sciences, Jodhpur 342005, India
| | - Mahendra K Garg
- Department of Medicine, All India Institute of Medical Sciences, Jodhpur 342005, India
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Rao PSK, Priyamvada PS, Bammigatti C. Snakebite envenomation-associated acute kidney injury: a South-Asian perspective. Trans R Soc Trop Med Hyg 2025:trae114. [PMID: 39749490 DOI: 10.1093/trstmh/trae114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 07/23/2024] [Accepted: 10/28/2024] [Indexed: 01/04/2025] Open
Abstract
Snakebite is a neglected public health problem in tropical countries. Snakebite envenomation-associated acute kidney injury (SBE-AKI) is a major complication accounting for significant morbidity and mortality. The pathogenesis of SBE-AKI may be multifactorial, including prerenal AKI secondary to hemodynamic alterations, intrinsic renal injury, immune-related mechanisms, venom-induced consumptive coagulopathy and capillary leak syndrome. Epidemiological factors include snake species, duration and severity of snakebite, traditional healers and native medication and accessibility to modern healthcare and antisnake venom. Renal histopathology observed consist of acute tubular necrosis, interstitial nephritis, cortical necrosis, disseminated intravascular coagulation, rhabdomyolysis and thrombotic microangiopathy. Glomerular involvement is rare. Proteinuria can be present rarely, hematuria is more common, most often due to venom-induced coagulopathy or hemolysis; it is only rarely due to renal injury. Management includes supportive care and renal replacement therapy when indicated. Progression to chronic kidney disease remains one of the biggest concerns of SBE-AKI. Hence the role and timing of renal biopsy remain controversial, given the risk involved and the benefit obtained in cases of interstitial nephritis. Various biomarkers, including cystatin C, neutrophil gelatinase-associated lipocalin, clusterin and beta-2-glycoprotein, have shown a tendency to predict AKI and also predict progression to chronic kidney disease.
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Affiliation(s)
- P Sai Kameshwar Rao
- Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry 605006, India
| | - P S Priyamvada
- Department of Nephrology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry 605006, India
| | - Chanaveerappa Bammigatti
- Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry 605006, India
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Dayasiri K, Caldera D, Suraweera N, Thadchanamoorthy V, Hettiarachchi M, Denipitiya T, Bandara S. Epidemiological patterns and trends of paediatric snakebites in Sri Lanka. BMC Res Notes 2024; 17:371. [PMID: 39702225 DOI: 10.1186/s13104-024-07036-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 12/11/2024] [Indexed: 12/21/2024] Open
Abstract
OBJECTIVES This study aimed to analyse the epidemiological patterns of paediatric snake bites in Sri Lanka over a 4-year period (2020-2024). METHODS A multi-centre, retrospective observational study was conducted from June 2020 to June 2024 across nine governmental hospitals in seven provinces of Sri Lanka. Data were collected based on 757 children presenting with snake bites. The snake bites were analysed based on age, gender, and seasonal variations. Data on the type of snake involved, geographic variations and the temporal trends in snake bite occurrences were also analysed. RESULTS The mean age of the 757 children recruited to the study was 10.3 years (SD-5.00, range-0.1-17 years). Males (57.7%) were significantly more affected than females (42.3%) (p < 0.05). Visual identification confirmed the snake species in 58.4% of cases. The hump-nosed viper (16.7%), Russell's viper (14.7%), and common krait (12.9%) were the most common medically important snakes identified in the study. Seasonal peaks in snake bites occurred in May-July and November-December. An increasing trend in snake bite incidence was noted over the first three years, with a slight decline in the final year. CONCLUSION Paediatric snake bites in Sri Lanka show significant age, gender, and seasonal patterns. Targeted public health interventions are needed to mitigate the impact on children.
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Affiliation(s)
- Kavinda Dayasiri
- Department of Paediatrics, Faculty of Medicine, University of Kelaniya, Thalagolla Road, PO Box 06, Ragama, Sri Lanka.
| | - Dihan Caldera
- Department of Paediatrics, Faculty of Medicine, University of Kelaniya, Thalagolla Road, PO Box 06, Ragama, Sri Lanka
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Cavalcante JS, Arruda SST, Riciopo PM, Pucca M, Ferreira Junior RS. Diagnosis of human envenoming by terrestrial venomous animals: Routine, advances, and perspectives. Toxicon X 2024; 24:100211. [PMID: 39507426 PMCID: PMC11539352 DOI: 10.1016/j.toxcx.2024.100211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 09/26/2024] [Accepted: 09/28/2024] [Indexed: 11/08/2024] Open
Abstract
Despite the development of new and advanced diagnostic approaches, monitoring the clinical evolution of accidents caused by venomous animals is still a challenge for science. In this review, we present the state of the art of laboratory tests that are routinely used for the diagnosis and monitoring of envenomings by venomous animals, as well as the use of new tools for more accurate and specific diagnoses. While a comprehensive range of tools is outlined, comprising hematological, biochemical, immunoassays, and diagnostic imaging tools, it is important to acknowledge their limitations in predicting the onset of clinical complications, since they provide an overview of organic damage after its development. Thus, the need for discovery, validation, and use of biomarkers that have greater predictive power, sensitivity and specificity is evident. This will help in the diagnosis, monitoring, and treatment of patients envenomated by venomous animals, consequently reducing the global burden of morbidity and mortality.
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Affiliation(s)
- Joeliton S. Cavalcante
- Graduate Program in Tropical Diseases, Botucatu Medical School (FMB), São Paulo State University (UNESP—Univ Estadual Paulista), Botucatu, 18618-687, São Paulo, Brazil
| | - Sabrina Santana Toledo Arruda
- Department of Bioprocess and Biotechnology, School of Agriculture, Agronomic Sciences School, São Paulo State University (UNESP—Univ Estadual Paulista), Botucatu, 18618-687, São Paulo, Brazil
| | - Pedro Marques Riciopo
- Department of Bioprocess and Biotechnology, School of Agriculture, Agronomic Sciences School, São Paulo State University (UNESP—Univ Estadual Paulista), Botucatu, 18618-687, São Paulo, Brazil
| | - Manuela Pucca
- Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University UNESP—Univ Estadual Paulista, Araraquara, 14800-903, Brazil
| | - Rui Seabra Ferreira Junior
- Graduate Program in Tropical Diseases, Botucatu Medical School (FMB), São Paulo State University (UNESP—Univ Estadual Paulista), Botucatu, 18618-687, São Paulo, Brazil
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP—Univ Estadual Paulista), Botucatu, 18610-307, São Paulo, Brazil
- Center for Translational Science and Development of Biopharmaceuticals FAPESP/CEVAP-UNESP, Botucatu, 18610-307, São Paulo, Brazil
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Matin A, Sobuj SA, Saha P, Sami CA. Respiratory Failure Following a Venomous Snakebite: Importance of Ambu Bag Ventilation in a Poor-Resource Setting. Clin Case Rep 2024; 12:e9627. [PMID: 39605850 PMCID: PMC11599159 DOI: 10.1002/ccr3.9627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 07/24/2024] [Accepted: 10/11/2024] [Indexed: 11/29/2024] Open
Abstract
Venomous snakebites are critical medical emergency. Most fatalities resulted from respiratory failure attributable to abrupt neuromuscular paralysis. A 35-year-old male was treated for a snakebite on the dorsum of his right foot, which occurred seven hours prior to hospital admission during sleep. The patient exhibited symptoms of headache, myalgia, extremity weakness, and altered consciousness. No hemorrhagic or myotoxic symptoms were observed. He subsequently had respiratory failure, necessitating emergency bedside intubation with an Ambu bag, followed by treatment initiated in the district hospital and continued in the intensive care unit of a medical college hospital. Timely diagnosis, immediate transport to a medical facility, and rapid bedside intubation can save the lives of individuals experiencing respiratory failure due to venomous snake bites.
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Salim A, Chandrasekharuni G, Almeida JR, Vaiyapuri R, Williams HF, Arumugam S, Senthilkumaran S, Patel K, Williams T, Norbert Zsidó A, Vaiyapuri S. Snake phobia among the general population of Tamil Nadu, India. PLoS Negl Trop Dis 2024; 18:e0012284. [PMID: 39499721 PMCID: PMC11567567 DOI: 10.1371/journal.pntd.0012284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 11/15/2024] [Accepted: 10/24/2024] [Indexed: 11/07/2024] Open
Abstract
BACKGROUND A specific phobia is an anxiety disorder that is characterised by persistent and excessive fear in the presence of the object of the phobia. Animal phobias are the most prevalent forms of specific phobia among humans. Fear of snakes (snake phobia) is present in non-human primates which suggests its evolutionary origins as the ability to detect the threat of snakes was critical for survival. Snake phobia is a critical factor in protecting snakes and mitigating snakebite burden. To date, only one standardised psychometric test [the Snake Questionnaire (SNAQ) developed in 1974] has been used to quantify snake phobia although this was not performed in snakebite-endemic countries. In this study, we aimed to determine snake phobia in India, where snakebites and resulting deaths, disabilities and socioeconomic impacts are high. METHODOLOGY/PRINCIPAL FINDINGS A modified version of the SNAQ (i.e. SNAQ12), which has previously demonstrated internal consistency, excellent reliability, and good discrimination between phobics and non-phobics in Europe was used in this study. SNAQ12 was developed both in English and Tamil and validated by testing on several individuals. Then, the final questionnaire was disseminated to members of the public through various methods including social media and in person through academic and clinical organisations. We received a total of 2032 responses, comprising 1086 [53.4%] males and 946 [46.6%] females, and these data were analysed to determine various aspects of snake phobia in the study population. CONCLUSIONS/SIGNIFICANCE The results demonstrated good internal consistency in using SNAQ12 to determine the phobia amongst the tested population. The data suggests that males are more snake-phobic in all age groups than females in India, in contrast to previous research that suggested that females are usually more snake-phobic. No other critical factors contribute to snake phobia in this study population. The use of the SNAQ12 allowed us to easily discriminate between individuals with phobia and non-clinical controls. This tool can be used as part of the One Health approach to better understand the relationships between snake phobia and snakebites and their impact on the mental health and well-being of vulnerable populations.
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Affiliation(s)
- Anika Salim
- School of Pharmacy, University of Reading, Reading, United Kingdom
| | - Gnaneswar Chandrasekharuni
- School of Pharmacy, University of Reading, Reading, United Kingdom
- Madras Crocodile Bank Trust, Chennai, Tamil Nadu, India
| | - José R. Almeida
- School of Pharmacy, University of Reading, Reading, United Kingdom
| | | | | | | | | | - Ketan Patel
- School of Biological Sciences, University of Reading, Reading, United Kingdom
| | - Timothy Williams
- Department of Psychology, University of Reading, Reading, United Kingdom
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Bijlwan A, Pandey P. The national action plan for prevention and control of snakebite envenoming in India (NAPSE): Its role, opportunities and challenges. J Family Med Prim Care 2024; 13:5438-5439. [PMID: 39723000 PMCID: PMC11668436 DOI: 10.4103/jfmpc.jfmpc_902_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 08/02/2024] [Indexed: 12/28/2024] Open
Affiliation(s)
- Aanchal Bijlwan
- Department of Community Medicine, RDGMC, Ujjain, Madhya Pradesh, India
| | - Pulkit Pandey
- Department of Community Medicine, RDGMC, Ujjain, Madhya Pradesh, India
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23
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Gerardo CJ, Carter RW, Kumar S, Shirazi FM, Kotehal SD, Akpunonu PD, Bhalla A, Schwartz RB, Bammigatti C, Manikath N, Mukherjee PP, Arnold TC, Wolk BJ, S Sheikh S, Sollee DR, Vearrier DJ, Francis SJ, Aizenberg A, Kumar H, Ravikumar MK, Sarkar S, Haston T, Micciche A, Oomman SC, Owen JL, Ritter BA, Samuel SP, Lewin MR, Platts-Mills TF. Oral varespladib for the treatment of snakebite envenoming in India and the USA (BRAVO): a phase II randomised clinical trial. BMJ Glob Health 2024; 9:e015985. [PMID: 39442939 PMCID: PMC11499837 DOI: 10.1136/bmjgh-2024-015985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 10/02/2024] [Indexed: 10/25/2024] Open
Abstract
INTRODUCTION Snakebite envenoming (SBE) results in over 500 000 deaths or disabling injuries annually. Varespladib methyl, an oral inhibitor of secretory phospholipase A2, is a nearly ubiquitous component of snake venoms. We conducted a phase II clinical trial to assess efficacy and safety of oral varespladib methyl in patients bitten by venomous snakes. METHODS This double-blind, randomised, placebo-controlled trial enrolled patients in emergency departments in India and the USA. Patients with SBE were randomly assigned (1:1) to receive varespladib methyl or placebo two times per day for 1 week. All patients received standard of care, including antivenom. The primary outcome was change in the composite Snakebite Severity Score (SSS) measuring the severity of envenoming, from baseline to the average composite SSS at 6 and 9 hours. RESULTS Among 95 patients randomised August 2021 through November 2022, the most common snakebites were from Russell's vipers (n=29), copperheads (n=18) and rattlesnakes (n=14). The SSS improved from baseline to the average at 6 and 9 hours by 1.1 (95% CI, 0.7 to 1.6) in the varespladib group versus 1.5 (95% CI, 1.0 to 2.0) in the placebo group (difference -0.4, 95% CI, -0.8 to 0.1, p=0.13). While key secondary outcomes were not statistically different by treatment group, benefit was seen in the prespecified subgroup initiating study drug within 5 hours of bite (n=37). For this early treatment group, clinically important differences were observed for illness severity over the first week, patient-reported function on days 3 and 7 and complete recovery. No death or treatment emergent serious adverse event occurred. CONCLUSION For emergency department treatment of snakebites, the addition of varespladib to antivenom did not find evidence of difference for the primary outcome based on the SSS. A potentially promising signal of benefit was observed in patients initiating treatment within 5 hours of snakebite.
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Affiliation(s)
| | | | | | - Farshad M Shirazi
- University of Arizona Medical Center, University Campus, Tucson, Arizona, USA
| | | | - Peter D Akpunonu
- University of Kentucky College of Medicine, Lexington, Kentucky, USA
| | - Ashish Bhalla
- Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India
| | | | | | - Neeraj Manikath
- Government Medical College Kozhikode, Kozhikode, Kerala, India
| | - Partha P Mukherjee
- Calcutta National Medical College and Hospital, Kolkata, West Bengal, India
| | - Thomas C Arnold
- Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana, USA
| | - Brian J Wolk
- Loma Linda University Medical Center, Loma Linda, California, USA
| | - Sophia S Sheikh
- University of Florida Health Science Center Jacksonville, Jacksonville, Florida, USA
| | - Dawn R Sollee
- University of Florida College of Medicine, Jacksonville, Jacksonville, Florida, USA
| | - David J Vearrier
- The University of Mississippi Medical Center, Jackson, Mississippi, USA
| | | | - Adiel Aizenberg
- University of Arizona Medical Center, University Campus, Tucson, Arizona, USA
| | - Harish Kumar
- Sardar Patel Medical College, Bikaner, Rajasthan, India
| | - Madhu K Ravikumar
- Mysore Medical College and Research Institute, Mysore, Karnataka, India
| | - Sujoy Sarkar
- Calcutta National Medical College and Hospital, Kolkata, West Bengal, India
| | - Taylor Haston
- Augusta University Medical College of Georgia, Augusta, Georgia, USA
| | - Andrew Micciche
- University of Kentucky College of Medicine, Lexington, Kentucky, USA
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Silva GMD, Chowdhury A. Enhancing snakebite management: The role of small molecule therapeutics in complementing antivenom strategies. Toxicon 2024; 249:108081. [PMID: 39197595 DOI: 10.1016/j.toxicon.2024.108081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/21/2024] [Accepted: 08/25/2024] [Indexed: 09/01/2024]
Abstract
The variability in snake composition presents a significant challenge in accessing an effective broad-spectrum antivenom. These highly complex mixtures can result in numerous deleterious effects affecting thousands of individuals worldwide, particularly in Asia, sub-Saharan Africa, and Latin America. While the administration of antivenom remains a recommended treatment for snakebite envenomation and is the primary means to prevent systemic damage, there are limitations concerning specificity, reversal of local effects, and economic factors that hinder the availability of these antibodies. In this review, we have compiled information on the use of small molecule therapeutics in initial first-aid treatments before antivenom administration. These enzyme inhibitors have shown promise as viable candidates to broaden our treatment approaches, simplify procedures, reduce costs, and improve the clinical outcomes of affected patients.
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Affiliation(s)
- Glória Maria da Silva
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas-ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
| | - Abhinandan Chowdhury
- Adaptive Biotoxicology Lab, School of Environment, University of Queensland, St. Lucia, QLD, 4072, Australia; Department of Biochemistry & Microbiology, North South University, Dhaka, Bangladesh
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25
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Kakati H, Patra A, Mukherjee AK. Composition, pharmacology, and pathophysiology of the venom of monocled cobra (Naja kaouthia)- a medically crucial venomous snake of southeast Asia: An updated review. Toxicon 2024; 249:108056. [PMID: 39111718 DOI: 10.1016/j.toxicon.2024.108056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/31/2024] [Accepted: 07/31/2024] [Indexed: 08/15/2024]
Abstract
The Monocled Cobra (Naja kaouthia), a category one medically significant snake from the Elapidae family, inflicts severe envenomation in South and Southeast Asian countries. N. kaouthia is distributed throughout the eastern and northeastern parts of India, Nepal, Bangladesh, Myanmar, Thailand, Vietnam, Malaysia, and southwestern China. Envenomation by N. kaouthia is a medical emergency, and the primary clinical symptoms are neurotoxicity and localized tissue destruction. Unfortunately, data on the actual magnitude of N. kaouthia envenomation is scarce due to poor record keeping, lack of diagnostic kits, and region-wise well-coordinated epidemiological surveys. The present review highlights the diversity in the composition of N. Kaouthia venom (NKV) across various geographical regions, as revealed through biochemical and proteomic analyses. The qualitative and quantitative differences in the toxin isoforms result in differences in lethality and pathophysiological manifestation that may limit the effectiveness of antivenom therapy. Studies on commercial polyvalent antivenom (PAV) effectiveness against distinct NKV samples have revealed varying toxicity and enzymatic activity neutralization. Additionally, the identification of snake venom's poorly immunogenic toxins by mass spectrometry, quantification of venom-specific antibodies, and implications for antivenom therapy against snakebites are highlighted. Future directions involve clinical studies on NK envenomation where the snake is frequently encountered and the correlation of this data with NKV composition in that region. For more efficient and superior hospital management of NK envenomation, research should enhance the current immunization procedure to boost the development of antibodies against less immunogenic venom components of this snake.
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Affiliation(s)
- Hirakjyoti Kakati
- Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur- 784028, Assam, India
| | - Aparup Patra
- Institute of Advanced Studies in Science and Technology, Vigyan Path Garchuk, Paschim Boragaon, Guwahati-781035, Assam, India; Amrita Research Centre, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, 121002, India
| | - Ashis K Mukherjee
- Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur- 784028, Assam, India; Institute of Advanced Studies in Science and Technology, Vigyan Path Garchuk, Paschim Boragaon, Guwahati-781035, Assam, India.
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26
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Shetty VU. Mobile Critical Care in Resource-Limited Settings: An Unmet Need. Ann Glob Health 2024; 90:59. [PMID: 39309761 PMCID: PMC11414459 DOI: 10.5334/aogh.4506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 09/01/2024] [Indexed: 09/25/2024] Open
Abstract
Care of the critically ill in resource-limited areas, inside or outside the intensive care unit (ICU), is indispensable. Murthy and Adhikari noted that about 70% of patients in low-middle income (LMIC) areas could benefit from good critical care. Many patients in resource-limited settings still die before getting to the hospital. Investing in capacity building by strengthening and expanding ICU capability and training intensivists, critical care nurses, respiratory therapists, and other ICU staff is essential, but this process will take years. Also, having advanced healthcare facilities that are still far from remote areas will not do much to alleviate distance and mode of transportation as barriers to achieving good critical care. This paper discusses the importance of mobile critical care units (MCCUs) in supporting and enhancing existing emergency medical systems. MCCUs will be crucial in addressing critical delays in transportation and time to receive appropriate lifesaving critical care in remote areas. They are incredibly versatile and could be used to transfer severely ill patients to a higher level of care from the field, safely transfer critically ill patients between hospitals, and, sometimes, almost more importantly, provide standalone short-term critical care in regions where ICUs might be absent or immediately inaccessible. MCCUs should not be used as a substitute for primary care or to bypass readily available services at local healthcare centers. It is essential to rethink the traditional paradigm of 'prehospital care' and 'hospital care' and focus on improving the care of critically ill patients from the field to the hospital.
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Affiliation(s)
- Varun U. Shetty
- Intensivist, Cleveland Clinic, Clinical Assistant Professor, Case Western Reserve University Lerner College of Medicine, OH, USA
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Barik AK, Mohanty CR, Behera S, Radhakrishnan RV. Snake envenomation in children: Experience from a tertiary care hospital in Northern India: Some concerns. Med J Armed Forces India 2024; 80:614-616. [PMID: 39309582 PMCID: PMC11411310 DOI: 10.1016/j.mjafi.2024.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 08/03/2024] [Indexed: 09/25/2024] Open
Affiliation(s)
- Amiya Kumar Barik
- Assistant Professor (Anaesthesia & Intensive Care) Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Chitta Ranjan Mohanty
- Additional Professor & Head (Trauma & Emergency), All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Srikant Behera
- Assistant Professor (General Medicine), All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
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Pahari N, Sharma BD, Ghimire S, Sharma S, Kafle B, Upadhaya T, Montasir AA. Neurotoxicity and acute renal injury secondary to Russell's viper bite in an individual: a case report from Nepal. Ann Med Surg (Lond) 2024; 86:5489-5491. [PMID: 39239067 PMCID: PMC11374281 DOI: 10.1097/ms9.0000000000002072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 04/07/2024] [Indexed: 09/07/2024] Open
Abstract
Introduction and importance Owing to the high number of envenomation and fatalities, the Russell's viper holds greater medicinal significance than any other Asian serpent. South East Asia is one of the most snakebite-prone regions in the world. Dense population, extensive agricultural practices, the abundance of venomous snake species, and an overall lack of knowledge about primary treatment (first aid) are the major culprits associated with snake bite-related morbidity and mortality. The venom of vipers is known to produce vasculotoxicity and contains hemotoxins. Case presentation The authors describe a patient who was bitten by a viperine snake and showed signs of both neurotoxicity and acute kidney injury (AKI). The 20 years male was treated in a tertiary care centre in Nepal. The patient developed respiratory failure and needed ventilator support. Further, more haemodialysis was also done to manage AKI. Later, the patient was discharged after a smooth recovery. Discussion Numerous clinical manifestations, such as neurotoxicity and vasculotoxicity, can result from a viperine bite. The majority of viperine snakebites are hemotoxic. Dual neurotoxic symptoms are possible after a viperine bite despite their rarity. The prevention of respiratory failure depends critically on the early detection of neurotoxicity. Conclusion Unusual neuromuscular paralysis is caused by Russell's vipers (Daboia russelii) in South East Asia. Physicians should know the exceptional presentations of snakebites to diagnose and treat patients.
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Affiliation(s)
- Nabin Pahari
- Department of Intensive Care, Lumbini Provincial Hospital
| | | | - Sagun Ghimire
- Deaprtment of Neurosurgery, B and B hospital, Lalitpur
| | - Shanta Sharma
- Department of Community Medicine, Devdaha Medical College, Rupandehi
| | - Bikram Kafle
- Department of Psychiatry, Devdaha Medical College, Rupandehi
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Ketor CE, Benneh CK, Mensah KB, Sarkodie E, Mensah A, Somuah SO, Akakpo S, Buabeng KO. Snakebites and Antisnake Venom Utilization in Ghana's Oti Region: A 6-Year Retrospective Study. BIOMED RESEARCH INTERNATIONAL 2024; 2024:6692421. [PMID: 39140000 PMCID: PMC11321883 DOI: 10.1155/2024/6692421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 02/21/2024] [Accepted: 06/11/2024] [Indexed: 08/15/2024]
Abstract
Background: Snakebite is a global environmental and occupational hazard and a significant public health threat. In rural areas, snakebite cases often go unreported and undocumented due to the lack of access to well-structured healthcare facilities/infrastructure. In some cases, the need for antisnake venom (ASV) far outstrips supply, negatively affecting treatment outcomes. This study, therefore, assessed the epidemiological characteristics of snakebite cases, their management, and how antivenoms are utilised at the selected hospital in the Jasikan District Hospital. Methods: A 6-year retrospective study using secondary data from antivenom return forms (pharmacy records), clinical records (patient folders), the District Health Information Management System-2 (DHIMS-2) database, and consulting room registers was carried out in selected hospitals in the Jasikan District, Oti, Ghana. Results: The predominant symptom of snakebite was localised pain (71.4%). The snakebite commonly occurred at home (19%) and on farms (18%). Of the 98 snakebite cases, ASV was administered to 73 (74.5%) cases. Supportive treatment applied included prophylactic antitetanus immunoglobulin (ATS) (80.6%), prophylactic antibiotics (63%), corticosteroids (80.6%), and analgesics (63%). 95% (n = 94) of complete recoveries were recorded; three were discharged against medical advice, and one was mortality. The supply and use of antivenom were erratic throughout the months of high incidence, partly due to inconsistent availability at the Regional Medical Stores. The average ASV vials and hospital stay duration were 1.23 ± 0.86 vials and 2.67 ± 1.97 days, respectively. Although the peak of snakebites occurs in April, May, and June, the demand for antivenom in April and May exceeded supply. Conclusion: The outcome of most snakebite case management was appropriate, irrespective of inadequate ASV supply in certain months. The erratic antivenom supply should be aligned with seasonal and facility-use patterns to enhance regional snakebite management.
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Affiliation(s)
- Courage Edem Ketor
- Pharmacy DepartmentJasikan District HospitalGhana Health Service, Jasikan, Ghana
- Department of Pharmacy PracticeSchool of PharmacyUniversity of Health and Allied Sciences, Ho, Ghana
| | - Charles Kwaku Benneh
- Department of Clinical Pharmacy and Pharmacy PracticeUlster University, Coleraine, UK
| | - Kofi Boamah Mensah
- Department of Pharmacy PracticeFaculty of Pharmacy and Pharmaceutical SciencesCollege of Health SciencesKwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Emmanuel Sarkodie
- University HospitalKwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Adelaide Mensah
- Department of PharmaceuticsSchool of PharmacyUniversity of Health and Allied Sciences, Ho, Ghana
| | - Samuel Owusu Somuah
- Department of Pharmacy PracticeSchool of PharmacyUniversity of Health and Allied Sciences, Ho, Ghana
| | | | - Kwame Ohene Buabeng
- Department of Pharmacy PracticeSchool of PharmacyUniversity of Health and Allied Sciences, Ho, Ghana
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Baleela RMH, Mohammad A, Saeed SAK. The role of social media in public health awareness during times of war in Sudan: snakebites and scorpion stings. BMC Public Health 2024; 24:1752. [PMID: 38956503 PMCID: PMC11218301 DOI: 10.1186/s12889-024-19156-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 06/14/2024] [Indexed: 07/04/2024] Open
Abstract
BACKGROUND Snakebite envenomation (SBE) and scorpion sting envenomation (SSE) are significant neglected tropical diseases that primarily affect impoverished communities in rural areas of developing nations. A lack of understanding about snake and scorpion species and their distribution exacerbates the disabilities and fatalities caused by SBE and SSE. In Sudan, particularly in regions affected by ongoing conflicts where healthcare resources are scarce, social media platforms offer a cost-effective approach to addressing public health challenges. Our aim in this study is to highlight the benefits of using social media for data collection and health promotion in such environments. METHODS We present a cost-effective communication and data collection strategy implemented at the Toxic Organisms Research Centre (TORC) of the University of Khartoum, focusing on a Facebook group, "Scorpions and Snakes of Sudan", as our primary social media platform. Additionally, we discuss the lessons learned and the initial impact of this strategy on enhancing population health literacy. RESULTS The group community is composed of ~ 5000 members from 14 countries. During the period from January 2023 to January 2024, we received 417 enquiries about snakes and scorpions belonging to 11 families and composed of 55 species. In addition, 53 other enquiries covered a range of organisms and their tracks (e.g., spiders, skinks, chameleons, foxes, sun spiders, centipedes, lizards, moth larvae, and insect tracks). The first photographic evidence of Malpolon monspessulanus in Sudan was via the group activities. The rare species Telescopus gezirae, the Blue Nile cat snake, is also documented via the group member's queries. Recognizing the evolving nature of social media use in public health, we also address the current limitations and evidence gaps that need to be addressed to effectively translate best practices into policy. CONCLUSION In conclusion, utilizing Facebook as an institutional platform to share scientific information in simple Arabic language underscores the proactive roles that citizens, scientists, and public health stakeholders can play in leveraging social media for eHealth, eAwareness, and public health initiatives. This approach highlights the potential for collaborative efforts, particularly during crises, to maximize the benefits of social media in advancing public health.
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Affiliation(s)
- Rania M H Baleela
- Toxic Organisms Research Centre, Faculty of Science, University of Khartoum, Khartoum, Sudan.
- Department of Zoology, Faculty of Science, University of Khartoum, Khartoum, Sudan.
| | | | - Sara A K Saeed
- Toxic Organisms Research Centre, Faculty of Science, University of Khartoum, Khartoum, Sudan
- Natural History Museum, Faculty of Science, University of Khartoum, Khartoum, Sudan
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31
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Nandana MB, Bharatha M, Praveen R, Nayaka S, Vishwanath BS, Rajaiah R. Dimethyl ester of bilirubin ameliorates Naja naja snake venom-induced lung toxicity in mice via inhibiting NLRP3 inflammasome and MAPKs activation. Toxicon 2024; 244:107757. [PMID: 38740099 DOI: 10.1016/j.toxicon.2024.107757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/06/2024] [Accepted: 05/10/2024] [Indexed: 05/16/2024]
Abstract
Naja naja snake bite causes thousands of deaths worldwide in a year. N. naja envenomed victims exhibit both local and systemic reactions that potentially lead to death. In clinical practice, pulmonary complications in N. naja envenomation are commonly encountered. However, the molecular mechanisms underlying N. naja venom-induced lung toxicity remain unknown. Here, we reasoned that N. naja venom-induced lung toxicity is prompted by NLRP3 inflammasome and MAPKs activation in mice. Treatment with dimethyl ester of bilirubin (BD1), significantly inhibited the N. naja venom-induced activation of NLRP3 inflammasome and MAPKs both in vivo and in vitro (p < 0.05). Further, BD1 reduced N. naja venom-induced recruitment of inflammatory cells, and hemorrhage in the lung toxicity examined by histopathology. BD1 also diminished N. naja venom-induced local toxicities in paw edema and myotoxicity in mice. Furthermore, BD1 was able to enhance the survival time against N. naja venom-induced mortality in mice. In conclusion, the present data showed that BD1 alleviated N. naja venom-induced lung toxicity by inhibiting NLRP3 inflammasome and MAPKs activation. Small molecule inhibitors that intervene in venom-induced toxicities may have therapeutic applications complementing anti-snake venom.
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Affiliation(s)
- Manuganahalli B Nandana
- Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India; Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India
| | - Madeva Bharatha
- Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India
| | - Raju Praveen
- Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India
| | - Spandan Nayaka
- Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India
| | - Bannikuppe S Vishwanath
- Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India.
| | - Rajesh Rajaiah
- Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India.
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Stephen S, Mohanty CR, Radhakrishnan RV, Issac A, Jacob J, Krishnan N, Vr V, Guru S, Muhammed Shaji I, Aggarwal A. Clinico-Epidemiological Profile, Trends, and Health-Related Outcomes of Snakebite Victims: A One-Year Prospective Study from Eastern India. Wilderness Environ Med 2024; 35:155-165. [PMID: 38634117 DOI: 10.1177/10806032241239628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2024]
Abstract
INTRODUCTION Snakebite envenomation is a significant life-threatening public health problem in Southeast Asia (SEA). In this region, India reported the largest number of snakebite deaths from 2000 to 2019 (1.2 million), with an average of 58,000 deaths yearly. METHODS This prospective observational study was carried out among snakebite victims at the emergency department (ED) of a tertiary care public sector hospital in eastern India. RESULTS A total of 145 cases of venomous snakebite were investigated. More than half (n = 81, 56%) of the snakebite victims were between 17 to 45 years. Most of the snakebite victims were male (68%) and were farmers (53%) by occupation. The majority of snakebites occurred during the daytime (76%) and while outdoors (67%). Most victims sustained a bite on the lower extremity (71%). The peak incidence of snakebites occurred from June to September (69%). Three-quarters of all patients were unaware of the required first aid measures following a snakebite. Among the 145 venomous snakebites, 48 were presumptively identified as the Indian cobra, 32 by the Indian krait, 56 by the Russel's viper, and 9 by saw-scaled viper. The mean duration from the snakebite to the onset of systemic effects in the Indian cobra was 52 ± 14.28 min, 66 ± 18.35 min in the Indian krait, 42 ± 13.47 min in Russel's viper, and 48 ± 16.38 min in saw-scaled viper. Respiratory failure was the commonly observed complication following an elapid envenomation. The mortality rate was 2.1% among the patients treated with antivenom. CONCLUSIONS Snakebite is considered an occupational hazard in India, commonly affecting the young population in their productive period. The peak incidence was during monsoon season, and the majority had neurotoxic envenomation following an elapid bite (55%) that contributed to the increased mortality and morbidity among young adults. Of the 145 patients, the majority (84%) recovered fully with treatment; 16% of the victims developed morbidity viz cellulitis, respiratory failure, acute renal failure, compartment syndrome, local tissue necrosis, intracerebral hemorrhage, and disseminated intravascular coagulation. Appropriate first aid measures and timely medical intervention can significantly improve the treatment outcome following snakebites.
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Affiliation(s)
- Shine Stephen
- College of Nursing, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India
| | - Chitta Ranjan Mohanty
- Department of Trauma and Emergency, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India
| | | | - Alwin Issac
- College of Nursing, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India
| | - Jaison Jacob
- College of Nursing, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India
| | - Nadiya Krishnan
- College of Nursing, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India
| | - Vijay Vr
- College of Nursing, All India Institute of Medical Sciences (AIIMS), Raebareli, India
| | - Satyabrata Guru
- Department of Trauma and Emergency, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India
| | - Ijas Muhammed Shaji
- Department of Trauma and Emergency, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India
| | - Achala Aggarwal
- Department of Nursing Services, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
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Naz H, Chamola R, Sarafraz J, Razabizadeh M, Jain S. An efficient densenet-based deep learning model for Big-4 snake species classification. Toxicon 2024; 243:107744. [PMID: 38701904 DOI: 10.1016/j.toxicon.2024.107744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/19/2024] [Accepted: 04/30/2024] [Indexed: 05/05/2024]
Abstract
Snakebite poses a significant health threat in numerous tropical and subtropical nations, with around 5.4 million cases reported annually, which results in 1.8-2.7 million instances of envenomation, underscoring its critical impact on public health. The 'BIG FOUR' group comprises the primary committers responsible for most snake bites in India. Effective management of snakebite victims is essential for prognosis, emphasizing the need for preventive measures to limit snakebite-related deaths. The proposed initiative seeks to develop a transfer learning-based image classification algorithm using DenseNet to identify venomous and non-venomous snakes automatically. The study comprehensively evaluates the image classification results, employing accuracy, F1-score, Recall, and Precision metrics. DenseNet emerges as a potent tool for multiclass snake image classification, achieving a notable accuracy rate of 86%. The proposed algorithm intends to be incorporated into an AI-based snake-trapping device with artificial prey made with tungsten wire and vibration motors to mimic heat and vibration signatures, enhancing its appeal to snakes. The proposed algorithm in this research holds promise as a primary tool for preventing snake bites globally, offering a path toward automated snake capture without human intervention. These findings are significant in preventing snake bites and advancing snakebite mitigation strategies.
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Affiliation(s)
- Huma Naz
- School of Computer Science and Engineering, University of Petroleum and Energy Studies Dehradun, India
| | - Rahul Chamola
- Department of Mechanical Engineering, School of Advanced Engineering, University of Petroleum and Energy Studies, Dehradun, India.
| | - Jaleh Sarafraz
- UMR7179 CNRS/MNHN, Département Àdaptations du vivant, Museum National d'Histoire Naturelle, Paris, France
| | - Mahdi Razabizadeh
- Department of Biodiversity, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
| | - Siddharth Jain
- Department of Mechanical Engineering, School of Advanced Engineering, University of Petroleum and Energy Studies, Dehradun, India
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Mb L, Parmar DS, Singh S, Britto C. An indigenously developed tele-ICU model to treat severe cases of envenomation in remote regions in India. BMJ Case Rep 2024; 17:e255786. [PMID: 38782437 DOI: 10.1136/bcr-2023-255786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024] Open
Abstract
In cases of severe envenomation due to snakebites, patients require antivenom, intensive care management, including respiratory support, haemodynamic monitoring and renal replacement therapy. Early recognition and treatment of complications such as acute kidney injury, rhabdomyolysis and coagulopathy are important to improve outcomes.Tele-ICU models can play a critical role in providing access to critical care expertise and nuanced support to remote healthcare facilities that may not have the necessary resources or expertise to manage complex cases of envenomation. With the help of telemedicine technology, remote intensivists can provide timely guidance on diagnosis and ongoing management, improving the quality of care and outcomes for patients. We discuss two patients in resource-constrained regions of India with severe envenomation who were managed with tele-ICU support.
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Affiliation(s)
- Lokesh Mb
- Cloudphysician Healthcare Pvt Ltd, Bengaluru, India
| | | | | | - Carl Britto
- Division of Critical CareDepartment of Anaesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA
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Das DS, Mohapatra RK, Mohanty RR, Patel RK. Acute ischaemic stroke and deep vein thrombosis following snakebite. BMJ Case Rep 2024; 17:e259071. [PMID: 38719248 PMCID: PMC11085697 DOI: 10.1136/bcr-2023-259071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2024] Open
Abstract
Snakebite envenomation remains a neglected tropical public health issue claiming thousands of lives every year. It is a common medical emergency and a threat to the impoverished populations of low-income and middle-income countries including India. A combination of ischaemic stroke and deep vein thrombosis is a devastating duo complication of snake bite, with no literature report to date. Here, the authors report an unusual case of a young woman developing ischaemic stroke and deep vein thrombosis following snakebite even after the use of antivenom. MRI brain showed right thalamic infarct with haemorrhagic transformation and, ultrasound Doppler revealed right lower limb deep vein thrombosis. The pathophysiology of deep vein thrombosis and ischaemic stroke is complex. It is believed that the activation of the coagulation cascade, complement system together with endothelial injury and immune activation leads to inflammation, thrombosis and occlusion of smaller and even larger vessels.
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Affiliation(s)
- Dhriti Sundar Das
- General Medicine, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, Odisha, India
| | - Rakesh Kumar Mohapatra
- General Medicine, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, Odisha, India
| | - Rashmi Ranjan Mohanty
- General Medicine, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, Odisha, India
| | - Ranjan Kumar Patel
- Radiodiagnosis, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, Odisha, India
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Chowdhury MAW, Müller J, Ghose A, Amin R, Sayeed AA, Kuch U, Faiz MA. Combining species distribution models and big datasets may provide finer assessments of snakebite impacts. PLoS Negl Trop Dis 2024; 18:e0012161. [PMID: 38768190 PMCID: PMC11142713 DOI: 10.1371/journal.pntd.0012161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 05/31/2024] [Accepted: 04/22/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND Snakebite is a major poverty-related neglected tropical disease. An integrated scientific approach is needed to understand the dynamics of this important health issue. Our objective was to estimate snakebite occurrence in a tropical area by using a blend of ecological modelling and robust statistical analysis. METHODS The present study used climatic, environmental, and human population density data to determine the area with snakebite occurrence-probability for the first time in Bangladesh. We also analysed a large, 16-year dataset of hospitalized snakebite cases to reveal the epidemiology of snakebite in the south-eastern zone of the country. FINDINGS Our results show that cobra bite is the most commonly occurring venomous snakebite in humans (around ~12% of the total yearly snakebite records), and men are more frequently bitten than women (2/3 of human victims are men). Most bites occur during the rainy season for cobra and green pit viper, while krait bites are not restricted to any particular season. As snakebite incidents are closely related to climate conditions, we can model snakebite risk using temperature and precipitation variables. Whereas there is a lack of snakebite reports from several parts of the study area in official records, our models predict that the entire study area is favourable for snakebite incidents. Based on the combined evidence we estimate that about 200,000 snakebite events occur every year in the south-eastern part of Bangladesh alone. Considering future global climate change, our model projections show that snakebite incidence in Bangladesh might not significantly decrease in the future (- 2070-); however, the distribution of probabilities might change, with a predicted increase of snakebite incidence in the hilly areas of the country. CONCLUSIONS Using climatic data to predict snakebite incidence in Bangladesh allowed us to provide estimations of the total annual number of snakebite cases in the study area. As in most countries, the scarcity of accurate epidemiological data in official records might have masked the real magnitude of this problem. Our analysis suggests that the problem of snakebite envenoming in Bangladesh might be worse than currently perceived. A long-term sustainable snakebite program plan should be designed and institutionalized, considering climatic, geographical and human demographic variables, to obtain better data and facilitate the implementation of accurate snakebite management programs for this country.
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Affiliation(s)
- Mohammad Abdul Wahed Chowdhury
- Department of Zoology, University of Chittagong, Chattogram, Bangladesh
- Museum für Naturkunde, Leibniz-Institut für Evolutions- und Biodiversitätsforschung, Berlin, Germany
- Institut für Biologie, Humboldt-Universität zu Berlin, Berlin, Germany
- Venom Research Centre, Department of Medicine, Chittagong Medical College, Chattogram, Bangladesh
| | - Johannes Müller
- Museum für Naturkunde, Leibniz-Institut für Evolutions- und Biodiversitätsforschung, Berlin, Germany
- Institut für Biologie, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Aniruddha Ghose
- Venom Research Centre, Department of Medicine, Chittagong Medical College, Chattogram, Bangladesh
- Department of Medicine, Chittagong Medical College, Chattogram, Bangladesh
| | - Robed Amin
- Venom Research Centre, Department of Medicine, Chittagong Medical College, Chattogram, Bangladesh
- Directorate General of Health Services, Ministry of Health and Family Welfare, Dhaka, Bangladesh
| | - Abdullah Abu Sayeed
- Venom Research Centre, Department of Medicine, Chittagong Medical College, Chattogram, Bangladesh
- Department of Medicine, Chittagong Medical College, Chattogram, Bangladesh
| | - Ulrich Kuch
- Venom Research Centre, Department of Medicine, Chittagong Medical College, Chattogram, Bangladesh
- Institute of Occupational Medicine, Social Medicine and Environmental Medicine, Goethe University, Frankfurt am Main, Germany
| | - Mohammad Abul Faiz
- Venom Research Centre, Department of Medicine, Chittagong Medical College, Chattogram, Bangladesh
- Dev Care Foundation, Chattogram, Bangladesh
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Afroz A, Siddiquea BN, Chowdhury HA, Jackson TNW, Watt AD. Snakebite envenoming: A systematic review and meta-analysis of global morbidity and mortality. PLoS Negl Trop Dis 2024; 18:e0012080. [PMID: 38574167 PMCID: PMC11020954 DOI: 10.1371/journal.pntd.0012080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 04/16/2024] [Accepted: 03/18/2024] [Indexed: 04/06/2024] Open
Abstract
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.
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Affiliation(s)
- Afsana Afroz
- Australian Venom Research Unit, Department of Biochemistry and Pharmacology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
| | - Bodrun Naher Siddiquea
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia
| | - Hasina Akhter Chowdhury
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia
| | - Timothy NW Jackson
- Australian Venom Research Unit, Department of Biochemistry and Pharmacology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
| | - Andrew D. Watt
- Australian Venom Research Unit, Department of Biochemistry and Pharmacology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
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Meena P, Bhargava V, Gupta P, Panda S, Bhaumik S. The kidney histopathological spectrum of patients with kidney injury following snakebite envenomation in India: scoping review of five decades. BMC Nephrol 2024; 25:112. [PMID: 38515042 PMCID: PMC10958888 DOI: 10.1186/s12882-024-03508-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 02/17/2024] [Indexed: 03/23/2024] Open
Abstract
INTRODUCTION Snakebite is a public health problem leading to about 58,000 deaths every year in India. Kidney injury subsequent to snakebite envenomation is common with a reported prevalence of up to 32%. The current study aims to elucidate the spectrum of kidney histopathology in acute kidney injury (AKI) cases associated with snake bites. METHODS We searched seven electronic database studies to identify studies describing the histopathological findings in the kidney with snakebite envenomation. Two reviewers independently conducted titles and abstract screening as well as full-text evaluation for the final inclusion decision. Data were extracted as per the standardized form. We conducted narrative synthesis. Studies done exclusively on autopsy findings, in vitro studies, and case reports were excluded. RESULTS We retrieved 1464 studies and finally included 28 studies which met the eligibility criteria in the analysis. Most studies were single-centre and the majority were cross-sectional. Overall we included a total of 534 renal biopsies. Russell's viper bite was the most common cause related to AKI. Acute tubular necrosis was the most common finding followed by acute interstitial nephritis, acute cortical necrosis (ACN), and thrombotic microangiopathy (TMA). Vasculitis changes in vessels were rarely reported. Lesions such as ACN and TMA were associated with poor outcomes. CONCLUSION This analysis supports the notion that renal biopsies are important to guide prognosis and increase our knowledge about post-snake bite AKI pathophysiology.
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Affiliation(s)
- Priti Meena
- Department of Nephrology, All India Institute Medical Sciences, Bhubaneswar, India.
| | - Vinant Bhargava
- Institute of Renal Science, Sir Gangaram Hospital, New Delhi, India
| | - Pallav Gupta
- Department of Pathology, Sir Gangaram Hospital, New Delhi, India
| | - Sandip Panda
- Department of Nephrology, All India Institute Medical Sciences, Bhubaneswar, India
| | - Soumyadeep Bhaumik
- Meta-research and evidence synthesis unit, The George Institute for Global Health, New Delhi, India
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Yiğit YD, Yiğit E. Single-center experience in a rural hospital in scorpio stings and snakebites. TOXICOLOGIE ANALYTIQUE ET CLINIQUE 2024; 36:90-96. [DOI: 10.1016/j.toxac.2023.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Nandana MB, Bharatha M, Vishwanath BS, Rajaiah R. Naja naja snake venom-induced local toxicities in mice is by inflammasome activation. Toxicon 2024; 238:107590. [PMID: 38163462 DOI: 10.1016/j.toxicon.2023.107590] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 12/26/2023] [Accepted: 12/28/2023] [Indexed: 01/03/2024]
Abstract
Snake bite envenomation causes tissue damage resulting in acute and chronic inflammatory responses. Inflammasome activation is one of the factors involved in tissue damage in a mouse model of snake envenomation. The present study examines the potency of Indian Big Four snake venoms in the activation of inflammasome and its role in local and systemic tissue toxicity. Among Indian Big Four snake venoms, Naja naja venom activated NLRP3 inflammasome in mouse macrophages. Activation of NLRP3 inflammasome was also observed in mouse foot paw and thigh muscle upon administration of N. naja venom. Intraperitoneal administration of N. naja venom cause systemic lung damage showed activation of NLRP3 inflammasome. Treatment with MCC950, a selective NLRP3 inflammasome inhibitor effectively inhibited N. naja venom-induced activation of caspase-1 and liberation of IL-1β in macrophages. In mice, MCC950 partially inhibited the activation of NLRP3 inflammasome in N. naja venom administered foot paw and thigh muscle. In conclusion, the present data showed that inflammasome is one of the host responses involved in N. naja snake venom-induced toxicities. The inhibition of inflammasome activation will provide new insight into better management of snake bite-induced local tissue damage.
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Affiliation(s)
- Manuganahalli B Nandana
- Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India; Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India
| | - Madeva Bharatha
- Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India
| | - Bannikuppe S Vishwanath
- Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India.
| | - Rajesh Rajaiah
- Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore, Karnataka, 570006, India.
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Maduwage K, Kodagoda Gamage S, Gutiérrez JM. First aid and pre-hospital practices in snakebite victims: The persistent use of harmful interventions. Toxicon 2024; 238:107582. [PMID: 38128838 DOI: 10.1016/j.toxicon.2023.107582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/07/2023] [Accepted: 12/18/2023] [Indexed: 12/23/2023]
Abstract
First aid intervention and pre-hospital (FAPH) practices are common in patients suffering from snakebite envenomation (SBE). In this study, we have reviewed the literature concerning the use of these practices in various regions of the world in the period 1947-2023 based on published prospective studies. A total of 71 publications fulfilled the inclusion criteria. In terms of the total number of patients in all studies that used each FAPH intervention, the most common practice was the application of tourniquets (45.8%). Other FAPH practices described include cuts/incisions (6.7%), the application of a variety of natural or synthetic substances at the bite site (5.6%), and ingestion of natural, usually herbal, remedies (2.9%). Washing the site of the bite was described in 9.1% of patients. There were other less frequent FAPH practices, including suction, splinting-immobilization, pressure-bandage, ice packs, application of a snake/black stone, and administration of alcoholic beverages. There were differences in the extent of application of FAPH interventions in different continents. Tourniquets were highest (55.7%) in Asia. Topical application of various products was common in South America, while pressure-bandage was only reported in Australia. We did not find any statistically significant variations in the frequency of the most frequent FAPH interventions at three-time intervals (before 2006, between 2006 and 2015, and after 2015). Our findings highlight the use of FAPH interventions in patients suffering SBE, some of which are known to be harmful. It is necessary to study these practices to a higher level of geographic granularity, using community-based surveys. Programs tailored to local contexts should be promoted, aimed at avoiding the use of harmful FAPH practices. It is also necessary to assess the efficacy and safety of some interventions through robust preclinical and clinical studies.
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Affiliation(s)
- Kalana Maduwage
- Discipline of Biomedical Sciences, University of New England, NSW, 2350, Australia.
| | | | - José María Gutiérrez
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
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Mahadevaiah V, Ravikumar K, Manjunath H. "Fanged to Peril": Interesting Snake Bite Case Series. Cureus 2024; 16:e53319. [PMID: 38435905 PMCID: PMC10906932 DOI: 10.7759/cureus.53319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2024] [Indexed: 03/05/2024] Open
Abstract
Snakebite is an acute life-threatening medical emergency and is included among the neglected tropical diseases in India. The incidence of snakebite mortality is particularly high in Southeast Asia and India has the highest number of cases of snakebites with a mortality of 35,000 to 50,000 cases per year according to the World Health Organization (WHO) direct estimation. There are three families of venomous snakes in Southeast Asia which mainly include Elapidae, Viperidae, and Colubridae. Snakebite victims show varied clinical presentations ranging from local signs to systemic signs of envenomation. WHO has detailed five syndromes based on various clinical presentations and the most probable family of snakes responsible for that syndrome. There are several cases reported on the initial clinical presentations in the literature; however, case series which include the presentation to ER, the hospital course, and management of complications have not been published in the literature. Following is a case series of five patients of diverse age groups who presented to the Emergency Medicine Department (ED) with a wide spectrum of clinical presentations, diverse clinical courses, and management strategies. These patients not only required the administration of anti-snake venom in the ED but also required additional interventional modalities including renal replacement therapy for acute kidney injury and biopsy-proven acute tubular necrosis, viper-induced consumptive coagulopathy, management of coagulopathy in pediatrics, management of compartment syndrome in pregnancy, mechanical ventilation for respiratory failure and management of neurotoxicity. We hereby emphasize that early recognition of signs of envenomation and early administration of anti-snake venom is imperative in the initial management of snakebites along with the monitoring of a snakebite victim for complications and timely management of the same.
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Affiliation(s)
- Vivek Mahadevaiah
- Department of Emergency Medicine, Vydehi Institute of Medical Sciences and Research Center, Bangalore, IND
| | - Kalpana Ravikumar
- Department of Emergency Medicine, Vydehi Institute of Medical Sciences and Research Center, Bangalore, IND
| | - Harismitha Manjunath
- Department of Emergency Medicine, Vydehi Institute of Medical Sciences and Research Center, Bangalore, IND
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Kumar A, Madni ZK, Chaturvedi S, Salunke DM. Recombinant human scFv antibody fragments against phospholipase A2 from Naja naja and Echis carinatus snake venoms: In vivo neutralization and mechanistic insights. Mol Immunol 2024; 165:55-67. [PMID: 38154407 DOI: 10.1016/j.molimm.2023.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 11/07/2023] [Accepted: 12/17/2023] [Indexed: 12/30/2023]
Abstract
Snake envenomation results in a range of clinical sequelae, and widely used animal-based conventional antivenoms exhibit several limitations including the adverse immunological effects in human snake bite victims. Therefore, human monoclonal anti-snake venom antibodies or fragments can be an alternate therapy for overcoming the existing limitations. We developed venom-neutralizing humanized scFv antibodies and analyzed biochemical mechanisms associated with the inhibition of toxicity. Tomlinson I and J human scFv antibody libraries were screened against Naja naja and Echis carinatus venoms, and seven unique scFv antibodies were obtained. Further, specific toxins of snake venom interacting with each of these scFvs were identified, and phospholipase A2 (PLA2) was found to be prominently captured by the phage-anchored scFv antibodies. Our study indicated PLA2 to be one of the abundant toxins in Naja naja and Echis carinatus venom samples. The scFvs binding to PLA2 were used to perform in vivo survival assay using the mouse model and in vitro toxin inhibition assays. scFv N194, which binds to acidic PLA2, protected 50% of mice treated with Naja naja venom. Significant prolongation of survival time and 16% survival were observed in Echis carinatus venom-challenged mice treated with scFv E113 and scFv E10, respectively. However, a combination comprised of an equal amount of two scFvs, E113 and E10, both interacting with basic PLA2, exhibited synergistically enhanced survival of 33% in Echis carinatus venom-challenged mice. No such synergistically enhanced survival was observed in the case of combinatorial treatment with anti-Naja naja scFvs, N194, and N248. These scFvs demonstrated partial inhibition of venom-induced myotoxicity, and E113 also inhibited hemolysis by 50%, which corroborates the enhanced survival during combinatorial treatment in Echis carinatus venom-challenged mice.
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Affiliation(s)
- Amit Kumar
- International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India
| | - Zaid Kamal Madni
- International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India
| | - Shivam Chaturvedi
- International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India
| | - Dinakar M Salunke
- International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
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Kumar SM, Shreekrishna HK, Singi Y. Clinico-epidemiological profile and outcome of snakebite patients presented to a teaching institute - A descriptive retrospective review. J Family Med Prim Care 2024; 13:151-156. [PMID: 38482274 PMCID: PMC10931906 DOI: 10.4103/jfmpc.jfmpc_743_23] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 07/27/2023] [Accepted: 08/02/2023] [Indexed: 11/02/2024] Open
Abstract
Introduction Snakebites are a significant cause of morbidity and mortality in India despite availability of anti-snake venom and the absence of a large number of highly venomous snakes. This may be attributed to treatment seeking behaviour of the population. The study aims to find out common clinical features, outcome, and delay in arrival time to the hospital in snakebite cases. Materials and Methods This is a cross-sectional retrospective record-based study among the patients presented with a history of snakebites to the Basaveshwara Medical College Hospital and Research Centre, Chitradurga, conducted from 1 January 2019 to 31 January 2021. Results Out of the 96 patients, the majority of snakebite victims were male and of an age group of 21-30 years. The most common site for snakebite was the lower limb, and about 57.2% of patients had visible fang marks. Among snake species identified, the most common was krait bites, followed by cobra bites. Neurotoxic envenomation manifestation and severe presentation were found in almost half (53.1%) of the cases. Almost half of the patients took 1-4 hours to arrive at the health facility. Surprisingly, only 35% cases arrived to the health care facility within an hour of snakebite. Most of the patients (82%) recovered with the treatment with very minimal fatality/mortality. Conclusion and Recommendations Although half of the patients presented with severe forms, only 35% of the patients arrived within an hour to the health care facility. This indicates the need for an information dissemination system to avoid severe disease as well as to prevent mortality.
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Affiliation(s)
- S. Mohan Kumar
- Department of Pharmacology, BMCH and RC, Chitradurga, Karnataka, India
| | - H. K. Shreekrishna
- Department of Forensic Medicine, BMCH and RC, Chitradurga, Karnataka, India
| | - Yatiraj Singi
- Department of Forensic Medicine, All India Institute of Medical Sciences, Bilaspur, Himachal Pradesh, India
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Sharma H, Baviskar A, Patil AD. Enhancing Primary Health-care Worker Training through High-fidelity Simulation for Snake Bite Management. J Emerg Trauma Shock 2024; 17:46. [PMID: 38681880 PMCID: PMC11044994 DOI: 10.4103/jets.jets_107_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 08/30/2023] [Indexed: 05/01/2024] Open
Affiliation(s)
- Hritika Sharma
- Medical Simulation Laboratory, D Y Patil University, Navi Mumbai, Maharashtra, India
| | - Ajit Baviskar
- Department of Emergency Medicine, D Y Patil University, School of Medicine, Navi Mumbai, Maharashtra, India
| | - Anant D. Patil
- Department of Pharmacology, D Y Patil University, School of Medicine, Navi Mumbai, Maharashtra, India
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Laprade W, Bartlett KE, Christensen CR, Kazandjian TD, Patel RN, Crittenden E, Dawson CA, Mansourvar M, Wolff DS, Fryer T, Laustsen AH, Casewell NR, Gutiérrez JM, Hall SR, Jenkins TP. Machine-learning guided Venom Induced Dermonecrosis Analysis tooL: VIDAL. Sci Rep 2023; 13:21662. [PMID: 38066189 PMCID: PMC10709447 DOI: 10.1038/s41598-023-49011-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 12/02/2023] [Indexed: 12/18/2023] Open
Abstract
Snakebite envenoming is a global public health issue that causes significant morbidity and mortality, particularly in low-income regions of the world. The clinical manifestations of envenomings vary depending on the snake's venom, with paralysis, haemorrhage, and necrosis being the most common and medically relevant effects. To assess the efficacy of antivenoms against dermonecrosis, a preclinical testing approach involves in vivo mouse models that mimic local tissue effects of cytotoxic snakebites in humans. However, current methods for assessing necrosis severity are time-consuming and susceptible to human error. To address this, we present the Venom Induced Dermonecrosis Analysis tooL (VIDAL), a machine-learning-guided image-based solution that can automatically identify dermonecrotic lesions in mice, adjust for lighting biases, scale the image, extract lesion area and discolouration, and calculate the severity of dermonecrosis. We also introduce a new unit, the dermonecrotic unit (DnU), to better capture the complexity of dermonecrosis severity. Our tool is comparable to the performance of state-of-the-art histopathological analysis, making it an accessible, accurate, and reproducible method for assessing dermonecrosis in mice. Given the urgent need to address the neglected tropical disease that is snakebite, high-throughput technologies such as VIDAL are crucial in developing and validating new and existing therapeutics for this debilitating disease.
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Affiliation(s)
- William Laprade
- Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Keirah E Bartlett
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Charlotte R Christensen
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Taline D Kazandjian
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Rohit N Patel
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Edouard Crittenden
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Charlotte A Dawson
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Marjan Mansourvar
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Darian S Wolff
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Thomas Fryer
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Andreas H Laustsen
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Nicholas R Casewell
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, UK
| | - José María Gutiérrez
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
| | - Steven R Hall
- Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, UK.
- Lancaster Medical School and Biomedical & Life Sciences, Lancaster University, Lancaster, UK.
| | - Timothy P Jenkins
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
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Suji S, Dinesh MD, Keerthi KU, Anagha KP, Arya J, Anju KV. Evaluation of Neutralization Potential of Naja naja and Daboiarusselii Snake Venom by Root Extract of Cyanthillium cinereum. Indian J Crit Care Med 2023; 27:821-829. [PMID: 37936805 PMCID: PMC10626242 DOI: 10.5005/jp-journals-10071-24567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 09/25/2023] [Indexed: 11/09/2023] Open
Abstract
Aim One of the main reasons for the death due to snake bites is the non-availability of antivenoms in the regions where they are needed. The use of medicinal plants and plant-based natural products as an alternative to antivenom will become a milestone in snake bite envenomation. The present study investigates the in vitro antivenom properties of Cyanthillium cinereum root extracts. Materials and methods The C. cinereum root's aqueous extract was prepared by the Soxhlet extraction method, and phytochemical screening was performed to detect the presence of various bioactive compounds. Thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) analysis were performed for the detection and identification of phytochemical constituents. In this study, an in vitro model is used to assess the antivenom capability of aqueous extract. Venom toxicity and neutralization assays were as follows: An in vitro pharmacological evaluation was performed by direct hemolysis assay, indirect hemolytic assay, proteolytic activity, neutralization of procoagulant activity, and gelatin liquefaction method. Results Qualitative analysis of phytochemicals by the standard method showed the presence of various phytochemical constituents. Also, GC-MS analysis showed the presence of three major compounds that possess antivenom activity from the obtained 60 bioactive compounds, and their chemical structures were also determined. Venom protein profiling was performed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The plant extract was able to neutralize the Naja naja (N. naja) and Daboia russelii (D. russelii) venom induced hemolysis and it was reduced below 50 and 40%, respectively and the extract was also able to reduce the hemolytic halo produced by venoms. Procoagulant activity and gelatin liquefaction assay showed that venom-induced clotting was neutralized by increasing the root extract concentration sufficiently. Conclusion The aqueous extract of the root of C. cinereum showed potent in vitro venom-neutralizing activity, and it can be used as a formidable therapeutic agent against N. naja and D. russelii envenomation. How to cite this article Suji S, Dinesh MD, Keerthi KU, Anagha KP, Arya J, Anju KV. Evaluation of Neutralization Potential of Naja naja and Daboia russelii Snake Venom by Root Extract of Cyanthillium cinereum. Indian J Crit Care Med 2023;27(11):821-829.
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Affiliation(s)
- S Suji
- Department of Microbiology, Nehru Arts and Science College, Coimbatore, Tamil Nadu, India
| | - MD Dinesh
- Department of Microbiology, Nehru Arts and Science College, Coimbatore, Tamil Nadu, India
| | - KU Keerthi
- Department of Microbiology, Nehru Arts and Science College, Coimbatore, Tamil Nadu, India
| | - KP Anagha
- Department of Biochemistry, MHES College of Arts and Science and Technology, Calicut, Kerala, India
| | - J Arya
- Ahalia Ayurveda Medical College Hospital, Ahalia Campus, Palakkad, Kerala, India
| | - KV Anju
- Department of Panchakarma, Vaidyaratnam Ayurveda College, Thrissur, Kerala, India
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Duque BR, Bruno SF, Ferreira V, Guedes TB, Machado C, Hamdan B. Venomous snakes of medical importance in the Brazilian state of Rio de Janeiro: habitat and taxonomy against ophidism. BRAZ J BIOL 2023; 83:e272811. [PMID: 37909585 DOI: 10.1590/1519-6984.272811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 08/19/2023] [Indexed: 11/03/2023] Open
Abstract
Snakebite envenoming is a major global health problem that kills or disables half a million people in the world's poorest countries. Identifying the biting snake and its habitat use is key to understanding snakebite eco-epidemiology and optimizing its clinical management. To prevent and combat the neglected snakebite disease, we characterize the morphology, geographic distribution, habitat use, and snakebites of medically important venomous snakes in the state of Rio de Janeiro (Brazil). Despite Philodryas spp. not being considered of medical importance by the Brazilian Ministry of Health, we also explore their data once the bites may require medical intervention, may cause death, and their consequences are underestimated. Methods: We assessed taxonomy and geographic data from specimens housed in scientific collections, the literature, and the Notifiable Diseases Information System. Our data revealed fragility in the morphological characters recommended to distinguish Bothrops jararaca from B. jararacussu, identify the subspecies of Crotalus durissus and distinguish the species of Philodryas. To help identify these species, we present an identification key to the venomous snake species from Rio de Janeiro based on the morphological data collected. We record the genera Bothrops and Micrurus in all mesoregions of the state. Here, we provide the first record of C. durissus in the Serrana region, supporting the hypothesis of geographic expansion of the species in the state. The crotalic antivenom must not be missing in Médio Paraíba, Centro-Sul Fluminense, and Serrana, where the rattlesnake C. durissus occurs. Bothrops bilineatus and Lachesis muta have historical records presented for the first time herein. However, these species are likely endangered or extinct in the state. There were 7,483 snakebites reported between 2001 and 2019, with an annual average of 393.8 cases. The Bothrops genus is responsible for the majority of accidents. The highest number of cases occurred in the Serrana region, the largest pole of family agriculture in Rio de Janeiro. We improve the identification of venomous snake species, better delimit their distribution, and update the number of cases of snakebites, thus providing greater precision in the attention to this problem in Rio de Janeiro. We emphasize the importance of clinical studies to test using bothropic-crotalic antivenom and heparin in all mesoregions to treat B. jararacussu envenomation; and mechanical ventilation, atropine, and anticholinesterases in the emergency health centers in the Metropolitana and Norte Fluminense regions due to the occurrence of the coral M. lemniscatus in these areas.
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Affiliation(s)
- B R Duque
- Instituto Vital Brazil - IVB, Laboratório de Coleções Biológicas e Biodiversidade, Diretoria Científica, Niterói, RJ, Brasil
- Universidade Federal do Estado do Rio de Janeiro - UNIRIO, Programa de Pós-graduação em Ecoturismo e Conservação, Rio de Janeiro, RJ, Brasil
| | - S F Bruno
- Universidade Federal Fluminense - UFF, Faculdade de Veterinária, Niterói, RJ, Brasil
| | - V Ferreira
- Instituto Vital Brazil - IVB, Laboratório de Coleções Biológicas e Biodiversidade, Diretoria Científica, Niterói, RJ, Brasil
| | - T B Guedes
- Universidade Estadual de Campinas - UNICAMP, Instituto de Biologia, Departamento de Biologia Animal, Campinas, SP, Brasil
- University of Gothenburg, Gothenburg Global Biodiversity Center - GGBC, Department of Biological and Environmental Sciences, Göteborg, Sweden
| | - C Machado
- Instituto Vital Brazil - IVB, Laboratório de Coleções Biológicas e Biodiversidade, Diretoria Científica, Niterói, RJ, Brasil
| | - B Hamdan
- Instituto Vital Brazil - IVB, Laboratório de Coleções Biológicas e Biodiversidade, Diretoria Científica, Niterói, RJ, Brasil
- Universidade Federal do Rio de Janeiro - UFRJ, Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Hemostase e Venenos, Rio de Janeiro, RJ, Brasil
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Gilliam LL, Gilliam J, Samuel SP, Carter RW, Ritchey J, Bulfone T, Gutiérrez JM, Williams DJ, Durkin DM, Stephens SI, Lewin MR. Oral and IV Varespladib Rescue Experiments in Juvenile Pigs with Weakness Induced by Australian and Papuan Oxyuranus scutellatus Venoms. Toxins (Basel) 2023; 15:557. [PMID: 37755983 PMCID: PMC10537020 DOI: 10.3390/toxins15090557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/02/2023] [Accepted: 08/17/2023] [Indexed: 09/28/2023] Open
Abstract
Antivenom is currently the standard-of-care treatment for snakebite envenoming, but its efficacy is limited by treatment delays, availability, and in many cases, species specificity. Many of the rapidly lethal effects of envenoming are caused by venom-derived toxins, such as phospholipase A2 (sPLA2); therefore, small molecule direct toxin inhibitors targeting these toxins may have utility as initial and adjunct therapies after envenoming. Varespladib (intravenous, IV) and varespladib-methyl (oral) have been shown to potently inhibit sPLA2s from snake venoms in murine and porcine models, thus supporting their further study as potential treatments for snakebite envenoming. In this pilot study, we tested the ability of these compounds to reverse neurotoxic effects of venom from the Australian and Papuan taipan (Oxyuranus scutellatus) subspecies in juvenile pigs (Sus domesticus). The mean survival time for control animals receiving Australian taipan venom (0.03 mg/kg, n = 3) was 331 min ± 15 min; for those receiving Papuan taipan venom (0.15 mg/kg, n = 3) it was 178 ± 31 min. Thirteen pigs received Australian taipan venom and treatment with either IV or oral varespladib (or with IV to oral transition) and all 13 survived the duration of the study (≥96 h). Eight pigs received Papuan taipan venom followed by treatment: Briefly: Two animals received antivenom immediately and survived to the end of the study. Two animals received antivenom treatment delayed 45 min from envenoming and died within 4 h. Two animals received similarly delayed antivenom treatment and were rescued by varespladib. Two animals were treated with varespladib alone after a 45-min delay. Treatment with varespladib only was effective but required repeat dosing over the course of the study. Findings highlight both the importance of early treatment and, as well, a half-life for the investigational inhibitors now in Phase II clinical trials for snakebite. Varespladib rapidly reversed weakness even when administered many hours post-envenoming and, overall, our results suggest that varespladib and varespladib-methyl could be efficacious tools in the treatment of sPLA2-induced weakness from Oxyuranus envenoming. Further clinical study as initial therapy and as potential method of rescue from some types of antivenom-resistant envenomings are supported by these data.
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Affiliation(s)
- Lyndi L. Gilliam
- Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA; (L.L.G.); (J.G.); (J.R.)
| | - John Gilliam
- Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA; (L.L.G.); (J.G.); (J.R.)
| | - Stephen P. Samuel
- Division of Research Ophirex, Inc., Corte Madera, CA 94925, USA; (S.P.S.); (R.W.C.); (S.I.S.)
| | - Rebecca W. Carter
- Division of Research Ophirex, Inc., Corte Madera, CA 94925, USA; (S.P.S.); (R.W.C.); (S.I.S.)
| | - Jerry Ritchey
- Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA; (L.L.G.); (J.G.); (J.R.)
| | - Tommaso Bulfone
- Center for Exploration and Travel Health, California Academy of Sciences, San Francisco, CA 94118, USA; (T.B.)
- School of Medicine, University of California, San Francisco, CA 94143, USA
| | - José María Gutiérrez
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 11501-2060, Costa Rica;
| | - David J. Williams
- Regulation and Prequalification Department (RPQ) at the World Health Organization (WHO), 1211 Geneva, Switzerland;
| | - Daniela M. Durkin
- Center for Exploration and Travel Health, California Academy of Sciences, San Francisco, CA 94118, USA; (T.B.)
| | - Sally I. Stephens
- Division of Research Ophirex, Inc., Corte Madera, CA 94925, USA; (S.P.S.); (R.W.C.); (S.I.S.)
| | - Matthew R. Lewin
- Division of Research Ophirex, Inc., Corte Madera, CA 94925, USA; (S.P.S.); (R.W.C.); (S.I.S.)
- Center for Exploration and Travel Health, California Academy of Sciences, San Francisco, CA 94118, USA; (T.B.)
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Ramkumar A, Tvsp M, Elanjeran R, Chaitanya YV, Harika K. Cortical Blindness and Thrombotic Microangiopathy Following a Hemotoxic Snake Envenomation: An Unusual Presentation. Cureus 2023; 15:e43109. [PMID: 37692596 PMCID: PMC10485869 DOI: 10.7759/cureus.43109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2023] [Indexed: 09/12/2023] Open
Abstract
Snake envenomation leads to significant morbidity and mortality with local, hematological, renal, and neurological complications. Hemotoxic envenomation activates a hemorrhagic cascade, leading to many manifestations ranging from skin bleeds to major organ bleeds and fatal intracranial hemorrhage. Although rare, ischemic manifestations are possible following a hemotoxic envenomation, and they may present as cortical blindness, an unusual ocular symptom. Snake envenomation is also known to cause multifactorial acute kidney injury (AKI), precipitated by hemodynamic disturbances secondary to rhabdomyolysis, hemoglobinuria, direct tubular toxicity, and thrombotic microangiopathy. Thrombotic microangiopathy (TMA) is often overlooked in snake bites, as the hematological manifestations are often conveniently attributed to venom-induced consumptive coagulopathy (VICC). The distinct clinical entity of thrombotic microangiopathy should factor into one's differential diagnosis in patients presenting with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury following a snake bite. We report a patient who developed cortical blindness and thrombotic microangiopathy following snake envenomation, which are uncommon sequelae.
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Affiliation(s)
- Anitha Ramkumar
- Department of Emergency Medicine, Aarupadai Veedu Medical College, Vinyaka Mission Research Foundation (Deemed University), Puducherry, IND
| | - Murthy Tvsp
- Department of Anaesthesiology, GSL Medical College, Rajahmundry, IND
| | - Rajkumar Elanjeran
- Department of Emergency Medicine, Aarupadai Veedu Medical College, Vinyaka Mission Research Foundation (Deemed University), Puducherry, IND
| | | | - Kari Harika
- Department of Emergency Medicine, GSL Medical College, Rajahmundry, IND
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