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The widespread geographical distribution of Russell's vipers (Daboia spp.) is associated with marked variations in the clinical outcomes of envenoming by species from different countries. This is likely to be due to differences in the quantity and potency of key toxins and, potentially, the presence or absence of some toxins in venoms across the geographical spectrum. In this study, we aimed to isolate and pharmacologically characterise the major neurotoxic components of D. siamensis venoms from Thailand and Java (Indonesia) and explore the efficacy of antivenom and a PLA2 inhibitor, Varespladib, against the neuromuscular activity. These data will provide insights into the link between venom components and likely clinical outcomes, as well as potential treatment strategies. Venoms were fractionated using RP-HPLC and the in vitro activity of isolated toxins assessed using the chick biventer cervicis nerve-muscle preparation. Two major PLA2 fractions (i.e., fractions 8 and 10) were isolated from each venom. Fraction 8 from both venoms produced pre-synaptic neurotoxicity and myotoxicity, whereas fraction 10 from both venoms was weakly neurotoxic. The removal of the two fractions from each venom abolished the in vitro neurotoxicity, and partially abolished myotoxicity, of the whole venom. A combination of the two fractions from each venom produced neurotoxic activity that was equivalent to the respective whole venom (10 µg/mL), but the myotoxic effects were not additive. The in vitro neurotoxicity of fraction 8 (100 nM) from each venom was prevented by the pre-administration of Thai Russell's viper monovalent antivenom (2× recommended concentration) or preincubation with Varespladib (100 nM). Additionally, the neurotoxicity produced by a combination of the two fractions was partially reversed by the addition of Varespladib (100–300 nM) 60 min after the fractions. The present study demonstrates that the in vitro skeletal muscle effects of Thai and Javanese D. siamensis venoms are primarily due to key PLA2 toxins in each venom. [ABSTRACT FROM AUTHOR]

Envenomation by Russell's viper [Daboia russelii (Shaw & Nodder, 1797)] is a major medical emergency in tropical countries. The antivenom therapy is a conventional remedy for such medical emergency, but it has limitations and side effects. Nanomedicine and nanotechnology are the most prospective areas of research in the current scenario. In the present study, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of crudeDaboia russelli venom (VRV) was performed. Alginic acid-based silver nanoparticles (AgNP-ALG) were synthesized and characterized using UV-Visible spectroscopy, Dynamic Light Scattering (DLS), Scanning electron microscope (SEM), and X-ray diffraction analysis (XRD). SNPs have average hydrodynamic size of 80.30 nm with 0.271 PDI. X-ray diffraction analysis of AgNP-ALG, which confirmed the cubic crystal shape of silver. SEM studies of AgNP-ALG showed particle sizes ranging from 10 to 50 nm. Spectroscopic analysis showed a decrease in the absorbance intensity of venom upon interaction with AgNP-ALG, indicating interaction with venom proteins. From the data available from fluorescence spectroscopy, it is evident that viper venom preincubated with AgNP-ALG causes quenching of fluorescence intensity. The results obtained by direct hemolytic assay,proteolytic activity and blood clotting test revealed venom action inhibition due to silver nanoparticles. Thus, in the present study we have emphasized that silver nanoparticles inhibit the action of Daboia russelli venom in vitro. [ABSTRACT FROM AUTHOR]

Snakebite envenoming and its resulting complications are serious threats to the health of vulnerable people living in rural areas of developing countries. The knowledge of the heterogeneity of symptoms associated with snakebite envenoming and their management strategies is vital to treat such life-threatening complications to save lives. Russell's viper envenomation induces a diverse range of clinical manifestations from commonly recognised haemotoxic and local effects to several rare conditions that are often not reported. The lack of awareness about these unusual manifestations can affect prompt diagnosis, appropriate therapeutic approaches, and positive outcomes for patients. Here, we report pulmonary thromboembolism that developed in three patients following Russell's viper envenomation and demonstrate their common clinical features and diagnostic and therapeutic approaches used. All patients showed clinical signs of local (oedema) and systemic (blood coagulation disturbances) envenomation, which were treated using polyvalent antivenom. They exhibited elevated heart rates, breathlessness, and reduced oxygen saturation, which are non-specific but core parameters in the diagnosis of pulmonary embolism. The recognition of pulmonary embolism was also achieved by an electrocardiogram, which showed sinus tachycardia and computed tomography and echocardiogram scans further confirmed this condition. Anti-coagulant treatment using low-molecular-weight heparin offered clinical benefits in these patients. In summary, this report reinforces the broad spectrum of previously unreported consequences of Russell's viper envenomation. The constant updating of healthcare professionals and the dissemination of major lessons learned in the clinical management of snakebite envenoming through scientific documentation and educational programs are necessary to mitigate the adverse impacts of venomous snakebites in vulnerable communities. [ABSTRACT FROM AUTHOR]

Abstract Introduction Snakebite envenomation poses a significant health risk, particularly in low-resource settings where access to proper treatment is limited. Case presentation This study reports two cases of Russell's viper bites in rural Bangladesh, involving 48 and 35-year-old Bangladesh males, respectively, and highlights the difficulties in providing adequate medical care and in treating any complications that may arise. Both cases involved delayed access to healthcare, initial visit to traditional healers, and the development of severe complications such as coagulopathy, renal failure. After the intervention both cases survived which is scarce in low resource settings. Conclusion The cases underscore the importance of early recognition, appropriate management, and improved healthcare infrastructure to optimize survival outcomes in snakebite cases in resource-limited settings. These cases will contribute valuable insights to the field of snakebite management and provide guidance for improving survival rates and outcomes among snakebite victims in Bangladesh.

The heterogeneity in venom composition and potency in disparate Eastern Russell's viper (Daboia siamensis) populations has repercussions for the efficacy of antivenoms. This is particularly pronounced in geographical areas in which the venom of the local species has not been well studied and locally produced antivenoms are unavailable. In such cases, alternative therapies following envenoming, which are not limited by species specificity, may be employed to complement antivenoms. We studied the neuromuscular activity of D. siamensis venom from Thailand and Java (Indonesia) and the ability of Thai antivenoms and/or Varespladib to prevent or reverse these effects. Both Thai and Javanese D. siamensis venoms displayed potent pre-synaptic neurotoxicity but weak myotoxicity in the chick biventer cervicis nerve–muscle preparation. Whilst the neurotoxicity induced by both venoms was abolished by the prior administration of Thai D. siamensis monovalent antivenom or pre-incubation with Varespladib, Thai neuro-polyvalent antivenom only produced partial protection when added prior to venom. Pre-synaptic neurotoxicity was not reversed by the post-venom addition of either antivenom 30 or 60 min after either venom. Varespladib, when added 60 min after venom, prevented further inhibition of indirect twitches. However, the subsequent addition of additional concentrations of Varespladib did not result in further recovery from neurotoxicity. The combination of Thai monovalent antivenom and Varespladib, added 60 min after venom, resulted in additional recovery of twitches caused by either Thai or Javanese venoms compared with antivenom alone. In conclusion, we have shown that Varespladib can prevent and partially reverse the pre-synaptic neurotoxicity induced by either Thai or Javanese D. siamensis venoms. The efficacy of Thai D. siamensis monovalent antivenom in reversing pre-synaptic neurotoxicity was significantly enhanced by its co-administration with Varespladib. Further work is required to establish the efficacy of Varespladib as a primary or adjunct therapy in human envenoming. [ABSTRACT FROM AUTHOR]

Introduction: Snakebite envenomation poses a significant health risk, particularly in low-resource settings where access to proper treatment is limited. Case presentation: This study reports two cases of Russell's viper bites in rural Bangladesh, involving 48 and 35-year-old Bangladesh males, respectively, and highlights the difficulties in providing adequate medical care and in treating any complications that may arise. Both cases involved delayed access to healthcare, initial visit to traditional healers, and the development of severe complications such as coagulopathy, renal failure. After the intervention both cases survived which is scarce in low resource settings. Conclusion: The cases underscore the importance of early recognition, appropriate management, and improved healthcare infrastructure to optimize survival outcomes in snakebite cases in resource-limited settings. These cases will contribute valuable insights to the field of snakebite management and provide guidance for improving survival rates and outcomes among snakebite victims in Bangladesh. [ABSTRACT FROM AUTHOR]

The widespread geographical distribution of Russell’s vipers (Daboia spp.) is associated with marked variations in the clinical outcomes of envenoming by species from different countries. This is likely to be due to differences in the quantity and potency of key toxins and, potentially, the presence or absence of some toxins in venoms across the geographical spectrum. In this study, we aimed to isolate and pharmacologically characterise the major neurotoxic components of D. siamensis venoms from Thailand and Java (Indonesia) and explore the efficacy of antivenom and a PLA2 inhibitor, Varespladib, against the neuromuscular activity. These data will provide insights into the link between venom components and likely clinical outcomes, as well as potential treatment strategies. Venoms were fractionated using RP-HPLC and the in vitro activity of isolated toxins assessed using the chick biventer cervicis nerve-muscle preparation. Two major PLA2 fractions (i.e., fractions 8 and 10) were isolated from each venom. Fraction 8 from both venoms produced pre-synaptic neurotoxicity and myotoxicity, whereas fraction 10 from both venoms was weakly neurotoxic. The removal of the two fractions from each venom abolished the in vitro neurotoxicity, and partially abolished myotoxicity, of the whole venom. A combination of the two fractions from each venom produced neurotoxic activity that was equivalent to the respective whole venom (10 µg/mL), but the myotoxic effects were not additive. The in vitro neurotoxicity of fraction 8 (100 nM) from each venom was prevented by the pre-administration of Thai Russell’s viper monovalent antivenom (2× recommended concentration) or preincubation with Varespladib (100 nM). Additionally, the neurotoxicity produced by a combination of the two fractions was partially reversed by the addition of Varespladib (100–300 nM) 60 min after the fractions. The present study demonstrates that the in vitro skeletal muscle effects of Thai and Javanese D. siamensis venoms are primarily due to key PLA2 toxins in each venom.

Snakebite envenoming and its resulting complications are serious threats to the health of vulnerable people living in rural areas of developing countries. The knowledge of the heterogeneity of symptoms associated with snakebite envenoming and their management strategies is vital to treat such life-threatening complications to save lives. Russell’s viper envenomation induces a diverse range of clinical manifestations from commonly recognised haemotoxic and local effects to several rare conditions that are often not reported. The lack of awareness about these unusual manifestations can affect prompt diagnosis, appropriate therapeutic approaches, and positive outcomes for patients. Here, we report pulmonary thromboembolism that developed in three patients following Russell’s viper envenomation and demonstrate their common clinical features and diagnostic and therapeutic approaches used. All patients showed clinical signs of local (oedema) and systemic (blood coagulation disturbances) envenomation, which were treated using polyvalent antivenom. They exhibited elevated heart rates, breathlessness, and reduced oxygen saturation, which are non-specific but core parameters in the diagnosis of pulmonary embolism. The recognition of pulmonary embolism was also achieved by an electrocardiogram, which showed sinus tachycardia and computed tomography and echocardiogram scans further confirmed this condition. Anti-coagulant treatment using low-molecular-weight heparin offered clinical benefits in these patients. In summary, this report reinforces the broad spectrum of previously unreported consequences of Russell’s viper envenomation. The constant updating of healthcare professionals and the dissemination of major lessons learned in the clinical management of snakebite envenoming through scientific documentation and educational programs are necessary to mitigate the adverse impacts of venomous snakebites in vulnerable communities.

Snakebite is an issue of concern, especially in India which accounts for half of the global deaths due to venomous snakebites every year. Saponins are glycosides of triterpenes and steroids known for their antivenom properties. The soap bark tree or Quillaya, Quillaja saponaria Molina represents the major resource of saponins for commercial applications. Here, we investigated the antivenom property of silver nanoparticle mediated saponins (AgNP-SP) from the Q. saponaria bark extract. AgNP-SP was prepared conducive to optimal temperature, pH of extract and concentration of AgNO3. UV-VIS, FT-IR, XRD, TEM and SEM interpretations were devised to characterize AgNP-SP. AgNP-SP was tested for its efficacy to neutralize venom lethality and increase in myotoxicity biomarkers (LDH) in animal models. AgNP-SP was synthesized optimally at a concentration of 50 mg/mL, extract (pH 6.8) and temperature (80°C) with AgNO3 (1 mM). The colour change and synthesis of AgNP-SP was examined by UV-Vis analysis at 430 nm. TEM studies showed the size for AgNP-SP to be 74.4 nm. FT-IR analysis showed peaks of AgNP-SP at 3422 cm-1 and 2926 (O-H stretching), 2358 cm-1 (O=C=O stretching), 1616 cm-1 (C=C stretching), 1097 cm-1 (C-F stretching), 813 cm-1 (C-CL stretching) and 651 cm-1 (C-Br stretching). The EDAX established the purity of the AgNP-SP. The biosynthesized AgNP-SP could significantly neutralize Vipera russelli venom (VRV) mediated elevation of biomarkers lactate dehydrogenase (LDH), serum glutamate pyruvate transaminase (SGPT) serum glutamic-oxaloacetic transaminase (SGOT), serum creatinine and serum uric acid. The present study, thus promulgates the therapeutic potential of silver nanoparticle mediated saponins (AgNP-SP) in ameliorating the biochemical and pharmacological effect of haemotoxic snake venom in animal models. [ABSTRACT FROM AUTHOR]

The Russell's viper (Daboia siamensis) is a medically important venomous snake in Myanmar. Next-generation sequencing (NGS) shows potential to investigate the venom complexity, giving deeper insights into snakebite pathogenesis and possible drug discoveries. mRNA from venom gland tissue was extracted and sequenced on the Illumina HiSeq platform and de novo assembled by Trinity. The candidate toxin genes were identified via the Venomix pipeline. Protein sequences of identified toxin candidates were compared with the previously described venom proteins using Clustal Omega to assess the positional homology among candidates. Candidate venom transcripts were classified into 23 toxin gene families including 53 unique full-length transcripts. C-type lectins (CTLs) were the most highly expressed, followed by Kunitz-type serine protease inhibitors, disintegrins and Bradykinin potentiating peptide/C-type natriuretic peptide (BPP-CNP) precursors. Phospholipase A2, snake venom serine proteases, metalloproteinases, vascular endothelial growth factors, L-amino acid oxidases and cysteine-rich secretory proteins were under-represented within the transcriptomes. Several isoforms of transcripts which had not been previously reported in this species were discovered and described. Myanmar Russell's viper venom glands displayed unique sex-specific transcriptome profiles which were correlated with clinical manifestation of envenoming. Our results show that NGS is a useful tool to comprehensively examine understudied venomous snakes. [ABSTRACT FROM AUTHOR]

Russell’s viper and hump-nosed viper are deadly venomous Viperidae snakes in Sri Lanka. Both these vipers are widely distributed in all climatic zones of the island. Russell’s viper causes systemic envenoming such as coagulopathy, neuroparalysis and acute kidney injury (AKI) whilst hump-nosed viper frequently causes local envenoming and rarely causes AKI and coagulopathy. These two snakes may cause atypical syndromes like thrombotic microangiopathy (TMA) and hemolytic uremic syndrome (HUS). We report two cases of HUS, a type of TMA and a rare complication of snakebites including the triad of AKI, thrombocytopenia and microangiopathic hemolysis.

Snakebite envenomation (SBE) is a life-threatening medical emergency with a high mortality rate. Common secondary complications following SBE, such as wound infections, are significant due to their impact on worsening local tissue damage and causing systemic infection. Antivenoms are not effective to treat wound infections following SBE. Moreover, in several rural clinical settings, broad-spectrum antibiotics are often used without clear guidelines or based on limited laboratory data, resulting in undesirable side effects and exacerbated treatment costs. Therefore, robust antibiotic strategies should be developed to tackle this critical issue. Currently, there is limited information available on the bacterial profiles of SBE-induced infections and antibiotic susceptibility. Hence, it is essential to improve the knowledge of bacterial profiles and their antibiotic sensitivity in SBE victims to develop better treatment strategies. This study aimed to address this issue by examining the bacterial profiles of SBE victims with a specific focus on Russell's viper envenomation. The most frequently found bacteria in the bites of SBE victims were Staphylococcus aureus, Klebsiella sp., Escherichia coli, and Pseudomonas aeruginosa. Linezolid, clindamycin, colistin, meropenem, and amikacin were some of the most effective antibiotics for commonly grown bacteria in SBE victims. Similarly, ciprofloxacin, ampicillin, amoxiclave, cefixime, and tetracyclin were the least effective antibiotics for common bacteria found in the wound swabs of SBE victims. These data provide robust guidance for infection management following SBE and offer useful insights to aid in designing effective treatment protocols for SBE with serious wound infections in rural areas where laboratory facilities may not be readily available. [ABSTRACT FROM AUTHOR]

Russell's viper (Daboia siamensis) is a medically important snake in Myanmar due to its high morbidity and mortality. The genome of Myanmar Russell's viper had not been sequenced until recently. Hence, RNA sequencing has been used to predict genes that encode this snake's toxins. This can lead to deeper insights into the pathogenesis of envenoming and potential drug discovery. Venom glands were dissected from four adult D. siamensis specimens (two males and two females) provided by a local Myanmar snake farm. The mRNA was extracted and sequenced on the Illumina HiSeq platform, then assembled de novo using the Trinity software. Candidate toxin genes were identified using the Venomix pipeline, and their expression levels were calculated using RSEM software. The identified toxin candidates were aligned with previously described venom proteins using Clustal Omega. Candidate venom transcripts were classified into 23 toxin gene families, which included 53 unique transcripts identified as full-length sequences. Among them, 28 full-length sequences represented the eight newly identified toxin gene families in D. siamensis, including neprilysin (2), cystatin (5), waprin (1), vipericidin (1), veficolin (1), endothelial lipases (9), vespryn (ohanin) (8), and three-finger toxins (1). Their expression levels were found to be moderate to low (TPM = 1.49 to 213.37). The majority of the toxin candidates resembled typical elapid toxins, which usually exhibit neurotoxic activities and tissue damage. A smaller proportion of candidate toxin transcripts were predicted to display antimicrobial activity and anti-metastatic effects. Our results suggest their functional activities. They should be studied further for potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Envenomings by Russell's viper (Daboia russelii), a species of high medical importance in India and other Asian countries, commonly result in hemorrhage, coagulopathies, necrosis, and acute kidney injury. Although bleeding complications are frequently reported following viper envenomings, thrombotic events occur rarely (reported only in coronary and carotid arteries) with serious consequences. For the first time, we report three serious cases of peripheral arterial thrombosis following Russell's viper bites and their diagnostic, clinical management, and mechanistic insights. These patients developed occlusive thrombi in their peripheral arteries and symptoms despite antivenom treatment. In addition to clinical features, computed tomography angiography was used to diagnose arterial thrombosis and ascertain its precise locations. They were treated using thrombectomy or amputation in one case that presented with gangrenous digits. Mechanistic insights into the pathology through investigations revealed the procoagulant actions of Russell's viper venom in standard clotting tests as well as in rotational thromboelastometry analysis. Notably, Russell's viper venom inhibited agonist-induced platelet activation. The procoagulant effects of Russell's viper venom were inhibited by a matrix metalloprotease inhibitor, marimastat, although a phospholipase A2 inhibitor (varespladib) did not show any inhibitory effects. Russell's viper venom induced pulmonary thrombosis when injected intravenously in mice and thrombi in the microvasculature and affected skeletal muscle when administered locally. These data emphasize the significance of peripheral arterial thrombosis in snakebite victims and provide awareness, mechanisms, and robust strategies for clinicians to tackle this issue in patients.

The venom of the Russell's viper (Daboia siamensis) contains neurotoxic and myotoxic phospholipase A2 toxins which can cause irreversible damage to motor nerve terminals. Due to the time delay between envenoming and antivenom administration, antivenoms may have limited efficacy against some of these venom components. Hence, there is a need for adjunct treatments to circumvent these limitations. In this study, we examined the efficacy of Chinese D. siamensis antivenom alone, and in combination with a PLA2 inhibitor, Varespladib, in reversing the in vitro neuromuscular blockade in the chick biventer cervicis nerve-muscle preparation. Pre-synaptic neurotoxicity and myotoxicity were not reversed by the addition of Chinese D. siamensis antivenom 30 or 60 min after venom (10 µg/mL). The prior addition of Varespladib prevented the neurotoxic and myotoxic activity of venom (10 µg/mL) and was also able to prevent further reductions in neuromuscular block and muscle twitches when added 60 min after venom. The addition of the combination of Varespladib and antivenom 60 min after venom failed to produce further improvements than Varespladib alone. This demonstrates that the window of time in which antivenom remains effective is relatively short compared to Varespladib and small-molecule inhibitors may be effective in abrogating some activities of Chinese D. siamensis venom. [ABSTRACT FROM AUTHOR]

India suffers the highest incidence of snakebite envenomation (SBE) in the world. Rural communities within India and other countries have long-held cultural beliefs surrounding snakes and SBE treatments, with snake statues present in numerous Hindu temples. While most cultural beliefs are well respected and do not affect anyone, some people worship live venomous snakes without any safety precautions. Moreover, they practice various inappropriate first aid and traditional treatments that exacerbate SBE-induced complications. We report an unusual case of SBE on the tongue of a patient who was bitten while worshipping Russell's viper following the advice of an astrologer based on the appearance of a snake in the patient's dream. Following the bite, the tongue was deeply incised by the priest as a first aid to mitigate SBE-induced complications. The patient suffered profuse bleeding and swelling of the tongue resulting in difficulties in intubating them. The patient regained consciousness after antivenom administration, intranasal ventilation, and blood removal from the mouth. The tongue underwent extensive surgery to restore movement and function. This report advises caution to those undertaking the extremely risky practice of worshipping live snakes and emphasises the urgent need to develop and enforce policies to mitigate such actions and educate rural communities. [ABSTRACT FROM AUTHOR]

Russell’s viper (Daboia siamensis) is a medically important snake in Myanmar due to its high morbidity and mortality. The genome of Myanmar Russell’s viper had not been sequenced until recently. Hence, RNA sequencing has been used to predict genes that encode this snake’s toxins. This can lead to deeper insights into the pathogenesis of envenoming and potential drug discovery. Venom glands were dissected from four adult D. siamensis specimens (two males and two females) provided by a local Myanmar snake farm. The mRNA was extracted and sequenced on the Illumina HiSeq platform, then assembled de novo using the Trinity software. Candidate toxin genes were identified using the Venomix pipeline, and their expression levels were calculated using RSEM software. The identified toxin candidates were aligned with previously described venom proteins using Clustal Omega. Candidate venom transcripts were classified into 23 toxin gene families, which included 53 unique transcripts identified as full-length sequences. Among them, 28 full-length sequences represented the eight newly identified toxin gene families in D. siamensis, including neprilysin (2), cystatin (5), waprin (1), vipericidin (1), veficolin (1), endothelial lipases (9), vespryn (ohanin) (8), and three-finger toxins (1). Their expression levels were found to be moderate to low (TPM = 1.49 to 213.37). The majority of the toxin candidates resembled typical elapid toxins, which usually exhibit neurotoxic activities and tissue damage. A smaller proportion of candidate toxin transcripts were predicted to display antimicrobial activity and anti-metastatic effects. Our results suggest their functional activities. They should be studied further for potential therapeutic applications.

Snakebite envenomation is a high priority neglected tropical disease that predominantly affects rural communities living in developing countries. Due to myriad of complications including coagulopathies, neurotoxicity, nephrotoxicity and local tissue destruction, treating snakebite victims is a major challenge for clinicians. Russell's viper (Daboia russelii) is one of the 'Big Four' venomous snakes in India, and it is responsible for the most snakebite-induced deaths and disabilities. Acute kidney injury occurs frequently following Russell's viper bites and it is a critical factor contributing to disabilities, deaths and excessive treatment costs. In addition to commonly observed envenomation effects, Russell's viper bites induce some rare complications such as priapism, sialolithiasis and splenic rupture. Here, we report a case of Wunderlich syndrome that developed in a 22-year-old male following a Russell's viper bite. The patient displayed severe coagulopathies, abdominal tenderness, and hypotension. Notably, a peri-nephric haematoma was identified through ultrasound and computerised tomographic imaging. The haemorrhage was successfully treated using angioembolisation, and the patient recovered without any difficulties. Although a clinical condition such as this is rare, it is important to create awareness among treating clinicians about its occurrence, diagnosis and clinical management. [Display omitted] • Snakebite-induced Wunderlich syndrome is a rare clinical event. • We report Russell's viper bite-induced Wunderlich syndrome (WS) in a young healthy victim. • The patient displayed peri-nephric haematoma around the right kidney along with coagulopathy, abdominal pain and hypotension typical for WS. • This condition was treated using angioembolisation. • Clinicians should be aware of WS and its symptoms when treating snakebite victims. [ABSTRACT FROM AUTHOR]

Daboia siamensis (Russell's viper) is a highly venomous and medically important snake in China, as well as much of Asia. There is minimal information on the pharmacological activity of the venom of the Chinese species, and currently no commercially available specific antivenom in China. This has led to the use of non-specific antivenoms to treat D. siamensis envenomation. In this study, the in vitro neurotoxicity and myotoxicity of D. siamensis venom was examined and the efficacy of four antivenoms was investigated, including the recently developed Chinese D. siamensis monovalent antivenom (C-DsMAV) and three commercially available antivenoms (Thai D. siamensis (Thai-DsMAV) monovalent antivenom, Deinagkistrodon acutus monovalent antivenom (DaAV), and Gloydius brevicaudus monovalent antivenom (GbAV). D. siamensis venom (10–30 µg/mL) caused the concentration-dependent inhibition of indirect twitches in the chick biventer cervicis nerve muscle preparation, without abolishing contractile responses to exogenous agonists ACh or CCh, indicating pre-synaptic neurotoxicity. Myotoxicity was also evident at these concentrations with inhibition of direct twitches, an increase in baseline tension, and the partial inhibition of ACh, CCh, and KCl responses. The prior addition of C-DsMAV or Thai-DsMAV prevented the neurotoxic and myotoxic activity of D. siamensis venom (10 µg/mL). The addition of non-specific antivenoms (GbAV and DaAV) partially prevented the neurotoxic activity of venom (10 µg/mL) but failed to neutralize the myotoxic effects. We have shown that D. siamensis venom exhibits in vitro weak presynaptic neurotoxicity and myotoxicity, which can be prevented by the pre-addition of the Chinese and Thai Russell's viper antivenoms. Non-specific antivenoms were poorly efficacious. There should be further development of a monospecific antivenom against D. siamensis envenomation in China. [ABSTRACT FROM AUTHOR]

The Russell’s viper (Daboia siamensis) is a medically important venomous snake in Myanmar. Next-generation sequencing (NGS) shows potential to investigate the venom complexity, giving deeper insights into snakebite pathogenesis and possible drug discoveries. mRNA from venom gland tissue was extracted and sequenced on the Illumina HiSeq platform and de novo assembled by Trinity. The candidate toxin genes were identified via the Venomix pipeline. Protein sequences of identified toxin candidates were compared with the previously described venom proteins using Clustal Omega to assess the positional homology among candidates. Candidate venom transcripts were classified into 23 toxin gene families including 53 unique full-length transcripts. C-type lectins (CTLs) were the most highly expressed, followed by Kunitz-type serine protease inhibitors, disintegrins and Bradykinin potentiating peptide/C-type natriuretic peptide (BPP-CNP) precursors. Phospholipase A2, snake venom serine proteases, metalloproteinases, vascular endothelial growth factors, L-amino acid oxidases and cysteine-rich secretory proteins were under-represented within the transcriptomes. Several isoforms of transcripts which had not been previously reported in this species were discovered and described. Myanmar Russell’s viper venom glands displayed unique sex-specific transcriptome profiles which were correlated with clinical manifestation of envenoming. Our results show that NGS is a useful tool to comprehensively examine understudied venomous snakes.

Snakebite envenomation (SBE) is a life-threatening medical emergency with a high mortality rate. Common secondary complications following SBE, such as wound infections, are significant due to their impact on worsening local tissue damage and causing systemic infection. Antivenoms are not effective to treat wound infections following SBE. Moreover, in several rural clinical settings, broad-spectrum antibiotics are often used without clear guidelines or based on limited laboratory data, resulting in undesirable side effects and exacerbated treatment costs. Therefore, robust antibiotic strategies should be developed to tackle this critical issue. Currently, there is limited information available on the bacterial profiles of SBE-induced infections and antibiotic susceptibility. Hence, it is essential to improve the knowledge of bacterial profiles and their antibiotic sensitivity in SBE victims to develop better treatment strategies. This study aimed to address this issue by examining the bacterial profiles of SBE victims with a specific focus on Russell’s viper envenomation. The most frequently found bacteria in the bites of SBE victims were Staphylococcus aureus, Klebsiella sp., Escherichia coli, and Pseudomonas aeruginosa. Linezolid, clindamycin, colistin, meropenem, and amikacin were some of the most effective antibiotics for commonly grown bacteria in SBE victims. Similarly, ciprofloxacin, ampicillin, amoxiclave, cefixime, and tetracyclin were the least effective antibiotics for common bacteria found in the wound swabs of SBE victims. These data provide robust guidance for infection management following SBE and offer useful insights to aid in designing effective treatment protocols for SBE with serious wound infections in rural areas where laboratory facilities may not be readily available.

Russell's viper (Daboia russelii), one of the 'Big Four' venomous snakes in India, is responsible for the majority of snakebite-induced deaths and permanent disabilities. Russell's viper bites are known to induce bleeding/clotting abnormalities, as well as myotoxic, nephrotoxic, cytotoxic and neurotoxic envenomation effects. In addition, they have been reported to induce rare envenomation effects such as priapism, sialolithiasis and splenic rupture. However, Russell's viper bite-induced pseudoaneurysm (PA) has not been previously reported. PA or false aneurysm is a rare phenomenon that occurs in arteries following traumatic injuries including some animal bites, and it can become a life-threatening condition if not treated promptly. Here, we document two clinical cases of Russell's viper bites where PA has developed, despite antivenom treatment. Notably, a non-surgical procedure, ultrasound-guided compression (USGC), either alone, or in combination with thrombin was effectively used in both the cases to treat the PA. Following this procedure and additional measures, the patients made complete recoveries without the recurrence of PA which were confirmed by subsequent examination and ultrasound scans. These data demonstrate the development of PA as a rare complication following Russell's viper bites and the effective use of a simple, non-surgical procedure, USGC for the successful treatment of PA. These results will create awareness among healthcare professionals on the development of PA and the use of USGC in snakebite victims following bites from Russell's vipers, as well as other viper bites. [ABSTRACT FROM AUTHOR]

Predation exerts a strong selective force on prey, and hence prey species have evolved a multitude of ways to escape predation. One strategy by which many mobile species escape predation is by fleeing when approached by predators. However, fleeing too early can have fitness costs. Thus, optimal escape theory suggests that escape behaviour in prey depends on the risk of being eaten and the fleeing costs. Several studies on mammals, birds and lizards lend support to this hypothesis. However, few studies have explored escape behaviour in snakes. Here, using radio telemetry to track snakes in the field, we study the escape behaviour in Russell's vipers, a highly venomous and cryptic snake, responsible for the highest number of snakebite deaths in India. We show that escape response, i.e., the decision to stay or flee, was influenced by intrinsic factors such as the snake's behaviour and body temperature. We also show that the flight initiation distance, the distance at which the snake flees, was mostly determined by habitat selection, i.e., the visibility of the snake and the distance to the nearest cover. Overall, we show that different factors could determine the decision to flee and when to flee. We also highlight how understanding escape response in such highly venomous, medically important yet secretive snakes could potentially help reduce human-snake encounters and mitigate the snakebite crisis. [ABSTRACT FROM AUTHOR]

Abdominal pain is known to be an early clinical predictor of severe systemic Russell's viper (RV) envenomation and is often associated with the later development of coagulopathy and neurotoxicity. The mechanism of abdominal pain is unknown, but we postulated it might be due to intestinal microvascular endothelial gut damage. Gut-toxicity can be detected using the novel biomarker Intestinal Fatty Acid Binding Protein (IFABP). We also wanted to explore the mechanisms and consequences of this toxicity by measuring procalcitonin as a specific marker of sepsis triggered by bacterial endotoxin, and serum cystatin-C (CysC) as a measure of acute kidney injury. We hypothesised that severe gut-injury might lead to gut-barrier failure, translocation of gastrointestinal microorganisms, associated sepsis and systemic inflammatory response syndrome (SIRS), with a possible exacerbation of snake-bite severity, including acute kidney injury that was previously attributed to direct venom effects. Serial plasma samples previously collected from 16 RV envenomations with abdominal pain, 15 RV envenomations without abdominal pain and 25 healthy controls were assayed for IFABP. A subgroup of these RV envenomations were assayed for procalcitonin (n = 24) and serum CysC (n = 11). The median peak IFABP for RV envenomations was much higher than healthy controls [3703.0 pg/mL (IQR 2250.1–13702.0 pg/mL) vs. 270.1 pg/mL (IQR 153.5–558.0 pg/mL) (p < 0.001)]. There was no difference in those with and without abdominal pain [3801.4 pg/mL (IQR 2080.5–22446.3 pg/mL) vs. 3696.6 pg/mL (IQR 2280.3–4664.7 pg/mL) (p = 1.0)]. Peak procalcitonin levels were elevated in envenomed patients 30.1 ng/ml (IQR: 13.1–59.7 ng/ml) with a level >2ng/mL indicative of severe sepsis] and also correlated with peak IFABP (r = 0.55, p = 0.006, n = 24). Peak serum CysC was also elevated and also correlated with IFABP (r = 0.71, p = 0.037, n = 9). IFABP is significantly elevated indicating enterocyte damage occurs in RV envenomation. IFABP correlated with markers of sepsis (procalcitonin) and acute kidney injury (serum CysC) suggesting that enterocyte damage resulting in translocation of microbial associated molecular patterns (MAMPs) contributes to RV envenomation associated SIRS and sepsis. [ABSTRACT FROM AUTHOR]

BackgroundVenom-induced consumption coagulopathy (VICC) is an important clinical consequence of Russell’s viper (Daboia russelii) envenoming. There is limited evidence for antivenom effectiveness in resolving VICC. We aimed to compare the recovery of VICC in patients who received and did not receive antivenom following Russell’s viper envenoming.Patients and MethodsThis was a non-randomized observational study comparing patients with VICC from Russell’s viper envenoming given antivenom for systemic envenoming and those not given antivenom. Antivenom administration was decided by the treating physicians. We included 44 patients with confirmed Russell’s viper bites with one or more International Normalized Ratio (INR) value ≥ 1.5 (VICC). We compared five patients who did not receive antivenom with 39 patients who did receive antivenom. The primary outcome was the proportion of patients with an INR < 1.5 by 48 h post-bite.ResultsThe antivenom group had higher peak serum venom concentrations [median (IQR) = 272 (96–1,076) ng/mL versus 21 (8–58) ng/mL] and more severe VICC compared to the no antivenom group. Twenty seven of 39 patients (69%) in the antivenom group had an INR < 1.5 at 48 h post-bite compared to none of the five patients (0%) in the no antivenom group (absolute difference: 69%; 95%CI: 13 to 83%; p = 0.006; Fisher’s exact test). The fibrinogen recovered in 32 of 39 patients (82%) in the antivenom group compared to one of five patients (20%) in the no antivenom group (absolute difference 62%; 95% CI: 28 to 95%; p = 0.001; Fisher’s exact test). Both INR and fibrinogen were significantly improved between 24 and 48 h post-bite in the antivenom group compared to the no antivenom group.ConclusionAntivenom accelerated the recovery of VICC in patients with Russell’s viper envenoming, compared to no recovery in a smaller group of patients with milder VICC not receiving antivenom. This supports the efficacy of antivenom in patients with VICC.

Russell's viper bites are known to cause a range of haemotoxic, neurotoxic, myotoxic, cytotoxic and nephrotoxic complications. However, the impact of Russell's viper bites as well as bites from other venomous snakes on sialolithiasis has not been previously reported. Here, we present an interesting case where a Russell's viper bite induced the rapid development of a calculus in submandibular gland in a 10-year-old boy. Upon admission, the victim did not show any symptoms of swelling and/or pain around his oral cavity. He received antivenom treatment to normalise his coagulation parameters, however, on day three he developed swelling and extreme pain around his right mandibular region. An ultrasound investigation revealed the presence of a calculus in his submandibular gland, which was removed using a minor surgical procedure. The histopathological examination revealed this as a poorly calcified salivary calculus, which is composed of cell debris, mucopolysaccharides and lipids. The mechanisms behind its rapid development following a snakebite are unclear although this could be linked to excessive inflammation or modifications to the composition of saliva induced by venom toxins or other unknown factors. This report reveals an unusual complication induced by a Russell's viper bite and alerts clinicians who treat snakebites to be aware of such envenomation effects. Moreover, this will lead to novel research to explore the relationship between venom toxins and functions of salivary glands. [Display omitted] • Impact of snakebites on salivary calculi formation has not been previously reported. • We report salivary calculus formation in a victim following Russell's viper bite. • Venom might have caused excessive inflammation which led to calculus formation. • The bite might have increased the pain from a previously developing calculus. • Clinicians should be aware of this rare event when treating snakebite victims. [ABSTRACT FROM AUTHOR]

Splenic rupture and/or splenectomy is/are not uncommon in clinical arena. Here we present this case of extensive haemorrhage-induced splenic rupture which resulted in splenectomy in a young healthy male (who did not have any previous medical conditions) following a Russell's viper bite. He developed upper abdominal and shoulder pain on his left side along with hypotension and reduced level of haemoglobin on the third day following bite despite antivenom treatment. Following confirmation of splenic rupture and haemoperitoneum by ultrasound and computed tomography scans, an emergency splenectomy was performed using laparotomy. Although Russell's viper bites are known to induce bleeding complications, splenic rupture due to haemorrhage in spleen has not been previously reported. Russell's viper venom toxins such as metalloproteases, serine proteases and phospholipase A 2 might have affected the vascular permeability resulting in excessive bleeding and increased pressure in the spleen leading to rupture. Further investigations are required to underpin the impact of snake venom toxins on the architecture and functions of spleen. However, the clinicians who treat snakebites should be aware of this type of rare complications so as to provide appropriate management for such victims. [Display omitted] • Snakebite-induced splenic rupture and subsequent splenectomy is a rare event. • We report Russell's viper bite-induced splenic rupture in a young healthy victim. • Splenic rupture has occurred due to excessive haemorrhage without any blood clots. • Russell's viper venom might have caused bleeding and vascular damage in spleen. • Clinicians should be aware of this rare event when treating snakebite victims. [ABSTRACT FROM AUTHOR]

The venom of the Russell’s viper (Daboia siamensis) contains neurotoxic and myotoxic phospholipase A2 toxins which can cause irreversible damage to motor nerve terminals. Due to the time delay between envenoming and antivenom administration, antivenoms may have limited efficacy against some of these venom components. Hence, there is a need for adjunct treatments to circumvent these limitations. In this study, we examined the efficacy of Chinese D. siamensis antivenom alone, and in combination with a PLA2 inhibitor, Varespladib, in reversing the in vitro neuromuscular blockade in the chick biventer cervicis nerve-muscle preparation. Pre-synaptic neurotoxicity and myotoxicity were not reversed by the addition of Chinese D. siamensis antivenom 30 or 60 min after venom (10 µg/mL). The prior addition of Varespladib prevented the neurotoxic and myotoxic activity of venom (10 µg/mL) and was also able to prevent further reductions in neuromuscular block and muscle twitches when added 60 min after venom. The addition of the combination of Varespladib and antivenom 60 min after venom failed to produce further improvements than Varespladib alone. This demonstrates that the window of time in which antivenom remains effective is relatively short compared to Varespladib and small-molecule inhibitors may be effective in abrogating some activities of Chinese D. siamensis venom.

India suffers the highest incidence of snakebite envenomation (SBE) in the world. Rural communities within India and other countries have long-held cultural beliefs surrounding snakes and SBE treatments, with snake statues present in numerous Hindu temples. While most cultural beliefs are well respected and do not affect anyone, some people worship live venomous snakes without any safety precautions. Moreover, they practice various inappropriate first aid and traditional treatments that exacerbate SBE-induced complications. We report an unusual case of SBE on the tongue of a patient who was bitten while worshipping Russell’s viper following the advice of an astrologer based on the appearance of a snake in the patient’s dream. Following the bite, the tongue was deeply incised by the priest as a first aid to mitigate SBE-induced complications. The patient suffered profuse bleeding and swelling of the tongue resulting in difficulties in intubating them. The patient regained consciousness after antivenom administration, intranasal ventilation, and blood removal from the mouth. The tongue underwent extensive surgery to restore movement and function. This report advises caution to those undertaking the extremely risky practice of worshipping live snakes and emphasises the urgent need to develop and enforce policies to mitigate such actions and educate rural communities.

Snake bite is predominantly an occupational hazard and causes severe health issues. Snake poisoning in India is a significant and prevalent cause of Acute Kidney Injury (AKI). In India, the occurrence of AKI after snake bite is 13-32%. All over the world every year, 1,50,000 people die as a result of it. Multiple mechanisms such as haemodynamic disturbances, direct tubular toxicity, coagulopathy, haemoglobinuria, and myoglobinuria can cause AKI after bites by snakes belonging to the Elapidae, Viperidae, and Colubridae families. Renal pathologic findings include acute tubular necrosis, cortical necrosis, interstitial nephritis, glomerulonephritis, and vasculitis. Thrombotic Microangiopathy (TMA) as a cause of snakebite-induced AKI is rarely reported in literature. Fewer details are known about the clinical course, optimal management, and overall prognosis of this entity. Haemolytic Uremic Syndrome (HUS) is a clinical disease that includes TMA, thrombocytopenia, and AKI as a triad. The HUS is a heterogeneity of illnesses with diverse aetiology which results in presentation, therapy and outcomes variance. Hereby, authors report a case of a 55-year-old female who was bitten by Russell’s viper and developed HUS. Patient eventually progressed to end stage renal disease and was advised lifelong haemodialysis. TMA should be taken into account as a probable cause of AKI following a snake bite. Plasma exchanges have yet to be determined in snake bite TMA.

Snakebite envenoming is a major neglected tropical health issue. The high incidence of snakebites in tropical rural communities suggests that venomous snakes and people are often in proximity but quantitative evidence is lacking. I used radio‐telemetry on a population of Russell's vipers (Daboia russelii), one of the most medically important snakes in the world, to quantify proximity between this venomous snake and people and estimate susceptibility to snakebite envenoming in India. I observed people ≤50 m of a radio‐equipped viper in ~17% of 2,066 snake relocations. People were more frequently observed in proximity to Russell's vipers in January and July compared to March, but all other contrasts were statistically similar. This pattern indicates that snakebite incidence, which peaks in summer in the study area, is not particularly linked to the encounter frequency between people and vipers. However, consistent with epidemiological data plantation workers were the most at‐risk part of the population. By integrating information about the locations of humans and snakes in space and time, this pioneering research highlights the need to include snake ecology into the study of the human–venomous‐snake conflict, and provides a model approach to help mitigate the burden caused by venomous snakes in the rural Tropics. [ABSTRACT FROM AUTHOR]

Background Coagulopathy is an important and common systemic clinical syndrome caused by snake envenoming. The major clinical effect of Russell's viper (RV) envenoming is haematotoxicity. The 20-min whole blood clotting test (WBCT20) is the standard test for identification of envenoming in resource-limited settings. However, its reliability as a diagnostic test has been questioned. Rotational thromboelastometry (ROTEM) assays different phases of clot formation from initiation to fibrinolysis. Our objective was to compare parameters of ROTEM with WBCT20 and the international normalized ratio (INR) as predictors of envenoming in RV bite patients. Methods Fifty-three patents with RV bite presenting to Anuradhapura Hospital, Sri Lanka were recruited. Epidemiological and clinical data were obtained. Venous blood samples were collected at admission for ROTEM, INR and WBCT20. Results A total of 46 of 53 patients with RV bites received antivenom serum (AVS); 74% had a non-clottable WBCT20. All 46 had at least one abnormal ROTEM parameter and 93% had a prolonged EXTEM clotting time (EXTEM-CT). The sensitivity of a prolonged INR was only 55%. Conclusions EXTEM-CT is a better predictor of envenoming and the need for AVS than WBCT20 in RV bites (p=0.02). It provides a numerical value that can be used post-AVS to objectively assess the response and decide on further treatment. [ABSTRACT FROM AUTHOR]

Russell's viper envenoming causes venom-induced consumption coagulopathy (VICC) within hours of a bite, which is associated with thrombotic microangiopathy (TMA) and acute kidney injury (AKI) in a proportion of cases. We report a juvenile Russell's viper bite in which a patient developed mild VICC after the usual 24-h observation period, which was subsequently associated with severe AKI due to TMA. This shows the clinical importance of detecting and treating mild VICC, which may be delayed or not detected with bedside clotting tests. [Display omitted] • Russell's viper bite causes venom-induced consumption coagulopathy. • Usually, its coagulopathy develops within hours, followed by the renal failure. • We report Russell's viper bite with coagulopathy on day two missed by bedside test. • Antivenom delayed resulting in thrombotic microangiopathy and severe renal failure. • Detecting and treating mild coagulopathy early could be clinically important. [ABSTRACT FROM AUTHOR]

Background: Envenoming by vipers Russell's and Echis Carinatus are common accidents faced by farmers and labors. Both viper venom toxins alter coagulation mechanism in the victim. The dose of snake antivenin to neutralize the venom is empirical and varies. Though the clinical manifestations in both vipers bite envenoming are nearly similar but dose of antivenin required is more in Russell's viper. We studied in detail about the correlation of clinical manifestations and confirmed species of snake. Methods: Cases of vipers snake bites admitted for last two successive years were studied. Analysis by local manifestations, systemic involvement, 20 minute whole blood clotting test (20WBCT), identification of snake responsible for clinical effects are confirmed by the snake species brought by victims or bystanders, in case of where victim saw the snake bur failed to kill. The victims identified from pictures of big four poisonous snakes (Russell's viper, Echis carinatus, Cobra, and krait). Further confirmation from the species responsible is done by showing the hospital preserved specimen to identify the culprits. Findings: About 77 cases of viper bite studied of these 57 has clinical syndrome suggestive of Russell's viper (RV) bite, one has dry bite, 23 victims brought the killed specimen confirmed RV, of these 18 identified the specimen picture and 5 wrongly locate the species in pictures, 20 victims correctly identified the hospital preserved specimen while 3 failed to recognize. There were 28 patients who saw the snake while bitten but failed to kill, of these 20 patients identify correctly the species on picture while 8 failed to identify. Only 22 correctly identified the culprit by looking at the hospital preserved specimen and 6 were confused. One dry bite victim correctly identified the bitten snake species in picture and hospital preserved specimen. Interpretation: In viper bite poisoning clinical pictures and hospital specimen help to confirm the species are highly supportive for clinical diagnosis.

Daboia siamensis (Russell’s viper) is a highly venomous and medically important snake in China, as well as much of Asia. There is minimal information on the pharmacological activity of the venom of the Chinese species, and currently no commercially available specific antivenom in China. This has led to the use of non-specific antivenoms to treat D. siamensis envenomation. In this study, the in vitro neurotoxicity and myotoxicity of D. siamensis venom was examined and the efficacy of four antivenoms was investigated, including the recently developed Chinese D. siamensis monovalent antivenom (C-DsMAV) and three commercially available antivenoms (Thai D. siamensis (Thai-DsMAV) monovalent antivenom, Deinagkistrodon acutus monovalent antivenom (DaAV), and Gloydius brevicaudus monovalent antivenom (GbAV). D. siamensis venom (10–30 µg/mL) caused the concentration-dependent inhibition of indirect twitches in the chick biventer cervicis nerve muscle preparation, without abolishing contractile responses to exogenous agonists ACh or CCh, indicating pre-synaptic neurotoxicity. Myotoxicity was also evident at these concentrations with inhibition of direct twitches, an increase in baseline tension, and the partial inhibition of ACh, CCh, and KCl responses. The prior addition of C-DsMAV or Thai-DsMAV prevented the neurotoxic and myotoxic activity of D. siamensis venom (10 µg/mL). The addition of non-specific antivenoms (GbAV and DaAV) partially prevented the neurotoxic activity of venom (10 µg/mL) but failed to neutralize the myotoxic effects. We have shown that D. siamensis venom exhibits in vitro weak presynaptic neurotoxicity and myotoxicity, which can be prevented by the pre-addition of the Chinese and Thai Russell’s viper antivenoms. Non-specific antivenoms were poorly efficacious. There should be further development of a monospecific antivenom against D. siamensis envenomation in China.

Russell’s viper (Daboia russelii), one of the ‘Big Four’ venomous snakes in India, is responsible for the majority of snakebite-induced deaths and permanent disabilities. Russell’s viper bites are known to induce bleeding/clotting abnormalities, as well as myotoxic, nephrotoxic, cytotoxic and neurotoxic envenomation effects. In addition, they have been reported to induce rare envenomation effects such as priapism, sialolithiasis and splenic rupture. However, Russell’s viper bite-induced pseudoaneurysm (PA) has not been previously reported. PA or false aneurysm is a rare phenomenon that occurs in arteries following traumatic injuries including some animal bites, and it can become a life-threatening condition if not treated promptly. Here, we document two clinical cases of Russell’s viper bites where PA has developed, despite antivenom treatment. Notably, a non-surgical procedure, ultrasound-guided compression (USGC), either alone, or in combination with thrombin was effectively used in both the cases to treat the PA. Following this procedure and additional measures, the patients made complete recoveries without the recurrence of PA which were confirmed by subsequent examination and ultrasound scans. These data demonstrate the development of PA as a rare complication following Russell’s viper bites and the effective use of a simple, non-surgical procedure, USGC for the successful treatment of PA. These results will create awareness among healthcare professionals on the development of PA and the use of USGC in snakebite victims following bites from Russell’s vipers, as well as other viper bites.

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., Competing Interests: None.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The pathophysiological effects of Russell's viper venom (RVV) and its fractions, including phospholipase A2 (RvPLA2), metalloprotease (RvMP), L-amino acid oxidase (RvLAAO), and phosphodiesterase (RvPDE) on renal functions were investigated using the isolated perfused rabbit kidney (IPK) model. Moreover, whether their effects on renal alterations were promoted by platelet activating factor (PAF) was tested using the PAF receptor antagonist, WEB 2086. There was a marked reduction in the perfusion pressure (PP) and renal vascular resistance (RVR) 10 min after RVV administration (1.0 mg/100 ml of perfusate), thereafter both PP and RVR gradually increased and approached the control level within 90 min. These effects were abolished by pretreatment with WEB2086 (2 μg/μl). Administration with RvPLA2 (280 μg/ml), RvMP (280 μg/ml), or RvLAAO (135 μg/ml) alone increased both the PP and RVR, whereas RvPDE (100 μg/ml) reduced both the PP and RVR. Pretreatment with WEB 2086 completely abolished the effects induced by RvMP, but not the other fractions. The RVV also caused a marked decrease in the glomerular filtration rate (GFR), urinary flow rate (UF), and osmolar clearance (Cosm), and these effects were not inhibited by pretreatment with WEB2086. Each RVV fraction also increased, to varying extents, the GFR, UF, and Cosm, and these effects induced by RvPLA2 or RvMP, but not the other fractions, were completely blocked by WEB 2086. Changes in percent filtered Na+ and K+ excreted in the IPK by RVV, RvPDE, and RvMP were abolished by pretreatment with WEB 2086. Histological evaluation profiled mainly tubulonephrosis in the treated kidney. These results reveal that the alterations in renal functions induced by RVV and its fractions are due to the synergistic action of the different components of snake venom, instead of the action of a single component. The effects of RVV and its fractions in rabbit IPK are mediated at least in part by PAF.

KG Sajeeth Kumar, Santhosh Narayanan, V Udayabhaskaran, NK Thulaseedharan Department of General Medicine, Government Medical College, Kozhikode, Kerala, India Background: Snake bites are a neglected public health problem in all tropical countries, and particularly in Malabar region of Kerala, India. Demographic characteristics and clinical parameters vary in this part of the world, and studies based on them are scarce. Increased incidence of capillary leak syndrome (CLS) in hemotoxic snake bites and emergence of cases of hump-nosed pit viper (HNPV, Hypnale hypnale) envenomation are some notable features seen here. Objectives: The study was conducted to assess the epidemiological profile and clinical features to identify factors contributing to outcome in patients with venomous snakebites. Materials and methods: An observational cross-sectional study was done among patients with snakebite envenomation, admitted to Government Medical College, Kozhikode, Kerala, from January 2012 to October 2016. Results: There were 1,500 cases of toxic snake bites, of which 65% of these cases were males. Forty eight percent of them were aged between 21 and 40 years. Hemotoxic snake bites predominated, accounting for 912 cases. Viperine bite was the most commonly observed snakebite, and 70% of this was due to Russell’s viper and 25% due to HNPV. Among the neurotoxic bites, common krait bites predominated. Overall mortality was 8.8%. CLS was the major cause of death (80%). The mean dose of antivenom given for neuroparalytic snakebite was 10.25 vials, and 18.5 vials for hemotoxic bites. Albuminuria, neutrophilic leucocytosis, thrombocytopenia, acute kidney injury (AKI), and early onset of symptoms were associated with poor outcome. Conclusion: This study emphasizes the importance of snakebite as a significant threat to the community in the tropics. CLS in hemotoxic snake bites is the leading cause of mortality and is often refractory to any treatment measures. This study also brings to light the graveness of complications caused by HNPV envenomation. Anti-snake venom with activity against HNPV venom needs to be manufactured. Lack of awareness, delayed presentation to the hospital, and treatment by nonmedical personnel also add to the risk of mortality. Keywords: hump-nosed pit viper, capillary leak, antivenom, Russell’s viper, hemotoxic, neurotoxic, snake bite

The snake genus Daboia (Viperidae: Viperinae; Oppel, 1811) contains five species: D. deserti, D. mauritanica, and D. palaestinae, found in Afro-Arabia, and the Russell’s vipers D. russelii and D. siamensis, found in Asia. Russell’s vipers are responsible for a major proportion of the medically important snakebites that occur in the regions they inhabit, and their venoms are notorious for their coagulopathic effects. While widely documented, the extent of venom variation within the Russell’s vipers is poorly characterised, as is the venom activity of other species within the genus. In this study we investigated variation in the haemotoxic activity of Daboia using twelve venoms from all five species, including multiple variants of D. russelii, D. siamensis, and D. palaestinae. We tested the venoms on human plasma using thromboelastography, dose-response coagulometry analyses, and calibrated automated thrombography, and on human fibrinogen by thromboelastography and fibrinogen gels. We assessed activation of blood factors X and prothrombin by the venoms using fluorometry. Variation in venom activity was evident in all experiments. The Asian species D. russelii and D. siamensis and the African species D. mauritanica possessed procoagulant venom, while D. deserti and D. palaestinae were net-anticoagulant. Of the Russell’s vipers, the venom of D. siamensis from Myanmar was most toxic and D. russelli of Sri Lanka the least. Activation of both factor X and prothrombin was evident by all venoms, though at differential levels. Fibrinogenolytic activity varied extensively throughout the genus and followed no phylogenetic trends. This venom variability underpins one of the many challenges facing treatment of Daboia snakebite envenoming. Comprehensive analyses of available antivenoms in neutralising these variable venom activities are therefore of utmost importance.

Snakebite-induced acute kidney injury (AKI) is frequently observed in patients following bites from vipers such as Russell’s viper (Daboia russelii) in India. Currently, the levels of serum creatinine are mainly used as a marker to determine the necessity for renal replacement therapy (RRT) (haemodialysis) in severe cases of AKI. However, it takes up to 48 h to ascertain a distinct change in creatinine levels compared to its baseline level upon admission. The time lost between admission and the 48 h timepoint significantly affects the clinical management of snakebite victims. Moreover, early diagnosis of AKI and decision on the necessity for RRT in snakebite victims is critical in saving lives, reducing long-term complications, and minimising treatment costs arising from expensive haemodialysis. Neutrophil gelatinase–associated lipocalin (NGAL) has been recently studied as a robust early marker for AKI in non-snakebite patients. However, its suitability for clinical use in snakebite victims has not been rigorously established. Here, we demonstrate the clinical significance of plasma NGAL as a robust marker for RRT following AKI using a large cohort (309) of Russell’s viper victims without any pre-existing health conditions. NGAL levels upon admission are positively correlated with creatinine levels at 48 h in different stages of AKI. Overall, NGAL acts as a robust early marker to ascertain the need for RRT following Russell’s viper bites. The quantification of NGAL can be recommended as a routine test in hospitals that treat snakebites to decide on RRT at early time points instead of waiting for 48 h to confirm the increase in creatinine levels. The diagnostic use of NGAL in Russell’s viper victims with pre-existing comorbidities and for other vipers should be evaluated in future studies.

Context: Thrombotic microangiopathy (TMA) resulting in acute kidney injury (AKI) is an important complication of venomous snakebites. We aimed to describe TMA secondary to Russell's viper (Daboia russelli) and hump-nosed viper (Hypnale spp.) bites and assess the effect of different treatments. Materials and methods: We undertook a prospective observational study of patients with AKI secondary to snakebite over a two-year period. Data recorded included: demographic details, clinical and laboratory features, treatment, complications and outcomes, until hospital discharge and at three months post-discharge. TMA was defined as the development of microangiopathic hemolytic anemia and thrombocytopenia along with AKI. Treatment with therapeutic plasma exchange (TPE; also known as plasmapheresis) and/or fresh frozen plasma (FFP) was determined by the treating clinician. Antivenom was given to all patients with evidence of systemic envenoming following Russell's viper bites. Results: Fifty-nine patients were included in the analysis. Thirty-three (56%) were males and median age was 56 years. Forty-five (76%) developed TMA while a further 11 and two developed isolated thrombocytopenia and microangiopathic hemolytic anemia, respectively. Presence of TMA was associated with increased dialysis requirements (5 vs. 3) and longer hospital stay (18 vs. 12 days). Of the patients with TMA, nine received TPE with or without FFP infusions. The use of TPE was not associated with improved outcomes in patients with TMA based on requirement for blood transfusion, recovery of thrombocytopenia, requirement of dialysis and duration of hospital stay. Patients who did not receive TPE had better renal function at three months compared to patients who received this treatment. Conclusion: Presence of TMA in patients with Daboia and Hypnale bites was associated with a more prolonged course of AKI. Patients with TMA who were treated with TPE did not have improved early or late outcomes compared to patients who were not treated with TPE. [ABSTRACT FROM AUTHOR]

Background: Out of four species of snakes in the family Viperidae in Sri Lanka, Russell's viper is widely distributed all over the country and causes severe envenoming manifestations such as coagulopathy and neuroparalysis. Most snakebite deaths occur due to its bites in Sri Lanka and systemic bleeding is the most trivial complication associated with coagulopathy caused by these snakes. Pulmonary hemorrhage is one effect which is rarely reported. Case presentation: A 30-year-old previously well male was bitten by a Russell's viper on his left foot and had mild local pain, moderate swelling and two fang punctures. Two hours after the bite, he developed vomiting with bilateral ptosis and external ophthalmoplegia, so he was given 20 vials of polyvalent antivenom after the prophylactic therapy. Later, he had prolonged whole blood clotting test associated with hematuria, followed by respiratory failure for which he was intubated. He also had blood stained endotracheal tube secretions and pulmonary hemorrhage, revealed by high-resolution computed tomography of the chest. He also developed acute kidney injury, rhabdomyolysis and deep vein thrombosis. He completely recovered and was discharged on day 23. Discussion: Snake venom serine proteinase, metalloprotease, snaclec and L-amino acid oxidase are hemotoxins of Russell's viper venom that cause venom induced consumption coagulopathy and hemorrhage. Metalloprotease has a direct action on lung microvasculature causing pulmonary hemorrhage. Conclusion: Severe fatal systemic manifestations like pulmonary hemorrhage may occur rarely following Russell's viper bites. [ABSTRACT FROM AUTHOR]

Background: Serum fibrinogen of less than 100 mg/dL is recommended for predicting systemic bleeding risk in hematotoxic snake bite patients, but it is not widely available. Data on using venous clotting time (VCT), 20-minute whole blood clotting test (20WBCT), platelets, prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT) to predict systemic bleeding in hematotoxic snake bite patients are limited. Objective: To determine association between clotting tests (VCT, 20WBCT, platelets, PT, PTT, and INR) and 1) serum fibrinogen of less than 100 mg/dL, and 2) systemic bleeding in patients bitten by green pit viper (GPV) or Russell's viper (RV). Materials and Methods: This prospective cohort study included patients bitten by GPV or RV at Sawanpracharak Hospital, Nakhon Sawan, Thailand, between October 2016 and December 2017. Patient's blood specimens were collected for fibrinogen, PT, INR, PTT, platelet count, VCT, and 20WBCT at initial presentation and every six hours until 24 hours of admission, or patients' recovery. The association were determined by using Fisher's exact test. Results: There were 30 patients, 21 were bitten by GPV, and nine were bitten by RV. One hundred sixty-one sets of blood specimens were collected. There were four cases with systemic bleeding. Factors associated with fibrinogen of less than 100 mg/dL were VCT of 20 minutes or more (p=0.01), unclotted 20WBCT (p=0.01), PT of more than 13 seconds (p=0.04), and INR of 1.2 or more (p<0.01). Factors that associated with systemic bleeding were VCT of 20 minutes or more (p<0.01), unclotted 20WBCT (p<0.01), INR of 1.2 or more (p=0.04), and fibrinogen of less than 100 mg/dL (p=0.01). Conclusion: VCT of 20 minutes or more, unclotted 20WBCT, and INR of 1.2 or more are associated with serum fibrinogen less than 100 mg/dL and systemic bleeding in GPV and RV envenomation. [ABSTRACT FROM AUTHOR]