A study to assess the clinical profile of patients with snake bites in a tertiary care hospital

Background: Snakebite is a life-threatening medical emergency. It occurs frequently among rural people, especially those working in the fields. Most houses in rural areas of India are made of mud and have many crevices where rodents flourish. Delay in seeking medical aid or ignorance among primary care physicians about the correct treatment of snakebite is responsible for the high morbidity and mortality. Authors objective was to study the clinical profile of snake bite at a rural tertiary care centre.Methods: A hospital based cross sectional study was conducted at M S Rammaih Medical College Bangalore from June 2017 to June 2018. The incidence of Snake bite in Karnataka is 0.5% and at 95% confidence interval with Margin of error at 1% the estimated sample size was 197, but in this study author were able to collect data of 237 cases, hence all the cases were included in the study and analyzed.Results: Majority of the respondents were middle aged between 21-50 years. Around 63.3% of the respondents were male and nearly 56.2% were farmers. The incidence of snake bite of Cobra was seen in 8.9%, Krait 5.1% and viper 4.2%. Around 70% patients had no significant complications following hospitalization in our study. Around 20% had hematotoxic like ARF, DIC and local gangrene.Conclusions: Snakebite is one of the common hazards especially in rural setup as agriculture being the main occupation. Snake bite can present with various manifestations at bite sites, neurotoxicity, hematotoxicity.

Neurotoxic Snakebite In Jammu Region: Is It Cobra Or Krait

Background: The aim of this study is to analyze the clinical profile and outcome of the neurotoxic envenomation in children inJammu region and to identify the species based on the syndromic approach developed by WHO.Materials and Methods: A retrospective hospital record based descriptive study which analyses the case records of childrenreporting to pediatric emergency with signs and symptoms of neurotoxic envenomation.Results: A total of 22 cases of the neurotoxic envenomation reported between April 15 and October 15. These included 14males and 8 females between the age group of 2.5 years and 16 years. The highest incidence of snakebite was observed inthe age group of 4–8 years. A total of seven cases presented neuroparalytic symptoms and local signs suggesting cobra bite.Bite was reported in the afternoon or evening hours between 12.30 pm and 10.30 pm and 83% bites were outdoors. A total of15 children presented with neuroparalytic symptoms with no local signs suggesting krait bite. 86% of the bites were indoor withonset of symptoms between 12 am and 7 am.Conclusion: Both cobra and krait cause neurotoxic envenomation in children in Jammu region with krait bite accounting for 68%of the total cases. Most of these cases are brought to the pediatric emergency late. Training of the peripheral doctors regardingearly recognition of neurotoxic snakebite, species diagnosis as per the WHO syndromic approach, prompt institution of initialmanagement with neostigmine and after visit summary, endotracheal intubations and AMBU bag ventilation, and quick referralto a center with ventilator facility should help in reducing the morbidity and mortality due to krait and cobra bite in children.

Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand

Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 µg/kg, i.m.) or 0.9% NaCl solution (50 µL, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Results: Administration of BC-NE or BC-S venom (50 µg/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (100­0.2 µg/ mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 =8 ± 1 µg/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 =15 ± 2 µg/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom. Conclusions: This study found that Malayan krait venoms from both populations possess myotoxic, cytotoxic and nephrotoxic activities. These findings may aid in clinical diagnosis and treatment of envenomed patients in the future.(AU)

Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand

Background: Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 g/kg, i.m.) or 0.9% NaCl solution (50 L, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Results: Administration of BC-NE or BC-S venom (50 g/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (1000.2 g/ mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 =8 ± 1 g/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 =15 ± 2 g/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom...

Antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom in experimental animal models.

Pain and inflammation are intimately associated with rheumatoid arthritis, a growing bone-joint related problem of the modern society. Though several therapeutic managements are available for arthritis, their side effects not only limit their use, but also advocate the quest for natural therapies. In this study, we explored the antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom (BFV) in experimental animal models. Rheumatoid arthritis was induced by Freund’s complete adjuvant (FCA) in male Wistar albino rats. Lyophilized BFV was diluted in 0.9% NaCl. Antiarthritic activity showed that BFV significantly reduced the paw and ankle diameters; urinary hydroxyproline, glucosamine levels and serum ACP/ALP/TNF-α/IL-1β/IL-17/Cathepsin-K/MMP-1 levels. These parameters were significantly increased in FCA induced arthritic animals. Joint histopathology study indicated the partial restoration of joint structure. Treatment with BFV significantly reduced the mean latency time of tail flick response, acetic acid induced writhing response and formalin induced licking response in male albino mice. BFV treatment also significantly reduced carrageenan induced paw edema and xylene induced ear edema in male albino mice. The results indicated that BFV possess antinociceptive, anti-inflammatory and antiarthritic properties and further studies are warranted to find the active constituents present in BFV.

Fatal neurotoxic envenomation following the bite of a greater black krait (Bungarus niger) in Nepal: a case report

Neurotoxic envenomation following bites by kraits (Bungarus species) is a leading cause of snakebite mortality in South Asia. Over a long time, this had been attributed only to one species, the common krait (Bungarus caeruleus). However, recent research has provided increasing evidence of the involvement of several krait species. Here, we report a fatal case of neurotoxic envenomation following the bite of a greater black krait (Bungarus niger) in Nepal. Case presentation A 33-year-old man was bitten in the outdoor corridor of his home in the eastern hills of Ilam district while handling a snake he thought to be non-venomous. He subsequently developed severe abdominal pain, frequent vomiting, and signs of neurotoxic envenomation leading to respiratory paralysis. The patient did not respond to Indian polyvalent antivenom given 4 h after the bite and died under treatment 8 h after the bite. This is the second time that a B. niger was observed in Nepal, the first documented case of envenomation by this species in the country and the sixth reported case worldwide. Conclusions Previous distribution records from eastern India and western Nepal, from western hills in Nepal, and from lowland localities in India and Bangladesh indicate risk of envenomation by B. niger throughout the low and intermediate elevations of Nepal up to at least 1,500 m above sea level. As very few people in Nepal bring killed snakes to healthcare centers and because there is a general belief among local people that there are no kraits in the hills, bites by B. niger are likely to be misdiagnosed and underreported.

Fatal neurotoxic envenomation following the bite of a greater black krait (Bungarus niger) in Nepal: a case report

Background Neurotoxic envenomation following bites by kraits (Bungarus species) is a leading cause of snakebite mortality in South Asia. Over a long time, this had been attributed only to one species, the common krait (Bungarus caeruleus). However, recent research has provided increasing evidence of the involvement of several krait species. Here, we report a fatal case of neurotoxic envenomation following the bite of a greater black krait (Bungarus niger) in Nepal. Case presentation A 33-year-old man was bitten in the outdoor corridor of his home in the eastern hills of Ilam district while handling a snake he thought to be non-venomous. He subsequently developed severe abdominal pain, frequent vomiting, and signs of neurotoxic envenomation leading to respiratory paralysis. The patient did not respond to Indian polyvalent antivenom given 4 h after the bite and died under treatment 8 h after the bite. This is the second time that a B. niger was observed in Nepal, the first documented case of envenomation by this species in the country and the sixth reported case worldwide. Conclusions Previous distribution records - from eastern India and western Nepal, from western hills in Nepal, and from lowland localities in India and Bangladesh - indicate risk of envenomation by B. niger throughout the low and intermediate elevations of Nepal up to at least 1,500 m above sea level. As very few people in Nepal bring killed snakes to healthcare centers and because there is a general belief among local people that there are no kraits in the hills, bites by B. niger are likely to be misdiagnosed and underreported.(AU)

Indian common krait envenomation presenting as fulminant myocarditis and coma: a case report.

Fulminant myocarditis is an unusual manifestation of cardiotoxicity with severe elapid snake envenoming and is meagrely reported with snake bite due to Indian common krait. We report a 12-year-old boy who was admitted in complete locked-in state and hemodynamic instability after severe neurotoxic snake envenoming by Bungarus caeruleus (Indian common krait). His hospital course was complicated with recurrent episodes of sustained ventricular tachycardia requiring defibrillation; and cardiogenic shock requiring inotropes, vasopressors and intraaortic balloon counterpulsation. Severe heart failure features secondary to fulminant toxic myocarditis persisted even after full neurological recovery requiring prolonged standard medical heart failure therapy. Patient subsequently achieved full clinical recovery and regained normal left ventricular systolic function. We also reviewed the literature on cardiac manifestations, possible mechanisms and treatment of patients with cardiotoxicity due to elapid snake bites. The importance of anticipating severe cardiovascular complications is highlighted to help formulate appropriate therapeutic strategy.

In vitro screening and evaluation of antivenom phytochemicals from Azima tetracantha Lam. leaves against Bungarus caeruleus and Vipera russelli

Snakebites are considered a neglected tropical disease that affects thousands of people worldwide. Although antivenom is the only treatment available, it is associated with several side effects. As an alternative, plants have been extensively studied in order to obtain an alternative treatment. In folk medicine, Azima tetracantha Lam. is usually used to treat snakebites. The present study aims to provide a scientific explanation for the use of this plant against snakebite. The extracts of shade dried leaves of A. tetracantha were tested for in vitro inhibitory activity on toxic venom enzymes like phosphomonoesterase, phosphodiesterase, acetylcholinesterase, hyaluronidase etc. from Bungarus caeruleus and Vipera russelli venoms.

In vitro screening and evaluation of antivenom phytochemicals from Azima tetracantha Lam. leaves against Bungarus caeruleus and Vipera russelli

Snakebites are considered a neglected tropical disease that affects thousands of people worldwide. Although antivenom is the only treatment available, it is associated with several side effects. As an alternative, plants have been extensively studied in order to obtain an alternative treatment. In folk medicine, Azima tetracantha Lam. is usually used to treat snakebites. The present study aims to provide a scientific explanation for the use of this plant against snakebite. The extracts of shade dried leaves of A. tetracantha were tested for in vitro inhibitory activity on toxic venom enzymes like phosphomonoesterase, phosphodiesterase, acetylcholinesterase, hyaluronidase etc. from Bungarus caeruleus and Vipera russelli venoms.

New approaches & technologies of venomics to meet the challenge of human envenoming by snakebites in India.

The direct estimate of 46,000 snakebite deaths in India in 2005 (1 for every 2 HIV/AIDS deaths), based on verbal autopsies, renders unrealistic the total of only 47,000 snakebite deaths in the whole world in 2010, obtained indirectly as part of the “Global Burden of Disease 2010” study. Persistent underestimation of its true morbidity and mortality has made snakebite the most neglected of all the WHO’s “neglected tropical diseases”, downgrading its public health importance. Strategies to address this neglect should include the improvement of antivenom, the only specific antidote to envenoming. To accommodate increased understanding of geographical intraspecific variation in venom composition and the range of snake species that are medically important in India, the design of antivenoms (choice of venom sources and species coverage) should be reconsidered. Methods of preclinical and clinical testing should be improved. The relatively new science of venomics involves techniques and strategies for assessing the toxin composition of snake venoms directly through proteomics-centred approaches or indirectly via high-throughput venom gland transcriptomics and bioinformatic analysis. Antivenomics is translational venomics: a proteomics-based protocol to quantify the extent of cross-reactivity of antivenoms against homologous and heterologous venoms. These approaches could revolutionize the preclinical assessment of antivenom efficacy, leading to a new generation of antivenoms that are clinically more effective.

Inhibition of toxic actions of phospholipase A2 isolated & characterized from the Indian Banded Krait (Bungarus fasciatus) venom by synthetic herbal compounds.

Background & objectives: Phospholipase A2 (PLA2) is one of the major constituents of krait venom associated with several pathophysiological actions like myotoxicity, cardiotoxicity, neurotoxicity, etc. As there was no specific antiserum available against Bungarus fasciatus venom, this study was done with synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum to neutralize the PLA2 induced toxicities in experimental models. Methods: B. fasciatus venom phospholipase A2 fraction 38 (BF-38) was isolated by ion exchange chromatography, molecular weight was determined by mass spectrometry and its N terminal amino acid sequence was identified. Monospecific rabbit antiserum was raised against the PLA2 in presence of Freund complete adjuvant. The neutralization of PLA2 induced toxicities was done in in vitro and in in vivo models using synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum. Results: A toxic PLA2 (BF-38) was purified from the B. fasciatus venom by CM-cellulose and HPLC, of 13.17 kDa and a minor band of 7.3 kDa using ESI-MS. The 13.17 kDa PLA2 sequence was NLYQFKNMIQC. The 7.3 kDa toxin sequence was RKCLTKYSQDNES and was found to be <10 per cent w/w. Anti PLA2 rabbit antiserum produced faint precipitant band in immunogel diffusion and showed low titre value. The commercial polyvalent snake venom antiserum, anti PLA2 rabbit antiserum and the synthetic herbal compounds neutralized the PLA 2 induced toxicities at different intensities. Interpretation & conclusions: Our results suggested that synthetic herbal compound (BA) along with antiserum might provide effective protection against PLA2 induced toxicities of B. fasciatus venom.

Unilateral lower motor neuron-type of facial palsy following snake bite presumably due to Krait (Bungarus Caeruleus).

We describe an unusual case of snake bite presumably due to Krait (Bungarus Caeruleus) in a 12-year-old child from Mohali, Punjab. He presented with a history of bite behind his left ear, while he was sleeping at night on floor. He had bilateral ptosis, dysphonia initially, which progressed gradually to cause respiratory paralysis. Child was managed with antisnake venom, ventilation and other supportive measures. He recovered gradually, but persisted to have lower motor neuron paralysis of left facial nerve, which was noted post extubation. This uncommon presentation could be because of exposure of the facial muscles to the venom, spreading directly from the injection site and destroying the nerve terminals of facial nerve in the muscle tissue. At three months follow-up, child showed complete recovery. Facial nerve involvement following snake bite, which usually has a good prognosis, remain an uncommon presentation in paediatric age group.

Enzymatic and biochemical characterization of Bungarus sindanus snake venom acetylcholinesterase

This study analyses venom from the elapid krait snake Bungarus sindanus, which contains a high level of acetylcholinesterase (AChE) activity. The enzyme showed optimum activity at alkaline pH (8.5) and 45ºC. Krait venom AChE was inhibited by substrate. Inhibition was significantly reduced by using a high ionic strength buffer; low ionic strength buffer (10 mM PO4 pH 7.5) inhibited the enzyme by 1. 5mM AcSCh, while high ionic strength buffer (62 mM PO4 pH 7.5) inhibited it by 1 mM AcSCh. Venom acetylcholinesterase was also found to be thermally stable at 45ºC; it only lost 5% of its activity after incubation at 45ºC for 40 minutes. The Michaelis-Menten constant (Km) for acetylthiocholine iodide hydrolysis was found to be 0.068 mM. Krait venom acetylcholinesterase was also inhibited by ZnCl2, CdCl2, and HgCl2 in a concentrationdependent manner. Due to the elevated levels of AChE with high catalytic activity and because it is more stable than any other sources, Bungarus sindanus venom is highly valuable for biochemical studies of this enzyme.(AU)

Krait bite poisoning in manipal region of Southern India.

Krait commonly inhabits the South Asian countries and is regarded as the most dangerous species of venomous snake in the Indian subcontinent. This prospective research included the consecutive cases of Krait bite cases admitted to Kasturba Hospital, Manipal during August 2003 and November 2005. All the victims of Krait bite were females aged between 17 and 35 years. Victims were from a rural background and most of them were bitten indoors and during the night time. Most of the bites involved the lower limbs. Signs of envenomation (neurological symptoms) were observed in 50% of the cases. In the only case of fatal outcome in our study, there was a delay in diagnosis of Krait bite owing to the absence of bite marks. The case emphasizes on the fact that the possibility of snake bite should be considered in an otherwise healthy person who presents with sudden onset of neuroparalytic features.