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1.  Bilateral blindness following Russell’s viper bite - a rare clinical presentation: a case report 
Introduction
Russell’s viper (Daboia russelii) is one of the most common medically important snakes reported in Sri Lanka. Its envenomation leads to significant mortality and morbidity with local, hematological, neurological and renal complications. Here we report the case of a patient who presented with bilateral blindness secondary to a bilateral posterior circulation ischemic stroke instead of the usual neurological manifestations of Russell’s viper envenomation. There were no reported cases of cortical blindness following a Russell’s viper bite. Only a few reported cases of ischemic strokes following a Russell’s viper bite were found in the literature.
Case presentation
A 54-year-old Sri Lankan woman developed bilateral blindness due to a posterior circulation infarct following Russell’s viper envenomation.
Conclusion
Ischemic stroke following a Russell’s viper bite is very rare and cortical blindness is not reported as the clinical presentation. Also, we emphasize the importance of considering the possibility of ischemic stroke in patients who develop unusual neurological manifestations following Russell’s viper envenomation.
doi:10.1186/1752-1947-8-99
PMCID: PMC3978077  PMID: 24661603
Blindness; Russell’s viper; Ischemic stroke
2.  Revisiting Russell's Viper (Daboia russelii) Bite in Sri Lanka: Is Abdominal Pain an Early Feature of Systemic Envenoming? 
PLoS ONE  2014;9(2):e90198.
The Russell's viper (Daboia russelii) is responsible for 30–40% of all snakebites and the most number of life-threatening bites of any snake in Sri Lanka. The clinical profile of Russell's viper bite includes local swelling, coagulopathy, renal dysfunction and neuromuscular paralysis, based on which the syndromic diagnostic tools have been developed. The currently available Indian polyvalent antivenom is not very effective in treating Russell's viper bite patients in Sri Lanka and the decision regarding antivenom therapy is primarily driven by clinical and laboratory evidence of envenoming. The non-availability of early predictors of Russell's viper systemic envenoming is responsible for considerable delay in commencing antivenom. The objective of this study is to evaluate abdominal pain as an early feature of systemic envenoming following Russell's viper bites. We evaluated the clinical profile of Russell's viper bite patients admitted to a tertiary care centre in Sri Lanka. Fifty-five patients were proven Russell's viper bite victims who produced the biting snake, while one hundred and fifty-four were suspected to have been bitten by the same snake species. Coagulopathy (159, 76.1%), renal dysfunction (39, 18.7%), neuromuscular paralysis (146, 69.9%) and local envenoming (192, 91.9%) were seen in the victims, ranging from mono-systemic involvement to various combinations. Abdominal pain was present in 79.5% of these patients, appearing 5 minutes to 4 hours after the bite. The severity of the abdominal pain, assessed using a scoring system, correlated well with the severity of the coagulopathy (p<0.001) and the neurotoxicity (p<0.001). Its diagnostic validity to predict systemic envenoming is – Sensitivity 81.6%, Specificity 82.4%, Positive predictive value 91.2%. Thus, abdominal pain is an early clinical feature of systemic Russell's viper bite envenoming in Sri Lanka. However, it is best to judge abdominal pain together with other clinical manifestations on decision making.
doi:10.1371/journal.pone.0090198
PMCID: PMC3936006  PMID: 24587278
3.  Cerebellar infarct with neurogenic pulmonary edema following viper bite 
Russell's viper (Daboia russelli) bites are well known to cause bleeding complications. However, thrombotic complications are rare. We present the case details of a female who was bitten by a Russell's viper (Daboia russelli) in her village. She then developed features of envenomation in the form of hemorrhagic episodes. She received 27 vials of polyvalent anti-snake venom to which the hemorrhagic complications responded. After about 48 h of the bite she developed features of cerebellar infarct along with pulmonary edema which was in all probability neurogenic in origin. She was managed with mechanical ventilation and extra ventricular drainage with good recovery. We discuss the likely pathogenesis of the infarct and pulmonary edema occurring in a patient with viper bite and other features of envenomation.
doi:10.4103/0976-3147.91954
PMCID: PMC3271624  PMID: 22346200
Cerebellar infarct; neurogenic pulmonary edema; viper bitee
4.  Acute myocardial infarction following a Russell’s viper bite: a case report 
Introduction
Snake bite is a common and devastating environmental hazard, especially in rural areas of tropical countries. Acute myocardial infarction caused by snakebite has rarely been reported. To our knowledge we found only 10 cases of Myocardial infarction following a viper bite in English literature.
Case presentation
We report a case of inferior ST elevation myocardial infarction following a Russell’s viper bite in a 37 year old healthy Sri Lankan (South Asian) female with no past history of cardiac disease or cardiac risk factors who died 30 hours following the bite.
Conclusion
The course of events with respect to myocardium suggests a direct toxic effect of the venom on myocardial tissue or coronary vasoconstriction. Physicians should bear in mind the complications and devastating sequela of Myocardial infarction following Russell’s viper bite.
doi:10.1186/1755-7682-6-7
PMCID: PMC3605354  PMID: 24499589
Snake bite; Russell’s viper; Myocardial infarction; ST elevation myocardial infarction
5.  A study of snake bite among children presenting to a paediatric ward in the main Teaching Hospital of North Central Province of Sri Lanka 
BMC Research Notes  2014;7:482.
Background
Snake bite is a common problem in the North Central province of Sri Lanka. Common krait (Bungarus careuleus), Ceylon krait (Bungarus ceylonicus), Cobra (Naja naja), Russell’s viper (Daboia russelii), Saw-scaled viper (Echis carinatus) and Hump-nosed pit viper (Hypnale hypnale) are the six species of venomous land snakes in Sri Lanka. A significant number of adults and children are bitten by snakes every year. However, the majority of research studies done in Sri Lanka and other countries show adults bitten by snakes and studies describing children bitten by snakes are very sparse.
Methods
A descriptive cross sectional study was performed in the Teaching Hospital Anuradhapura in the North Central Province of Sri Lanka from May 2010 to 2011 May to describe the characteristics associated with cases of snake bite.
Results
There were 24 males and 20 females. The highest numbers of bites (48%) were in the range of ages 6-12 years. The majority of the bites occurred between 6 pm to 6 am (59%).The foot was the most common bitten site (48%). Out of all the venomous bites, the Hump-nosed pit viper (Hypnale hypnale) accounted for the highest number (44%) and Russell’s viper (Daboia ruselii) accounted for the second highest number (27%). A significant number of venomous bites occurred indoors while sleeping (22%). Antivenom serum was given to (39%) of venomous bites. Deaths occurred in (11%) of the venomous bites.
Conclusions
Hump-nosed pit viper (Hypnale hypnale) accounted for the highest number of venomous bites. Majority of the bites occurred between 6 pm and 6 am. Foot was the most common bitten site. A significant number of venomous bites occurred indoor while sleeping. Antivenom serum was given to a significant number of venomous bites. Educating the public on making their houses snake proof and using a torch when going out during night time will help in the prevention of getting bitten by snakes.
doi:10.1186/1756-0500-7-482
PMCID: PMC4122051  PMID: 25073710
Snake bite; Pediatrics; Venomous; Sri Lanka
6.  Detection of Venom after Antivenom Is Not Associated with Persistent Coagulopathy in a Prospective Cohort of Russell's Viper (Daboia russelii) Envenomings 
Background
Venom recurrence or persistence in the circulation after antivenom treatment has been documented many times in viper envenoming. However, it has not been associated with clinical recurrence for many snakes, including Russell's viper (Daboia spp.). We compare the recovery of coagulopathy to the recurrence or persistence of venom in patients with Russell's viper envenoming.
Methodology/Principal Findings
The study included patients with Russell's viper (D. russelii) envenoming presenting over a 30 month period who had Russell's viper venom detected by enzyme immunoassay. Demographics, information on the snake bite, and clinical effects were collected for all patients. All patients had serum collected for venom specific enzyme immunoassay and citrate plasma to measure fibrinogen levels and prothrombin time (international normalised ratio; INR). Patients with venom recurrence/persistence were compared to those with no detectable recurrence of venom. There were 55 patients with confirmed Russell's viper envenoming and coagulopathy with low fibrinogen concentrations: 31 with venom recurrence/persistence, and 24 with no venom detected post-antivenom. Fibrinogen concentrations increased and INR decreased after antivenom in both the recurrence and non-recurrence patients. Clinical features, laboratory parameters, antivenom dose and length of hospital were similar for both groups. Pre-antivenom venom concentrations were higher in patients with venom recurrence/persistence with a median venom concentration of 385 ng/mL (16–1521 ng/mL) compared to 128 ng/mL (14–1492 ng/mL; p = 0.008).
Conclusion
Recurrence of Russell's viper venom was not associated with a recurrence of coagulopathy and length of hospital stay. Further work is required to determine if the detection of venom recurrence is due to the venom specific enzyme immunoassay detecting both venom-antivenom complexes as well as free venom.
Author Summary
Snakebite is a major public health problem and understanding the effectiveness of antivenom is essential to improving health outcomes. The measurement of venom in blood has been used to assess the effectiveness of antivenom. The absence of venom post-antivenom indicating that sufficient antivenom has been given, and the persistence or recurrence of venom indicating that insufficient antivenom has been given. There are numerous reports of venom recurrence with viper bites, including Russell's viper bites. However, it remains unclear if venom recurrence is always an indicator of inadequate antivenom and recurrence of clinical envenoming. In this study, we compare patients with and without the persistence or recurrence of venom who develop coagulopathy after Russell's viper bites. There was no difference in the recovery of the coagulopathy between the two groups of patients demonstrating that for Russell's viper envenoming, venom recurrence or persistence was not associated with the recurrence or persistence of clinical effects such as coagulopathy. Patients with detectable venom after antivenom did have higher pre-antivenom venom concentrations. Further investigation is required to interpret venom concentrations post-antivenom.
doi:10.1371/journal.pntd.0003304
PMCID: PMC4270487  PMID: 25521820
7.  Bioinformatics and Multiepitope DNA Immunization to Design Rational Snake Antivenom 
PLoS Medicine  2006;3(6):e184.
Background
Snake venom is a potentially lethal and complex mixture of hundreds of functionally diverse proteins that are difficult to purify and hence difficult to characterize. These difficulties have inhibited the development of toxin-targeted therapy, and conventional antivenom is still generated from the sera of horses or sheep immunized with whole venom. Although life-saving, antivenoms contain an immunoglobulin pool of unknown antigen specificity and known redundancy, which necessitates the delivery of large volumes of heterologous immunoglobulin to the envenomed victim, thus increasing the risk of anaphylactoid and serum sickness adverse effects. Here we exploit recent molecular sequence analysis and DNA immunization tools to design more rational toxin-targeted antivenom.
Methods and Findings
We developed a novel bioinformatic strategy that identified sequences encoding immunogenic and structurally significant epitopes from an expressed sequence tag database of a venom gland cDNA library of Echis ocellatus, the most medically important viper in Africa. Focusing upon snake venom metalloproteinases (SVMPs) that are responsible for the severe and frequently lethal hemorrhage in envenomed victims, we identified seven epitopes that we predicted would be represented in all isomers of this multimeric toxin and that we engineered into a single synthetic multiepitope DNA immunogen (epitope string). We compared the specificity and toxin-neutralizing efficacy of antiserum raised against the string to antisera raised against a single SVMP toxin (or domains) or antiserum raised by conventional (whole venom) immunization protocols. The SVMP string antiserum, as predicted in silico, contained antibody specificities to numerous SVMPs in E. ocellatus venom and venoms of several other African vipers. More significantly, the antiserum cross-specifically neutralized hemorrhage induced by E. ocellatus and Cerastes cerastes cerastes venoms.
Conclusions
These data provide valuable sequence and structure/function information of viper venom hemorrhagins but, more importantly, a new opportunity to design toxin-specific antivenoms—the first major conceptual change in antivenom design after more than a century of production. Furthermore, this approach may be adapted to immunotherapy design in other cases where targets are numerous, diverse, and poorly characterized such as those generated by hypermutation or antigenic variation.
Editors' Summary
Background.
Of the 3,000 species of snakes worldwide, about 600 are poisonous; poisonous snakes are a particular problem in Africa and Southeast Asia. Because not all victims of snake bites get to hospital, estimates of illness and death caused are very approximate. However, one estimate quoted by the World Health Organization is that 2.5 million snake bites occur each year and 125,000 are fatal. The effects of snake bites vary, obviously depending on which snake does the biting, but immediate effects include swelling (around the bite or of other parts of the body), death of the area around the bite, and blood clotting problems. Nowadays, snake bite is treated with “antivenoms,” which are usually made from immunizing horses or sheep with snake venom. However, these antivenoms contain many different proteins that can themselves trigger unpleasant reactions in the recipient. One problem with developing antivenoms is that venoms contain many hundreds of different proteins, many of which may contribute to the toxic effect.
Why Was This Study Done?
Recent scientific discoveries have led to new ways of finding which parts of an animal's genetic sequence are active in any one particular part of the body, and also whether the proteins produced from these genes are likely to cause illness. A snake's venom gland, where the venom is made, can be analysed this way. The researchers wanted to use this information to develop a more rational way of designing antivenoms.
What Did the Researchers Do and Find?
They studied the venom glands of the carpet viper (Echis ocellatus), the most medically important snake in West Africa. They isolated expressed sequence tags (ESTs) produced by the venom glands. Each EST is a small part of the active part of a gene. They then focused on one group of genes that make proteins called snake venom metalloproteinases (SVMPs), which destroy other proteins, and which cause many of the severe symptoms, such as bleeding, seen after snake bite. They identified seven parts of these SVMPs that were likely to be clinically important, and engineered them into a single string of DNA. This product is known as an immunogen—that is, it can produce an immune response in an animal. And when this immunogen was injected into mice, the researchers found that the serum (the part of the blood that contains antibodies) from these mice did have a specific effect against the SVMPs in snake venom. It also had some effect, again in mice, against bleeding caused by small doses of snake venom.
What Do These Findings Mean?
These results suggest that it is possible to use some of the newest genetic techniques to design immunogens that can be used to make highly specific, toxin-neutralizing antisera. These immunogens are a possible improvement over conventional antivenoms that are raised against whole venom. This approach could mean that lower doses of antivenoms would be needed than for conventional antivenoms. In addition, it may also be possible to design antivenoms that work against different species of snake venom. Results such as this may persuade a company that it is worth investing further in such antivenoms; as with many diseases of the poorer parts of the world, snake bites have not been of great interest to large pharmaceutical companies. In another paper published in PLoS Medicine, José María Gutiérrez et al. discuss the global problem of snake bites.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030184
•  World Health Organization page on animal bites, including snakes
•  MedlinePlus Medical Encyclopedia pages of health information (these pages are most relevant in the US)
Seven epitopes were identified providing valuable sequence and structure/function information of viper venom hemorrhagins. This has created a new opportunity to design toxin-specific antivenoms.
doi:10.1371/journal.pmed.0030184
PMCID: PMC1472699  PMID: 16737347
8.  In Vitro and In Vivo Evaluation of Polyherbal Formulation against Russell's Viper and Cobra Venom and Screening of Bioactive Components by Docking Studies 
The present study emphasizes to reveal the antivenom activity of Aristolochia bracteolata Lam., Tylophora indica (Burm.f.) Merrill, and Leucas aspera S. which were evaluated against venoms of Daboia russelli russelli (Russell's viper) and Naja naja (Indian cobra). The aqueous extracts of leaves and roots of the above-mentioned plants and their polyherbal (1 : 1 : 1) formulation at a dose of 200 mg/kg showed protection against envenomed mice with LD50 doses of 0.44 mg/kg and 0.28 mg/kg against Russell's viper and cobra venom, respectively. In in vitro antioxidant activities sample extracts showed free radical scavenging effects in dose dependent manner. Computational drug design and docking studies were carried out to predict the neutralizing principles of type I phospholipase A2 (PLA2) from Indian common krait venom. This confirmed that aristolochic acid and leucasin can neutralize type I PLA2 enzyme. Results suggest that these plants could serve as a source of natural antioxidants and common antidote for snake bite. However, further studies are needed to identify the lead molecule responsible for antidote activity.
doi:10.1155/2013/781216
PMCID: PMC3600290  PMID: 23533518
9.  Immune Response to Snake Envenoming and Treatment with Antivenom; Complement Activation, Cytokine Production and Mast Cell Degranulation 
Background
Snake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment.
Methodology/Principal Findings
Plasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor α (TNFα), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and after treatment with antivenom. Immune mediator concentrations were correlated with envenoming features and the severity of antivenom-induced reactions including anaphylaxis. Envenoming was associated with complement activation and increased cytokine concentrations prior to antivenom administration, which correlated with non-specific systemic symptoms of envenoming but not with coagulopathy or neurotoxicity. Typical hypersensitivity reactions to antivenom occurred in 77/120 patients (64%), satisfying criteria for a diagnosis of anaphylaxis in 57/120 (48%). Pyrogenic reactions were observed in 32/120 patients (27%). All patients had further elevations in cytokine concentrations, but not complement activation, after the administration of antivenom, whether a reaction was noted to occur or not. Patients with anaphylaxis had significantly elevated concentrations of MCT and histamine.
Conclusions/Significance
We have demonstrated that Sri Lankan snake envenoming is characterized by significant complement activation and release of inflammatory mediators. Antivenom treatment further enhances the release of inflammatory mediators in all patients, with anaphylactic reactions characterised by high levels of mast cell degranulation but not further complement activation. Anaphylaxis is probably triggered by non allergen-specific activation of mast cells and may be related to the quality of available antivenom preparations, as well as a priming effect from the immune response to the venom itself.
Author Summary
Snakebites cause life-threatening symptoms including uncontrolled bleeding and paralysis. The body's immune responses to snake venom may contribute to the severity of these symptoms but have not been well characterized in humans. Treatment with antivenom is potentially lifesaving, but also carries risk, as severe allergic reactions (anaphylaxis) are common. Anaphylaxis occurs when mast cells, triggered by either allergen-specific antibodies, other immunological mechanisms, or non-immune mechanisms, release mediators that cause skin rashes, shortness of breath and, in severe cases, life-threatening hypotension and/or hypoxia. We have studied 120 snakebite victims in Sri Lanka, both before and after treatment with antivenom. Our results have shown snakebite triggers activation of the complement cascade (an important part of the body's innate immune defence) and production of proinflammatory mediators. In addition, we have demonstrated a quite astonishing level of immune activation after antivenom treatment in virtually every person treated, regardless of whether they had a reaction to the antivenom. Half of the patients treated experienced anaphylaxis, with clear evidence of mast cell activation. Anaphylaxis to antivenom is unlikely to be triggered by allergen-specific antibodies, as patients had not been previously exposed to antivenom, but may be related to the quality of available antivenom preparations, as well as a priming effect from the immune response to the venom itself.
doi:10.1371/journal.pntd.0002326
PMCID: PMC3723557  PMID: 23936562
10.  Acute Demyelinating Encephalomyelitis After Anti-venom Therapy in Russell’s Viper Bite 
Journal of Medical Toxicology  2010;6(3):318-321.
Introduction
Russell’s viper is a commonly encountered venomous snake in India. Morbidity and mortality following envenomation and the treatment thereof are frequent. We report a rarely seen complication after a treated Russell’s viper bite.
Case Report
A 36-year-old male farmer received 30 vials polyvalent anti-snake venom after a viper bite to his right leg. Improvement in initial hematemesis and circulatory shock was followed by acute renal failure managed with regular hemodialysis. He displayed no abnormalities on neurological examination at admission. Fourth day onwards his neurologic status started deteriorating with development of behavioral abnormalities, hemi-spatial neglect of left upper limb, paralysis of left facial nerve, left upper limb, and right lower limb. Acute disseminated encephalomyelitis was confirmed on magnetic resonance imaging (MRI) of brain with typical spectroscopic characteristics. High dose methyl prednisolone was administered and a rapid recovery followed.
Conclusion
Russels viper bite followed by treatment with antivenom may be complicated by the development of immune complex mediated demyelination and development of acute disseminated encephalomyelitis. MRI spectroscopy helps in early identification of demyelination and in a definite diagnosis. Treatment with corticosteroids was associated with resolution of symptoms in this case.
doi:10.1007/s13181-010-0015-8
PMCID: PMC3550494  PMID: 20237970
Snake bite; Acute disseminated encephalomyelitis; Antivenom
11.  Active compound from the leaves of Vitex negundo L. shows anti-inflammatory activity with evidence of inhibition for secretory Phospholipase A2 through molecular docking 
Bioinformation  2011;7(4):199-206.
Novel compounds with significant medicinal properties have gained much interest in therapeutic approaches for treating various inflammatory disorders like arthritis, odema and snake bites and the post-envenom (impregnating with venom) consequences. Inflammation is caused by the increased concentration of secretory Phospholipases A2 (sPLA2s) at the site of envenom. A novel compound Tris(2,4-di-tert-butylphenyl) phosphate (TDTBPP) was isolated from the leaves of Vitex negundo and the crystal structure was reported recently. The acute anti-inflammatory activity of TDTBPP was assessed by Carrageenan-induced rat paw odema method. TDTBPP reduced the raw paw odema volume significantly at the tested doses of 50 mg/kg and 70 mg/kg body weight. Molecular docking studies were carried out with the X-ray crystal structures of Daboia russelli pulchella's (Vipera russelli, Indian Russell's viper) venom sPLA2 and Human non-pancreatic secretory PLA2 (Hnps PLA2) as targets to illustrate the antiinflammatory and antidote activities of TDTBPP. Docking results showed hydrogen bond (H-bond) interaction with Lys69 residue lying in the anti-coagulant loop of D. russelli's venom PLA2, which is essential in the catalytic activity of the enzyme and hydrophobic interactions with the residues at the binding site (His48, Asp49). Docking of TDTBPP with Hnps PLA2 structure showed coordination with calcium ion directly as well as through the catalytically important water molecule (HOH1260) located at the binding site.
PMCID: PMC3218522  PMID: 22102777
Vitex negundo; Tris(2,4-di-tert-butylphenyl) phosphate; Anti-inflammatory; Carrageenan; Antidote; PLA2; Induced Fit Docking
12.  Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial 
PLoS Medicine  2011;8(5):e1000435.
In a factorial randomized trial conducted in Sri Lanka, de Silva and colleagues evaluate the safety and efficacy of pretreatments intended to reduce the risk of serious reactions to antivenom following snakebite.
Background
Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial.
Methods and Findings
In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline.
Conclusions
Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized.
Trial registration
www.ClinicalTrials.gov NCT00270777
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Of the 3,000 or so snake species in the world, about 600 are venomous. Venomous snakes, which are particularly common in equatorial and tropical regions, immobilize their prey by injecting modified saliva (venom) into their prey's tissues through their fangs—specialized hollow teeth. Snakes also use their venoms for self-defense and will bite people who threaten, startle, or provoke them. A bite from a highly venomous snake such as a pit viper or cobra can cause widespread bleeding, muscle paralysis, irreversible kidney damage, and tissue destruction (necrosis) around the bite site. All these effects of snakebite are potentially fatal; necrosis can also result in amputation and permanent disability. It is hard to get accurate estimates of the number of people affected by snakebite, but there may be about 2 million envenomings (injections of venom) and 100,000 deaths every year, many of them in rural areas of South Asia, Southeast Asia, and sub-Saharan Africa.
Why Was This Study Done?
The best treatment for snakebite is to give antivenom (a mixture of antibodies that neutralize the venom) as soon as possible. Unfortunately, in countries where snakebites are common (for example, Sri Lanka), antivenoms are often of dubious quality, and acute allergic reactions to them frequently occur. Although some of these reactions are mild (for example, rashes), in up to 40% of cases, anaphylaxis—a potentially fatal, whole-body allergic reaction—develops. The major symptoms of anaphylaxis—a sudden drop in blood pressure and breathing difficulties caused by swelling of the airways—can be treated with adrenaline. Injections of antihistamines (for example, promethazine) and hydrocortisone can also help. In an effort to prevent anaphylaxis, these drugs are also widely given before antivenom, but there is little evidence that such “prophylactic” treatment is effective or safe. In this randomized double-blind controlled trial (RCT), the researchers test whether low-dose adrenaline, promethazine, and/or hydrocortisone can prevent acute adverse reactions to antivenom. In an RCT, the effects of various interventions are compared to a placebo (dummy) in groups of randomly chosen patients; neither the patients nor the people caring for them know who is receiving which treatment until the trial is completed.
What Did the Researchers Do and Find?
The researchers randomized 1,007 patients who had been admitted to secondary referral hospitals in Sri Lanka after snakebite to receive low-dose adrenaline, promethazine, hydrocortisone, or placebo alone and in all possible combinations immediately before treatment with antivenom. The patients were monitored for at least 96 hours for adverse reactions to the antivenom; patients who reacted badly were given adrenaline, promethazine, and hydrocortisone as “rescue medication.” Three-quarters of the patients had acute reactions—mostly moderate or severe—to the antivenom. Most of the acute reactions occurred within an hour of receiving the antivenom, and nearly half of all the patients were given rescue medication during the first hour. Compared with placebo, pretreatment with adrenaline reduced severe reactions to the antivenom by 43% at one hour and by 38% over 48 hours. By contrast, neither hydrocortisone nor promethazine given alone reduced the rate of adverse reactions to the antivenom. Moreover, adding hydrocortisone negated the beneficial effect of adrenaline.
What Do These Findings Mean?
These findings show that pretreatment with low-dose adrenaline is safe and reduces the risk of acute severe reactions to snake antivenom, particularly during the first hour after infusion. They do not provide support for pretreatment with promethazine or hydrocortisone, however. Indeed, the findings suggest that the addition of hydrocortisone could negate the benefits of adrenaline, although this finding needs to be treated with caution because of the design of the trial, as does the observed increased risk of death associated with pretreatment with hydrocortisone. More generally, the high rate of acute adverse reactions to antivenom in this trial highlights the importance of improving the quality of antivenoms available in Sri Lanka and other parts of South Asia. The researchers note that the recent World Health Organization guidelines on production, control, and regulation of antivenom should help in this regard but stress that, for now, it is imperative that physicians carefully monitor patients who have been given antivenom and provide prompt treatment of acute reactions when they occur.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000435.
The MedlinePlus Encyclopedia has pages on snakebite and on anaphylaxis (in English and Spanish)
The UK National Health Service Choices website also has pages on snakebite and on anaphylaxis
The World Health Organization has information on snakebite and on snake antivenoms (in several languages); its Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins are also available
The Global Snakebite Initiative has information on snakebite
A PLoS Medicine Research Article by Anuradhani Kasturiratne and colleagues provides data on the global burden of snakebite
A PLoS Medicine Neglected Diseases Article by José María Gutiérrez and colleagues discusses the neglected problem of snakebite envenoming
doi:10.1371/journal.pmed.1000435
PMCID: PMC3091849  PMID: 21572992
13.  Life threatening intracerebral haemorrhage following saw- scaled viper (Echis carinatus) envenoming-authenticated case report from Sri Lanka 
Background
Echis carinatus (Saw scaled viper {SSV}) is a venomous snake found in the parts of Middle East and Central Asia. SSV envenoming is characterized by local swelling and coagulopathy. Various bleeding manifestations are commonly seen with SSV envenoming. In contrast to other part of Asia, saw scale viper envenoming has not been reported to cause life threatening haemorrhagic manifestations in Sri Lanka.
Case presentation
We report a 19 years old healthy boy who developed massive left temporo-parietal intra cerebral haemorrhage following Echis carinatus (Saw scaled viper) bite in Sri Lanka.
Conclusion
Although subspecies of SSV in Sri Lanka is regarded as a ‘non lethal venomous snake’, the occurrence of rare potentially fatal complications such as intracerebral haemorrhage should be considered in their management. This case report is intended to bring the awareness of this fatal complication of SSV envenoming in Sri Lanka.
doi:10.1186/1471-227X-13-5
PMCID: PMC3636000  PMID: 23565979
14.  Viper and Cobra Venom Neutralization by Alginate Coated Multicomponent Polyvalent Antivenom Administered by the Oral Route 
Background
Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals.
Methodology/Principal Findings
To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.
Conclusions/Significance
Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to counter such dilemma in snake bite management by promoting control release and oral antivenom rendered as a first aid.
Author Summary
Antivenom, the only effective therapy against snake bite in practice, is successful in controlling mortality in developed countries, but not in developing countries. Unavailability of antivenom at the proper time and place of snake bite in developing countries is a major factor in this account, which results not only from production deficit but also from dependence on hospitals located too faraway for intravenous administration. It lengthens the period between bite and treatment, and thereby worsens the outcome. To make antivenom available immediately after bite, we need to develop an oral formulation which, by its property of controlled release, can supply antivenom as first aid until further hospitalization. In this work, multiple components of antivenom were entrapped in alginate, an economic, biodegradable polymer, which retained the functional property of the antivenom even after intestinal absorption and showed in vivo and in vitro venom neutralization effects. This study promises the development of an effective first aid against snake envenomation, thereby increasing chances of survival of the victim.
doi:10.1371/journal.pntd.0003039
PMCID: PMC4125299  PMID: 25102172
15.  The Global Burden of Snakebite: A Literature Analysis and Modelling Based on Regional Estimates of Envenoming and Deaths 
PLoS Medicine  2008;5(11):e218.
Background
Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites.
Methods and Findings
The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually.
Conclusions
Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.
Janaka de Silva and colleagues estimate that globally at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite.
Editors' Summary
Background.
Of the 3,000 or so snake species that exist in the world, about 600 are venomous. Venomous snakes—which exist on every continent except Antarctica—immobilize their prey by injecting modified saliva (venom) that contains toxins into their prey's tissues through their fangs—specialized, hollow teeth. Snakes also use their venoms for self defense and will bite people who threaten, startle or provoke them. Snakebites caused by the families Viperidae (for example, pit vipers) and Elapidae (for example, kraits and cobras) are particularly dangerous to people. The potentially fatal effects of being “envenomed” (having venom injected) by these snakes include widespread bleeding, muscle paralysis, and tissue destruction (necrosis) around the bite site. Bites from these snakes can also cause permanent disability. For example, snakebite victims, who tend to be young and male, may have to have a limb amputated because of necrosis. The best treatment for any snakebite is to get the victim to a hospital as soon as possible where antivenoms (mixtures of antibodies that neutralize venoms) can be given.
Why Was This Study Done?
Although snakebites occur throughout the world, envenoming snakebites are thought to pose a particularly important yet largely neglected threat to public health. This is especially true in rural areas of tropical and subtropical countries where snakebites are common but where there is limited access to health care and to antivenoms. The true magnitude of the public-health threat posed by snakebites in these countries (and elsewhere in the world) is unknown, which makes it hard for public-health officials to optimize the prevention and treatment of snakebites in their respective countries. In this study, therefore, the researchers develop and apply a new method to estimate the global burden of snakebite.
What Did the Researchers Do and Find?
The researchers systematically searched the scientific literature for publications on snakebites and deaths from snakebites and extracted data on snakebite deaths in individual countries from the World Health Organization (WHO) mortality database. They also contacted Ministries of Health, National Poison Centers, and snakebite experts for unpublished information (“grey” literature) on snakebites. Together, these three approaches provided data on the number of snakebite envenomings and deaths for 135 and 162 countries, respectively. The researchers then grouped the 227 countries of the world into 21 geographical regions, each of which contained countries with similar population characteristics, and used the results of studies done in individual countries within each region to estimate the numbers of snakebite envenomings and deaths for each region. Finally, they added up these estimates to obtain an estimate of the global burden of snakebite. Using this method, the researchers estimate that, worldwide, at least 421,000 envenomings and 20,000 deaths from snakebite occur every year; the actual numbers, they suggest, could be as high as 1.8 million envenomings and 94,000 deaths. Their estimates also indicate that the highest burden of snakebite envenomings and death occurs in South and Southeast Asia and in sub-Saharan Africa, and that India is the country with the highest annual number of envenomings (81,000) and deaths (nearly 11,000).
What Do These Findings Mean?
These findings indicate that snakebites cause considerable illness and death around the world. Because of the careful methods used by the researchers, their global estimates of snakebite envenomings and deaths are probably more accurate than previous estimates. However, because the researchers had to make many assumptions in their calculations and because there are so few reliable data on the numbers of snakebites and deaths from the rural tropics, the true regional and global numbers of these events may differ substantially from the estimates presented here. In particular, the regional estimates for eastern sub-Saharan Africa, a region where snakebites are very common and where antivenoms are particularly hard to obtain, are likely to be inaccurate because they are based on a single study. The researchers, therefore, call for more studies on snakebite envenoming and deaths to be done to provide the information needed to deal effectively with this neglected public-health problem.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050218.
This study is further discussed in a PLoS Medicine Perspective by Chippaux
The MedlinePlus Medical Encyclopedia has a page on snakebites (in English and Spanish)
The UK National Health Service Direct health encyclopedia has detailed information about all aspects of snakebites
Wikipedia has pages on venomous snakes and on snakebites (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The World Health Organization provides information about antivenoms and about efforts to increase access to antivenoms in developing countries (available in several languages)
A previous article in PLoS Medicine also discusses the neglected problem of snakebite envenoming: Gutiérrez JM, Theakston RDG, Warrell DA (2006) Confronting the Neglected Problem of Snake Bite Envenoming: The Need for a Global Partnership. PLoS Med 3(6): e150
doi:10.1371/journal.pmed.0050218
PMCID: PMC2577696  PMID: 18986210
16.  A Randomised Controlled Trial of Two Infusion Rates to Decrease Reactions to Antivenom 
PLoS ONE  2012;7(6):e38739.
Background
Snake envenoming is a major clinical problem in Sri Lanka, with an estimated 40,000 bites annually. Antivenom is only available from India and there is a high rate of systemic hypersensitivity reactions. This study aimed to investigate whether the rate of infusion of antivenom reduced the frequency of severe systemic hypersensitivity reactions.
Methods and Findings
This was a randomized comparison trial of two infusion rates of antivenom for treatment of non-pregnant adult patients (>14 y) with snake envenoming in Sri Lanka. Snake identification was by patient or hospital examination of dead snakes when available and confirmed by enzyme-immunoassay for Russell’s viper envenoming. Patients were blindly allocated in a 11 randomisation schedule to receive antivenom either as a 20 minute infusion (rapid) or a two hour infusion (slow). The primary outcome was the proportion with severe systemic hypersensitivity reactions (grade 3 by Brown grading system) within 4 hours of commencement of antivenom. Secondary outcomes included the proportion with mild/moderate hypersensitivity reactions and repeat antivenom doses. Of 1004 patients with suspected snakebites, 247 patients received antivenom. 49 patients were excluded or not recruited leaving 104 patients allocated to the rapid antivenom infusion and 94 to the slow antivenom infusion. The median actual duration of antivenom infusion in the rapid group was 20 min (Interquartile range[IQR]:20–25 min) versus 120 min (IQR:75–120 min) in the slow group. There was no difference in severe systemic hypersensitivity reactions between those given rapid and slow infusions (32% vs. 35%; difference 3%; 95%CI:−10% to +17%;p = 0.65). The frequency of mild/moderate reactions was also similar. Similar numbers of patients in each arm received further doses of antivenom (30/104 vs. 23/94).
Conclusions
A slower infusion rate would not reduce the rate of severe systemic hypersensitivity reactions from current high rates. More effort should be put into developing better quality antivenoms.
Trial Registration
www.slctr.lk SLCTR/2007/005
doi:10.1371/journal.pone.0038739
PMCID: PMC3377702  PMID: 22719932
17.  A Study of Clinical Profile of Snake Bite at a Tertiary Care Centre 
Toxicology International  2014;21(2):203-208.
Background:
Snake bite is an important occupational and rural hazard because India has always been a land of Exotic snakes. In Maharashtra, common poisonous snakes are Cobra, Russell's Viper, Saw Scaled Viper, and Krait. It is a fact that inspite of heavy morbidity and mortality, very little attention is paid by the clinicians to this occupational hazard.
Aims:
To study the prevalence of poisonous and non-poisonous snake bites in part of Western Maharashtra with reference to age, sex, occupation, part of body bitten, time of bite and seasonal variation, and the types of poisonous snakes common in this locality and their clinical manifestations along with the systemic envenomation from various types of poisonous snakes and their effective management in reducing the mortality rate.
Materials and Methods:
This was a retrospective study conducted between May 2010 to May 2012 at a tertiary health care center in Maharashtra.
Result:
A total of 150 patients were studied in our hospital. Out of 150, 76 patients were of poisonous snake bite and 74 patients were of non-poisonous snake bite. Out of these 76 poisonous snake bites, 42 were viperine snake bites, 21 were neuroparalytic snake bites and 13 were locally toxic (LT) snake bites.
Conclusion:
Snake bite is a common life-threatening emergency in the study area. Delay in hospitalization is associated with poor prognosis and increased mortality rate due to consumptive coagulopathy, renal failure, and respiratory failure. Unusual complications like pulmonary edema, intracerebral hemorrhage, Disseminated intravascular coagulation (DIC) were observed in present study.
doi:10.4103/0971-6580.139811
PMCID: PMC4170564  PMID: 25253932
Non-poisonous bite; neuroparalytic bite; poisonous bite; vasculotoxic bite
18.  Purification and Functional Characterisation of Rhiminopeptidase A, a Novel Aminopeptidase from the Venom of Bitis gabonica rhinoceros 
Background
Snake bite is a major neglected public health issue within poor communities living in the rural areas of several countries throughout the world. An estimated 2.5 million people are bitten by snakes each year and the cost and lack of efficacy of current anti-venom therapy, together with the lack of detailed knowledge about toxic components of venom and their modes of action, and the unavailability of treatments in rural areas mean that annually there are around 125,000 deaths worldwide. In order to develop cheaper and more effective therapeutics, the toxic components of snake venom and their modes of action need to be clearly understood. One particularly poorly understood component of snake venom is aminopeptidases. These are exo-metalloproteases, which, in mammals, are involved in important physiological functions such as the maintenance of blood pressure and brain function. Although aminopeptidase activities have been reported in some snake venoms, no detailed analysis of any individual snake venom aminopeptidases has been performed so far. As is the case for mammals, snake venom aminopeptidases may also play important roles in altering the physiological functions of victims during envenomation. In order to further understand this important group of snake venom enzymes we have isolated, functionally characterised and analysed the sequence-structure relationships of an aminopeptidase from the venom of the large, highly venomous West African gaboon viper, Bitis gabonica rhinoceros.
Methodology and Principal Findings
The venom of B. g. rhinoceros was fractionated by size exclusion chromatography and fractions with aminopeptidase activities were isolated. Fractions with aminopeptidase activities showed a pure protein with a molecular weight of 150 kDa on SDS-PAGE. In the absence of calcium, this purified protein had broad aminopeptidase activities against acidic, basic and neutral amino acids but in the presence of calcium, it had only acidic aminopeptidase activity (APA). Together with the functional data, mass spectrometry analysis of the purified protein confirmed this as an aminopeptidase A and thus this has been named as rhiminopeptidase A. The complete gene sequence of rhiminopeptidase A was obtained by sequencing the PCR amplified aminopeptidase A gene from the venom gland cDNA of B. g. rhinoceros. The gene codes for a predicted protein of 955 amino acids (110 kDa), which contains the key amino acids necessary for functioning as an aminopeptidase A. A structural model of rhiminopeptidase A shows the structure to consist of 4 domains: an N-terminal saddle-shaped β domain, a mixed α and β catalytic domain, a β-sandwich domain and a C-terminal α helical domain.
Conclusions
This study describes the discovery and characterisation of a novel aminopeptidase A from the venom of B. g. rhinoceros and highlights its potential biological importance. Similar to mammalian aminopeptidases, rhiminopeptidase A might be capable of playing roles in altering the blood pressure and brain function of victims. Furthermore, it could have additional effects on the biological functions of other host proteins by cleaving their N-terminal amino acids. This study points towards the importance of complete analysis of individual components of snake venom in order to develop effective therapies for snake bites.
Author Summary
Snake bite is a major neglected public health issue causing an estimated 125,000 deaths each year, predominantly within poor communities living in rural areas of countries in South East Asia and Africa. Current treatments for snake bites are costly and have limited effectiveness, thus there is a need to develop novel therapeutics. In order to do this the toxic components of snake venom need to be clearly understood. Enzymes called aminopeptidases have been noticed in several snake venoms, but their functions have not been characterised. Related enzymes are also present in mammals, where they are involved in the maintenance of blood pressure and brain function. To further understand this important group of enzymes within snake venom we have purified and analysed the function and structure of an aminopeptidase from the venom of the West African gaboon viper. Our results suggest that this enzyme could also affect the maintenance of blood pressure and brain function in victims of snake bites. Along with other snake venom components, aminopeptidases might be a potential therapeutic target for developing novel treatments for snake bites.
doi:10.1371/journal.pntd.0000796
PMCID: PMC2919393  PMID: 20706583
19.  Comparative in-vivo toxicity of venoms from South Asian hump-nosed pit vipers (Viperidae: Crotalinae: Hypnale) 
BMC Research Notes  2012;5:471.
Background
Envenoming by south Asian hump-nosed pit vipers (Genus: Hypnale) is a significant health issue in Sri Lanka and in peninsular India. Bites by these snakes frequently lead to local envenoming, coagulopathy and acute renal failure even resulting in death. Recently the genus was revised and the existence of three species viz H. hypnale, H. nepa and H. zara were recognized. There is, however, a paucity of information on the toxicity of the venoms of these species. Hence, we compared the toxic effects of the three Hypnale venoms using BALB/c mice.
Findings
Intraperitoneal median lethal doses (LD50) for H. hypnale, H. zara and H. nepa venoms were 1.6, 6.0 and 9.5 μg protein/g respectively. Minimum haemorrhagic doses for venoms of H. hypnale, H. zara and H. nepa were 3.4, 11.0 and 16.6 μg protein/mouse respectively. The minimum necrotic doses for the same venoms were 15.0, 55.1 and 68.2 μg protein/mouse respectively. Severe congestion and petecheal haemorrhages were observed in lungs, kidneys, liver and the alimentary tract. Histopathogical examination of kidneys revealed proximal tubular cell injury and acute tubular necrosis with intact basement membrane indicating possible direct nephrotoxicity. Hypnale venoms caused pulmonary oedema, hepatocellular degeneration and necrosis, focal neuronal degeneration in brain and extramedullary haemopoiesis in spleen. H. hypnale venom caused all above histopathological alterations at lower doses compared to the other two.
Conclusion
Hypnale venoms cause similar pathological changes with marked differences in the severity of the toxic effects in vivo. Therefore, differences in the severity of the clinical manifestations could possibly be seen among bite victims of the three Hypnale species.
doi:10.1186/1756-0500-5-471
PMCID: PMC3494509  PMID: 22932058
Hypnale; Nepa; Zara; Venom; Toxicity; Histopathology
20.  Viper bites complicate chronic agrochemical nephropathy in rural Sri Lanka 
Snakebite is a common occupational health hazard among Sri Lankan agricultural workers, particularly in the North Central Province. Viperine snakes, mainly Russell’s viper envenomation, frequently lead to acute renal failure. During the last two decades, an agrochemical nephropathy, a chronic tubulointerstitial disease has rapidly spread over this area leading to high morbidity and mortality. Most of the epidemiological characteristics of these two conditions overlap, increasing the chances of co-occurrence. Herein, we describe four representative cases of viperine snakebites leading to variable clinical presentations, in patients with chronic agrochemical nephropathy, including two patients presented with acute and delayed anuria. These cases suggest the possibility of unusual manifestations of snakebite in patients with Sri Lankan agrochemical nephropathy, of which the clinicians should be aware. It could be postulated that the existing scenario in the Central America could also lead to similar clinical presentations.
doi:10.1186/1678-9199-20-33
PMCID: PMC4136642  PMID: 25136354
Snakebite; Chronic kidney disease; Agricultural nephropathy; Epidemiology; Anuria
21.  Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes 
Toxins  2014;6(6):1873-1881.
Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins, might be attributed to the rich composition of high molecular weight enzymes in the case of viper venoms.
doi:10.3390/toxins6061873
PMCID: PMC4073134  PMID: 24926799
scorpion; snake; venoms; animal toxins; lethal activity; toxicity
22.  A Study on the Clinico-Epidemiological Profile and the Outcome of Snake Bite Victims in a Tertiary Care Centre in Southern India 
Background: Snake bite is a common medical emergency and an occupational hazard, more so in tropical India, where farming is a major source of employment. The available data on the epidemiology of snake bite from the Indian subcontinent are sparse. Snake bite is a neglected disease that afflicts the most impoverished inhabitants of the rural areas in the tropical developing countries.
Aims: This study was carried out to describe the epidemiology, arrival delays, clinical features, complications, and the outcome of snakebites which were seen in a tertiary care hospital of southern India.
Setting: Sri Chamarajendra District Hospital which is attached to the Hassan Institute of Medical Sciences, Hassan, Karnataka, India.
Study Design: A record–based, retrospective, descriptive study.
Materials and Methods: One hundred eighty patients of snake bite were studied from January 2010 to December 2011. The data on the demographic factors, clinical features and complications, details of the treatment which was received and the outcome of the snake bite victims were recorded and analyzed.
Results: Among a total 180 cases of snake bite, there were 108 cases of viper bite which presented with haematotoxic manifestations and 74 elapid bites had neuroparalytic manifestations. The victims were predominantly males (60.5%) and they were aged 20-40 years. A majority of the victims are from the rural areas (81.1%) and most of the bites occurred during the day time (70.5%), mainly on the lower limbs (67.2%). The highest number of cases occurred during July- September. Most of the victims were farmers (54.4%) and plantation workers (30.5%), which suggested that snake bite was an occupational hazard. A reaction to the ASV was noted in 12.7% of the patients and the mortality rate in our study was 3.8%.
Conclusion: In the tropics, snake bite is a rural and an occupational hazard among farmers, plantation workers, herders and hunters. Regular public health programmes regarding the prevention, pre –hospital management (first aid) and the importance of the early transfer to the hospital should be emphasized.
doi:10.7860/JCDR/2012/4842.2685
PMCID: PMC3576766  PMID: 23450135
Anti-snake venom; Envenomation; Epidemiology; Snake-bite; Southern India
23.  Presumptive thrombotic thrombocytopenic purpura following a hump-nosed viper (Hypnale hypnale) bite: a case report 
Hump-nosed viper bites are frequent in southern India and Sri Lanka. However, the published literature on this snakebite is limited and its venom composition is not well characterized. In this case, we report a patient with thrombotic thrombocytopenic purpura-like syndrome following envenoming which, to the best of our knowledge, has not been reported in the literature before. A 55-year-old woman from southern Sri Lanka presented to the local hospital 12 hours after a hump-nosed viper (Hypnale hypnale) bite. Five days later, she developed a syndrome that was characteristic of thrombotic thrombocytopenic purpura with fever, thrombocytopenia, microangiopathic hemolysis, renal impairment and neurological dysfunction in the form of confusion and coma. Her clinical syndrome and relevant laboratory parameters improved after she was treated with therapeutic plasma exchange. We compared our observations on this patient with the current literature and concluded that thrombotic thrombocytopenic purpura is a theoretically plausible yet unreported manifestation of hump-nosed viper bite up to this moment. This study also provides an important message for clinicians to look out for this complication in hump-nosed viper bites since timely treatment can be lifesaving.
doi:10.1186/1678-9199-20-26
PMCID: PMC4077548  PMID: 24987409
Thrombotic thrombocytopenic purpura; Hump-nosed viper; Thrombotic microangiopathy; Snakebite; Hemolytic uremic syndrome
24.  Purification, crystallization and preliminary X-ray structural studies of a 7.2 kDa cytotoxin isolated from the venom of Daboia russelli russelli of the Viperidae family 
A cytotoxin from Indian Russell’s viper (D. russelli russelli) venom having multifunctional activity has been crystallized in space group P41. Larger crystals diffracted to 1.5 Å but were found to be twinned; preliminary data were therefore collected (2.93 Å) from a smaller crystal.
A cytotoxin (MW 7.2 kDa) from Indian Russell’s viper (Daboia russelli russelli) venom possessing antiproliferative activity, cardiotoxicity, neurotoxicity and myotoxicity has been purified, characterized and crystallized. The crystals belong to the tetragonal space group P41, with unit-cell parameters a = b = 47.94, c = 50.2 Å. Larger crystals, which diffracted to 1.5 Å, were found to be twinned; diffraction data were therefore collected to 2.93 Å resolution using a smaller crystal. Molecular-replacement calculations identified two molecules of the protein in the asymmetric unit, which is in accordance with the calculated V M value.
doi:10.1107/S1744309106005963
PMCID: PMC2197197  PMID: 16511326
cytotoxins; Russell’s viper; antiproliferative activity
25.  Cost-effectiveness of Antivenoms for Snakebite Envenoming in Nigeria 
Background
Snakebite envenoming is a major public health problem throughout the rural tropics. Antivenom is effective in reducing mortality and remains the mainstay of therapy. This study aimed to determine the cost-effectiveness of using effective antivenoms for Snakebite envenoming in Nigeria.
Methodology
Economic analysis was conducted from a public healthcare system perspective. Estimates of model inputs were obtained from the literature. Incremental Cost Effectiveness Ratios (ICERs) were quantified as deaths and Disability-Adjusted-Life-Years (DALY) averted from antivenom therapy. A decision analytic model was developed and analyzed with the following model base-case parameter estimates: type of snakes causing bites, antivenom effectiveness to prevent death, untreated mortality, risk of Early Adverse Reactions (EAR), mortality risk from EAR, mean age at bite and remaining life expectancy, and disability risk (amputation). End-user costs applied included: costs of diagnosing and monitoring envenoming, antivenom drug cost, supportive care, shipping/freezing antivenom, transportation to-and-from hospital and feeding costs while on admission, management of antivenom EAR and free alternative snakebite care for ineffective antivenom.
Principal Findings
We calculated a cost/death averted of ($2330.16) and cost/DALY averted of $99.61 discounted and $56.88 undiscounted. Varying antivenom effectiveness through the 95% confidence interval from 55% to 86% yield a cost/DALY averted of $137.02 to $86.61 respectively. Similarly, varying the prevalence of envenoming caused by carpet viper from 0% to 96% yield a cost/DALY averted of $254.18 to $78.25 respectively. More effective antivenoms and carpet viper envenoming rather than non-carpet viper envenoming were associated with lower cost/DALY averted.
Conclusions/Significance
Treatment of snakebite envenoming in Nigeria is cost-effective with a cost/death averted of $2330.16 and cost/DALY averted of $99.61 discounted, lower than the country's gross domestic product per capita of $1555 (2013). Expanding access to effective antivenoms to larger segments of the Nigerian population should be a considered a priority.
Author Summary
Snake bite is a major public health problem throughout rural communities in West Africa and leads to a significant number of deaths and disabilities per year. Even though effective antivenoms exist against the locally prevalent carpet viper and other poisonous snakes, they are generally not available in community settings, possibly because of their high acquisition cost. We evaluated the cost-effectiveness of making antivenom more broadly available in Nigeria by comparing the treatment costs associated with antivenom therapy against their medical benefit in reducing the risk of mortality. We find that the incremental cost effectiveness ratio (ICER) associated with making antivenom available in Nigeria was $2,330 per death averted and $100 per disability adjusted life year (DALY) averted. Both of these suggest that snakebite antivenom is highly cost-effective in Nigeria and they also compare very favorably against other commonly funded health interventions for which similar estimates exist. Since a substantial reduction in mortality and DALYs could be achieved at a relatively modest upfront cost, expanding access to antivenom to broader parts of the population should be a priority consideration for future investments in healthcare.
doi:10.1371/journal.pntd.0003381
PMCID: PMC4287484  PMID: 25569252

Results 1-25 (610401)