Polyvalent Snake Antivenom Research Articles

Snake bite mortality in children: beyond bite to needle time

ObjectiveTo study the clinical characteristics and predictors of mortality from snake bite envenomation in children.DesignProspective observational study with a one-group cohort design.SettingPaediatric intensive care unit of a tertiary care hospital...

Managing snake bite patients – our experience from a tertiary care center of North East India

Introduction: Snake bite is a common problem in North East India as most of the demography includes forests, cultivated land and tea gardens which are a natural habitat to various species of snakes. Snake bite comprises a significant number of hospitalizations with fatalities in this part of the country. We studied all the cases of snake bite poisoning that came to our hospital during the monsoon seasons in the department of medicine of a tertiary care hospital. Materials And Methods: All adult patients coming to the department of Emergency or out patients department in Assam Medical College and Hospital over a period of 1 year from July 2014 to June 2015 were include in our prospective observational study. A detailed clinical history was taken, local examination was done and all necessary laboratory examinations especially those related to bleeding and coagulation profile was done. Results And Observations: 116 patients were included in the study which included 70 (60.3%) male and 46 (39.7%) female patients, the male to female ratio being 1.52:1. Out of 116, 42 (36.2%) were poisonous snake bites and 74 (63.8%) were non poisonous. Out of the 42 cases of poisonous snake bites, 34 (80.9%) patients presented with hematologic symptoms, 8 (19.1%) patients had neurological symptoms and 4 (9.5%) patients expired during their hospital stay. Most common symptom was fright which was noted in 107 (92.2%) patients. This was followed by local swelling (78.4%), tingling and numbness (65.5%) and pain at the site of bite (58.6%). Only 9.5% patients reached tertiary care center within 4 hours of snake bite and majority (55.2%) were delayed by more than 12 hours. The whole blood clotting time, prothrombin time and INR was significantly high in patients with hematotoxic snake bite poisoning. Polyvalent Anti Snake venom (PASV) was administered in 22 (52.4%) cases out of 42 poisonous snake bite cases. 16 (47%) cases of hematotoxic snake bite and 6 (75%) cases of neurotoxic snake bite received PASV. 18 (52.9%) cases of hematotoxic snake bite received only fresh frozen plasma (FFP), 9 (26.5%) received FFP and PASV, 7 (20.6%) received only PASV. Two patients developed reaction to PASV which was managed successfully with adrenalin and steroids. Neostigmine was used in all 8 cases of neurotoxic snake bite poisoning. Conclusion: Though most of the snake bites were non poisonous, use of tourniquet and other alternative medicines caused morbidity. Hematotoxic snake bite was more common but was managed by use of polyvalent anti snake venom (PASV) and/or fresh frozen plasma. Neurotoxic snake poisoning were less common and managed by PASV and neostigmine. Two patient of hematotoxic snake bite died due to renal failure and two cases of neurotoxic snake bite died due to respiratory failure. Keyword : Snake bite poisoning, Polyvalent Anti Snake Venom, Hematotoxic snake, Neurotoxin snake

Rapid and selective detection of experimental snake envenomation – Use of gold nanoparticle based lateral flow assay

In this study, we have developed a gold nanoparticle based simple, rapid lateral flow assay (LFA) for detection of Indian Cobra venom (CV) and Russell’s viper venom (RV). Presently, there is no rapid, reliable, and field diagnostic test available in India, where snake bite cases are rampant. Therefore, this test has an immense potential from the public health point of view. The test is based on the principle of the paper immunochromatography assay for detection of two snake venom species using polyvalent antisnake venom antibodies (ASVA) raised in equines and species-specific antibodies (SSAbs) against venoms raised in rabbits for conjugation and impregnation respectively. The developed, snake envenomation detection immunoassay (SEDIA) was rapid, selective, and sensitive to detect venom concentrations up to 0.1 ng/ml. The functionality of SEDIA strips was confirmed by experimental envenomation in mice and the results obtained were specific for the corresponding venom. The SEDIA has a potential to be a field diagnostic test to detect snake envenomation and assist in saving lives of snakebite victims.

Clinical presentation and management of an Aruban rattlesnake bite in the Netherlands

Bites by Aruban Rattlesnake (Crotalus durissus unicolor) are rare and not known to induce severe envenomations. Here, we present a case of a 57 year-old man bitten by his pet Aruban Rattlesnake (Crotalus durissus unicolor). He was admitted to hospital within 15 min. Three and a half hours later his fibrinogen concentration decreased to 0.6 g/L (normal: 2.0–4.0). Nine hours post-bite, he was treated with polyvalent snake antivenom covering Crotalus durissus. Three hours later his fibrinogen became undetectable while at that time clotting times were prolonged (PT 38.7 s (normal: 12.5–14.5) and aPTT 40 s (normal: 25–35)). His platelet count remained within normal limits. Creatine kinase (CK) concentrations reached a maximum of 1868 U/L (normal: <200) 16 h post-bite. After a second antivenom dose, 10.5 h after the first antivenom administration, clotting times returned to normal. Fibrinogen was restored to normal within three days. He was discharged from hospital on day five. In conclusion, administration of polyvalent snake antivenom covering Crotalus durissus snakebites shows cross-neutralization and is effective in the treatment of patients bitten by Crotalus durissus unicolor.

Development of Modified Caprylic Acid Fractionation Method for the Enhanced Yield and Purity of Equine Polyvalent Antisnake Venom Immunoglobulins

Polyvalent antivenom IgG s produced in equines against different snake venom are used for treatment in snakebite cases. For this, hyperimmune equine plasma is fractionated and purified before use. Hence, serum related side effects are common. To reduce it, search for more effective method with high yield and purity, is of concern. In the present study, a modified caprylic acid method for the fractionation of IgG, has been described. The method was also compared with routine method and previously described caprylic acid methods. The results indicated that modified caprylic acid method at concentration 1.5%, pH 4.8 with stirring for 60 minutes, was superior in terms of yield, and purity as compared to other methods (p<0.05). The purified lgG were also found to have better neutralizing potency against all the four venoms viz., Cobra (Naja naja), Krait (Bungarus caeruleus), Russell’s viper (Vipra russelli), and Saw Scaled viper (Echis carinatus). The results suggest that modified caprylic acid method, could be of great value for commercial scale production of antivenom with respect to its efficacy, simplicity, low cost, reduced production time and above all high yield of colorless lgG finished product.

The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits.

The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p>0.05). Infusion of an additional 2ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.

Quality Control Testing for Tracking Endotoxin-Producing Gram-Negative Bacteria during the Preparation of Polyvalent Snake Antivenom Immunoglobulin.

Snake bites represent a serious public health problem, particularly in rural areas worldwide. Antitoxic sera preparations are antibodies from immunized animals and are considered to be the only treatment option. The purification of antivenom antibodies should aim at obtaining products of consistent quality, safety, efficacy, and adherence to good manufacturing practice principles. Endotoxins are an integral component of the outer cell surface of Gram-negative bacteria. They are common contaminates of the raw materials and processing equipment used in the manufacturing of antivenoms. In this work, and as a part of quality control testing, we establish and examine an environmental monitoring program for identification of potential sources of endotoxin-producing Gram-negative bacteria throughout the whole steps of antivenom preparation. In addition, we follow all the steps of preparation starting from crude plasma till finished product using a validated sterility and endotoxin testing.Samples from air, surface, and personnel were collected and examined through various stages of manufacturing for the potential presence of Gram-negative bacteria. A validated sterility and endotoxin test was carried out in parallel at the different production steps. The results showed that air contributed to the majority of bacterial isolates detected (48.43%), followed by surfaces (37.5%) and then personnel (14%). The most common bacterial isolates detected were Achromobacter xylosoxidans, Ochrobactrum anthropi, and Pseudomonas aeruginosa, which together with Burkholderia cepacia were both also detected in cleaning water and certain equipment parts. A heavy bacterial growth with no fungal contamination was observed in all stages of antivenom manufacturing excluding the formulation stage. All samples were positive for endotoxin including the finished product.Implementation and continued evaluation of quality assurance and quality improvement programs in aseptic preparation is essential in ensuring the safety and quality of these products. Antitoxic sera preparations are the only treatment option for snake bites worldwide. They are prepared by immunizing animals, usually horses, with snake venom and collecting horse plasma, which is then subjected to several purification steps in order to finally prepare the purified immunoglobulins. Components of the bacterial cell wall known as endotoxins can constitute a potential hazardous contamination known as pyrogen in antisera, which can lead to fever and many other adverse reactions to the person subjected to it.In this work, we monitored the environment associated with the different steps of production and purification of snake antivenom prepared from immunized horses. We examined the air quality, surface, and personnel for possible sources of contamination, particularly the presence of Gram-negative bacteria, which is the major source of endotoxin presence. We also monitored all stages of preparation by sterility and endotoxin testing. Our results showed that air contributed to the majority of bacterial isolates. Sterility testing revealed the presence of bacterial contamination in all the intermediate steps, as only the final preparation after filtration was sterile. Endotoxin was present in all tested samples and the final product. Good manufacturing practice procedures are essential in any facility involved in antisera production.

Unusual Presentation of Snake Bite - a Case Report

Snake bite is a commonest condition in tropical countries like India, Pakistan and Bangladesh, we have reported 4 cases of Neurotoxic snake Krait bite with an unusual presentations at our Rural Medical college Hospital, all the four cases are admitted in the intensive care unit under department of paediatrics, the most common and early presentation in all the 4 cases are Pain Abdomen, vomiting and autonomic disturbance followed by altered sensorium and developed neurotoxic Manifestations, In all the four cases the time of snake bite was mid night and early hours of the night, all the cases were treated with Polyvalent Anti snake venom with Artificial ventilation support.

A retrospective study of use of polyvalent anti-snake venom and risk factors for mortality from snake bite in a tertiary care setting.

Aims:Envenomation with poisonous snakes is associated with considerable morbidity and mortality. The present study was undertaken with the objectives of assessing anti-snake venom (ASV) use, early adverse reactions to ASV, premedication and clinical outcomes in snake bite patients. Association of various risk factors (age, gender, dose of ASV, time gap between snake bite and ASV administration, use of mechanical ventilation and type of snake bite) with mortality was also assessed.Settings and Design:This retrospective study was conducted at two Tertiary Care Teaching Hospitals.Subjects and Methods:The medical records of 176 patients of snake bite with documented use of ASV were retrospectively analyzed to retrieve relevant data.Statistical Analysis:Descriptive statistics was used to express results about ASV use, early adverse reactions to ASV, premedication and clinical outcomes. Univariate and multivariate analysis was performed to find out significant risk factors associated with mortality.Results:The main indication for ASV was vasculotoxic snake bite (75%) followed by neurotoxic snake bite (16%). Mean dose of ASV was 18.63 ± 14.52 vials. Prophylactic premedication with corticosteroids alone or in combination with antihistaminic was used in more than 70% patients. Early adverse reactions to ASV were seen in 4% patients. Neurotoxic snake bite was a significant risk factor associated with mortality in multivariate analysis.Conclusions:Neurotoxic snake bite is an independent predictor of mortality in snake bite patients. Currently used polyvalent ASV may be less effective in treating neurotoxic snake bite.

AN EXPERIENCE WITH MANUAL VENTILATION IN RESPIRATORY PARALYSIS DUE TO INDIAN COMMON KRAIT (BUNGARUS CAERULEUS) BITE

Background: Bungarus caeruleus (common krait) bite during monsoon season is common in northwest India. Respiratory failure is responsible for high mortality in the victims. In this study we report our experience with manual ventilation using bag valve mask (BVM) in patients with neuroparalysis due to common krait bite. Methods:This prospective study was conducted between June 2009 and December 2009. All consecutive patients with diagnosis of common krait bite who were manually ventilated by BVM were studied. The duration of ventilation and complications associated with ventilation were noted. Polyvalent anti snake venom was administered as per the national snake bite protocol and patients were followed up until final outcome. Results: Thirty-four patients (70.6% men) were studied. All patients except two came from rural areas and they were hospitalized between June and September. Majority of patients were bitten during the night while sleeping on the floor. The mean time interval between bite and arrival to hospital was 4.4 hours. Ptosis (100%) was he most common clinical finding followed by ophtalmoplegia (80%) and limb muscle weakness (74%). Twenty-four patients (70%) developed respiratory symptoms and 20 (59%) were intubated and manually ventilated by BVM. Mean duration of assisted ventilation was 34.6 ± 12.8 hours. Hoarseness of voice and throat pain were noted in all intubated patients following extubation, which responded to conservative therapeutic measures. The mean duration of hospitalization was 6 ± 1.6 days. All patients except one survived. Conclusion: Manual ventilation with BVM in patients with neuroparalysis due to common krait bite is a safe and effective modality in resource constraint settings.

Evaluation of health status of horses immunized with snake venom and montanide adjuvants, IMS 3012 (nanoparticle), ISA 206 and ISA 35 (emulsion based) during polyvalent snake antivenom production: Hematological and biochemical assessment

Several biochemical and hematological changes in horses are observed during production of snake antivenom. Although conventional adjuvants like Freund's (Complete and Incomplete) are good immunopotentiators, they produce considerable local reactions in animals. Variety of commercial adjuvants, like montanide adjuvants, having high immunopotentiation and showing lesser side effects are available. The prime objective during antivenom production is to strike a balance between safety of immunized horses and efficacy of the product. In our earlier work, efficacy of montanide group of adjuvants in antivenom production has already been established. The aim of the present work was to assess the safety parameters in horses, viz.: biochemical and hematological, during production of snake antivenom. In the present study, 33 new horses were randomly divided into four groups and hyperimmunized using mixture of snake venoms, viz.: Cobra venom, Russell's viper venom, Krait venom and Echis venom along with montanide adjuvants, IMS 3012, ISA 206, ISA 35 and Incomplete Freund's adjuvant as a control adjuvant; through subcutaneous route at intervals of two weeks. During the immunization period, biochemical and hematological parameters were monitored at 0th, 14th, 21st, 30th and 42nd weeks. The mean hemoglobin values dropped slightly during initial immunization but subsequently regained to normal levels. The mean serum total protein values and globulin levels showed an increment in all the four groups, compared to day zero, vice-versa a slight drop was observed in albumin levels. No significant changes were observed in serum creatinine, bilirubin, alkaline phosphatase and blood urea nitrogen values. Finally, we conclude that montanide adjuvants could be a safer alternative to the conventional adjuvants for primary phase of immunization in antivenom production.

Neurotoxic Manifestation of Snake Bite in Bangladesh

Introduction: Snake bite is a potentially life threatening emergency situation physician has to encounter in rural areas of tropical countries in South-East Asia including Bangladesh. Among the venomous snakes in Bangladesh, Neurotoxic snakes like Cobra and Krait are the commonest. In this study neurotoxic manifestation of venomous snakes are clinically observed. Methods: In this series a total 35 snakebite patients with neurological features from May 1999 to June 2001 were included and preexisting neurological cases were excluded. Results: Among the 537 total snake bite cases, the neurotoxic snake bite was 10% with 51 cobra bite and 12 kraits bite. The victims age are in the range of 3.5 years to 85 years with 70% cases are under 30 years of old. There is slight male preponderence with almost same number of bite at home and outside. The common clinical neurotoxic features are ptosis, (100%) external ophthalmoplegia, dysphagia, dysphonia and broken neck sign. The chest movements were reduced in 20 % cases. All 35 cases (100%) were treated with Haffkine polyvalent anti snake venom with 8.6% cases needed 2nd dose. All 35 cases with neurotoxic features were also treated with anti cholinesterses (100%) and among them 14.2% needed ventilatory support. Anti-snake venom reaction was very common in the with pyrogenic reaction (80.64%) and anaphylactic reaction (64.51%). The outcome of snake bite was excellent with 97% recovery with one residual neurological deficit and no fatality. Conclusion: The neurotoxic snake bite has definite characteristics neurological sign and symptoms which could lead to fatality with respiratory paralysis.

Management of snake bite victims in a Tertiary Care Intensive Care Unit in North India.

Sir, We read with interest the clinical profile and manifestations of snakebite patients from a Medical College in Rural Area of Himachal Pradesh.[1] We would like to share our experience and emphasize on the different management regimes being followed world over. Twenty-five cases of snake bite were admitted in our Intensive Care Unit (ICU) from October 2012 to September 2013; three-fourth of them presented from June 2013 to September 2013. Patients with fang marks and swelling, cellulitis, bleeding, and blisters formation at the local site were included; any patient with suspicion of snake bite but no direct evidence was excluded. Mean age was 31.16 years (range: 13-70 years) and male to female ratio was 18:4. All patients presented with neuroparalytic features and reported of snake bite in the night during sleep. The mean duration of the ICU stay was 4.32 days (range: 3-13 days). The mean dose of equine polyvalent antisnake venom (ASV) administered was 48.63 vials (range: 40-60 vials). No patient had any adverse reactions to the antivenom. No other complication, namely acute renal failure, acute respiratory distress syndrome, cortical venous thrombosis or disseminated intravascular coagulation was reported during hospitalization. They were mechanically ventilated for a mean period of 3.18 days. Dose of ASV used by Raina et al.[1] was 292.69 ml ± 196.27 ml (range: 50-950 ml) which is 6 times higher than that reported in our series. They have thus reported allergic reactions in 7% of patients. Test doses have not been shown to have predictive value in predicting anaphylactic reaction or late serum sickness and are not recommended neutralizing power of antivenoms varies from batch to batch and this may be partially responsible for the difference. National Snakebite Management Protocol prepared by Ministry of Health and Family Welfare, India clearly defines the dose and routes of administration of ASV.[2] The recommended initial dose of ASV is 8-10 vials administered via intravenous route over a period of 1 h. Repeat doses for hemotoxic species is based on the 6 h rule; maximum recommended dose is 30 vials. Repeat doses for neurotoxic is based on the 1-2 h rule; maximum dose is 20 vials. Only the lyophilized polyvalent ASV is available in India. Anticholinesterase drugs have a variable, but potentially useful effect in patients with neurotoxic envenoming. Atropine sulfate (0.6 mg for adults; 50 μg/kg for children) followed by neostigmine in a dose range of 0.01-0.04 mg/kg every 1-3 h up to a maximum of 10 mg/24 h can be administered by intramuscular or intravenous route. Patients are observed over 30-60 min for improved neuromuscular transmission. Neostigmine appears to have no useful role in confirmed presynaptic envenoming, that is poisoning by common kraits and Russell's viper. It is effective in postsynaptic neurotoxins such as those of cobra.[3]“anticholinesterase test” (e.g. “tensilon test”) needs to be performed first to check responsiveness of the patient to the drug as is performed for patients with suspected myasthenia gravis. The use of these drugs will help reduce the consumption of ASV, which is generally limited in a developing country like ours.[4] Awareness of the health care providers on this issue needs to be increased and comparative trials need to be done to quantify its dose sparing effect.

Snake bite and stroke: Our experience of two cases.

Sir, We report two cases of ischemic stroke following snake bite. This report sensitizes the practicing physicians that snake bite could be one of the etiological factors of stroke in young patients where other factors have been ruled out. A 36-year-old male developed epistaxis and hematemesis following a snake bite over the left thumb. He was treated with equine polyvalent anti-snake venom (ASV) at a local hospital. Later he developed generalized seizures and was referred to our hospital. Examination revealed right pupil of 3 mm with normal reaction while left pupil was 5 mm with sluggish reaction. He had left horizontal gaze palsy and brainstem reflexes were absent with asymmetrical motor weakness (right > left) with bilateral extensor planter response. He required mechanical ventilation as the Glasgow coma scale was 7/15. Laboratory parameters revealed a normal coagulation profile and no hematuria. Biochemical profile, electrocardiogram, X-ray chest and 2D-echocardiography were normal. He had no repeat bleeding or seizure. Magnetic resonance imaging (MRI) showed acute infarcts in left cerebellar hemisphere, bilateral occipital lobe and left thalamus suggestive of basilar artery stroke [Figure 1]. He was managed with ASV, tetanus toxoid, antibiotics, anti-edema measures and anti-platelets. Consciousness and weakness improved and was discharged on the 15th day. Figure 1 Magnetic resonance imaging of the brain showing acute ischemic infarcts in left cerebellar hemisphere, bilateral occipital lobe and left thalamus The other case was a 40-year-old male brought to hospital 9 h after snake bite. He was drowsy with two deep fang marks on the foot. The vitals were stable and higher mental function examination revealed Broca's aphasia. Neurological examination was normal. Complete blood count including platelets, bleeding studies and prothrombin time were normal. Fibrinogen degradation products, antinuclear antibody test were within the normal range, as were chest X-ray, electrocardiogram and echocardiogram. MRI [Figure 2] showed infarct in the superior division of left middle cerebral artery. He was treated with ASV in addition to the supportive treatment and was discharged on the 10th day (mRS 1) with some residual dysfunction of naming. Figure 2 Magnetic resonance imaging of the brain showing acute ischemic infarct in the left superior division of middle cerebral artery territory Cerebral complications, particularly ischemic infarcts after snake bite are rare. Mosquera et al. in their study have reported 8 patients (2.6%) with cerebro-vascular complications following snake bite (7 hemorrhagic; 1 ischemic).[1] Ischemic stroke is reported in nine out of 500 victims after envenoming in a report from Sri Lanka.[2] The mechanisms by which cerebral infarction occurs in snake envenomation can be multi-factorial and are as follows: The venom exhibits anticoagulant and procoagulant effects that can lead to small and even large vessel occlusions due to the microthrombi resulting in cerebral infarction[3] Haemorrhagins are complement mediated toxic components of snake venom that may result in severe vascular spasm, endothelial damage and increased vascular permeability. All of these may lead to toxic vasculitis and result in thrombosis.[2] A preexisting procoagulant state, due to deficiencies of protein C or S or antithrombin III and antiphospholipid antibodies could account for a tendency towards thrombosis in large vessels Hypotension can occur due to hypovolaemia from sweating, vomiting, decreased fluid intake and bleeding tendencies leading to low flow state and watershed infarct Hyperviscosity caused by hypovolemia and hypoperfusion secondary to hypotension and hypercoagulation may also contribute to vessel occlusion[4] Direct cardiotoxic effects of venom could lead to dysrrhythmias, causing cardiac thromboembolism. Both these patients were young with no risk factors for stroke. Their clinical and radiological presentation strongly suggested a vascular thrombosis as a cause for their deficit. It could result from toxic vasculitis or toxin induced vascular spasm and endothelial damage. Hypotension as a cause of infarction was not considered because infarction did not involve watershed zones and blood pressure recordings were always normal. Case 1 had a history of bleeding prior to developing seizure and upper limb weakness but the coagulation profile obtained was normal. However, early treatment with ASV could have resulted in normal coagulation profile. Altered sensorium in the hours after the bite could be related to direct arterial endothelial injuries by venom leading to cerebral edema or toxic encephalopathy. These two cases illustrate the occurrence of ischemic snake bite, with abnormalities in the coagulation cascade as the likely causative factor. Learning point form these cases is that snake bite should be one of the differential diagnosis for any young patient with stroke. We call to attention, particularly physicians working in rural areas, to look for such less recognized etiologies of stroke in tropical countries so that victims of snakebite with neurological complications can be given more effective and timely treatment.

A case of bilateral occipital lobe infarcts following Indian tree viper bite.

A case of bilateral occipital lobe infarcts following Indian tree viper bite.

The Availability of Antidotes in Public Hospitals in Kuwait: A Cross Sectional Survey

Objective: Inadequate availability of essential antidotes is reported in many countries. Information on the availability of antidotes in Kuwait is not available. The aim is to determine whether there are adequate stocks of antidotes in public hospitals in Kuwait and to identify the presence of guidelines for antidote stocking and sharing and to determine the presence of emergency medicine pharmacists in the emergency departments. Methods: A cross-sectional study was carried out using a questionnaire distributed to chief pharmacists of six public hospitals in Kuwait. The questionnaire enquired on the availability of 29 antidotes. Results: All the chief pharmacists responded to the survey. The antidotes that were not available in any of the hospitals were botulinum antitoxin, calcium gluconate gel, dicobaltedetate, fomepizole, sodium calcium edetate, sodium thiosulphate, succimer and unithiol. There was substantial variation in the availability of antidotes, especially for cyanide poisoning, ranging from no hospitals for sodium thiosulphate to one hospital each for sodium nitrite and hydroxocobalamin. Only two hospitals had stocks of the polyvalent snake antivenom. Only three hospitals had sharing agreements. Kuwait does not have guidelines for stocking antidotes. None of the hospitals had emergency medicine pharmacists. Conclusion: The six general hospitals in Kuwait have inadequate availability of certain antidotes. Urgent measures, by creating a national guideline for antidote stocking and enforcing antidote hazard vulnerability assessment and establishing a poison control centre, are needed to reduce morbidity and mortality of poisoned patients in Kuwait.

Cross neutralization of common Southeast Asian viperid venoms by a Thai polyvalent snake antivenom (Hemato Polyvalent Snake Antivenom)

Snake envenomation is a serious public health threat in many rural areas of Asia and Africa. Antivenom has hitherto been the definite treatment for snake envenomation. Owing to a lack of local production of specific antivenom, most countries in these regions fully depend on foreign supplies of antivenoms. Often, the effectiveness of the imported antivenoms against local medically important species has not been validated. This study aimed to assess cross-neutralizing capacity of a recently developed polyvalent antivenom, Hemato Polyvalent Snake Antivenom (HPAV), against venoms of a common viper and some pit vipers from Southeast Asia. Neutralisation assays showed that HPAV was able to effectively neutralize lethality of the common Southeast Asian viperid venoms examined (Calloselasma, Crytelytrops, Popeia, and Daboia sp.) except for Tropidolaemus wagleri venom. HPAV also effectively neutralized the procoagulant and hemorrhagic activities of all the venoms examined, corroboratively supporting the capability of HPAV in neutralizing viperid venoms which are principally hematoxic. The study also indicated that HPAV fully prevented the occurrence of hematuria and proteinuria in mice envenomed with Thai Daboia siamensis venom but was only partially effective against venoms of Myanmar D. siamensis. Thus, HPAV appears to be useful against its homologous venoms and venoms from Southeast Asian viperids including several medically important pit vipers belonging to the Trimeresurus complex. Nevertheless, the effectiveness of HPAV as a paraspecific antivenom for treatment of viperid envenomation in Southeast Asian region requires further assessment from future clinical trials

Clinical Features, Management and Outcome of Snake Bite in Children in Manipal Teaching Hospital

Background: Snake bite is a widely distributed and neglected condition with a significant mortality. Medically significant snakes are: Elapidae, which are mainly neurotoxic and Viperidae, which are hemotoxic. Most studies on snake bites are done in Terai belt of Nepal and this is a first study of its kind in children in western region of Nepal. Methods: This was a 7 year retrospective study in Pediatric unit of Manipal Teaching Hospital, Pokhara, Nepal. Relevant data from all cases of snake bite in children up to 18 years of age was collected in a structured proforma and analyzed. Results: Among the 39 cases of Snake bites; it was more in boys (M: F=1.16:1), from rural areas (62%) and was more common during monsoon (64%). The commonest site of bite was foot (64%). Snakes were identifiable in only 23% of the cases. Local swelling (77%) and pain (74%) were common clinical features. Coagulation profile was deranged in 80% of the patients, hematuria was observed in 13% patients and 15% patients had thrombocytopenia. Most of the snakes were hemotoxic (77%) and only 1 case (2.5%) was neurotoxic. Only 44% of the patients received polyvalent anti-snake venom and blood products were required in 51% of the patients. Most patients improved (75%) and the case fatality rate was 2.5%. Conclusion: Most snakes found in mountainous region of Nepal are hemotoxic and lead to deranged coagulation profile. Mortality is low in hemotoxic as compared to neurotoxic envenomations. Nepal Journal of Medical Sciences | Volume 02 | Number 02 | July-December 2013 | Page 119-124 DOI: http://dx.doi.org/10.3126/njms.v2i2.8954

Production of high titre antibody response against Russell's viper venom in mice immunized with ethanolic extract of fruits of Piper longum L. (Piperaceae) and piperine

Piper longum L. fruits have been traditionally used against snakebites in north-eastern and southern region of India. The aim of the study was to assess the production of antibody response against Russell's viper venom in mice after prophylactic immunization with ethanolic extract of fruits of Piper longum L. and piperine. The mice sera were tested for the presence of antibodies against Russell's viper venom by in vitro lethality neutralization assay and in vivo lethality neutralization assay. Polyvalent anti-snake venom serum (antivenom) manufactured by Haffkine Bio-Pharmaceutical Corporation Ltd. was used as standard. Further confirmation of presence of antibodies against the venom in sera of mice immunized with PLE and piperine was done using indirect enzyme-linked immunosorbent assay (ELISA) and double immunodiffusion test. Treatment with PLE-treated mice serum and piperine-treated mice serum was found to inhibit the lethal action of venom both in the in vitro lethality neutralization assay and in vivo lethality neutralization assay. ELISA testing indicated that there were significantly high (p<0.01) levels of cross reactions between the PLE and piperine treated mice serum and the venom antigens. In double immunodiffusion test, a white band was observed between the two wells of antigen and antibodies for both the PLE-treated and piperine-treated mice serum. Thus it can be concluded that immunization with ethanolic extract of fruits of Piper longum and piperine produced a high titre antibody response against Russell's viper venom in mice. The antibodies against PLE and piperine could be useful in antivenom therapy of Russell's viper bites. PLE and piperine may also have a potential interest in view of the development of antivenom formulations used as antidote against snake bites.

An examination of cardiovascular collapse induced by eastern brown snake (Pseudonaja textilis) venom

The Pseudonaja genus (Brown snakes) is widely distributed across Australia and bites account for significant mortality. Venom-induced consumption coagulopathy (VICC) and, less often, early cardiovascular collapse occur following envenoming by these snakes. We have previously examined possible mechanism(s) behind the early cardiovascular collapse following Papuan taipan (Oxyuranus scutellatus) envenoming. In the present study, we investigate early cardiovascular collapse in anaesthetized rats following administration of eastern brown snake (Pseudonaja textilis) venom, and prevention of this effect with prior administration of ‘priming’ doses (i.e. doses of venom which caused a transient hypotensive response) of venom. P. textilis venom (5–10μg/kg, i.v.) induced cardiovascular collapse in anaesthetized rats, characterized by a rapid decrease in systolic blood pressure until non recordable. Prior administration of ‘priming’ doses of P. textilis venom (2 and 3μg/kg) or, at least, 4–5 doses of O. scutellatus (2μg/kg, i.v.) or Daboia russelii limitis (20μg/kg, i.v.) venoms prevented cardiovascular collapse induced by P. textilis venom. Moreover, early collapse was also inhibited by prior administration of 2 discrete doses of Acanthophis rugosus venom. Prior administration of commercial polyvalent snake antivenom (500–3000units/kg, i.v.) or heparin (300units/kg, i.v.) also inhibited P. textilis venom-induced cardiovascular collapse. Our results indicate that P. textilis venom-induced cardiovascular collapse can be prevented by prior administration of sub-lethal doses of venom from P. textilis, O. scutellatus, A. rugosus and D. russelii limitis. This suggests that sudden cardiovascular collapse following envenoming is likely to involve a common mechanism/pathway activated by different snake venoms.