Snakebite Deaths Research Articles

Taxon-selective venom variation in adult and neonate Daboia russelii (Russell's Viper), and antivenom efficacy

Major variations in venom composition can occur between juvenile and adult venomous snakes. However, due to logistical constraints, antivenoms are produced using adult venoms in immunising mixtures, possibly resulting in limited neutralisation of juvenile snake venoms. Daboia russelii is one of the leading causes of snakebite death across South Asia. Its venom is potently procoagulant, causing stroke in prey animals but causing in humans consumptive coagulopathy—a net anticoagulant state—and sometimes death resulting from hemorrhage. In this in vitro study, we compared the venom activity of—and antivenom efficacy against—six 2-week-old D. russelii relative to that of their parents. Using a coagulation analyser, we quantified the relative coagulotoxicity of these venoms in human, avian, and amphibian plasma. The overall potency on human plasma was similar across all adult and neonate venoms, and SII (Serum Institute of India) antivenom was equipotent in neutralising these coagulotoxic effects. In addition, all venoms were also similar in their action upon avian plasma. In contrast, the neonate venoms were more potent on amphibian plasma, suggesting amphibians make up a larger proportion of neonate diet than adult diet. A similar venom potency in human and avian plasmas but varying selectivity for amphibian plasma suggests ontogenetic differences in toxin isoforms within the factor X or factor V activating classes, thereby providing a testable hypothesis for future transcriptomics work. By providing insights into the functional venom differences between adult and neonate D. russelii venoms, we hope to inform clinical treatment of patients envenomated by this deadly species and to shed new light on the natural history of these extremely medically important snakes.

Analysis of snakebite data in Volta and Oti Regions, Ghana, 2019.

Introductionglobally about 5.4 million people are affected by snakebite annually leading to 2.7 million cases of snakebite envenoming and 81,000-138,000 deaths. In sub-Saharan Africa, the burden of disease caused by snakebite is often underestimated despite its status as a category A neglected tropical disease. We reviewed snakebite data to determine the magnitude of snakebite by person, place, and time in the Volta and Oti Regions of Ghana.Methodswe conducted a descriptive secondary data analysis using snakebite data from 2014-2018 extracted from the District Health Information and Management Systems (DHIMS 2) database. Data were analyzed descriptively by person, place, and time using summary statistics and results were presented in proportions and graphs. Missed outbreaks were determined through calculation of cumulative sum (CUSUM 2).Resultsa total of 2,973 cases of snakebites were reported over the 5 years of which 1675 (56.3%) were males. Majority 867 (29.2%) of snakebite victims were between 20-34 years of age with recorded 5-year average incidence of 24 snakebite cases per 100,000. Nkwanta North District recorded the highest cases 499 (16.8%) with most of the snakebite cases 2,411 (81%) recorded in the rainy season. Overall, there was a decreasing trend of snakebites and four missed snakebite outbreaks occurred during the period. No snakebite death was recorded.Conclusiona 5-year average snakebite incidence of 24 cases per 100,000 persons was recorded and Nkwanta North District recorded the highest cases with peaks occurring in rainy and harvesting seasons. Four outbreaks were missed. There is a need to conduct periodic data analysis for effective intervention programs.

Thrombotic microangiopathy, hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: Rare manifestations of Russell’s viper (Daboia russelii) envenoming in Sri Lanka

Background: Russell’s viper (Daboia russelii) of Family Viperidae is a highly venomous snake in Sri Lanka and is responsible for the most snakebite deaths. It commonly causes coagulopathy and neuroparalysis. Thrombotic microangiopathy (TMA) including the triad of acute kidney injury (AKI), thrombocytopenia and microangiopathic hemolysis is a rare complication of its bites. There are two clinical entities of TMA including hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) of which, only few records of TMA and HUS following Russell’s viper bites are available in literature.Case presentation: Two patients presented with TMA following Russell’s viper bites. A 36-year-old male who got coagulopathy, respiratory failure, AKI, signs of HUS, and he completely recovered with antivenom and 8 cycles of hemodialysis and discharged on day 19 of snakebite. The other patient was a 66-year-old female who had delayed coagulopathy and persistent drowsiness, the signs of TTP. She required antivenom with 9 cycles of hemodialysis and 6 cycles of therapeutic plasma exchange and got recovered after 30 days in hospital that included intensive care treatments.Discussion: Russell’s viper venom causes activation of Factor V and X which results venom induced consumption coagulopathy and bleeding. The venom also blocks neuromuscular junction and causes neuroparalysis, which are commonly manifested as ptosis and external ophthalmoplegia. It also has direct nephrotoxic effects and there are fibrin depositions in renal microvasculature thereby, causing renal ischemia. In the spectrum of HUS-TTP of TMA, HUS is suggested when there is a severe renal involvement, and TTP is diagnosed when neurological impairment is prominent.Conclusion: Atypical presentations like TMA and HUS may rarely occur following Russell’s viper bites. Further evidence of similar observations is needed to confirm the clinical entity of TTP following Daboia russelii bites.

Profile of Snake Bite Deaths in South India: An Autopsy based Stud

Background: The burden due to the morbidity and mortality of snake bite in India is significantly higher. Itis estimated around 1.2 million snakebite deaths (average 58,000/year) has occurred in India from the year2000 to 2019. However the real burden of snake bite is unknown due to under reporting. This study aims tobring out region specific data on fatal snake bitesResults: The study was conducted at the dep of forensic medicine from 2016 to 2020. A total of 75 cases offatal snake bite cases were autopsied. The number of female cases 39 (52.3) and males were 36 (48.0). Themaximum no 52 (69.4%) cases were reported between the months of April to September. The common timefor snake bite was in the night 40 (53.3%) followed by the daytime 33 (44.0%). The place of incidence wheremost of the bites happened was in and around the homes of the victims 46 (61.3) followed by the workplaces29 (38.7%). The commonest site were the bite mark was noted in the lower limbs 33 (44%) cases. Around 22(23.9%) cases were seen in age groups of 45 to 59 years and 19 (25.3%) cases in 35 to 44 years. The speciesof snake in majority of the cases i.e., 65 (86.7%) was unknown. Around 40 (53.3%) cases of kidney samplesshowed acute tubular followed by congestion.Conclusion: The number of fatal bites were comparatively higher than that of the statistics available. Most ofthe findings of our study was consistent with the similar studies. The species of snake was largely unknownin this study because new snake species like hump nose pit viper can inflict fatal bites and are difficult toidentify. Region specific data on snake bite will reflect the exact volume of snake bites in the country andwould largely help in drafting policies to reduce mortality

A Cross Sectional Study of Deaths Due to Snakebite: Autopsied at a Tertiary Care Centre, Hubballi

Worldwide, Snakebite is an important and preventable health hazard in many of the tropical and subtropicalcountries. Death following snake bite is a cumulative effect of all the toxic reactions that are producedby the snake venom in the body of the victim.1Globally it is estimated that the true incidence of snakeenvenomation could exceed 3 million per year and about 1,00,000 of these develop severe sequelae. Withthis background, a study has been conducted to determine the pattern of snakebite death cases, autopsied atKIMS, Hubballi, Karnataka. The study revealed that maximum number of snakebite cases were recorded inthe rainy season (34.9%) followed by the winter season (31.7%).In a greater number of cases the incidenceof snake bite occurred predominantly in lower limb (54%) as compared to upper limb (46%).Peak incidenceof snake bite was recorded in the time between 08:00 am to 04:00 pm (41.3%) followed by 04:00 pmto midnight (30.2%). Majority of the cases were declared dead (47.61%) within 24 hours of initiation ofanti-snake venom. The cause of death in majority of the study population was respiratory failure (92.06%)followed by shock (7.93%).

Perceptions, awareness on snakebite envenoming among the tribal community and health care providers of Dahanu block, Palghar District in Maharashtra, India.

India has remarkably the highest number of snakebite cases contributing to nearly 50% of the global snakebite deaths. Despite this fact, there is limited knowledge and awareness regarding the management practices for snakebite in the Indian population. The study aimed to explore the knowledge, awareness, and perception of snakes and snakebites, first aid, and treatment amongst the community and the frontline health workers in a tribal block of Dahanu, Maharashtra, India. A cross-sectional study was carried out from June 2016 to October 2018 in the Dahanu Block, Maharashtra. Perceptions, knowledge, awareness, and first-aid practices on the snakebites among the community were studied through focus group discussions (FGDs). Semi-structured questionnaires were used to assess the knowledge, awareness, and experience of the traditional faith healers, snake rescuers, frontline health workers on the snakebites and their management. A facility check survey was conducted using pre-tested questionnaires for different levels of the government health care facilities. Most of the tribal community was aware of the commonly found snakes and their hiding places. However, there was inadequate knowledge on the identification and classification of venomous snakes. Belief in a snake god, the perception that snakes will not come out during thunderstorms, change in taste sensation, the ability of tamarind seeds or magnet to reduce the venom effect were some of the superstitions reported by the tribal community. The application of a harmful method (Tourniquet) as the first aid for snakebite was practiced by the tribal community. They preferred herbal medicines and visiting the traditional faith healers before shifting the patient to the government health facility. The knowledge on the ability to identify venomous snakebites and anti-venom was significantly higher amongst nurses and accredited social health activists (ASHAs) than auxiliary nurse midwives (ANMs) and multi-purpose workers (MPWs) (p < 0.05). None of the traditional faith healers; but nearly 60% of snake rescuers were aware of anti-venom. Fifty percent of the medical officers in Dahanu block did not have correct knowledge about the Krait bite symptoms, and renal complications due to the Russell viper bite. Inappropriate perception, inadequate awareness, and knowledge about snakes and snakebites may predispose the tribal community to increased risks of venomous snakebites. Unproven and harmful methods for snakebite treatment practiced by the community and traditional faith healers could be dangerous leading to high mortality. Therefore, a multi-sectoral approach of community awareness, mapping of vulnerable populations, capacity building of health care facility, empowerment of health care workers (HCWs) could be useful for reducing the mortality and morbidity due to snakebite envenoming in India.

Potential of herbal cocktail of medicinal plant extracts against ‘big four’ snake venoms from India

BackgroundVenomous snake bites cause acute medical emergencies and are fatal. India accounts for large proportion of snake-bite deaths globally. Medically important ‘BIG FOUR’ snakes of India are Bungarus caeruleus (krait), Naja naja (cobra), Echis carinatus (saw-scaled viper) and Daboia russelii (Russell's viper). Polyherbal formulations have been proved to be effective in treatment of diseases than a single formulation. Objective(s)To evaluate aqueous ethanolic extract cocktail of Azadirachata indica, Butea monosperma, Citrus limon, Clerodendrum serratum and Areca catechu for antidote potential against BIG FOUR venoms in ex vivo and in vivo model. Materials and methodsAnti-hemorrhagic and venom neutralization studies were performed in seven-day old chick embryo model for ex vivo studies. In vivo studies were performed using male Swiss albino mice for antivenom potential of herbal cocktail by performing anti-edematic, anti-hemorrhagic, anti-myotoxic activity, and venom neutralization. ResultsHerbal cocktail exhibited differential venom inhibition potential against four venoms tested. Hemorrhagic activity was completely neutralized by the herbal cocktail; myotoxic activities of krait and Russell's viper venom were neutralized; while anti-edematic activity was observed for krait and cobra venom. Herbal cocktail completely neutralized venom lethality (3∗LD50) of krait and saw-scaled viper venom. ConclusionInhibitions of various venom components of all four venoms suggests presence of phytochemicals in herbal cocktail with therapeutic properties. Further studies would help in the development of a formulation as a first-aid towards treatment of snake bite victims.

Retrospective hospital-based study on snakebite envenomation in Sudan.

BackgroundSnakebite statistics are lacking in Sudan despite the high estimated burden. In this study we aimed to describe the incidence of snakebite envenomation and death in Sudan and to show the state-wise distribution of snakebite episode.MethodsWe retrospectively analyzed hospital-based data on snakebite for 2014–2018. Data were obtained from the annual health statistical reports of the Ministry of Health. Descriptive statistics were used to illustrate the results.ResultsA total of 63 160 people were envenomed during 2014–2018 with an average of 12 632 cases/year. The death rate between inpatient cases was 2.5%. The annual incidence was 18– 47 cases/100 000 population. Gadarif state recorded the highest incidence (132/100 000 population) of snakebite envenomation in Sudan whereas Northern state had the least incidence (5/100 000 population). The 15–24 y age group experienced the highest risk of snakebite and males were more exposed to snakebites than females.ConclusionsAlthough hospital-based records underestimate the burden of snakebite, they can still provide an insight regarding the actual numbers. Here, we highlight the at-risk states in Sudan to be targeted for further questionnaire-based epidemiological studies and to guide health authorities to reduce the burden of snakebite envenomation by insuring proper antivenom distribution to the highly affected areas.

A Quest for a Universal Plasma-Derived Antivenom Against All Elapid Neurotoxic Snake Venoms.

This review describes the research aimed at the development of universal antivenom against elapid neurotoxic snake venoms. The antivenoms produced in Thailand in the 1980s were of low potency, especially against the elapid venoms. This was thought to be due to the low immunogenicity of the α-neurotoxins, which are the most lethal toxins in these venoms. Comparisons of various α-neurotoxin conjugates and polymers, and also different immunological adjuvants, showed that the adjuvant used is the major determinant in the antibody response in horses. The potent Freund’s adjuvant was not used due to its severe local side-effect in horses. Therefore, a novel immunization protocol termed ‘low dose, low volume multi-site’ was developed for use in horses. This immunization protocol has led to the production of highly potent monospecific antivenoms against several elapid and viperid venoms, and two potent polyspecific antivenoms, one against 4 neurotoxic and another against 3 hematotoxic venoms. The immunization protocol has also led to other improvements in antivenom production including: several fold increases in antiserum potency, a reduction in the time required to reach therapeutically useful antibody titers, a 90% reduction in the amount of venom used, and 100% of the horses responding to the immunization program. This development is partly responsible for significant decrease in the Thailand’s annual snakebite death toll from a few dozens to mostly nil in recent years. Finally, a simple and novel immunization strategy, using a ‘diverse toxin repertoire’ composed of numerous elapid toxin fractions as immunogen, was proposed and tested. This immunization procedure has resulted in the successful production of a widely paraspecific antiserum against at least 36 neurotoxic venoms of 28 species encompassing 10 genera and from 20 countries on four continents, and possibly against all elapid venoms with α-neurotoxins as the lethal toxins. These results indicate that, with optimizations of the composition of the ‘diverse toxin repertoire’, the immunization scheme and antibody fractionation to increase the antivenom neutralizing potency, an effective universal antivenom against the neurotoxic elapid snakes of the world can be produced.

English

Snake bite is a major health concern in India. Common krait is one of the most dangerous and poisonous neurotoxic snakes. Snake bite is a medical emergency. India has the highest snake bite death rate in the world.1 Elapidae, viperidae, pit viper and hydrophiidae are the main poisonous snake families in India. Elapidae family includes common cobra, king cobra and common krait.2 Common Indian krait is about 10 times more poisonous than cobra. Snake toxins are neurotoxic or haematotoxic. Krait is neurotoxic, which interrupts neuromuscular transmission of impulse and causes paralysis of muscles. Neostigmine which is an anticholinesterase can reverse the neurological manifestations of the venom.3 Treatment of neurotoxic snake bite includes administration of anti-snake venom, neostigmine with atropine and invasive ventilation if there is respiratory muscle weakness or paralysis. Maximum dose of neostigmine to reverse neuromuscular blockade is 10 mg over 24 hours. 4 Here we report a case of a 60-years-old male who presented with a snake bite followed by respiratory distress and bilateral ptosis. The patient was treated as per standard protocol. However, his ptosis did not improve as per expectations. Hence, neostigmine was given for prolonged period to revert ptosis in neurotoxic snake bite. In this case study we are discussing about maximum dose of neostigmine given to revert ptosis in a neurotoxic snake bite, as their no case report regarding it.

Secular trends of grossly underreported snakebite burden in India, 2009-2018: analysis of data from India's National Health Profile.

India's National Health Profile (NHP) documents snakebite cases and deaths based on hospital-based reports, hence underrepresenting the actual burden. We describe secular trends of NHP data using population denominators for 2009-2018. We abstracted the data on snakebite cases and deaths and calculated incidence and case fatality rate (CFR) by gender and by states using population denominators. We estimated the change in incidence and CFR over time by using a Poisson regression model. We computed the incidence rate ratio (IRR) and 95% confidence interval (CI) using Stata 14.0. The incidence of snakebites ranged from 89 to 141 per million population and without any specific pattern during 2009-2018 as per NHP reports. The incidence increased by 3% per year (IRR 1.03 [95% CI 0.99 to 1.07]). The incidence was higher among males (range 97-163) than females (range 71-115) and there was no difference in trends by gender (IRR 1.07 [95% CI 0.37 to 3.12]). The CFR was 5-13 deaths per 1000 cases, with an annual decline of 12% (IRR 0.88 [95% CI 0.85 to 0.92]). The CFR did not differ by gender (male 5-12, female 6-13; IRR 0.48 [95% CI 0.20 to 1.17]). India's NHP snakebite data, representing an underestimate of the actual burden, suggests no specific secular trend and points to areas documenting consistent and significant burden.

The in vitro laboratory tests and mass spectrometry-assisted quality assessment of commercial polyvalent antivenom raised against the ‘Big Four’ venomous snakes of India

India has recorded the maximum snakebite deaths in the world. Intravenous administration of polyvalent antivenom (PAV) raised against the ‘Big Four’ venomous snakes of India (Naja naja, Daboia russelli, Echis carinatus, and Bungarus caeraleus) is the only choice of treatment. The WHO has recommended the evaluation of quality and safety of commercial antivenom by in vitro laboratory tests prior to their pre-clinical evaluation in animal model and therapeutic use. Therefore, in this study an attempt has been made to evaluate the quality of commercial polyvalent antivenom produced in India by simple, and affordable laboratory tests. Proteomic analysis revealed that PAVs contained 78.7–94.8% IgG/F(ab’)2 and small quantities of plasma proteins. The PAVs showed batch-to-batch variations with varying amounts of undigested IgG and its aggregates, and moderate complement activation. However, absence of IgE, negligible endotoxin contamination, and recommended limit of preservative (cresol) in PAVs were observed. The PAVs contain varying proportions and least amount of venom-specific antibodies against venoms of the ‘Big Four’ snakes from different locales of India, and against eastern India N. kaouthia venom, respectively. The importance of independent in vitro laboratory tests for the quality control and safety assessment for improving the quality of Indian commercial PAV is reinforced.

A Pilot Study on Snake Bite Deaths in the District of Malda, West Bengal, India

A Pilot Study on Snake Bite Deaths in the District of Malda, West Bengal, India

101 Thromboelastography versus Conventional Coagulation Tests in Pit Viper Envenomation and Antivenom Response

Pit viper envenomations represent a significant burden of disease worldwide, leading to severe hematologic derangements such as venom-induced consumptive coagulopathy (VICC). Recognizing this problem, the WHO recently launched a campaign to cut snake bite deaths in half by 2030. Immediacy in detection and treatment of coagulopathy with antivenom is paramount to reducing morbidity and mortality. Traditionally, administration of the pit viper antivenom, CroFab®, has been based on clinical signs and symptoms and conventional coagulation tests (CCT) such as fibrinogen, PT, PTT and INR. The purpose of this study was to assess the efficacy of TEG in detecting response to antivenom administration. Blood samples from 25 healthy adult volunteers were mixed with different concentrations of western diamondback rattlesnake (Crotalus atrox) venom (50% and 100% LD50). Each group of envenomated blood samples was treated with 4, 6, and 10 vial equivalents (vialeq) of CroFab®. All samples were assessed with CCTs including: PT, PTT, INR and Fibrinogen, as well as with TEG measures of reaction time (R), amplification (k), rate of clot formation (alpha angle), and clot strength (MA). Data was analyzed to determine the rate of return to normal range CCT and TEG values as a surrogate for return to normal coagulation. For the 50% LD50 group, CCT parameters of PT, PTT and INR returned to normal in 24%-32% of samples across all CroFab® doses. For the same group, 72% of Fibrinogen samples returned to normal at 4 vialeq with a max of 88% at 10 vialeq. TEG parameters R, k, alpha angle and MA returned to normal at a rate of 80%-96% across all CroFab doses. For the 100% LD50 group, CCT parameters of PT, PTT, and INR had a maximum of 24% return to normal for all CroFab® doses. For the same group, 16% of Fibrinogen samples returned to normal at 4 vialeq with a max of 88% at 10 vialeq. TEG parameters showed incremental increases towards normal range with 92-96% of samples in range at 10 vialeq. Pit viper envenomations are a global health threat with significant morbidity and mortality and suboptimal methods to guide the utilization of the expensive and often limited CroFab® antivenom. In this in vitro model, TEG was shown to be more sensitive than CCTs in tracking antivenom-induced recovery from VICC. Additionally, our findings represent a step towards developing a dose-response curve for antivenom administration with the potential to reduce both the amount of antivenom used and the side effects associated with its use.

Trends in snakebite deaths in India from 2000 to 2019 in a nationally representative mortality study

The World Health Organization call to halve global snakebite deaths by 2030 will require substantial progress in India. We analyzed 2833 snakebite deaths from 611,483 verbal autopsies in the nationally representative Indian Million Death Study from 2001 to 2014, and conducted a systematic literature review from 2000 to 2019 covering 87,590 snakebites. We estimate that India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. Nearly half occurred at ages 30-69 years and over a quarter in children < 15 years. Most occurred at home in the rural areas. About 70% occurred in eight higher burden states and half during the rainy season and at low altitude. The risk of an Indian dying from snakebite before age 70 is about 1 in 250, but notably higher in some areas. More crudely, we estimate 1.11-1.77 million bites in 2015, of which 70% showed symptoms of envenomation. Prevention and treatment strategies might substantially reduce snakebite mortality in India.

Forensic toxinology and snakebite death

Forensic toxinology and snakebite death

Burden and risk factors for snakebite in India: protocol for a systematic review.

Introduction: Snakebite is a neglected tropical disease with a high burden in South and South-East Asia and sub-Saharan Africa. In 2019, the World Health Organization (WHO) released a roadmap which aims for a 50% reduction in death and disability due to snakebite globally by 2030. It is estimated that India has the highest number of snakebite deaths in the world. Objective: To synthesize evidence on the burden (incidence/ prevalence, mortality, morbidity, health facility and economic), and risk factors for snakebite in India. Methods: We will search for peer-reviewed literature and grey literature in six electronic databases (MEDLINE, EMBASE, Global Health, PsychInfo, CENTRAL, SafetyLit) and hand-search IndMed, conference abstracts, relevant websites and citation tracking. Two reviewers will screen and extract data independently with a third reviewer acting as an arbiter for any inconsistencies. Quality of the included studies will be assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. For burden, data from facility based and community-based studies will be synthesised and reported separately, except for studies conducted concurrently. We will conduct meta-analysis for community-based studies at state-level for incidence/prevalence, mortality and morbidity , if appropriate. The PROGRESS Plus lens will be used to explore equity . Analyses for each individual risk factor-outcome pair will be conducted and reported separately. If appropriate, meta-analyses will be conducted as per JBI guidelines, assessing heterogeneity using Tau-squared, Cochran's Q test and Chi-squared (p > 0.05) tests. We plan to conduct sub-group analyses based on pre-specific parameters. A funnel plot will be generated if there are more than nine studies included in a specific meta-analysis, to assess publication bias When meta-analysis is not appropriate, structured tabulation of results across studies and/or by vote counting based on the direction of effect as per guidelines in the Cochrane Handbook.

Burden and risk factors for snakebite in India: protocol for a systematic review

Introduction: Snakebite is a neglected tropical disease with a high burden in South and South-East Asia and sub-Saharan Africa. In 2019, the World Health Organization (WHO) released a roadmap which aims for a 50% reduction in death and disability due to snakebite globally by 2030. It is estimated that India has the highest number of snakebite deaths in the world. Objective: To synthesize evidence on the burden (incidence/ prevalence, mortality, morbidity, health facility and economic), and risk factors for snakebite in India. Methods: We will search for peer-reviewed literature and grey literature in six electronic databases (MEDLINE, EMBASE, Global Health, PsychInfo, CENTRAL, SafetyLit) and hand-search IndMed, conference abstracts, relevant websites and citation tracking. Two reviewers will screen and extract data independently with a third reviewer acting as an arbiter for any inconsistencies. Quality of the included studies will be assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. For burden, data from facility based and community-based studies will be synthesised and reported separately, except for studies conducted concurrently. We will conduct meta-analysis for community-based studies at state-level for incidence/prevalence, mortality and morbidity , if appropriate. The PROGRESS Plus lens will be used to explore equity . Analyses for each individual risk factor-outcome pair will be conducted and reported separately. If appropriate, meta-analyses will be conducted as per JBI guidelines, assessing heterogeneity using Tau-squared, Cochran’s Q test and Chi-squared (p > 0.05) tests. We plan to conduct sub-group analyses based on pre-specific parameters. A funnel plot will be generated if there are more than nine studies included in a specific meta-analysis, to assess publication bias When meta-analysis is not appropriate, structured tabulation of results across studies and/or by vote counting based on the direction of effect as per guidelines in the Cochrane Handbook.

Burden and risk factors for snakebite in India: protocol for a systematic review

Introduction: Snakebites are a neglected tropical disease with a high burden in South and South-East Asia and sub-Saharan Africa. In 2019, the World Health Organization (WHO) released a roadmap which aims for a 50% reduction in death and disability due to snakebite globally by 2030. It is estimated that India has the highest number of snakebite deaths in the world. Objective: To synthesize evidence on the burden (incidence/ prevalence, mortality, morbidity, health facility and economic), and risk factors for snakebite in India. Methods: We will search for peer-reviewed literature and grey literature in six electronic databases (MEDLINE, EMBASE, Global Health, PsychInfo, CENTRAL, SafetyLit) and hand-search IndMed, conference abstracts, relevant websites and citation tracking. Two reviewers will screen and extract data independently with a third reviewer acting as an arbiter for any inconsistencies. Quality of the included studies will be assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. For burden, data from facility based and community-based studies will be synthesised and reported separately, except in the case of studies conducted concurrently. We will conduct narrative analyses with the aim of understanding patterns in data through tabulation for both burden and risk factors evidence synthesis. The PROGRESS Plus lens will be used to explore equity pertaining to burden of snakebites. Analyses for each individual risk factor-outcome pair will be conducted and reported separately. If appropriate, meta-analyses will be conducted as per JBI guidelines, assessing heterogeneity using Tau-squared, Cochran's Q test and Chi-squared (p > 0.05) tests. We plan to conduct sub-group analyses based on setting, study design, sex/gender, age-groups, tribal people and occupation. A funnel plot will be generated if there are more than nine studies included in a specific meta-analysis, to assess publication bias. Asymmetry of the funnel plot will be adjudged using the Egger, Begg and Harbord tests.

22 Thromboelastography Detects Coagulopathy Faster than Standard Coagulation Studies in Simulated Pit Viper Envenomation

Venomous snakebites pose a significant risk of morbidity and mortality in rural and austere environments, so it is not surprising that the World Health Organization recently set a goal of reducing snakebite deaths by half by 2030. Many of these envenomations are due to pit vipers, leading to severe hematologic derangements, such as venom-induced consumptive coagulopathy (VICC). Immediacy in detection of envenomations is crucial for ameliorating morbidity and mortality, but diagnosis of envenomization can be challenging, requiring access to clinical laboratory facilities. Further, the laboratory-based evaluations of coagulation function take more than an hour to conduct. In contrast, thromboelastography (TEG) is promising as a rapid, portable, bedside test of coagulation that produces meaningful results in less than 15 minutes. Therefore, the primary objective of this study was to assess the efficacy of TEG compared to standard lab tests in detecting pit viper venom at increasing concentrations. Blood samples drawn from 19 healthy adult volunteers were mixed with varying concentrations of western diamond back rattlesnake (Crotalus atrox) venom (none, 0.5%, 1%, 2%, 33%, 66%, and 100% of LD50), then assessed with standard laboratory-based tests of coagulation function (labs), including prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), D-dimer, and Fibrinogen, as well as with TEG measures of reaction time (R), amplification (K), rate of clot formation (Angle), and clot strength (MA). Data were analyzed as changes from baseline and categorized as percent of samples out of normal physiologic range, then analyzed using ANOVA and binomial statistics at the p<.05 threshold for statistical significance. TEG and standard labs were both excellent (100%) at detecting higher concentrations of venom (33%, 66%, 100%), save D-dimer. Importantly, at low venom concentration levels (0.5%, 1%, 2%), the TEG measures of R, K, alpha, and MA were similar to laboratory-based evaluations of PT and INR at detecting venom, and were significantly superior to PTT, D-dimer, and Fibrinogen. TEG provides a sensitive, real-time quantitative evaluation of coagulation derangements during simulated pit viper envenomation that is faster than standard laboratory tests. TEG was sensitive at low venom concentrations, outperforming multiple traditional laboratory evaluations of VICC. While the present study was limited to in vitro analyses, our findings suggest that TEG is a fast, effective, and portable point-of-care testing modality to assist the emergency physician community to rapidly and accurately diagnose patients stricken with venomous snake bites.