Crotalidae Polyvalent Immune Fab and Cost-Effective Management of Hospital Admissions for Snakebites.

BACKGROUND: Venomous snakebites are a common clinical scenario in the Southeastern United States. CroFab® (Crotalidae Polyvalent Immune Fab (Ovine), BTG, Wales, UK) antivenom is indicated in cases involving pit vipers and is known to be expensive. The treatment protocol for snakebites is based on clinically subjective measures triggering the application, or escalation of, antivenom administration. The purpose of this study is to characterize the use of CroFab at our institution and to evaluate the impact of its use regarding cost and overall outcomes. We suspect that it is often used but potentially less often needed. We hypothesized that CroFab use was associated with increased length of stay (LOS) without an observed difference in patient outcomes. MATERIALS AND METHODS: A retrospective chart review of snakebite patients at our level-1 trauma center from 2000 to 2016 was performed. Snakebite location, snake species, number of vials of CroFab administered, hospital LOS, intensive care unit (ICU) LOS, and complications were identified for each patient. Patients were divided into CroFab (C) and no CroFab (NC) groups. RESULTS: One hundred ninety patients with venomous snakebites were included. 53.7% of patients received CroFab. There was no difference in the complication rate of C versus NC groups, (P = .1118). CroFab use was associated with longer hospital LOS (P < .0001) and ICU LOS (P < .0001). DISCUSSION: CroFab use was associated with increased LOS in our patient population. There was no difference in observed outcomes between the C and NC groups. These findings imply that CroFab is potentially over-used in our patient population.

BITES study: A qualitative analysis among emergency medicine physicians on snake envenomation management practices.

INTRODUCTION: Antivenom is currently considered standard treatment across the full spectrum of severity for snake envenomation in the United States. Although safe and effective antivenoms exist, their use in clinical practice is not universal. OBJECTIVE: This study explored physicians' perceptions of antivenom use and experience with snake envenomation treatment in order to identify factors that influence treatment decisions and willingness to administer. METHODS: We conducted a qualitative study including in-depth interviews via online video conferencing with physicians practicing in emergency departments across the United States. Participants were selected based on purposive sampling methods. Data analysis followed inductive strategies, conducted by two researchers. The codebook and findings were discussed within the research team. FINDINGS: Sixteen in-depth interviews with physicians from nine states across the US were conducted. The participants' specialties include emergency medicine (EM), pediatric EM, and toxicology. The experience of treating snakebites ranged from only didactic education to having treated over 100 cases. Emergent themes for this manuscript from the interview data included perceptions of antivenom, willingness to administer antivenom and influencing factors to antivenom usage. Overall, cost-related concerns were a major barrier to antivenom administration, especially in cases where the indications and effectiveness did not clearly outweigh the potential financial burden on the patient in non-life- or limb-threatening cases. The potential to decrease recovery time and long-term functional impairments was not commonly reported by participants as an indication for antivenom. In addition, level of exposure and perceived competence, based on prior education and clinical experience, further impacted the decision to treat. Resources such as Poison Center Call lines were well received and commonly used to guide the treatment plan. The need for better clinical guidelines and updated treatment algorithms with clinical and measurable indicators was stated to help the decision-making process, especially among those with low exposure to snake envenomation patients. CONCLUSIONS: A major barrier to physician use of antivenom is a concern about cost, cost transparency and cost-benefit for the patients. Those concerns, in addition to the varying degrees of awareness of potential long-term benefits, further influence inconsistent clinical treatment practices.

Evaluation of Protection by Caffeic Acid, Chlorogenic Acid, Quercetin and Tannic Acid against the In Vitro Neurotoxicity and In Vivo Lethality of Crotalus durissus terrificus (South American Rattlesnake) Venom.

Systemic envenomation by Crotalus durissus terrificus (South American rattlesnake) can cause coagulopathy, rabdomyolysis, acute kidney injury, and peripheral neuromuscular blockade, the latter resulting in flaccid paralysis. Previous studies have shown that plant products such as tannic acid and theaflavin can protect against the neuromuscular blockade caused by C. d. terrificus venom in vitro. In this work, we used mouse-isolated phrenic nerve-diaphragm preparations to examine the ability of caffeic acid, chlorogenic acid, and quercetin to protect against C. d. terrificus venom-induced neuromuscular blockade in vitro. In addition, the ability of tannic acid to protect against the systemic effects of severe envenomation was assessed in rats. Preincubation of venom with caffeic acid (0.5 mg/mL), chlorogenic acid (1 mg/mL), or quercetin (0.5 mg/mL) failed to protect against venom (10 µg/mL)-induced neuromuscular blockade. In rats, venom (6 mg kg-1, i.p.) caused death in ~8 h, which was prevented by preincubation of venom with tannic acid or the administration of antivenom 2 h post-venom, whereas tannic acid given 2 h post-venom prolonged survival (~18.5 h) but did not prevent death. Tannic acid (in preincubation protocols or given 2 h post-venom) had a variable effect on blood creatinine and urea and blood/urine protein levels and prevented venom-induced leukocytosis. Tannic acid attenuated the histological lesions associated with renal damage in a manner similar to antivenom. The protective effect of tannic acid appeared to be mediated by interaction with venom proteins, as assessed by SDS-PAGE. These findings suggest that tannic acid could be a potentially useful ancillary treatment for envenomation by C. d. terrificus.

Observation of Bothrops atrox Snake Envenoming Blister Formation from Five Patients: Pathophysiological Insights.

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds.

Case Report: Anaphylactoid Shock Associated with Snakebite Envenoming in Portugal.

Although rare in Portugal, snakebite envenoming entails severe morbidity and mortality. We present the case of a 65-year-old woman bitten on her leg in a northern coastal region in Portugal, on a walk during the COVID-19 pandemic lockdown. Despite first looking for help at the nearest pharmacy, she developed anaphylactoid shock and was promptly driven to a tertiary hospital, where antivenom was administered in a timely manner under close monitoring. Prophylactic antibiotics were started and maintained based on elevated inflammatory markers and signs of wound inflammation. She evolved favorably, with rapid weaning of vasopressors and resolution of end-organ dysfunction. This case highlights the importance of prompt recognition and describes crucial steps in envenomation management in a country where snakebite is infrequent, but potentially fatal.

Investigating myotoxicity following Australian red-bellied black snake (Pseudechis porphyriacus) envenomation.

BACKGROUND: Myotoxicity is one of the common clinical manifestations of red-bellied black snake (Pseudechis porphyriacus) envenomation characterised by elevated creatine kinase (CK) concentrations of greater than 1000 U/L. This study aimed to investigate the occurrence of myotoxicity in patients following envenomation. METHODS/PRINCIPAL FINDINGS: Patient characteristics and serial blood samples (timed venom concentrations and CK concentrations, pre- and post- antivenom) from 114 patients (median age 41, 2-90y; 80 male) were extracted from the Australian Snakebite Project database. Patients were categorised into three groups based on peak CK concentrations [no myotoxicity (<1000 U/L), mild (1000-10,000 U/L) and severe (>10,000 U/L)]. The odds of (mild or severe) myotoxicity was lower in patients that received early antivenom (within 6 hours post-bite) compared to those that received late or no antivenom (odd ratio was 0.186; 95% confidence interval, 0.052-0.664). A population pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the relationship between the time course of venom (a mixture of toxins) and effect (elevated CK). In addition, a kinetic-pharmacodynamic (KPD) model was developed to describe the relationship between time course of a theoretical toxin and effect. Model development and parameter estimation was performed using NONMEM v7.3. No single set of parameter values from either the PKPD or KPD models were found that could accurately describe the time course of different levels of severity of myotoxicity. The predicted theoretical toxin half-life from the KPD model was 11 ± 3.9 hours compared to the half-life of venom of 5.3 ± 0.36 hours. This indicates that the putative causative toxin's concentration-time profile does not parallel that of venom. CONCLUSION: Early antivenom administration reduces the incidence of myotoxicity. The venom concentration profile does not appear to be the driver for myotoxicity following envenomation. Additional factors that affect the sensitivity of the patient to snake venom/toxins must be explored to understand the relationship with myotoxicity.

How beliefs in traditional healers impact on the use of allopathic medicine: In the case of indigenous snakebite in Eswatini.

Snakebite is a major public health problem in Eswatini and serious envenomations can be responsible for considerable morbidity and mortality if not treated correctly. Antivenom should be administered in hospital in case of adverse reactions and any delays due to distance, transport, costs, antivenom availability and cultural beliefs can be critical. Myths and superstition surround snakes, with illness from snakebite considered a supernatural phenomenon best treated by traditional medicine since healers can explore causes through communication with the ancestors. Traditional consultations can cause significant delays and the remedies may cause further complications. Four rural focus group discussions were held in varying geographical regions to establish why people may choose traditional medicine following snakebite. The study revealed four themes, with no apparent gender bias. These were 'beliefs and traditions', 'logistical issues', 'lack of knowledge' and 'parallel systems'. All snakes are feared, regardless of geographical variations in species distribution. Deep-seated cultural beliefs were the most important reason for choosing traditional medicine, the success of which is largely attributed to the 'placebo effect' and positive expectations. Collaboration and integration of the allopathic and traditional systems assisted by the regulation of healers and their methods could improve future treatment success. The plight of victims could be further improved with more education, lower costs and improved allopathic facilities.

Development of a Broad-Spectrum Antiserum against Cobra Venoms Using Recombinant Three-Finger Toxins.

Three-finger toxins (3FTXs) are the most clinically relevant components in cobra (genus Naja) venoms. Administration of the antivenom is the recommended treatment for the snakebite envenomings, while the efficacy to cross-neutralize the different cobra species is typically limited, which is presumably due to intra-specific variation of the 3FTXs composition in cobra venoms. Targeting the clinically relevant venom components has been considered as an important factor for novel antivenom design. Here, we used the recombinant type of long-chain α-neurotoxins (P01391), short-chain α-neurotoxins (P60770), and cardiotoxin A3 (P60301) to generate a new immunogen formulation and investigated the potency of the resulting antiserum against the venom lethality of three medially important cobras in Asia, including the Thai monocled cobra (Naja kaouthia), the Taiwan cobra (Naja atra), and the Thai spitting cobra (Naja Siamensis) snake species. With the fusion of protein disulfide isomerase and the low-temperature settings, the correct disulfide bonds were built on these recombinant 3FTXs (r3FTXs), which were confirmed by the circular dichroism spectra and tandem mass spectrometry. Immunization with r3FTX was able to induce the specific antibody response to the native 3FTXs in cobra venoms. Furthermore, the horse and rabbit antiserum raised by the r3FTX mixture is able to neutralize the venom lethality of the selected three medically important cobras. Thus, the study demonstrated that the r3FTXs are potential immunogens in the development of novel antivenom with broad neutralization activity for the therapeutic treatment of victims involving cobra snakes in countries.

The Snake Study: Survey of National Attitudes and Knowledge in Envenomation.

Despite recent reviews of best practice for the treatment of Australian venomous bites and stings, there is controversy about some aspects of care, particularly the use of antivenom. Our aim was to understand current attitudes and practice in the management of suspected snake envenoming. A single-stage, cross-sectional survey of Australian emergency care physicians who had treated snake envenomation in the previous 36 months was conducted. Hospital pharmacists were also invited to complete a survey about antivenom availability, usage, and wastage in Australian hospitals. The survey was available between 5 March and 16 June 2019. A total of 121 snake envenoming cases were reported, and more than a third (44.6%) of patients were not treated with antivenom. For those treated with antivenom (n = 67), 29 patients (43%) received more than one ampoule. Nearly a quarter of respondents (21%) identified that antivenom availability was, or could be, a barrier to manage snake envenoming, while cost was identified as the least important factor. Adverse reactions following antivenom use were described in 11.9% of cases (n = 8). The majority of patients with suspected envenoming did not receive antivenom. We noted variation in dosage, sources of information, beliefs, and approaches to the care of the envenomed patient.

Case Report: Treatment of a Severe Puff Adder Snakebite Without Antivenom Administration.

Antivenoms are the treatment of choice for managing lethal snakebites. However, antivenoms may not be available in instances where non-native vipers are kept in captivity. We report a case of a puff adder (Bitis arietans) bite treated without antivenom. A 23-year-old man was bitten on his left hand by a puff adder that he illegally kept in his house. The swelling spread rapidly to the upper arm and there was a risk of bleeding, suggesting the need for antivenom administration, but this could not be acquired because of lack of stock. We initiated fluid resuscitation and administered recombinant thrombomodulin (rTM) to prevent venom-induced consumption coagulopathy. In addition, hyperbaric oxygen (HBO) treatment was also performed to reduce local swelling. The patient recovered without complications after the multidisciplinary treatment. Further studies are needed to prove the safety and efficacy of rTM administration and HBO therapy as an adjunct or alternative therapy with antiserum for fatal snakebite.

Awareness of the Standard of Care for Snakebite Management Among Physicians in Kerala: A Cross-sectional Study.

Snakebite remains a largely neglected yet important cause of morbidity as well as mortality in Kerala. This study aimed to assess the knowledge about the standard of care for snakebite management among physicians in Kerala. This was a cross-sectional study using a questionnaire-based survey among 110 physicians from Kerala. The overall knowledge levels were assessed using a questionnaire with answers being scored as 0 for wrong answers and as 1 for correct answers. The total knowledge scores for all respondents were calculated, with a maximum possible score of 14 and a minimum possible score of 0. Comparisons were made between subsets of respondents. The questionnaire was administered to 110 physicians who fulfilled the predetermined criteria. The overall mean knowledge score during the study was 10.7 (standard deviation ± 2.9). However, there were certain pitfalls associated with the management of snakebite. In particular, questions about tourniquet use, bringing a dead snake to the physician, and the anti-snake venom test dose had high proportions of incorrect answers. Significantly higher knowledge levels were also observed in certain subgroups. There seems to be varying knowledge gaps associated with various aspects of snakebite management for certain subsets of respondents who are likely to benefit from specific training.

Health and economic burden estimates of snakebite management upon health facilities in three regions of southern Burkina Faso.

BACKGROUND: Snakebite has become better recognized as a significant cause of death and disability in Sub-Saharan Africa, but the health economic consequences to victims and health infrastructures serving them remain poorly understood. This information gap is important as it provides an evidence-base guiding national and international health policy decision making on the most cost-effective interventions to better manage snakebite. Here, we assessed hospital-based data to estimate the health economic burden of snakebite in three regions of Burkina Faso (Centre-Ouest, Hauts Bassins and Sud-Ouest). METHODOLOGY: Primary data of snakebite victims admitted to regional and district health facilities (eg, number of admissions, mortality, hospital bed days occupied) was collected in three regions over 17 months in 2013/14. The health burden of snakebite was assessed using Disability-Adjusted Life Years (DALYs) calculations based upon hospitalisation, mortality and disability data from admitted patients amongst other inputs from secondary sources (eg, populations, life-expectancy and age-weighting constants). An activity-based costing approach to determine the direct cost of snake envenoming included unit costs of clinical staff wages, antivenom, supportive care and equipment extracted from context-relevant literature. FINDINGS: The 10,165 snakebite victims admitted to hospital occupied 28,164 hospital bed days over 17 months. The annual rate of hospitalisation and mortality of admitted snakebite victims was 173 and 1.39/100,000 population, respectively. The estimated annual (i) DALYs lost was 2,153 (0.52/1,000) and (ii) cost to hospitals was USD 506,413 (USD 49/hospitalisation) in these three regions of Burkina Faso. These costs appeared to be influenced by the number of patients receiving antivenom (10.90% in total) in each area (highest in Sud-Ouest) and the type of health facility. CONCLUSION: The economic burden of snake envenoming is primarily shouldered by the rural health centres closest to snakebite victims-facilities that are typically least well equipped or resourced to manage this burden. Our study highlights the need for more research in other regions/countries to demonstrate the burden of snakebite and the socioeconomic benefits of its management. This evidence can guide the most cost-effective intervention from government and development partners to meet the snakebite-management needs of rural communities and their health centres.

Acute Exposure to European Viper Bite in Children: Advocating for a Pediatric Approach.

Viper bite is an uncommon but serious cause of envenoming in Europe, especially in children. Our study aim is to better describe and analyze the clinical course and treatment of viper bite envenoming in a pediatric population. We retrospectively reviewed 24 cases of pediatric viper bites that were admitted to the Pediatric Emergency Department and the Pediatric Intensive Care Unit of the Bambino Gesù Children Hospital in Rome between 2000 and 2020. Epidemiological characteristics of the children, localization of the bite, clinical and laboratory findings, and treatment approaches were evaluated. The median age of the patients was 4.2 years, with male predominance. Most cases of viper bite occurred in the late summer. Most patients required admission to the ward for prolonged observation. The most common presenting signs were pain, local oedema, and swelling. Patients with a high severity score also had a significantly higher white blood cell count and an increase of INR, LDH, and CRP levels. No fatality was reported. Viper bite envenomation is a rare pediatric medical emergency in Italy but may sometimes be severe. A new pediatric severity score may be implemented in the screening of children with viper bites to favor a selective and prompt administration of antivenom.

Influential Factors of Local Tissue Necrosis after Taiwan Cobra Bites: A Secondary Analysis of the Clinical Significance of Venom Detection in Patients of Cobra Snakebites.

Local tissue swelling, inflammation, and wound necrosis are observed in Taiwan cobra bites. Knowledge of the factors influencing local tissue necrosis after cobra bites might improve the cobra bite treatment strategy. Therefore, we aimed to explore the factors influencing local tissue necrosis after cobra bites. This was a retrospective observational cohort study. All patients clinical presentations including serum venom levels for determining the influential factors in this study were obtained from Hung et al.'s previous study. Clinical features, such as bite information, initial swelling, patient presentation time, serum venom levels, and antivenom, use were extracted. The measurement outcome was the development of wound necrosis. The factors influencing wound necrosis were investigated using univariate and logistic regression analyses. The influential factors of local tissue necrosis and their areas under the curve were: initial limb swelling, 0.88; presentation time × serum level, 0.80; initial necrosis, 0.75; patient presentation time, 0.70. Serum venom level alone cannot be used as a predictive factor. The development of tissue necrosis might be associated with the venom factor, time factor, and their interaction. These influential factors can be used in future studies to evaluate antivenom efficacy.

Pediatric Snakebites: Comparing Patients in Two Geographic Locations in the United States.

BACKGROUND: Management of children with snakebites may vary based on subjective criteria, geographic, and climatic factors. We reviewed the incidence and management of snakebite injuries in children at two tertiary referral centers in separate geographic and climatic location to assess differences in management and outcomes of these patients. METHODS: After institutional review board approval, a retrospective chart review was performed for patients ≤18 years with snakebite injuries at emergency departments (ED) of two American College of Surgeons verified trauma centers (2006-2013). One center is in southeast US and experiences a sub-tropical climate whereas the other is in southwest US and experiences a semi-arid climate. Demographic and clinical parameters were extracted. RESULTS: A total of 108 patients (59% male), median age of 9 y (1 y-17 y), were included. Snake type was identified by bystanders in 55.5% cases; copperhead was the most common (37%) subtype. Approximately 30% of patients received antivenom. One quarter of all patients were discharged from the ED. Two patients received surgical intervention in the first 48 hours after presentation. Compared to patients who sustained a snakebite in semi-tropical regions, patients in semi-arid areas had shorter bite-to-ED time, presented directly to the referral center, were more frequently bitten by a rattlesnake, had longer lengths of hospital stay, required antivenom more frequently and at higher doses, and were more frequently admitted to the ICU. No differences were seen in gender, age at presentation, severity of wound, location of bite, abnormalities in coagulation profile or rate of admission to hospital amongst the two sites. CONCLUSIONS: Patients sustaining snakebites in semi-arid climates were more commonly exposed to dangerous snake types, resulting in higher antivenom requirement, as well as longer hospital stays and need for intensive monitoring. Although no fatalities were reported in our study, our data supports early transfer of snakebite victims to higher levels of care, especially in semi-arid or high-risk areas.

Single-Arm, Multicenter Phase I/II Clinical Trial for the Treatment of Envenomings by Massive Africanized Honey Bee Stings Using the Unique Apilic Antivenom.

We evaluated the safety, optimal dose, and preliminary effectiveness of a new-approach Africanized honeybee (Apis mellifera) Antivenom (AAV) in a phase I/II, multicenter, non-randomized, single-arm clinical trial involving 20 participants with multiple stings. Participants received 2 to 10 vials of AAV depending on the number of stings they suffered, or a predefined adjuvant, symptomatic, and complementary treatment. The primary safety endpoint was the occurrence of early adverse reactions within the first 24 h of treatment. Preliminary efficacy based on clinical evolution, including laboratory findings, was assessed at baseline and at various time points over the four following weeks. ELISA assays and mass spectrometry were used to estimate venom pharmacokinetics before, during, and after treatment. Twenty adult participants, i.e., 13 (65%) men and 7 (35%) women, with a median age of 44 years and a mean body surface area of 1.92 m2 (median = 1.93 m2) were recruited. The number of stings ranged from 7 to > 2,000, with a median of 52.5. Symptoms of envenoming were classified as mild, moderate, or severe in 80% (16), 15% (3), and 5% (1) of patients, respectively; patients with mild, moderate, or severe envenoming received 2, 6, and 10 vials of AAV as per the protocol. None of the patients had late reactions (serum sickness) within 30 d of treatment. There was no discontinuation of the protocol due to adverse events, and there were no serious adverse events. One patient had a moderate adverse event, transient itchy skin, and erythroderma. All participants completed the intravenous antivenom infusion within 2 h, and there was no loss to follow-up after discharge. ELISA assays showed venom (melittin and PLA2) concentrations varying between 0.25 and 1.479 ng/mL prior to treatment. Venom levels decreased in all patients during the hospitalization period. Surprisingly, in nine cases (45%), despite clinical recovery and the absence of symptoms, venom levels increased again during outpatient care 10 d after discharge. Mass spectrometry showed melittin in eight participants, 30 d after treatment. Considering the promising safety results for this investigational product in the treatment of massive Africanized honeybee attack, and its efficacy, reflected in the clinical improvements and corresponding immediate decrease in blood venom levels, the AAV has shown to be safe for human use. Clinical Trial Registration: UTN: U1111-1160-7011, identifier [RBR-3fthf8].

Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients.

Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab')2 fragments (European viper venom antiserum, also called "Zagreb" antivenom) in V.ammodytes-envenomed patients. This was a prospective study of V.ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab')2 fragments that were given intramuscularly only on admission. F(ab')2 fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 h, respectively). In V.ammodytes-envenomed patients, the intramuscular use of specific F(ab')2 fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented.

Population pharmacokinetics of Pseudechis porphyriacus (red-bellied black snake) venom in snakebite patients.

OBJECTIVES: Understanding the time course of venom exposure in snakebite patients is important for the optimisation of treatment including antivenom dose and timing. We aimed to investigate the pharmacokinetics of red-bellied black snake (RBBS; Pseudechis porphyriacus) venom in envenomed patients. METHODS: Timed venom concentration data were obtained from patients with RBBS envenomation recruited to the Australian Snakebite Project (ASP), including demographics and antivenom treatment. Venom concentrations were measured using an enzyme immunoassay. Data were modelled using NONMEM version 7.3. Uncertainty in venom "dose" was accounted for by arbitrarily fixing the average amount to 1 mg and incorporating between-subject variability on relative bioavailability. A scale parameter for venom clearance was implemented to account for the rapid venom clearance following antivenom dosing. A sensitivity analysis was performed to determine the magnitude of venom clearance amplification. RESULTS: There were 457 venom concentrations in 114 patients (median age 41, 2-90 y; 80 male). Antivenom was administered to 54 patients a median of 4.2 h post-bite (0.67 to 32 h). A one-compartment model with first-order absorption and elimination provided the best description of the data. The estimated clearance and volume of distribution were 5.21 L/h and 39.9 L, respectively. The calculated elimination half-life of P. porphyriacus venom from the final pharmacokinetic model was 5.35 ± 0.36 h. The variability in the relative dose of injected venom was 140%. Antivenom administration increased venom clearance by 40-fold. Ten patients showed evidence of a double peak in the absorption profile. CONCLUSION: The information on the exposure time of venom in the body following envenomation will help improve treatment and the timing of antivenom.

Evaluation of Allergic Reactions Following Intravenous Infusion of Polyvalent Antivenom in Snakebite Patients.

BACKGROUND: Antivenom is a gold-standard treatment for snakebite envenoming. However, adverse reactions to snake antivenom are common in many parts. OBJECTIVE: The aim of this study was to evaluate the allergic reactions following intravenous administration of antivenom sera. METHODS: This was retrospective study conducted on snakebites patients referred to the Rahimi Hospital in Khorramabad. The files of these patients were accessed for demographic data, snakebite-related data, treatment provided, clinical presentation and allergic reaction status as a result of antivenom treatment. RESULTS: 141 cases were investigated, including 73.8% male and 26.2% female patients. The mean age of the patients was 38.1±17.1 years. Age group 30-39 years accounted for the highest number of snakebite cases (24.1%). A majority of victims (89.4%) were from rural areas. Most of the patients (51.8%) were bitten in the spring and highest number of snakebite were reported in May (39.1%). The most common site of snakebite was lower extremities (50.4%) and upper extremities (44.7%). Among clinical feature of snakebite, pain was the most prevalent in 135 cases (95.7%) followed by swelling (83.7%). The mean antivenom vials used were 6.5±3.7 vials. Allergic reactions occurred in 6 patients (4.26%); reactions were mild in 5 patients and severe in 1 patient. The commonest presentation was maculopapular rash (1.4%) and the least common were headache (0.71%), nausea (0.71%), fever (0.71) and hypotension (0.71%). CONCLUSION: Snakebite is one of the significant life-threatening environmental events. Immediate antivenom treatment can reduce mortality however, patients should be carefully monitored for adverse allergic reactions.

Health professionals' overestimation of knowledge on snakebite management, a threat to the survival of snakebite victims-A cross-sectional study in Ghana.

BACKGROUND: According to the World Health Organization, snakebites, a common occupational hazard in developing countries accounts for an annual loss of between 81,000 and 138, 000 lives following 5 million bites of which 2.7 million results in envenomation. Since snakebite-associated morbidity and mortality are more prevalent in agricultural economies such as Ghana, health professionals should be optimally knowledgeable on how to manage the incidence of snakebites. Lack of knowledge or overestimation of a professional's knowledge can affect heath delivery especially for emergencies such as snakebites. The three rurally situated Tongu districts in South-Eastern Ghana with agriculture as the major source of livelihood for their inhabitants, are prone to snakebites. This study, therefore, brings up the need to assess whether the health professionals in these districts are well-equipped knowledge-wise to handle such emergencies and whether they can rightly estimate their knowledge with regards to snakebite management. METHODOLOGY/PRINCIPAL FINDINGS: Data was collected using a de novo semi-structured questionnaire administered through google form whose link was sent via WhatsApp to 186 health workers made up of nurses, midwives, physician assistants, medical doctors, pharmacists, and pharmacy technicians. This data was analyzed using Statistical Package for the Social Sciences (SPSS) Version 25. Association between variables was determined using the appropriate tools where necessary, using a confidence interval of 95% and significance assumed when p ≤ 0.05. This study found male health workers significantly more knowledgeable about snakebite management (11.53±5.67 vs 9.64±5.46; p = 0.022) but it was the females who overestimated their knowledge level (27.9% vs 24.1%). The medical doctors exhibited the best knowledge on snakebite management with the registered general nurses least knowledgeable. Although most professionals overestimated their knowledge, the registered general nurses were the worst at that (53.7%). Overall knowledge of health care professionals on snakebite management was below average [10.60±5.62/22 (48.2%)] but previous in-service training and involvement in the management of snakebite were associated with better knowledge. Respondents who had no previous training overestimated their knowledge level compared to those who had some post-qualification training on snakebite management (38.1% vs 7.5%). The greatest knowledge deficit of respondents was on the management of ASV associated adverse reactions. CONCLUSION: Health workers in rural Ghana overestimated their knowledge about snakebite management although their knowledge was low. Training schools, therefore, need to incorporate snakebite management in their curriculum and health authorities should also expose health workers to more in-service training on this neglected tropical disease.