Snakebite Management: The Need of Reassessment, International Relations, and Effective Economic Measures to Reduce the Considerable SBE Burden.

The sole treatment for snakebite envenomation (SBE), the anti-snake venom (ASV), suffers from considerable drawbacks, including side effects and limited species specificity. Additionally, despite its existence for more than a century, uniform availability of good quality ASV does not yet exist. The present review describes the journey of a SBE victim and highlights the global crisis of SBE management. A detailed analysis of the current ASV market has also been presented along with the worldwide snake distribution. The current production of country specific licensed ASV throughout the globe along with their manufacturers has been examined at the snake species level. Furthermore, a detailed analysis of on-ground situation of SBE management in antivenom manufacturing countries has been done using the most recent literature. Additionally, the export and import of different ASVs have been discussed in terms of procurement policies of individual countries, their shortcomings, along with the possible solution at the species level. It is interesting to note that in most countries, the existence of ASV is really either neglected or overstated, implying that it is there but unsuitable for use, or that it is not present but can be obtained from other countries. This highlights the urgent need of significant reassessment and international collaborations not just for development and production, but also for procurement, distribution, availability, and awareness. A PROMISE (Practical ROutes for Managing Indigenous Snakebite Envenoming) approach has also been introduced, offering simple, economical, and easy to adopt steps to efficiently alleviate the worldwide SBE burden.

A Nationwide Study on the Risks of Complications and Healthcare Costs of Snakebite Envenomation in Taiwan.

In Taiwan, six medically important venomous snakes, Trimeresurus stejnegeri stejnegeri, Protobothrops mucrosquamatus, Deinagkistrodon acutus, Daboia siamensis, Naja atra, and Bungarus multicinctus, are found. However, comprehensive research on the complications and associated healthcare costs of snakebite envenomation (SBE) is lacking. We retrospectively analyzed pertinent information from the Taiwan National Health Insurance Research Database dated January 2002 to December 2014. We investigated the risk factors for complications and their impact on healthcare costs. Among the 12,542 patients with SBE, those from N. atra or B. multicinctus were more likely to experience wound infections and neurological complications than were those from T. s. stejnegeri or P. mucrosquamatus. In addition, being female, being elderly, and having a Charlson Comorbidity Index equal to or greater than 3 points were associated with an increased likelihood of wound infections and psychological complications. The annual national economic burden averaged US$1,083,624, with an average healthcare cost of US$1,129 per SBE. Snakebite envenomations from N. atra or B. multicinctus, as well as various complications, resulted in significantly higher costs. It is crucial to comprehend the risk factors for complications and their role in increasing expenses to provide insight for tailored healthcare interventions, mitigate complications, and reduce the economic burdens associated with SBEs.

Use of Thromboelastography in Assessment of Snake Bite Coagulopathy.

Background: Monitoring for envenomation coagulopathy following snake bites has traditionally involved using serial coagulation studies.Purpose: Thromboelastography (TEG), with its real-time assessment, could offer an alternative to standard of care. This study aims to evaluate the use of TEG with traditional coagulation labs in the assessment of snake bite coagulopathy.Research Design: A retrospective review of patients who presented to a level 1 trauma center between 2014 and 2020 with snake bite envenomation was conducted, comparing traditional coagulation studies to TEG plus coagulation studies.Results: The 12 patients who had studies within the stipulations of our review were tracked and subsequently progressed well clinically with no adverse effects and ultimately discharged home with an average hospital stay of 2.2 days.Conclusions: Our data suggests that patients can be observed clinically without needing repeat coagulation studies if initial TEG and TCS are within normal limits.

"I sold my towel and shoes to pay the traditional healer": Care-seeking costs and productivity losses among snakebite victims in Eastern Province, Rwanda.

Snakebite envenomation (SBE) is endemic to sub-Saharan Africa and generally over-represented in rural, remote, and impoverished agricultural communities. While poverty is an established risk factor, little research has been done to investigate the economic consequences of SBE. This cross-sectional, quantitative study aimed to measure out-of-pocket spending and lost income when a household member was bitten by a snake. In 2020, 732 snakebite survivors from Eastern Province (Rwanda) agreed to complete a survey administered by telephone. The survey focused on participant demographics, income, direct medical and non-medical costs, care-seeking decisions, and lost work during convalescence. Our results suggested that patients incurred the highest mean expenses when they sought care from hospitals (11 307 RWF or 12 USD) or traditional healers (5 836 RWF or 6 USD) but that the highest maximum cost was incurred from traditional healers (300 000 RWF or 313 USD). Across all victims, the total amount paid to traditional healers (3.4 million RWF or 3 537 USD) was 4.7 times higher than all other care providers combined. On average, families lost 111 814 RWF (117 USD) per snakebite in direct treatment costs and indirect productivity losses. Many victims sought care from traditional healers despite being eligible for free medical care. Altogether, this study serves as a reminder of the serious physical and financial consequences associated with SBE and provides justification for new investments into SBE prevention and care.

Snakebites in Northeastern Brazil: accessing clinical-epidemiological profile as a strategy to deal with Neglected Tropical Diseases.

BACKGROUND: Brazil ranks first in the number of snakebites in South America. A detailed analysis of these cases is required to improve the public health planning. In this study, we retrospectively examined the clinical and epidemiological profiles of snakebites in Maranhão between January 2009 and December 2019. METHODS: Data were obtained from the compulsory notification forms provided by the Health Department of Maranhão. RESULTS: A total of 17,658 cases were recorded during the study period. Most of the bites were from snakes belonging to the genus Bothrops. Medical care was mostly within three hours after the bite. Most cases were classified as mild and most victims recovered; however, 139 deaths were recorded. Most bites occurred among people aged 20-39 years, mainly among rural workers. The most frequent local clinical manifestations were pain, edema, and ecchymosis. The most common systemic clinical manifestations include neuroparalysis, vagal syndrome, and myolysis. Most snakebites occurred between January and March. The municipalities with the highest number of notifications were Buriticupu (936 cases), Arame (705 cases), and Grajaú (627 cases). CONCLUSIONS: The clinical profile of snakebites in Maranhão is similar to that observed in other states of Northeast Brazil. However, we found that some systemic manifestations are not compatible with the etiology of snakebites, which leads us to believe that the problem could be the lack of knowledge of the health professionals at the site of envenomation, who may not be ready for attendance, and an important lack of health centers with snake antivenom to treat snakebites.

Identifying key factors contributing to treatment costs for snakebite envenoming in private tertiary healthcare settings in Tamil Nadu, India.

BACKGROUND: India suffers ~58,000 annual deaths due to snakebites. The 'Big Four' snakes (Russell's viper, Indian cobra, common krait, and saw-scaled viper) that are responsible for most bites cause diverse clinical effects. Delayed treatment increases the risk of serious complications and treatment costs. Although government hospitals offer free treatment for snakebites in India, most patients opt for private healthcare, which is an out-of-pocket expense as they often lack health insurance coverage. This study aims to analyse snakebite treatment costs in private tertiary care hospitals in Tamil Nadu, India and identifies the key factors contributing to treatment costs. METHODOLOGY/PRINCIPAL FINDINGS: The treatment cost details for 913 snakebite victims were collected from 10 private tertiary care hospitals across Tamil Nadu. The data were classified into hospital, pharmacy, investigation, and laboratory costs, and analysed to determine various factors that contribute to the costs. The results demonstrate that the average treatment costs vary widely for different snakes. The hospital and pharmacy costs are higher than investigation and laboratory costs for all snakebites. Notably, Russell's viper bites cost significantly more than the bites from other snakes. Overall, the type of snake, nature of complications, specialist treatments required, and arrival time to hospitals were identified as some of the key factors for higher treatment costs. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that ~80% of snakebite patients can be treated with INR 100,000 (~GBP 1000 or USD 1200) or less. This study emphasises the urgent need to improve rural medical care by providing appropriate training for healthcare professionals and essential resources to facilitate early assessment of patients, administer the initial dose of antivenom and refer the patients to tertiary care only when needed. Moreover, the outcome of this study forms a basis for developing appropriate policies to regulate snakebite treatment costs and provide affordable medical insurance for vulnerable communities.

Barriers and opportunities for improving management of snakebites: Perspectives of healthcare workers in Northern Uganda.

BACKGROUND: Snakebites are a neglected public health problem that pose a significant burden on affected individuals and communities in many sub-Saharan African countries, including Uganda. However, the barriers and facilitators to snakebite management within healthcare settings are not as well understood and well-documented. The aim of this study was to explore the experiences and perspectives of healthcare workers involved in handling snakebite incidents at individual and health system levels in Arua and Gulu districts in Northern Uganda. We sought to understand how healthcare workers manage snakebite cases, what challenges they encounter, and what opportunities they perceive for improvement. METHODS: We conducted a qualitative study using in-depth interviews with 18 healthcare workers from different cadres, seniority levels, and facility types. We used iterative thematic analysis to explore the management procedures, challenges, and opportunities for snakebite management. Using thematic analysis, we identified the overarching themes and subthemes related to snakebite management and associated barriers and opportunities. RESULTS: The main barriers to snakebite management identified by healthcare workers were inadequate knowledge and skills; limited availability of antivenom; lack of protocols for snakebite management; delayed treatment-seeking for patients; and poor referral systems. The main opportunities for improvement were regular in-service training; increasing public education and awareness about snakebite prevention and management; and increased funding and research. CONCLUSION: This study highlights the need for interventions to address the identified barriers while leveraging the existing opportunities to enhance snakebite management in Uganda. Specifically, we recommend the provision of regular training and support to healthcare workers, developing clinical guidelines, and improving the availability of antivenoms.

Development of a high-throughput in vitro screening method for the assessment of cell-damaging activities of snake venoms.

Snakebite envenoming is a globally important public health issue that has devastating consequences on human health and well-being, with annual mortality rates between 81,000 and 138,000. Snake venoms may cause different pathological effects by altering normal physiological processes such as nervous transfer and blood coagulation. In addition, snake venoms can cause severe (local) tissue damage that may result in life-long morbidities, with current estimates pointing towards an additional 450,000 individuals that suffer from permanent disabilities such as amputations, contractions and blindness. Despite such high morbidity rates, research to date has been mainly focusing on neurotoxic and haemotoxic effects of snake venoms and considerably less on venom-induced tissue damage. The molecular mechanisms underlaying this pathology include membrane disruption and extracellular matrix degradation. This research describes methods used to study the (molecular) mechanisms underlaying venom-induced cell- and tissue damage. A selection of cellular bioassays and fluorescent microscopy were used to study cell-damaging activities of snake venoms in multi-well plates, using both crude and fractionated venoms. A panel of 10 representative medically relevant snake species was used, which cover a large part of the geographical regions most heavily affected by snakebite. The study comprises both morphological data as well as quantitative data on cell metabolism and viability, which were measured over time. Based on this data, a distinction could be made in the ways by which viper and elapid venoms exert their effects on cells. We further made an effort to characterise the bioactive compounds causing these effects, using a combination of liquid chromatography methods followed by bioassaying and protein identification using proteomics. The outcomes of this study might prove valuable for better understanding venom-induced cell- and tissue-damaging pathologies and could be used in the process of developing and improving snakebite treatments.

Structural capacity and continuum of snakebite care in the primary health care system in India: a cross-sectional assessment.

BACKGROUND: In 2019, the World Health Organization, set a target to halve the burden of snakebite, by 2030, and identified 'health systems strengthening' as a key pillar of action. In India, the country with most snakebite deaths, the Union Government identified (in September 2022) training of health workers as a priority action area. In this policy context, we provide empirical evidence by analysing the most recent nationwide survey data (District Level Household and Facility Survey - 4), to assess structural capacity and continuum of snakebite care in primary health care system in India. METHODOLOGY: We evaluated structural capacity for snakebite care under six domains: medicines, equipment, infrastructure, human resources, governance and finance, and health management information systems (HMIS). We categorised states (aspirant, performer, front-runner, achiever) based on the proportion of primary health centres (PHC) and community health centres (CHC), attaining highest possible domain score. We assessed continuum of snakebite care, district-wise, under five domains (connectivity to PHC, structural capacity of PHC, referral from PHC to higher facility, structural capacity of CHC, referral from CHC to higher facility) as adequate or not. RESULTS: No state excelled ( front-runner or achiever) in all six domains of structural capacity in PHCs or CHCs. The broader domains (physical infrastructure, human resources for health, HMIS) were weaker compared to snakebite care medicines in most states/UTs, at both PHC and CHC levels. CHCs faced greater concerns regarding human resources and equipment availability than PHCs in many states. Among PHCs, physical infrastructure and HMIS were aspirational in all 29 assessed states, while medicines, equipment, human resources, and governance and finance were aspirational in 8 (27.6%), 2 (6.9%), 17 (58.6%), and 12 (41.4%) states respectively. For CHCs, physical infrastructure was aspirational in all 30 assessed states/UTs, whereas HMIS, medicines, equipment, human resources, and governance and finance were aspirational in 29 (96.7%), 11 (36.7%), 27 (90%), 26 (86.7%), and 3 (10%) states respectively. No district had adequate continuum of snakebite care in all domains. Except for transport availability from CHC to higher facilities (48% of districts adequate) and transport availability from PHC to higher facilities (11% of districts adequate), fewer than 2% of districts were adequate in all other domains. CONCLUSION: Comprehensive strengthening of primary health care, across all domains, and throughout the continuum of care, instead of a piece-meal approach towards health systems strengthening, is necessitated to reduce snakebite burden in India, and possibly other high-burden nations with weak health systems. Health facility surveys are necessitated for this purpose.

How and why snakebite became a global health priority: a policy analysis.

BACKGROUND: Snakebite was added to the WHO neglected tropical disease (NTD) list in 2017, followed by a World Health Assembly resolution in 2018, and an explicit global target being set to reduce the burden in 2019. We aimed to understand how and why snakebite became a global health priority. METHODS: We conducted a policy case study, using in-depth interviews, and documents (peer-reviewed and grey literature) as data sources. We drew on Shiffman et al's framework on global health network to guide the analysis. RESULTS: We conducted 20 interviews and examined 91 documents. The prioritisation of snakebite occurred in four phases: pre-crescendo, crescendo, de-crescendo and re-crescendo. The core snakebite network consisted of academics, which expanded during the re-crescendo phase to include civil society organisations and state actors. The involvement of diverse stakeholders led to better understanding of WHO processes. The use of intersecting and layered issue framing, framing solutions around snake antivenoms, in a background of cross-cultural fascination and fear of snakes enabled prioritisation in the re-crescendo phase. Ebbs and flows in legitimacy of the network and reluctant acceptance of snakebite within the NTD community are challenges. CONCLUSION: Our analyses imply a fragile placement of snakebite in the global agenda. We identify two challenges, which needs to be overcome. The study highlights the need to review the WHO criteria for classifying diseases as NTD. We propose that future prioritisation analysis should consider identifying temporal patterns, as well as integrating legitimacy dimensions, as in our study.

Eastern Mediterranean Health Journal [2023; Vol.29, Issue 8]

Eastern Mediterranean Health Journal is the official health journal published by the Eastern Mediterranean Regional Office of the World Health Organization. It is a forum for the presentation and promotion of new policies and initiatives in health services; and for the exchange of ideas concepts epidemiological data research findings and other information with special reference to the Eastern Mediterranean Region. It addresses all members of the health profession medical and other health educational institutes interested NGOs WHO Collaborating Centres and individuals within and outside the Region

المجلة الصحية لشرق المتوسط هى المجلة الرسمية التى تصدرعن المكتب الاقليمى لشرق المتوسط بمنظمة الصحة العالمية. وهى منبر لتقديم السياسات والمبادرات الجديدة فى الصحة العامة والخدمات الصحية والترويج لها، و لتبادل الاراء و المفاهيم والمعطيات الوبائية ونتائج الابحاث وغير ذلك من المعلومات، و خاصة ما يتعلق منها باقليم شرق المتوسط. وهى موجهة الى كل اعضاء المهن الصحية، والكليات الطبية وسائر المعاهد التعليمية، و كذا المنظمات غير الحكومية المعنية، والمراكز المتعاونة مع منظمة الصحة العالمية والافراد المهتمين بالصحة فى الاقليم و خارجه

La Revue de Santé de la Méditerranée Orientale est une revue de santé officielle publiée par le Bureau régional de l’Organisation mondiale de la Santé pour la Méditerranée orientale. Elle offre une tribune pour la présentation et la promotion de nouvelles politiques et initiatives dans le domaine de la santé publique et des services de santé ainsi qu’à l’échange d’idées de concepts de données épidémiologiques de résultats de recherches et d’autres informations se rapportant plus particulièrement à la Région de la Méditerranée orientale. Elle s’adresse à tous les professionnels de la santé aux membres des instituts médicaux et autres instituts de formation médico-sanitaire aux ONG Centres collaborateurs de l’OMS et personnes concernés au sein et hors de la Région

A retrospective analysis of epidemiology, clinical features of envenomation, and in-patient management of snakebites in a model secondary hospital of Assam, North-east India.

Assam, a Northeastern State of India, is inhabited by several venomous snake species causing substantial morbidity and mortality. The data on the epidemiology of snakebites and their management is underreported in this region. Hence, a secondary health-based retrospective study was carried out at Demow Model Hospital, Sivasagar, Assam, to evaluate the clinical and epidemiological profile of snakebite cases reported in this rural hospital and their management. Snakebites occurring between April 2018 to August 2022 were reviewed based on socio-demographic details of the patient, clinical symptoms, and treatment using a standard questionnaire. Out of the 1011 registered snakebite cases, 139 patients (13.7%) counted for venomous bites, among which 92 patients (66.19%) accounted for viper bites (green pit viper and Salazar's pit viper), and 30 patients (21.5%) were bitten by elapid snakes (Indian monocled Cobra, banded krait, and greater/lesser black krait). A maximum number of snakebite cases (80.5%) were reported from the interior rural villages and documented from July to September (51.3%). Elapid snake envenomed patients, except one, were successfully treated with commercial antivenom, neostigmine, and glycopyrrolate. Because commercial polyvalent antivenom against "Big Four" venomous snakes of India showed poor neutralization of pit-vipers envenomation; therefore, pit-viper bite patients were treated with repurposed drugs magnesium sulfate and glycerin compression dressing. Adverse serum reactions were reported only in 3 (11.1%) cases. The preventive measures and facilities adopted at the Demow Model Hospital significantly reduce snakebite death and morbidity; therefore, they can be s practised across various states in India as a prototype.

Recent advancements in snake antivenom production.

Snakebite envenoming (SBE), a neglected tropical disease, claims lives of about 138,000 people globally, and antivenom is the only approved treatment worldwide. However, this century-old therapy has serious limitations, including limited efficacy and some side effects. Although alternative and adjunct therapies are being developed, their commercialization will take time. Hence, improving existing antivenom therapy is crucial for immediate reduction in the global SBE burden. The neutralization potential and immunogenicity of antivenoms depend primarily on the venom pool used for animal immunization and the production host, along with antivenom purification procedure and quality control. Enhancing antivenom quality and production capacity are also critical actions of the World Health Organization (WHO) roadmap 2021 against SBE. The present review details the latest developments in antivenom production, such as immunogen preparation, production host, antibody purification methods, antivenom testing-including alternative animal models, in vitro assays, and proteomics and in silico methodologies, and storage, reported from 2018 to 2022. Based on these reports, we propose that production of broadly specific, affordable, safe, and effective (BASE) antivenoms is fundamental to realizing the WHO roadmap and reducing the global SBE burden. This concept can also be applied during the designing of alternative antivenoms.

Healthcare practitioners' knowledge of snakebite management and associated factors in high-burden, low-resource settings in Uganda.

BACKGROUND: Snakebites cause significant morbidity and mortality in Uganda. Effective management of snakebites requires knowledge of the appropriate first aid measures, as well as knowledge of the appropriate antivenom to use, but little is known about familiarity with effective snakebite management techniques and associated factors among healthcare practitioners (HCPs) in Uganda. METHODS: In May 2022, we collected data on sociodemographic characteristics, knowledge of snakebite first aid, envenomation signs, diagnosis and antivenom administration among 311 HCPs from two snakebite high-incidence districts in Uganda using a semi-structured questionnaire. RESULTS: Of the 311 HCPs, 64.3% had ever treated snakebite cases, 87.1% were confident to provide supportive treatment, but only 9.6% had ever been trained on snakebite management. Overall, 22.8% of HCPs had high knowledge of snakebite management. Higher education (at least degree vs certificate; PR=2.21 95% CI 1.508 to 4.56), older age (30-45 vs <30 y; PR=1.97, 95% CI 1.22 to 3.21) and previous training (PR=1.82, 95% CI 1.08 to 3.05) were associated with high knowledge of snakebite diagnosis and management. CONCLUSIONS: Overall, knowledge of snakebite management was limited. Training, level of education and age of the HCP all had an impact on knowledge. Deliberate efforts are required to increase HCPs' knowledge of snakebite case care in high-burden regions to manage incident cases.

Point-of-care ultrasound assessment of a swollen limb following snakebite envenomation - an adjunct to avoid fasciotomy.

SUMMARY: Acute limb compartment syndrome can occur with cytotoxic snake envenomation. Ultrasound (US) assessment of the affected limb has been suggested as an adjunct to the administration of snakebite polyvalent antivenom to ameliorate the systemic and local effects. US may also aid in the diagnosis of compartment syndrome and the need for fasciotomy to prevent limb loss. This report presents an adult male who had severe soft tissue swelling from a puff adder bite to the wrist and highlights the use of US in assessing and monitoring the degree of swelling in subcutaneous and fascial compartments of the arm. This US monitoring in conjunction with frequent physical examination avoided the need for a fasciotomy and its attendant morbidity, resulting in complete resolution of the swelling and full recovery of limb function.

Clinical aspects of snakebite envenoming and its treatment in low-resource settings.

There is increasing recognition of the public health importance of snakebite envenoming. Worldwide annual incidence is likely to be 5 million bites, with mortality exceeding 150 000 deaths, and the resulting physical and psychological morbidity leads to substantial social and economic repercussions. Prevention through community education by trained health workers is the most effective and economically viable strategy for reducing risk of bites and envenoming. Clinical challenges to effective treatment are most substantial in rural areas of low-resource settings, where snakebites are most common. Classic skills of history taking, physical examination, and use of affordable point-of-care tests should be followed by monitoring of evolving local and systemic envenoming. Despite the profusion of new ideas for interventions, hyperimmune equine or ovine plasma-derived antivenoms remain the only specific treatment for snakebite envenoming. The enormous interspecies and intraspecies complexity and diversity of snake venoms, revealed by modern venomics, demands a radical redesign of many current antivenoms.

Neuromuscular Weakness and Paralysis Produced by Snakebite Envenoming: Mechanisms and Proposed Standards for Clinical Assessment.

Respiratory and airway-protective muscle weakness caused by the blockade of neuromuscular transmission is a major cause of early mortality from snakebite envenoming (SBE). Once weakness is manifest, antivenom appears to be of limited effectiveness in improving neuromuscular function. Herein, we review the topic of venom-induced neuromuscular blockade and consider the utility of adopting clinical management methods originally developed for the safe use of neuromuscular blocking agents by anesthesiologists in operating rooms and critical care units. Failure to quantify neuromuscular weakness in SBE is predicted to cause the same significant morbidity that is associated with failure to do so in the context of using a clinical neuromuscular block in surgery and critical care. The quantitative monitoring of a neuromuscular block, and an understanding of its neurophysiological characteristics, enables an objective measurement of weakness that may otherwise be overlooked by traditional clinical examination at the bedside. This is important for the initial assessment and the monitoring of recovery from neurotoxic envenoming. Adopting these methods will also be critical to the conduct of future clinical trials of toxin-inhibiting drugs and antivenoms being tested for the reversal of venom-induced neuromuscular block.

Decomplexation proteomic analysis and purity assessment of a biologic for snakebite envenoming: Philippine Cobra Antivenom.

BACKGROUND: Philippine Cobra Antivenom (PCAV) is the only snake antivenom manufactured in the Philippines. It is used clinically to treat envenoming caused by the Philippine Spitting Cobra (Naja philippinensis). While PCAV is effective pharmacologically, it is crucial to ensure the safety profile of this biologic that is derived from animal plasma. METHODS: This study examined the composition purity of PCAV through a decomplexation proteomic approach, applying size-exclusion chromatography (SEC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and tandem mass spectrometry liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: SDS-PAGE and SEC showed that the major protein in PCAV (constituting ∼80% of total proteins) is approximately 110 kDa, consistent with the F(ab')2 molecule. This protein is reducible into two subunits suggestive of the light and heavy chains of immunoglobulin G. LC-MS/MS further identified the proteins as equine immunoglobulins, representing the key therapeutic ingredient of this biologic product. However, protein impurities, including fibrinogens, alpha-2-macroglobulins, albumin, transferrin, fibronectin and plasminogen, were detected at ∼20% of the total antivenom proteins, unveiling a concern for hypersensitivity reactions. CONCLUSIONS: Together, the findings show that PCAV contains a favorable content of F(ab')2 for neutralization, while the antibody purification process awaits improvement to minimize the presence of protein impurities.