Fibrinogenolytic potential of venoms of medically important Brazilian snakes.

One of the main clinical manifestations presented by victims of snake bite envenoming are coagulation disorders. Considering that fibrinogen is a key molecule for crosslinked fibrin clot formation, the objective of this work was the quantitative analysis of the fibrinogenolytic activity of snakes of medical importance in Brazil and neutralization by specific antivenom. For this, pools of three genera of medical importance (Bothrops, Crotalus and Lachesis) that are used for the production of antivenom were used, and three pools of species of the genus Bothrops that are not part of the pool for the production of antivenom. The Lachesis pool had the highest fibrinogenolytic activity, even demonstrating partial cleavage (42.9 % consumption) of the fibrinogen gamma chain. The Bothrops genus venom pools have shown subtle variations between them. The Crotalus pool, despite not showing total cleavage of any fibrinogen chain, began cleavage of fibrinogen by the beta chain. The specific antivenoms used were able to delay the cleavage of fibrinogen in all the venoms used, which could be the first step towards implementing previous in vitro tests to analyze the quality of the batches of antivenoms produced, thus potentially reducing the use of animals used in this process.

Design, development and preclinical assessment of MENAVip-ICP, a new snake antivenom with potential coverage of species in the Middle East and North Africa regions.

Snakebite in the Middle East and North Africa (MENA) is a public health problem whose magnitude is not fully known. Several antivenoms are available in these regions, but these formulations are designed for restricted geographical settings. Many countries do not have local production of antivenoms and must access products whose clinical performance has not been demonstrated. We hypothesize that it is possible to unify the treatment for viperid snakebites of MENA in a single antivenom formulation. Hereby we describe the design, development and preclinical evaluation of an antivenom of broad geographical coverage for this region (MENAVip-ICP). We produced this antivenom from the plasma of horses immunized with eight medically important venoms of viperid snake species from MENA. For this, we used a strategy based on two stages: first, immunization of horses with North African (NA) venoms, followed by a second immunization stage, on the same horses, with MENA venoms. We purified antivenoms from both stages: the Anti-NA and the final product Anti-MENA (MENAVip-ICP). Anti-NA was considered as intermediate formulation and was purified with the intention to study the progression of the immunoglobulin immune response of the horses. Antivenoms from both stages neutralized lethal, hemorrhagic, and procoagulant activities of homologous venoms. Compared to Anti-NA, MENAVip-ICP improved the neutralization profile of intravenous lethality and in vitro procoagulant activities of venoms. A notable finding was the difference in the neutralization of lethality when MENAVip-ICP was assessed intraperitoneally versus intravenously in the murine model. Intraperitoneally, MENAVip-ICP appears more effective in neutralizing the lethality of all venoms. Furthermore, MENAVip-ICP neutralized the lethal activity of venoms of species from other regions of MENA, Central/East Asia, and Sub-Saharan Africa that were not included in the immunization protocol. Our results showed that MENAVip-ICP neutralizes the main toxic activities induced by viperid MENA venoms at the preclinical level. Consequently, it is a promising product that could be clinically assessed for the treatment of snakebite envenomings in this region.

Venom-induced myocarditis: An unusual case attributable to Vipera aspis bite.

Venomous bites are medical emergencies that may result in life-threatening clinical effects. Cardiovascular complications are uncommon but they can be dangerous if not early detected and treated. Cerebral and myocardial infarction are described; myocarditis as consequence of viper envenomation in humans are very rare, almost anedoctal. We present the case of a 33-year-old man, working as keeper in a reptile zoo, who arrived after a viper bite of the Vipera aspis species, on the left wrist. The patient presented with clouded sensorium, edema of the lips and tongue, rapidly worsened with angioedema, and the need for oro-tracheal intubation; severe thrombocytopenia and anemia were treated with transfusions of platelet, plasma and red blood cells. The left hand and arm worsened, with compartment syndrome, treated with surgical fasciotomy. From a cardiological point of view, the patient presented a sudden drop in blood pressure, electrocardiographic anterior and infero-lateral ST depression, pericardial effusion and hypokinesia of the interventricular septum on echocardiography, and a significant increase in troponin T. Cardiac magnetic resonance imaging confirmed the myocarditis, with the presence of septal and anterior intramyocardial edema in T2 weighted sequences, with prolonged T2 time at T2 mapping analysis, without late gadolinium enhancement areas. Cardiological and general clinical conditions gradually improved only after the antivenom was administred. This is one of the rare cases of viper bite myocarditis with echocardiographic and magnetic resonance imaging documentation in Europe; it emphasizes the importance of identifying uncommon complications of venomous snake-bites and the prompt administration of antivenom, even though snake bites are less frequent at our latitudes.

A retrospective observational study of mangrove pit viper envenomation presented to selangor middle zone cluster hospitals in Malaysia.

OBJECTIVE: There is very limited published experience on mangrove pit viper envenomation in the medical literature. This study aims to analyze the clinical characteristics, treatment modalities and outcomes of patients presenting to Selangor middle zone cluster Hospitals in Malaysia with confirmed mangrove pit viper bites. METHODS: We conducted a retrospective observational study, reviewing medical records of patients treated for mangrove pit viper bites between July 1, 2020 to June 30, 2023. Data on patient demographics, clinical characteristic, laboratory findings, treatment modalities and clinical outcomes were collected and analyzed. RESULTS: A total of 25 patients were included in this study. The majority of the patients were male (n = 23, 92%) with the mean age of 38.7 ± 17.6 years. Most frequent anatomical region involved is foot (n = 12, 48%). Common clinical presentation included localized pain (n = 24, 96%), swelling (n = 22, 88%) and fang mark (n = 22, 88%). Systemic symptoms were less common, with 1 patient exhibiting coagulopathy with clinical bleeding at 28 h post bite. Antivenom was administered to 68% (n = 17) of the patients. The majority of the patients (n = 23, 92%) recovered without significant morbidity while 8% (n = 2) of the patients developed skin infection that required antibiotic therapy. No fatalities were reported. CONCLUSION: Mangrove pit viper envenomation encountered in these regions predominantly causes local symptoms while systemic symptoms were less common. This study provides a glimpse to the clinical characteristics and management of mangrove pit viper envenomation, coagulopathy may be delayed due to characteristic of the snake venom and patient's preexisting illness. Further research is needed to enhance our understanding of this snakebite envenomation.

Multiple Ventricular Premature Complexes Following Equatorial Spitting Cobra (Naja sumatrana) Envenomation.

Naja species bite is the commonest cause for consultation to Remote Envenomation Consultancy Services in Malaysia. Envenomation by Naja species may result in neuroparalysis and cardiotoxic effects including arrhythmias, hypertension, tachycardia, atrioventricular blocks, ventricular tachycardia, and ventricular fibrillation. We report a case of cardiotoxicity as an early manifestation following an equatorial spitting cobra, Naja sumatrana bite, preceding early paralytic envenomation manifestation. A 14-year-old boy presented to an emergency department with mild local envenomation. ECG showed multiple ventricular premature complexes. Subsequently patient developed ptosis. Complete resolution of ptosis and resumption of normal sinus rhythm occurred following administration of the appropriate antivenom. The patient was discharged well after two days of hospitalization. The patient's ECG findings and neurotoxic manifestation suggested acute systemic envenomation. High index of suspicion for cardiotoxicity with close serial monitoring is recommended to ensure timely administration of antivenom.

Bide Your Time With Bites: A Case of Rattlesnake Envenomation in Pennsylvania.

This case report represents a 26-year-old male with no significant past medical history who presented to the emergency department in western Pennsylvania following a western diamondback rattlesnake (Crotalus Atrox) bite to his hand. His initial swelling was mild, and his coagulation studies were unremarkable, with minimal changes on repeat studies, and poison control recommended against antivenom administration. He was discharged home with oral antibiotics and analgesics due to his stable clinical course. However, he returned to the emergency department about 12 hours later with worsening pain and swelling that extended to his elbow. He was then given antivenom and transferred to a larger center for higher-level care, ultimately having symptom resolution after further antivenom administration. This report serves to underline the importance of clinician education regarding envenomation management throughout the United States, including areas without indigenous venomous snakes.

Characterization of hypofibrinogenemia following rattlesnake envenomation treated with crotalidae immune F(ab')2 (equine) antivenom.

INTRODUCTION: Hemotoxicity is common following rattlesnake envenomation. Published experiences with equine-derived crotalidae immune F(ab')2 antivenom have characterized hemotoxicity as delayed, recurrent, or persistent. This study investigated recovery of hypofibrinogenemia following rattlesnake envenomation treated with equine-derived crotalidae immune F(ab')2 antivenom. METHODS: This is a retrospective analysis of human rattlesnake envenomations reported to the Arizona Poison and Drug Information Center over four years. We included rattlesnake-envenomated patients who developed hypofibrinogenemia (<1,500 mg/L) and were treated with equine-derived crotalidae immune F(ab')2 antivenom. The primary outcomes were recovery period (h) and recovery rate (mg/L/h) of hypofibrinogenemia following equine-derived crotalidae immune F(ab')2 antivenom administration. Collected data included demographics, laboratory values, and antivenom administered. Statistics used were percentages, medians, and Kruskall-Wallis test. RESULTS: There were 527 rattlesnake envenomations treated with antivenom, of which 80 met the inclusion criteria. Patients receiving treatment with F(ab')2 antivenom and had a median fibrinogen concentration recovery rate of 62.3 mg/L/h (IQR: 42.0-74.3 mg/L/h) and median recovery period of 19.2 h (IQR: 13.8-26.2 h). There were statistically significant differences between categories for time to antivenom for the median recovery period (P = 0.0154). DISCUSSION: Hypofibrinogenemia is a common laboratory finding following rattlesnake envenomation in Arizona. This study investigated rattlesnake envenomated patients treated with F(ab')2 antivenom and monitored fibrinogen concentrations as a surrogate marker of venom toxicity. Additionally, time to administration of F(ab')2 antivenom was a statistical significant marker of the recovery period from hypofibrinogenemia. Limitations of this study included the geographic coverage of the poison center and exclusion of patients with insufficient laboratory monitoring or those who received another antivenom. CONCLUSIONS: Following rattlesnake envenomation in Arizona, recovery from hypofibrinogenemia was able characterized in a rate (mg/L/h) and period (h) with the quantity and time to administration of antivenom. More studies are needed to assess this finding with other antivenoms and its clinical significance.

Identification of antigenic proteins from the venom of Malaysian snakes using immunoprecipitation assay and tandem mass spectrometry (LC-MS/MS).

Snake envenomation poses a significant risk to Malaysians and country visitors. Malaysia witnesses an estimated 650 snake bites per 100,000 population annually. The primary treatment for snake envenomation involves administering antivenom derived from horses, despite its drawbacks, such as anaphylactic reactions and serum sickness. Identifying the venom proteome is crucial for understanding and predicting the clinical implications of envenomation and developing effective treatments targeting specific venom proteins. In this study, we employ an immunoprecipitation assay followed by LC-MS/MS to identify antigenic proteins in five common venomous snakes in Malaysia compassing of two families which are pit vipers, (Calloselasma rhodostoma and Cryptelytrops purpureomaculatus) and cobras (Ophiophagus hannah, Naja kaouthia, and Naja sumatrana). The immunoprecipitation assay utilises a 2 % agarose gel, allowing antigenic proteins to diffuse and bind with antibodies in the antivenom. The antivenom utilised in this research was procured from the Queen Saovabha Memorial Institute (QSMI), Thailand, including king cobra antivenom (KCAV), cobra antivenom (CAV), Malayan pit viper antivenom (MPAV), Russell's viper antivenom (RPAV), hematopolyvalent antivenom (HPAV), neuropolyvalent antivenom (NPAV), banded krait antivenom (BKAV), and Malayan krait antivenom (MKAV). The protein identified through these interactions which are exclusive to the cobras are three-finger toxins (3FTXs) while snake C-type lectins (Snaclecs) are unique to the pit vipers. Common protein that are present in both families are L-amino acid oxidase (LAAO), Phospholipase A2 (PLA2), and snake venom metalloproteinase (SVMP). Identifying these proteins is vital for formulating a broad-spectrum antivenom applicable across multiple species.

Managing scorpion envenomations: A Gabes emergency department case study of 60 patients.

INTRODUCTION: Scorpion envenomation constitutes a major public health issue in Tunisia, especially in arid regions such as the Gulf of Gabes. It is necessary to understand the epidemiological and clinical characteristics of this condition and the importance of early management. AIM: This study aims to assess the epidemiological and clinical profile of patients admitted to the emergency department of Gabes University Hospital for scorpion envenomation, as well as the timing of management and intra-hospital evolution. METHODS: A retrospective descriptive study of 60 patients admitted for scorpion envenomation to the Acute Assessement unit at the Emergency Department of the Gabes University Hospital from January 2020 to January 2023. RESULTS: The average age was 35 years [1-85 years]. A slight male predominance (51.7%) was noted. Patients with chronic somatic diseases accounted for (25%) of our series. The predominant scorpion species was Androctonus australis (71.7%). The majority of incidents occurred during the nighttime (71.7%). Most patients were of rural origin (58.3%). The most common sting sites were the lower limbs (48.8%) and upper limbs (36.7%). Scorpion envenomation stages at admission were: Stage I (3.3%), Stage II (83.3%), and Stage III (8.33%). The average time to management was 2 hours. Patients classified as Stage II at admission or afterward were seen after an average of 3 hours. Patients initially classified as Stage III were seen after an average of 3 hours and 30 minutes, and those classified as Stage III during the hospitalization were seen after an average of 4 hours. The average time to management for patients transferred from the Emergency Department to the Intensive Care Unit was 4 hours. CONCLUSION: This study highlights the importance of early management of scorpion envenomation.

Taipan envenoming south of the border.

We present a case of severe taipan envenoming in northern New South Wales in a 68-year-old man. He developed severe neurotoxicity requiring intubation and ventilation, venom-induced consumption coagulopathy, myotoxicity and thrombotic microangiopathy with acute kidney injury requiring dialysis. He was administered brown and tiger snake antivenom consistent with guidelines and snake occurrence in the region. Taipan venom was detected in serum (72 ng/ml) following concern about the severity of neurotoxicity, clinical toxicology consultation and a concurrent report of a taipan in the area. Based on this it would be prudent to stock and consider treating with polyvalent antivenom in north-eastern New South Wales and south-eastern Queensland.

Pilot-scale evaluation of a dynamic body-feed filtration system for primary clarification of snake antivenoms produced by the caprylic acid method.

The performance of dynamic body-feed filtration (DBF) in the removal of bulky solids produced during the manufacturing of snake antivenoms using the caprylic acid method was evaluated. For this purpose, diatomites with different filterability properties were compared in a bench-scale study to assess their effectiveness in removing the precipitated material formed after the addition of caprylic acid to equine hyperimmune plasma. C1000 diatomite at a concentration of 90 g/L of precipitated plasma showed the best performance. Then, the process was scaled up to three batches of 50 L of hyperimmune horse plasma. At this pilot scale, 108 ± 4% of the immunoglobulins present following plasma precipitation were recovered after DBF. The antivenoms generated using this procedure met quality specifications. When compared to open filtration systems commonly used at an industrial scale by many antivenom manufacturers, DBF has a similar yield and produces filtrates with comparable physicochemical characteristics. However, DBF ensures the microbiological quality of the primary clarification in a way that open systems cannot. This is because: 1) DBF is performed in a single-use closed device of depth filters which prevents microbial contamination, and 2) DBF removes bulky material in few minutes instead of the more than 24 h needed by open filtration systems, thus reducing the risk of contamination. It was concluded that DBF is a cost-effective, easily validated, and GMP-compliant alternative for primary clarification following caprylic acid precipitation of plasma in snake antivenom production.

Antivenom Properties and Chemical Profiling via Molecular Networking of Mimosa gracilis Extracts.

The species Mimosa gracilis var. capillipes (Benth.) Barneby is used for its antivenom properties in the Coqueiros community, municipality of Catalão, state of Goiás. This study focused on three varieties: M. gracilis Benth. var. gracilis, M. gracilis var. capillipes (Benth.) Barneby, and M. gracilis var. invisiformis Barneby. The chemical profiles of extracts from these varieties were analysed using molecular networking through liquid chromatography with tandem mass spectrometry. Additionally, the study investigated the inhibitory potential of these three varieties against the proteolytic, coagulant, and phospholipase activities of Bothrops and Crotalus venoms. In vitro results confirmed the antivenom potential of nine extracts. Remarkably, the ethanolic extracts of roots from M. gracilis var. capillipes (Benth.) Barneby and the leaves from M. gracilis Benth. var. gracilis exhibited 100 % inhibition of the tested activities. The study also revealed 19 annotated compounds through molecular networking, reported for the first time in the species M. gracilis.

Web of venom: exploration of big data resources in animal toxin research.

Research on animal venoms and their components spans multiple disciplines, including biology, biochemistry, bioinformatics, pharmacology, medicine, and more. Manipulating and analyzing the diverse array of data required for venom research can be challenging, and relevant tools and resources are often dispersed across different online platforms, making them less accessible to nonexperts. In this article, we address the multifaceted needs of the scientific community involved in venom and toxin-related research by identifying and discussing web resources, databases, and tools commonly used in this field. We have compiled these resources into a comprehensive table available on the VenomZone website (https://venomzone.expasy.org/10897). Furthermore, we highlight the challenges currently faced by researchers in accessing and using these resources and emphasize the importance of community-driven interdisciplinary approaches. We conclude by underscoring the significance of enhancing standards, promoting interoperability, and encouraging data and method sharing within the venom research community.

Novel insights into the application of recombinant mutated phospholipases D as antigens for developing new strategies against Loxoscelism.

Loxoscelism is the pathological condition triggered by a brown spider bite. The venom of these spiders is rich in phospholipases D (PLDs), which can induce virtually all local and systemic manifestations. Recombinant mutated PLDs from clinically relevant Loxosceles species in South America have been investigated as potential antigens to develop novel therapeutic strategies for loxoscelism. However, certain gaps need to be addressed before a clinical approach can be implemented. In this study, we examined the potential of these recombinant mutated PLDs as antigens by testing some variations in the immunization scheme. Furthermore, we evaluated the efficacy of the produced antibodies in neutralizing the nephrotoxicity and sphingomyelinase activity of brown spider venoms. Our findings indicate that the number of immunizations has a greater impact on the effectiveness of neutralization compared to the amount of antigen. Specifically, two or three doses were equally effective in reducing dermonecrosis and edema. Additionally, three immunizations proved to be more effective in neutralizing mice lethality than one or two. Moreover, immunizations mitigated the signs of kidney injury, a crucial aspect given that acute renal failure is a serious systemic complication. In vitro inhibition of the sphingomyelinase activity of Loxosceles venoms, a key factor in vivo toxicity, was nearly complete after incubation with antibodies raised against these antigens. These findings underscore the importance of implementing an effective immunization scheme with multiple immunizations, without the need for high antigen doses, and enhances the spectrum of neutralization exhibited by antibodies generated with these antigens. In summary, these results highlight the strong potential of these antigens for the development of new therapeutic strategies against cutaneous and systemic manifestations of loxoscelism.

Development and characterization of nanobody against envenomation by Naja naja oxiana.

Snakebites are considered a significant health issue. Current antivenoms contain polyclonal antibodies, which vary in their specificity against different venom components. Development and characterization of next generation antivenoms including nanobodies against Naja naja oxiana was the main aim of this study. Crude venom was injected into the Sephadex G50 filtration gel chromatography column and then toxic fractions were obtained. Then the corresponding fraction was injected into the HPLC column and the toxic peaks were identified. N. naja oxiana venom was injected into a camel and specific nanobodies screening was performed against the toxic peak using phage display technique. The obtained results showed that among the 12 clones obtained, N24 nanobody was capable of neutralizing P1, the most toxic peak obtained from HPLC chromatography. The molecular weight of P1 was measured with a mass spectrometer and was found to be about seven kDa. The results of the neutralization test of crude N. naja oxiana venom with N24 nanobody showed that 250 µg of recombinant nanobody could neutralize the toxic effects of 20 µg equivalent to LD50 × 10 of crude venom in mice. The findings indicate the potential of the developed nanobody to serve as a novel antivenom therapy.

Paraspecific neutralization capacity of polyvalent snake antivenom against Montivipera wagneri venom.

PURPOSE: This study aims to measure the paraspecific neutralization capacity of nationally produced HSGM polyvalent snake antivenom (HSGM-PSAV), produced using Macrovipera lebetina obtusa, Montivipera xanthina, and Vipera ammodytes montandoni venom, against the lethal effect of the venom of Montivipera wagneri, which is endemic to the Eastern Black Sea and Eastern Anatolia regions of Turkey. METHODS: The neutralization capacity of HSGM-PSAV against the lethal effect of M. wagneri venom was studied using the potency determination testing method specified in the Turkish and European Pharmacopoeia. Lethal dose 50 (LD50) values of the venoms used in immunization, M. wagneri venom in mice, and effective dose 50 (ED50) values of HSGM-PSAV against four types of venoms were calculated using two-fold dilutions. RESULTS: HSGM-PSAV neutralized the lethal effect of M. wagneri venom in mice. The ED50 of the HSGM-PSAV against M. wagneri venom was calculated as 304.42 LD50/mL. CONCLUSION: As a result of this in-vivo study, it was determined that HSGM-PSAV neutralized M.wagneri venom above the antivenom neutralization capacity threshold values (≥50 LD50/mL) specified in the Turkish and European Pharmacopoeia. This result is important preclinical data regarding the usability of HSGM-PSAV in the treatment of poisoning due to M. wagneri bites.

Successful use of anti-venom cross-neutralization effects in the clinical management of Shore Pit Viper envenomation.

As the landscape becomes more urbanized, snakebites have increasingly become uncommon presentations to the emergency departments in Singapore, while snakebites causing significant envenomation are even rarer. In this case report, we discuss a 55-year-old man who had significant envenomation from a Shore Pit Viper (Trimeresurus Purpureomaculatus) and who was successfully treated with haemato-toxic polyvalent antivenom (HPAV). He initially presented with pain, swelling and bleeding over his wound. Due to a deterioration in his coagulation profile, he was given two doses of HPAV which is typically reserved for viperid snakes instead. Following administration of the anti-venom, the patient's coagulation profile improved, and the local soft tissue effects of the venom resolved. He did not manifest any adverse effects and was discharged uneventfully about 72 h after the snakebite. The cross-neutralization potential of HPAV for Shore Pit Viper (Trimeresurus Purpureomaculatus) venom in this case study suggests that there may be a possible common underlying chemical structure and pathophysiology among the venom proteins of various snake species. Given that Trimeresurus-specific antivenom is unavailable in most countries, this cross-neutralization strategy deserves further consideration and evaluation in similar circumstances.

Importance of the Cysteine-Rich Domain of Snake Venom Prothrombin Activators: Insights Gained from Synthetic Neutralizing Antibodies.

Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans that are bitten. While animal-derived polyclonal antivenoms are the primary treatment for snakebites, they often have limitations in efficacy and can cause severe adverse side effects. Building on recent efforts to develop improved antivenoms, notably through monoclonal antibodies, requires a comprehensive understanding of venom toxins. Among these toxins, snake venom metalloproteinases (SVMPs) play a pivotal role, particularly in viper envenomation, causing tissue damage, hemorrhage and coagulation disruption. One of the current challenges in the development of neutralizing monoclonal antibodies against SVMPs is the large size of the protein and the lack of existing knowledge of neutralizing epitopes. Here, we screened a synthetic human antibody library to isolate monoclonal antibodies against an SVMP from saw-scaled viper (genus Echis) venom. Upon characterization, several antibodies were identified that effectively blocked SVMP-mediated prothrombin activation. Cryo-electron microscopy revealed the structural basis of antibody-mediated neutralization, pinpointing the non-catalytic cysteine-rich domain of SVMPs as a crucial target. These findings emphasize the importance of understanding the molecular mechanisms of SVMPs to counter their toxic effects, thus advancing the development of more effective antivenoms.

Snakebites and Antisnake Venom Utilization in Ghana's Oti Region: A 6-Year Retrospective Study.

Background: Snakebite is a global environmental and occupational hazard and a significant public health threat. In rural areas, snakebite cases often go unreported and undocumented due to the lack of access to well-structured healthcare facilities/infrastructure. In some cases, the need for antisnake venom (ASV) far outstrips supply, negatively affecting treatment outcomes. This study, therefore, assessed the epidemiological characteristics of snakebite cases, their management, and how antivenoms are utilised at the selected hospital in the Jasikan District Hospital. Methods: A 6-year retrospective study using secondary data from antivenom return forms (pharmacy records), clinical records (patient folders), the District Health Information Management System-2 (DHIMS-2) database, and consulting room registers was carried out in selected hospitals in the Jasikan District, Oti, Ghana. Results: The predominant symptom of snakebite was localised pain (71.4%). The snakebite commonly occurred at home (19%) and on farms (18%). Of the 98 snakebite cases, ASV was administered to 73 (74.5%) cases. Supportive treatment applied included prophylactic antitetanus immunoglobulin (ATS) (80.6%), prophylactic antibiotics (63%), corticosteroids (80.6%), and analgesics (63%). 95% (n = 94) of complete recoveries were recorded; three were discharged against medical advice, and one was mortality. The supply and use of antivenom were erratic throughout the months of high incidence, partly due to inconsistent availability at the Regional Medical Stores. The average ASV vials and hospital stay duration were 1.23 ± 0.86 vials and 2.67 ± 1.97 days, respectively. Although the peak of snakebites occurs in April, May, and June, the demand for antivenom in April and May exceeded supply. Conclusion: The outcome of most snakebite case management was appropriate, irrespective of inadequate ASV supply in certain months. The erratic antivenom supply should be aligned with seasonal and facility-use patterns to enhance regional snakebite management.

The OROCHI (Observational Research of Clinical Course After mamusHI) Study: A Prospective, Observational, Multicenter Study on the Efficacy of Mamushi (Gloydius blomhoffii) Antivenom Serum.

BACKGROUND: Evidence on the efficacy of mamushi antivenom serum is limited. OBJECTIVE: To investigate the effectiveness of mamushi (Gloydius blomhoffii) antivenom serum. METHODS: The Observational Research Of the Clinical course after mamusHI bite (OROCHI) study was a prospective multicenter study conducted at 24 hospitals in Japan. Patients hospitalized due to mamushi bite were registered. The primary endpoint was the length of hospital stay. Secondary endpoints were adverse effects, pain (numerical rating scale), and grade of swelling. We performed a cohort analysis to compare outcomes between patients treated with mamushi antivenom serum (antivenom group) and those who were not treated with the serum (no-antivenom group). RESULTS: Overall, 106 patients were registered across 18 hospitals between April 22, 2020, and October 31, 2022. Of these, 92 were eligible for the analyses, with 53 and 39 in the antivenom and no-antivenom groups. The median (interquartile) length of hospital stay was not significantly different between the antivenom and no-antivenom groups (5 (3-6) days vs. 3 (1-8) days, P = 0.369). In multivariable analysis, the adjusted odds ratio for a hospital stay of >4 days was 1.331 in patients treated with mamushi antivenom serum (95% confidence interval (CI) = 0.744‒2.015, P = 0.574) and 6.154 in patients treated with cepharanthine (95% CI = 1.442-26.258, P = 0.014). Pain and the grade of swelling were worse in the antivenom group than in the no-antivenom group up to 24 h after arrival, but there were no differences in these outcomes after 48 h. CONCLUSION: Although the effectiveness of mamushi antivenom serum in reducing the length of hospitalization was not demonstrated, beneficial effects on pain and swelling were observed.