Antivenom Administration Research Articles

Serum IgE against galactose-alpha-1,3-galactose is common in Laotian patients with snakebite envenoming but not the major trigger for early anaphylactic reactions to antivenom.

Snake antivenom is the only specific treatment for snakebite envenoming, but life-threatening anaphylaxis is a severe side effect and drawback for the use of these typically mammalian serum products. The present study investigates the hypotheses whether serum IgE antibodies against the epitope galactose-alpha-1,3-galactose (α-gal) located on the heavy chain of non-primate mammalian antibodies are a possible cause for hypersensitivity reactions to snake antivenom. Serum samples from 55 patients with snakebite envenoming were obtained before administration of snake antivenom and tested for serum IgE (sIgE) against α-gal and total IgE. Early anaphylactic reactions (EARs) during the first 3 h after antivenom administration were classified into mild, moderate or severe and correlated with the presence of sIgE against α-gal. Fifteen (27%) out of 55 patients (37 male, 18 female, median 34 years, range 9–90 years) developed EARs after antivenom administration. Eleven, three and one patients had mild, moderate and severe EARs, respectively. Serum IgE against α-gal was detected in 17 patients (31%); in five (33%) out of 15 patients with EARs and in 12 (30%) out of 40 patients without EAR (Odds Ratio = 1.2; 95%-confidence interval: 0.3–4.2) with no correlation to severity. Although the prevalence of serum IgE against α-gal was high in the study population, very high levels of total IgE in the majority of patients question their clinical relevance and rather indicate unspecific sIgE binding instead of allergy. Lack of correlation between α-gal sIgE and EARs together with significantly increased total IgE levels suggest that sIgE against α-gal is not the major trigger for hypersensitivity reactions against snake antivenom.

Vipera snakebite in Europe: a systematic review of a neglected disease.

In 2009, snakebites were included in the list of the World Health Organization (WHO) neglected diseases. Dermatological literature lacks current and up-to-date articles about snakebites and their management, despite the fact that dermatologists, especially from rural hospitals, can be called into the emergency room to consult the management of suspected snakebites. In this systematic review, we highlighted the main clinical and laboratory aspects of snakebites from Vipera spp. in Europe, by reviewing 3574 studies initially retrieved from PubMed, Embase and Cochrane CENTRAL databases. Of these, 78 were finally included in the systematic review. We found that the most involved taxon was V.berus in 63.3% and the most involved anatomic site of the bite was the upper limbs 53.1% with fang marks reported in 90.5%. The mean age of the patients was 32.9years, and bites were slightly more common among males (58.2%). A wound washing was performed in 86.9% of cases before the hospitalization. The most frequently reported grade of envenomation was G2 (42.2%). In addition to local dermatological symptoms (extended erythema, oedema, cutaneous necrosis, hives, purpura, petechiae, acute compartment syndrome), numerous systemic symptoms have also been reported, including fatigue (14.4%), pain (75.3%), fever (49.2%), direct anaphylactoid reaction (5.3%), anxiety (60.8%), cranial nerve neurotoxicity (14.8%), dysesthesia/paraesthesia (7.9%), vomiting (33.7%), abdominal pain (23.3%), diarrhoea (15.4%), dyspnoea (6.3%), proteinuria (10.6%) and haematuria (9.3%). Secondary infections were present in 3.5% and disseminated intravascular coagulation in 3.1% of cases, and fasciotomy was performed in 4.2% cases, while an amputation in 6.9%. Only 0.9% of patients died. Antivenom was administered in 3053 cases. In conclusion, there is a pressing need for robust multi-centre randomized control trials, standardized protocol for snakebite management and antivenom administration across Europe and a National snakebite register for each European country.

Analysis of resource utilization in pediatric snake bites: An 11-year analysis

Introduction: Pediatric snake bite management is not well-defined and frequently requires intensive care unit (ICU) hospitalization with expensive antivenom administration. This study aims to review snake bite outcomes at our institution in order to refine resource management. Methods: A retrospective single-center review included all pediatric patients with a snake bite admitted to our emergency department from January 2008 to December …

Engineered antigen containing epitopes from Loxosceles spp. spider toxins induces a monoclonal antibody (Lox-mAb3) against astacin-like metalloproteases

Loxoscelism pose a health issue in the South America. The treatment for these accidents is based on the administration of antivenom produced in animals immunized with Loxosceles venom. In this work, a previously produced non-toxic multiepitopic chimeric protein (rMEPlox), composed of epitopes derived from the main toxins families (sphyngomielinase-D, metalloproteases, and hyaluronidases) of Loxosceles spider venoms, was used as antigen to produce monoclonal antibodies (mAbs). A selected anti-rMEPlox mAb (Lox-mAb3) reacted with metalloprotease from L. intermedia venom and showed cross-reactivity with metalloproteses from Brazilian and Peruvian Loxosceles laeta and Loxosceles gaucho venoms in immunoassays. The sequence recognized by Lox-mAb3 (184ENNTRTIGPFDYDSIMLYGAY205) corresponds to the C-terminal region of Astacin-like metalloprotease 1 and the amino acid sequence IGPFDYDSI, conserved among the homologs metalloproteases sequences, is important for antibody recognition. Lox-mAb3 neutralizes the fibrinogenolytic activity caused by metalloprotease from L. intermedia spider venom in vitro, which may lead to a decrease in hemorrhagic disturbances caused by Loxosceles envenomation. Our results show, for the first time, the use of a non-toxic multiepitopic protein for the production of a neutralizing monoclonal antibody against a metalloprotease of medically important Loxosceles venoms. These results contribute for the production improvement of therapeutic antivenom against loxoscelism.

Identification of cross-reactive human single-chain variable fragments against phospholipases A2 from Lachesis muta and Bothrops spp venoms

Bushmasters (Lachesis spp) and lancehead vipers (Bothrops spp) are two of the most dangerous snakes found in Latin America. Victims of envenoming by these snakes require urgent administration of antivenom. Here, we report the identification of a small set of broadly neutralizing human monoclonal single-chain variable fragment (scFv) antibodies targeting key phospholipases A2 from Lachesis and Bothrops spp using phage display technology and demonstrate their in vitro efficacy using a hemolysis assay.

Case Report: Management of Pit Viper Envenoming without Antivenom: A Case Series.

Pit viper envenoming is common in the hilly and the Himalayan regions of Nepal. Antivenom present in Nepal is unlikely to neutralize the venom of these pit vipers, although it has been used often by the healthcare providers in the clinical practice. Here, we report 15 cases of snakebite with a deranged coagulation profile. All patients recovered from envenoming on conservative management and without the administration of antivenom.

Descending Cervical-Sacral Pain after the Administration of Antivenom to the Scorpion Sting Poisoning: A Case Report

Introduction. Scorpion stings occur mainly in spring and summer, with an estimate of 1.2 million cases per year worldwide. About 300,000 poisonings occur within a year, primarily affecting children and adults older than 65 years. In 2019, Guanajuato (Mexico) ranked third in poisoning by scorpion sting with a total of 43,913 cases. The intoxication grades are three where the signs and symptoms are varied. There are two types of antivenom in the Mexican market, and we use Alacramyn® in our case. Case presentation. A 70-year-old female —with grade 1 scorpion sting poisoning, 30 minutes of evolution, with type 2 diabetes and high blood pressure— received two vials of antivenom according to current regulations. She presented transient vagal reaction and subsequent transient pain in the cervical region that radiates to the sacral region. At discharge, there are no data compatible with scorpion sting poisoning. Conclusions. Transient pain in the cervical region to the sacral region may be secondary to an anxiety crisis, hypersensitivity to IgG, or secondary reaction to administration in less time than recommended by the provider. The benefit was greater than the reactions that occurred.

Liver gene regulation of hemostasis-related factors is altered by experimental snake envenomation in mice.

Few studies have addressed gene expression of hemostasis-related factors during acute thrombo-hemorrhagic diseases. Bites by the lanced-headed viper Bothrops jaracaca induce rapid hemostatic disturbances in victims, leading to systemic bleedings, thrombocytopenia and consumption coagulopathy. Although circulating levels of coagulation factors recover rapidly after administration of specific antivenom therapy, it is unclear if B. jararaca venom (BjV) upregulates the mRNA synthesis of hepatic hemostasis-related factors, or if the recovery occurs under basal conditions after the neutralization of venom components by antivenom. Thus, we aimed to investigate if BjV regulates gene expression of important hemostasis-related factors synthetized by the liver. On that account, Swiss mice were injected with saline or BjV (1.6 mg/kg b.w, s.c.), and after 3, 6 and 24 h blood samples and liver fragments were collected to analyze mRNA expression by real-time qPCR. Increased gene expression of fibrinogen chains, haptoglobin and STAT3 was observed during envenomation, particularly at 3 and 6 h. At 24h, mRNA levels of F10 were raised, while those of Serpinc1, Proc and Adamts13 were diminished. Surprisingly, F3 mRNA levels were steadily decreased at 3 h. Gene expression of Thpo, F7, F5 Tfpi, Mug1 was unaltered. mRNA levels of Vwf, P4hb, F8, F2, Plg, and Serpinf2 were minimally altered, but showed important associations with Nfkb1 gene expression. In conclusion, snakebite envenomation upregulates hepatic mRNA synthesis particularly of fibrinogen chains, and acute-phase markers. This response explains the fast recovery of fibrinogen levels after antivenom administration to patients bitten by B. jararaca snakes.

Epidemiological and clinical profile of paediatric snake bite patients at a tertiary care centre of Himachal Pradesh, India

Background: Pediatric snake bite cases are frequently encountered at health care centers of Himachal Pradesh. It is a medical emergency which require early hospitalisation and immediate medical intervention. This study determines the epidemiological and envenomation details along with clinical profile and management of pediatric snake bite patients in Himachal Pradesh, India.Methods: This prospective clinico-epidemiologic study included 30 paediatric snake bite cases reported at Department of Paediatrics, IGMC, Shimla. Demography, envenomation details, first aid and treatment, antivenom administration and outcome were recorded for all patients.Results: Of the total 30 cases, 56.6% were males and 43.3% were females. All patients were resident of rural areas and most of them belonged to middle socioeconomic status. Most (56.7%) snake bites occurred between 6pm to 12am and peak time was during rainy season. More cases of hemotoxic envenomation were observed as compared to neuroparalytic envenomation. Most common hematologic abnormalities were hematuria (4.8%) and epistaxis (4.8%). Respiratory paralysis, ptosis and opthalmoplegia were the most common presentation in patients with neuroparalytic envenomation. Clinical profile of patients showed thrombocytopenia (26.7%), prolonged PT/INR (76.6%) and 36.7% had prolonged activated partial thromboplastin time. All symptomatic patients were given ASV as primary treatment out of which 79.2% patients required more than 10 vials of ASV. Most common complication observed in neuroparalytic envenomation was respiratory failure (33.3%) and in hemotoxic envenomation was coagulation failure (66.7%). Only 3.3% case fatality was observed in this study.Conclusions: Snake bite in children is a medical emergency in hilly state of Himachal Pradesh where people still follow traditional first aid methods and treatment protocol. A widespread awareness programme is needed to propagate the newly advised first aid methods to prevent mortality by early hospitalization and administration of ASV.

Administration of a Second Dose Antivenom in the Early Period: Is It Effective in Scorpion Stings?

Administration of a Second Dose Antivenom in the Early Period: Is It Effective in Scorpion Stings?

Assessment of Inflammatory and Cardiac Status of Echis ocellatus Snake-bite Victims in Jos Metropolis, Plateau State, Nigeria

Background: This study was designed to evaluate the inflammatory and cardiac status of snakebite victims using serum levels of C-reactive protein (CRP), troponin-I (TnI), total cholesterol (TC) and triglycerides (TG) as markers in Echis ocellatus snakebite victims before and after administration of EchiTAb-G antivenom.
 Materials and Methods: A total of 80subjects (40 Echis ocellatus bite victims and 40 apparently healthy indivuals as test and control subjects respectively) were purposively recruited for this study. Venous blood samples were collected within 4hours after bite. The whole blood clotting time (WBCT20) was determined immediately. Another batch of samples were collected from same snakebite victims, 2days post administration of the anti-venom. CRP and Troponin-I levels were evaluated using the enzyme linked immunosorbent assay technique while serum total cholesterol, and triglyceride levels were assayed spectrophotometrically.
 Results: The mean serum levels of troponin-I (2.98±5.75) and CRP (36.64±29.01) were significantly higher in Echis ocellatus bite victims before administration of anti-venom compared with control subjects (0.007±0.3 and 0.99±0.28) and after post administration of anti-venom (0.16±1.39 and 15.96±17.36) (P<0.05) respectively. Conversely, the mean plasma levels of total cholesterol and triglyceride were significantly lower (p<0.05) in snake bite subjects before anti-venom administration when compared with control and snake bite subjects after post administration of anti-venom. Furthermore, the mean serum levels of troponin-I and CRP correlated significantly positive when correlated between snake bite subjects before (r=0.498, p=0.001) and after (r=0.430, p=0.006) anti-venom administration respectively.
 Conclusion: The research findings therefore suggest that Echis ocellatus envenomation triggers inflammatory reaction which could be the reason behind the alteration in cardiac markersas evidenced by the significant elevations in serum troponin-I and CRP levels amongst snake bite victims compared to the non-snake bite control groups thus, could cause cardiac arrest before anti-venom administration.

Coagulation factor activity patterns of venom-induced consumption coagulopathy in naturally occurring tiger snake (Notechis scutatus) envenomed dogs treated with antivenom

BackgroundVenom-induced consumption coagulopathy (VICC) from tiger snake (Notechis scutatus) envenomation results in a dose-dependent coagulopathy that is detectable on coagulometry. However, individual coagulation factor activities in dogs with tiger snake envenomation have not been determined. This study aimed to characterise VICC and the time course of recovery in tiger snake envenomed dogs and to investigate an association between tiger snake venom (TSV) concentrations and factor activity. MethodsThis was a prospective, observational, cohort study. The study cohort was 11 dogs of any age, breed, sex, body weight >10 kg, confirmed serum TSV on ELISA and treated with antivenom. Blood was collected at enrolment before antivenom administration, then at 3, 12 and 24 h after antivenom administration. Tiger snake venom concentrations were detected with a sandwich ELISA. Fibrinogen was measured using a modified Clauss method, and coagulation factors (F) II, V, VII, VIII and X were measured with factor-deficient human plasma using a modified prothrombin (PT) and activated partial thromboplastin (aPTT) method. Linear mixed models, with multiple imputations of censored observations, were used to determine the effect of time and TSV concentration on the coagulation times and factor activity. This cohort was compared to 20 healthy controls. ResultsAt enrolment, there were severe deficiencies in fibrinogen, FV and FVIII, with predicted recovery by 10.86, 11.75 and 13.14 h after antivenom, respectively. There were modest deficiencies in FX and FII, with predicted recovery by 20.57 and 32.49 h after antivenom, respectively. No changes were detected in FVII. Prothrombin time and aPTT were markedly prolonged with predicted recovery of aPTT by 12.58 h. Higher serum TSV concentrations were associated with greater deficiencies in FII, FV and FVIII, and greater prolongations in coagulation times. The median (range) serum TSV concentration was 57 (6–2295) ng/mL. ConclusionsIn tiger snake envenomed dogs, we detected a profound, TSV-concentration-related consumption of select coagulation factors, that rapidly recovered toward normal. These findings allowed further insight into tiger snake VICC in dogs.

Treatment in Scorpion Sting: Which is Correct?

Background: The scorpion sting is a condition that requires management in emergency department. Anti-allergic, analgesic and anti-venom administrations are commonly used, particularly in pediatric patients. In this study, it was aimed to present data from patients who presented with scorpion sting and underwent various treatments. Material and method: We retrospectively reviewed 50 patients who presented to our hospital with scorpion sting. Demographic characteristics, severity of clinical presentation, treatments employed and anti-venom administration were evaluated. In patients underwent anti-venom treatment, we evaluated whether or not anti-venom caused systemic signs or additional pathology. Results: Mean age was 9.88 ± 4.58 years in the study population. There were 18 girls (36%) and 32 boys (64%). It was found that electrocardiogram was performed in all patients and that there was sinus tachycardia in 6 patients (12%). No systemic sign was detected during followup. It was found that anti-venom treatment was used in only 7 patients (14%). No significant difference was detected between anti-venom treatment and other therapeutic modalities used in ED. Conclusion: Scorpion sting is one of the leading causes of insect bites presenting to pediatric emergency departments in Turkey. It was observed that, even in tertiary care settings, antivenom treatment is used in scorpion sting without systemic signs. Based on this study, no anti-venom indication was present in this patient group. Thus, anti-venom decision should be assessed by relevant unit or pediatric emergency clinicians in cases requiring anti-venom treatment. Unnecessary anti-venom use should be avoided by training clinicians in primary care.

A Web of Coagulotoxicity: Failure of Antivenom to Neutralize the Destructive (Non-Clotting) Fibrinogenolytic Activity of Loxosceles and Sicarius Spider Venoms.

Envenomations are complex medical emergencies that can have a range of symptoms and sequelae. The only specific, scientifically-validated treatment for envenomation is antivenom administration, which is designed to alleviate venom effects. A paucity of efficacy testing exists for numerous antivenoms worldwide, and understanding venom effects and venom potency can help identify antivenom improvement options. Some spider venoms can produce debilitating injuries or even death, yet have been largely neglected in venom and antivenom studies because of the low venom yields. Coagulation disturbances have been particularly under studied due to difficulties in working with blood and the coagulation cascade. These circumstances have resulted in suboptimal spider bite treatment for medically significant spider genera such as Loxosceles and Sicarius. This study identifies and quantifies the anticoagulant effects produced by venoms of three Loxoscles species (L. reclusa, L. boneti, and L. laeta) and that of Sicarius terrosus. We showed that the venoms of all studied species are able to cleave the fibrinogen Aα-chain with varying degrees of potency, with L. reclusa and S. terrosus venom cleaving the Aα-chain most rapidly. Thromboelastography analysis revealed that only L. reclusa venom is able to reduce clot strength, thereby presumably causing anticoagulant effects in the patient. Using the same thromboelastography assays, antivenom efficacy tests revealed that the commonly used Loxoscles-specific SMase D recombinant based antivenom failed to neutralize the anticoagulant effects produced by Loxosceles venom. This study demonstrates the fibrinogenolytic activity of Loxosceles and Sicarius venom and the neutralization failure of Loxosceles antivenom, thus providing impetus for antivenom improvement.

Review of North American pit viper antivenoms.

For the first time in nearly 20 years, 2 antigen-binding fragment (Fab) antivenoms are available to treat patients who incur North American pit viper snakebites: Crotalidae polyvalent immune Fab (ovine), or simply FabAV; and Crotalidae immune F(ab')2 (equine), or simply F(ab')2. Pharmacists are in a key position for the selection, dosing, reconstitution, administration, and monitoring of antivenom therapy; however, they encounter inconsistent exposure and experience with these drugs. Thus, an updated review of the literature is necessary. The search strategy and selection incorporated both controlled vocabulary terms and keywords to describe concepts relevant to the search. Retrieval was limited to literature published from 1997 to the present in English, Portuguese, or Spanish. Given the paucity of available prospective literature, the authors elected to include all prospective evidence to best describe the role of antivenom. For the primary literature review, manuscripts were excluded if they were observational studies, conference abstracts, narrative or opinion articles, letters to the editor, or in-progress studies. While there is limited evidence-based guidance on the superiority of F(ab')2 to FabAV, or vice versa, individual and regional considerations should contribute to formulary decisions. Pharmacists must play a role in the development of clinical pathways to ensure appropriate evaluation, supportive care, and antivenom procurement, administration, and monitoring.

Comparison of antivenom effects between pediatric and adult patients presented to emergency department with scorpion stings

The aim of this study was to compare the use of antivenom, and admission to ICU, scorpinism between adult and pediatric patients. This study included 99 patients who were admitted to the emergency department with scorpion sting within 1 year. Patients� demographics including age and gender, and clinical findings such as ionized Ca values, body region of sting contact and complications were recorded from the patient files and hospital records. In addition, regarding management of patients with scorpionism the use of antivenoms, admission to intensive care unit and complications developed by the patients were also recorded. Patients were divided into two groups according to age as the pediatric group including patients aged ≤ 18 years (Group 1) old and the adult group consisting of patients aged> 18 years old (Group 2). Antivenom administration was performed in 12 patients (12.2%). Antivenom was administered in 38% (n=8) of the patients in Group 1 and 5.13% (n=4) of the patients in Group 2. The mean age of patients who received antivenom was statistically significantly lower than the patients who did not receive antivenom (p

A prospective multicenter observational study of Viperidae polyvalent immune F(ab')2 antivenom administration for the treatment of viper envenomation in dogs.

To test an equine-derived polyvalent viperid antivenom (EPVA) in the treatment of dogs with evidence of viper envenomation. Prospective, multicenter observational study. Veterinary emergency and critical care hospitals. A total of 82 client-owned dogs with progressive clinical signs after viperid snakebite were enrolled in the study. Equine-derived polyvalent viperid antivenom was administered at a dosage of 1 mL/kg body weight, either by IV infusion or SC injection. A standardized snakebite severity score (SSS) was used to characterize the severity of envenomation and the clinical course after EPVA treatment. Most dogs had improved SSS both at 4 (65.8%) and 8 hours (81.7%) following EPVA administration. Five dogs died. At the 4-week assessment, 3 dogs had slightly abnormal hematological or coagulation parameters; all other surviving dogs showed no abnormalities. Antivenom-related acute or intermediate reactions occurred in 12 dogs (14.6%). In the first study on antivenom in dogs in Italy, the effects of progressive viper envenomation were stabilized or reversed in the large majority of dogs receiving EPVA, as confirmed by the SSS analyses.

Unwitnessed Snake Bite in Children - A Challenge in Diagnosis and Management: A Case Report

The clinical diagnosis of snakebite is critical, particularly in Southeast Asia where venomous snakebites are a public health concern. Additionally, cases involving unwitnessed snakebite with no species identification, especially in non-verbal children posed a challenge in the emergency setting. A 2-year-2-month-old boy presented to our emergency department with signs of neurotoxicity. He was restless and mildly bradypnoeic with the respiratory rate of 24 to 28 breaths per minute. He also had bilateral ptosis with absent gag reflex. There were faint fang marks noted over the medial aspect of his left ankle with local swelling and bruises, despite no history of animal bite and no eyewitness. A high index of suspicion of neurotoxic envenomation was prompted and a total of 6 vials of neuro-polyvalent anti-venom were administered in scheduled batches. Progressive clinical recovery was subsequently observed after the first batch of anti-venom administration. The case illustrated the importance of clinical recognition of neurotoxic envenomation in the absence of snake bite history or species identification. Early administration of anti-venom may potentially reverse the neurotoxic effects of systemic envenomation and saves lives.

Utilization of the Plant Clusia Fluminensis Planch & Triana Against Some Toxic Activities of the Venom of Bothrops jararaca and B. jararacussu Snake Venom Toxic Activities.

In Brazil, the Bothrops genus accounts for 87% of registered snakebites, which are characterized by hemorrhage, tissue necrosis, hemostatic disturbances, and death. The treatment recommended by governments is the administration of specific antivenoms. Although antivenom efficiently prevents venom-induced lethality, it has limited efficacy in terms of preventing local tissue damage. Thus, researchers are seeking alternative therapies able to inhibit the main toxic effects of venoms, without compromising safety. The study aimed to test the ability of aqueous extracts of leaves, stems, and fruits of the plant Clusia fluminensis to neutralize some toxic effects induced by the venoms of Bothrops jararaca and Bothrops jararacussu. The plant extracts were incubated with venoms for 30 min. at 25 °C, and then in vitro (coagulant and proteolytic) and in vivo (hemorrhagic, myotoxic, and edematogenic) activities were evaluated. In addition, the extracts were administered to animals (by oral, intravenous or subcutaneous routes) before or after the injection of venom samples, and then hemorrhage and edema assays were performed. In addition, a gel solution of the fruit extract was produced and tested in terms of reducing hemorrhage effects. A chemical prospection was performed to identify the main classes of compounds present in the extracts. All the extracts inhibited the activities of the two venoms, regardless of the experimental protocol or route of administration of the extracts. Moreover, the gel of the fruit extract inhibited the venom-induced-hemorrhage. The extracts comprised of tannins, flavonoids, saponins, steroids, and terpenoids. Antivenom properties of C. fluminensis extracts deserve further investigation in order to gain detailed knowledge regarding the neutralization profile of these extracts.

Evaluation of the geographical utility of Eastern Russell's viper (Daboia siamensis) antivenom from Thailand and an assessment of its protective effects against venom-induced nephrotoxicity.

BackgroundDaboia siamensis (Eastern Russell’s viper) is a medically important snake species found widely distributed across Southeast Asia. Envenomings by this species can result in systemic coagulopathy, local tissue injury and/or renal failure. While administration of specific antivenom is an effective treatment for Russell’s viper envenomings, the availability of, and access to, geographically-appropriate antivenom remains problematic in many rural areas. In this study, we determined the binding and neutralizing capability of antivenoms manufactured by the Thai Red Cross in Thailand against D. siamensis venoms from four geographical locales: Myanmar, Taiwan, China and Thailand.Methodology/Principle findingsThe D. siamensis monovalent antivenom displayed extensive recognition and binding to proteins found in D. siamensis venom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also uses D. siamensis venom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all four geographical venom variants neutralized by both the D. siamensis monovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. These in vitro findings translated into therapeutic efficacy in vivo, as the D. siamensis monovalent antivenom was found to effectively protect against the lethal effects of all four geographical venom variants preclinically. Assessments of in vivo nephrotoxicity revealed that D. siamensis venom (700 μg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration of D. siamensis monovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity and prevented renal morphological changes, although lower doses had no therapeutic effect.Conclusions/SignificanceThis study highlights the potential broad geographical utility of the Thai D. siamensis monovalent antivenom for treating envenomings by the Eastern Russell’s viper. However, only the early delivery of high antivenom doses appears to be capable of preventing venom-induced nephrotoxicity.