Antivenom surveillance: An audit of antivenom stock within South Australia.

OBJECTIVES: Antivenoms are important emergency medications to be held within Australia, particularly in regional and remote locations. We audited current antivenom holdings in hospitals and health services across South Australia (SA) and compared to recommendations in the 'Snakebite and Spiderbite Management Guidelines' from the State's Toxinology service. The process also assessed the feasibility of 'real-time' remote stock monitoring. METHODS: Fifty-three sites listed in the guideline were recommended to hold antivenom, though only 49 are currently operational. Interrogation of antivenom stock for 29 sites was possible using electronic reports generated from the State Pharmacy database. The 20 remaining centres had their stock levels confirmed by calling the centres directly. Data obtained were then compared to recommended levels of antivenom holdings in the guideline with discrepancies and associated costs documented. A separate report verification process was used to determine 'real-time' accuracy of the electronic reports. RESULTS: Thirty-seven sites (75%) held more than the recommended number of antivenom vials, totalling 129 vials in excess with an approximate total cost of $110 000. Twelve sites (24%) held inadequate stock to deliver a treatment dose for 19 envenoming events. The report verification revealed variances in the electronic reports. CONCLUSIONS: This audit has demonstrated a significant disparity between recommended and actual antivenom holdings across most sites in SA and has also revealed that 'real-time' remote monitoring of state antivenom holdings is not currently feasible. Correction of stock levels to that recommended may result in financial benefit for State Health while also addressing inequity in regional and remote healthcare provision.

Evaluation of venom diversity and antivenom quality from the venom of long-term captive vs recently wild captured Pseudocerastes persicus snake: An In vitro and In vivo study.

Snakebite envenomation is a life-threatening condition and antivenoms are used as the most effective treatment. Venom obtained from snakes in long-term captivity showed some variations in comparison to the venom of the wild snakes. The objective of this study is to compare the venom of the Pseudocerastes persicus under long-term captivity and wild conditions as well as the antivenom obtained from these venoms. We have analyzed venom samples and produced trivalent antivenoms using the venom of long-term captive (LTC) or recently wild-captured (RWC) Pseudocerastes persicus, and RWC Macrovipera lebetina, and Echis carinatus. The HPLC analysis revealed that the RWC snakes' venom had three peaks that were not present in the LTC snake's venom. Further analysis using MALDI-TOF and MS/MS showed that the fraction with a retention time (RT) of 14 min contained a toxin from the Kunitz-type serine protease inhibitor (KUT) class, while the fraction with RT 21 a peptide identified within the snake venom metalloproteinase (SVMP) class. The third peak was identified as a sphingolipid. Interestingly, the in vivo preclinical tests showed no significant differences in the effectiveness of the antivenoms. which could be due to the cross-immunogenicity or cross-reactivity between different toxins in the venom. According to our results, small variations in the venom composition of a species do not lead to a decrease in the efficacy of the polyvalent antivenom.

Antivenom supply and demand: An analysis of antivenom availability and utilization in South Africa.

Introduction: Snakebites are a neglected tropical disease. In many areas, envenoming incidence and antivenom administration rates are unknown. This study compared antivenom (AV) availability to rates of envenoming and recommendations to treat (RTT) in South Africa. Methods: This retrospective study identified, extracted, and reviewed all cases of envenoming (snake bites and spits) reported to the Poisons Information Helpline of the Western Cape of South Africa (PIHWC) from June 1, 2015 to May 31, 2020 by public hospitals in the Western Cape. A standardized interview was administered to the pharmacies of the 40 hospitals in winter and summer to determine how many vials of monovalent and polyvalent AV they had on hand at the time of the call and their expiration dates. Descriptive analysis was used to compare rates of envenoming and recommendations to treat to antivenom stock in winter and summer and by hospital type and location. Results: Public hospitals reported 300 envenomings, 122 from snakes. The PIHWC recommended antivenom administration in 26% of cases (N = 32). All hospital pharmacies queried answered our questions. Our study demonstrates urban district hospitals have higher ratios of AV vials compared to mean annual rates of envenoming and RTT than rural district hospitals at both the winter and summer timepoints. Conclusion: This study evaluates antivenom supply and demand in a province of South Africa. The findings suggest South African urban hospitals have a relative excess of antivenom, and thus more capacity to meet demand, than their rural counterparts. It supports consideration of a redistribution of antivenom supply chains to match seasonal and local rates of envenoming. It indicates a need for higher quality, prospective data characterizing envenoming incidence and treatment.

Picadura de escorpión en Bolivia: una revisión crítica de la literatura

Las picaduras son frecuentes y se consideran un verdadero problema de salud pública. Objetivo: describir las especies de escorpiones, propiedades del veneno, fisiopatología, manifestaciones clínicas, diagnóstico y su manejo en la unidad de cuidados intensivos. Metodología: se realizó una búsqueda de la literatura en las bases de datos SciELO, LILACS, Scopus, PubMed-MedLine, Google Académico, así como en los servicios ClinicalKeys, se extrajo la información relevante, se seleccionaron aquellos estudios de tipo serie de casos, artículos originales o revisiones narrativas, de alcance y sistemáticas. Desarrollo: en Bolivia, fue descrita la especie Tityus (Tityus) sorataensis. El 66 al 90 por ciento de las picaduras tienen signos y síntomas limitados a dolor local, parestesias y cambios en la piel. Los efectos sistémicos se hacen evidentes a los 30 minutos y por lo general, dentro de las cuatro horas posteriores a la picadura. El tratamiento puede ser empírico, aplicar medidas generales, manejo del dolor y si está presente algunas complicaciones como edema pulmonar, choque cardiogénico es necesario su manejo en una sala de cuidados intensivos. Conclusiones: la intoxicación por picadura de escorpión, es rara, es un reto terapéutico, parece ser recomendable la administración del antídoto (antiveneno) junto al tratamiento de sostén. un mejor conocimiento de los escorpiones, puede alentar el interés en realizar nuevas investigaciones.

Bites are frequent and are considered a real public health problem. Objective: describe the species of scorpions, properties of the venom, pathophysiology, clinical manifestations, diagnosis and its management in the intensive care unit. Methodology: a literature search was carried out in the SciELO, LILACS, Scopus, PubMed-MedLine, Google Scholar databases, as well as in the ClinicalKeys services, in the period February-April 2023. Relevant information was extracted, They selected case series studies, original articles or narrative, scoping and systematic reviews. Development: in Bolivia, the species Tityus (Tityus) sorataensis was described. 66 to 90 percent of bites have signs and symptoms limited to local pain, paresthesias, and skin changes. Systemic effects become apparent within 30 minutes and generally within four hours of being bitten. The treatment can be empirical, apply general measures, pain management and if some complications are present such as pulmonary edema, cardiogenic shock, it is necessary to manage it in an intensive care room. Conclusions: Scorpion sting poisoning is rare, it is a therapeutic challenge, it seems to be advisable to administer the antidote (antivenoin) together with supportive treatment. a better understanding of scorpions may encourage interest in further research.

Toxicology in the emergency department: what's new?

Intentional and accidental drug overdose, recreational drug use and exposure to toxic substances are common reasons for people presenting to emergency departments. Although the mortality rate associated with these presentations is low in the UK, they can lead to significant morbidity and prolonged hospital admissions. This review discusses new developments in the management of paracetamol overdose. Several new protocols for the infusion of acetylcysteine, the antidote for paracetamol overdose, have been proposed in the past decade and evaluated in clinical studies. The 12-hour Scottish and Newcastle Acetylcysteine Protocol regimen and 20-hour Australian two-infusion bag protocol have been widely adopted into clinical practice and endorsed in national guidelines because of their shorter duration, reduction in adverse effects and efficacy in treating overdose. This article includes a care pathway that can facilitate the implementation of the Scottish and Newcastle Acetylcysteine Protocol. This article also discusses the emergency management of ingested button batteries, describes the emerging threat of novel psychoactive substances, and provides an update on new UK antidote guidelines. Further up-to-date guidance on management of clinical toxicology is available to healthcare professionals on the internet database TOXBASE.

Accident ofídic / Accidente ofídico / Ophidic accident

Introducció. L’accident ofídic és un motiu d’hospitalitzacióa Catalunya, sobretot en època estival. Tot i que és unmotiu d’ingrés infreqüent, presenta una mortalitat no negligible. Sobre la base d’un cas clínic, se’n revisa el maneig iel tractament, sovint desconegut.Cas clínic. Pacient de 12 anys ingressada per accident ofídic i reacció al verí amb afectació cutània local i analítica.Necessita ingrés a la unitat de cures intensives, administració de sèrum antiofídic i dessensibilització a aquestabans de l’administració subcutània.Comentaris. Es presenta el cas amb l’objectiu de revisar els criteris d’ingrés, les proves analítiques i els criteris d’administració (via i dosi) del sèrum antiofídic. (AU)

Introducción. El accidente ofídico es un motivo de hospitalizaciónen Cataluña, sobre todo en época estival. Aunque es un motivo deingreso infrecuente, presenta una mortalidad no despreciable. Enbase a un caso clínico, se intenta revisar su manejo y tratamiento,a menudo desconocido.Caso clínico. Paciente de 12 años ingresada en el centro por accidente ofídico y reacción al veneno con afectación cutánea local yanalítica. Precisa ingreso hospitalario en unidad de cuidados intensivos, administración de suero antiofídico y realización de desensibilización a este, antes de su administración subcutánea.Comentarios. Se presenta el caso con el objetivo de revisar loscriterios de ingreso, pruebas analíticas y criterios de administración (vía y dosis) del suero antiofídico. (AU)

Introduction. Ophidic accidents are a cause for hospitalization inCatalonia, especially during summer. Despite their rarity, mortalityrate is not negligible. In this report we review the management ofophidic accidents.Case report. A 12-year-old patient was admitted to the hospital dueto an ophidic accident with severe local reaction to the venom,together with laboratory alterations, who required hospitalization in the intensive care unit and administration of antiophidic serumwith previous desensitization.Comments. The case is presented with the aim of reviewing theadmission criteria, laboratory tests and administration criteria(route and dose) of the antiophidic serum. (AU)

The clinical course and treatment of black mamba (Dendroaspis polylepis) envenomations: a narrative review.

CONTEXT: The black mamba (Dendroaspis polylepis) is, due to its extremely toxic venom, one of the most dangerous snake species in Sub-Saharan Africa. A D. polylepis bite is a medical emergency and requires adequate action to prevent severe complications. However, there are no comprehensive reviews available based on clinical cases, and no readily accessible guidelines for standardized treatment. Therefore, we aim to provide an overview regarding the currently available clinical literature on D. polylepis envenomations; in order to promote knowledge on symptomatology and treatment options. METHODS: We searched for cases reporting humans bitten by D. polylepis in PubMed, Embase, Scopus, and Sabinet. We searched the reference lists of all eligible articles for additional articles. After quality assessment, 29 cases were included in this review. We used descriptive analysis to create an overview of the collected parameters. DISCUSSION: Among the included case reports and case series, D. polylepis envenomations most frequently resulted in decreased respiratory function, sweating and paralysis. The onset of symptoms usually occurred within 60 minutes. Neurological symptoms occurred more often than symptoms of autonomic dysfunction. In the reported cases most patients (26/29) received antivenom and most survived (25/29). We recommend the reporting of additional structured case reports to improve future analyses on the clinical course of envenomations, in order to improve public health response to D. polylepis envenomations.

Use of Crotalidae equine immune F(ab')2 antivenom for treatment of an Agkistrodon envenomation.

INTRODUCTION: Anavip (F(ab')2AV) is a lyophilized F(ab')2 immunoglobulin fragment derived from horses immunized with venom from Bothrops asper and Crotalus durissus. It was approved by the FDA in 2015 for treatment of North American rattlesnake envenomation but not for Agkistrodon envenomation. Published data regarding the efficacy and safety of Anavip in treating Agkistrodon envenomations is limited. We present a case of a patient treated with Anavip after confirmed Agkistrodon laticinctus envenomation. CASE DETAILS: A 77 year-old man was bitten on his fifth finger by a captive A. laticinctus. He was taken to a local emergency department where he received a 10 vial initial dose of F(ab')2AV for pain and swelling and was transferred. At the receiving facility, his pain had improved and his swelling had not progressed. Over the next 30 h, his platelets declined to 132,000/mm3 and he received an additional 4 vials of F(ab')2AV. The remainder of his course was unremarkable with complete recovery by 3 months. DISCUSSION: This case provides an additional published datapoint on the use of this F(ab')2AV in the treatment of envenomation by Agkistrodon.

Moderate-to-severe Vipera berus envenoming requiring ViperaTAb antivenom therapy in the UK.

BACKGROUND: Bites by the European adder (Vipera berus) in the UK are uncommon but potentially life threatening, and can be associated with marked limb swelling and disability. Following an interruption in Zagreb Imunoloski zavod antivenom supply around 2012, the UK changed its national choice of antivenom for Vipera berus to ViperaTAb, an ovine Fab monospecific antivenom. In the absence of randomised controlled trials, we established an audit to review its use in clinical practice. METHODS: A prospective audit of ViperaTAb use was conducted from March 2016 until November 2020 by the UK National Poison Information Service (NPIS). Users of the NPIS online toxicology database, TOXBASE, considering the use of antivenom for V. berus envenoming were invited to discuss the case with the on-call clinical toxicology consultant. Information was collected prospectively on indications, administration, adverse reactions and outcome of patients administered ViperaTAb antivenom. RESULTS: One hundred and seventy patients were administered ViperaTAb antivenom over five years. One hundred and thirty-two were adults and 38 children (median age and range: 38, 2-87 years). Bites occurred across the UK, but most commonly in coastal regions of Wales and of South-West and East England. Median time to presentation was 2.1 (IQR 1.5-4.0) h and to antivenom administration from presentation was 2.0 (IQR 0.9-3.6) h. A minority of patients presented to hospital more than 12 h after being bitten (n = 19, 11.2%) or received antivenom more than 12 h after presenting to hospital (n = 17, 10.0%). Features of systemic envenoming were present in 64/170 (37.6%) patients, including 23 (13.5%) with anaphylaxis and 26 (15.3%) with hypotension (nine with both). Clinician assessment considered the initial antivenom to have been effective in 122/169 (72.2%) patients. Repeated dosing was common, occurring in 55/169 (32.5%), predominantly due to persisting or worsening local effects (46/51, 90.2%). There were three cases of probable early adverse reaction. No deaths occurred during the study. Complications of envenoming were rare but included four patients that underwent surgery, three patients each with acute kidney injury, mild coagulopathy, or thrombocytopenia (one severe). The median duration of hospital stay was 43.7 (IQR 22.5-66.5) h, longer for children than adults (52.5 vs 41.3 h). CONCLUSION: ViperaTAb antivenom appears to be effective and safe and should be administered as soon as possible for patients meeting clinical criteria. Patients require close observation following antivenom to detect adverse reactions and progression or recurrence of envenoming. Close collaboration with expert NPIS consultant advice can help optimise antivenom timing, ensure repeated dosing is given appropriately, and avoid unnecessary surgical intervention. All hospitals, particularly those located in areas of relatively high incidence, should stock sufficient antivenom available at short notice, 24 h a day.

Novel Treatment Strategy for Patients with Venom-Induced Consumptive Coagulopathy from a Pit Viper Bite.

Pit viper venom commonly causes venom-induced consumptive coagulopathy (VICC), which can be complicated by life-threatening hemorrhage. VICC has a complex pathophysiology affecting multiple steps of the coagulation pathway. Early detection of VICC is challenging because conventional blood tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) are unreliable for early-stage monitoring of VICC progress. As the effects on the coagulation cascade may differ, even in the same species, the traditional coagulation pathways cannot fully explain the mechanisms involved in VICC or may be too slow to have any clinical utility. Antivenom should be promptly administered to neutralize the lethal toxins, although its efficacy remains controversial. Transfusion, including fresh frozen plasma, cryoprecipitate, and specific clotting factors, has also been performed in patients with bleeding. The effectiveness of viscoelastic monitoring in the treatment of VICC remains poorly understood. The development of VICC can be clarified using thromboelastography (TEG), which shows the procoagulant and anticoagulant effects of snake venom. Therefore, we believe that TEG may be able to be used to guide hemostatic resuscitation in victims of VICC. Here, we aim to discuss the advantages of TEG by comparing it with traditional coagulation tests and propose potential treatment options for VICC.

Snake bites by European vipers in Mainland France in 2017-2018: comparison of two antivenoms Viperfav® and Viperatab®.

Context: Today, immunotherapy with Fab or F(ab')2 fragments is considered as a gold standard treatment for patients bitten by vipers. We compared the efficiency of two antivenoms, Viperfav® and Viperatab®, in mainland France in 2017-2018 with data provided by the French poison control centre (PCC).Methods: Patients with a moderate (2a and 2b) or severe (3) envenomation after a European viper bite and treated with immunotherapy were included and the markers chosen were the risk of post-antivenom treatment worsening, duration of hospital stay and persistent functional discomfort on day 15. Statistical studies were based on multivariate data analysis.Results: Two hundred and ninety-seven cases were recorded. One hundred and eighty-two (61.3%) patients received Viperfav® and 115 (38.7%) received Viperatab®. Compared to Viperfav®, use of Viperatab® significantly increased the risk of post-antivenom treatment worsening (OR* 12.05; 95%CI [3.11; 46.70]; p < .001). No significant difference between these antivenoms was recorded with respect to the duration of hospital stay and persistent functional discomfort on day 15. Viperfav® and Viperatab® have a similar tolerance (p > .21). Otherwise, duration of hospitalisation was significantly increased by a delay of immunotherapy infusion of more than 12 h (OR 2.70; 95%CI [1.45-5.06]; p = .002) or a preventive administration of LMWH (OR 6.55; 95%CI [1.58-27.13]; p=.02).Discussion: While Viperfav® and Viperatab® have a similar tolerance, our data show that Viperatab® was associated with a higher risk of post-antivenom treatment worsening compared to Viperfav®. Furthermore, this study confirms that the antivenom should be used as soon as possible. Indeed, patients receiving the immunotherapy infusion from the grade 2b presented significantly more frequent exacerbated symptoms (OR 3.99; 95%CI [1.16-13.73]; p=.028) after the antivenom infusion compared to grade 2a group.Conclusions: Whereas no significant difference between these antivenoms was recorded with respect to the duration of hospital stay and persistent functional discomfort on day 15, use of Viperatab®, compared to Viperfav®, significantly increased the risk of post-antivenom treatment worsening (OR* 12.05; 95%CI [3.11; 46.70]; p < .001). Taken together, these data show that Viperfav® is the treatment of choice for the management of snake bites in France.

Cottonmouth snake bites reported to the ToxIC North American snakebite registry 2013-2017.

Introduction: The majority of venomous snake exposures in the United States are due to snakes from the subfamily Crotalinae (pit vipers). There are three types of US pit vipers: rattlesnakes (Crotalus and Sisturus spp.) copperheads (Agkistrodon contortrix), and cottonmouths (Agkistrodon piscivorus) also known as water moccasins. Cottonmouth bites are reported less frequently than other pit viper envenomations, and data on cottonmouth envenomation are limited. Our objective was to describe the epidemiology, clinical manifestations, and management of cottonmouth envenomations using prospective data reported to the Toxicology Investigators Consortium's (ToxIC) North American Snakebite Registry (NASBR)Methods: Cottonmouth envenomation cases reported to NASBR for the period from January 1, 2013, through December 31, 2017 were reviewed. Variables collected included patient demographics, bite location, clinical manifestations, and management.Results: Thirty-one cottonmouth envenomations were reported. Most bites occurred in children aged 7-12 (39%). Most bites involved the lower extremity (72%). Intentional interaction with the snake occurred in three cases (10%). Swelling was the most reported clinical effect and occurred in all patients. Gastrointestinal symptoms were reported in 19% of patients, and 19% developed coagulopathy. Antivenom treatment was used in 84% of patients. Nineteen patients (61%) required hospital stays of >24 hours.Discussion: Our study represents the first systematic prospective data collection on cottonmouth bites. Our data demonstrate that cottonmouth envenomations cause primarily local effects and, occasionally, systemic toxicity. Our study also demonstrates that antivenom is often indicated for these envenomations per published guidelines and recommendations.Conclusions: Cottonmouth envenomations are relatively infrequent. However, they can cause significant local and systemic toxicity. Most cottonmouth envenomations in this series were treated with antivenom and were hospitalized beyond 24 hours.

Risk factors associated with snake antivenom reaction and the role of skin test.

Antivenom reactions are a common complication of snake antivenom. This study aimed to identify predicators of antivenom reaction and the involvement of antivenom skin test in antivenom reaction development. This retrospective cohort study was conducted in six medical institutions in Taiwan. Data were extracted from the Chang Gung Research Database (CGRD) from January 2006 to December 2016. The association between antivenom reaction and patient demographics, type and dose of antivenom, and skin test results was analyzed. The study enrolled 799 patients, including 219 who developed antivenom reactions. Compared to patients receiving both freeze-dried hemorrhagic (FH) and freeze-dried neurotoxic (FN) antivenom, those administered a single type had a lower antivenom reaction risk (adjusted odds ratios [aORs]: 0.5 and 0.4, 95% confidence interval [CI]: 0.35-0.74 and 0.24-0.69, FH and FN respectively). Patients administered a higher antivenom dose (≥ 5 vials) had higher antivenom reaction risk (aOR: 1.8, 95% CI: 1.23-2.76). A positive skin test result was also associated with antivenom reaction (aOR: 16.7, 95% CI: 5.42-51.22). The skin test showed high specificity (98.5%, 95% CI: 97.49%-99.83%) but low sensitivity (17.5%, 95% CI: 10.74%-24.18%). The antivenom skin test should be abolished because of the extremely low sensitivity and possible misinterpretation of results because of the limitation of this examination.

Recovery from Copperhead Snake Envenomation: Role of Age, Sex, Bite Location, Severity, and Treatment.

INTRODUCTION: Few data exist to understand the recovery phase of pit viper envenomation. A recently published placebo-controlled clinical trial affords this opportunity. The purpose of this study is to examine the time course of recovery from copperhead snake (Agkistrodon contortrix) envenomation patients managed with and without the use of antivenom, stratified by age, sex, anatomic site of envenomation, initial severity of envenomation, and geographic region. METHODS: This is a post-hoc subgroup analysis of data from a multi-center double-blinded clinical trial of Fab antivenom (FabAV) vs. placebo. Outcomes were the Patient-Specific Functional Scale (PSFS) score at 3, 7, 10, and 14 days after envenomation. Least-squares mean PSFS score curves were calculated for each subgroup, and repeated measures ANOVA was used to estimate between-group comparisons. RESULTS: Seventy-two subjects were included, of whom 44 received FabAV. Males demonstrated better overall recovery than females (model predicted PSFS score 6.18 vs 4.99; difference 1.19; 95% CI 0.12 to 2.25; p = 0.029). No sex difference was found in response to FabAV. Overall recovery and effect of FabAV were similar in adult vs adolescent patients, patients with upper vs lower extremity envenomation, and patients with initially mild vs moderate envenomation signs. Analysis by geographic location was not successful due to ANOVA mode instability. CONCLUSIONS: Male victims of copperhead snake envenomation demonstrate slightly better recovery than females, but response to Fab antivenom overall is similar across all subgroups studied.

[Situation of public laboratories manufacturing antivenoms in Latin AmericaA situação dos laboratórios públicos produtores de soros antivenenos na América Latina]. / Situación de los laboratorios públicos productores de antivenenos en América Latina.

The situation of public laboratories manufacturing antivenoms in Latin America was analyzed, based on the results of a workshop coordinated by the Pan American Foot-and-Mouth Disease Center (PANAFTOSA) of the Pan American Health Organization (PAHO). Nine countries in the region have 12 public laboratories that produce and distribute antivenoms for use against different venomous animals. The situation of each laboratory was discussed, and an analysis was conducted of the current scenario, which is characterized by increasing regulatory requirements that vary in terms of infrastructure and production capacity. The authors identified a need to organize regional cooperation processes to improve the availability of antivenoms, including: research and development projects to improve processes and technologies; studies of the capacity of antivenoms to neutralize different poisons; and technical training programs for professionals and technical personnel. In the current context, in which the World Health Organization has prepared a global strategy for the prevention and control of snakebite envenoming, PANAFTOSA has taken on coordination of this initiative in the Americas. Improving the availability of antivenoms is the priority. As a result of the workshop, the RELAPA network was created, bringing together public laboratories that manufacture antivenoms in Latin America, in order to strengthen these laboratories and increase the availability of, and access to effective and safe antivenoms throughout Latin America.

A situação dos laboratórios públicos produtores de soros antivenenos na América Latina foi analisada com base nas conclusões de um seminário coordenado pelo Centro Pan-Americano de Febre Aftosa (PANAFTOSA) da Organização Pan-Americana da Saúde (OPAS). Em nove países da Região, encontram-se 12 laboratórios públicos que produzem e distribuem soros contra venenos de diferentes animais peçonhentos. Examinou-se a situação de cada laboratório, analisou-se o panorama atual marcado por crescentes demandas de regulação e pela heterogeneidade da infraestrutura e capacidade produtiva dos laboratórios e destacou-se a necessidade de um esforço concertado de cooperação regional com vistas a aumentar a disponibilidade de soros antivenenos, englobando projetos de pesquisa e desenvolvimento para o avanço dos processos e tecnologias, estudos do perfil da capacidade de neutralização dos soros contra diversos venenos e programas de capacitação técnica de profissionais e pessoal técnico. No contexto atual, em que uma estratégia mundial de prevenção e controle de acidentes ofídicos foi elaborada pela Organização Mundial da Saúde e que a coordenação das ações relacionadas na Região das Américas foi assumida pelo PANAFTOSA, melhorar a disponibilidade de soros antivenenos é prioridade. Como resultado deste seminário, a Rede de Laboratórios Públicos Produtores de Soros Antivenenos da América Latina (RELAPA) foi formada com o objetivo de fortalecer os laboratórios e aumentar a disponibilidade e a acessibilidade de soros antivenenos eficazes e seguros em toda América Latina.

Early pathology in venom-induced consumption coagulopathy by Rhabdophis tigrinus (Yamakagashi snake) envenomation.

Objective:Rhabdophis tigrinus (Yamakagashi in Japanese) is a venomous non-front-fanged colubroid snake capable of inflicting envenoming with life-threatening defibrinating coagulopathy. However, because of the uncommon incidence of bites and tendency for late development of symptoms/signs, the early effects of the venom on the coagulation system are poorly known. Case report: We describe a boy bitten by a wild R. tigrinus and report his clinical course starting at 30 min after the bite. Results: At 30 min after envenomation, only the thrombin-antithrombin complex (TAT) level was elevated. At 90 min after envenomation, laboratory data revealed a prolonged activated partial thromboplastin time (APTT) and increased prothrombin time international normalized ratio (PT-INR) with elevated fibrinogen degeneration product (FDP). At 5.5 h after envenomation, APTT and PT-INR increased beyond a measurable range, and fibrinogen levels dropped below the detection limit. We administered recombinant human soluble thrombomodulin and antivenom prepared against R. tigrinus antivenom. Venom-induced consumption coagulopathy (VICC), which is sometimes reported as disseminated intravascular coagulation (DIC), subsequently improved rapidly. Discussion: We found that TAT is the earliest marker to detect R. tigrinus envenomation and subsequent VICC occurrence. Although rTM was effective in this case, further studies are necessary to prove its safety and efficacy.

Incidence of allergic reactions to Crotalidae polyvalent immune Fab.

CONTEXT: The administration of Crotalidae polyvalent immune Fab (FabAV) currently requires close observation, so patients can be monitored for hypersensitivity reactions. The objective of this study was to evaluate the occurrence of hypersensitivity reactions to FabAV. METHOD: This was a retrospective cohort study utilizing data from a statewide poison center database in the United States. Records of all patients envenomated by a rattlesnake and treated with FabAV between January 2002 and December 2014 were evaluated. Patients with acute hypersensitivity reactions were identified, and reactions were evaluated descriptively. RESULTS: A total of 1340 adult and pediatric patients received FabAV during the study period. Of these, 19 (1.4%) patients had a potential reaction to FabAV, with 10 requiring a reduction in infusion rate, but none requiring discontinuation of the antivenom. Reactions occurred during the loading dose (n = 10), maintenance doses (n = 4), or were delayed reactions (n = 6). Symptoms recorded included pruritus (n = 8), hives (n = 8), rash (n = 7), vomiting (n = 7), nausea (n = 6), dyspnea or wheezing (n = 4), diaphoresis (n = 3), throat irritation (n = 2), and mild hypotension (n = 2). One patient was given a concomitant administration of low dose epinephrine infusion until completion of the antivenom course. However, none of the reactions were considered to be life-threatening. CONCLUSION: FabAV appears to be associated with a low incidence of acute hypersensitivity reactions. Patients may not require placement in a location capable of detecting and rapidly responding to hemodynamic and/or airway issues for FabAV monitoring alone.

Early administration of Fab antivenom resulted in faster limb recovery in copperhead snake envenomation patients.

BACKGROUND: No previous research has studied whether early snake antivenom administration leads to better clinical outcomes than late antivenom administration in North American pit viper envenomation. METHODS: A secondary analysis of data from a clinical trial of Fab antivenom (FabAV) versus placebo for copperhead snake envenomation was conducted. Patients treated before the median time to FabAV administration were classified as receiving early treatment and those treated after the median time were defined as the late treatment group. A Cox proportional hazards model was used to compare time to full recovery on the Patient-Specific Functional Scale (PSFS) instrument between groups. Secondary analyses compared estimated mean PSFS scores using a generalized linear model and the estimated proportion of patients with full recovery at each time point using logistic regression. To evaluate for confounding, the main analysis was repeated using data from placebo-treated subjects. RESULTS: Forty-five subjects were treated with FabAV at a median of 5.47 h after envenomation. Patients in the early treatment group had a significantly shorter time to full recovery than those treated late (median time: 17 versus 28 days, p = .025). Model-estimated PSFS scores were numerically higher at each time point in the early group. No difference was found between patients treated early versus late with placebo. CONCLUSIONS: In this secondary analysis of trial data, recovery of limb function was faster when Fab antivenom was administered soon after envenomation, as opposed to late administration.

Analysis of effectiveness of Iranian snake antivenom on Viper venom induced effects including analysis of immunologic biomarkers in the Echis carinatus sochureki envenomed victims.

Snakebite is an important toxicologic emergency with the potential of triggering local and systemic inflammation. Antivenom has remained the mainstay of treatment for snakebite envenomation. In this study we sought to investigate the effectiveness of Iranian antivenom in a series of 44 viper envenomed patients through analysis of changes in clinical severity and the levels of inflammatory markers. Clinical envenomation severity assessed by snakebite severity score (SSS) and laboratory exams of the patients were recorded before (baseline visit) and after antivenom therapy. During 12-h antivenom therapy, the median (range) score of SSS significantly decreased from 3.5 (2-10) on admission to 1 (0-5) in the last visit (P < 0.001). Moreover, a significant decrease in prothrombin time and international normalized ratio was found (P = 0.006 and 0.008; respectively). Plasma concentrations of interleukin (IL) 1-ß, IL-6, IL-8, tumor necrosis factor α (TNF-α), complement hemolytic activity (CH50) were also measured in 10 severely Echis carinatus sochureki envenomed victims and 10 age and gender-matched healthy controls. Except IL-8, the baseline levels of IL-1ß, IL-6 and TNF-α in victims were significantly higher than healthy controls (P = 0.005, <0.001 and < 0.001, respectively). Moreover, the baseline level of CH50 was significantly lower in the patients compared to healthy controls (P < 0.001). After 12-h antivenom therapy, the plasma levels of IL-1ß, IL-6 and TNF-α significantly decreased (P = 0.032, 0.006 and 0.003, respectively), the levels of IL-8 remained relatively unchanged and the CH50 significantly increased (P = 0.011). Iranian snake antivenom was effective in treating viper bite envenomation as it reversed clinical venom effects and restored near normal underlying inflammatory status. This study is the first to ascertain and report the effectiveness of this antivenom in human subjects.

Situación de los laboratorios públicos productores de antivenenos en América Latina / Situation of public laboratories manufacturing antivenoms in Latin America

The situation of public laboratories manufacturing antivenoms in Latin America was analyzed, based on the results of a workshop coordinated by the Pan American Foot-and-Mouth Disease Center (PANAFTOSA) of the Pan American Health Organization (PAHO). Nine countries in the region have 12 public laboratories that produce and distribute antivenoms for use against different venomous animals. The situation of each laboratory was discussed, and an analysis was conducted of the current scenario, which is characterized by increasing regulatory requirements that vary in terms of infrastructure and production capacity. The authors identified a need to organize regional cooperation processes to improve the availability of antivenoms, including: research and development projects to improve processes and technologies; studies of the capacity of antivenoms to neutralize different poisons; and technical training programs for professionals and technical personnel. In the current context, in which the World Health Organization has prepared a global strategy for the prevention and control of snakebite envenoming, PANAFTOSA has taken on coordination of this initiative in the Americas. Improving the availability of antivenoms is the priority. As a result of the workshop, the RELAPA network was created, bringing together public laboratories that manufacture antivenoms in Latin America, in order to strengthen these laboratories and increase the availability of, and access to effective and safe antivenoms throughout Latin America.