Use Of Antivenom Research Articles

Unpredicted late-, new-onset thrombocytopenia and hypofibrinogenemia in Fab antivenom-treated rattlesnake envenomation

The use of Fab antivenom (Crotalidae Polyvalent Immune Fab (Ovine) (CroFab); Boston Scientific) against North American Crotalidae envenomation is associated with the development of late- (≥4 days post-envenomation), new-onset of hematological abnormalities. Although attempts have been made to identify predictive indicators during the acute phase of an envenomation, of patients who are not at-risk of late-, new-onset of hematological abnormalities, there has been at least one prior report of a patient who developed thrombocytopenia that was unpredicted by current indicators. We add three cases of unpredicted, late-, new-onset of hematological abnormalities in patients with Fab-treated rattlesnake bite.

Molecular Docking in Drug Discovery: A Review on Anti-snake Venom Development

Snakebite is a frequent accident faced by rural community's dwellers, and it has remained a neglected public health problem in many countries. Snake venom is a complex mixture of proteins, and they participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The only approved and accepted treatment for snakebite envenoming is the use of antivenoms produced by the purification of IgG immunoglobulins immunized against specific snake venom. However, various technological approaches are being pursued by different research groups, including the use of small-molecule inhibitors, antibody-based bio-therapeutics and peptide-based aptamer against enzymatic toxins and non-enzymatic toxins in snake venom. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review presents molecular docking studies of potential targeted key enzymes in snake venom.

Review of Scorpion Stings and Snakebites Treated by the French Military Health Service During Overseas Operations Between 2015 and 2017

Depending on their theatre of operation, French soldiers may potentially be exposed to scorpion stings and snakebites. Following the recommendations of a French military health service (FMHS) technical committee for envenomation, the FMHS provides antivenoms appropriate to each deployment. This work aimed to evaluate this risk of envenomation and to assess the antivenoms used by the FMHS in operational theatres since the creation of this committee in 2015. Cases were identified based on a review of temporary authorization of use application forms for the use of antivenom. Data were collected retrospectively from these forms, and prescribing physicians were contacted for any missing data. Between 2015 and 2017, 28 requests for temporary authorization of use were identified: 19 for Scorpifav (Sanofi-Pasteur, Lyon, France) and 9 for Fav-Afrique (Sanofi-Pasteur). The FMHS treated 15 soldiers and 4 civilians for scorpion envenomation with Scorpifav: 15 in Mali, 3 in Chad, and 1 in Niger. Systemic signs were observed in 7 patients. Two soldiers and 7 civilians were treated with Fav-Afrique for ophidian envenomation: 5 in Djibouti, 3 in Mali, and 1 in the Republic of Côte d'Ivoire. These 28 patients were treated without sequelae. Other than moderate erythema that resolved with an antihistamine, no adverse effects were reported. Medical evacuation to France was unnecessary. This study shows that the risk of envenomation for soldiers on deployment is low but real. Antivenoms used by the FMHS were efficient and well tolerated, preserving the operational capacity of deployed troops.

Dagestan blunt-nosed viper, Macrovipera lebetina obtusa (Dwigubsky, 1832), venom. Venomics, antivenomics, and neutralization assays of the lethal and toxic venom activities by anti-Macrovipera lebetina turanica and anti-Vipera berus berus antivenoms.

We have applied a combination of venomics, in vivo neutralization assays, and in vitro third-generation antivenomics analysis to assess the preclinical efficacy of the monospecific anti-Macrovipera lebetina turanica (anti-Mlt) antivenom manufactured by Uzbiopharm® (Uzbekistan) and the monospecific anti-Vipera berus berus antivenom from Microgen® (Russia) against the venom of Dagestan blunt-nosed viper, Macrovipera lebetina obtusa (Mlo). Despite their low content of homologous (anti-Mlt, 5–10%) or para-specific (anti-Vbb, 4–9%) F(ab')2 antibody fragments against M. l. obtusa venom toxins, both antivenoms efficiently recognized most components of the complex venom proteome's arsenal, which is made up of toxins derived from 11 different gene families and neutralized, albeit at different doses, key toxic effects of M. l. obtusa venom, i.e., in vivo lethal and hemorrhagic effects in a murine model, and in vitro phospholipase A2, proteolytic and coagulant activities. The calculated lethality neutralization potencies for Uzbiopharm® anti-Mlt and anti-Vbb Microgen® antivenoms were 1.46 and 1.77 mg/mL, indicating that 1 mL of Uzbiopharm® and Microgen® antivenoms may protect mice from 41 to 50 LD50s of Mlo venom, respectively. The remarkable degree of conservation of immunogenic determinants between species of the clades of European and Oriental viper, which evolved geographically segregated since the early Miocene, suggests an eventual window of opportunity for the treatment of envenomings by Eurasian snakes. Clearly, the rational use of heterologous antivenoms requires establishing their para-specificity landscapes. This paper illustrates the analytical power of combining in vitro and in vivo preclinical quantitative assays toward this goal.

Scorpion envenomation: state of the art.

Scorpion envenomation is common in the tropical and subtropical regions. It poses a major public health problem with some patients having serious clinical manifestations and severe complications including death. Old World and New World scorpions are usually contrasted because of differences in venom composition, clinical presentation and severity, and, accordingly, different therapeutic approaches. The majority of scorpion stings are either dry or result in low amounts of injected venom, thus explaining why up to 95% of scorpion stings ensue only in local signs. For a clinical envenomation to occur, it has been suggested that the interaction between the quantity of venom introduced in the body of the prey and the distribution volume should ensue in a critical threshold of scorpion toxin plasma concentration. In this case, there is a massive release of neurohormonal mediators (mainly catecholamine), with systemic vasoconstrictor effects eliciting a sharp increase in systemic arterial pressure and LV-filling pressure and decreased cardiac output. This early phase of cardiac dysfunction, also called "vascular phase", is followed by a severe cardiomyopathy, a form of Takotsubo cardiomyopathy, involving both ventricles and reversible in days to weeks. The more comprehensive understanding of the disease pathophysiology has allowed for a well-codified symptomatic treatment, thus contributing to a substantial reduction in the death toll of scorpion envenomation over the past few decades. The standard intensive-care treatment (when available) overcomes envenomation's consequences such as acute pulmonary edema and cardiogenic shock. Even though it continues to inspire many evaluative studies, immunotherapy seems less attractive because of the major role held by mediators in the pathogenesis of envenomation, and unfavorable pharmacokinetic properties to existing sera compared to venom. Meta-analyses of controlled trials of immunotherapy in severe scorpion envenomation reached similar conclusions: there is an acceptable level of evidence in favor of the use of scorpion antivenom (Fab'2) against Centruroides sp. in USA/Mexico, while there is still a need for a higher level of evidence for immunotherapy in the Old World envenomation.

TOXINOLOGY IN COLOMBIA: CONTRIBUTIONS OF PROGRAMA DE OFIDISMO/ESCORPIONISMO AND OTHER RESEARCH GROUPS

Background: Toxinology is a field of toxicology involved in studying toxins from animals, plants and microorganisms. In Colombia, in last thirty years, this area has been mainly studied by Programa de Ofidismo/Escorpionismo of the Universidad de Antioquia, however, some other research groups have been also contributed in our knowledge of venoms, toxin, effects and treatments. Objective: highlights the most important findings in toxinology made by Programa de Ofidismo/Escorpionismo and other research groups in Colombia. Methods: we collected and analyze119 manuscripts dealing with the history of ophidiology and toxinology in Colombia. Results: we describe some useful terms to understand the toxinology and their scopes. In addition, we build a brief history of ophidiology beginning with the period corresponding to the discovery of America, and ending with recent findings. Finally, we perform a great description of several results related to toxin isolation, characterization, antivenoms, clinical trials, new species descriptions, pretoemic and transcriptomic, among other. The nineteens was characterized by the study of snakebites, their clinic manifestations and the use of antivenoms. In addition, the ethnopharmacological studies of medicinal plants used in snakebite treatments began to be explored. The 2000s included the newly ethnopharmacology, toxin isolation, clinical trials, inhibitor studies, scorpion venom characterization and scorpion stings features. Finally, from 2010 until today, proteomic and transcriptomic gave the most important findings. Conclusions: Toxinology works in Colombia have contributed in our knowledge about endemic species, clinical manifestations of snakebites and scorpion stings, however, we invite to Colciencias and other funding agencies to have more resources in order to support more researchers in this field, since, snakebite is a public neglected disease and need more attention from governments and academic people. Finally, we still have ignorance about the venoms of some species and their possible mode of action. In addition, given the complexity of venoms, we ignore the potential use of toxins in current biomedicine. Thus, we must continue performing studies in toxinology.

Venom diversity in the Neotropical scorpion genus Tityus: Implications for antivenom design emerging from molecular and immunochemical analyses across endemic areas of scorpionism

Scorpions of the Neotropical genus Tityus are responsible for most severe envenomations in the Caribbean, South America, and Lower Central America (LCA). Although Tityus is taxonomically complex, contains high toxin polymorphism, and produces variable clinical manifestations, treatment is limited to antivenoms produced against species with restricted distributions. In this study, we explored the compositional and antigenic diversity of Tityus venoms to provide improved guidelines for the use of available antivenoms at a broader geographic scale. We used immunoblotting, competitive ELISA, and in vivo studies to compare reactivity against commercial antivenoms from Brazil, Venezuela, and Mexico, as well as MALDI-TOF mass spectrometry, cDNA sequencing, and phylogenetic analyses to assess venom sodium channel-active toxin (NaTx) content from medically important Tityus populations inhabiting Brazil, Colombia, Costa Rica, Ecuador, Panama, Trinidad and Tobago, and Venezuela. Additionally, we raised rabbit antibodies against Tityus venoms from LCA to test for cross-reactivity with congeneric species. The results suggest that Tityus spp. possess high venom antigenic diversity, underlying the existence of four toxinological regions in Tropical America, based on venom composition and immunochemical criteria: LCA/Colombia/Amazonia (Region I), Venezuela (Region II), southeast South America (Region III), and a fourth region encompassing species related to toxinologically divergent Tityus cerroazul. Importantly, our molecular and cross-reactivity results highlight the need for new antivenoms against species inhabiting Region I, where scorpions may produce venoms that are not significantly reactive against available antivenoms.

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

Naja atra venom-spit ophthalmia in Taiwan: An epidemiological survey from 1990 to 2016.

Venomous snakebites are common during hot seasons in Taiwan. However, rarely is venom spat directly into the subject's eyes, causing eye injury. Despite being uncommon, analytical data regarding venom-spit ophthalmia in Taiwan have been lacking. This study thus aimed to conduct an epidemiological survey on Naja atra venom-spit ophthalmia in Taiwan during the past decades to improve future care of such patients. Registered records of cases with snake venom injuries at the Taiwan National Poison Control Center from 1990 to 2016 were retrospectively reviewed, enrolling those with records of cobra venom-spit eye injuries and excluding exotic species. Demographic data, clinical symptoms, snake species, ocular conditions, management, and outcomes were recorded and analyzed. A total of 39 cases suffering from Naja atra venom-spit ophthalmia were enrolled. The overall incidence rate was 1.6 cases per million people from 1990 to 2016. Among the included cases, most were unilaterally injured (82%), male (95%), aged 18 to 59 years (90%), injured during catching (51%), and injured in spring and summer (92%). Ocular symptoms occurred in 90% of the cases, majority of which included ocular pain (90%) and redness (85%). Conjunctivitis (67%) and corneal injury (59%) of involved eyes were common. Immediate water irrigations were done in all cases, most of whom received further topical eye drops, including antibiotics, corticosteroids, and vasoconstrictors. Although topical or intravenous antivenoms were administered in 11 cases, no obviously superior outcome was observed. Most cases (77%) were symptom free after the acute stage. Although Naja atra venom-spit ophthalmia in Taiwan is uncommon, the risk for transient ocular symptoms and corneal/conjunctival injury does exists. Prompt ocular irrigation and professional ophthalmic care after envenomation help prevent serious ocular sequelae. Moreover, superior outcomes were not achieved with the use of antivenom. Nonetheless, further studies are required to clarify the role antivenoms play in venom-spit ophthalmia.

Plants used for the treatment of snakebite among Hausa-Fulani Tribes in Tsiga District, Bakori Local Government Area Katsina State Nigeria

Traditional snakebite Healers farmers and Fulani cattle rearers in some villages in Tsiga District, Bakori local government Area Katsina State, were interviewed through the use of structured questionnaires for the various ways they manage snakebite in their livestock and among the people of their community they provided information on plants and parts used, mode of preparation and administration, habit, source and availability of medicinal plants. Field excursions were conducted along forest trails taking traditional healers as guides and voucher specimens of cited medicinal plants were collected. Result obtained showed that at least 83% of the respondents rely on the use of plants in managing snakebite on people or their livestock. Plants belonging to 12 different families were encountered. The common venomous snakes found in the study area include Black necked spiting Cobra (Naja nigricollis), puff adder (Bitis arietans), and saw scaled viper (Echis carinatus) polyvalent anti-snake venom is the only known therapeutic agent available throughout the world major drawback of serum therapy is its prohibitive cost and chance that victims may avail untimely medical care because of remote locations when bitten. The present article presents plants used for the treatment of snakebite randomness or the use of a variety of species in different families appear to be a feature of traditional snakebite treatments. Plants encountered can provide an alternative to the use of conventional antivenom.

Venomics and antivenomics of the poorly studied Brazil's lancehead, Bothrops brazili (Hoge, 1954), from the Brazilian State of Pará.

ABSTRACTBackground:The Brazil’s lancehead, Bothrops brazili, is a poorly studied pit viper distributed in lowlands of the equatorial rainforests of southern Colombia, northeastern Peru, eastern Ecuador, southern and southeastern Venezuela, Guyana, Suriname, French Guiana, Brazil, and northern Bolivia. Few studies have been reported on toxins isolated from venom of Ecuadorian and Brazilian B. brazili. The aim of the present study was to elucidate the qualitative and quantitative protein composition of B. brazili venom from Pará (Brazil), and to carry out a comparative antivenomics assessment of the immunoreactivity of the Brazilian antibothropic pentavalent antivenom [soro antibotrópico (SAB) in Portuguese] against the venoms of B. brazili and reference species, B. jararaca.Methods:We have applied a quantitative snake venomics approach, including reverse-phase and two-dimensional electrophoretic decomplexation of the venom toxin arsenal, LC-ESI-MS mass profiling and peptide-centric MS/MS proteomic analysis, to unveil the overall protein composition of B. brazili venom from Pará (Brazil). Using third-generation antivenomics, the specific and paraspecific immunoreactivity of the Brazilian SAB against homologous (B. jararaca) and heterologous (B. brazili) venoms was investigated. Results:The venom proteome of the Brazil’s lancehead (Pará) is predominantly composed of two major and three minor acidic (19%) and two major and five minor basic (14%) phospholipase A2 molecules; 7-11 snake venom metalloproteinases of classes PI (21%) and PIII (6%); 10-12 serine proteinases (14%), and 1-2 L-amino acid oxidases (6%). Other toxins, including two cysteine-rich secretory proteins, one C-type lectin-like molecule, one nerve growth factor, one 5'-nucleotidase, one phosphodiesterase, one phospholipase B, and one glutaminyl cyclase molecule, represent together less than 2.7% of the venom proteome. Third generation antivenomics profile of the Brazilian pentabothropic antivenom showed paraspecific immunoreactivity against all the toxin classes of B. brazili venom, with maximal binding capacity of 132.2 mg venom/g antivenom. This figure indicates that 19% of antivenom's F(ab')2 antibodies bind B. brazili venom toxins. Conclusion:The proteomics outcome contribute to a deeper insight into the spectrum of toxins present in the venom of the Brazil’s lancehead, and rationalize the pathophysiology underlying this snake bite envenomings. The comparative qualitative and quantitative immunorecognition profile of the Brazilian pentabothropic antivenom toward the venom toxins of B. brazili and B. jararaca (the reference venom for assessing the bothropic antivenom's potency in Brazil), provides clues about the proper use of the Brazilian antibothropic polyvalent antivenom in the treatment of bites by the Brazil’s lancehead.

Clinical characteristics of jellyfish stings in Japan.

AimJellyfish known as “habu‐kurage” (Chironex yamaguchii) inhabit the waters surrounding Okinawa and Amami, Japan, and jellyfish stings are limited to areas outside the Japanese main island. However, the shifts promoted by global warming and increasingly intensive interactions with people have led to concerns regarding the possibility of increased jellyfish stings on the main island of Japan. Similar concerns are being raised all over the world. However, studies examining clinical characteristics of jellyfish stings have been limited to Australia, the USA, Europe, and South‐East Asia. Thus, this study aimed to examine for the first time the clinical characteristics of jellyfish stings in Japan.MethodsWe undertook retrospective questionnaire surveys from January 2013 to December 2017 to determine patient characteristics, treatment, and clinical outcomes. We compared patient characteristics between tourists and non‐tourists. The primary end‐point of the present study was to clarify the clinical characteristics of jellyfish stings.ResultsOver the 5‐year study period, 204 patients were identified from eight hospitals based on the basic questionnaire, and 35 patients with moderate‐to‐severe jellyfish stings were also identified. All patients recovered well, including five patients with severe jellyfish stings. Antivenom was not given. The time intervals from the occurrence of jellyfish stings to hospital arrival significantly differed between tourists and non‐tourists (P = 0.049), and all tourists visited the emergency department (P = 0.009).ConclusionsApproximately 40 cases of jellyfish stings occurred annually in Japan between 2013 and 2017. Patients recovered well without the use of antivenom.

336 Recovery From Copperhead Snake Envenomation: Role of Age, Sex, Bite Location, Severity, and Treatment

Few data exist to understand the recovery phase of pit viper envenomation and whether specific patients recover more quickly, or respond differently to antivenom therapy, than others. This study examines 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.

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

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. This is a post-hocsubgroup 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 14days after envenomation. Least-squares mean PSFS score curves were calculated for each subgroup, and repeated measures ANOVA was used to estimate between-group comparisons. Seventy-two subjects were included, of whom 44 received FabAV. Malesdemonstrated better overall recovery thanfemales (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. Male victims of copperhead snake envenomation demonstrate slightly better recovery than females, but response to Fab antivenom overall is similar across all subgroups studied.

Edematic and coagulant effects caused by the venom of Bothrops rhombeatus neutralized by the ethanolic extract of Piper auritum

Ethnopharmacological relevanceIn Colombia, the only authorized treatment to cure snakebite envenomation is with the use of antivenom. The antivenom neutralizes the systemic effects properly, but is not very effective at neutralizing local effects, thus several cases have lead to complications. On the other hand, rural communities turn to the use of plants that are easily accessible and available for basic health care. One of these plants is named Piper auritum (PA), which is traditionally highlighted in some indigenous communities of Antioquia and Chocó. Aim of the studyThe main objective of this work was to characterize the venom's toxicity by determining the Minimum Edema Dose (MED), the Minimum Coagulant Dose-Plasma (MCD-P), the Minimum Hemorrhagic Dose (MHD) and to determine the neutralizing power of the Total Ethanolic Extract (TEE) from leaves of PA on the localized and systemic effects caused by the Bothrops rhombeatus venom. Materials and methodsTo begin, the minimum dose that causes edema-forming, coagulant and hemorrhagic activities was determined. The protocols investigated include coagulant and edematic activities caused by the venom of Bothrops rhombeatus which were neutralized by the TEE of PA. ResultsThe MCD-P was found to be 0.206 ± 0.026 μg, the MED is the same at 0.768 ± 0.065 μg, and the MHD is 3.553 ± 0.292 μg, which are different from the reports for Bothrops asper and Bothrops ayerbei. Next, a phytochemical screening was done to the TEE where mainly triterpenes, steroids, coumarins, saponins, and lignans were identified. Also present were 43,733 ± 2106 mg AG/g ES of phenols, which are secondary metabolites that are probably responsible for the neutralization of coagulant and edematic activities at rates of 2363.870 μL and 1787.708 μL of extract/mg of venom, respectively. As a comparative parameter, the National Institute Health's (NHI) effective dose of the antivenom was used as a comparative parameter. In addition, we determined the toxicity of the TEE of PA on to Artemia salina, being moderately toxic at 6 and 24 h, while the essential oil of PA at the same observation hours is in the extremely toxic range. ConclusionsThe results reflect that the extract of P. auritum has an anti-inflammatory effect similar to that of the NIH serum. It could be used as a complement of NIH antivenom, using them together so it contributes to effectively reduce inflammation and the socio-economic impact generated by the permanence of a patient victim of snakebite in health centers. ClassificationsImmunological products and vaccines.

A 10-year retrospective review of stonefish sting injury in Hong Kong

Background: Stonefish sting injury is one of the common marine stings in Hong Kong. It is commonly sustained during maritime activities, and it could be regarded as occupational hazard for chefs or domestic hazard for family. Its envenomation could lead to significant local symptoms (pain or swelling) and serious complications, including infection and compartment syndrome. Objectives: This study is to review its clinical presentation and various treatment modalities. Methodology and study design: Reported cases of stonefish stings to Hong Kong Poison Information Centre from October 2008 to October 2018 were included in the study. The cases were retrieved from the Hong Kong Poison Information Centre electronic database. Information on patient demographic data, clinical parameters (e.g. the site of injury, presenting symptoms), and various treatment modalities (e.g. analgesics, hot water immersion, and use of antivenom) was collected. Results: There were 32 eligible patients included in this case series. All of them sustained the injury over either their fingers or hands. All patients reported pain over the site of injury. Other reported symptoms included numbness (41%), swelling (81%), and redness (47%). Twenty-five patients (78%) had radiograph done, and one of them was noted to have foreign body retained at the site of envenomation. All patients received hot water immersion to the affected part at 40°C–45°C for at least 30 min. Altogether eight patients (25%) received stonefish antivenom for pain relief. One patient developed compartment syndrome and received emergency operation of fasciotomy of right hand and forearm. Conclusion: Stonefish envenomation can cause extreme pain, swelling, and erythema, which can be managed with hot water immersion, analgesics, and prophylactic antibiotics. Use of antivenom can be considered in selected case.

Antivenom Treatment Is Associated with Fewer Patients using Opioids after Copperhead Envenomation

IntroductionCopperhead envenomation causes local tissue destruction, leading people to seek treatment for the pain and swelling. First-line treatment for the pain is opioid medications. There is rising concern that an initial opioid prescription from the emergency department (ED) can lead to long-term addiction. This analysis sought to determine whether use of Fab antivenom (FabAV) for copperhead envenomation affected opioid use.MethodsWe performed a secondary analysis using data from a randomized clinical trial designed to determine the effect of FabAV on limb injury recovery following mild to moderate copperhead envenomation. Opioid use was a defined secondary outcome in the parent trial. Patients were contacted after discharge, and data were obtained regarding medications used for pain and the patients’ functional status. This analysis describes the proportion of patients in each treatment group reporting opioid use at each time point. It also assesses the interaction between functional status and use of opioids.ResultsWe enrolled 74 patients in the parent trial (45 received FabAV, 29 placebo), of whom 72 were included in this secondary analysis. Thirty-five reported use of any opioids after hospital discharge. A smaller proportion of patients treated with FabAV reported opioid use: 40.9% vs 60.7% of those in the placebo group. The proportion of patients using opioids remained smaller in the FabAV group at each follow-up time point. Controlling for confounders and interactions between variables, the model estimated that the odds ratio of using opioids after hospital discharge among those who received placebo was 5.67 times that of those who received FabAV. Patients who reported higher baseline pain, those with moderate as opposed to mild envenomation, and females were more likely to report opioid use at follow-up. Patients with ongoing limitations to functional status had an increased probability of opioid use, with a stronger association over time. Opioid use corresponded with the trial’s predefined criteria for full recovery, with only two patients reporting opioid use in the 24 hours prior to achieving full limb recovery and no patients in either group reporting opioid use after full limb recovery.ConclusionIn this study population, the proportion of patients using opioids for pain related to envenomation was smaller in the FabAV treatment group at all follow-up time points.

Bites by Tomodon dorsatus (serpentes, dipsadidae): Clinical and epidemiological study of 86 cases

A total of 86 proven cases of Tomodon dorsatus bites admitted to Hospital Vital Brazil (HVB) of Butantan Institute, in São Paulo, Brazil, between 1945 and 2018, were retrospectively analyzed. The cases included were those in which the snake was brought to HVB and was correctly identified. Of the 86 cases of snake bites, it was possible to describe the sex of the snake in 52 cases; 31 (59.6%) snakes were male. Only 52 snakes out of 86 could be studied because of their preservation status. The length of snakes (snout–vent length) ranged from 180 to 770 mm. Of the 86 snakes, 72 could be distinguished as adults (n = 63, 87.5%) or juveniles (n = 9, 12.5%). Most bites occurred in the spring and summer seasons (n = 57, 66.3%) and during warmer periods of the day (n = 61, 72.6%), between 9 a.m. and 3 p.m.The mean (±standard deviation) age of the victims was 26.9 ± 17.2 years, and 60 (69.8%) were men. Approximately 90% of the patients sought medical care within 6 h after the bite. Both upper (n = 45, 52.3%) and lower (n = 37, 43.0%) limbs were the most frequently bitten, particularly the feet and hands (n = 54, 62.8%). The local clinical manifestations were pain (n = 55, 64.0%), transitory bleeding (n = 23, 26.7%), erythema (n = 22, 25.6%), edema (n = 14, 16.3%), paresthesia (n = 9, 10.5%), and ecchymosis (n = 3, 3.5%). Only 10 (11.6%) patients reported non-specific systemic symptoms characterized by transient dizziness or mild headache, and 21 (24.4%) patients showed no evidence of envenomation. A 20 min whole blood clotting test was performed in 31 (36.0%) patients on admission and all of them had coagulable blood. Supportive treatment was offered to 38 (44.2%) patients, namely, antiseptic (n = 20, 23.3%), antihistamines (n = 12, 14.0%), and analgesics (n = 9, 10.5%). Four (4.7%) patients were inappropriately treated with Bothrops antivenom before their admission to HVB. No sequelae or relevant complications were observed in patients, and the prognosis was benign. Therefore, although T. dorsatus bites can cause mild local symptomatology, it is important that health professionals know how to make the correct diagnosis to avoid unnecessary use of antivenom.

Fatal Snakebite Envenoming and Agricultural Work in Brazil: A Case-Control Study.

We investigated the association between fatal snakebite envenoming and agricultural work in Brazil, considering the effects of relevant covariables. A nested case-control study was performed using 1,119 fatal cases of snakebite envenoming among persons aged ≥ 10 years, notified to the Brazilian official reporting system, from 2004 to 2015. As controls, 4,476 cases were randomly selected from the 115,723 nonfatal cases of snakebite, without missing data, that occurred in the same time period. The main predictor was occupation in the agriculture sector; the main outcome was death by snakebite envenoming. Logistic regression analysis was used to investigate the main association, controlling for the effects of relevant covariables. Fatal cases had a 20% greater chance (odds ratio [OR] = 1.20; 95% confidence interval [CI]: 1.00-1.39) of being among farmers than the controls. However, late (≥ 6 hours) time to treatment (OR = 2.00; 95% CI: 1.70-2.36); adequate antivenom with an insufficient (OR = 1.25; 95% CI: 1.04-1.50) or excessive (OR = 4.89; 95% CI: 4.10-6.03) number of vials; inadequate antivenom and insufficient or excessive number of vials (OR = 3.87; 95% CI: 2.40-6.24); no use of antivenom (OR = 2.05; 95% CI: 1.60-2.64); and age ≥ 60 years (OR = 1.98; 95% CI: 1.61-2.44) were more strongly associated with lethality. Lethality was 1.0% in the period, being 0.47% among those receiving early and adequate treatment. We concluded that in Brazil, fatal snakebite envenoming was associated with agricultural work, controlling for relevant covariates. However, quality of health care provided and greater age were much more strongly associated with lethality.

Study on the obtaining of Tityus trivittatus venom in Argentina

Envenomation by scorpions of the genus Tityus is an important public health problem in Argentina, involving near 8000 stings and 2 deaths each year. Treatment for envenomation is the use of specific antivenom and intensive hospital care. Antivenom is produced by the Ministry of Health and freely distributed throughout the country. For antivenom production it is necessary to collect scorpion venom, which is a difficult task because although scorpions can be found in Argentina, they are less abundant than in warmer latitudes. For this reason venom collection constitutes a bottleneck for antivenom production. Although in Argentina several species of Tityus can be found, most of the accidents are caused by Tityus trivittatus, and the venom of this scorpion has historically been the venom used for antivenom production. We analyzed retrospectively 26 pools of telson homogenates (6964 telsons) and 37 pools of milked venom obtained by electrical stimulation (equivalent to 6841 milkings). Lethal potencies of samples from different provinces were very similar, although venom from scorpions of Buenos Aires city showed the lowest potency. The venom obtained by milking (median LD50 12.3 μg), provided batches containing LD50s more potent when compared with the venom obtained from telson homogenates (p < 0.0001). Many batches of telson homogenates (30%) showed lower potencies than acceptable for antivenom production and control. In addition to the study of the venom yield, the records of immunization of horses, the potency of the batches and the protein content of each batch of anti-scorpion antivenom produced were analyzed, comparing those produced using milked venom with those using telson homogenates as immunogens. Batches produced using milked venom required a shorter period of immunization (p < 0.0001), rendered higher neutralizing titers (p 0.0350) and possessed lower protein content (p 0.0092). Results clearly showed that the milking of scorpions is a more efficient tool to obtain venom for antivenom production in comparison to the use of telson homogenates.