Multiple thromboembolic strokes in a toddler associated with Australian Eastern Brown snake envenomation.
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SUBMITTER: Smith H
PROVIDER: S-EPMC6586992 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMyotoxicity is one of the common clinical manifestations of red-bellied black snake (Pseudechis porphyriacus) envenomation characterised by elevated creatine kinase (CK) concentrations of greater than 1000 U/L. This study aimed to investigate the occurrence of myotoxicity in patients following envenomation.Methods/principal findingsPatient characteristics and serial blood samples (timed venom concentrations and CK concentrations, pre- and post- antivenom) from 114 patients (median age 41, 2-90y; 80 male) were extracted from the Australian Snakebite Project database. Patients were categorised into three groups based on peak CK concentrations [no myotoxicity (<1000 U/L), mild (1000-10,000 U/L) and severe (>10,000 U/L)]. The odds of (mild or severe) myotoxicity was lower in patients that received early antivenom (within 6 hours post-bite) compared to those that received late or no antivenom (odd ratio was 0.186; 95% confidence interval, 0.052-0.664). A population pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the relationship between the time course of venom (a mixture of toxins) and effect (elevated CK). In addition, a kinetic-pharmacodynamic (KPD) model was developed to describe the relationship between time course of a theoretical toxin and effect. Model development and parameter estimation was performed using NONMEM v7.3. No single set of parameter values from either the PKPD or KPD models were found that could accurately describe the time course of different levels of severity of myotoxicity. The predicted theoretical toxin half-life from the KPD model was 11 ± 3.9 hours compared to the half-life of venom of 5.3 ± 0.36 hours. This indicates that the putative causative toxin's concentration-time profile does not parallel that of venom.ConclusionEarly antivenom administration reduces the incidence of myotoxicity. The venom concentration profile does not appear to be the driver for myotoxicity following envenomation. Additional factors that affect the sensitivity of the patient to snake venom/toxins must be explored to understand the relationship with myotoxicity.
| S-EPMC8432874 | biostudies-literature
Project description:De novo whole genome sequencing of the eastern brown snake, Pseudonaja textilis.
| PRJEB27869 | ENA
Project description:Snakebite being a quick progressing serious situation needs immediate and aggressive therapy. Snake venom antiserum is the only approved and effective treatment available, but for selected snake species only. The requirement of trained staff for administration and serum reactions make the therapy complicated. In tropical countries where snakebite incidence is high and healthcare facilities are limited, mortality and morbidities associated with snake envenomation are proportionately high. Traditional compilations of medical practitioners' personal journals have wealth of plant-based snake venom antidotes. Relatively, very few plants or their extractives have been scientifically investigated for neutralization of snake venom or its components. None of these investigations presents enough evidence to initiate clinical testing of the agents. This review focuses on curating Indian traditional snake envenomation therapies, identifying plants involved and finding relevant evidence across modern literature to neutralize snake venom components. Traditional formulations, their method of preparation and dosing have been discussed along with the investigational approach in modern research and their possible outcomes. A safe and easily administrable small molecule of plant origin that would protect or limit the spread of venom and provide valuable time for the victim to reach the healthcare centre would be a great lifesaver.
| S-EPMC9227218 | biostudies-literature
Project description:Snake envenomation is considered a public health problem in tropical countries, where they occur in a high incidence. The present study reports the snake envenomation that occurred in Mato Grosso do Sul state (Brazil) between 2007 and 2017. Epidemiological data were obtained from the online platform of the Notification Disease Information System and were analyzed according to biome. A total of 5568 cases of snake envenomations were recorded during the study period, where the highest frequency was registered between October and April. The majority of envenomations occurred in working-age males (20 to 39 years), caused mainly by Bothrops snakes, and the duration of care after the envenomation in most cases took three hours. The municipalities that showed the highest snake envenomations case per 100,000 inhabitants presents low population density, and have their economy based on agricultural activity, which is a risk factor to snake envenomations. To the Mato Grosso do Sul state, the total number of snake envenomations had a positive relationship with the size of the municipality. Since this, larger areas usually have a mosaic of environments, which may harbor higher richness and abundance of snakes, and can cause more snake encounters with the population, resulting in more snake envenomations.
| S-EPMC8452014 | biostudies-literature
Project description:Australia has some of the most venous snakes in the world, and envenomations of domestic dogs are common, but clinical signs as well as the diagnostic procedures and treatments of snake envenomations are poorly described. Therefore, we invited veterinary clinics in the state of Queensland, Australia, to provide detailed data on snake envenomation cases in dogs. A total of 230 cases were reported from 19 veterinary hospitals, with an average of 12.1 dogs per clinic, per year. Detailed case data were provided from 20 dogs-of these, 65.0% (13/20) were envenomated during the daytime, with collapse and paresis being the most common signs reported by owners. The median time between the onset of clinical signs and admission to the veterinary hospital was 60 min. Clinical signs were the sole diagnostic modality utilised by veterinarians in 30.0% (6/20) of cases. Activated clotting time was the most common diagnostic procedure conducted, while snake venom detection kits (SVDK) were only used in 15.0% (3/20) of cases. Of the dogs that received antivenom (85.0%, 17/20), the tiger/multibrown combination (3000 units tiger/4000 units brown) was predominately (13/17) provided. Three of the 17 dogs that received antivenom (17.6%) died or were euthanised. About 82.4% (14/17) of the dogs treated with antivenom, but only 33.3% (1/3) of the dogs not treated with antivenom, recovered (p = 0.140). Overall, veterinarians relied frequently on medical history, clinical signs, and diagnostic tests other than the SVDK and, thus, most likely, administered snake envenomation treatment based on their clinical experience.
| S-EPMC7909414 | biostudies-literature
Project description:BackgroundAlthough much is known about signs, symptoms, and management in the acute phase of crotaline snake envenomation, little is known about signs, symptoms, function, and quality of life during the recovery phase. The purpose of this observational pilot investigation is to evaluate the utility of several clinical outcome instruments in the setting of copperhead snakebite, and to characterize the clinical course of recovery.MethodsThis is a multi-center prospective, open-label, observational study of patients envenomated by copperhead snakes. We administered the Disabilities of the Arm, Shoulder, and Hand (DASH), Lower Extremity Functional Scale (LEFS), Patient-Specific Functional Scale (PSFS), Work Productivity and Ability Impairment: Special Health Problem (WPAI: SHP), Patients' Global Impression of Change (PGIC), Patient's Global Assessment of Recovery (PGAR), and SF-36 instruments, obtained numeric pain rating scales, and measured grip strength, walking speed, and swelling prior to hospital discharge and 3, 7, 14, 21, and 28 days after envenomation.Results20 subjects were enrolled; none were lost to follow-up. Most (80%) had moderate severity swelling, and most (75%) received antivenom. Across the broad range of measures, abnormalities of pain, swelling, impairments of physical and role function, and quality of life persisted for 7-14 days in most subjects. Validated self-reported outcome measures, such as the DASH, LEFS, PSFS, PGIC, SF-36, and the daily activities impairment portion of the WPAI: SHP were more responsive than measurements of swelling or walking speed. Data quality issues limited the utility of the work impairment portion of the WPAI: SHP. Residual signs, symptoms, and impairment in some subjects lasted through the 28-day study period. The study design precluded any assessment of the effectiveness of antivenom.ConclusionsSigns, symptoms, impaired function, and decreased quality of life typically last 7 - 14 days after copperhead envenomation. Several tools appear responsive and useful in studying recovery from pit viper envenomation.Trial registrationClinicalTrials.gov NCT01651299.
| S-EPMC4449608 | biostudies-literature
Project description:Diagnosis of snake envenomation is challenging but critical for deciding on antivenom use. Phospholipase A2 enzymes occur commonly in snake venoms and we hypothesized that phospholipase activity detected in human blood post-bite may be indicative of envenomation. Using a simple assay, potentially a bedside test, we detected high phospholipase activity in sera of patients with viper and elapid envenomation compared to minimal activity in non-envenomed patients.
| S-EPMC4003729 | biostudies-other
Project description:BackgroundNaja annulifera is a medically important venomous snake occurring in some of the countries in Sub-Saharan Africa. Accidental bites result in severe coagulation disturbances, systemic inflammation and heart damage, as reported in dogs, and death, by respiratory arrest, in humans. Despite the medical importance of N. annulifera, little is known about its venom composition and the pathogenesis of envenomation. In this paper, the toxic, inflammatory and immunogenic properties of N. annulifera venom were analyzed.Methodology/principal findingsVenom proteomic analysis identified 79 different proteins, including Three Finger Toxins, Cysteine Rich Secretory Proteins, Metalloproteinases, Phospholipases A2 (PLA2), Hyaluronidase, L-amino-acid oxidase, Cobra Venom Factor and Serine Proteinase. The presence of PLA2, hyaluronidase, fibrinogenolytic and anticoagulant activities was detected using functional assays. The venom was cytotoxic to human keratinocytes. In an experimental murine model of envenomation, it was found that the venom induced local changes, such as swelling, which was controlled by anti-inflammatory drugs. Moreover, the venom caused death, which was preceded by systemic inflammation and pulmonary hemorrhage. The venom was shown to be immunogenic, inducing a strong humoral immune response, with the production of antibodies able to recognize venom components with high molecular weight and to neutralize its lethal activity.Conclusions/significanceThe results obtained in this study demonstrate that N. annulifera venom contains toxins able to induce local and systemic inflammation, which can contribute to lung damage and death. Moreover, the venom is immunogenic, an important feature that must be considered during the production of a therapeutic anti-N. annulifera antivenom.
| S-EPMC6338361 | biostudies-literature
Project description:Textilinin-1 is a Kunitz-type serine protease inhibitor from Australian brown snake venom. Its ability to potently and specifically inhibit human plasmin (K(i) = 0.44 nM) makes it a potential therapeutic drug as a systemic anti-bleeding agent. The crystal structures of the human microplasmin-textilinin-1 and the trypsin-textilinin-1 complexes have been determined to 2.78 Å and 1.64 Å resolution respectively, and show that textilinin-1 binds to trypsin in a canonical mode but to microplasmin in an atypical mode with the catalytic histidine of microplasmin rotated out of the active site. The space vacated by the histidine side-chain in this complex is partially occupied by a water molecule. In the structure of microplasminogen the χ(1) dihedral angle of the side-chain of the catalytic histidine is rotated by 67° from its "active" position in the catalytic triad, as exemplified by its location when microplasmin is bound to streptokinase. However, when textilinin-1 binds to microplasmin the χ(1) dihedral angle of this amino acid residue changes by -157° (i.e. in the opposite rotation direction compared to microplasminogen). The unusual mode of interaction between textilinin-1 and plasmin explains textilinin-1's selectivity for human plasmin over plasma kallikrein. This difference can be exploited in future drug design efforts.
| S-EPMC3545990 | biostudies-literature
Project description:IntroductionFew 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.MethodsThis 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.ResultsSeventy-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.ConclusionsMale victims of copperhead snake envenomation demonstrate slightly better recovery than females, but response to Fab antivenom overall is similar across all subgroups studied.
| S-EPMC6942102 | biostudies-literature