Neurotoxic envenomation by rattlesnakes has been of great concern throughout the Americas and in Arizona. In addition to clinical weakness, patients sometimes display myokymia, a disordered fasciculation of skeletal muscle, which is mediated by Mojave toxin. As neurotoxic venoms have been associated with increased release of creatine kinase (CK) activity and concordant increases in length of stay (LOS) in the hospital, it was retrospectively determined if point-of-care ultrasound detected myokymia at the bite site was associated with increased CK activity, LOS, and healthcare cost compared to rattlesnake envenomations not associated with myokymia. The Arizona Poison and Drug Information Center patient database was queried for patients with point-of-care ultrasound exam results at or near the bite site from 2017 to 2021. Using point-of-care ultrasound to detect subclinical myokymia, thirty-seven patients that met inclusion criteria were determined to have myokymia (n = 16) and/or not display it (n = 21). Patients with myokymia had twice the CK activities, double the LOS, and two-fold the healthcare costs of patients without myokymia detected. These findings serve as a rationale for future investigations to link ultrasound detected myokymia with patient outcomes.

Snakebite-induced local tissue damage remains a challenge in snakebite envenoming management because venom toxins rapidly disrupt vascular and extracellular matrix integrity at the bite site. This study evaluated the inhibitory effect of marimastat, an inhibitor of zinc-dependent metalloproteinases, against local tissue damage induced by Indonesian Trimeresurus insularis and Calloselasma rhodostoma venoms in a mouse skin model. The minimum hemorrhagic dose (MHD) of C. rhodostoma venom was determined in BALB/c mice and estimated to be 7.07 µg, while the MHD of T. insularis was adopted from a previous study. Mice received intradermal injections of venom at 2× MHD, either alone or pre-incubated with marimastat at venom:marimastat ratios of 1:1, 1:5, and 1:10 based on MHD equivalents. Macroscopic hemorrhage and histopathological changes, including erythrocyte extravasation, inflammatory cell infiltration, and collagen degradation, were assessed three hours after injection. Both venoms induced marked hemorrhagic lesions and tissue damage. Marimastat reduced venom-induced hemorrhage in both models, with near-complete inhibition in the T. insularis 1:10 group and complete inhibition in the C. rhodostoma 1:10 group. Marimastat also decreased erythrocyte extravasation, inflammatory infiltration, and collagen degradation, indicating preservation of microvascular and dermal matrix integrity. These findings support the central role of snake venom metalloproteinases in local viperid tissue damage and highlight marimastat as a promising adjunctive treatment for reducing venom-induced skin injury.

Snakebite envenomation caused by Deinagkistrodon acutus is a severe public health problem. Growing evidence indicates that snake venom exhibits obvious intraspecific geographic variation, which directly affects toxicity, organ damage, and antivenom efficacy. However, systematic studies on the geographic heterogeneity of D. acutus venom remain insufficient. In this study, we collected venoms from different geographical populations of D. acutus in China and performed a comprehensive analysis of lethality, plasma biochemistry, coagulation function, histopathology, proteomics, and antivenom neutralization. The results showed that venoms from different regions exhibited significant differences in LD50. Histopathological examination revealed that the spleen and lung were the main target organs, and the severity of multi-organ injury varied greatly among regions. Proteomic analysis revealed that all venoms shared a core protein set, whereas the composition and abundance of phospholipase A2 and snake venom metalloproteinase exhibited marked geographic diversity, and these compositional differences were closely correlated with variations in venom potency. Importantly, commercial antivenom showed effective neutralization against venoms from eastern regions but significantly reduced protective efficacy against southern and western populations. In conclusion, D. acutus venoms from different geographical origins present remarkable heterogeneity in toxicity, organ pathogenicity, toxin composition, and antivenom reactivity. This study provides key evidence for understanding venom geographic variation and offers an important theoretical basis for optimizing clinical treatment and developing region-adapted antivenoms.

Snake envenomation remains a critical global public health challenge. In Brazil, the genus Bothrops is responsible for most accidents, typically resulting in coagulopathy, hemorrhage, and renal failure. Despite its clinical prevalence, the molecular mechanisms driving plasma protein disturbances remain poorly understood. In this study, we applied mass spectrometry to characterize the plasma proteome and peptidome of mice following a sub-lethal dose of Bothrops jararaca venom and subsequent single dose antivenom treatment at timepoints 3, 6 and 24 h. From a total of 781 identified proteins, quantification of 590 revealed systemic pathological signatures such as the lower abundance of key coagulation and complement proteins, indicating coagulopathy and immune disruption. Simultaneously, an increase in tissue damage markers, innate immune response proteins, and Damage-Associated Molecular Patterns was detected. In the acute phase, the biological response was highly conserved regardless of antivenom administration, while by 24 h the group treated only with venom exhibited prolonged inflammation and metabolic stress, whereas the venom + antivenom group transitioned to cellular recovery and detoxification. The peptidomic analysis identified a large degradome of 1964 unique peptides, showing proteolysis of fibrinogen, apolipoprotein A-I, complement factors and protease inhibitors, among others. The analysis of cleavage sites implicated the activity of cysteine-, metallo-, and serine proteases in this process. Our results demonstrate that B. jararaca venom induced a rapid, dramatic systemic imbalance and proteostasis disruption that was only partially mitigated by antivenom. These findings underscore the necessity of developing complementary therapies that target both the primary toxins and secondary host-driven pathology.

Snakebite globally claims more than 100,000 lives per year and results in morbidity for 400,000 survivors. Current treatment uses antibody-based antivenoms which are constrained by their efficacy, safety, and cost. In this study we evaluated the efficacy of previously described repurposed drugs against viperid snakes of the medically important Bothrops genus. Despite variable toxin representation and bioactivity across this central and south American genus, we found that the lead inhibitors targeting metalloproteinases (marimastat and DMPS) and phospholipases (varespladib) demonstrated pan-species neutralisation in enzymatic assays, whilst nafamostat (serine protease inhibitor) had variable activity. The metalloproteinase inhibitors protected against the procoagulant and haemorrhagic effects of several venoms in phenotypic assays. Collectively these findings demonstrate that repurposed drugs may be of great value as early interventions for the treatment of bothropic envenoming in the Neotropics and thus provide a strong rationale for their progression into future preclinical and clinical evaluation for snakebite indication.

Antivenoms are the only specific medications available for the treatment of snakebite envenomation, which represents an important global public health concern. The success of treatment depends, in part, on the ability of the antivenom used to bind to and neutralize the toxins present in the venom. To achieve this efficacy, it is important that the immunizing venom pool be representative of the snake fauna to be covered, which is challenging given the inter- and intraspecific variability among snake venoms. In Brazil, snakes of the genus Bothrops are responsible for most snakebite accidents, and the antivenom used in the country is produced from a pool of five different Bothrops venoms (B. jararaca, B. jararacussu, B. alternatus, B. moojeni, and B. neuwiedi). However, quality control of antivenom efficacy during the production process was carried out exclusively against B. jararaca venom. Thus, the aim of this study was to develop and standardize an avidity ELISA for the analysis of serum samples obtained from horses immunized with the Bothrops venom pool against the different venoms that comprise this pool, also including B. atrox venom, as an auxiliary tool for evaluating antivenom efficacy. The avidity ELISA revealed variations in avidity both among the four batches of equine serum samples analyzed (inter-batch variation) and among the six Bothrops venoms included in the study (intra-batch variation).The avidity ELISA showed good applicability for Bothrops venoms and good intra- and inter-plate repeatability, suggesting the potential of this assay for implementation in preliminary efficacy evaluations of Bothrops antivenom production.

Crotaline snake species are endemic to the USA and are responsible for most cases of snakebite envenomation nationally. There is limited data reporting the incidence of unwitnessed snakebite envenomation in the USA; however, this is likely not an uncommon occurrence. In these cases, diagnosis is challenging as clinical findings can be non-specific and laboratory testing may be of limited use. Herein, we present a case of an unwitnessed crotaline snakebite envenomation that initially mimicked bacterial cellulitis. This case highlights the need for clinicians to maintain a high level of suspicion for snakebite envenomation in cases without a witnessed snakebite.

The Likiang pitviper (Gloydius monticola) is a high-altitude species endemic to northwestern Yunnan Province, China, and its venom effects on humans have not previously been documented. We report the first confirmed case of human envenomation by G. monticola, resulting in severe and progressive coagulopathy. A 34-year-old male was bitten on the hand while photographing an adult specimen at approximately 3500 m elevation. Initial local pain and swelling were followed by delayed but catastrophic coagulopathy, characterized by profound hypofibrinogenemia, markedly prolonged clotting times, elevated fibrin degradation products, and secondary haemorrhagic manifestations. Early administration of Gloydius brevicaudus monovalent antivenom did not prevent progression of coagulopathy. In contrast, subsequent treatment with Deinagkistrodon acutus monovalent antivenom was possibly associated with gradual and sustained recovery of coagulation parameters. This case demonstrates that G. monticola venom can induce life-threatening coagulopathy and should be regarded as medically significant. The possible differential clinical response to antivenoms highlights the limitations of phylogenetic relatedness as a predictor of antivenom efficacy and underscores the need for venom characterization and systematic evaluation of antivenom cross-neutralization for understudied pitviper species.

Snakebite envenoming by Crotalus snakes is a relevant public health problem in Brazil. From 2015 to 2024, 26,021 cases were reported in DataSUS, with 78,329 antivenom vials administered. However, only 27,257 vials had the specific antivenom type recorded, indicating 51,072 undocumented vials. In addition, the database records the administration of antivenoms that are not typically indicated for crotalic envenoming. Because these data originate from a secondary surveillance system, such discrepancies may reflect documentation gaps, data entry errors, or potential inconsistencies in antivenom selection. These findings highlight important limitations in national reporting systems and reinforce the need to strengthen clinical training, surveillance quality, and antivenom stewardship policies in Brazil.