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. Snakebites are a major health problem, particularly in rural parts of tropical countries. Every year, millions of people are bitten by venomous snakes, causing more than 100,000 deaths and leaving many others with permanent disabilities. The World Health Organization classifies snakebite as a neglected tropical disease because, despite its devastating impact, it has received relatively little attention and investment. The only approved treatment for snakebite is antivenom. Antivenom is made by stimulating animals to produce antibodies against snake venom and must be given intravenously in a hospital. While it can be lifesaving, it has important limitations: it is often only effective against certain snake species, can cause serious side effects, and is frequently unavailable where snakebites occur. In remote regions, such as parts of the Amazon, people may have to travel five hours or more before reaching medical care. Earlier treatment could greatly improve survival and reduce permanent injuries. Researchers are therefore investigating new treatments that could be given soon after a bite, before a patient reaches hospital. One promising approach is to repurpose existing small molecule drugs that block the harmful toxins found in snake venom. Three drugs – varespladib, marimastat and DMPS – have already shown promise because they can block two major groups of venom toxins responsible for much of the damage caused by snakebites. Clare et al. wanted to further evaluate the suitability of these drugs, together with another drug called nafamostat, against venom from seven species of Bothrops snakes. Bothrops snakes are responsible for most serious snakebites in Latin America, and their venoms contain a mixture of toxins that damage tissues, disrupt blood clotting and cause severe haemorrhage. The researchers carried out a series of laboratory experiments to measure how well the drugs blocked different venom effects, including toxin activity, blood clotting problems and haemorrhage. Although the venoms varied between snake species, the drugs targeting two major toxin groups consistently worked across all seven species in laboratory tests. In contrast, nafamostat showed more variable effects. The experiments also showed that marimastat and DMPS, which target enzymes responsible for tissue damage and haemorrhage, provided the strongest overall protection. The drugs targeting the other toxin groups also showed promise but require further development. Overall, the findings of Clare et al. suggest that repurposed drugs could become valuable early treatments for Bothrops snakebites in Latin America. Because these medicines can be taken by mouth, they could potentially be given in the community soon after a bite, buying valuable time before patients reach a hospital for antivenom treatment. The study also highlights the need to develop additional drugs that target other important venom toxins, helping pave the way for more effective treatments for snakebite in the future.
Understanding the ecological origin of snakes has remained a century-old challenge1,2, hindered by an extremely sparse early fossil record and conflicting interpretations of fossil ecologies. Here we describe an exceptionally preserved Cretaceous fossil snake, Tametara mirim gen. et sp. nov., from Brazil, representing one of the earliest-diverging stem snakes. High-resolution micro-CT scans reveal unprecedented details of cranial nerves, inner ear and brain anatomy, enabling the most integrated reconstruction of stem snake neuroanatomy to date. Quantitative and qualitative endocast analyses demonstrate that Tametara had a brain morphology distinct from both other stem and extant snakes, revealing substantial early neuroanatomical disparity-and probably sensory functions-in snake evolution. Independent evidence from telencephalon shape and bone microstructure converges on a fossorial lifestyle for Tametara and non-fossorial for another stem snake: Dinilysia. These results indicate that major ecological transitions occurred early in snake evolution, and that known stem species do not represent the ancestral condition of crown snakes. Early snake evolution thus involved complex shifts in habitat use and sensory ecology, revealing greater ecological and neuroanatomical diversity than previously thought.
Research indicates that the human visual system is highly efficient at detecting snakes, yet less is known about how ecological visual contexts modulate this advantage. We conducted two experiments with university students (N = 58 each) to test whether background complexity influences snake-detection efficiency using a dual-task paradigm. In Experiment 1, stimuli were presented on a uniform grey background. Here, snakes were detected and visually fixated significantly faster than non-snake control animals, consistent with previous findings. Crucially, this advantage was not influenced by participants' self-reported fear of snakes or anxiety levels. In Experiment 2, the same stimuli were embedded in a complex leaf-litter background. Under these conditions, non-snake stimuli were detected earlier than snakes, and overall accuracy declined. This indicates that the snake detection advantage is sensitive to changes in perceptual and contextual conditions, which may attenuate or reverse the pattern observed under simplified settings. Subjective fear scores again showed no moderating effect. Overall, these findings are consistent with an evolved sensitivity to snake-related visual features, but show that this advantage is context-dependent and can be attenuated or even reversed under ecologically complex visual conditions, independently of self-reported fear. They underscore the necessity of incorporating ecological variables into threat-detection research.
Lead exposure has been documented in a multitude of bird and mammal species but less frequently in reptiles. Of the studies that have evaluated lead concentrations in reptiles, few have focused on snakes. We analyzed lead concentrations in liver and two types of bone from 24 gophersnakes (Pituophis catenifer; Pc) and 12 Great Basin rattlesnakes (Crotalus oreganus lutosus; Col) found dead along roads in the Morley Nelson Snake River Birds of Prey National Conservation Area in southwestern Idaho, U.S.A from 2018 to 2021. Because this area has been heavily impacted by both military and recreational activity, we also quantified lead concentrations in the soil near where the dead snakes were found. All soil samples had detectable lead (median: 12.53 µg/g; range: 0.07-16.77). Within individuals of both species, dry weight lead concentrations in liver generally were lower than those in bone (n samples < LOQ Liver: 9 of 13 (Pc), 9 of 10 (Col) (only a subset of individuals were in good enough condition to provide liver samples); Bone: 0 of 24 (Pc), 3 of 12 (Col). We did not detect any differences in lead concentrations between the species for either tissue type, nor between bone from the front (anterior) or back (posterior) of the snake skeleton. Additionally, we did not detect any correlation between lead concentration in soil collected at the roadkill sites and the tissue in the snakes. These data provide baseline information for lead exposure of two snake species in southwestern Idaho and demonstrate how lead is present in higher trophic levels within this ecosystem.
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.
Snakebite is a neglected tropical disease with a high burden in South Asia, particularly India. Acute kidney injury (AKI) is one of the most serious complications of snake envenomation, which has significant morbidity, mortality, and risk of chronic kidney disease (CKD). The present study aimed to evaluate the incidence, predictors, and outcomes of snakebite-associated AKI (SBE-AKI) in a tertiary care center. We retrospectively analyzed 325 patients with snakebite envenomation, admitted to our institution. Demographic, clinical, laboratory, and treatment variables were compared between patients with and without AKI. AKI was staged according to KDIGO criteria. Renal biopsy was performed selectively in patients with prolonged renal failure, dialysis dependence, delayed renal recovery, or suspicion of irreversible renal injury. Outcomes assessed included recovery, progression to CKD, and mortality. Of the 325 patients, 79 (32.1%) developed AKI. Patients with AKI were significantly younger (mean age 34 vs. 45 years, p = 0.001). Delay in antisnake venom (ASV) administration (5 vs. 9 h, p = 0.001), need for inotropes (41.8% vs. 14.2%, p = 0.001), and mechanical ventilation (36.7% vs. 6.9%, p = 0.001) were strong predictors. Proteinuria was more frequent in AKI (80% vs. 32.5%). Among AKI patients, 57% had Stage 3 AKI; 39.2% required dialysis. Biopsy (n = 8) showed acute tubular necrosis in 37.5% and cortical necrosis in 25%. Outcomes included 77.2% recovery, 6.3% progression to CKD, and 16.5% mortality. SBE-AKI is a common and serious complication of snakebite. Delay in ASV administration, hemodynamic instability, proteinuria, advanced AKI stage, and cortical necrosis predict poor outcomes. Early ASV, timely dialysis, and long-term nephrology follow-up are essential to improve survival and reduce CKD progression.
Snakebite envenomation is a neglected tropical disease that disproportionately affects children in low- and middle-income countries. Pediatric patients are uniquely vulnerable due to smaller body mass, increased venom-to-body-weight ratios, and behavioral risk factors such as outdoor play. The pre-hospital phase is critical in determining outcomes, yet inappropriate first-aid and harmful indigenous practices often characterize it. Despite the recognized importance of early interventions, global evidence on pediatric-specific pre-hospital care remains fragmented. This systematic review synthesizes available literature on first-aid measures, pre-hospital interventions, and harmful traditional practices in pediatric snakebite envenomation. Following PRISMA 2020 guidelines, a comprehensive search was conducted in PubMed/MEDLINE, Scopus, and Lens.org, covering publications from 1973 to December 2025. Eligible studies included children and adolescents (0-18 years) with snakebite envenomation, reporting first-aid or pre-hospital practices and associated outcomes. Observational, interventional, and qualitative designs were included, while case reports, reviews, and non-English publications were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale, Joanna Briggs Institute checklist, and CASP qualitative tool. Due to heterogeneity, findings were synthesized narratively. Forty-four studies were included, representing South Asia, Sub-Saharan Africa, Latin America, the Middle East, Europe, and North America. Harmful practices were most prevalent in South Asia and Africa, where tourniquet use ranged from 38-78%, incision and suction from 22-64%, and herbal remedies from 28-58%. Consultation with traditional healers was frequent, reported in 40-73% of cases. Median delays in hospital presentation were longest in Africa and South Asia, often exceeding 6-18 hours, and each hour of delay increased severity odds by 1.4‑fold. Mortality varied regionally, from 0.06% in North America to 8-10% in Africa, with inappropriate first‑aid identified as an independent predictor of poor outcomes. Knowledge gaps were consistent across regions, with fewer than 20% of parents able to identify appropriate first‑aid and 67% of healthcare providers reporting inadequate training. This review demonstrates that harmful indigenous practices remain pervasive in pediatric snakebite management worldwide, contributing to preventable morbidity and mortality. Evidence underscores the urgent need for standardized, evidence-based pre-hospital guidelines, culturally sensitive community education, and targeted training for healthcare providers. Addressing these gaps through policy development and educational interventions is essential to reduce the global burden of pediatric snakebite envenomation.
Snakebite envenomation remains an important public health concern in Namibia, particularly following bites from the zebra spitting cobra (Naja nigricincta nigricincta) and the puff adder (Bitis arietans). However, the clinical presentations and management outcomes of these snakebites remain poorly characterized. This prospective, observational, descriptive study investigated the clinicopathological features, wound progression, management, and functional outcomes of snakebite patients treated at two major referral hospitals in Namibia. A total of 20 hospitalized patients were included. The majority of patients were male (65%) and children aged 0-15 years (65%). Zebra spitting cobra bites accounted for 60% of cases. Eighty percent of patients presented with predominantly cytotoxic envenomation. Neurological symptoms were documented in a small number of patients (33% of zebra spitting cobra cases and 13% of puff adder cases), but were mild and nonspecific. Antivenom was administered to only 15% of patients. Zebra spitting cobra envenomation was associated with laboratory abnormalities consistent with systemic involvement such as anemia, hemolysis, rhabdomyolysis, hepatic involvement, and renal impairment, whereas puff adder bites demonstrated minimal systemic involvement. Surgical intervention was frequently required, including debridement, fasciotomy, and amputations (15%); however, no fatalities were recorded. These findings highlight the substantial morbidity associated with snakebite envenomation in Namibia and emphasize the importance of early referral, appropriate wound management, and improved access to effective antivenom. However, these findings should be interpreted within the limitations of the small sample size, convenience sampling, and incomplete laboratory investigations in some patients. Nevertheless, this study provides important baseline clinical data to support future snakebite management strategies and region-specific treatment guidelines in Namibia.
Arboreal animals face potentially substantial torques when reaching across gaps, which may limit the size of the gap they can cross with non-dynamic behaviors. Snakes can experience particularly large torques during gap crossing, because they must counteract both pitching and buckling torques while extending into the gap in a cantilever-like posture. Pitching and buckling limits may impose different constraints on gap-crossing locomotion, but their relative importance remains unclear. To investigate this problem, we analyzed kinematic and morphological data related to gap crossing in Dendrelaphis snakes, complemented by data from their sister taxon, Chrysopelea, to test predictions from a theoretical model of cantilever failure. Specifically, we evaluated whether the existing model of buckling predicts maximum observed cantilever performance in these snakes, and compared those predictions with pitching limits estimated from body mass distributions. The buckling model produced estimates far below observed cantilever extents, even across plausible ranges of tendon ratio and multi-articular span, indicating that the current model does not yet capture the mechanics of buckling in cantilevering snakes. By contrast, snakes switched to dynamic movements close to their theoretical pitching limit, supporting the idea that pitching torques constrain cantilever abilities. These results suggest that pitching torque is a major constraint on cantilever-based gap crossing, while also identifying the need for improved buckling models with higher anatomical fidelity. More broadly, this study shows how testing mechanical models against behavior can reveal both the limits shaping locomotor performance and the limitations of existing models.
Snakebite envenoming is a neglected tropical disease causing approximately 81,410-137,880 deaths globally each year and four-fold more disabilities than mortality rate. Despite the availability of antivenoms for treatment, several in vitro and in vivo preclinical studies have shown that their efficacy is limited by many factors including regional venom variation and poor neutralization of major venom toxins. To address these limitations, the potential of alternatives including aptamers, recombinant monoclonal antibodies, camelid antibodies, small molecule inhibitors, and natural product-based inhibitors targeting key venom proteins have been explored. Among these, small molecule inhibitors targeting key enzymatic snake venom proteins are emerging as adjuvants to antivenom treatment. Most of these small molecules are repurposed drugs with established safety, oral bioavailability, and lower cost compared to antivenoms. In this regard, this review tries to compile available information regarding the use of small molecule inhibitors to counteract envenomation with special emphasis on three major enzymatic snake venom protein families: phospholipase A2, snake venom metalloproteinases, and snake venom serine proteases. In vitro studies have shown that these small molecule inhibitors used either alone or in combination with antivenom can potentially reduce the adverse effects of venom-induced coagulopathy, neurotoxicity, tissue damage, and inflammation. However, critical gaps remain including limited human clinical trial data, uncertain efficacy across diverse venoms, and undefined dosing strategies. Overall, small molecules represent a mechanistically targeted and clinically promising adjunct to antivenom therapy, warranting further validation through randomized trials, pharmacokinetic studies, and development of field-applicable treatment protocols.
Axial elongation has evolved repeatedly in vertebrates, and previous research has revealed insights into the developmental and evolutionary mechanisms that shape this body plan. Snakes, with their elongated, functionally limbless bodies, offer an exceptional system to investigate how vertebral regions are organised or modified throughout elongation. Recent work suggests that snakes retain ancestral regionalisation and that heart position coincides with the boundary between two regions, but how methodological choices such as vertebral sampling density and landmark dimensionality affect the detectability of these regions remain untested. Here, we used three-dimensional geometric morphometrics (3D GM) and segmented linear regressions on complete vertebral columns from 12 elapid snakes to investigate regionalisation and interspecific differences. We compared multiple subsampling strategies (every vertebra, or sampling every 2%, 2.5%, 4% or 5%) to assess how resolution can influence the detection of regional boundaries. We also tested various landmarking schemes, examining if previously utilised landmarking schemes differ greatly in region detection. Our analyses reveal a 4- or 5-region model to be most suitable among elapids, including a short cervical region spanning 2%-4% of the column, a robust morphological shift at ~20% of the column aligning strongly with heart position and a distinct lumbar boundary in the final 5%. Interspecific shape differences were detected but lacked sufficient distinction to identify reliably. Fine-scale sampling improves the detection of small regions, decaying with coarser subsampling. Our results determined that the coarsest reliable sampling method was found at the 2.5% mark. These findings show that despite axial elongation, snakes retained a short cervical and lumbar region, with most of the elongation happening in the thoracic region. This, in turn, has resulted in the thoracic region undergoing axial repatterning, with three modules detected within the thoracic region. This study refines our understanding of vertebral modularity and highlights how regionalisation evolves in elongated vertebrates.
Snakebite maims or kills several hundred thousand people each year. For more than a century, treatment has relied on antivenoms derived from animals immunized with whole venoms, but their efficacy, safety, and availability are highly variable, and it is often not well understood which specific venom components must be inhibited to prevent mortality and major morbidities. New therapeutic approaches are needed. Here, we take an evolutionary approach to antivenom design inspired by the longstanding observation that vipers have evolved serum-borne toxin inhibitors that confer resistance to their own venoms. We have investigated the abilities of a family of four rattlesnake metalloproteinase (MP) inhibitors derived from the ancestral serum glycoprotein Fetuin-A (FETUAs) to neutralize the enzymatic, hemorrhagic, and lethal activities of viper venoms. We find that while certain individual FETUA proteins are able to inhibit enzymatic or hemorrhagic activity, they are unable or only partially able to inhibit venom lethality. However, we show that specific combinations of FETUA proteins complement one another's activities and are sufficient to fully neutralize rattlesnake venom lethality with approximately 10 times greater potency than commercial antivenom. Moreover, we demonstrate that FETUA proteins are well conserved among viper subfamilies and that rattlesnake FETUAs are able to inhibit the MPs and neutralize the lethality of several evolutionarily distant pit viper or true viper venoms. Our results highlight the critical importance of inhibiting MPs in hemorrhagic venoms and the potential general utility of combinations of naturally evolved, recombinant MP inhibitors in the treatment of viper snakebite.
Snakebite is a neglected tropical disease of major public health importance in India, contributing to significant morbidity and mortality. Acute kidney injury (AKI) is among the most serious complications of envenomation, particularly with viperid and some elapid species, and is associated with long-term chronic kidney disease (CKD) risk. This article aims to provide evidence-based recommendations for the recognition, evaluation, and management of snakebite-envenomation-associated AKI (SAKI), integrating global best practices with national treatment protocols and resource realities. The authors reviewed available literature through PubMed and international recommendations, including the Government of India's Standard Treatment Guidelines (STG), World Health Organization (WHO) guidance, and Kidney Disease Improving Global Outcomes (KDIGO) AKI guidelines. As per the available evidence, the recommendations were formulated through expert panel deliberations. Key recommendations include early recognition of envenomation syndromes, prompt administration of polyvalent antisnake venom (ASV), protocolized monitoring of coagulation and renal parameters, and standardized use of kidney replacement therapy (KRT) according to KDIGO indications. Supportive management of venom-induced consumption coagulopathy (VICC), rhabdomyolysis, and thrombotic microangiopathy (TMA) is emphasized. Special considerations have been outlined for children, pregnant women, patients with preexisting kidney disease, and those bitten by non-"Big Four" snakes. SAKI is preventable and treatable with timely intervention, but survivors remain at risk of CKD. With these recommendations, the authors have tried to standardize the diagnostic and therapeutic approach across general medicine, nephrology, and critical care medicine teams in India, aiming to reduce mortality and improve renal outcomes.
Venom-induced compartment syndrome (VICS) is a rare but severe complication of snakebite which poses unique challenges in diagnosis and treatment. Published literature largely focuses on VICS in the North American context, while information on clinical presentations, diagnostic and treatment approaches, clinical outcomes and associated challenges from the world's most snakebite endemic regions remain fragmented and scarce. A scoping review using PRIMSA-ScR methodology of the global literature on VICS was performed by searching the PubMed, Embase, and Cochrane databases. Literature was divided into 1) Case reports on VICS and 2) General literature. Clinical data from eligible case reports was extracted to describe management of VICS and associated challenges. Available evidence on diagnostic and treatment strategies was extracted from the general literature. Of 115 cases of VICS analyzed, most were from Europe (40%); Only 13% and 6% were reported from South-East Asia and Africa respectively. Viperids caused 73% of bites and upper extremities were most frequently affected (63%). Compartment pressure was measured in 38% of patients. Compartment pressure was more commonly measured in the 12% of non-surgically treated patients, none of whom developed ischaemic contracture or required amputation. Coagulopathy was the most common systemic toxicity, present in 40% of patients at admission. Results from eight animal studies support the use of antivenom for treating VICS. Analysis of 17 human observational studies suggests an overdiagnosis of VICS using clinical symptoms alone, highlighting the need to investigate diagnostic tools, such as ultrasound, for diagnosing compartment swelling. Antivenom as first-line treatment for VICS is supported by animal and human observational studies. However, additional data is needed to inform decision-making on when fasciotomy is indicated as a rescue therapy. Improved evidence generation will depend on the collection of high-quality clinical and diagnostic observational data from patients treated with antivenom in snakebite-endemic regions.
Snakebites are common emergencies in tropical countries, usually presenting with hematotoxic, neurotoxic, or myotoxic effects. Vascular thrombosis as a systemic complication is extremely rare. We report a case of superior mesenteric artery (SMA) thrombosis following a viper bite, leading to acute mesenteric ischemia. A 39-year-old male patient presented with abdominal pain, vomiting, loose stools, and reduced urine output following a snakebite with Daboia russelii to the right index finger. He had received 20 vials of anti-snake venom at a peripheral hospital. On examination, he was tachycardic with abdominal distension, diffuse tenderness, guarding, and rigidity. Blood investigations suggested leukocytosis, thrombocytopenia, and elevated creatinine levels. Imaging revealed dilated small bowel loops and near-complete thrombosis of the jejunal and ileal branches of the SMA. The patient underwent exploratory laparotomy, with resection of gangrenous small bowel, with double-barrel stoma. Despite emergent surgical intervention and intensive supportive care, the patient's condition deteriorated rapidly. The patient succumbed to multi-organ failure and died on postoperative day two. This case highlights the rare but lethal complication of acute mesenteric ischemia following viper envenomation. Early recognition and timely surgical intervention are critical for favorable outcomes.
Marimastat is a pan-catalytic MMP inhibitor that is emerging as an alternative therapy for venom bite lesions because it can antagonise metalloproteinases in snake venom, without being constrained by the production or storage requirements of antivenoms or intravenous administration. Metalloproteinases are important effector enzymes in many aspects of tissue damage caused by snake bites, so inhibition of their action should interfere with both systemic haemorrhage and local necrosis. Preclinical studies and proteomics studies have shown its effectiveness in many species of snakes and might be particularly attractive given that venom therapy requires only a short duration of treatment (3-5 days), unlike other uses of MMP inhibitors that can produce musculoskeletal toxicity. Marimastat, alone or in combination with sPLA2 inhibitors, is the basis of ongoing tests in phase II clinical trials. This drug holds the potential to complement future therapies for bringing patients to the hospital, where more treatment can be given.
Caudal vertebrae of caenophidian snakes are characterized by the presence of paired haemapophyses-a pattern observed from the earliest-diverging acrochordid lineage to the most derived viperids, and documented in the fossil record from the Late Cretaceous onward, including the basalmost known extinct caenophidian forms. Using micro-computed tomography scanning, we document an extraordinary deviation from this pattern. We examined five species across three genera of the Asian family Calamariidae (Reed snakes) and demonstrate that they, uniquely among Colubroidea, lack haemapophyses throughout the caudal vertebral series, possessing instead prominent haemal keels-a condition that represents a novel diagnostic feature for Calamariidae. This simplification of vertebral morphology, coupled with an extremely reduced number of caudal vertebrae, likely correlates with the fossorial lifestyle characteristic of this snake family. Furthermore, we identify and illustrate unexpected modifications of subcentral structures in certain other caenophidian taxa, that is, a pareid and several distantly related elapoid species. Our findings underscore the significant taxonomic and diagnostic value of caudal vertebral morphology, a skeletal element that has been largely overlooked.
In this study, by combining morphological and molecular data (18S rRNA gene), we identified four species of Hepatozoon in snakes from the Brazilian Amazonia region. We describe a new species of Hepatozoon infecting Bothrops atrox, provide the first molecular data for Hepatozoon luhei from Corallus hortulana, and record Hepatozoon cuestensis in Zonateres lanei and Hepatozoon odwyerae in Chironius carinatus. Furthermore, through a literature survey, we present an overview of studies on the genus Hepatozoon in snakes in Brazil, spanning over 120 years of research, highlighting species richness and sampling bias, particularly the knowledge gap in the northern region. Our results broaden the knowledge about the diversity, geographic distribution, and phylogenetic relationships of these hemogregarines, reinforcing the importance of integrative approaches to reveal the hidden diversity of parasites in the Amazonia.
L-amino acid oxidase (LAAO) is a major component of snake venoms and contributes to several pathological effects associated with envenomation. However, the identification of immunodominant B-cell epitopes within this toxin remains poorly explored. In this study, native LAAO from Bothrops atrox venom was purified and used to generate polyclonal antibodies in rabbits. Anti-LAAO IgG antibodies were purified and employed in SPOT synthesis-based epitope mapping using a peptide array comprising 122 overlapping pentadecapeptides covering the complete amino acid sequence of B. atrox LAAO (GenBank: ALL27300.1). Five antigenic regions distributed throughout the N-terminal, central, and C-terminal portions of the toxin were identified. Subsequent bioinformatic analyses, including epitope prediction and structural evaluation, identified PEP1 (VGEVNKDPGVLEYPVKPSEVGKS) as the most promising candidate. This peptide was synthesized and evaluated as an immunogen in mice. Immunization with PEP1 elicited antibodies capable of recognizing both the synthetic peptide and native LAAO, as well as cross-reacting with crude B. atrox venom. Sequence alignment demonstrated that this epitope is highly conserved among LAAOs from different snake species. These findings identify a conserved and immunoreactive linear B-cell epitope of LAAO, providing a basis for future studies exploring its use in immunogen design and antivenom development.
Thrombotic microangiopathy (TMA) is an uncommon but serious complication of hemotoxic snakebite envenomation, which remains a significant cause of morbidity and mortality in tropical regions. TMA is characterized by microvascular thrombosis and hemolytic injury, which may lead to multiorgan dysfunction. We report the case of a 31-year-old male factory worker with an alleged viper bite to the right great toe. Despite administration of multiple doses of anti-snake venom and intensive supportive care, his condition progressively deteriorated, and he succumbed. Medicolegal autopsy revealed a hemorrhagic lesion at the bite site, diffuse subdural and subarachnoid hemorrhages, and petechial hemorrhages over the heart. Toxicological analysis of preserved skin tissue from the bite site confirmed the presence of hematotoxic venom. Histopathological examination of the kidneys showed renal cortical necrosis with thrombosis of the afferent arterioles and glomerular capillary loops, along with red blood cell extravasation, consistent with thrombotic microangiopathy secondary to envenomation. An incidental finding of fibrotic thickening of the mitral and aortic valves with myxoid degeneration and the presence of Anitschkow cells was consistent with rheumatic valvular disease. This case highlights the importance of autopsy, toxicological confirmation, and histopathological examination in establishing a diagnosis of venom-induced thrombotic microangiopathy and identifying occult cardiac pathology with potential medicolegal relevance.