Snakebite Research Articles

Phage display-derived alpaca nanobodies as potential therapeutics for Naja atra snake envenomation.

Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs.

Venomics and Peptidomics of Palearctic Vipers: A Clade-Wide Analysis of Seven Taxa of the Genera Vipera, Montivipera, Macrovipera, and Daboia across Türkiye.

Snake venom variations are a crucial factor to understand the consequences of snakebite envenoming worldwide, and therefore it is important to know about toxin composition alterations between taxa. Palearctic vipers of the genera Vipera, Montivipera, Macrovipera, and Daboia have high medical impacts across the Old World. One hotspot for their occurrence and diversity is Türkiye, located on the border between continents, but many of their venoms remain still understudied. Here, we present the venom compositions of seven Turkish viper taxa. By complementary mass spectrometry-based bottom-up and top-down workflows, the venom profiles were investigated on proteomics and peptidomics level. This study includes the first venom descriptions of Vipera berus barani, Vipera darevskii, Montivipera bulgardaghica albizona, and Montivipera xanthina, as well as the first snake venomics profiles of Turkish Macrovipera lebetinus obtusa, and Daboia palaestinae, including an in-depth reanalysis of M. bulgardaghica bulgardaghica venom. Additionally, we identified the modular consensus sequence pEXW(PZ)1-2P(EI)/(KV)PPLE for bradykinin-potentiating peptides in viper venoms. For better insights into variations and potential impacts of medical significance, the venoms were compared against other Palearctic viper proteomes, including the first genus-wide Montivipera venom comparison. This will help the risk assessment of snakebite envenoming by these vipers and aid in predicting the venoms' pathophysiology and clinical treatments.

A Nationwide Study on the Risks of Complications and Healthcare Costs of Snakebite Envenomation in Taiwan.

In Taiwan, six medically important venomous snakes, Trimeresurus stejnegeri stejnegeri, Protobothrops mucrosquamatus, Deinagkistrodon acutus, Daboia siamensis, Naja atra, and Bungarus multicinctus, are found. However, comprehensive research on the complications and associated healthcare costs of snakebite envenomation (SBE) is lacking. We retrospectively analyzed pertinent information from the Taiwan National Health Insurance Research Database dated January 2002 to December 2014. We investigated the risk factors for complications and their impact on healthcare costs. Among the 12,542 patients with SBE, those from N. atra or B. multicinctus were more likely to experience wound infections and neurological complications than were those from T. s. stejnegeri or P. mucrosquamatus. In addition, being female, being elderly, and having a Charlson Comorbidity Index equal to or greater than 3 points were associated with an increased likelihood of wound infections and psychological complications. The annual national economic burden averaged US$1,083,624, with an average healthcare cost of US$1,129 per SBE. Snakebite envenomations from N. atra or B. multicinctus, as well as various complications, resulted in significantly higher costs. It is crucial to comprehend the risk factors for complications and their role in increasing expenses to provide insight for tailored healthcare interventions, mitigate complications, and reduce the economic burdens associated with SBEs.

Evaluation of the Role of Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio and Mean Platelet Volume as Predictors of the Outcome in Patients with Hemotoxic Snake Bite: A Prospective Study on Patients in Poison Control Centers Ain Shams University Hospitals and Assiut University Hospitals

Abstract Background Snakebite envenomation is considered a major health problem especially in developing centuries. Snakebite envenomation cause major morbidities, disabilities and mortalities. Novel biomarkers as; neutrophils to lymphocytes Ratio (NLR) and plateletto lymphocytes Ratio (PLR)are hematological inflammatory indices that can be a guide for diagnosis, prognosis of the snakebite envenomation. Methodology This was a prospective case control study, which was carried out on 60 hemotoxic snake bite envenomed patients that admitted at Poisoning Control Center AinShams University Hospitals (PCCAUH) and Assiut University Hospitals (AUH) in the period from 1st of July 2019 to 31st of October 2021. In addition, 60 healthy volunteers were used as control subjects. The study aimed to evaluate the role of NLR, PLR and Mean Platelet Volume (MPV) at admission as predictors of the outcome in patients with hemotoxic snakebite envenomation. The patients were divided into mild, moderate and severe groups according to severity of snake envenomation. Result Sixty hemotoxic snake bite envenomed patients (28 patients admitted at PCC-ASUH and 32 admitted at AUH), were divided into (38.4%) mild, (31.6%) moderate and (30%) severe groups according to the severity of snake envenomation. Maximum incidence was found in male (95%) from rural areas (80%) and were farmers (43.3%) from total cases. It was observed that bite was more frequent at lower limbs (70%), outdoors (81.6%), at night (51%) and during autumn season (43.3%). It was found that there was significant positive correlation between NLR at admission and duration of hospitalization, PLR, creatine phosphokinase (CPK) level and whitebloodcells (WBCs) count. While, significant negative correlation was found between NLR and prothrombin concentration (PC), red blood cells(RBCs) and plateletcounts. Also, significant positive correlation was found between PLR at admission and duration of hospitalization, NLR, CPK level and platelets count. Inaddition, significant positive correlation was found between MPV and PT. About 47 (78.33%) patients had complete recovery and about 13 (21.67%) patients recovered with complications including; local complications in (21.67%), systemic complications in (13.33%) and chronic complications In (5%). There were no recorded deaths in the study. It was found that hemotoxic snake bit eenvenomed patients Admitted at PCC-ASUH were significantly more severe,required more antivenom vials and more intensive care unit(ICU) admission than those admitted at AUH. Conclusion NLR and PLR values at admission were significantly high in hemotoxic snake bite envenomed patients and can be used as predictors for diagnosis and prognosis of hemotoxic snake envenomation.In addition, NLR and PLR had significant association with severity of envenomation, duration of hospitalization.

Identification of purinergic system components in the venom of Bothrops mattogrossensis and the inhibitory effect of specioside extracted from Tabebuia aurea.

Snake bites are a severe problem in the countryside of Brazil and are usually attributed to snakes of the genera Bothrops, Crotalus, and Lachesis. Snake venom can release ectoenzymes and nucleotidases that modulate the purinergic system. In addition to serum therapy against snake poisoning, medicinal plants with anti-inflammatory activities, such as Tabebuia aurea, is empirically applied in accidents that occur in difficult-to-access areas. This study aimedwas to verify the presence and activity of nucleotidases in the crude venom of Bothrops mattogrossensis (BmtV) in vitro and characterize the modulation of purinergic components, myeloid differentiation, and inflammatory/oxidative stress markers by BmtV in vivo and in vitro. Moreover, our study assessed the inhibitory activities of specioside, an iridoid isolated from Tabebuia aurea, against the effects of BmtV. Proteomic analysis of venom content and nucleotidase activity confirm the presence of ectonucleotidase-like enzymes in BmtV. In in vivo experiments, BmtV altered purinergic component expression (P2X7 receptor, CD39 and CD73), increased neutrophil numbers in peripheral blood, and elevated oxidative stress/inflammatory parameters such as lipid peroxidation and myeloperoxidase activity. BmtV also decreased viability and increased spreading index and phagocytic activity on macrophages. Specioside inhibited nucleotidase activity, restored neutrophil numbers, and mediate the oxidative/inflammatory effects produced by BmtV. We highlight the effects produced by BmtV in purinergic system components, myeloid differentiation, and inflammatory/oxidative stress parameters, while specioside reduced the main BmtV-dependent effects.

A Review on the Phytochemistry and Pharmacology of the Genus Sterculia.

The Sterculia genus is comprised of approximately 300 species, which have been widely used as traditional medicines to treat inflammation, snake bites, gastrointestinal diseases, skin diseases, microbial infections and many other diseases. To gain a comprehensive understanding of the therapeutic potential of Sterculia plants, an extensive literature search was conducted in CNKI, Bing, Wanfang Database, Springer Database, Elsevier Database, Google Scholar, Baidu Scholar, PubMed, and other similar websites from January 1971 to March 2024. The research indicated that Sterculia species predominantly contain flavonoids, terpenoids, phenylpropanoids, fatty acids, alkaloids and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, antioxidant, antibacterial and other biological activities have been reported. Nevertheless, there isn't much scholarly research on the therapeutic material basis of the genus Sterculia. This review reports the ethnobotany, phytochemicals, and biological activities of the plants in the Sterculia genus as herbal remedies.

Improving the Snakebite Envenoming First Aid Treatment of Farmers in Rural Areas of Indonesia: An Educational Intervention Program

Introduction: Snakebite Envenoming (SBE) cases are a worldwide health problem. Farmers have a big risk of becoming victims of SBE. SBE management is an issue that needs to be resolved due to a lack of information regarding the appropriate management of SBE. This study aimed to analyze the effectiveness of educational intervention programs on the knowledge, attitude, practice, and self-efficacy of farmers toward SBE management. Methods: The design of this study was a non-blinded cluster randomized controlled trial design, applied to 80 farmers in six subdistricts from rural areas of Indonesia. A multistage sampling was used to select participants. Data collection tools included a three-part questionnaire that consisted of demographics, knowledge, self-efficacy, and an observation checklist for SBE first aid practices for farmers. Education and training sessions were carried out for eight weeks for the intervention group by providing eight sessions of education and training activities. The effectiveness of the intervention was analyzed using a dependent t-test, and analysis of covariance (ANCOVA) with p<0.05 was considered significant. Results: The results of this study showed that there were significant differences in knowledge, attitude, practice, and self-efficacy (p<0.05) of farmers in SBE first aid before and after the program. The intervention group showed better results compared to the control group after the follow-up. Conclusion: The educational intervention programs using the digital health education method with snakebite first aid applications have proven positive effect in increasing knowledge, attitudes, practices, and self-efficacy of SBE first aid among farmers.

Snake envenomation in children: Experience from a tertiary care hospital in Northern India

BackgroundSnakebite in children is a medical emergency of significant public health concern. Owing to physiological differences, the potential of snake venom causing tissue damage and long-term sequelae is more pronounced in paediatric age group. We aimed to determine the clinical profile and outcome in children suffering with snake envenomation. MethodsThe retrospective observational study reviewed the clinical case records of children aged 0–18 years, admitted with features of snake envenomation from January 2021 to December 2022 Demographic profile, clinical features, treatment and outcome were analysed using descriptive statistics. ResultsEleven children with snakebite were admitted during the study period. The mean age of study population was 11.63 (±3.9) years. Nine children (81.8%) were residing in rural area, majority (72.7%) of the children experienced the snakebite between May and August. Extremities were the most commonly affected site as seen in seven (63.6%) children. Pain and swelling at the bite site were the commonest symptoms seen in nine (81.8%) children, neurotoxic features were evident in seven (54.5%) cases, while four (36.3%) cases manifested vasculotoxic features. Invasive ventilatory support was required in four (36.3%) cases and all such children were extubated with successful outcome. Anti-snake venom (ASV) was administered in all 11 children and no adverse reactions were observed. No mortality was reported during the study. ConclusionEnvenomation toxidrome depends on the prevalent snake species inhabiting the various geographic regions within the same country.

CTXP, The Major Cobra Toxin Peptide from Naja Naja Oxiana Venom; A Promising Target for Antivenom Agent Development.

Snakebite envenoming is a serious public health issue causing more than 135,000 annual deaths worldwide. Naja Naja Oxiana is one of the most clinically important venomous snakes in Iran and Central Asia. Conventional animal-derived polyclonal antibodies are the major treatment of snakebite envenoming. Characterization of venom components helps to pinpoint the toxic protein responsible for clinical manifestations in victims, which aids us in developing efficient antivenoms with minimal side effects. Therefore, the present study aimed to identify the major lethal protein of Naja Naja Oxiana by top-down proteomics. Venom proteomic profiling was performed using gel filtration (GF), reversed-phase (RP) chromatography, and intact mass spectrometry. The toxicity of GF-, and RP-eluted fractions was analyzed in BALB/c mice. The rabbit polyclonal antisera were produced against crude venom, GF fraction V (FV), and RP peak 1 (CTXP) and applied in neutralization assays. Toxicity studies in BALB/c identified FV as the major toxic fraction of venom. Subsequently, RP separation of FV resulted in eight peaks, of which peak 1, referred to as "CTXP" (cobra toxin peptide), was identified as the major lethal protein. In vivo neutralization assays using rabbit antisera showed that polyclonal antibodies raised against FV and CTXP are capable of neutralizing at least 2-LD50s of crude venom, FV, and CTXP in all tested mice. Surprisingly, the Anti-CTXP antibody could neutralize 8-LD50 of the CTXP peptide. These results identified CTXP (a 7 kDa peptide) as a potential target for the development of novel efficient antivenom agents.

Relationship between the root processing method and quality of herbal medicine of Rauvolfia serpentina cultivated in Japan

Rauvolfia serpentina roots are used as herbal medicine for snake and insect bites, fever, malaria, abdominal pain, hypertension, and dysentery in Southeast Asian countries. This study evaluates the content of reserpine, ajmaline, and ajmalicine in R. serpentina roots obtained with an efficient root processing method. The plants were cultivated in Tanegashima Island in southern part of Japan, where NIBIOHN's experimental farm station is located. We examined both the type of cork layer removal method (manual work, drum mixer washing, and high-pressure washing) and dried roots. We found that the resulting active ingredient contents were not significantly different between manual work and 30 min of drum mixer washing, and high-pressure washing. The washing in a drum mixer for 30 min could be an efficient root processing method. The amount of each active ingredient was compared in each root part (large-, middle-, and small-diameter roots), and there were no significant difference in their contents. In conclusion, R. serpentina roots having a diameter ≥ 0.5 cm contain a similar amount of active ingredients, suggesting that the quality of the crude drug does not vary in the root part. Thus, our study provides significant insights into the use of R. serpentina roots for herbal medicine applications as well as constituents of active ingredients.

A study to evaluate the effectiveness of self-instructional module on knowledge regarding first aid management of snake bite among selected PU college students at Ankola, Uttara Kannada District, Karnataka

A study to evaluate the effectiveness of self-instructional module on knowledge regarding first aid management of snake bite among selected PU college students at Ankola, Uttara Kannada District, Karnataka

Snake species assemblages across habitat types in four departments of the Republic of Congo, with emphasis on medically-relevant venomous species

Snakebite is a neglected public health crisis in sub-Saharan Africa. There is a particular lack of data (on snakes and snakebite) from the central African region. This study was conducted in the departments of Likouala, Sangha, Cuvette-Ouest and Kouilou, in the Republic of Congo. The objective was to inventory snakes in the four localities with particular emphasis on medically relevant venomous snakes in order to improve knowledge of snakes in order to minimize the risks of snakebite envenomation to humans. Two methods (active and passive) were used to collect specimens from different habitats. Fifty-one (51)snake specimens including 14 medically relevant snake specimens representing 3 families, 3 subfamilies, 5 genera, and 6 species, in addition to 22 harmless species, were collected. We found a high number of medically important venomous species in Okoyo, Mokéko and Mvouti districts with 3 species each. The highest number of medically important venomous species was recorded in natural forests and human habitations, five and four species respectively. The species obtained (Atheris squamigera, Bitis arietans, Bitis gabonica, Dendroaspis jamesoni, Naja melanoleuca and Toxicodryas blandingii) are medically relevant toxic species according to the WHO classification. Further studies would be necessary to assess the epidemiology of bite risks snakes and educate the public to minimize accidental human-snake contact.

Expanding anti-venom strategies: Camelid polyclonal antibodies with high capacity to recognize snake venom

Camelid immunoglobulins represent a unique facet of antibody biology, challenging conventional understandings of antibody diversification. IgG2 and IgG3 in particular are composed solely of heavy chains and exhibit a reduced molecular weight (90 kDa); their elongated complementarity determining region (CDR) loops play a pivotal role in their functioning, delving deep into enzyme active sites with precision. Serum therapy stands as the primary venom-specific treatment for snakebite envenomation, harnessing purified antibodies available in diverse forms such as whole IgG, monovalent fragment antibody (Fab), or divalent fragment antibody F (ab')2. This investigation looks into the intricacies of IgGs derived from camelid serum previously immunized with crotamine and crotoxin, toxins predominantly in Crotalus durissus venom, exploring their recognition capacity, specificity, and cross-reactivity to snake venoms and its toxins. Initially, IgG purification employed affinity chromatography via protein A and G columns to segregate conventional antibodies (IgG1) from heavy chain antibodies (IgG2 and IgG3) of camelid isotypes sourced from Lama glama serum. Subsequent electrophoretic analysis (SDS-PAGE) revealed distinct bands corresponding to molecular weight profiles of IgG's fractions representing isotypes in Lama glama serum. ELISA cross-reactivity assays demonstrated all three IgG isotypes' ability to recognize the tested venoms. Notably, IgG1 exhibited the lowest interactivity in analyses involving bothropic and crotalic venoms. However, IgG2 and IgG3 displayed notable cross-reactivity, particularly with crotalic venoms and toxins, albeit with exceptions such as PLA2-CB, showing reduced reactivity, and C. atrox, where IgGs exhibited insignificant reactivity. In Western blot assays, IgG2 and IgG3 exhibited recognition of proteins within molecular weight (≈15 kDa) of C. d. collilineatus to C. d. terrificus, with some interaction observed even with bothropic proteins despite lower reactivity. These findings underscore the potential of camelid heavy-chain antibodies, suggesting Lama glama IgGs as prospective candidates for a novel class of serum therapies. However, further investigations are imperative to ascertain their suitability for serum therapy applications.

Vulnerability factors of snake bite patients in China

ObjectiveTo analyze the vulnerability factors of snakebite patients in China.MethodsMulti-stage random sampling was used as the main sampling method and snowball sampling as the auxiliary sampling method. The knowledge, attitude and behavior of snakebite among Chinese residents were investigated. Non-parametric test was used to compare the percentage differences in residents’ knowledge, attitude and behavior of snakebite, and generalized linear regression analysis was used to analyze the influencing factors, and the vulnerability factors of snakebite patients were comprehensively analyzed.ResultsA total of 6338 subjects were included in this study, of which 68.4% were males, and 58.6% were farmers, workers and service personnel. The median total score of knowledge, attitude, and behavior was 26 (22,36). The patients who were improperly treated after injury were ligation proximal to the affected area (23.43%), squeezing (21.82%), and oral and suction wounds (8.74%). Did not go to hospital due to poverty (1351 cases) and did not receive antivenom (2068 cases). There were 21.32% and 32.63%, respectively. Among 4270 patients injected with antivenom 30.7% were vaccinated within 2 h. Among the patients who went to the hospital for treatment (4987), 75.0% arrived at the hospital within 6 h; Among the 4,761 patients who made emergency calls, 37.4% were treated within 0.5 h.ConclusionsSnakebite patients in China have weak knowledge about snakebite, low awareness of medical treatment, lack of correct prevention and emergency treatment measures, dependence on folk remedies, poor housing and so on. In addition, there are low availability of antivenoms and unreasonable distribution of medical resources in some areas of China. Multisectoral and multidisciplinary cooperation should be developed to prevent and control snakebites in order to reduce the burden caused by snakebites.

Development, Optimization and Evaluation of a Sensitive Enzyme-Linked Immunosorbent Assay (ELISA) Prototype for Detection of Chicken-Based IgY Polyclonal Antibodies against Toxins of D. polylepis Venom.

Life-threatening medical issues can result from snakebite, and hence this is a public health concern. In many tropical and subtropical nations such as Kenya, where a wide variety of poisonous snakes are prevalent, diagnosis of snakebite in health facilities is imperative. Different antivenoms are needed to treat the venom of different snake species. Nonetheless, it might be difficult for medical professionals to identify the exact snake species that envenomated a patient due to the similarities of several snake envenomations' clinical symptoms. Therefore, the necessity for an assay or technique for identifying venomous species is critical. The current study sought to develop a sensitive ELISA prototype for the detection of D. polylepis venom in Kenya using generated chicken-based IgY polyclonal antibodies. Serum samples containing specific chicken-based IgY antibodies previously raised against D. polylepis venom toxins were used in the assay development. ELISA parameters were optimized, and the developed assay was assessed for applicability. The limit of detection (LoD) of the ELISA for neurotoxic venoms was determined to be 0.01 µg/mL. Successful discrimination between neurotoxic and cytotoxic venoms was achieved by the ensuing inhibition ELISA assay. The developed assay showed the capability of identifying venoms in blood samples (from spiked and venom-challenged blood samples) of BALB/c mice, providing compelling evidence of the strategy's usefulness. This assay could help physicians diagnose and manage victims of snakebites through the evaluation of clinical samples.

Dual therapy with phospholipase and metalloproteinase inhibitors from Sinonatrix annularis alleviated acute kidney and liver injury caused by multiple snake venoms

Snakebite envenomation often induces acute kidney injury (AKI) and acute liver injury (ALI), leading to augmented injuries and poor rehabilitation. Phospholipase A2 (PLA2) and metalloproteinase (SVMP) present in venom are responsible for the envenomation-associated events. In this study, mice envenomed with Deinagkistrodon acutus, Naja atra, or Agkistrodon halys pallas venom exhibited typical AKI and ALI symptoms, including significantly increased plasma levels of myoglobin, free hemoglobin, uric acid, aspartate aminotransferase, and alanine aminotransferase and upregulated expression of kidney NGAL and KIM-1. These effects were significantly inhibited when the mice were pretreated with natural inhibitors of PLA2 and SVMP isolated from Sinonatrix annularis (SaPLIγ and SaMPI). The inhibitors protected the physiological structural integrity of the renal tubules and glomeruli, alleviating inflammatory infiltration and diffuse hemorrhage in the liver. Furthermore, the dual therapy alleviated oxidative stress and apoptosis in the kidneys and liver by mitigating mitochondrial damage, thereby effectively reducing the lethal effect of snake venom in the inhibitor-treated mouse model. This study showed that dual therapy with inhibitors of metalloproteinase and phospholipase can effectively prevent ALI and AKI caused by snake bites. Our findings suggest that intrinsic inhibitors present in snakes are prospective therapeutic agents for multi-organ injuries caused by snake envenoming.

Cardio-nephrotoxicity mediated by Echis ocellatus venom and its amelioration through kaempferol’s suppressive effect on oxidative stress, inflammation, and apoptosis expression

BackgroundEchis ocellatus venom toxins have the ability to impact multiple organ systems subsequent to envenomation. Kaempferol have been reported to have several therapeutic benefits. In this study, the therapeutic value of kaempferol was investigated in relation to the cardio-nephrotoxicity in rats resulting from E. ocellatus envenoming.MethodsFifty male wistar rats were allotted unbiased into five groups (n = 10) for this study. Group 1 was the control, while rats in groups 2 to 5 were envenomed with LD50 of E. ocellatus venom (0.22 mg/kg bw; i.p.). Group 2 was not treated after envenomation while groups 3, 4 and 5 were treated with polyvalent antivenom, 4 and 8 mg/kg of kaempferol, respectively.ResultsE. ocellatus envenomation caused considerable reduction in organ weight and relative organ weight in the envenomed untreated rats. The venom induced intense oxidative stress, inflammation, apoptotic damage to the cardiac and renal tissues accompanied with severe histomorphology in the organ tissues of untreated envenomed rats. In contrast, kaempferol treatment post-envenomation attenuated the venom-induced cardio-nephrotoxic responses in a dose dependent effect. Kaempferol substantially (p < 0.05) decreased malondialdehyde levels while enhancing reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities in the heart and kidney of envenomed treated rats. Treatment of envenomed rats with kaempferol successfully decreased nitric oxide levels and myeloperoxidase activity. Overexpression of apoptotic caspase 3 and caspase 9 in cardiac and renal tissues were suppressed by kaempferol (p < 0.05). The histopathological result supports kaempferol’s ameliorative ability by convalescing the severe morphological alterations of cardiac and renal tissues induced by the venom.ConclusionFindings elucidate the significance of kaempferol as promising agent in the management of cardio-nephrotoxicity resulting from snakebite envenoming.

Successful management of viper envenomation in a Labrador dog

A nine months old male Labrador dog was presented to the Veterinary Clinical Complex, Gannavaram with a history of snake bite. Clinical signs exhibited include dullness, depression, frothy salivation, ataxia, edema and discoloration at paw region. Upon clinical examination fang marks were observed at left metatarsal region. Based on the history, identification of snake by the owner, clinical signs and whole blood clotting test it was diagnosed as viper snakebite. Neutrophilia, polycythemia and marginal lymphocytopenia were noticed. Treatment with poly valent anti snake venom, fluid therapy, tetanus toxoid, an antibiotic was carried out and the dog had uneventful recovery

Investigating Snake-Venom-Induced Dermonecrosis and Inflammation Using an Ex Vivo Human Skin Model.

Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local envenoming, defined by morbidity-causing local tissue necrosis, remains poorly understood, and human-tissue responses are ill-defined. Here, for the first time, an ex vivo, non-perfused human skin model was used to investigate temporal histopathological and immunological changes following subcutaneous injections of venoms from medically important African vipers (Echis ocellatus and Bitis arietans) and cobras (Naja nigricollis and N. haje). Histological analysis of venom-injected ex vivo human skin biopsies revealed morphological changes in the epidermis (ballooning degeneration, erosion, and ulceration) comparable to clinical signs of local envenoming. Immunostaining of these biopsies confirmed cell apoptosis consistent with the onset of necrosis. RNA sequencing, multiplex bead arrays, and ELISAs demonstrated that venom-injected human skin biopsies exhibited higher rates of transcription and expression of chemokines (CXCL5, MIP1-ALPHA, RANTES, MCP-1, and MIG), cytokines (IL-1β, IL-1RA, G-CSF/CSF-3, and GM-CSF), and growth factors (VEGF-A, FGF, and HGF) in comparison to non-injected biopsies. To investigate the efficacy of antivenom, SAIMR Echis monovalent or SAIMR polyvalent antivenom was injected one hour following E. ocellatus or N. nigricollis venom treatment, respectively, and although antivenom did not prevent venom-induced dermal tissue damage, it did reduce all pro-inflammatory chemokines, cytokines, and growth factors to normal levels after 48 h. This ex vivo skin model could be useful for studies evaluating the progression of local envenoming and the efficacy of snakebite treatments.

Compartment Syndrome Following Snake Envenomation in the United States: A Scoping Review of the Clinical Literature.

Local tissue destruction following envenomation from North American snakes, particularly those within the Crotalinae subfamily, has the potential to progress to compartment syndrome. The pathophysiology of venom-induced compartment syndrome (VICS) is a debated topic and is distinct from trauma/reperfusion-induced compartment syndrome. Heterogeneity exists in the treatment practices of VICS, particularly regarding the decision to progress to fasciotomy. Associations with functional outcomes and evolution in clinical practice since the introduction of Crotalidae polyvalent immune Fab (FabAV) have not been well defined. Our goal was to identify the potential gaps in the literature regarding this phenomenon, as well as illuminate salient themes in the clinical characteristics and treatment practices of VICS. We conducted this systematic scoping-style review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Records were included if they contained data surrounding the envenomation and hospital course of one or more patients who were envenomated by a snake species native to North America and were diagnosed with compartment syndrome from 1980-2020. We included 19 papers: 10 single- or two-patient case reports encompassing 12 patients, and nine chart reviews providing summary statistics of the included patients. In case reports, the median compartment pressure when reported was 60 millimeters of mercury (interquartile range 55-68), 66% underwent fasciotomy, and functional outcomes varied. Use of antivenom appeared to be more liberal with FabAV than the earlier antivenin Crotalidae polyvalent. Rapid progression of swelling was the most commonly reported symptom. Among the included retrospective chart reviews, important data such as compartment pressures, consistent laboratory values, and snake species was inconsistently reported. Venom-induced compartment syndrome is relatively rare. Existing papers generally describe good outcomes even in the absence of surgical management. Significant gaps in the literature regarding antivenom dosing practices, serial compartment pressure measurements, and functional outcomes highlight the need for prospective studies and consistent standardized reporting.