The bridge relationships of PTSD and depression symptoms among snakebite victims: a cross-sectional community-based survey.

BACKGROUND: The incidence of comorbid depression and post-traumatic stress disorder (PTSD) symptoms is higher in snakebite victims. However, the present state and contributing factors of depression and PTSD among Chinese snakebite victims remain unclear. METHODS: A representative sample of 6837 snakebite victims were assessed with the Post-traumatic Stress Disorder Checklist (Civilian Version) and The Center for Epidemiologic Studies Depression Scale. Multivariate analyses, including network analysis, evaluated the contributing factors of PTSD and depression symptoms caused by snake bites, as well as the bridge symptoms of comorbidity networks. RESULTS: Among 6,837 snakebite victims, 79.5% reported PTSD symptoms and 81.4% reported depression symptoms. Comorbidity of PTSD and depression symptoms was found in 75.1%. Key factors included the presence sequelae after snakebite (ORPTSD = 2.31, ORDepression = 1.89), time to medical facilities (6-8 h: ORPTSD = 3.17, ORDepression = 2.46), and marital status (divorced/widowed: ORPTSD = 1.78, ORDepression = 1.76). Symptoms I1 ("Repeated disturbing memories") and D1 ("Bothered by things that don't usually bother me") bridged PTSD and depression networks. CONCLUSION: The primary psychological challenges for snakebite victims in China are PTSD and depression symptoms, which is concerning. Standardized diagnosis and treatments, timely medical care, and stable marital relationships can reduce risks. Additional psychological support and management of negative memories, especially for those with severe bridge symptoms, can be beneficial. Further research should concentrate on understanding victims' psychological states and developing effective interventions.

Strikes and stripes of the Saw-scaled Viper in the Western Ghats-A case series.

We describe 5 cases of envenomation and complications related to saw scaled viper (Echis carinatus) bites from the Western Ghats region of Karnataka over a period of 5 years (December 2019-May 2023). Although the smallest member of the Big Four, Saw Scaled viper envenomation is associated with significant morbidity. In our region, envenomation appears to be rare. The careful review of all these cases has suggested VICC with one patient having persistent coagulopathy despite adequate ASV administration, and three patients developing anaphylaxis. It needs to be brought to notice that the complications due to envenoming run high, despite timely administration of ASV. Through these cases, we want to contribute evidence suggesting variable efficacy of Indian polyvalent ASV for Echis carinatus bites and the need for updating protocols for the same.

Design, development and preclinical assessment of MENAVip-ICP, a new snake antivenom with potential coverage of species in the Middle East and North Africa regions.

Snakebite in the Middle East and North Africa (MENA) is a public health problem whose magnitude is not fully known. Several antivenoms are available in these regions, but these formulations are designed for restricted geographical settings. Many countries do not have local production of antivenoms and must access products whose clinical performance has not been demonstrated. We hypothesize that it is possible to unify the treatment for viperid snakebites of MENA in a single antivenom formulation. Hereby we describe the design, development and preclinical evaluation of an antivenom of broad geographical coverage for this region (MENAVip-ICP). We produced this antivenom from the plasma of horses immunized with eight medically important venoms of viperid snake species from MENA. For this, we used a strategy based on two stages: first, immunization of horses with North African (NA) venoms, followed by a second immunization stage, on the same horses, with MENA venoms. We purified antivenoms from both stages: the Anti-NA and the final product Anti-MENA (MENAVip-ICP). Anti-NA was considered as intermediate formulation and was purified with the intention to study the progression of the immunoglobulin immune response of the horses. Antivenoms from both stages neutralized lethal, hemorrhagic, and procoagulant activities of homologous venoms. Compared to Anti-NA, MENAVip-ICP improved the neutralization profile of intravenous lethality and in vitro procoagulant activities of venoms. A notable finding was the difference in the neutralization of lethality when MENAVip-ICP was assessed intraperitoneally versus intravenously in the murine model. Intraperitoneally, MENAVip-ICP appears more effective in neutralizing the lethality of all venoms. Furthermore, MENAVip-ICP neutralized the lethal activity of venoms of species from other regions of MENA, Central/East Asia, and Sub-Saharan Africa that were not included in the immunization protocol. Our results showed that MENAVip-ICP neutralizes the main toxic activities induced by viperid MENA venoms at the preclinical level. Consequently, it is a promising product that could be clinically assessed for the treatment of snakebite envenomings in this region.

Multiple Ventricular Premature Complexes Following Equatorial Spitting Cobra (Naja sumatrana) Envenomation.

Naja species bite is the commonest cause for consultation to Remote Envenomation Consultancy Services in Malaysia. Envenomation by Naja species may result in neuroparalysis and cardiotoxic effects including arrhythmias, hypertension, tachycardia, atrioventricular blocks, ventricular tachycardia, and ventricular fibrillation. We report a case of cardiotoxicity as an early manifestation following an equatorial spitting cobra, Naja sumatrana bite, preceding early paralytic envenomation manifestation. A 14-year-old boy presented to an emergency department with mild local envenomation. ECG showed multiple ventricular premature complexes. Subsequently patient developed ptosis. Complete resolution of ptosis and resumption of normal sinus rhythm occurred following administration of the appropriate antivenom. The patient was discharged well after two days of hospitalization. The patient's ECG findings and neurotoxic manifestation suggested acute systemic envenomation. High index of suspicion for cardiotoxicity with close serial monitoring is recommended to ensure timely administration of antivenom.

Characterization of patients with a snakebite presenting to healthcare facilities and reported to poison and drug information centers-Arizona, 2017-2021.

INTRODUCTION: Envenomation after a North American rattlesnake (Crotalus spp. and Sistrusus spp.) bite is associated with substantial morbidity. Arizona reports the highest number of rattlesnake envenomations annually in the United States. We evaluated the performance of poison and drug information centers for snakebite surveillance, compared with the hospital and emergency department discharge database. We used both datasets to improve the characterization of epidemiology, healthcare costs, and clinical effects of snakebite envenomations in Arizona. METHODS: We identified patients with a snakebite during 2017-2021 using Arizona hospital and emergency department discharge data and snakebite consults with two regional Arizona poison centers. Patients were matched using name and birthdate. The performance of poison center data for snakebite surveillance was evaluated using the percentage of snakebite patients in hospital and emergency department discharge data that consulted with poison centers. Patient demographics, healthcare characteristics, clinical effects, and context of snakebite events were described using both datasets. RESULTS: In total, 1,288 patients with a snakebite were identified using the Arizona hospital and emergency department discharge data, which resulted in 953 (74%) consultations with poison centers. The median age of patients was 48 years (IQR 28-62 years), and they were predominantly male (66%), White (90%), and non-Hispanic (84%). The median billed charges were US$ 84,880 (IQR US$ 13,286-US$ 168,043); the median duration of a healthcare stay was 34 h (IQR 13-48 h), and 29% of patients were transferred between healthcare facilities. Among 953 consulted poison center calls for a snakebite, a median of 14 vials of antivenom was administered per patient; 375 (60%) bites occurred near the home, and 345 (43%) patients were bitten on a lower extremity. One death was identified. DISCUSSION: Snakebites in Arizona can cause severe morbidity and require extensive healthcare resources for treatment. Poison centers are valuable for monitoring venomous snakebites in Arizona. CONCLUSIONS: Using hospital and emergency department discharge data with poison center records can improve public health surveillance data regarding snakebite epidemiology and human-snake interaction information and be used to tailor interventions to increase awareness of snake encounters and prevent snakebites.

Limb circumference measurements contributing to the diagnosis of snake venom-induced compartment syndrome.

Background: The present study aimed to investigate the relationship between swollen limb circumference and compartment pressure after a snakebite and to evaluate the diagnostic value of the circumference difference between the healthy and affected sides and the circumference growth rate for snake venom-induced compartment syndrome (CS). Method: The study was based on a prospective cohort study of snakebite patients at the emergency department of West China Hospital from May 2021 to October 2022. The snakebite patients were divided into the CS and non-compartment syndrome (NCS) groups. The diagnostic value of the circumference of the swollen limb for the CS after snakebite was evaluated using a receiver-operating characteristic curve analysis, and the cut-off value of the circumference of the swollen limb for CS after snakebite was calculated with sensitivity and specificity. Result: The present study enrolled 115 patients with severely swollen limbs after snakebite. The mean age was 59.1 ± 13.6 years, with 58 (50.4 %) female cases and 57 (49.6 %) male cases. There were 33 (28.7 %) cases where the upper limbs were injured and 82 (71.3 %) cases where the lower limbs were injured. These patients were divided into CS (n = 19) and NCS (n = 96) groups. The area under the curve (AUC) for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella was 0.683 (95 % CI 0.508 to 0.858, P = 0.037), and 0.685 (95 % CI 0.512 to 0.858, P = 0.035). The optimal cut-off values for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella to distinguish CS and NCS were 2.8 cm (sensitivity = 76.9 %, specificity = 66.7 %) and 7 % (sensitivity = 76.9 %, specificity = 66.7 %), respectively. Conclusion: Limb circumference measurement is a non-invasive, convenient, effective, and repeatable bedside test that can assist clinicians in the early detection of suspected snake venom-induced CS in patients exhibiting limb swelling after snake bites.

The Chinese guideline for management of snakebites.

In 2009, the World Health Organization included snakebite on the list of neglected tropical diseases, acknowledging it as a common occupational hazard for farmers, plantation workers, and others, causing tens of thousands of deaths and chronic physical disabilities every year. This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims. These recommendations are based on clinical experience and clinical research evidence. This guideline focuses on the following topics: snake venom, clinical manifestations, auxiliary examination, diagnosis, treatments, and prevention.

Taipan envenoming south of the border.

We present a case of severe taipan envenoming in northern New South Wales in a 68-year-old man. He developed severe neurotoxicity requiring intubation and ventilation, venom-induced consumption coagulopathy, myotoxicity and thrombotic microangiopathy with acute kidney injury requiring dialysis. He was administered brown and tiger snake antivenom consistent with guidelines and snake occurrence in the region. Taipan venom was detected in serum (72 ng/ml) following concern about the severity of neurotoxicity, clinical toxicology consultation and a concurrent report of a taipan in the area. Based on this it would be prudent to stock and consider treating with polyvalent antivenom in north-eastern New South Wales and south-eastern Queensland.

Understanding pediatric snakebites: Clinical and epidemiological insights from a healthcare center in Bihar, India.

Background: Snakebites are a common medical emergency and occupational hazard for children in India, particularly in rural areas where poverty is prevalent. However, there is limited data on the epidemiology of snakebites on the Indian subcontinent. Objective: This cross-sectional, observational study aims to investigate the epidemiology, major clinical manifestations, and outcomes of snakebites in children under the age of 15 who were admitted to a tertiary care center in Bihar, a state in East India, and draw attention to this public health concern. Methods: A cross-sectional observational study was conducted at the Department of Paediatrics, Patna Medical College and Hospital, Patna. The study included all cases of snakebites with features of envenomation involving patients less than 15 years of age who were brought to the department over a 2-year period. Data were collected using a data collection form and analyzed using the Statistical Package for the Social Sciences, version 11.0 (SPSS Inc., Chicago, IL, USA). Results: A total of 59 cases were recorded, with 62.71% (n = 37) being male and 37.28% (n = 22) being female. Kraits were responsible for 38.9% (n = 23) of cases, vipers for 42.3% (n = 25), and cobras for 5% (n = 3). Fang marks were present in 67.7% (n = 40) of cases, and the majority of bites (84.7%, n = 50) occurred on a lower limb during the day. The age distribution showed that 16.9% (n = 10) were below 5 years old, 44% (n = 26) were between 5 and 10 years old, and 22% (n = 13) were above 10 years old. Traditional treatment was used in 44.7% (n = 22) of cases, with the most common treatments being local incision + tourniquet (22%, n = 13) and no traditional treatment (55.9%, n = 33). The highest number of cases occurred during July-September (35.5%, n = 21). Conclusion: Snakebites are a significant public health issue in Bihar, India, with the majority of cases occurring in rural areas. The study highlights the importance of increased awareness and preparedness among healthcare providers and the general public, particularly during the monsoon season. Early hospital transfer, prehospital management, and prevention should be promoted through regular public health initiatives.

Enhancing snakebite management: The role of small molecule therapeutics in complementing antivenom strategies.

The variability in snake composition presents a significant challenge in accessing an effective broad-spectrum antivenom. These highly complex mixtures can result in numerous deleterious effects affecting thousands of individuals worldwide, particularly in Asia, sub-Saharan Africa, and Latin America. While the administration of antivenom remains a recommended treatment for snakebite envenomation and is the primary means to prevent systemic damage, there are limitations concerning specificity, reversal of local effects, and economic factors that hinder the availability of these antibodies. In this review, we have compiled information on the use of small molecule therapeutics in initial first-aid treatments before antivenom administration. These enzyme inhibitors have shown promise as viable candidates to broaden our treatment approaches, simplify procedures, reduce costs, and improve the clinical outcomes of affected patients.

Snakebites by venomous snakes in Brazilian serpentaria and zoos over a 10-year period (2012-2021).

Despite the wide range of institutions that maintain venomous snakes in captivity in Brazil there are no comprehensive data on the occurrence of snakebites and envenomations in these places. We examined the range of native and exotic species of venomous snakes kept by Brazilian zoos and serpentaria (scientific and commercial) and assessed the frequency of snakebites in workers handling these snakes during a 10-year period (2012-2021). Twenty-two (73.3%) of 30 institutions returned a standard questionnaire, including 15 serpentaria and 7 zoos that together kept 10,607 venomous snakes in 2022/2023. Commercial and scientific serpentaria had many more snakes (n = 10,550, consisting of 10,499 native specimens and 51 exotic specimens) than zoos (n = 57 native specimens), with two genera accounting for the majority of native species (Bothrops spp. = 84.5% and Crotalus durissus ssp. = 13.5%). Thirty-seven snakebites were reported and involved primarily the hands (33), seven of which occurred during venom extraction and 30 in other circumstances, most of them while handling/manipulating the cages or snake boxes (10) and restraining (9) or feeding (5) the snake. In addition, there were two cases of venom accidently sprayed on the face, including the eyes. Most bites were caused by Bothrops spp. (31), followed by C. durissus ssp. (4), Lachesis muta (1) and Micrurus corallinus (1). Thirty-three bites (89.2%) were treated with antivenom, with four bites to the fingers by Bothrops spp. resulting in local functional sequelae. There were 366,918 venom extractions with a ratio of 1.9 bites/100,000 extractions; no bites were recorded in the six institutions that sedated the snakes prior to venom extraction, which accounted for 22.7% of all extractions. These findings show that although snakebites are rare in Brazilian zoos and serpentaria, severe envenomation may occur. The occurrence of snakebites could be reduced by measures such as sedation of the snakes before venom extraction.

Paraspecific neutralization capacity of polyvalent snake antivenom against Montivipera wagneri venom.

PURPOSE: This study aims to measure the paraspecific neutralization capacity of nationally produced HSGM polyvalent snake antivenom (HSGM-PSAV), produced using Macrovipera lebetina obtusa, Montivipera xanthina, and Vipera ammodytes montandoni venom, against the lethal effect of the venom of Montivipera wagneri, which is endemic to the Eastern Black Sea and Eastern Anatolia regions of Turkey. METHODS: The neutralization capacity of HSGM-PSAV against the lethal effect of M. wagneri venom was studied using the potency determination testing method specified in the Turkish and European Pharmacopoeia. Lethal dose 50 (LD50) values of the venoms used in immunization, M. wagneri venom in mice, and effective dose 50 (ED50) values of HSGM-PSAV against four types of venoms were calculated using two-fold dilutions. RESULTS: HSGM-PSAV neutralized the lethal effect of M. wagneri venom in mice. The ED50 of the HSGM-PSAV against M. wagneri venom was calculated as 304.42 LD50/mL. CONCLUSION: As a result of this in-vivo study, it was determined that HSGM-PSAV neutralized M.wagneri venom above the antivenom neutralization capacity threshold values (≥50 LD50/mL) specified in the Turkish and European Pharmacopoeia. This result is important preclinical data regarding the usability of HSGM-PSAV in the treatment of poisoning due to M. wagneri bites.

Successful use of anti-venom cross-neutralization effects in the clinical management of Shore Pit Viper envenomation.

As the landscape becomes more urbanized, snakebites have increasingly become uncommon presentations to the emergency departments in Singapore, while snakebites causing significant envenomation are even rarer. In this case report, we discuss a 55-year-old man who had significant envenomation from a Shore Pit Viper (Trimeresurus Purpureomaculatus) and who was successfully treated with haemato-toxic polyvalent antivenom (HPAV). He initially presented with pain, swelling and bleeding over his wound. Due to a deterioration in his coagulation profile, he was given two doses of HPAV which is typically reserved for viperid snakes instead. Following administration of the anti-venom, the patient's coagulation profile improved, and the local soft tissue effects of the venom resolved. He did not manifest any adverse effects and was discharged uneventfully about 72 h after the snakebite. The cross-neutralization potential of HPAV for Shore Pit Viper (Trimeresurus Purpureomaculatus) venom in this case study suggests that there may be a possible common underlying chemical structure and pathophysiology among the venom proteins of various snake species. Given that Trimeresurus-specific antivenom is unavailable in most countries, this cross-neutralization strategy deserves further consideration and evaluation in similar circumstances.

Snakebites and Antisnake Venom Utilization in Ghana's Oti Region: A 6-Year Retrospective Study.

Background: Snakebite is a global environmental and occupational hazard and a significant public health threat. In rural areas, snakebite cases often go unreported and undocumented due to the lack of access to well-structured healthcare facilities/infrastructure. In some cases, the need for antisnake venom (ASV) far outstrips supply, negatively affecting treatment outcomes. This study, therefore, assessed the epidemiological characteristics of snakebite cases, their management, and how antivenoms are utilised at the selected hospital in the Jasikan District Hospital. Methods: A 6-year retrospective study using secondary data from antivenom return forms (pharmacy records), clinical records (patient folders), the District Health Information Management System-2 (DHIMS-2) database, and consulting room registers was carried out in selected hospitals in the Jasikan District, Oti, Ghana. Results: The predominant symptom of snakebite was localised pain (71.4%). The snakebite commonly occurred at home (19%) and on farms (18%). Of the 98 snakebite cases, ASV was administered to 73 (74.5%) cases. Supportive treatment applied included prophylactic antitetanus immunoglobulin (ATS) (80.6%), prophylactic antibiotics (63%), corticosteroids (80.6%), and analgesics (63%). 95% (n = 94) of complete recoveries were recorded; three were discharged against medical advice, and one was mortality. The supply and use of antivenom were erratic throughout the months of high incidence, partly due to inconsistent availability at the Regional Medical Stores. The average ASV vials and hospital stay duration were 1.23 ± 0.86 vials and 2.67 ± 1.97 days, respectively. Although the peak of snakebites occurs in April, May, and June, the demand for antivenom in April and May exceeded supply. Conclusion: The outcome of most snakebite case management was appropriate, irrespective of inadequate ASV supply in certain months. The erratic antivenom supply should be aligned with seasonal and facility-use patterns to enhance regional snakebite management.

Metabolomic analysis of Agkistrodon haly venom poisoning mouse treatment by Jidesheng snake pill based on GC-MS.

Introduction: Snakebites are acute systemic toxic diseases caused by snake venom entering the body through wounds. Failure to use antivenom immediately and difficulty in obtaining antivenoms are frequently responsible for worsening disease. Traditional Chinese medicine is commonly used to supplement and replace antivenom in treating snakebites. The Jidesheng snake pill (JDS) is a widely used traditional Chinese medicine that has achieved good clinical therapeutic effects; however, its mechanism remains unclear. Therefore, metabolomics techniques were employed to explore the pathophysiological mechanisms of JDS treatment of Agkistrodon halys (Ah) snake venom-poisoned mice. Methods: The Ah group mouse model was established by intramuscular injection of Ah venom into the hind legs of the mice. The Ah venom + JDS group model was established using JDS after the affected area was treated with Ah venom. Hematoxylin and eosin (HE) staining was used to evaluate the severity of gastrocnemius injury. Quantitative polymerase chain reaction (qPCR) was utilized to detect the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), muscle-specific creatine kinase (CKM), thrombin antithrombin complex (TAT), and tumor necrosis factor-alpha (TNF-α). Gas chromatography-mass spectrometry (GC-MS) was performed with multivariate statistical analysis to provide new insights into the global metabolic profile of Ah venom-poisoned mice. Results: HE staining revealed increased red cell necrosis, local hemorrhage, and neutrophil infiltration in the Ah venom group than in the control group. Several compounds were identified, including lipids, amino acids, peptides, and organooxygen. Eighty differential metabolites were screened between the control group and the Ah venom group, and 24 were screened between the Ah venom and JDS groups. The mechanism of Ah venom poisoning in mice may involve aminoacyl-tRNA biosynthesis, various amino acid metabolism disorders, tricarboxylic acid circulation disorders, and abnormal fatty acid metabolism. JDS may reduce symptoms by affecting long-chain fatty acid and amino acid metabolism and promoting nicotinamide-nicotinamide metabolism. Conclusion: Our results suggest that metabolomics has huge prospects for elucidating the pathophysiology of Agkistrodon haly venom poisoning and therapeutic mechanisms of JDS.

[Snakebite in Switzerland - a potentially life-threatening event?] / Schlangenbiss im Glarnerland ­ ein potenziell lebensbedrohliches Ereignis?

INTRODUCTION: A 39-year-old healthy patient accidentally stepped barefoot on an adder and was then bitten into the foot. After initially only local complaints, severe systemic symptoms developed within 10-15 minutes with swelling of the lips and soft palate, recurrent vomiting, bradycardia, weakly palpable peripheral pulse, hypotension, dyspnea and intermittent somnolence. The potentially life-threatening consequences of this severe poisoning could be avoided by using adequate emergency measures and immediate intravenous administration of antivenin.

Faith healing: the threat of "Surucucu" and the local cure of Amazon floodplain dwellers.

BACKGROUND: Snakebites are considered a neglected tropical disease responsible for many accidents, some fatal, and are related to poverty. The Brazilian Amazon has the highest incidence of snakebites per inhabitant, with the state of Pará having the most reported cases. For those who have difficult access to hospitals and pharmacies, this issue is even more urgent. METHODS: In this research, we worked together with the population of five riverine communities in Aritapera (Santarém-PA), a fluvial island located in the Lower Amazon floodplain (várzeas), in order to identify the species of venomous snakes and create a record of snakebites in the region and treatments carried out. RESULTS: Dwellers reported a high frequency of encounters throughout the year and mentioned five venomous ethnospecies, although we identified only Bothrops atrox. Approximately 28.7% of the participants had already been bitten, and in 15.8% of the interviews, they mentioned deaths from snakebites. The treatments varied between hospitalization (42.8%), home treatments (23.8%), both together (25.4%) and healers (7.9%). There were cases where no treatment, or just religious treatment, was performed. In general, no serious sequelae were reported. Although home treatments were more common in the past, many people maintained the practice of using them before going to the hospital. Among the most used are Pau X and the fat of the Amazon River Dolphin. The latter appears to be a recent discovery by locals and is considered very efficient both for humans and animals. CONCLUSION: Difficult access to health centers, a lack of energy to store antivenom and a high rate of encounters with snake place Aritapera dwellers in a vulnerable situation regarding snakebite accidents. In this context, they discovered treatments that improved their well-being until hospitalization. As the Amazon River dolphin is an endangered species, the use of its fat requires attention. In this sense, the dissemination of this knowledge is important to encourage studies that investigate which properties of this fat act as counterpoisons. By discovering substitutes that can be incorporated in other rural and remote communities, an economic and ecologically viable option for the health of residents can be promoted, in addition to valuing traditional knowledge.

Reported snakebite mortality and state compensation payments in Madhya Pradesh, India, from 2020 to 2022.

BACKGROUND: India experiences the highest snakebite burden globally, with 58 000 predicted deaths annually. The central Indian state of Madhya Pradesh is thought to have a substantial snakebite burden and provides compensation to families who can demonstrate by postmortem and hospital treatment reports that their relatives have died due to snakebite. This study represents the first report on the frequency of distribution of compensation for snakebite deaths in Madhya Pradesh. METHODS: Statewide snakebite death compensation data from 2020-2021 and 2021-2022, provided by the Madhya Pradesh health authorities, were analysed alongside interviews with 15 families that described the events that ultimately led to their compensation claims. RESULTS: Compensation was paid to a total of 5728 families, with a total value equating to 22 912 Lakhs (approximately US${\$}$27.94 million). Families described commonly recognised snakebite risk factors and behaviours in the events that resulted in their relatives' deaths. CONCLUSIONS: The snakebite burden in Madhya Pradesh is significant, both in terms of mortality and economic expenditure of the state. Sustained investment in preventative interventions, as well as monitoring of the rate of compensation payouts due to snakebite death as a measure of intervention effectiveness, should be considered to substantially reduce snakebite incidence and mortality.

Inhibitors and activators for myotoxic phospholipase A2-like toxins from snake venoms - A structural overview.

Snakebite envenomations result in acute and chronic physical and psychological health effects on their victims, leading to a substantial socio-economic burden in tropical and subtropical countries. Local necrosis is one of the serious effects caused by envenomation, primarily induced by snake venoms from the Viperidae family through the direct action of components collectively denominated as myotoxins, including the phopholipase A2-like (PLA2-like) toxins. Considering the limitations of antivenoms in preventing the rapid development of local tissue damage caused by envenomation, the use of small molecule therapeutics has been suggested as potential first-aid treatments or as adjuvants to antivenom therapy. In this review, we provide an overview of the structural interactions of molecules exhibiting inhibitory activity toward PLA2-like toxins. Additionally, we discuss the implications for the myotoxic mechanism of PLA2-like toxins and the molecules involved in their activation, highlighting key differences between activators and inhibitors. Finally, we integrate all these results to propose a classification of inhibitors into three different classes and five sub-classes. Taking into account the structural and affinity information, we compare the different inhibitors/ligands to gain a deeper understanding of the structural basis for the effective inhibition of PLA2-like toxins. By offering these insights, we aim to contribute to the search for new and efficient inhibitor molecules to complement and improve current therapy by conventional antivenoms.