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1.
BMJ Case Rep ; 17(5)2024 May 23.
Article in English | MEDLINE | ID: mdl-38782420

ABSTRACT

Certain snake envenomation patients with consumptive coagulopathy, termed venom-induced consumption coagulopathy, develop thrombotic microangiopathy (TMA). Due to predominant renal involvement, TMA is said to resemble haemolytic uraemic syndrome and is treated with haemodialysis. We present a case of a young male who presented to the emergency department after being bitten by a white-lipped pit viper (Trimeresurus albolabris). He developed heart failure in addition to acute kidney injury secondary to TMA. He was treated with 30 vials of anti-snake venom according to national guidelines and underwent haemodialysis. Despite haemodialysis, the patient's ventilatory parameters continued to worsen, necessitating invasive mechanical ventilation. Thus, he was initiated on plasma exchange therapy, to which the patient responded well. TMA has not been reported in Trimeresurus envenomations yet, to the best of our knowledge. Additionally, plasma exchange therapy can be considered an adjunctive therapy for snakebite patients who develop TMA.


Subject(s)
Plasma Exchange , Snake Bites , Thrombotic Microangiopathies , Humans , Snake Bites/complications , Snake Bites/therapy , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/therapy , Male , Animals , Plasma Exchange/methods , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Trimeresurus , Antivenins/therapeutic use , Adult , Renal Dialysis , Heart Failure/etiology , Heart Failure/therapy
2.
BMJ Case Rep ; 17(5)2024 May 22.
Article in English | MEDLINE | ID: mdl-38782437

ABSTRACT

In cases of severe envenomation due to snakebites, patients require antivenom, intensive care management, including respiratory support, haemodynamic monitoring and renal replacement therapy. Early recognition and treatment of complications such as acute kidney injury, rhabdomyolysis and coagulopathy are important to improve outcomes.Tele-ICU models can play a critical role in providing access to critical care expertise and nuanced support to remote healthcare facilities that may not have the necessary resources or expertise to manage complex cases of envenomation. With the help of telemedicine technology, remote intensivists can provide timely guidance on diagnosis and ongoing management, improving the quality of care and outcomes for patients. We discuss two patients in resource-constrained regions of India with severe envenomation who were managed with tele-ICU support.


Subject(s)
Antivenins , Snake Bites , Telemedicine , Humans , India , Snake Bites/therapy , Snake Bites/complications , Antivenins/therapeutic use , Antivenins/administration & dosage , Male , Critical Care/methods , Intensive Care Units , Adult , Acute Kidney Injury/therapy , Acute Kidney Injury/etiology , Animals , Female
3.
Nat Commun ; 15(1): 4310, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773068

ABSTRACT

Oligoclonal mixtures of broadly-neutralizing antibodies can neutralize complex compositions of similar and dissimilar antigens, making them versatile tools for the treatment of e.g., infectious diseases and animal envenomations. However, these biotherapeutics are complicated to develop due to their complex nature. In this work, we describe the application of various strategies for the discovery of cross-neutralizing nanobodies against key toxins in coral snake venoms using phage display technology. We prepare two oligoclonal mixtures of nanobodies and demonstrate their ability to neutralize the lethality induced by two North American coral snake venoms in mice, while individual nanobodies fail to do so. We thus show that an oligoclonal mixture of nanobodies can neutralize the lethality of venoms where the clinical syndrome is caused by more than one toxin family in a murine challenge model. The approaches described may find utility for the development of advanced biotherapeutics against snakebite envenomation and other pathologies where multi-epitope targeting is beneficial.


Subject(s)
Antibodies, Neutralizing , Coral Snakes , Single-Domain Antibodies , Animals , Single-Domain Antibodies/immunology , Mice , Antibodies, Neutralizing/immunology , Coral Snakes/immunology , Disease Models, Animal , Antivenins/immunology , Elapid Venoms/immunology , Female , Snake Bites/immunology , Snake Bites/therapy , Epitopes/immunology , Mice, Inbred BALB C , Cell Surface Display Techniques
4.
J Am Anim Hosp Assoc ; 60(3): 114-119, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38662995

ABSTRACT

Snake envenomation is relatively common in small animals, particularly in endemic areas. Effects and outcomes of envenomation during pregnancy are poorly described in humans and more so in veterinary patients. Two young pregnant female dogs presented to a university teaching hospital with a history of acute soft tissue swelling and bleeding. History, physical examination findings, and diagnostics were consistent with envenomation by crotalid snakes. Medical management of one of the dogs included administration of antivenin. Both dogs survived envenomation with minimal complications and went on to whelp without complications, and all fetuses survived. This is the first description of the management of pit viper envenomation in pregnant dogs.


Subject(s)
Antivenins , Dog Diseases , Snake Bites , Animals , Dogs , Snake Bites/veterinary , Snake Bites/therapy , Snake Bites/complications , Female , Pregnancy , Dog Diseases/etiology , Dog Diseases/pathology , Antivenins/therapeutic use , Pregnancy Complications/veterinary , Crotalid Venoms/poisoning , Crotalid Venoms/toxicity , Viperidae
5.
A A Pract ; 18(4): e01744, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38557929

ABSTRACT

Snakebite pain can be challenging to control. We describe our experience managing intolerable pain after conventional treatment failed. A 35-year-old man, presented after a viper snakebite, suffering from intolerable pain in the affected extremity. He had no significant past medical history. All attempts to control the pain conventionally were unsuccessful. Treatment with a supraclavicular nerve block resulted in immediate relief. After the block receded, only a dull pain remained, which later disappeared without recurrence. This experience illustrates the need for personalized pain treatment to avoid subsequent complications.


Subject(s)
Brachial Plexus Block , Daboia , Snake Bites , Viperidae , Male , Animals , Humans , Adult , Snake Bites/complications , Snake Bites/therapy , Pain , Peripheral Nerves
6.
Toxicon ; 242: 107704, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38565396

ABSTRACT

Members of the genus Protobothrops are amongst the more than twenty-eight range-restricted Indian pit viper species. Their bites and envenomings are rarely documented from India. Pit viper envenomings can be challenging to treat in the Indian setting, since available antivenoms do not satisfactorily neutralize their venoms. Herein, we present the first Indian reports on bites and envenoming by Protobothrops jerdonii and Protobothrops himalayanus resulting in local effects, coagulopathy and acute kidney injury in the case of the former and possible mild, isolated coagulopathy in the case of the latter; and discuss management-related challenges in the context of absent specific antivenoms.


Subject(s)
Antivenins , Crotalid Venoms , Crotalinae , Poison Control Centers , Snake Bites , Snake Bites/therapy , India , Animals , Humans , Antivenins/therapeutic use , Male , Acute Kidney Injury/therapy , Adult , Female , Middle Aged
7.
PLoS Negl Trop Dis ; 18(4): e0012080, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38574167

ABSTRACT

BACKGROUND: Snakebite envenoming represents a significant and often neglected public health challenge, particularly in rural communities across tropical and subtropical regions. An estimated 1.2-5.5 million people are envenomed by snakebites annually. More than 125,000 of these bites are fatal, and 3-4 times as many results in disability/disfigurement. Despite its prevalence, collecting accurate epidemiological data on snakebite is challenging. This systematic review and meta-analysis collates global epidemiology data on snakebite morbidity and mortality. METHODS: Medline, Embase, Cochrane and CINAHL Plus databases were searched for articles published between 2001-2022. Pooled incidence and mortality were obtained using random effects modelling, heterogeneity (I2) was tested, and sensitivity analyses performed. Newcastle-Ottawa Scale assessed study quality. RESULTS: Out of the four databases, 5,312 articles were found. After removing duplicates, 3,953 articles were screened by title and abstract and 65 articles containing information on snakebite epidemiology, encompassing 663,460 snakebites, were selected for analysis. The people most at risk for snakebite were men (59%), engaged in agricultural labour (27.5%), and residing in rural areas (66.7%). More than half (57%) of the reported bites resulted in envenoming. Incidents occurred frequently in the summer season (38.5%), during daytime (56.7%), and bites were most often to the lower limb (56.4%). Envenoming severity was frequently mild (46.7%), treated in hospital (68.3%), and was treated with anti-venom (64.7%). The pooled global incidence and mortality was 69.4 /100,000 population (95%CI: 36.8 to 101.9) and 0.33/100,000 population (95%CI, 0.14 to 0.52) per year, respectively. Stratified by continents, Asia had the highest incidence of 130.7/100,000 population (95%CI: 48.3 to 213.1) while Europe has the lowest with 0.7/100,000 population (95%CI: -0.2 to 1.5). The highest mortality was reported in Asia at 0.96/100,000 population (95% CI: 0.22 to 1.70), and Africa 0.44/100,000 population (95%CI: -0.03 to 0.84). Incidence was highest among inhabitants of lower-middle-income countries 132.7/100,000 population (95%CI: 55.4 to 209.9) while mortality was highest in low-income countries at 0.85/100,000 population (95% CI: -0.06 to 2.31). CONCLUSION: Incidence and mortality rates noted here highlight the global impact of snakebite and underscore the critical need to address the burden of snakebite envenoming. It also reveals that while reported snakebite incidence was higher in lower-middle-income countries, the burden of mortality was greatest among inhabitants of low-income countries, again emphasising the need for greater efforts to tackle this neglected tropical disease.


Subject(s)
Snake Bites , Male , Humans , Female , Snake Bites/therapy , Antivenins , Incidence , Asia , Prevalence
8.
PLoS One ; 19(4): e0299814, 2024.
Article in English | MEDLINE | ID: mdl-38573972

ABSTRACT

BACKGROUND: Snakebites are a dangerous and significant medical emergency that occurs worldwide. The World Health Organization has recommended that teaching and training in the prevention and management of snakebites be included in the curriculum of nursing schools and other educational activities. Identification of venomous snakes and first aid would be more critical in the prevention of occupational danger worldwide. This study aims to assess the knowledge in identifying venomous snakes, snakebites, and first aid methods of snakebites among nursing students in the Southern Province of Sri Lanka. METHODS: A descriptive, cross-sectional study was performed among 425 nursing students who were studying in different educational settings: undergraduates at the University of Ruhuna, and nursing students in the three schools of nursing in Galle, Matara, and Hambantota. Data were gathered by incorporating a pre-tested self-administered questionnaire after obtaining institutional permission. The total score of whole knowledge ranged from 0 to 34 for the identification of venomous snakes. Data collection was performed after obtaining ethical clearance from the Ethics Review Committee, Faculty of Allied Health Sciences, University of Ruhuna, Sri Lanka. RESULTS: Most of the students (82.6%) were in the 24-26 age category and the majority were females. Most of the sample (64.7%) had low knowledge of identifying venomous snakes. A higher percentage of students (57.4%) had a sufficient level of knowledge about first aid methods associated with snakebites and 169 participants (39.8%) had a high level of knowledge regarding first aid methods. Further, a significant impact on students' knowledge and knowledge of first aid methods was reported. CONCLUSION AND RECOMMENDATION: The overall knowledge of identifying venomous snakes among the nursing students was inadequate. However, the knowledge about the first aid methods was at a moderate level. Strategies are needed to improve knowledge in identifying venomous snakes and first aid methods of snakebites amongst nursing students in both educational settings.


Subject(s)
Snake Bites , Students, Nursing , Animals , Female , Humans , Male , Snake Bites/diagnosis , Snake Bites/epidemiology , Snake Bites/therapy , Venomous Snakes , Snakes , Cross-Sectional Studies , First Aid
11.
Toxicon ; 241: 107682, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38460605

ABSTRACT

Hemorrhagic stroke is a severe complication reported in cases of Bothrops atrox snakebite envenomation. We report an unusual case of a patient who evolved with an intracranial hemorrhagic stroke and was in a coma for more than five years in a tertiary hospital located in Manaus, Amazonas. 52-year-old man, carpenter, resident in the rural area of the municipality of Tabatinga, located 1106 km from Manaus, capital of Amazonas, Brazil, victim of an accident involving Bothrops atrox evolution with cardiorespiratory arrest, acute kidney injury and hemorrhagic stroke. After 43 days of hospitalization in the ICU, he was transferred to the ward, without contact with the environment and family, sent for home treatment, however, without acceptance by family members. During a long hospital stay for a period of 6 years, totally dependent on special care, in a flexed position, using a tracheostomy and mechanical ventilation, diagnosed and treated for hospital infections throughout his hospitalization, he died due to bacterial pneumonia. Losses of autonomy can result in an individual being completely disconnected from social life - a "social death before physical death".


Subject(s)
Bothrops , Crotalid Venoms , Hemorrhagic Stroke , Snake Bites , Male , Animals , Humans , Middle Aged , Snake Bites/complications , Snake Bites/therapy , Bothrops atrox , Brazil , Hemorrhagic Stroke/complications , Hospitals , Antivenins
12.
Toxicon ; 241: 107686, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38508243

ABSTRACT

Envenomations by the common green racer (Chlorosoma viridissimum) are seldom reported in the literature. Herein, we report three cases caused by the same specimen of C. viridissimum in three different victims in the Brazilian Amazon. In all cases, the victims were either a biologist or biology students that were handling the animal and were bitten in their upper limbs. The victims showed only local symptoms, such as edema, tooth marks, pain, erythema, ecchymoses and bleeding. One of the patients presented extensive ecchymosis. Two patients sought medical care, but were only treated for local manifestations and evolved without complications. Chlorosoma viridissimum is capable of provoking mild to moderate signs and symptoms.


Subject(s)
Colubridae , Snake Bites , Animals , Humans , Snake Bites/therapy , Brazil , Pain/etiology , Hemorrhage/complications , Antivenins
14.
PLoS Negl Trop Dis ; 18(3): e0012052, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38530781

ABSTRACT

BACKGROUND: Progress in snakebite envenoming (SBE) therapeutics has suffered from a critical lack of data on the research and development (R&D) landscape. A database characterising this information would be a powerful tool for coordinating and accelerating SBE R&D. To address this need, we aimed to identify and categorise all active investigational candidates in development for SBE and all available or marketed products. METHODOLOGY/PRINCIPAL FINDINGS: In this landscape study, publicly available data and literature were reviewed to canvas the state of the SBE therapeutics market and research pipeline by identifying, characterising, and validating all investigational drug and biologic candidates with direct action on snake venom toxins, and all products available or marketed from 2015 to 2022. We identified 127 marketed products and 196 candidates in the pipeline, describing a very homogenous market of similar but geographically bespoke products and a diverse but immature pipeline, as most investigational candidates are at an early stage of development, with only eight candidates in clinical development. CONCLUSIONS/SIGNIFICANCE: Further investment and research is needed to address the shortfalls in products already on the market and to accelerate R&D for new therapeutics. This should be accompanied by efforts to converge on shared priorities and reshape the current SBE R&D ecosystem to ensure translation of innovation and access.


Subject(s)
Snake Bites , Toxins, Biological , Humans , Antivenins , Data Management , Snake Bites/therapy
15.
Ann Afr Med ; 23(1): 104-106, 2024.
Article in English | MEDLINE | ID: mdl-38358180

ABSTRACT

Ischemic stroke following snake bite is rare. We report a posterior circulation infarct involving bilateral cerebellum and occipital lobe following Russell's viper bite in a previously healthy individual. A 50 years old healthy individual, soon after being bitten by the Russel viper on the left foot he developed pain and swelling followed by drooping of eyelids, slurring of speech and giddiness with multiple episodes of vomiting. The patient was administered ASV as well as neostigmine and atropine injections. Following this, the neurological manifestations resolved except dysarthria. CT brain study done was normal. On day 2 of hospitalization, he developed left cerebellar signs (positive finger nose finger test, rebound phenomenon, dysdiadochokinesia, a positive heel shin test). Subsequently, an MRI with MR angiogram was done which showed acute infarcts in bilateral cerebellar hemispheres, with the left superior cerebellar peduncle showing restricted diffusion and low ADC values. Ischemic infarction following viper envenomation has been described by only few authors. In majority of the cases reported, ischemic infarction involved the anterior circulation. The possible mechanisms of infarction in this scenario are discussed. Patient was treated with anti-snake venom and showed a good recovery. Early imaging and early treatment with anti-snake venom is important for a favourable outcome.


Résumé L'AVC ischémique consécutif à une morsure de serpent est rare. Nous rapportons un infarctus de la circulation postérieure impliquant le cervelet et le lobe occipital bilatéraux suite à une morsure de vipère de Russell chez un individu auparavant en bonne santé. Un individu en bonne santé de 50 ans, peu de temps après avoir été mordu par la vipère Russel au pied gauche, il a développé une douleur et un gonflement suivis d'un affaissement des paupières, d'un trouble de l'élocution et de vertiges avec de multiples épisodes de vomissements. Le patient a reçu de l'ASV ainsi que des injections de néostigmine et d'atropine. Suite à cela, les manifestations neurologiques ont disparu sauf la dysarthrie. L'étude cérébrale réalisée par TDM était normale. Au 2ème jour d'hospitalisation, il a développé des signes cérébelleux gauches (test doigt nez doigt positif, phénomène de rebond, dysdiadochokinésie, test talon tibia positif). Par la suite, une IRM avec angiographie IRM a été réalisée qui a montré des infarctus aigus dans les hémisphères cérébelleux bilatéraux, le pédoncule cérébelleux supérieur gauche montrant une diffusion restreinte et de faibles valeurs d'ADC. L'infarctus ischémique consécutif à une envenimation par vipère n'a été décrit que par quelques auteurs. Dans la majorité des cas rapportés, l'infarctus ischémique impliquait la circulation antérieure. Les mécanismes possibles de l'infarctus dans ce scénario sont discutés. Le patient a été traité avec du venin anti-serpent et a montré une bonne récupération. Une imagerie précoce et un traitement précoce avec du venin anti-serpent sont importants pour un résultat favorable. Mots-clés: Infarctus cérébelleux, étude cérébrale par imagerie par résonance magnétique, morsure de vipère.


Subject(s)
Brain Ischemia , Daboia , Snake Bites , Male , Animals , Humans , Middle Aged , Snake Bites/complications , Snake Bites/therapy , Magnetic Resonance Imaging , Infarction , Antivenins
16.
J Med Case Rep ; 18(1): 56, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38355606

ABSTRACT

INTRODUCTION: Snakebite envenomation poses a significant health risk, particularly in low-resource settings where access to proper treatment is limited. CASE PRESENTATION: This study reports two cases of Russell's viper bites in rural Bangladesh, involving 48 and 35-year-old Bangladesh males, respectively, and highlights the difficulties in providing adequate medical care and in treating any complications that may arise. Both cases involved delayed access to healthcare, initial visit to traditional healers, and the development of severe complications such as coagulopathy, renal failure. After the intervention both cases survived which is scarce in low resource settings. CONCLUSION: The cases underscore the importance of early recognition, appropriate management, and improved healthcare infrastructure to optimize survival outcomes in snakebite cases in resource-limited settings. These cases will contribute valuable insights to the field of snakebite management and provide guidance for improving survival rates and outcomes among snakebite victims in Bangladesh.


Subject(s)
Blood Coagulation Disorders , Daboia , Renal Insufficiency , Snake Bites , Animals , Humans , Male , Blood Coagulation Disorders/complications , Public Health Infrastructure , Snake Bites/complications , Snake Bites/therapy , Adult , Middle Aged
17.
Wilderness Environ Med ; 35(2): 219-222, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38379495

ABSTRACT

Although sea snakes (Elapidae) are commonly encountered by fishermen, accurately authenticated envenomings by them are uncommon in clinical literature. We report an authenticated case of Shaw's short, or spine-bellied, sea snake (Hydrophis curtus) bite in a young fisherman from northern Sri Lanka. The patient had clinical and biochemical evidence of mild transient myotoxicity but no evidence of neuromuscular paralysis or significant renal injury. Consideration of the clinical manifestations suggests either a mild envenoming or a dry bite. The patient completely recovered without any antivenom therapy and was discharged on the fourth day. Prolonged observation may be beneficial to exclude complications of sea snake envenoming.


Subject(s)
Hydrophiidae , Snake Bites , Animals , Snake Bites/complications , Snake Bites/therapy , Humans , Sri Lanka , Male , Myotoxicity/etiology , Adult
18.
Emerg Med Pract ; 26(Suppl 2): 1-44, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38350100

ABSTRACT

There are approximately 10,000 emergency department visits in the United States for snakebites every year, and one-third of those involve venomous species. Venomous North American indigenous snakes include species from the Crotalinae (pit vipers) and Elapidae (coral snakes) subfamilies. Treatment relies on supportive care, plus antivenom for select cases. While certain principles of management are widely accepted, controversies exist with regard to prehospital use of pressure immobilization, antivenom use, coagulation testing after copperhead envenomation, and fasciotomy. An evidence-based approach to management of North American venomous snakebites will be discussed, along with a review of the current controversies.


Subject(s)
Snake Bites , United States/epidemiology , Humans , Snake Bites/diagnosis , Snake Bites/therapy , Antivenins/therapeutic use , Emergency Service, Hospital , North America/epidemiology
19.
J Int Med Res ; 52(1): 3000605231225540, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38258738

ABSTRACT

OBJECTIVE: To identify risk factors associated with snakebite severity and determine whether tourniquet use can affect the severity and outcome of snakebites. METHODS: The clinical data of patients who sustained limb snakebites from 1 March 2021 to 31 October 2022 were reviewed. The patients were divided into three groups according to snakebite severity: mild (517 cases), moderate (112 cases), and severe (8 cases). We compared the clinical data of mild versus moderate to severe snakebites. Multivariate logistic regression was used to determine the independent risk factors for moderate to severe snakebites. RESULTS: The study involved 637 patients. There were statistically significant differences in age, tourniquet use, onset time, white blood cell increase, platelet decrease, creatine kinase (CK) increase, activated partial thromboplastin time shortening, and length of stay between patients with mild snakebites and those with moderate to severe snakebites. Multivariate logistic regression analysis showed that age, tourniquet use, and CK increase were independent risk factors for moderate to severe snakebites. CONCLUSION: The overall severity of snakebites in Chongqing is mild, and the prognosis is good. Age, tourniquet use, and CK increase are independent risk factors for the severity of snakebites. We do not recommend tourniquet use after snakebites in Chongqing.


Subject(s)
Snake Bites , Humans , Retrospective Studies , Snake Bites/therapy , Tourniquets , China/epidemiology , Blood Platelets , Creatine Kinase
20.
Trans R Soc Trop Med Hyg ; 118(4): 287-292, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38073610

ABSTRACT

BACKGROUND: Venomous snakebite is a neglected yet an important public health problem in China, and few studies have focused on them so far. The aim of this study is to investigate clinical characteristics of snakebites patients in a tertiary hospital in Hangzhou, southeast China. METHODS: A total of 416 snakebite cases were included in this retrospective study. The data were collected from the medical records including demographics, clinical manifestations, management and outcomes. RESULTS: Of the 416 patients with venomous snakebites, 248 were male, and the average age was 54.6 years. The majority of cases occurred in rural in May to September. Out of all the venomous bites, Gloydius brevicaudus accounted for the highest percentage (55.3%). Hands were the most vulnerable site to snakebites (47.4%). Patients had clinical manifestations of pain (100%), swelling (100%), wound necrosis (25.7%), hemorrhagic blister (18.3%), and blister (8.7%). Three hundred and ninety-two patients received antivenom administration, and most were treated within six hours after bites. Twenty-six patients received surgical treatments, and 90 patients developed venom-induced consumption coagulopathy. No deaths have occurred in this study. CONCLUSION: Hangzhou is one of the regions with high affecting of snakebites in China. The results of this study will increase the understanding of the clinical characteristics of venomous snakebites in Hangzhou area.


Subject(s)
Crotalinae , Snake Bites , Venomous Snakes , Humans , Male , Middle Aged , Female , Snake Bites/complications , Snake Bites/epidemiology , Snake Bites/therapy , Tertiary Care Centers , Retrospective Studies , Blister/chemically induced , Blister/drug therapy , Incidence , Antivenins/therapeutic use , China/epidemiology
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