Wound Infections from Taiwan Cobra (Naja atra) Bites: Determining Bacteriology, Antibiotic Susceptibility, and the Use of Antibiotics-A Cobra BITE Study.

Wound necrosis and secondary infection are common complications after Naja atra bites. Clinical tools to evaluate the infection risk after Taiwan cobra bites are lacking. In this Cobra BITE study, we investigated the prevalence of wound infection, bacteriology, and corresponding antibiotic usage in patients presenting with Taiwan cobra snakebites. Patients with wound infection lacking tissue necrosis were included in developing Cobra BITE score utilizing univariate and multiple logistic regression, as patients with wound necrosis require antibiotics for infection treatment. 8,295,497 emergency department visits occurred in the span of this study, with 195 of those patients being diagnosed as having cobra bites. Of these patients, 23 had wound necrosis, and 30 had wound infection, resulting in a wound infection rate of 27.2% (53/195). Enterococcus faecalis and Morganella morganii were the main bacteria identified in the culture report regardless of whether patients' wounds had necrosis. As per our Cobra BITE score, the three factors predicting secondary wound infection after cobra bites are hospital admission, a white blood cell count (in 103/µL) × by neu-trophil-lymphocyte ratio value of ≥114.23, and the use of antivenin medication. The area under the receiver operating characteristic curve for the Cobra BITE score system was 0.88; ideal sensitivity and specificity were 0.89 and 0.76. This scoring system enables the assessment of wound infections after N. atra bites, and it could be modified and improved in the future for other Naja spp. bites.

Knowledge of health workers on snakes and snakebite management and treatment seeking behavior of snakebite victims in Bhutan.

BACKGROUND: Published information on snakebite is rare in Bhutan although remarkably higher number of snakebites and associated deaths are reported from other South Asian countries. AIMS AND METHODOLOGY: Structured questionnaire was used to collect knowledge of health workers in snakebite management and health seeking behavior of snakebite victims as observed by health workers. Study was conducted in purposively sampled 10 Dzongkhags (district level administrative units) with higher incidence of snakebites. RESULT: Heath workers scored 27-91% (with an average of 63%, SD = 14) for 52 questions related to snake identification and snakebite management. Among 118 health workers interviewed, 23% had adequate knowledge on snakes and snakebite management while 77% had inadequate knowledge. Among 32 Doctors, 63% of them scored above or equal to 75%. Health workers from Sarpang scored higher (76%, SD = 11) than those from other Dzongkhags. Snakebite victim's visit to local (traditional) healers prior to seeking medical help from hospital was observed by 75 (63%) health workers. Fifty one percent of health workers observed patients treated with local methods such as the use of black stone called Jhhar Mauro (believed to absorb snake venom), application of honey, rubbing of green herbal paste made up of Khenpa Shing (Artemisia myriantha Wallich ex Besser var. paleocephala [Pamp] Ling) and consumption of fluid made up of Neem leaf (Azadirachta indica Juss). Use of tight tourniquet as a first aid to snakebite was observed by 80% of the health workers. CONCLUSION: Health workers lack confidence in snakebite management. Snakebite victims are likely to suffer from harmful local practices and traditional beliefs on local treatment practices. Empowering health workers with adequate knowledge on snakebite management and making locals aware in pre-hospital care of snakebites are needed to improve the pre- and in-hospital management of snakebite in Bhutan.

Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy.

In the field of antivenom research, development, and manufacture, it is often advised to follow the World Health Organization's (WHO) guidelines for the production, control, and regulation of snake antivenom immunoglobulins, which recommend the use of preincubation assays to assess the efficacy of snakebite therapeutics. In these assays, venom and antivenom are mixed and incubated prior to in vivo administration to rodents, which allows for a standardizable comparison of antivenoms with similar characteristics. However, these assays are not necessarily sufficient for therapeutics with significantly different pharmacological properties than antibody-based antivenoms, such as small molecule inhibitors, nanoparticles, and other modalities. To ensure that the in vivo therapeutic utility of completely novel toxin-neutralizing molecules with no history of use in envenoming therapy and variable pharmacokinetics is properly evaluated, such molecules must also be tested in preclinical rescue assays, where rodents are first challenged with appropriate doses of venoms or toxins, followed by the administration of neutralizing modalities after an appropriate time delay to better mimic the real-life scenarios faced by human snakebite victims. Such an approach takes the venom (or toxin) toxicokinetics, the drug pharmacokinetics, and the drug pharmacodynamics into consideration. If new modalities are only assessed in preincubation assays and not subjected to evaluation in rescue assays, the publication of neutralization data may unintentionally misrepresent the actual therapeutic efficacy and suitability of the modality being tested, and thus potentially misguide strategic decision making in the research and development of novel therapies for snakebite envenoming.

Camelid Single-Domain Antibodies (VHHs) against Crotoxin: A Basis for Developing Modular Building Blocks for the Enhancement of Treatment or Diagnosis of Crotalic Envenoming.

Toxic effects triggered by crotalic envenoming are mainly related to crotoxin (CTX), composed of a phospholipase A2 (CB) and a subunit with no toxic activity (CA). Camelids produce immunoglobulins G devoid of light chains, in which the antigen recognition domain is called VHH. Given their unique characteristics, VHHs were selected using Phage Display against CTX from Crotalus durissus terrificus. After three rounds of biopanning, four sequence profiles for CB (KF498602, KF498603, KF498604, and KF498605) and one for CA (KF498606) were revealed. All clones presented the VHH hallmark in FR2 and a long CDR3, with the exception of KF498606. After expressing pET22b-VHHs in E. coli, approximately 2 to 6 mg of protein per liter of culture were obtained. When tested for cross-reactivity, VHHs presented specificity for the Crotalus genus and were capable of recognizing CB through Western blot. KF498602 and KF498604 showed thermostability, and displayed affinity constants for CTX in the micro or nanomolar range. They inhibited in vitro CTX PLA2 activity, and CB cytotoxicity. Furthermore, KF498604 inhibited the CTX-induced myotoxicity in mice by 78.8%. Molecular docking revealed that KF498604 interacts with the CA–CB interface of CTX, seeming to block substrate access. Selected VHHs may be alternatives for the crotalic envenoming treatment.

Medicinal plants used to treat snakebite in Central America: Review and assessment of scientific evidence.

ETHNOPHARMACOLOGICAL RELEVANCE: Every year between 1.2 and 5.5 million people worldwide are victims of snakebites, with about 400,000 left permanently injured. In Central America an estimated 5500 snakebite cases are reported by health centres, but this is likely to be an underestimate due to unreported cases in rural regions. The aim of this study is to review the medicinal plants used traditionally to treat snakebites in seven Central American countries: Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama. MATERIALS AND METHODS: A literature search was performed on published primary data on medicinal plants of Central America and those specifically pertaining to use against snakebites. Plant use reports for traditional snakebite remedies identified in primary sources were extracted and entered in a database, with data analysed in terms of the most frequent numbers of use reports. The scientific evidence that might support the local uses of the most frequently reported species was also examined. RESULTS: A total of 260 independent plant use reports were recorded in the 34 sources included in this review, encompassing 208 species used to treat snakebite in Central America. Only nine species were reported in at least three studies: Cissampelos pareira L., Piper amalago L., Aristolochia trilobata L., Sansevieria hyacinthoides (L.) Druce, Strychnos panamensis Seem., Dorstenia contrajerva L., Scoparia dulcis L., Hamelia patens Jacq., and Simaba cedron Planch. Genera with the highest number of species used to treat snakebite were Piper, Aristolochia, Hamelia, Ipomoea, Passiflora and Peperomia. The extent of the scientific evidence available to understand any pharmacological basis for their use against snakebites varied between different plant species. CONCLUSION: At least 208 plant species are traditionally used to treat snakebite in Central America but there is a lack of clinical research to evaluate their efficacy and safety. Available pharmacological data suggest different plant species may target different symptoms of snakebites, such as pain or anxiety, although more studies are needed to further evaluate the scientific basis for their use.

Challenges in diagnosing and treating snakebites in a rural population of Tamil Nadu, India: The views of clinicians.

Snakebites cause death, disability and economic devastation to their victims, people who live almost exclusively in rural areas. Annually an estimated two million venomous bites cause as many as 100,000 deaths worldwide as well as hundreds of thousands of deformities and amputations. Recent studies suggest that India has the highest incidence of snakebite and associated deaths worldwide. In this study, we interviewed 25 hospital-based clinicians who regularly treat snakebites in Tamil Nadu, India, in order to gauge their opinions and views on the diagnostic tools and treatment methods available at that time, the difficulties encountered in treating snakebites and improvements to snakebite management protocols they deem necessary. Clinicians identified the improvement of community education, training of medical personnel, development of standard treatment protocols and improved medication as priorities for the immediate future.

Effect of distance and delay in access to care on outcome of snakebite in rural north-eastern Nigeria.

INTRODUCTION: Snakebite envenoming is a major cause of morbidity and mortality in rural areas of the tropics. Timely administration of effective antivenom remains the mainstay of management. METHODS: The study was a quantitative descriptive study aimed at exploring the causes and effects of delay, distance and time taken to access care on snakebite outcomes in Nigeria. All prospective snakebite victims reporting to Kaltungo General Hospital were enrolled. Data on demography, date and time bitten, date and time admitted, site of bite, circumstances of snakebite, responsible snake, clinical features, 20-minute whole-blood clotting test, antivenom administered and outcome were recorded. Delay arising from use of traditional first aid (TFA), time elapsed from snakebite to presentation and the shortest distance from bite location to the hospital was calculated or obtained using a global positioning system. RESULTS: The association between delay before hospital presentation and poor outcome was not statistically significant, even though there was a 2% higher likelihood of poor outcome among those with a 1-hour delay compared to those without delay (odds ratio 1.02, 95% confidence interval 1.00-1.03). There was no difference in distance from bite location to hospital between those with a poor outcome (74) compared to those with a good outcome (325). Those with a poor outcome had more severe envenomation requiring more antivenoms and longer hospital stays. Given poor access to antivenom therapy at distant locations ≥100 km, victims were more likely to use TFA such as black 'snake' stone, with consequent prolonged delays. Antivenoms should be more readily available at distant places. CONCLUSIONS: Community education on avoiding potentially harmful TFA and prompt access to care is recommended. There is a need to provide snakebite care to multiple peripheral, relatively more rural inaccessible areas.

Pediatric envenomations: don't get bitten by an unclear plan of care.

Children are frequently victims of terrestrial animal and insect bites and stings. While the majority of these bites or stings are nondangerous, pediatric patients occasionally encounter a venomous animal. In such cases, children may present to the emergency department for evaluation and management. This review presents the basic epidemiology of bites and stings of spiders, bees and wasps, fire ants, scorpions, and snakes, but it primarily focuses on the underlying pathophysiology and clinical presentation of the envenomated patient. While the pathophysiology and much of the presentation and treatment are the same for both children and adults, there are occasionally subtle differences, which will be highlighted. The management and disposition of pediatric patients for each type of bite or sting will also be discussed.

Overlooked issues of snakebite management: time for strategic approach.

Snakebite is a medical emergency in many parts of the world, particularly in the temperate regions. According to 2007 World Health Organization (WHO) report, there are about 5 million snakebite incidences resulting in 2.5 million envenoming, and 125,000 deaths occur annually. Most affected are the healthy individuals like children and farming populations with resource poor settings and away from health care centers in low-income countries of Africa, Asia and Latin America. In view of this, the WHO has declared snakebite as an ignored health crisis and a tropical disease. Although the death rate has reduced markedly due to anti-venom regiment, several limitations of it offer scope for better understanding of various ignored issues. Currently, snakebite therapeutics facing plethora of scientific, technological and public health challenges, including secondary/long term complications that have not been given importance so far. Because of dearth of knowledge, venom researchers and medical practitioners from affected countries worldwide should join together to accomplish this scenario. In view of this, the present review provides a broader perspective on the possible production and application of highly effective therapeutic master anti-venom, designing master diagnostic kit and also to deal with the inefficacy of anti-venom therapy against local manifestations and secondary complications of snakebite. The review demands thorough understanding of venom pharmacology, inculcating new strategies to handle and to enhance the efficacy of snakebite management and urge the governing systems of affected countries to take steps to curtail accidental debilitation and death rate of healthy individuals due to snakebite.

[Three case-reports of viperin envenoming in Morocco]. / A propos de trois observations d'envenimations vipérines graves au Maroc.

Snake bites are responsible for a high mortality rate in Africa. Problems for the early care of the victims are many. We published three observations of Moroccan typical viperin severe envenomings (rapidly extensive edema, necrosis, haemorrhagic shock) are presented. The overall mortality of those bites is 4%. In the Maghreb, viperin syndromes are the result of the lebetin viper (Vipera lebetina), the horned viper or sand viper (Cerastes cerastes), sometimes Bitis or Echis sp. Immunotherapy remains effective against haemorrhage, even when administered late, in severe disease (bleeding). Death remains inevitable if antivenin is not being administered or if it is at the stage of multiorgan failure. Heparin is contra-indicated in the acute context, but at distance from the bite, the persistence of inflammatory syndrome can cause phlebitis or pulmonary embolism. Fresh frozen plasma and corticosteroids are ineffective and unnecessary. Signs of gravity are rapidly extensive swelling and systemic manifestations, particularly bleeding. The severity of poisoning is related to the difficulties of access to health centers, the use of traditional medicine for more than half of the victims, the lack of training of caregivers, finally and most importantly, the lack of antivenomous serum,that is not within reach of prescribing at the appropriate places and times. Despite its cost and allergic risk (become rare with the current serums), immunotherapy which is the only weapon effective against the venom, should be part of emergency essential drugs.

Envenomations.

Numerous types of envenomations may be encountered by health care workers depending on where in North America they work. Clinicians should be familiar with the animals in their region that may lead to envenomation.A rational approach with use of poison center or medical toxicology consultation services ensures that cases are managed appropriately.

Acidentes por animais peçonhentos / Envenomation caused by poisonous animals

Säo descritos alguns aspectos da fisiopatologia e os dados fundamentais sobre a clínica e terapêutica dos acidentes provocados por animais peçonhentos mais frequentes na regiäo Sudeste do Brasil. Säo abordados os acidentes por serpentes peçonhentas do gênero Bothrops, Crotalus e Micrurus e os aracnídeos, escorpiöes do gênero Tityus e aranhas dos gêneros Loxosceles e Phoneutria. Quando indicada, a soroterapia antiveneno (SAV) deve ser aplicada intravenosamente, gota a gota, sem diluiçäo, precedida por antihistamínicos (anti-H1 e anti-H2) e corticóides, visando a proteçäo contra possíveis reaçöes de hipersensibilidade e sem que sejam realizados testes cutâneos previamente