Clinical aspects of snakebite envenoming and its treatment in low-resource settings.

There is increasing recognition of the public health importance of snakebite envenoming. Worldwide annual incidence is likely to be 5 million bites, with mortality exceeding 150 000 deaths, and the resulting physical and psychological morbidity leads to substantial social and economic repercussions. Prevention through community education by trained health workers is the most effective and economically viable strategy for reducing risk of bites and envenoming. Clinical challenges to effective treatment are most substantial in rural areas of low-resource settings, where snakebites are most common. Classic skills of history taking, physical examination, and use of affordable point-of-care tests should be followed by monitoring of evolving local and systemic envenoming. Despite the profusion of new ideas for interventions, hyperimmune equine or ovine plasma-derived antivenoms remain the only specific treatment for snakebite envenoming. The enormous interspecies and intraspecies complexity and diversity of snake venoms, revealed by modern venomics, demands a radical redesign of many current antivenoms.

Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors.

αδ-Bungarotoxins, a novel group of long-chain α-neurotoxins, manifest different affinity to two agonist/competitive antagonist binding sites of muscle-type nicotinic acetylcholine receptors (nAChRs), being more active at the interface of α-δ subunits. Three isoforms (αδ-BgTx-1-3) were identified in Malayan Krait (Bungarus candidus) from Thailand by genomic DNA analysis; two of them (αδ-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to α-bungarotoxin (α-BgTx), a classical blocker of muscle-type and neuronal α7, α8, and α9α10 nAChRs. The toxicity of αδ-BgTx-1 (LD50 = 0.17-0.28 µg/g mouse, i.p. injection) is essentially as high as that of α-BgTx. In the chick biventer cervicis nerve-muscle preparation, αδ-BgTx-1 completely abolished acetylcholine response, but in contrast with the block by α-BgTx, acetylcholine response was fully reversible by washing. αδ-BgTxs, similar to α-BgTx, bind with high affinity to α7 and muscle-type nAChRs. However, the major difference of αδ-BgTxs from α-BgTx and other naturally occurring α-neurotoxins is that αδ-BgTxs discriminate the two binding sites in the Torpedo californica and mouse muscle nAChRs showing up to two orders of magnitude higher affinity for the α-δ site as compared with α-ε or α-γ binding site interfaces. Molecular modeling and analysis of the literature provided possible explanations for these differences in binding mode; one of the probable reasons being the lower content of positively charged residues in αδ-BgTxs. Thus, αδ-BgTxs are new tools for studies on nAChRs.

Vulnerability to snakebite envenoming: a global mapping of hotspots.

BACKGROUND: Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed. METHODS: We assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but <5 species occurrence records), and group C (EOR map and ≥5 species occurrence records). For group C species, we did a multivariate environmental similarity analysis using the 2008 WHO EOR maps and newly available evidence. Using these data and the EOR maps, we produced contemporary range maps for medically important venomous snake species at a 5 × 5 km resolution. We subsequently triangulated these data with three health system metrics (antivenom availability, accessibility to urban centres, and the Healthcare Access and Quality [HAQ] Index) to identify the populations most vulnerable to snakebite morbidity and mortality. FINDINGS: We provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within the lowest decile are at risk of exposure to any snake for which no effective therapy exists compared with 519·46 million individuals (27·79%) within the highest HAQ Index decile, showing a disproportionate coverage in reported antivenom availability. Antivenoms were available for 119 (43%) of 278 snake species evaluated by WHO, while globally 750·19 million (10·95%) of those living within snake ranges live more than 1 h from population centres. In total, we identify about 92·66 million people living within these vulnerable geographies, including many sub-Saharan countries, Indonesia, and other parts of southeast Asia. INTERPRETATION: Identifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease. FUNDING: Bill & Melinda Gates Foundation.

Louse-borne relapsing fever (Borrelia recurrentis infection).

Louse-borne relapsing fever (LBRF) is an epidemic disease with a fascinating history from Hippocrates' times, through the 6th century 'Yellow Plague', to epidemics in Ireland, Scotland and England in the 19th century and two large Afro-Middle Eastern pandemics in the 20th century. An endemic focus persists in Ethiopia and adjacent territories in the Horn of Africa. Since 2015, awareness of LBRF in Europe, as a re-emerging disease, has been increased dramatically by the discovery of this infection in dozens of refugees arriving from Africa.The causative spirochaete, Borrelia recurrentis, has a genome so similar to B. duttonii and B. crocidurae (causes of East and West African tick-borne relapsing fever), that they are now regarded as merely ecotypes of a single genomospecies. Transmission is confined to the human body louse Pediculus humanus corporis, and, perhaps, the head louse P. humanus capitis, although the latter has not been proved. Infection is by inoculation of louse coelomic fluid or faeces by scratching. Nosocomial infections are possible from contamination by infected blood. Between blood meals, body lice live in clothing until the host's body temperature rises or falls, when they seek a new abode.The most distinctive feature of LBRF, the relapse phenomenon, is attributable to antigenic variation of borrelial outer-membrane lipoprotein. High fever, rigors, headache, pain and prostration start abruptly, 2-18 days after infection. Petechial rash, epistaxis, jaundice, hepatosplenomegaly and liver dysfunction are common. Severe features include hyperpyrexia, shock, myocarditis causing acute pulmonary oedema, acute respiratory distress syndrome, cerebral or gastrointestinal bleeding, ruptured spleen, hepatic failure, Jarisch-Herxheimer reactions (J-HR) and opportunistic typhoid or other complicating bacterial infections. Pregnant women are at high risk of aborting and perinatal mortality is high.Rapid diagnosis is by microscopy of blood films, but polymerase chain reaction is used increasingly for species diagnosis. Severe falciparum malaria and leptospirosis are urgent differential diagnoses in residents and travellers from appropriate geographical regions.High untreated case-fatality, exceeding 40% in some historic epidemics, can be reduced to less than 5% by antibiotic treatment, but elimination of spirochaetaemia is often accompanied by a severe J-HR.Epidemics are controlled by sterilising clothing to eliminate lice, using pediculicides and by improving personal hygiene.

A multicomponent strategy to improve the availability of antivenom for treating snakebite envenoming.

Snakebite envenoming is a common but neglected public health problem, particularly in impoverished rural regions of sub-Saharan Africa, Asia and Latin America. The only validated treatment for this condition is passive immunotherapy with safe and effective animal-derived antivenoms. However, there is a long-lasting crisis in the availability of these life-saving medications, particularly in sub-Saharan Africa and parts of Asia. We herein advocate a multicomponent strategy to substantially improve the availability of safe and effective antivenoms at the global level. This strategy is based on: (i) preparing validated collections of representative venom pools from the most medically dangerous snakes in high-risk regions of the world; (ii) strengthening the capacity of national antivenom manufacturing and quality control laboratories and their regulatory authorities and establishing new facilities in developing countries through technology transfer, as an integral part of efforts to develop their biological products industry; (iii) getting established laboratories to generate antivenoms for various regions of the world; and (iv) getting governments and relevant organizations to give snakebite envenoming due recognition within national and international public health policy frameworks. These ways of making antivenom available should be complemented by actions to improve health information systems, the accessibility of antivenoms, the training of medical and nursing staff, and community-based education. Such a multicomponent strategy involving stakeholders on many levels could help consolidate sustainable improvements in antivenom availability worldwide.

L'envenimation par morsure de serpent est un problème de santé publique fréquent, mais négligé, en particulier dans les régions rurales pauvres de l'Afrique subsaharienne, de l'Asie et de l'Amérique latine. Le seul traitement validé pour soigner cet état est l'immunothérapie passive avec des sérums antivenimeux d'origine animale sûrs et efficaces. Cependant, une crise durable limite actuellement la disponibilité de ces médicaments vitaux, surtout en Afrique subsaharienne et dans certaines parties de l'Asie. Nous préconisons ici une stratégie à composants multiples pour améliorer considérablement la disponibilité des sérums antivenimeux sûrs et efficaces à l'échelle mondiale. Cette stratégie repose sur: (i) la préparation de collections validées de groupes représentatifs de venins prélevés sur les serpents les plus dangereux sur le plan médical dans les régions à haut risque du monde; (ii) le renforcement de la capacité de production nationale des sérums antivenimeux, des laboratoires de contrôle qualité et de leurs organismes de réglementation, et la création de nouvelles installations dans les pays en développement par transfert de technologies, en tant que partie intégrante de la stratégie de développement de leur industrie de produits biologiques; (iii) la production par les laboratoires déjà établis de sérums antivenimeux pour les différentes régions du monde; et (iv) la reconnaissance officielle par les gouvernements et les organisations compétentes de l'envenimation par morsure de serpent dans le cadre des politiques de santé publique nationales et internationales. Ces façons de rendre disponibles les sérums antivenimeux devraient être complétées par des actions visant à améliorer les systèmes d'informations sanitaires, l'accessibilité des sérums antivenimeux, la formation du personnel médical et infirmier et les programmes communautaires d'éducation. Une telle stratégie à composants multiples impliquant des acteurs à différents niveaux pourrait contribuer à consolider les améliorations durables en matière de disponibilité des sérums antivenimeux dans le monde entier.

El envenenamiento por mordedura de serpiente es un problema de salud pública común pero desatendido, especialmente en las regiones rurales más pobres de África subsahariana, Asia y América Latina. El único tratamiento reconocido contra estas mordeduras es la inmunoterapia pasiva con sueros antiofídicos de origen animal seguros y eficaces. Sin embargo, la disponibilidad de estos medicamentos esenciales para salvar vidas lleva mucho tiempo en crisis, en particular en África subsahariana y en algunas zonas de Asia. En el presente documento, abogamos por una estrategia multicomponente para mejorar de forma sustancial la disponibilidad de sueros antiofídicos seguros y eficaces en todo el mundo. La estrategia se basa en: (i) preparar colecciones reconocidas de sueros antiofídicos representativos de las serpientes más peligrosas en zonas de alto riesgo del mundo; (ii) reforzar la capacidad nacional de producción de sueros antiofídicos y la calidad de los laboratorios de control y sus autoridades normativas, así como crear instalaciones nuevas en los países en desarrollo por medio de la transferencia de tecnología como parte integral de los esfuerzos por desarrollar su industria de productos biológicos; (iii) conseguir que los laboratorios consolidados fabriquen sueros antiofídicos para varias regiones del mundo; y (iv) conseguir que los gobiernos y las organizaciones pertinentes otorguen al envenenamiento por mordedura de serpiente el reconocimiento debido dentro del marco de las políticas nacionales e internacionales de salud pública. Estas tareas dirigidas a facilitar el suero antiofídico deben complementarse con acciones para mejorar los sistemas de información sobre la salud, la accesibilidad de los antiofídicos, la formación del personal médico y de enfermería, y la educación comunitaria. Una estrategia multicomponente de ese tipo, que incluye a los interesados a varios niveles, podría ayudar a consolidar mejoras sostenibles en la disponibilidad de antiofídicos en todo el mundo.

New approaches & technologies of venomics to meet the challenge of human envenoming by snakebites in India.

The direct estimate of 46,000 snakebite deaths in India in 2005 (1 for every 2 HIV/AIDS deaths), based on verbal autopsies, renders unrealistic the total of only 47,000 snakebite deaths in the whole world in 2010, obtained indirectly as part of the "Global Burden of Disease 2010" study. Persistent underestimation of its true morbidity and mortality has made snakebite the most neglected of all the WHO's "neglected tropical diseases", downgrading its public health importance. Strategies to address this neglect should include the improvement of antivenom, the only specific antidote to envenoming. To accommodate increased understanding of geographical intraspecific variation in venom composition and the range of snake species that are medically important in India, the design of antivenoms (choice of venom sources and species coverage) should be reconsidered. Methods of preclinical and clinical testing should be improved. The relatively new science of venomics involves techniques and strategies for assessing the toxin composition of snake venoms directly through proteomics-centred approaches or indirectly via high-throughput venom gland transcriptomics and bioinformatic analysis. Antivenomics is translational venomics: a proteomics-based protocol to quantify the extent of cross-reactivity of antivenoms against homologous and heterologous venoms. These approaches could revolutionize the preclinical assessment of antivenom efficacy, leading to a new generation of antivenoms that are clinically more effective.

A case of envenoming by a Persian false-horned viper Pseudocerastes persicus (Duméril, Bibron & Duméril, 1854) (Serpentes: Viperidae) in Southeastern Iran.

Despite the wide distribution of the Persian false-horned viper (Pseudocerastes persicus) in the Middle East, few identified bites have been reported. A 33-year-old herpetologist bitten on the hand by Pseudocerastes persicus in Kerman Province, Southeastern Iran, developed local pain and extensive swelling with mild non-specific systemic symptoms and minimal laboratory evidence of systemic envenoming.

Sudden death after a bite by a lowland swamp viper (Proatheris superciliaris) in Malawi: Dying of fright?

Proatheris superciliaris, the lowland swamp viper, has a limited distribution along lakeshores and rivers in Malawi, Southern Tanzania, and central Mozambique. Its venom is known to be procoagulant. Only five P. superciliaris bites have been reported, all inflicted by captive snakes, and none was fatal. Here we present a case of sudden death following a bite by Proatheris superciliaris in rural Malawi that cannot be attributed to envenoming. A healthy 32-year-old woman was planting rice in a flooded rice paddy field when she suddenly told her sister in a quiet voice that she had been bitten by a snake. She then collapsed face-upwards into the ankle-deep water. She remained motionless while her sister and uncle carried her out of the rice paddy onto dry land a few meters away. The victim did not regain consciousness. Her uncle heard one exhalation but no further breathing. The snake responsible was killed by a friend. Although the venom of this species can cause life-threatening coagulopathy, this woman's death occurred too rapidly to be attributable to envenoming. Only two explanations seem plausible: anaphylaxis, or vasovagal shock triggered by fear. In the present case, the victim died within minutes of the bite, closely observed by her anxious relatives, but showed no features of anaphylaxis. In Malawi, as in much of sub-Saharan Africa, many people are reportedly terrified of snakes, believing that bites by almost any species can cause rapid death. In this case, death occurred less than 2 min after a bite from Proatheris superciliaris. We believe that the cause of death was most likely a severe vasovagal attack, in response to the fear and pain of the snakebite that triggered vasodilatation, bradycardia, and hypotension leading to cardiac arrest.

Medically important snakes and snakebite envenoming in Iran.

Snakebite is a relatively common health condition in Iran with a diverse snake fauna, especially in tropical southern and mountainous western areas of the country with a plethora of snake species. The list of medically important snakes, circumstances and effects of their bite, and necessary medical care require critical appraisal and should be updated regularly. This study aims to review and map the distributions of medically important snake species of Iran, re-evaluate their taxonomy, review their venomics, describe the clinical effects of envenoming, and discuss medical management and treatment, including the use of antivenom. Nearly 350 published articles and 26 textbooks with information on venomous and mildly venomous snake species and snakebites of Iran, were reviewed, many in Persian (Farsi) language, making them relatively inaccessible to an international readership. This has resulted in a revised updated list of Iran's medically important snake species, with taxonomic revisions of some, compilation of their morphological features, remapping of their geographical distributions, and description of species-specific clinical effects of envenoming. Moreover, the antivenom manufactured in Iran is discussed, together with treatment protocols that have been developed for the hospital management of envenomed patients.

Epidemiology of scorpion stings in the West Bank, occupied Palestinian territory.

Background: Scorpionism (scorpion sting envenoming) is an endemic public health concern in many Arab Middle Eastern countries. However, our knowledge of the epidemiology of scorpion stings in the West Bank is limited. Aim: To investigate the epidemiology of scorpion stings in 4 districts of the West Bank over a specified period. Methods: We obtained scorpion sting records from the main hospitals in 4 districts of the West Bank for 2012 and 2014-2020. A total of 2175 cases were analyzed retrospectively using SPSS version 17. Results: The average age and standard deviation (±SD) for both sexes was 24.7±17.5 years (22.7±16.5 and 27.1±18.4 years for males and females, respectively). The median age was 20 years and 47.2% were children under 18 years. Most cases were reported during the summer months, between June and October, with a peak in July-August. By anatomic site, the right hand was the most commonly stung in both sexes, followed by the right foot. The chest, buttocks and scrotum were the least affected body parts. Clinical data were available for 405 cases, in which pain, vomiting and sweating were the most common symptoms. The overall incidence of stings was 26.32 per 100 000 inhabitants per year over the study period of 8 years (59.21-171.67, 95% CI). Conclusion: Scorpion stings are commonly encountered by adults and children in the West Bank. There is a need for awareness among the West Bank populations on how to avoid being stung, to train medical staff to better manage sting cases, and to evaluate the antivenom currently being used by physicians for scorpion stings.

Exotic (non-native) snakebite envenomation in Japan: A review of the literature between 2000 and 2022.

A limited number of studies have investigated the clinical characteristics of snakebite envenomation by exotic (non-native) snakes in Japan. This study reviewed the literature to determine the status and risk of bites by exotic pet snakes in Japan. We reviewed reports of snakebite due to exotic snakes in Japan published between 2000 and 2022, excluding reports of bites by snakes native to Japan, such as Gloydius blomhoffii, Rhabdophis tigrinus, and Protobothrops flavoviridis. During the study period, 11 exotic snakebites were recorded, involving 11 species. The majority of those bitten (10/11 cases) were male, all cases were hand injuries, and there were no fatalities. The snakes responsible belonged to the Colubridae (4/11 cases), Viperidae (4/11 cases), and Elapidae (3/11 cases) families. Cases of envenomation by G. brevicaudus, Bungarus candidus, and Dendroaspis angusticeps were of particular interest. Ten of the eleven patients developed local cytotoxic signs, and three developed "compartment syndrome," in which the surgeons performed decompressive incisions. Two bites from elapid snakes and one from a viperid snake resulted in respiratory failure. Antivenom was given in two cases. Complications were observed, such as acute kidney injury, rhabdomyolysis, coagulopathy, and residual dysfunction of the affected finger. Emergency rooms should be prepared to manage patients who have been bitten by exotic snakes, even though the number of reported cases is not high in Japan. Initial stabilization of patients is crucial, before a definitive diagnosis is made, as with native snakebite envenomation. Finger bites are reported in most cases, which may result in functional impairment of the fingers. In order to collect more comprehensive patient data in Japan, a reporting system for all snakebite envenomations should be considered.

A case series of samar cobra, Naja samarensis Peters, 1861 (Elapidae) envenomation.

The Samar cobra, Naja samarensis Peters, 1861 is one of the World Health Organization's category I venomous snakes in the Philippines. Although N. samarensis is known to inhabit Eastern Visayas, unlike N. philippinensis in Luzon, no clinical case reports have yet been published in the international literature. No immuno-diagnostic assays have been developed for venomous snakes in the Philippines, even for research purposes. Therefore, identification of the causative snake in hospitals is challenging. In vivo pre-clinical tests using mice showed that locally-produced antivenom raised against N. philippinensis venom ["Purified Cobra Antivenom (PCAV)"] cross-neutralised N. samarensis venom. Here, we present five snakebite envenomation cases where causative snakes were confirmed in photos as N. samarensis by an expert local herpetologist. Patients' symptoms and signs varied, from mild to extensive local cytotoxic to systemic neurotoxic envenomation. In one case, venom had been spat into the eye. Out of five patients, two underwent surgical debridement of necrotic tissue at the bite site. One paediatric patient was intubated because of cardiopulmonary arrest. Except for the spitting cobra case, four cases were successfully treated with PCAV and supportive management. These are the first clinical case reports of confirmed N. samarensis envenomation.

Snakebites in Jordan: A clinical and epidemiological study.

The epidemiology features and clinical symptoms associated with 121 cases of snakebite requiring admission to 24 hospitals in Jordan, during 2018-2020, are discussed. Ninety-six of them (79%) brought with them to the hospital the snake that bit them or a photograph of it. Echis coloratus was responsible for 68 of the bites and 6 fatalities. Sex ratio was 3.2 males: 1 female, with an overall average age of 27 ± 14.36 years. The highest incidence of bites was reported in September. Bites were most common on hands and legs. The period of hospitalization ranged from 1 to 36 days. Irbid and Karak governorates had the highest number of snakebites, most cases being reported from agricultural areas and among farmers. Clinical symptoms associated with five species of venomous snakes are described along with illustrative case histories. Symptoms associated with Echis coloratus bites included local swelling and necrosis, coagulopathy and bleeding, microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and chronic renal failure. Daboia palaestinae victims exhibited ecchymoses, local swelling and necrosis, with one case of angioedema. Other symptoms included thrombocytopenia, coagulopathy, microangiopathic hemolysis and local and systemic bleeding, as well as AKI. A single case of envenoming by Macrovipera lebetinus developed the following symptoms; swelling, severe pain, extensive ecchymoses, neutrophil leukocytosis, normochromic normocytic anemia and aggregated platelets with thrombocytopenia. Symptoms associated with two cases of Pseudocerastes fieldi included swelling that spread from bitten hands, and mild abnormalities of platelet count and bleeding time. Four cases of envenoming by Atractaspis engaddensis exhibited severe pain, local swelling, erythema, numbness and tissue necrosis. One of them developed acute systemic symptoms. The only antivenom currently available in Jordan, is VINS "Snake venom antitoxin (Biosnake)", manufactured in India using venoms of three African snakes that do not occur in Jordan. It proved clinically ineffective against envenoming by Jordanian Viperidae, failing to correct coagulopathy and life-threatening hemorrhage, and to prevent AKI.

First report of a confirmed case of Montivipera latifii (Latifi's viper) envenoming and a literature review of envenoming by Montivipera species.

Latifi's viper (Montivipera latifii), also known as Lar Valley or Damavandi viper, is endemic to Iran. It has rarely been recorded, as it occurs in a highly-protected national park. In this first clinical report of a confirmed bite by this species, a teenage girl was bitten on the chin, causing rapidly-progressive swelling of the face and oropharyngeal mucosa. At a local hospital, a misleading history given by the patient's relatives of a wasp sting and inadequate inspection of the bite wound misled the physicians from making the correct diagnosis, resulting in a considerable delay in the administration of antivenom. This allowed the development of partial obstruction of the upper airway causing respiratory distress. After transfer to a tertiary hospital, attempts at endotracheal intubation failed, necessitating tracheostomy, but this was not implemented early enough to prevent her developing respiratory failure and losing consciousness. After she was stabilized, snakebite envenoming was diagnosed by a clinical toxicologist who observed two fang puncture marks on her chin. This was later confirmed when a snake, identified as M. latifii, was discovered at the room where the bite had occurred. Her facial swelling and ecchymosis, attributable to envenoming, were effectively controlled by high-dose antivenom therapy. However, she did not recover consciousness, remaining in a vegetative state. About three weeks after the bite, she died as an indirect result of hypoxic brain damage complicated by septicemia. Prompt diagnosis, relief of upper airway obstruction and timely antivenom therapy might have prevented this tragic fatal outcome.

Snake venomics of African spitting cobras: toxin composition and assessment of congeneric cross-reactivity of the pan-African EchiTAb-Plus-ICP antivenom by antivenomics and neutralization approaches.

Venomic analysis of the venoms of Naja nigricollis, N. katiensis, N. nubiae, N. mossambica, and N. pallida revealed similar compositional trends. The high content of cytotoxins and PLA(2)s may account for the extensive tissue necrosis characteristic of the envenomings by these species. The high abundance of a type I α-neurotoxin in N. nubiae may be responsible for the high lethal toxicity of this venom (in rodents). The ability of EchiTAb-Plus-ICP antivenom to immunodeplete and neutralize the venoms of African spitting cobras was assessed by antivenomics and neutralization tests. It partially immunodepleted 3FTx and PLA(2)s and completely immunodepleted SVMPs and CRISPs in all venoms. The antivenom neutralized the dermonecrotic and PLA(2) activities of all African Naja venoms, whereas lethality was eliminated in the venoms of N. nigricollis, N. mossambica, and N. pallida but not in those of N. nubiae and N. katiensis. The lack of neutralization of lethality of N. nubiae venom may be of medical relevance only in relatively populous areas of the Saharan region. The impaired activity of EchiTAb-Plus-ICP against N. katiensis may not represent a major concern. This species is sympatric with N. nigricollis in many regions of Africa, although very few bites have been attributed to it.

Snake bite.

Snake bite is a common and frequently devastating environmental and occupational disease, especially in rural areas of tropical developing countries. Its public health importance has been largely ignored by medical science. Snake venoms are rich in protein and peptide toxins that have specificity for a wide range of tissue receptors, making them clinically challenging and scientifically fascinating, especially for drug design. Although the full burden of human suffering attributable to snake bite remains obscure, hundreds of thousands of people are known to be envenomed and tens of thousands are killed or maimed by snakes every year. Preventive efforts should be aimed towards education of affected communities to use proper footwear and to reduce the risk of contact with snakes to a minimum through understanding of snakes' behaviour. To treat envenoming, the production and clinical use of antivenom must be improved. Increased collaboration between clinicians, epidemiologists, and laboratory toxinologists should enhance the understanding and treatment of envenoming.

The greater black krait (Bungarus niger), a newly recognized cause of neuro-myotoxic snake bite envenoming in Bangladesh.

Prospective studies of snake bite patients in Chittagong, Bangladesh, included five cases of bites by greater black kraits (Bungarus niger), proven by examination of the snakes that had been responsible. This species was previously known only from India, Nepal, Bhutan and Burma. The index case presented with descending flaccid paralysis typical of neurotoxic envenoming by all Bungarus species, but later developed generalized rhabdomyolysis (peak serum creatine kinase concentration 29,960 units/l) with myoglobinuria and acute renal failure from which he succumbed. Among the other four patients, one died of respiratory paralysis in a peripheral hospital and three recovered after developing paralysis, requiring mechanical ventilation in one patient. One patient suffered severe generalized myalgia and odynophagia associated with a modest increase in serum creatine kinase concentration. These are the first cases of Bungarus niger envenoming to be reported from any country. Generalized rhabdomyolysis has not been previously recognized as a feature of envenoming by any terrestrial Asian elapid snake, but a review of the literature suggests that venoms of some populations of Bungarus candidus and Bungarus multicinctus in Thailand and Vietnam may also have this effect in human victims. To investigate this unexpected property of Bungarus niger venom, venom from the snake responsible for one of the human cases of neuro-myotoxic envenoming was injected into one hind limb of rats and saline into the other under buprenorphine analgesia. All animals developed paralysis of the venom-injected limb within two hours. Twenty-four hours later, the soleus muscles were compared histopathologically and cytochemically. Results indicated a predominantly pre-synaptic action (ß-bungarotoxins) of Bungarus niger venom at neuromuscular junctions, causing loss of synaptophysin and the degeneration of the terminal components of the motor innervation of rat skeletal muscle. There was oedema and necrosis of extrafusal muscle fibres in envenomed rat soleus muscles confirming the myotoxic effect of Bungarus niger venom, attributable to phospholipases A2. This study has demonstrated that Bungarus niger is widely distributed in Bangladesh and confirms the risk of fatal neuro-myotoxic envenoming, especially as no specific antivenom is currently manufactured. The unexpected finding of rhabdomyolysis should prompt further investigation of the venom components responsible. The practical implications of having to treat patients with rhabdomyolysis and consequent acute renal failure, in addition to the more familiar respiratory failure associated with krait bite envenoming, should not be underestimated in a country that is poorly equipped to deal with such emergencies.

The first reported snakebite by an African snake-eater, Polemon spp. (Atractaspididae, Aparallactinae); Local envenoming by Reinhardt's snake-eater, Polemon acanthias (Reinhardt, 1860).

The first reported snakebite by an African snake-eater, Polemon spp. (Atractaspididae, Aparallactinae); Local envenoming by Reinhardt's snake-eater, Polemon acanthias (Reinhardt, 1860). Toxicon XX, xxx. A 51-yr-old male herpetologist was bitten on the left index finger by a captive male Polemon acanthias while manually removing fragments of incompletely shed skin from the specimen. The snake sustained its bite for approximately 2 mins, advancing its jaws several times. The victim rapidly developed moderate pain, erythema, progressive edema that ultimately extended to the left wrist; a blister later developed in the wound site, as well as joint stiffness in the bitten and adjacent two fingers that limited flexion and extension. These effects regressed during the week following the bite, but recurred thereafter and were similar to the effects that developed immediately post-envenoming. There were no systemic signs or symptoms. The victim sought medical advice and was treated with broad-spectrum antibiotics, antihistamines and wound care; no laboratory investigations were conducted. He improved during the subsequent month with complete resolution in 5 and one-half weeks. This is the first documented bite by a Polemon spp. and the victim's clinical course suggests the development of local effects from venom components. The phylogenetic relationship of Polemon spp. with the burrowing asps (Atractaspis spp.) and the similarity of some of the features of this local envenoming by P. acanthias with mild/moderate envenoming by some Atractaspis spp., suggests that none of these snakes should be handled; they should be considered capable of inflicting potentially serious envenoming.

Scorpions and scorpion sting envenoming (scorpionism) in the Arab Countries of the Middle East.

The twelve Arab countries of the Middle East are inhabited by 117 species of scorpions of varying medical importance within six families. Scorpion stings are a very common occurrence throughout the region. Twenty-two scorpion species are considered to be dangerously venomous, causing potentially life threatening stings. Accessible literature in English and Arabic on scorpions, scorpion stings and available antivenoms was reviewed to document the scorpion fauna and scorpion stings in each country. Saudi Arabia, Iraq and Jordan report the highest numbers of stings and envenomings. Clinically, the most important toxins in Old World scorpion venoms are α-toxins that target voltage-gated sodium (Nav) channels at neurotoxin binding site 3, causing sympathetic excitation and the endogenous release of catecholamines that is responsible for transient, but life-threatening myocardial damage. Most victims of scorpion stings suffer severe local pain, but a few, especially children, develop systemic envenoming which, in the case of most Middle Eastern buthid species, such as Androctonus and Leiurus species, is dominated by the cardiovascular and respiratory consequences of hypercatecholinaemic myocarditis. Other syndromes include paralysis (Parabuthus leiosoma), coagulopathy (Nebo hierichonticus and Hemiscorpius species), and local tissue damage, haemolysis and acute kidney injury (H. lepturus). Early antivenom treatment is recommended but its value remains controversial. However, intensive care, with the ancillary use of vasoactive drugs such as prazosin and dobutamine, has proved effective.