Such pathological alterations are due to the direct action of locally acting toxins in the venom (mostly metalloproteinases and phospholipases A 2), together with an indirect effect promoted by local inflammatory events and ischemia secondary to venom-induced vascular damage and increased intracompartmental pressure. assess global snake bite mortality was the survey undertaken by Swaroop and Grabb in 1954, which was based largely on hospital admissions [ 3]. Subsequent work has revealed gross underreporting LX7101 of deaths in this studyfor example, LX7101 in Nigeria [ 5] and Thailand [ 1, 6]. One reason is that records of patients treated by traditional methods are missing from official databased statistics, and deaths reported at the hamlet or district level may not be sent on to ministry headquarters. Accepting these limitations, the fragmentary evidence available suggests that several million bites and envenomings occur worldwide each year, with tens of thousands of deaths [ 2, 3]. Properly designed population surveys are likely to give a far more accurate picture of snake bite incidence, morbidity, and mortality. In Asia, the highest recorded mortality was 162 snake bite deaths per 100,000 people per year, in the Eastern Terai of Nepal [ 7]. In Africa, for instance, the incidence of snake bites in the Benue Valley of northeastern Nigeria was 497 per 100,000 people per year, with a mortality of 12.2% [ LX7101 5]. The reasons for the high levels of snake bite mortality in tropical developing countries include scarcity of antivenoms, poor health services, and difficulties with rapid access to health centres [ 8]. Large numbers of victims survive with permanent physical and psychological sequelae, mostly due to the tissue-damaging effects of snake venoms. Young agricultural workers, especially males, are the most highly affected group, making snake bite envenoming a truly occupational diseasea fact that is frequently overlooked by national authorities. Children are also common victims of snake bites. There is significant seasonal variation in snake bite incidence that is attributable to climate, especially to rain fall and temperature, which determine annual cycles of agricultural activity. Species That Cause High Morbidity and Mortality Most severe cases of snake bite envenoming are inflicted by species of the family Elapidae (cobras, kraits, mambas, Australasian species, and sea snakes) and the family Viperidae (rattlesnakes, lance-headed pit vipers, and true vipers). The species causing the largest numbers of bites and fatalities are sp. (saw-scaled vipers) in northern Africa, and (lance-headed pit vipers) in Central and South America, and sp. (cobras) and sp. (kraits) in Asia [ 6, 9C11] ( Figure 1). Many other species, although not responsible for a large number of cases worldwide, constitute a serious problem in specific regions. Open in a separate window Figure 1 Snakes Causing High Incidence of Envenomings in Africa, Asia, and Latin America(A) (saw-scaled viper, family Viperidae, from Nigeria), (B) (cobra, family Elapidae, from Sri Lanka), and (C) (terciopelo or equis, family Viperidae, from Costa Rica) are IL4R responsible for many snake bite envenomings in sub-Saharan Africa, Asia, and Central America, respectively. Envenomings by and and other Asiatic cobras induce systemic neurotoxic effects and local necrosis. (Image: D. A. Warrell [A and B]; Mahmood Sasa [C]) Clinical Features of Snake Bite Envenoming Envenomings by most viperid snakes inflict prominent local tissue damage, characterised by swelling, blistering, haemorrhage, and necrosis of skeletal muscle ( Figure 2). Bites by some elapids, such as African spitting cobras and some Asian cobras, also induce local necrosis. Such local pathology is mostly due to the action of phospholipases A 2 and zinc-dependent metalloproteinases [ 12, 13]. These local effects develop rapidly after the bite; consequently, a delay in the access to health facilities frequently results in drastic tissue damage and permanent disability. Systemic effects of envenoming are also common and more immediately life-threatening. In elapid snake bites, neurotoxicity is a typical consequence, attributable to effects of pre- and/or postsynaptically acting neurotoxins targeting neuromuscular junctions. These toxins cause progressive descending paralysis, which may become life-threatening when bulbar and respiratory muscles are involved. In envenomings by several elapid snakes and some viperids, such as South American rattlesnakes, there is a generalised rhabdomyolysis induced by phospholipases A 2, which may cause myoglobinaemia, hyperkalaemia,.