Emilie Alirol; Sanjib Kumar Sharma; Himmatrao Saluba Bawaskar; Ulrich Kuch; François Chappuis

“ When envenoming does occur, it can be rapidly life-threatening. Snake venom is a complex mixture of toxins and enzymes, each of which may be responsible for one or more distinct toxic actions. In bites by South Asian viperid snakes, envenoming results in local pain and tissue damage, characterised by swelling, blistering, bleeding, and necrosis at the bite site, sometimes extending to the whole limb [40] . Viperid venoms can also induce coagulopathy and platelet dysfunction, leading to spontaneous systemic haemorrhages and persistent bleeding from fang marks, wounds, or gums (Figure 1) . ”

“ Bites are more frequent in young men, and generally occur on lower limbs. The incidence of snake bites is higher during the rainy season and during periods of intense agricultural activity [12] , [13] . Snake bite incidence and mortality also increase sharply during extreme weather events such as floods. During the 2007 monsoon flood disaster in Bangladesh, snake bite was the second most common cause of death, after drowning, eclipsing mortality from diarrheal and respiratory diseases and illustrating how important snake bite can be in this region compared to other health problems [14] . ”

“ Clinical Features of Snake Bite Envenoming
A widespread belief is that snake bites inevitably result in envenoming. However, bites by nonvenomous snakes are common and bites by venomous species are not always accompanied by the injection of venom (dry bites) . A large survey conducted in ten hospitals of southern Nepal revealed that envenoming occurred in only 10% of the victims [10] . In Kerala, India, only 219 out of 635 patients (34%) with proven snake bite developed signs of systemic envenoming [18] . ”

“ While sub-Saharan Africa faces a dramatic crisis in antivenom production and supply [110] , [111] , shortage of antivenom is not the most pressing issue in South Asia. Indeed, it is estimated that India produces around one million vials of antivenom each year [112] . Despite these large volumes of production, several challenges persist that prevent appropriate management of snake bite victims in South Asia. Poor access to often inadequately equipped and staffed medical centres in rural areas, high cost of treatment, and inadequate use of antivenoms are major concerns [113] , [114] . ”

“ Improving the knowledge of care-givers at all levels of the health system is a challenge of paramount importance and great urgency in South Asia. Papua New Guinea, where snake bite management training programmes have been implemented in both rural and urban hospitals, could serve as an inspiring model in this regard. ”

“ In fact, time of transport was shown to be a crucial determinant of snake bite mortality in eastern Nepal [11] , and studies in southern India confirmed that delayed antivenom administration was associated with an increased risk of complications [18] , [88] . The bite victim should be reassured, the bitten limb immobilized with a makeshift splint or sling, and the patient transported. Walking is contraindicated, because muscular contractions promote venom absorption. ”

“ Among the true vipers, Russell's viper (Daboia russelii) is associated with the highest morbidity and mortality. In Anuradhapura District, Sri Lanka, up to 73% of all admitted snake bites are attributed to this species [15] whose distribution extends north to the Indus valley of Pakistan and Kashmir, to the foothills of the Himalayas in Nepal and Bhutan and to Bangladesh in the east. Saw-scaled vipers (Echis carinatus and E. sochureki) are other very important viperine species that inhabit open and dry environments. ”

“ Increased attention and means should be dedicated to snake bite envenoming by researchers, funding agencies, pharmaceutical industries, public health authorities, and supranational organisations, as all have contributed to keeping this important public health problem a truly neglected disease. ”

“ The highest figures reported in Asia so far come from a community-based survey conducted in southeast Nepal in 2002, which revealed annual incidence and mortality rates of 1,162/100,000 and 162/100,000, respectively [11] . Figures of a similar magnitude were recently also obtained in a nation-wide community-based survey in Bangladesh (M. R. Rahman, personal communication) .
Snake bite is an important occupational injury affecting farmers, plantation workers, herders, and fishermen. ”

“ Access to care is hindered both by the remoteness of snake bite–prone areas and by the cost of snake bite management. A community survey in Nepal showed that snake bite envenoming represents a substantial financial burden for rural households [11] . Despite the mushrooming of well-equipped private clinics in some rural areas of India, poor villagers rarely have access to mechanical ventilation or dialysis. ”

“ The majority of victims first report to traditional healers [89] , [17] , [19] , [21] . Popular traditional treatments include chanting, incisions, attempts to suck venom from the bite site, and the application of herbal medicine or snake stones. Two studies in Nepal and Bangladesh showed that 90% and 98% of snake bite victims, respectively, used tourniquets (Figure 3) [17] , [33] . In Bangladesh, incisions at and around the bite site were made in 28% of envenomed victims and in 13%–14% of those without signs of envenoming [17] . ”

“ However, a number of other species that contribute to morbidity and mortality in the region have not been considered, and envenoming by these species usually does not respond adequately to existing antivenoms [54] , [56] .
The success of antivenom therapy depends on the ability of immunoglobulins to bind, extract, and eliminate toxins present in the body. While their efficacy in restoring haemostasis and cardiovascular functions is well established, the ability of antivenoms to prevent tissue damage and to reverse neurotoxicity is more controversial [20] , [98] , [99] . ”

“ Once paralysis reaches the diaphragm and the intercostal muscles, victims usually die of respiratory failure if they are not adequately ventilated. Hospital-based studies in Sri Lanka showed that 48%–64% of B. caeruleus victims developed respiratory paralysis and required mechanical ventilation [13] , [20] . Although many clinical signs of neurotoxic envenoming by cobras and kraits are similar, with both genera able to cause respiratory failure within 30 minutes of the bite [72] , [73] , krait bite envenoming is often associated with a delayed onset and prolonged total period of paralysis. ”

“ Although monovalent antivenom has often been considered more efficacious, the production of polyvalent antivenom is preferred in many countries as snake species identification is generally not possible for the attending physician. Antivenoms have been available in South Asia for the past 60 years, and all existing products are manufactured by Indian companies. Traditionally, the production has focused on four species believed to be responsible for most deaths: N. naja, B. caeruleus, D. russelii, and E. carinatus. ”

“ In Pakistan, 40,000 bites are reported annually, which result in up to 8,200 fatalities [3] , [4] . In Nepal, more than 20,000 cases of envenoming occur each year, with 1,000 recorded deaths [5] . In Sri Lanka, around 33,000 envenomed snake bite victims are reported annually from government hospitals [3] , [6] . A postal survey conducted in 21 of the 65 administrative districts of Bangladesh estimated an annual incidence of 4.3 per 100,000 population and a case fatality of 20% [7] . ”

“ They represent the vast majority of living snakes, and may be mistaken for venomous snakes and/or involved in snake bite in South Asia. Rat snakes (Ptyas species, Coelognathus species) are large, rapidly moving snakes that are often confused with cobras. Most notoriously, several genera of small nonvenomous snakes share the same colour pattern as kraits [65] , [66] . Wolf snakes (Lycodon species) are of particular concern in this regard because some of them (e.g., Lycodon aulicus) are very common inside and around houses and bite aggressively if disturbed [17] . ”

“ Field diagnostic tests for snake species identification do not exist and treatment mainly relies on the administration of antivenoms that do not cover all of the important venomous snakes of the region. ”

“ Most experts agree that snake bite victims should be transported as quickly as possible to a medical centre where they can be clinically evaluated by qualified medical staff, and where antivenoms are available. ”

“ This method is, however, contraindicated for viper and cobra bites as it may increase local tissue damage [93] , [96] and may contribute to delaying transport of the victim to a treatment centre.
Antivenoms
Immunotherapy is the only specific treatment for snake bite envenoming. Antivenoms are produced by fractionation of plasma obtained from immunized animals, usually horses [97] . They can be either monovalent or polyvalent, depending on the number of species (single or multiple, respectively) whose venoms are used for immunization. ”

“ Open-style habitation and the practice of sleeping on the floor also expose people to bites from nocturnal snakes. As summarized in Table 1, several epidemiological studies have outlined characteristics of snake bite victims in the region. ”

“ Thatched roofs, and mud and straw walls are favoured hiding places for snakes and should be checked frequently. Many bites occur when people walking barefoot or wearing only sandals accidentally step on a snake. ”

“ Tourniquet on a 43-year-old woman presenting at a rural health post in Nepal.First-aid methods applied throughout South Asia are largely inadequate. Tourniquets in particular can have deleterious effects. This patient consulted after being bitten by a nonvenomous rat snake (Ptyas mucosa) that she had killed and brought for identification. After reassurance, local treatment, and observation, she was uneventfully discharged from the health post. Image credit: E. Alirol. In 1979, Sutherland et al. recommended the pressure-immobilization method as an effective alternative first aid method [92] . ”

“ For example, many doctors in India and Pakistan appear to be unaware of the criteria for antivenom administration [87] . Education of rural communities on snake bite, avoidance of useless or dangerous first-aid measures, and the importance of rapid transport of victims to treatment centres should be widely implemented [11] .The authors have declared that no competing interests exist.The work of UK is supported by the LOEWE Programme of the State Government of Hessen, Germany and by the Wellcome Trust (Research grant GR079027MA) . ”

“ Patients are often unable to protrude their tongue beyond the incisors and may present with difficulty speaking or swallowing. Limb weakness, loss of deep tendon reflexes, and fixed dilated pupils may follow. ”

“ Yunus, EB & Das, JC, “A hospital based study of snake bite in Chittagong Medical College.”, J Bangladesh Coll Phys Surg 13: 3–8 ↑ Warrell, DA, “Snake venoms in science and clinical medicine. 1. Russell's viper: biology, venom and treatment of bites.”, Trans R Soc Trop Med Hyg 83: 732–740, pmid:2533418 ↑ Jayakumar, M; Prabahar, MR; Fernando, EM; Manorajan, R & Venkatraman, R, “Epidemiologic trend changes in acute renal failure–a tertiary center experience from South India.”, Ren Fail 28: 405–410, pmid:16825090 1 2 Reid, HA, “Cobra-Bites.”, Br Med J 2: 540–545, pmid:14173184 ↑ Meier, J ”