Beyond the 'big four': Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies
Beyond the 'big four': Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies
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DOI：
10.1371/journal.pntd.0007899
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发表时间：
2019-12-01
影响因子：
3.8
通讯作者：
Sunagar, Kartik
中科院分区：
文献类型：
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作者：
Laxme, R. R. Senji;Khochare, Suyog;Sunagar, Kartik
蛇咬伤在印度每年造成的死亡率（46，000）和残疾率（140，000）比任何其他国家都高。抗蛇毒血清是治疗蛇咬伤的主要药物，其生产工艺在过去的世纪中基本保持不变。在印度，一种多价抗蛇毒血清被生产用于治疗所谓的“四大”蛇：眼镜蛇（Naja naja），普通金环蛇（Bungarus caeruleus），罗素蝰蛇（Daboia russelii）和锯鳞蝰蛇（Echis carinatus）。除了“四大毒蛇”，印度还有许多其他种类的毒蛇，这些毒蛇有可能对人类咬伤的受害者造成严重的临床甚至致命的毒液。不幸的是，具体的抗蛇毒血清不产生对这些物种，而是，'大四'抗蛇毒血清是常规用于treatment.MethodsWe特点的毒液成分，生化和药理学活性和毒性概况（小鼠模型）的主要被忽视的，但医学上重要的印度蛇（E。C. sochureki，B. sindanus，B. fasciatus和两个种群的N. Kaouthia）和它们最接近的“四大”同源物。通过执行世卫组织推荐的体外和体内临床前试验，我们评估了商业销售的印度抗蛇毒血清在认识毒液和中和envenomations由这些被忽视的species.FindingsAs不同的生态和饮食的后果的效率，医学上重要的蛇调查表现出显着的种间和种内差异，他们的毒液配置文件。目前市售的抗蛇毒血清被发现对“被忽视的许多”表现出不良的剂量功效和毒液识别潜力。优质血清抗蛇毒血清未能中和许多被忽视的物种和“四大”蛇之一（北印度种群B。caeruleus）.ConclusionsThis study unravels disturbing deficiencies in dose efficacy and neutralisation capabilities of the currently marketed Indian antivenoms，and emphasizes the immediate need to develop regional specific snakebite therapy for the“ignored many”.
BackgroundSnakebite in India causes the highest annual rates of death (46,000) and disability (140,000) than any other country. Antivenom is the mainstay treatment of snakebite, whose manufacturing protocols, in essence, have remained unchanged for over a century. In India, a polyvalent antivenom is produced for the treatment of envenomations from the so called 'big four' snakes: the spectacled cobra (Naja naja), common krait (Bungarus caeruleus), Russell's viper (Daboia russelii), and saw-scaled viper (Echis carinatus). In addition to the 'big four', India is abode to many other species of venomous snakes that have the potential to inflict severe clinical or, even, lethal envenomations in their human bite victims. Unfortunately, specific antivenoms are not produced against these species and, instead, the 'big four' antivenom is routinely used for the treatment.MethodsWe characterized the venom compositions, biochemical and pharmacological activities and toxicity profiles (mouse model) of the major neglected yet medically important Indian snakes (E. c. sochureki, B. sindanus, B. fasciatus, and two populations of N. kaouthia) and their closest 'big four' congeners. By performing WHO recommended in vitro and in vivo preclinical assays, we evaluated the efficiencies of the commercially marketed Indian antivenoms in recognizing venoms and neutralizing envenomations by these neglected species.FindingsAs a consequence of dissimilar ecologies and diet, the medically important snakes investigated exhibited dramatic inter- and intraspecific differences in their venom profiles. Currently marketed antivenoms were found to exhibit poor dose efficacy and venom recognition potential against the 'neglected many'. Premium Serums antivenom failed to neutralise bites from many of the neglected species and one of the 'big four' snakes (North Indian population of B. caeruleus).ConclusionsThis study unravels disturbing deficiencies in dose efficacy and neutralisation capabilities of the currently marketed Indian antivenoms, and emphasises the pressing need to develop region-specific snakebite therapy for the 'neglected many'.