Mender Mender M, Bolton Fiona, Berry Colin, Young Mark
School of Bioscience, Cardiff University, Cardiff, United Kingdom; Department of Research and Development, MicroPharm Ltd, Newcastle Emlyn, United Kingdom.
Department of Research and Development, MicroPharm Ltd, Newcastle Emlyn, United Kingdom.
Adv Protein Chem Struct Biol. 2022;129:435-477. doi: 10.1016/bs.apcsb.2021.11.004. Epub 2021 Dec 28.
Snakebite envenoming (SBE) leads to significant morbidity and mortality, resulting in over 90,000 deaths and approximately 400,000 amputations annually. In sub-Saharan Africa (SSA) alone, SBE accounts for over 30,000 deaths per annum. Since 2017, SBE has been classified as a priority Neglected Tropical Disease (NTD) by the World Health Organisation (WHO). The major species responsible for mortality from SBE within SSA are from the Bitis, Dendroaspis, Echis and Naja genera. Pharmacologically active toxins such as metalloproteinases, serine proteinases, 3-finger toxins, kunitz-type toxins, and phospholipase As are the primary snake venom components. These toxins induce cytotoxicity, coagulopathy, hemorrhage, and neurotoxicity in envenomed victims. Antivenom is currently the only available venom-specific treatment for SBE and contains purified equine or ovine polyclonal antibodies, collected from donor animals repeatedly immunized with low doses of adjuvanted venom. The resulting plasma or serum contains a high titre of specific antibodies, which can then be collected and stored until required. The purified antibodies are either whole IgG, monovalent fragment antibody (Fab) or divalent fragment antibody F(ab'). Despite pharmacokinetic and pharmacodynamic differences, all three are effective in the treatment of SBE. No antivenom is without adverse reactions but, the level of their impact and severity varies from benign early adverse reactions to the rarely occurring fatal anaphylactic shock. However, the major side effects are largely reversible with immediate administration of adrenaline and corticosteroids. There are 16 different antivenoms marketed within SSA, but the efficacy and safety profiles are only published for less than 50% of these products.
蛇咬伤中毒(SBE)会导致严重的发病和死亡,每年造成超过90000人死亡和约400000例截肢。仅在撒哈拉以南非洲(SSA),蛇咬伤中毒每年就导致超过30000人死亡。自2017年以来,蛇咬伤中毒已被世界卫生组织(WHO)列为重点被忽视热带病(NTD)。在SSA范围内,导致蛇咬伤中毒死亡的主要蛇种来自膨蝰属、树眼镜蛇属、锯鳞蝰属和眼镜蛇属。金属蛋白酶、丝氨酸蛋白酶、三指毒素、库尼茨型毒素和磷脂酶A等具有药理活性的毒素是主要的蛇毒成分。这些毒素会在中毒受害者体内引发细胞毒性、凝血病、出血和神经毒性。抗蛇毒血清是目前唯一可用于治疗蛇咬伤中毒的特异性抗毒剂,它含有从用低剂量佐剂化毒液反复免疫的供体动物中收集的纯化马或羊多克隆抗体。由此产生的血浆或血清含有高滴度的特异性抗体,然后可以收集并储存以备需要时使用。纯化的抗体可以是完整的免疫球蛋白G(IgG)、单价片段抗体(Fab)或双价片段抗体F(ab')₂。尽管它们在药代动力学和药效学上存在差异,但这三种抗体在治疗蛇咬伤中毒方面都有效。没有一种抗蛇毒血清没有不良反应,但其影响程度和严重程度各不相同,从良性的早期不良反应到罕见的致命过敏性休克。然而,通过立即注射肾上腺素和皮质类固醇,主要副作用在很大程度上是可逆的。在SSA市场上销售的抗蛇毒血清有16种不同的产品,但其中不到50%的产品公布了疗效和安全性数据。