Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom.
Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom.
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DOI：
10.1371/journal.pntd.0000851
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发表时间：
2010-10-26
影响因子：
3.8
通讯作者：
Harrison RA
中科院分区：
文献类型：
--
作者：
Casewell NR;Cook DA;Wagstaff SC;Nasidi A;Durfa N;Wüster W;Harrison RA
蛇咬伤是撒哈拉以南非洲生存农业人口死亡和残疾的一个重要原因。抗蛇毒血清是最有效的治疗毒液中毒的药物，它是由对马/羊的毒液免疫的IgG制成的，但由于复杂的财政原因，撒哈拉以南非洲缺乏抗蛇毒血清。为了解决尼日利亚萨凡纳草原数千名蛇咬伤受害者的困境，EchiTAb研究小组组织了抗蛇毒血清的生产、测试和交付，这些抗蛇毒血清旨在治疗该地区最具医学重要性的蛇的毒液中毒。锯鳞蛇在非洲分布广泛，具有重要的医疗价值。为了最大限度地发挥非洲稀有抗蛇毒血清资源的临床效用，我们的目的是在临床前水平上确定E。专门为尼日利亚设计的眼蜱特异性EchiTAbG抗蛇毒血清，中和了来自另外两种非洲物种的毒液的致命活性，即E. E. leakeyi和E. coloratus。尽管显然相当独特的毒液蛋白质的配置文件，我们观察到广泛的跨物种的相似性，在Echis物种特异性抗血清的免疫反应性配置文件。使用WHO标准临床前体内试验，我们确定单特异性EchiTAbG抗蛇毒血清在中和E. E. leakeyi和E. coloratus对E.眼斑毒在本试验的限制条件下，抗蛇毒血清对非非洲Echis种E. [医]鸡眼使用WHO推荐的临床前试验，我们已经证明了新的抗E。针对尼日利亚相当大的蛇咬伤引起的死亡率和发病率而开发的ocellatus单特异性抗蛇毒血清EchiTAbG中和了来自Echis物种的毒液的致死作用，Echis物种代表了非洲该属的每个分类组。这表明，这种单特异性抗蛇毒血清有可能治疗大多数，也许是所有的非洲Echis物种的毒液中毒。蛇咬伤主要是农村贫困社区的一个健康问题。在撒哈拉以南非洲，自给农业的蛇咬伤风险很高，而且缺乏有效的抗蛇毒血清，这意味着许多社区仍然难以接受地容易受到蛇咬伤死亡率和发病率的影响。因此，迫切需要最大化可用的蛇咬伤疗法的效用。为了解决尼日利亚严重的蛇咬伤问题，政府资助了一个由政府官员、抗蛇毒血清制造商和学者组成的合作组织（EchiTAb研究小组），以生产、测试和提供抗蛇毒血清。因此，我们制备了EchiTAbG，一种对锯鳞蝰蛇（E. ocellatus），这是负责在尼日利亚的蛇咬伤死亡的80%。自E.眼斑蚊广泛分布于西非萨凡纳，EchiTAbG在该地区的许多国家提供了相当大的治疗前景。由于其他Echis物种代表了非洲其他地方的公共卫生问题，因此本研究的目的是检查EchiTAbG的临床前属内毒液中和功效。我们的研究结果表明，EchiTAbG（尼日利亚注册号：A6-0078）对Echis envenoming具有泛非疗效，表明可能不需要对区域特异性抗蛇毒血清进行昂贵的投资。这是一个重要的进展，以尽量减少开发成本，并最大限度地提供蛇咬伤治疗的大陆。
Snakebite is a significant cause of death and disability in subsistent farming populations of sub-Saharan Africa. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses/sheep but, because of complex fiscal reasons, there is a paucity of antivenom in sub-Saharan Africa. To address the plight of thousands of snakebite victims in savannah Nigeria, the EchiTAb Study Group organised the production, testing and delivery of antivenoms designed to treat envenoming by the most medically-important snakes in the region. The Echis saw-scaled vipers have a wide African distribution and medical importance. In an effort to maximise the clinical utility of scarce antivenom resources in Africa, we aimed to ascertain, at the pre-clinical level, to what extent the E. ocellatus-specific EchiTAbG antivenom, which was designed specifically for Nigeria, neutralised the lethal activity of venom from two other African species, E. pyramidum leakeyi and E. coloratus. Despite apparently quite distinctive venom protein profiles, we observed extensive cross-species similarity in the immuno-reactivity profiles of Echis species-specific antisera. Using WHO standard pre-clinical in vivo tests, we determined that the monospecific EchiTAbG antivenom was as effective at neutralising the venom-induced lethal effects of E. pyramidum leakeyi and E. coloratus as it was against E. ocellatus venom. Under the restricted conditions of this assay, the antivenom was ineffective against the lethal effects of venom from the non-African Echis species, E. carinatus sochureki. Using WHO-recommended pre-clinical tests we have demonstrated that the new anti-E. ocellatus monospecific antivenom EchiTAbG, developed in response to the considerable snakebite-induced mortality and morbidity in Nigeria, neutralised the lethal effects of venoms from Echis species representing each taxonomic group of this genus in Africa. This suggests that this monospecific antivenom has potential to treat envenoming by most, perhaps all, African Echis species. Snakebite is principally a health concern of rural poor communities. The high snakebite risk of subsistence farming and paucity of effective antivenoms in sub-Saharan Africa means that many communities remain unacceptably vulnerable to snakebite mortality and morbidity. There is therefore a compelling need to maximise the utility of the snakebite therapies that are available. To address Nigeria's severe snakebite problem, the government funded a collaboration of ministry officials, antivenom manufacturers and academics (the EchiTAb Study Group) to produce, test and deliver antivenom. Accordingly, we prepared EchiTAbG, an antivenom specific for envenoming by the saw-scaled viper (E. ocellatus) which is responsible for 80% of snakebite deaths in Nigeria. Since E. ocellatus is widely distributed across the West African savannah, EchiTAbG offers considerable therapeutic promise in many countries in the region. Since other Echis species represent public health concerns elsewhere in Africa, the objective of this study was to examine the pre-clinical intra-generic venom-neutralising efficacy of EchiTAbG. Our results suggest that EchiTAbG (Nigeria registration: A6-0078) has pan-African efficacy against Echis envenoming indicating that costly investment in region-specific antivenoms therefore may not be required. This represents an important progression to minimise development costs and maximise the delivery of snakebite therapy for the continent.
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DOI：
10.1016/j.trstmh.2004.09.014
发表时间：
2005-06-01
影响因子：
2.2
作者：
Gutiérrez, JM;Rojas, E;Rojas, G
通讯作者：
Rojas, G
影响因子：
1.4
作者：
Kochar, D. K.;Tanwar, P. D.;Simpson, Ian D.
通讯作者：
Simpson, Ian D.
影响因子：
2.8
作者：
Cook, Darren A. N.;Owen, Timothy;Harrison, Robert A.
通讯作者：
Harrison, Robert A.
影响因子：
15.8
作者：
Kasturiratne A;Wickremasinghe AR;de Silva N;Gunawardena NK;Pathmeswaran A;Premaratna R;Savioli L;Lalloo DG;de Silva HJ
通讯作者：
de Silva HJ
影响因子：
15.8
作者：
Gutiérrez JM;Theakston RD;Warrell DA
通讯作者：
Warrell DA