Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Parkville, Vic, 3010, Australia.
J Proteomics. 2011 Aug 24;74(9):1735-67. doi: 10.1016/j.jprot.2011.05.027. Epub 2011 May 19.
The development of snake antivenoms more than a century ago should have heralded effective treatment of the scourge of snakebite envenoming in impoverished, mostly rural populations around the world. That snakebite still exists today, as a widely untreated illness that maims, kills and terrifies men, women and children in vulnerable communities, is a cruel anachronism. Antivenom can be an effective, safe and affordable treatment for snakebites, but apathy, inaction and the politicisation of public health have marginalised both the problem (making snakebite arguably the most neglected of all neglected tropical diseases) and its solution. For lack of any coordinated approach, provision of antivenoms has been pushed off the public health agenda, leading to an incongruous decline in demand for these crucial antidotes, excused and fed by new priorities, an absence of epidemiological data, and a poor regulatory framework. These factors facilitated the infiltration of poor quality products that degrade user confidence and undermine legitimate producers. The result is that tens of thousands are denied an essential life-saving medicine, allowing a toll of human suffering that is a summation of many individual catastrophes. No strategy has been developed to address this problem and to overcome the intransigence and inaction responsible for the global tragedy of snakebite. Attempts to engage with the broader public health community through the World Health Organisation (WHO), GAVI, and other agencies have failed. Consequently, the toxinology community has taken on a leadership role in a new approach, the Global Snakebite Initiative, which seeks to mobilise the resources, skills and experience of scientists and clinicians for whom venoms, toxins, antivenoms, snakes and snakebites are already fields of interest. Proteomics is one such discipline, which has embraced the potential of using venoms in bio-discovery and systems biology. The fields of venomics and antivenomics have recently evolved from this discipline, offering fresh hope for the victims of snakebites by providing an exciting insight into the complexities, nature, fundamental properties and significance of venom constituents. Such a rational approach brings with it the potential to design new immunising mixtures from which to raise potent antivenoms with wider therapeutic ranges. This addresses a major practical limitation in antivenom use recognised since the beginning of the 20th century: the restriction of therapeutic effectiveness to the specific venom immunogen used in production. Antivenomic techniques enable the interactions between venoms and antivenoms to be examined in detail, and if combined with functional assays of specific activity and followed up by clinical trials of effectiveness and safety, can be powerful tools with which to evaluate the suitability of current and new antivenoms for meeting urgent regional needs. We propose two mechanisms through which the Global Snakebite Initiative might seek to end the antivenom drought in Africa and Asia: first by establishing a multidisciplinary, multicentre, international collaboration to evaluate currently available antivenoms against the venoms of medically important snakes from specific nations in Africa and Asia using a combination of proteomic, antivenomic and WHO-endorsed preclinical assessment protocols, to provide a validated evidence base for either recommending or rejecting individual products; and secondly by bringing the power of proteomics to bear on the design of new immunising mixtures to raise Pan-African and Pan-Asian polyvalent antivenoms of improved potency and quality. These products will be subject to rigorous clinical assessment. We propose radically to change the basis upon which antivenoms are produced and supplied for the developing world. Donor funding and strategic public health alliances will be sought to make it possible not only to sustain the financial viability of antivenom production partnerships, but also to ensure that patients are relieved of the costs of antivenom so that poverty is no longer a barrier to the treatment of this important, but grossly neglected public health emergency.
一个多世纪前开发的蛇抗毒液本应预示着有效治疗全世界贫穷、以农村为主的地区中蛇咬伤这一祸害。然而,时至今日,这种广泛未经治疗的疾病仍然存在,使弱势社区的男女老幼致残、致死和惊恐不安,这是一个残酷的时代错误。抗蛇毒血清可以作为蛇咬伤的有效、安全且负担得起的治疗方法,但冷漠、不作为和公共卫生的政治化使这一问题(使蛇咬伤成为所有被忽视热带病中最被忽视的疾病之一)及其解决方案边缘化。由于缺乏任何协调一致的方法,抗蛇毒血清的供应已从公共卫生议程中被剔除,导致对这些关键解毒剂的需求急剧下降,而这一情况被新的优先事项、缺乏流行病学数据以及不完善的监管框架所辩解和助长。这些因素为质量低劣的产品的渗透提供了便利,这些产品降低了用户的信心,并破坏了合法生产商的利益。结果是数以万计的人被剥夺了救命的救命药,任由这些人遭受痛苦,这是许多人个人灾难的总和。目前还没有制定出解决这个问题的策略,也没有克服导致全球蛇咬伤悲剧的顽固和不作为。通过世界卫生组织(WHO)、全球疫苗和免疫联盟(GAVI)和其他机构与更广泛的公共卫生界接触的尝试都失败了。因此,毒素学领域在一个新的方法中发挥了领导作用,即全球蛇咬伤倡议,该倡议旨在调动科学家和临床医生的资源、技能和经验,因为毒液、毒素、抗蛇毒血清、蛇和蛇咬伤已经是他们感兴趣的领域。蛋白质组学就是这样一门学科,它已经接受了利用毒液进行生物发现和系统生物学的潜力。毒肽组学和抗蛇毒血清组学最近从该学科中发展而来,为蛇咬伤受害者带来了新的希望,通过深入了解毒液成分的复杂性、性质、基本特性和意义,为他们提供了一个令人兴奋的见解。这种合理的方法带来了设计新的免疫混合物的潜力,从中可以产生更广泛治疗范围的高效抗蛇毒血清。这解决了自 20 世纪初以来抗蛇毒血清使用的一个主要实际限制:治疗效果仅限于生产中使用的特定毒液免疫原。抗蛇毒血清组学技术使我们能够详细检查毒液和抗蛇毒血清之间的相互作用,如果与特定活性的功能测定相结合,并通过有效性和安全性的临床试验进行跟踪,那么这些技术将成为评估当前和新型抗蛇毒血清是否适合满足紧急区域需求的有力工具。我们提出了两种机制,通过这些机制,全球蛇咬伤倡议可能会寻求结束非洲和亚洲的抗蛇毒血清干旱:首先,建立一个多学科、多中心、国际合作,使用蛋白质组学、抗蛇毒血清组学和世界卫生组织认可的临床前评估方案,对来自非洲和亚洲特定国家的具有医学重要性的蛇的毒液进行评估,对现有抗蛇毒血清进行评估,以提供一个经过验证的证据基础,无论是推荐还是拒绝个别产品;其次,通过将蛋白质组学的力量应用于新免疫混合物的设计,以提高具有更高效力和质量的泛非和泛亚多价抗蛇毒血清。这些产品将接受严格的临床评估。我们建议从根本上改变为发展中国家生产和供应抗蛇毒血清的基础。将寻求捐助者供资和战略公共卫生联盟,以使不仅有可能维持抗蛇毒血清生产伙伴关系的财务可行性,而且还确保患者免除抗蛇毒血清的费用,以便贫困不再成为治疗这一重要但严重被忽视的公共卫生紧急情况的障碍。