Ending the drought: New strategies for improving the flow of affordable, effective antivenoms in Asia and Africa

Abstract

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: fi...

Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms

“…Of all venomous animals, snakes are the most wellknown because of their medical importance: As many as 90,000 people die each year as the result of snakebite, with the majority of those inhabiting rural poor regions of the tropics (2,3). This substantial mortality burden of snakebite victims is surprising because antivenom treatment (immunoglobulins from venom-immunized horses/sheep) can be highly effective at neutralizing the toxic components present in snake venom (4,5). However, the efficacy of these therapies is largely restricted to the snake species whose venom was used in manufacture.…”

“…Importantly, the extent of this variation is not simply reflected by taxonomic distance (9)(10)(11) and, therefore, cannot be readily predicted. The consequence of venom variation is that antivenoms raised against any particular species of snake are often ineffective in treating snakebite by different, even closely related, species (5,12,13).…”

Needs and availability of snake antivenoms: relevance and application of international guidelines

“…To improve global availability, larger laboratories require clearer descriptions of market sizes and needs, in order to plan longterm manufacturing strategies (3,10). The end of the 20th century saw a dramatic reduction in antivenom producers: Behringerwerke AG in Germany, which produced antivenoms for Africa and the Middle East, stopped production in the 1980s, South African producers have been fraught with difficulties, and CSL Australia stopped research activities into antivenoms, yet continues production only for Australian antivenoms (12). Production expenses, production complexity, and lack of a lucrative market largely drove such shutdowns.…”

“…The result of low output and high production costs are antivenoms that are unaffordable to those who need them most. There is a global deficiency of appropriate antivenom supply, and the poor rural areas most burdened by snakebite, such as Sub-Saharan Africa and parts of Asia suffer most from this limited availability, resulting in poor treatment outcomes (8,12,17). A commendable step was taken with the publication of the WHO Guidelines on production, control and regulation of snake antivenom immunoglobulins in 2008 (18).…”

“…However, possibly due to the absence of follow up meetings or updates since, problems in the implementation of these guidelines in high-burden regions have arisen. In order to combat some issues of access, the WHO has included snake antivenom immunoglobulins in the WHO Model List for Essential Medicines, encouraging countries to do the same and thereby ensuring national antivenom stocks; this has yet to show an increase in global access to antivenoms (11,12,14). The reasons behind this have not yet been thoroughly researched, creating a need to investigate the barriers to antivenom accessibility.…”