Abstract
Snakebite envenoming represents a neglected tropical disease that has a heavy public health impact worldwide, mostly affecting poor people involved in agricultural activities in Africa, Asia, Latin America and Oceania. A key issue that complicates the treatment of snakebite envenomings is the poor availability of the only validated treatment for this disease, antivenoms. Antivenoms can be an efficacious treatment for snakebite envenoming, provided they are safe, effective, affordable, accessible and administered appropriately. The shortage of antivenoms in various regions, particularly in Sub-Saharan Africa and some parts of Asia, can be significantly alleviated by optimizing the use of current antivenoms and by the generation of novel polyspecific antivenoms having a wide spectrum of efficacy. Complementing preclinical testing of antivenom efficacy using in vivo and in vitro functional neutralization assays, developments in venomics and antivenomics are likely to revolutionize the design and preclinical assessment of antivenoms by being able to test new antivenom preparations and to predict their paraspecific neutralization to the level of species-specific toxins.
Highlights
Snakebite Envenoming and the Challenge of Generating Effective AntivenomsSnakebite envenoming is largely a neglected threat to public health that affects some of the world’s poorest rural communities, mainly those involved in subsistence farming and livestock grazing activities in tropical and subtropical regions of Africa, Asia, Latin America and Oceania
In the case of coagulant and defibrinogenating activities, neutralization is expressed as the effective dose (ED), defined as the antivenom/venom ratio at which the clotting time of plasma is prolonged three times when compared to plasma incubated with venom alone or as the antivenom/venom ratio in which blood clots form in all animals injected [39]
The shortage of antivenoms in various parts of the planet can be in part counteracted through the improved deployment of currently existing antivenoms, and through the design and production of next-generation polyspecific antivenoms of a wide neutralizing spectrum
Summary
Snakebite envenoming is largely a neglected threat to public health that affects some of the world’s poorest rural communities, mainly those involved in subsistence farming and livestock grazing activities in tropical and subtropical regions of Africa, Asia, Latin America and Oceania. A key technical issue concerning the generation of new antidotes for snakebite envenoming is the design of improved immunization mixtures in such a way that the resulting antivenoms are effective against most venoms of the medically-relevant snake species within the geographical range where these antivenoms are intended to be used. The routine quality control of antivenoms involves the neutralization of lethal activity, when a new antivenom is being developed or when an existing antivenom is introduced to a new geographical setting, a comprehensive preclinical analysis of neutralizing efficacy should be performed against the most relevant toxic effects of the most important snake venoms in that particular region. In the case of coagulant and defibrinogenating activities, neutralization is expressed as the effective dose (ED), defined as the antivenom/venom ratio at which the clotting time of plasma is prolonged three times when compared to plasma incubated with venom alone (for coagulant activity) or as the antivenom/venom ratio in which blood clots form in all animals injected (for defibrinogenating effect) [39]
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