**1. Introduction**

Snakebite envenoming is a potentially fatal disease that normally occurs as a result of the injection of venom following the bite of a venomous snake. Snakebite envenoming can also be caused by the spraying of venom into a person's eyes by particular snake species that are capable of spitting venom as a defense tool.

Envenoming results from an estimated 50–55% of all snakebites. Snake venoms are made up of complex mixtures of proteins and peptide toxins, which vary from one species to another and within species. Snakebite envenoming in humans and animals affects multiple organ systems based on the specific snake species and the groups of toxins present in the venom and can cause *inter alia* neuromuscular paralysis, hemorrhage and protracted disruption of hemostasis, cardiotoxicity, tissue necrosis, thrombosis, and myolysis (muscle degeneration) [1, 2].

Consistent with other neglected tropical diseases (NTDs), estimation of global morbidity, disability, and mortality occurring as a result of snakebite envenoming is problematic [2]. However, according to data [1], as many as 2.7 million people are affected by snakebite envenoming annually, majority of whom reside in some of the world's most disadvantaged, poorly developed, and politically side-lined rural tropical communities. This results in an annual mortality of 81,000 to 138,000, and an estimated 400,000 surviving victims left with permanent physical and psychological disabilities, as well as stigmatizing disfigurements. Available data on mortality suggests that deaths from snakebites are highest in Asia, notably in India followed by sub-Saharan Africa [3]. In Africa, where data issues are even more problematic, an estimated 1 million snakebites occur annually, with about half requiring specific treatment [4]. Also, in Africa alone, about 8000 amputations are believed to occur each year as a result of snakebite envenoming [5, 6]. Snakebite envenoming is, thus, a disease that warrants urgent attention.

As the case with many poverty-related diseases, snakebite envenoming has been unsuccessful at attracting the needed public health policy inclusion and investment required to drive sustainable efforts aimed at reducing the medical and social burden. This is largely attributed to the demographics of the populations affected coupled with their lack of political voice [7]. Snakebites also pose significant additional socioeconomic burden on the remote and already penurious communities to the extent that the most economically productive (10–40-year-olds) are those who suffer the most [8].

Snakebite is a high morbidity/high mortality neglected tropical disease (NTD), and for that matter, one of the most under-researched and under-resourced NTDs. This is demonstrated by the fact that a majority of the antivenoms used to treat victims of snakebite in sub-Saharan Africa are of untested and indeterminate efficacy [3]. Furthermore, the plights of snakebite victims in this part of the continent have been exacerbated by a crisis in the supply of affordable and effective antivenoms, a phenomenon that was first reported in 2000 [3].

In the view of the World Health Organization, the unavailability of effective antivenoms to treat snake envenoming in various parts of the world has assumed a critical health status at the global level. This crisis is believed to have reached its highest intensity in sub-Saharan Africa [2]. It is, therefore, anticipated that the reintroduction of snakebite envenoming into the WHO NTD portfolio in 2017 following intense advocacy by stakeholders would give the needed attention to the disease and consequently lead to strategies to prevent, reduce, and control the snakebite burden [7].

The methods used in producing most antivenoms from the hyperimmune plasma of horses or sheep have not changed significantly in the last 50 to 60 years. As a result, the quality and safety of some of these antivenoms remain poor [9, 10]. The WHO recommends the development of polyspecific antivenoms, particularly for countries inhabited by several medically important snake species [2]. However, reports [3] suggest that the high costs of most polyspecific antivenoms over the last two decades resulted in decreased demand, and hence depressed commercial production volumes, resulting in the influx of less expensive antivenoms of untested efficacy. According to

## *Perspective Chapter: Diagnostic and Antivenom Immunotherapeutic Approaches… DOI: http://dx.doi.org/10.5772/intechopen.112147*

published data [11], some of these antivenoms have proven dangerously ineffective in many African countries. This is supported by reports from Ghana, Central African Republic, and Chad to the effect of an increased case fatality rate (from less than 2% to over 12%) due to the use of such antivenoms [11].

The generation of toxin-specific antibodies would lead to an increase in the dose efficacy of antivenoms and consequently reduce the risk of early anaphylactoid and late serum reactions that typify the administration of large volumes of horse and sheep-derived antivenoms. Toxin-specific antibodies have the potential to neutralize the venoms of medically important snake species [12]. The dose efficacy of monovalent antivenoms is usually higher than that of polyvalent antivenoms. For instance, the curative dose of EchiTAbG, a monovalent antivenom is reported to be one vial whiles that of EchiTAb-Plus-ICP, a polyvalent antivenom is three vials, implying that monovalent antivenoms present a better treatment alternative in terms of cost-effectiveness [13] but only if the specificity of the treatment can be assessed ahead of application. Also, in Nigeria, a monovalent *Echis ocellatus* antivenom was found to be preferred to a polyvalent product because the former was up to 4-fold more effective in neutralizing *E. ocellatus* venom relative to the latter [14]. Most parts of the world affected by snakebite envenoming depend on broad-spectrum polyspecific antivenoms that are known to contain a low content of case-specific efficacious immunoglobulins. Thus, advances in toxin-specific monoclonal antibodies hold much promise as far as future treatment strategies for snakebite envenoming are concerned. Monoclonal or other toxin-specific treatment options offer advantages such as fewer adverse reactions, case-specificity, increased efficacy, and cost-effectiveness as compared to past and present treatment approaches [15].

Furthermore, previous studies [16, 17] indicate that polyvalent antivenoms, although touted as effective and also credited with saving the lives of thousands of snakebite victims for nearly a century, are linked with serious allergic reactions, serum sickness, as well as other side effects. In addition, available data [16] show that monoclonal antibodies when included in antivenoms are able to neutralize all the medically important toxins present in a given venom and/or abrogate the synergistic effect of toxins in a venom sample. This, therefore, presupposes that the administration of toxin-specific or monoclonal-based monospecific antivenoms could mitigate the treatment-related challenges associated with polyspecific antivenoms, and hence make the former a preferred option for therapy. Thus, novel strategies, such as monoclonal antibodies, hold much promise with prognostic and diagnostic applications in snakebite envenoming (SBE). In this chapter, there will be a brief discussion of the modern concepts of snake envenoming and general discussion on the diagnostic and antivenom immunotherapeutic approaches to management of snake envenoming.
