Abstract
The toxin composition of snake venoms and, thus, their functional activity, can vary between and within species. Intraspecific venom variation across a species’ geographic range is a major concern for antivenom treatment of envenomations, particularly for countries like French Guiana that lack a locally produced antivenom. Bothrops asper and Bothrops atrox are the most medically significant species of snakes in Latin America, both producing a variety of clinical manifestations, including systemic bleeding. These pathophysiological actions are due to the activation by the venom of the blood clotting factors Factor X and prothrombin, thereby causing severe consumptive coagulopathy. Both species are extremely wide-ranging, and previous studies have shown their venoms to exhibit regional venom variation. In this study, we investigate the differential coagulotoxic effects on human plasma of six venoms (four B. asper and two B. atrox samples) from different geographic locations, spanning from Mexico to Peru. We assessed how the venom variation of these venom samples affects neutralisation by five regionally available antivenoms: Antivipmyn, Antivipmyn-Tri, PoliVal-ICP, Bothrofav, and Soro Antibotrópico (SAB). The results revealed both inter- and intraspecific variations in the clotting activity of the venoms. These variations in turn resulted in significant variation in antivenom efficacy against the coagulotoxic effects of these venoms. Due to variations in the venoms used in the antivenom production process, antivenoms differed in their species-specific or geographical neutralisation capacity. Some antivenoms (PoliVal-ICP, Bothrofav, and SAB) showed species-specific patterns of neutralisation, while another antivenom (Antivipmyn) showed geographic-specific patterns of neutralisation. This study adds to current knowledge of Bothrops venoms and also illustrates the importance of considering evolutionary biology when developing antivenoms. Therefore, these results have tangible, real-world implications by aiding evidence-based design of antivenoms for treatment of the envenomed patient. We stress that these in vitro studies must be backed by future in vivo studies and clinical trials before therapeutic guidelines are issued regarding specific antivenom use in a clinical setting.
Highlights
Venomous snakebites across the Americas result in an estimated 652 to 3466 deaths per year [1], with the majority of these snakebites by pit-vipers [2–5]
Antivenoms did not have any effect on clotting as antivenom control values were similar to the spontaneous clotting time: Antivipmyn (n = 4) = 485.63 ± 54.41 s, PoliVal-ICP (n = 4) = 483.15 ± 27.93 s, Antivipmyn-Tri (n = 4) = 486.45 ± 20.97 s, Bothrofav (n = 4) = 521.45 ± 9.32 s, and Soro Antibotrópico (SAB)
It was hypothesised that both intraand interspecific venom variation would be observed and would result in differential antivenom efficacy
Summary
Venomous snakebites across the Americas result in an estimated 652 to 3466 deaths per year [1], with the majority of these snakebites by pit-vipers [2–5]. Epidemiological data suggest that across South America, 70–96.6% of envenomings are inflicted by the Bothrops species [3–6]. Most of these bites are from B. atrox in Amazon regions [6,7] or B. asper in northern South America [8]. Similar values are reported across Central America, with 50–80% of all snakebites attributed to B. asper [8,9]. Epidemiological data on Mexican B. asper bites are scarce, the incidence is approximately 6 bite cases per 100,000 people per year [8]. In a more recent study, Chippaux [10] reported 3.3 snakebite cases per 100,000 people per year in Mexico, the species responsible for these bites is not made clear. Collectively across the Americas, B. asper and B. atrox may be considered the two species responsible for most medically significant snakebite envenomations
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