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Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom.

Casewell NR, Cook DA, Wagstaff SC, Nasidi A, Durfa N, Wüster W, Harrison RA - PLoS Negl Trop Dis (2010)

Bottom Line: Using WHO standard pre-clinical in vivo tests, we determined that the monospecific EchiTAbG antivenom was as effective at neutralising the venom-induced lethal effects of E. pyramidum leakeyi and E. coloratus as it was against E. ocellatus venom.Under the restricted conditions of this assay, the antivenom was ineffective against the lethal effects of venom from the non-African Echis species, E. carinatus sochureki.Using WHO-recommended pre-clinical tests we have demonstrated that the new anti-E. ocellatus monospecific antivenom EchiTAbG, developed in response to the considerable snakebite-induced mortality and morbidity in Nigeria, neutralised the lethal effects of venoms from Echis species representing each taxonomic group of this genus in Africa.

View Article: PubMed Central - PubMed

Affiliation: Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

ABSTRACT

Background: Snakebite is a significant cause of death and disability in subsistent farming populations of sub-Saharan Africa. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses/sheep but, because of complex fiscal reasons, there is a paucity of antivenom in sub-Saharan Africa. To address the plight of thousands of snakebite victims in savannah Nigeria, the EchiTAb Study Group organised the production, testing and delivery of antivenoms designed to treat envenoming by the most medically-important snakes in the region. The Echis saw-scaled vipers have a wide African distribution and medical importance. In an effort to maximise the clinical utility of scarce antivenom resources in Africa, we aimed to ascertain, at the pre-clinical level, to what extent the E. ocellatus-specific EchiTAbG antivenom, which was designed specifically for Nigeria, neutralised the lethal activity of venom from two other African species, E. pyramidum leakeyi and E. coloratus.

Methodology/principal findings: Despite apparently quite distinctive venom protein profiles, we observed extensive cross-species similarity in the immuno-reactivity profiles of Echis species-specific antisera. Using WHO standard pre-clinical in vivo tests, we determined that the monospecific EchiTAbG antivenom was as effective at neutralising the venom-induced lethal effects of E. pyramidum leakeyi and E. coloratus as it was against E. ocellatus venom. Under the restricted conditions of this assay, the antivenom was ineffective against the lethal effects of venom from the non-African Echis species, E. carinatus sochureki.

Conclusions/significance: Using WHO-recommended pre-clinical tests we have demonstrated that the new anti-E. ocellatus monospecific antivenom EchiTAbG, developed in response to the considerable snakebite-induced mortality and morbidity in Nigeria, neutralised the lethal effects of venoms from Echis species representing each taxonomic group of this genus in Africa. This suggests that this monospecific antivenom has potential to treat envenoming by most, perhaps all, African Echis species.

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Extensive cross-specific immunological reactivity between Echis venoms and Echis species-specific IgG antisera revealed by End Point Titration ELISA.Venom from E. ocellatus (blue bars), E. p. leakeyi (red bars), E. coloratus (green bars) and E. c. sochureki (purple bars) were incubated with serial dilutions (horizontal axis) of IgG antisera raised against E. ocellatus (A), E. p. leakeyi (B), E. coloratus (C) and E. c. sochureki (D) and the optical density determined (vertical axis).
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pntd-0000851-g003: Extensive cross-specific immunological reactivity between Echis venoms and Echis species-specific IgG antisera revealed by End Point Titration ELISA.Venom from E. ocellatus (blue bars), E. p. leakeyi (red bars), E. coloratus (green bars) and E. c. sochureki (purple bars) were incubated with serial dilutions (horizontal axis) of IgG antisera raised against E. ocellatus (A), E. p. leakeyi (B), E. coloratus (C) and E. c. sochureki (D) and the optical density determined (vertical axis).

Mentions: The immunogenicity of each Echis venom was assessed using the EPT ELISA assay to determine the IgG titre of each of the four Echis species-specific IgG antisera to each Echis venom (Figure 3A–D). The overall plateau and then decline of IgG titre after successive IgG dilution was strikingly similar for each of the IgG antisera; as reflected in the assigned EPT IgG titres (Table 1). The slightly slower decline of the E. coloratus venom-antisera profiles against each of the venoms (except the E. c. sochureki venom, Figure 3D) suggested that E. coloratus venom is perhaps more immunogenic than the other Echis venoms. Similarly, because the E. p. leakeyi IgG antisera showed the most rapid decline in IgG titre against its homologous and the heterologous venoms, it could be surmised that E. p. leakeyi venom is the least immunogenic. However, these differences were minor and we therefore caution against assigning much immunological significance to these observations.


Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom.

Casewell NR, Cook DA, Wagstaff SC, Nasidi A, Durfa N, Wüster W, Harrison RA - PLoS Negl Trop Dis (2010)

Extensive cross-specific immunological reactivity between Echis venoms and Echis species-specific IgG antisera revealed by End Point Titration ELISA.Venom from E. ocellatus (blue bars), E. p. leakeyi (red bars), E. coloratus (green bars) and E. c. sochureki (purple bars) were incubated with serial dilutions (horizontal axis) of IgG antisera raised against E. ocellatus (A), E. p. leakeyi (B), E. coloratus (C) and E. c. sochureki (D) and the optical density determined (vertical axis).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2964286&req=5

pntd-0000851-g003: Extensive cross-specific immunological reactivity between Echis venoms and Echis species-specific IgG antisera revealed by End Point Titration ELISA.Venom from E. ocellatus (blue bars), E. p. leakeyi (red bars), E. coloratus (green bars) and E. c. sochureki (purple bars) were incubated with serial dilutions (horizontal axis) of IgG antisera raised against E. ocellatus (A), E. p. leakeyi (B), E. coloratus (C) and E. c. sochureki (D) and the optical density determined (vertical axis).
Mentions: The immunogenicity of each Echis venom was assessed using the EPT ELISA assay to determine the IgG titre of each of the four Echis species-specific IgG antisera to each Echis venom (Figure 3A–D). The overall plateau and then decline of IgG titre after successive IgG dilution was strikingly similar for each of the IgG antisera; as reflected in the assigned EPT IgG titres (Table 1). The slightly slower decline of the E. coloratus venom-antisera profiles against each of the venoms (except the E. c. sochureki venom, Figure 3D) suggested that E. coloratus venom is perhaps more immunogenic than the other Echis venoms. Similarly, because the E. p. leakeyi IgG antisera showed the most rapid decline in IgG titre against its homologous and the heterologous venoms, it could be surmised that E. p. leakeyi venom is the least immunogenic. However, these differences were minor and we therefore caution against assigning much immunological significance to these observations.

Bottom Line: Using WHO standard pre-clinical in vivo tests, we determined that the monospecific EchiTAbG antivenom was as effective at neutralising the venom-induced lethal effects of E. pyramidum leakeyi and E. coloratus as it was against E. ocellatus venom.Under the restricted conditions of this assay, the antivenom was ineffective against the lethal effects of venom from the non-African Echis species, E. carinatus sochureki.Using WHO-recommended pre-clinical tests we have demonstrated that the new anti-E. ocellatus monospecific antivenom EchiTAbG, developed in response to the considerable snakebite-induced mortality and morbidity in Nigeria, neutralised the lethal effects of venoms from Echis species representing each taxonomic group of this genus in Africa.

View Article: PubMed Central - PubMed

Affiliation: Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

ABSTRACT

Background: Snakebite is a significant cause of death and disability in subsistent farming populations of sub-Saharan Africa. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses/sheep but, because of complex fiscal reasons, there is a paucity of antivenom in sub-Saharan Africa. To address the plight of thousands of snakebite victims in savannah Nigeria, the EchiTAb Study Group organised the production, testing and delivery of antivenoms designed to treat envenoming by the most medically-important snakes in the region. The Echis saw-scaled vipers have a wide African distribution and medical importance. In an effort to maximise the clinical utility of scarce antivenom resources in Africa, we aimed to ascertain, at the pre-clinical level, to what extent the E. ocellatus-specific EchiTAbG antivenom, which was designed specifically for Nigeria, neutralised the lethal activity of venom from two other African species, E. pyramidum leakeyi and E. coloratus.

Methodology/principal findings: Despite apparently quite distinctive venom protein profiles, we observed extensive cross-species similarity in the immuno-reactivity profiles of Echis species-specific antisera. Using WHO standard pre-clinical in vivo tests, we determined that the monospecific EchiTAbG antivenom was as effective at neutralising the venom-induced lethal effects of E. pyramidum leakeyi and E. coloratus as it was against E. ocellatus venom. Under the restricted conditions of this assay, the antivenom was ineffective against the lethal effects of venom from the non-African Echis species, E. carinatus sochureki.

Conclusions/significance: Using WHO-recommended pre-clinical tests we have demonstrated that the new anti-E. ocellatus monospecific antivenom EchiTAbG, developed in response to the considerable snakebite-induced mortality and morbidity in Nigeria, neutralised the lethal effects of venoms from Echis species representing each taxonomic group of this genus in Africa. This suggests that this monospecific antivenom has potential to treat envenoming by most, perhaps all, African Echis species.

Show MeSH
Related in: MedlinePlus