TY - UNPB

T1 - Preclinical Evaluation of the Neutralising Efficacy of Three Monospecific Antivenoms Against the Venoms of Five African Echis Species, Including the Recently Partitioned E. ocellatus and E. romani

AU - Edge, Rebecca J.

AU - Marriott, Amy E.

AU - Keen, Molly

AU - Xie, Tiffany

AU - Crittenden, Edouard

AU - Dawson, Charlotte A.

AU - Wilkinson, Mark C.

AU - Wüster, Wolfgang

AU - Casewell, Nicholas R.

AU - Ainsworth, Stuart

AU - Menzies, Stefanie K.

PY - 2024/3/19

Y1 - 2024/3/19

N2 - Background: The genus Echis is of high medical importance across Africa. Recently the taxonomy of its most medically important species, Echis ocellatus, underwent a revision, resulting in a splitting of the species into E. romani and E. ocellatus, and leading to uncertainty of the efficacy of antivenoms indicated for treatment of ‘E. ocellatus’ envenomings against the two redefined species.Methods: We compared the in vitro and murine preclinical venom-neutralising efficacy of three antivenoms (EchiTAbG, SAIMR Echis and Echiven) raised against E. ocellatus sensu lato against the venoms of E. romani and E. ocellatus, and investigated cross-reactivity to E. coloratus, E. leucogaster, and E. pyramidum leakeyi.Findings: In preclinical assays of envenoming, all three antivenoms neutralised Nigerian E. romani venom, though all three were less protective against Cameroonian E. romani. SAIMR Echis and Echiven neutralised E. ocellatus venom whereas EchiTAbG was less protective. SAIMR Echis and Echiven showed strong cross-reactivity to E. p. leakeyi and E. leucogaster, whilst EchiTAbG showed weaker cross-reactivity. All three antivenoms exhibited poor neutralisation of E. coloratus venom.Interpretation: This represents the first detailed analysis of differences between E. ocellatus and E. romani venom bioactivities and the impact of antivenom on these two species. Our findings demonstrate that SAIMR Echis and Echiven antivenoms are preclinically efficacious against the lethal effects of several species of Echis. These products, in addition to EchiTAbG, seem likely to meet the WHO recommendation of three antivenoms required for treatment of Echis envenomings across sub-Saharan Africa, though clinical evidence is required to confirm these findings.

AB - Background: The genus Echis is of high medical importance across Africa. Recently the taxonomy of its most medically important species, Echis ocellatus, underwent a revision, resulting in a splitting of the species into E. romani and E. ocellatus, and leading to uncertainty of the efficacy of antivenoms indicated for treatment of ‘E. ocellatus’ envenomings against the two redefined species.Methods: We compared the in vitro and murine preclinical venom-neutralising efficacy of three antivenoms (EchiTAbG, SAIMR Echis and Echiven) raised against E. ocellatus sensu lato against the venoms of E. romani and E. ocellatus, and investigated cross-reactivity to E. coloratus, E. leucogaster, and E. pyramidum leakeyi.Findings: In preclinical assays of envenoming, all three antivenoms neutralised Nigerian E. romani venom, though all three were less protective against Cameroonian E. romani. SAIMR Echis and Echiven neutralised E. ocellatus venom whereas EchiTAbG was less protective. SAIMR Echis and Echiven showed strong cross-reactivity to E. p. leakeyi and E. leucogaster, whilst EchiTAbG showed weaker cross-reactivity. All three antivenoms exhibited poor neutralisation of E. coloratus venom.Interpretation: This represents the first detailed analysis of differences between E. ocellatus and E. romani venom bioactivities and the impact of antivenom on these two species. Our findings demonstrate that SAIMR Echis and Echiven antivenoms are preclinically efficacious against the lethal effects of several species of Echis. These products, in addition to EchiTAbG, seem likely to meet the WHO recommendation of three antivenoms required for treatment of Echis envenomings across sub-Saharan Africa, though clinical evidence is required to confirm these findings.

KW - Snakebite envenoming

KW - Antivenom

KW - Echis

KW - Venom

KW - Preclinical

U2 - 10.2139/ssrn.4763108

DO - 10.2139/ssrn.4763108

M3 - Preprint

SP - 1

BT - Preclinical Evaluation of the Neutralising Efficacy of Three Monospecific Antivenoms Against the Venoms of Five African Echis Species, Including the Recently Partitioned E. ocellatus and E. romani

PB - Social Science Research Network (SSRN)

ER -