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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

37 Pages Posted: 19 Mar 2024

See all articles by Rebecca J. Edge

Rebecca J. Edge

Liverpool School of Tropical Medicine

Amy E. Marriott

Liverpool School of Tropical Medicine

Molly Keen

Liverpool School of Tropical Medicine

Tiffany Xie

University of Tübingen

Edouard P. Crittenden

Liverpool School of Tropical Medicine

Charlotte A. Dawson

Liverpool School of Tropical Medicine

Mark C. Wilkinson

Liverpool School of Tropical Medicine

Wolgang Wüster

Bangor University

Nicholas R. Casewell

Liverpool School of Tropical Medicine

Stuart Ainsworth

Liverpool School of Tropical Medicine

Stefanie K. Menzies

Liverpool School of Tropical Medicine

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Abstract

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.

Funding: Horizon 2020 FET Open #899670, UKRI FLF grant MR/S03398X/1, Wellcome Trust grant 221712/Z/20/Z and NC3Rs grant NC/X001172/1.

Declaration of Interest: SKM and NRC communicated with the antivenom manufacturer VINS Bioproducts to obtain a sample of Echiven antivenom for testing. The antivenom manufacturer had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The Centre for Snakebite Research and Interventions (CSRI) at LSTM was historically involved in the development of EchiTAbG and EchiTAb-Plus0ICP antivenoms, though none of the authors from CSRI were directly involved in this work. NRC was previously employed by the manufacturer of EchiTAbG antivenom (MicroPharm, UK) between 2010 and 2012. NRC and CAD are currently collaborators of the EchiTAbG manufacturer MicroPharm, UK. Micropharm had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

Ethical Approval: Animal experiments were conducted under protocols approved by the Animal Welfare and Ethical Review Boards of the Liverpool School of Tropical Medicine and the University of Liverpool, and under project licence P24100D38 approved by the UK Home Office in accordance with the UK Animal (Scientific Procedures) Act 1986.

Keywords: Snakebite envenoming, Antivenom, Echis, Venom, Preclinical

Suggested Citation

Edge, Rebecca J. and Marriott, Amy E. and Keen, Molly and Xie, Tiffany and Crittenden, Edouard P. and Dawson, Charlotte A. and Wilkinson, Mark C. and Wüster, Wolgang and Casewell, Nicholas R. and Ainsworth, Stuart and Menzies, Stefanie K., 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. Available at SSRN: https://ssrn.com/abstract=4763108 or http://dx.doi.org/10.2139/ssrn.4763108

Rebecca J. Edge

Liverpool School of Tropical Medicine ( email )

Amy E. Marriott

Liverpool School of Tropical Medicine ( email )

Molly Keen

Liverpool School of Tropical Medicine ( email )

Liverpool
United Kingdom

Tiffany Xie

University of Tübingen ( email )

Edouard P. Crittenden

Liverpool School of Tropical Medicine ( email )

Liverpool
United Kingdom

Charlotte A. Dawson

Liverpool School of Tropical Medicine ( email )

Liverpool
United Kingdom

Mark C. Wilkinson

Liverpool School of Tropical Medicine ( email )

Liverpool
United Kingdom

Wolgang Wüster

Bangor University ( email )

King Edward VII Avenue Cardiff
WALES, CF10 3NS
United Kingdom

Nicholas R. Casewell

Liverpool School of Tropical Medicine ( email )

Liverpool
United Kingdom

Stuart Ainsworth

Liverpool School of Tropical Medicine ( email )

Stefanie K. Menzies (Contact Author)

Liverpool School of Tropical Medicine ( email )

Liverpool
United Kingdom