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Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing

BACKGROUND: Snakebite is a major public health concern in Eswatini, where treatment relies upon one antivenom—SAIMR Polyvalent. Although effective in treating snakebite, SAIMR Polyvalent is difficult to source outside its manufacturing country (South Africa) and is dauntingly expensive. We compared...

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Autores principales: Menzies, Stefanie K., Litschka-Koen, Thea, Edge, Rebecca J., Alsolaiss, Jaffer, Crittenden, Edouard, Hall, Steven R., Westhorpe, Adam, Thomas, Brent, Murray, James, Shongwe, Nondusimo, Padidar, Sara, Lalloo, David G., Casewell, Nicholas R., Pons, Jonathan, Harrison, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529146/
https://www.ncbi.nlm.nih.gov/pubmed/36108067
http://dx.doi.org/10.1371/journal.pntd.0010496
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author Menzies, Stefanie K.
Litschka-Koen, Thea
Edge, Rebecca J.
Alsolaiss, Jaffer
Crittenden, Edouard
Hall, Steven R.
Westhorpe, Adam
Thomas, Brent
Murray, James
Shongwe, Nondusimo
Padidar, Sara
Lalloo, David G.
Casewell, Nicholas R.
Pons, Jonathan
Harrison, Robert A.
author_facet Menzies, Stefanie K.
Litschka-Koen, Thea
Edge, Rebecca J.
Alsolaiss, Jaffer
Crittenden, Edouard
Hall, Steven R.
Westhorpe, Adam
Thomas, Brent
Murray, James
Shongwe, Nondusimo
Padidar, Sara
Lalloo, David G.
Casewell, Nicholas R.
Pons, Jonathan
Harrison, Robert A.
author_sort Menzies, Stefanie K.
collection PubMed
description BACKGROUND: Snakebite is a major public health concern in Eswatini, where treatment relies upon one antivenom—SAIMR Polyvalent. Although effective in treating snakebite, SAIMR Polyvalent is difficult to source outside its manufacturing country (South Africa) and is dauntingly expensive. We compared the preclinical venom-neutralising efficacy of two alternative antivenoms with that of SAIMR Polyvalent against the lethal and tissue-destructive effects of venoms from five species of medically important snakes using in vivo murine assays. The test antivenoms were ‘Panafrican’ manufactured by Instituto Clodomiro Picado and ‘PANAF’ manufactured by Premium Serums & Vaccines. PRINCIPAL FINDINGS: In vivo murine preclinical studies identified both test antivenoms were equally or more effective than SAIMR Polyvalent at neutralising lethal and tissue-destructive effects of Naja mossambica venom. Both test antivenoms were less effective than SAIMR Polyvalent at neutralising the lethal effects of Bitis arietans, Dendroaspis polylepis, Hemachatus haemachatus and Naja annulifera venoms, but similarly effective at neutralising tissue damage induced by B. arietans and H. haemachatus venoms. In vitro immunological assays identified that the titres and toxin-specificities of immunoglobulins (iGs) in the test antivenoms were comparable to that of SAIMR Polyvalent. Plasma clotting disturbances by H. haemachatus and N. mossambica were neutralised by the test antivenoms, whereas SAIMR Polyvalent failed to neutralise this bioactivity of N. mossambica venom. B. arietans SVMP activity was equally reduced by all three antivenoms, and H. haemachatus and N. mossambica PLA(2) activities were neutralised by all three antivenoms. CONCLUSIONS: While both Panafrican and PANAF antivenoms exhibited promising preclinical efficacies, both were less poly-specifically effective than SAIMR Polyvalent in these murine assays. The efficacy of these antivenoms against the lethal and tissue-destructive effects of N. mossambica venom, the most common biting species in Eswatini, identify that Panafrican and PANAF antivenoms offer effective alternatives to SAIMR Polyvalent for the treatment of snakebite in Eswatini, and potentially for neighbouring countries.
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spelling pubmed-95291462022-10-04 Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing Menzies, Stefanie K. Litschka-Koen, Thea Edge, Rebecca J. Alsolaiss, Jaffer Crittenden, Edouard Hall, Steven R. Westhorpe, Adam Thomas, Brent Murray, James Shongwe, Nondusimo Padidar, Sara Lalloo, David G. Casewell, Nicholas R. Pons, Jonathan Harrison, Robert A. PLoS Negl Trop Dis Research Article BACKGROUND: Snakebite is a major public health concern in Eswatini, where treatment relies upon one antivenom—SAIMR Polyvalent. Although effective in treating snakebite, SAIMR Polyvalent is difficult to source outside its manufacturing country (South Africa) and is dauntingly expensive. We compared the preclinical venom-neutralising efficacy of two alternative antivenoms with that of SAIMR Polyvalent against the lethal and tissue-destructive effects of venoms from five species of medically important snakes using in vivo murine assays. The test antivenoms were ‘Panafrican’ manufactured by Instituto Clodomiro Picado and ‘PANAF’ manufactured by Premium Serums & Vaccines. PRINCIPAL FINDINGS: In vivo murine preclinical studies identified both test antivenoms were equally or more effective than SAIMR Polyvalent at neutralising lethal and tissue-destructive effects of Naja mossambica venom. Both test antivenoms were less effective than SAIMR Polyvalent at neutralising the lethal effects of Bitis arietans, Dendroaspis polylepis, Hemachatus haemachatus and Naja annulifera venoms, but similarly effective at neutralising tissue damage induced by B. arietans and H. haemachatus venoms. In vitro immunological assays identified that the titres and toxin-specificities of immunoglobulins (iGs) in the test antivenoms were comparable to that of SAIMR Polyvalent. Plasma clotting disturbances by H. haemachatus and N. mossambica were neutralised by the test antivenoms, whereas SAIMR Polyvalent failed to neutralise this bioactivity of N. mossambica venom. B. arietans SVMP activity was equally reduced by all three antivenoms, and H. haemachatus and N. mossambica PLA(2) activities were neutralised by all three antivenoms. CONCLUSIONS: While both Panafrican and PANAF antivenoms exhibited promising preclinical efficacies, both were less poly-specifically effective than SAIMR Polyvalent in these murine assays. The efficacy of these antivenoms against the lethal and tissue-destructive effects of N. mossambica venom, the most common biting species in Eswatini, identify that Panafrican and PANAF antivenoms offer effective alternatives to SAIMR Polyvalent for the treatment of snakebite in Eswatini, and potentially for neighbouring countries. Public Library of Science 2022-09-15 /pmc/articles/PMC9529146/ /pubmed/36108067 http://dx.doi.org/10.1371/journal.pntd.0010496 Text en © 2022 Menzies et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Menzies, Stefanie K.
Litschka-Koen, Thea
Edge, Rebecca J.
Alsolaiss, Jaffer
Crittenden, Edouard
Hall, Steven R.
Westhorpe, Adam
Thomas, Brent
Murray, James
Shongwe, Nondusimo
Padidar, Sara
Lalloo, David G.
Casewell, Nicholas R.
Pons, Jonathan
Harrison, Robert A.
Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing
title Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing
title_full Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing
title_fullStr Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing
title_full_unstemmed Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing
title_short Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing
title_sort two snakebite antivenoms have potential to reduce eswatini’s dependency upon a single, increasingly unavailable product: results of preclinical efficacy testing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529146/
https://www.ncbi.nlm.nih.gov/pubmed/36108067
http://dx.doi.org/10.1371/journal.pntd.0010496
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