Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.

Background Antivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high cos...

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Published in:PLOS Neglected Tropical Diseases
Main Authors: Robert A Harrison, George O Oluoch, Stuart Ainsworth, Jaffer Alsolaiss, Fiona Bolton, Ana-Silvia Arias, José-María Gutiérrez, Paul Rowley, Stephen Kalya, Hastings Ozwara, Nicholas R Casewell
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2017
Subjects:
Online Access:https://doi.org/10.1371/journal.pntd.0005969
https://doaj.org/article/6290f15992bb4bf1a83af208945cf200
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spelling ftdoajarticles:oai:doaj.org/article:6290f15992bb4bf1a83af208945cf200 2023-05-15T15:16:35+02:00 Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa. Robert A Harrison George O Oluoch Stuart Ainsworth Jaffer Alsolaiss Fiona Bolton Ana-Silvia Arias José-María Gutiérrez Paul Rowley Stephen Kalya Hastings Ozwara Nicholas R Casewell 2017-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005969 https://doaj.org/article/6290f15992bb4bf1a83af208945cf200 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0005969 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005969 https://doaj.org/article/6290f15992bb4bf1a83af208945cf200 PLoS Neglected Tropical Diseases, Vol 11, Iss 10, p e0005969 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005969 2022-12-31T15:12:18Z Background Antivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high costs of the most polyspecifically-effective antivenoms have sequentially reduced demand, commercial manufacturing incentives and production volumes that have combined to create a continent-wide vacuum of effective snakebite therapy. This was quickly filled with new, less expensive antivenoms, many of which are of untested efficacy. Some of these successfully marketed antivenoms for Africa are inappropriately manufactured with venoms from non-African snakes and are dangerously ineffective. The uncertain efficacy of available antivenoms exacerbates the complexity of designing intervention measures to reduce the burden of snakebite in sub-Saharan Africa. The objective of this study was to preclinically determine the ability of antivenoms available in Kenya to neutralise the lethal effects of venoms from the most medically important snakes in East Africa. Methods We collected venom samples from the most medically important snakes in East Africa and determined their toxicity in a mouse model. Using a 'gold standard' comparison protocol, we preclinically tested the comparative venom-neutralising efficacy of four antivenoms available in Kenya with two antivenoms of clinically-proven efficacy. To explain the variant efficacies of these antivenoms we tested the IgG-venom binding characteristics of each antivenom using in vitro IgG titre, avidity and venom-protein specificity assays. We also measured the IgG concentration of each antivenom. Findings None of the six antivenoms are preclinically effective, at the doses tested, against all of the most medically important snakes of the region. The very limited snake polyspecific efficacy of two locally available antivenoms is of concern. In vitro assays of the abilities of 'test' ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 10 e0005969
institution Open Polar
collection Directory of Open Access Journals: DOAJ Articles
op_collection_id ftdoajarticles
language English
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Robert A Harrison
George O Oluoch
Stuart Ainsworth
Jaffer Alsolaiss
Fiona Bolton
Ana-Silvia Arias
José-María Gutiérrez
Paul Rowley
Stephen Kalya
Hastings Ozwara
Nicholas R Casewell
Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.
topic_facet Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
description Background Antivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high costs of the most polyspecifically-effective antivenoms have sequentially reduced demand, commercial manufacturing incentives and production volumes that have combined to create a continent-wide vacuum of effective snakebite therapy. This was quickly filled with new, less expensive antivenoms, many of which are of untested efficacy. Some of these successfully marketed antivenoms for Africa are inappropriately manufactured with venoms from non-African snakes and are dangerously ineffective. The uncertain efficacy of available antivenoms exacerbates the complexity of designing intervention measures to reduce the burden of snakebite in sub-Saharan Africa. The objective of this study was to preclinically determine the ability of antivenoms available in Kenya to neutralise the lethal effects of venoms from the most medically important snakes in East Africa. Methods We collected venom samples from the most medically important snakes in East Africa and determined their toxicity in a mouse model. Using a 'gold standard' comparison protocol, we preclinically tested the comparative venom-neutralising efficacy of four antivenoms available in Kenya with two antivenoms of clinically-proven efficacy. To explain the variant efficacies of these antivenoms we tested the IgG-venom binding characteristics of each antivenom using in vitro IgG titre, avidity and venom-protein specificity assays. We also measured the IgG concentration of each antivenom. Findings None of the six antivenoms are preclinically effective, at the doses tested, against all of the most medically important snakes of the region. The very limited snake polyspecific efficacy of two locally available antivenoms is of concern. In vitro assays of the abilities of 'test' ...
format Article in Journal/Newspaper
author Robert A Harrison
George O Oluoch
Stuart Ainsworth
Jaffer Alsolaiss
Fiona Bolton
Ana-Silvia Arias
José-María Gutiérrez
Paul Rowley
Stephen Kalya
Hastings Ozwara
Nicholas R Casewell
author_facet Robert A Harrison
George O Oluoch
Stuart Ainsworth
Jaffer Alsolaiss
Fiona Bolton
Ana-Silvia Arias
José-María Gutiérrez
Paul Rowley
Stephen Kalya
Hastings Ozwara
Nicholas R Casewell
author_sort Robert A Harrison
title Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.
title_short Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.
title_full Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.
title_fullStr Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.
title_full_unstemmed Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.
title_sort preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in east africa.
publisher Public Library of Science (PLoS)
publishDate 2017
url https://doi.org/10.1371/journal.pntd.0005969
https://doaj.org/article/6290f15992bb4bf1a83af208945cf200
geographic Arctic
geographic_facet Arctic
genre Arctic
genre_facet Arctic
op_source PLoS Neglected Tropical Diseases, Vol 11, Iss 10, p e0005969 (2017)
op_relation https://doi.org/10.1371/journal.pntd.0005969
https://doaj.org/toc/1935-2727
https://doaj.org/toc/1935-2735
1935-2727
1935-2735
doi:10.1371/journal.pntd.0005969
https://doaj.org/article/6290f15992bb4bf1a83af208945cf200
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container_title PLOS Neglected Tropical Diseases
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