Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots.
Background Snakebite in India results in over 58,000 fatalities and a vast number of morbidities annually. The majority of these clinically severe envenomings are attributed to Russell's viper (Daboia russelii), which has a near pan-India distribution. Unfortunately, despite its medical signifi...
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ftdoajarticles:oai:doaj.org/article:587a6cc414954a13a3262a822baacd61 2023-05-15T15:12:47+02:00 Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. R R Senji Laxme Suyog Khochare Saurabh Attarde Vivek Suranse Ashwin Iyer Nicholas R Casewell Romulus Whitaker Gerard Martin Kartik Sunagar 2021-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009247 https://doaj.org/article/587a6cc414954a13a3262a822baacd61 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009247 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009247 https://doaj.org/article/587a6cc414954a13a3262a822baacd61 PLoS Neglected Tropical Diseases, Vol 15, Iss 3, p e0009247 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009247 2022-12-31T05:52:39Z Background Snakebite in India results in over 58,000 fatalities and a vast number of morbidities annually. The majority of these clinically severe envenomings are attributed to Russell's viper (Daboia russelii), which has a near pan-India distribution. Unfortunately, despite its medical significance, the influence of biogeography on the composition and potency of venom from disparate D. russelii populations, and the repercussions of venom variation on the neutralisation efficacy of marketed Indian antivenoms, remain elusive. Methods Here, we employ an integrative approach comprising proteomic characterisation, biochemical analyses, pharmacological assessment, and venom toxicity profiling to elucidate the influence of varying ecology and environment on the pan-Indian populations of D. russelii. We then conducted in vitro venom recognition experiments and in vivo neutralisation assays to evaluate the efficacy of the commercial Indian antivenoms against the geographically disparate D. russelii populations. Findings We reveal significant intraspecific variation in the composition, biochemical and pharmacological activities and potencies of D. russelii venoms sourced from five distinct biogeographic zones across India. Contrary to our understanding of the consequences of venom variation on the effectiveness of snakebite therapy, commercial antivenom exhibited surprisingly similar neutralisation potencies against the majority of the investigated populations, with the exception of low preclinical efficacy against the semi-arid population from northern India. However, the ability of Indian antivenoms to counter the severe morbid effects of Daboia envenoming remains to be evaluated. Conclusion The concerning lack of antivenom efficacy against the north Indian population of D. russelii, as well as against two other 'big four' snake species in nearby locations, underscores the pressing need to develop pan-India effective antivenoms with improved efficacy in high snakebite burden locales. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Indian PLOS Neglected Tropical Diseases 15 3 e0009247 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 R R Senji Laxme Suyog Khochare Saurabh Attarde Vivek Suranse Ashwin Iyer Nicholas R Casewell Romulus Whitaker Gerard Martin Kartik Sunagar Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Snakebite in India results in over 58,000 fatalities and a vast number of morbidities annually. The majority of these clinically severe envenomings are attributed to Russell's viper (Daboia russelii), which has a near pan-India distribution. Unfortunately, despite its medical significance, the influence of biogeography on the composition and potency of venom from disparate D. russelii populations, and the repercussions of venom variation on the neutralisation efficacy of marketed Indian antivenoms, remain elusive. Methods Here, we employ an integrative approach comprising proteomic characterisation, biochemical analyses, pharmacological assessment, and venom toxicity profiling to elucidate the influence of varying ecology and environment on the pan-Indian populations of D. russelii. We then conducted in vitro venom recognition experiments and in vivo neutralisation assays to evaluate the efficacy of the commercial Indian antivenoms against the geographically disparate D. russelii populations. Findings We reveal significant intraspecific variation in the composition, biochemical and pharmacological activities and potencies of D. russelii venoms sourced from five distinct biogeographic zones across India. Contrary to our understanding of the consequences of venom variation on the effectiveness of snakebite therapy, commercial antivenom exhibited surprisingly similar neutralisation potencies against the majority of the investigated populations, with the exception of low preclinical efficacy against the semi-arid population from northern India. However, the ability of Indian antivenoms to counter the severe morbid effects of Daboia envenoming remains to be evaluated. Conclusion The concerning lack of antivenom efficacy against the north Indian population of D. russelii, as well as against two other 'big four' snake species in nearby locations, underscores the pressing need to develop pan-India effective antivenoms with improved efficacy in high snakebite burden locales. |
format |
Article in Journal/Newspaper |
author |
R R Senji Laxme Suyog Khochare Saurabh Attarde Vivek Suranse Ashwin Iyer Nicholas R Casewell Romulus Whitaker Gerard Martin Kartik Sunagar |
author_facet |
R R Senji Laxme Suyog Khochare Saurabh Attarde Vivek Suranse Ashwin Iyer Nicholas R Casewell Romulus Whitaker Gerard Martin Kartik Sunagar |
author_sort |
R R Senji Laxme |
title |
Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. |
title_short |
Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. |
title_full |
Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. |
title_fullStr |
Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. |
title_full_unstemmed |
Biogeographic venom variation in Russell's viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. |
title_sort |
biogeographic venom variation in russell's viper (daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0009247 https://doaj.org/article/587a6cc414954a13a3262a822baacd61 |
geographic |
Arctic Indian |
geographic_facet |
Arctic Indian |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 3, p e0009247 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009247 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009247 https://doaj.org/article/587a6cc414954a13a3262a822baacd61 |
op_doi |
https://doi.org/10.1371/journal.pntd.0009247 |
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PLOS Neglected Tropical Diseases |
container_volume |
15 |
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3 |
container_start_page |
e0009247 |
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