Medical Management after Lancehead Snakebite in North Amazon: A Case Report of Long-Term Disability

Oliveira, Isadora Sousa de; Ananias, Carla B.; Medeiros, Jilvando M.; Franco, Michelle V. S.; Ferreira, Isabela Gobbo; Cerni, Felipe Augusto; Sandri, Eliseu Adilson; Monteiro, Wuelton Marcelo; Pucca, Manuela Berto

doi:10.3390/toxins14070494

Cited by 8 publications

(11 citation statements)

References 26 publications

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“…Snakebite can result in catastrophic healthcare expenditure, as well as subsequent loss of livelihood, due to the loss or incapacitation of the primary earner in a household ( Herzel et al, 2018 ; Harrison et al, 2019 ). In addition, the psychological impact of surviving a snakebite and related socio-economic implications (e.g., social stigma, ostracization and loss of time in education) can cause substantial long-term impacts on individuals and their families ( Williams et al, 2011a ; Harrison et al, 2019 ; Kasturiratne et al, 2021 ; Oliveira et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Snakebite drug discovery: high-throughput screening to identify novel snake venom metalloproteinase toxin inhibitors

Clare,

Dawson,

Westhorpe

et al. 2024

Front. Pharmacol.

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Snakebite envenoming results in ∼100,000 deaths per year, with close to four times as many victims left with life-long sequelae. Current antivenom therapies have several limitations including high cost, variable cross-snake species efficacy and a requirement for intravenous administration in a clinical setting. Next-generation snakebite therapies are being widely investigated with the aim to improve cost, efficacy, and safety. In recent years several small molecule drugs have shown considerable promise for snakebite indication, with oral bioavailability particularly promising for community delivery rapidly after a snakebite. However, only two such drugs have entered clinical development for snakebite. To offset the risk of attrition during clinical trials and to better explore the chemical space for small molecule venom toxin inhibitors, here we describe the first high throughput drug screen against snake venom metalloproteinases (SVMPs)—a pathogenic toxin family responsible for causing haemorrhage and coagulopathy. Following validation of a 384-well fluorescent enzymatic assay, we screened a repurposed drug library of 3,547 compounds against five geographically distinct and toxin variable snake venoms. Our drug screen resulted in the identification of 14 compounds with pan-species inhibitory activity. Following secondary potency testing, four SVMP inhibitors were identified with nanomolar EC50s comparable to the previously identified matrix metalloproteinase inhibitor marimastat and superior to the metal chelator dimercaprol, doubling the current global portfolio of SVMP inhibitors. Following analysis of their chemical structure and ADME properties, two hit-to-lead compounds were identified. These clear starting points for the initiation of medicinal chemistry campaigns provide the basis for the first ever designer snakebite specific small molecules.

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Section: Introductionmentioning

confidence: 99%

Snakebite drug discovery: high-throughput screening to identify novel snake venom metalloproteinase toxin inhibitors

Clare,

Dawson,

Westhorpe

et al. 2024

Front. Pharmacol.

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“…Snakebite envenomations (SBEs) are considered an important public health problem ( 1 ). According to WHO, it is estimated that up to 2.7 million SBEs globally, resulting in approximately 400,000 disabilities, and 80,000 to 140,000 deaths per year ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

“…As other lancehead venoms, B. atrox venom cocktail presents proteolytic, coagulant, and hemorrhagic activities ( 5 ), resulting in hemostatic disturbances and tissue damage ( 6 ). Hemostatic disturbances can induce coagulopathies clinically manifested as hemorrhages and ecchymosis ( 1 , 6 ). Bleedings may occur mostly by metalloprotease-induced activity ( 7 , 8 ), promoting disturbances in the coagulation through factor X, II, and II activation, or indirectly, by factor VII activation ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

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Acute mesenteric ischemia following lancehead snakebite: an unusual case report in the Northernmost Brazilian Amazon

Galan

Silva

et al. 2023

Front. Med.

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Snakebites have a great impact in the Brazilian Amazon, being the lancehead Bothrops atrox the species responsible for most accidents, disabilities, and deaths. This study shows a case report of an indigenous patient from the Yanomami ethnicity, male, 33 years-old, envenomed by a B. atrox snake. Envenoming caused by B. atrox are characterized by local manifestations (e.g., pain and edema) and systemic manifestations, mainly coagulation disorders. The indigenous victim was admitted in the main hospital of Roraima and evolved with an unusual complication, an ischemia and necrosis of the proximal ileum, requiring segmental enterectomy with posterior side-to-side anastomosis. The victim was discharge after 27 days of hospitalization with no complaints. Snakebite envenomations may evolve with life-threatening complications, which can be treated by the antivenom following access to a healthcare unit, often late in indigenous population. This clinical case shows the need of strategies that aim improvement in the access to the healthcare by indigenous people, as well as demonstrates an unusual complication that may result from lancehead snakebites. The article also discusses the decentralization of snakebites clinical management to indigenous community healthcare centers to mitigate complications.

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“…These effects manifest themselves clinically in signs and symptoms such as pain, swelling, regional lymphadenopathy, ecchymosis, blistering, and necrosis [ 19 ]. Severe cases can progress to compartment syndrome, atrophy, loss of limb function and even amputation [ 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Children Growing Up with Severe Disabilities as a Result of Snakebite Envenomations in Indigenous Villages of the Brazilian Amazon: Three Cases and Narratives

Farias

Cristino

Arévalo³

et al. 2023

Toxins

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Snakebites are a major public health problem in the Brazilian Amazon and may lead to local complications and physical deficiencies. Access to antivenom treatment is poorer in indigenous populations compared to other populations. In this study, we report three cases of long-term severe disabilities as a result of Bothrops atrox snakebites in indigenous children, according to the narratives of the parents. The three cases evolved to compartment syndrome, secondary bacterial infection and extensive necrosis. The cases are associated with delayed antivenom treatment due to very fragmented therapeutic itineraries, which are marked by several changes in means of transport along the route. The loss of autonomy at such an early stage of life due to a disability caused by a snakebite, as observed in this study, may deprive children of sensory and social experiences and of learning their future roles in the community. In common to all cases, there was precarious access to rehabilitation services, which are generally centralized in the state capital, and which leads to a prolonged hospitalization of patients with severe snakebite, and distances them from their territory and family and community ties. Prospective studies should be conducted in the Amazon that estimate the burden of disabilities from snakebites in order to formulate public policies for the treatment and rehabilitation of patients through culturally tailored interventions.

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Medical Management after Lancehead Snakebite in North Amazon: A Case Report of Long-Term Disability

Cited by 8 publications

References 26 publications

Snakebite drug discovery: high-throughput screening to identify novel snake venom metalloproteinase toxin inhibitors

Snakebite drug discovery: high-throughput screening to identify novel snake venom metalloproteinase toxin inhibitors

Acute mesenteric ischemia following lancehead snakebite: an unusual case report in the Northernmost Brazilian Amazon

Children Growing Up with Severe Disabilities as a Result of Snakebite Envenomations in Indigenous Villages of the Brazilian Amazon: Three Cases and Narratives

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