Venomous Bites, Stings and Poisoning by European Vertebrates as an Overlooked and Emerging Medical Problem: Recognition, Clinical Aspects and Therapeutic Management

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Abstract

Europe presents a high number of venomous and poisonous animals able to elicit medically relevant symptoms in humans. However, since most of the accidents involving venomous or poisonous animals in Europe are unreported, their incidence and morbidity are severely overlooked. Here we provide an overview of the European vertebrate species of greatest toxicological interest, the clinical manifestations their toxins can cause, and their treatment. We report the clinical symptoms induced by envenomations and poisoning caused by reptiles, fishes, amphibians and mammals in Europe, ranging from mild, local symptoms (e.g., erythema, edema) to systemic and potentially deadly. The present work constitutes a tool for physicians to recognize envenomation/poisoning symptoms caused by the most medically relevant European vertebrates and to decide which approach is the most appropriate to treat them.

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Fishes of the World

Joseph Nelson, Terry Grande, Mark V. H. Wilson (2016)

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Vulnerability to snakebite envenoming: a global mapping of hotspots

Joshua Longbottom, Freya Shearer, Maria Devine … (2018)

Summary Background Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed. Methods We assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but <5 species occurrence records), and group C (EOR map and ≥5 species occurrence records). For group C species, we did a multivariate environmental similarity analysis using the 2008 WHO EOR maps and newly available evidence. Using these data and the EOR maps, we produced contemporary range maps for medically important venomous snake species at a 5 × 5 km resolution. We subsequently triangulated these data with three health system metrics (antivenom availability, accessibility to urban centres, and the Healthcare Access and Quality [HAQ] Index) to identify the populations most vulnerable to snakebite morbidity and mortality. Findings We provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within the lowest decile are at risk of exposure to any snake for which no effective therapy exists compared with 519·46 million individuals (27·79%) within the highest HAQ Index decile, showing a disproportionate coverage in reported antivenom availability. Antivenoms were available for 119 (43%) of 278 snake species evaluated by WHO, while globally 750·19 million (10·95%) of those living within snake ranges live more than 1 h from population centres. In total, we identify about 92·66 million people living within these vulnerable geographies, including many sub-Saharan countries, Indonesia, and other parts of southeast Asia. Interpretation Identifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease. Funding Bill & Melinda Gates Foundation.

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The ADAM metalloproteinases

Dylan R. Edwards, Madeleine Handsley, Caroline Pennington (2008)

The ADAMs (a disintegrin and metalloproteinase) are a fascinating family of transmembrane and secreted proteins with important roles in regulating cell phenotype via their effects on cell adhesion, migration, proteolysis and signalling. Though all ADAMs contain metalloproteinase domains, in humans only 13 of the 21 genes in the family encode functional proteases, indicating that at least for the other eight members, protein–protein interactions are critical aspects of their biological functions. The functional ADAM metalloproteinases are involved in “ectodomain shedding” of diverse growth factors, cytokines, receptors and adhesion molecules. The archetypal activity is shown by ADAM-17 (tumour necrosis factor-α convertase, TACE), which is the principal protease involved in the activation of pro-TNF-α, but whose sheddase functions cover a broad range of cell surface molecules. In particular, ADAM-17 is required for generation of the active forms of Epidermal Growth Factor Receptor (EGFR) ligands, and its function is essential for the development of epithelial tissues. Several other ADAMs have important sheddase functions in particular tissue contexts. Another major family member, ADAM-10, is a principal player in signalling via the Notch and Eph/ephrin pathways. For a growing number of substrates, foremost among them being Notch, cleavage by ADAM sheddases is essential for their subsequent “regulated intramembrane proteolysis” (RIP), which generates cleaved intracellular domains that translocate to the nucleus and regulate gene transcription. Several ADAMs play roles in spermatogenesis and sperm function, potentially by effecting maturation of sperm and their adhesion and migration in the uterus. Other non-catalytic ADAMs function in the CNS via effects on guidance mechanisms. The ADAM family are thus fundamental to many control processes in development and homeostasis, and unsurprisingly they are also linked to pathological states when their functions are dysregulated, including cancer, cardiovascular disease, asthma, Alzheimer’s disease. This review will provide an overview of current knowledge of the human ADAMs, discussing their structure, function, regulation and disease involvement.

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Matteo Riccardo Di Nicola: (View ORCID Profile)

Ignazio Avella: (View ORCID Profile)

Journal

Journal ID (publisher-id): LBSIB7

Title: Life

Abbreviated Title: Life

Publisher: MDPI AG

ISSN (Electronic): 2075-1729

Publication date Created: June 2023

Publication date (Electronic): May 23 2023

Volume: 13

Issue: 6

Page: 1228

Article

DOI: 10.3390/life13061228

PMC ID: 10305571

PubMed ID: 37374011

SO-VID: 56932775-af77-49e8-abbb-187a3ee8e74d

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https://creativecommons.org/licenses/by/4.0/

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Venomous Bites, Stings and Poisoning by European Vertebrates as an Overlooked and Emerging Medical Problem: Recognition, Clinical Aspects and Therapeutic Management

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Most cited references 156

Fishes of the World

Vulnerability to snakebite envenoming: a global mapping of hotspots

The ADAM metalloproteinases

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