Clinical management of snakebite envenoming: Future perspectives

Abstract

Snakebite envenoming is a major cause of morbidity and mortality in rural communities throughout the tropics. Generally, the main clinical features of snakebites are local swelling, tissue necrosis, shock, spontaneous systemic hemorrhage, incoagulable blood, paralysis, rhabdomyolysis, and acute kidney injury. These clinical manifestations result from complex biochemical venom constituents comprising of cytotoxins, hemotoxins, neurotoxins, myotoxins, and other substances. Timely diagnosis of envenoming and identification of the responsible snake species is clinically challenging in many parts of the world and necessitates prompt and thorough clinical assessment, which could be supported by the development of reliable, affordable, widely-accessible, point-of-care tests. Conventional antivenoms based on polyclonal antibodies derived from animals remain the mainstay of therapy along with supportive medical and surgical care. However, while antivenoms save countless lives, they are associated with adverse reactions, limited potency, and are relatively inefficacious against presynaptic neurotoxicity and in preventing necrosis. Nevertheless, major scientific and technological advances are facilitating the development of new molecular and immunologic diagnostic tests, as well as a new generation of antivenoms comprising human monoclonal antibodies with broader and more potent neutralization capacity and less immunogenicity. Repurposed pharmaceuticals based on small molecule inhibitors (e.g., marimastat and varespladib) used alone and in combination against enzymatic toxins, such as metalloproteases and phospholipase A 2 s, have shown promise in animal studies. These orally bioavailable molecules could serve as early interventions in the out-of-hospital setting if confirmed to be safe and efficacious in clinical studies. Antivenom access can be improved by the usage of drones and ensuring constant antivenom supply in remote endemic rural areas. Overall, the improvement of clinical management of snakebite envenoming requires sustained, coordinated, and multifaceted efforts involving basic and applied sciences, new technology, product development, effective clinical training, implementation of existing guidelines and therapeutic approaches, supported by improved supply of existing antivenoms.

Aspectos clínicos y terapéuticos del accidente ofídico en hospitales nacionales de Guatemala

“…La secuela más frecuente en los pacientes tratados en el HRE fue la rabdomiólisis (siete casos de 169 = 4.14 %). La rabdomiólisis es el daño al tejido muscular, causado principalmente por las miotoxinas presentes en los venenos de las víboras (Aye et al, 2017;Hamza et al, 2021). Otras secuelas menos comunes presentadas por pacientes atendidos en el HRE fueron síndromes compartimentales, necrosis y fasciotomías terapéuticas.…”

Discovery of a broadly-neutralizing human antibody that can rescue mice challenged with neurotoxin-rich snake venoms

“…Each year, snakebite envenoming exacts a high death toll and leaves hundreds of thousands of other victims maimed for life 1 . Antivenoms based on polyclonal antibodies isolated from the plasma of immunized animals are currently the only specific treatment option against severe envenomings 2,3 . While these medicines are essential and life-saving, and will remain a cornerstone in snakebite therapy for years to come, an opportunity now exists to modernize treatment by exploiting the benefits of recombinant DNA and antibody technology 4 .…”

Prototyping of a lateral flow assay based on monoclonal antibodies for detection of Bothrops venoms

“…However, the presence of such effects cannot be used to confirm a lachetic envenoming, equally, their absence cannot be used to exclude it [6]. These overlapping syndromes can complicate matters for healthcare providers trying to identify the optimal treatment, especially as not all healthcare providers have received adequate training in clinical snakebite management [9]. This is unfortunate, as early and correct treatment has been shown to correlate with better patient outcomes for snakebite victims both in Brazil and abroad [10][11][12][13][14].…”