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A supervised machine learning statistical design of experiment approach to modeling the barriers to effective snakebite treatment in Ghana
(2024-12-13) Nyarko, Eric; Fosu Agyemang, Edmund; Ameho, Ebenezer Kwesi; Agyekum, Louis; Gutiérrez Gutiérrez, José María; Fernandez, Eduardo Alberto
Snakebite envenoming, a severe condition, affects 2.5 million people and causes 81,000–138,000 deaths annually, particularly in tropical and subtropical regions of Africa, Asia, and Latin America. The World Health Organization aims to reduce this burden by 50% by 2030. However, significant barriers exist to achieving these targets, especially in Sub-Saharan Africa. These barriers include limited rigorous research evidence and the lack of investment in effective antivenoms for local snake species. Meeting this goal will require innovative research to gather better data on snakebite incidence and treatment. Artificial intelligence is one promising field that can contribute to this effort. For the first time, we have demonstrated how MaxDiff statistical experiment designs and machine learning algorithms can be explored to predict the barriers to effective snakebite treatment, such as the high cost of antivenoms, increased use of harmful practices, lack of access to effective antivenoms in remote areas, and resorting to unorthodox and harmful practices in addition to hospital treatment. Addressing these barriers through targeted policy interventions, including intensified advocacy, continuous education, community engagement, healthcare worker training, and strategic investments, can enhance the effectiveness of snakebite treatment. Robust regulatory frameworks and increased local antivenom production are also needed to address these barriers.
Characterization of α-Neurotoxin and Phospholipase A2 Activities from Micrurus Venoms
(2024-08-31) Rosso, Jean-Pierre; Vargas-Rosso, Orietta; Gutiérrez Gutiérrez, José María; Rochat, Hervé; Bougis, Pierre E.
New World elapids are coral snakes that belong to the genus Micrurus, and for which the venom biochemistry is mostly unknown. Analysis has been difficult because the coral snakes produce small quantities of venom. Clinical observations following bites show mainly neurotoxic effects. Experimentally, cardiotoxic, haemolytic and myotoxic activities are also reported. An experimental approach, using reverse-phase high-performance liquid chromatography and specific assays for α-neurotoxin and phospholipase A2 activities, was conducted on milligram quantities of venoms from three Micrurus species from Costa Rica; M. nigrocinctus nigrocinctus, M. alleni yatesi and M. multifasciatus. Neurotoxicity was determined by competition binding experiments with the Torpedo marmorata acetylcholine receptor. Phospholipase A2 activity was measured by fluorimetry using a pyrene lipid substrate. In this way, we purified and characterized seven α-neurotoxins, five phospholipases A2 and four toxin homologs. The amino acid sequence of the major α-neurotoxin from M. nigrocinctus nigrocinctus venom was fully determined and compared to Old Word representatives. Distance matrix data were generated to set up phylogeny relationships among elapid short-chain α-neurotoxins, which proved to be in accordance with the taxonomic classification and geographical distribution of snake species.
Enzyme immunoassays for detection and quantification of venoms of Sri Lankan snakes: application in the clinical setting
(2020-10-05) Maduwage, Kalana Prasad; Gawarammana, Indika Bandara; Gutiérrez Gutiérrez, José María; Kottege, Chaminda; Dayaratne, Rohana; Premawardena, Nuwan Prasada; Jayasingha, Sujeewa
Snakebite is a major medical and public health problem in tropical agricultural world. Detection of the type of snake venom and measurement of venom levels in blood are important for snakebite research, selecting the appropriate antivenom, and assessing venom levels in blood at the clinical setting. Currently, a snake venom detection platform is not available in clinical practice in Sri Lanka. This study aimed to develop a double sandwich enzyme immunoassays (EIA) to differentiate and quantify venoms of Russell’s viper (Daboia russelii), saw-scaled viper (Echis carinatus), common cobra (Naja naja), Indian krait (Bungarus caeruleus), and hump-nosed pit viper (Hypnale hypnale) in blood samples of envenomed patients in Sri Lanka. The EIA developed used biotin-streptavidin amplification for detection of venom antigens and showed high analytical sensitivity. The assay allowed the quantification of venoms of the five species in blood samples from envenomed patients. Low level of cross reactivity was noted between species, except in the case of closely related Hypnale species. The presence of D. russelii venom after antivenom treatment is reported, a finding that has implications in the dosing of antivenom in these envenomings. Lack of specific antivenom for H. hypnale envenoming offered an opportunity of study the remaining venom antigen in circulation up to 24 hr post bite. The EIA developed constitutes a useful tool to detect and quantify the five types of Sri Lankan snake venoms, and should be useful for research purposes, as well as for the diagnosis and therapy evaluation of clinical cases of envenomings in this country, and for forensic purposes.
Platelets support a protective immune response to LCMV by preventing splenic necrosis
(2013) David Loria, Gilbert; Romagnoli, Pablo Alberto; Moseley, Nelson B.; Rucavado Romero,; Altman, John D.
Severe arenaviral infections in humans are characterized by clinical findings common to other viral hemorrhagic fevers (VHFs), including thrombocytopenia, leukopenia, skin and internal organ hemorrhages, high viral replication, splenic necrosis, and death. Host responses, rather than direct damage by the arenaviral replication, account for most of the observed pathology, but it is not known what protective roles platelets may have in each of the manifestations. To address this issue in an animal model, we compared nondepleted (100%), partially depleted (15%), and profoundly (< 2.5%) platelet-depletedmice infected with the mouse arenavirus lymphocytic choriomeningitis virus (LCMV). Here, we describe that systemic bleedings and death were seen only in those animals receiving the stronger depletion treatment. Furthermore, we showed that the nonhemorrhagic but partially platelet-depleted mice were unable to control the viral replication because of generalized splenic necrosis, affecting innate and adaptive immune cells. These data suggest that, by their supportive roles in hemostasis, platelets may be preventing the severe pathology observed in human arenaviral infections.
Neutralización de los efectos locales del veneno de Bothrops asper por un antiveneno polivalente
(1981-12) Gutiérrez Gutierrez, José Maria; Chaves Mora, Fernando A.; Bolaños Herrera, Róger; Cerdas Fallas, Luis; Rojas Umaña, Ermila Maria; Arroyo Gutierrez, Olga; Portilla Brizuela, Elsa
Neutralization of lethality, myonecrosis, hemorrhage and edema induced by Bothrops asper venom in mice was studied using the polyvalent antivenom produced in the Instituto Clodomiro Picado. The neutralizing effect (ed50) on each of these toxic activities varied; the neutralization of lethal and hemorrhagic effects being more effective than the neutralization of myonecrosis and edema. With independent inoculation of venom and antivenom, antivenom was not effective in neutralizing edema-forming activity. The myonecrotic effect was only partially neutralized when serum was given i.v. immediately after envenomation; however, antivenin effectively neutralized the hemorrhagic activity. The ineffectiveness of antivenom in neutralizing edema and myonecrosis could be partially explained by the rapid development of these effects. Hence, the time interval between envenomation and antivenom administration and the route of serum administration both play an important role in the neutralization of local effects.