{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:13:11Z","timestamp":1792789991023,"version":"4.5.0"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T00:00:00Z","timestamp":1714780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SBS, Soci\u00e9t\u00e9 Belakhdim Services"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Scorpion envenomation poses a global public health issue, with an estimated 1,500,000 cases worldwide annually resulting in 2600 deaths. North Africa, particularly Morocco, experiences severe envenomations, mainly attributed to Androctonus mauretanicus and Buthus occitanus in Morocco, and Buthus occitanus and Androctonus australis hector in Algeria and Tunisia, with case numbers often underestimated. Current treatment relies mainly on symptomatic approaches, except in Morocco, where management is limited to symptomatic treatment due to controversies regarding specific treatment. In Morocco, between 30,000 and 50,000 scorpion envenomation cases are reported annually, leading to hundreds of deaths, mainly among children. Controversies among clinicians persist regarding the appropriate course of action, often limiting treatments to symptomatic measures. The absence of a specific antivenom for the venoms of the most lethal scorpions further exacerbates the situation. This study aims to address this gap by developing a monovalent antivenom against the endemic and most dangerous scorpion, Androctonus mauretanicus. The antivenom was produced by immunizing albino rabbits with a mixture of Androctonus mauretanicus venom collected from high-risk areas in Morocco. Immunizations were performed by subcutaneous injections at multiple sites near the lymphatic system, following an immunization schedule. Production control of neutralizing antibody titers was conducted through immunodiffusion. Once a sufficient antibody titer was achieved, blood collection was performed, and the recovered plasma underwent affinity chromatography. The efficacy of purified IgG was evaluated by determining the ED50 in mice, complemented by histological and immunohistochemical studies on its ability to neutralize venom-induced tissue alterations and the neutralization of toxins bound to receptors in the studied organs. The monovalent antivenom demonstrated specificity against Androctonus mauretanicus venom and effective cross-protection against the venom of the scorpions Buthus occitanus and Androctonus australis hector, highly implicated in lethal envenomations in the Maghreb. This study shows that the developed monovalent antivenom exhibits notable efficacy against local scorpions and a surprising ability to neutralize the most lethal envenomations in North Africa. These results pave the way for a new, more specific, and promising therapeutic approach to countering severe scorpion envenomations, especially in Morocco, where specific treatment is lacking.<\/jats:p>","DOI":"10.3390\/toxins16050214","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T13:27:00Z","timestamp":1715002020000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Development and Efficacy of the Antivenom Specific to Severe Envenomations in Morocco and North Africa: Advancements in Scorpion Envenomation Management"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5547-2684","authenticated-orcid":false,"given":"Bouchra","family":"Darkaoui","sequence":"first","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco, 1 Place Louis Pasteur, Casablanca 20250, Morocco"},{"name":"Laboratory of Molecular Genetics, Physiopathology and Biotechnology, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, B.P 5366 Maarif, Casablanca 20000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5743-4174","authenticated-orcid":false,"given":"Ines","family":"Hilal","sequence":"additional","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco, 1 Place Louis Pasteur, Casablanca 20250, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5489-9187","authenticated-orcid":false,"given":"Soukaina","family":"Khourcha","sequence":"additional","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco, 1 Place Louis Pasteur, Casablanca 20250, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0303-8525","authenticated-orcid":false,"given":"Ayoub","family":"Lafnoune","sequence":"additional","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco, 1 Place Louis Pasteur, Casablanca 20250, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Chakir","sequence":"additional","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco, 1 Place Louis Pasteur, Casablanca 20250, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayoub","family":"Aarab","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomical Pathology Marrakech, Agadir 80000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7610-789X","authenticated-orcid":false,"given":"Abdellah","family":"Moustaghfir","sequence":"additional","affiliation":[{"name":"Laboratory of Research Odontological, Biomaterials and Nanotechnology, Department of Fundamental Sciences, Faculty of Dental Medicine, Mohammed V University in Rabat, B.P 6212 Madinat Al Irfane, Rabat 10000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ouafaa Aniq","family":"Filali","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Physiopathology and Biotechnology, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, B.P 5366 Maarif, Casablanca 20000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoual","family":"Oukkache","sequence":"additional","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco, 1 Place Louis Pasteur, Casablanca 20250, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1051\/medsci\/2009252197","article-title":"Incidence Mondiale et Prise en Charge des Envenimations Ophidiennes et Scorpioniques","volume":"25","author":"Chippaux","year":"2009","journal-title":"M\u00e9decine\/Sci."},{"key":"ref_2","unstructured":"Rein, O., and The Scorpion Files (2021, August 23). Norwegian University of Science and Technology Trondheim. Available online: https:\/\/www.ntnu.no\/ub\/scorpion-files\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2147\/DDDT.S24754","article-title":"Emerging Options for the Management of Scorpion Stings","volume":"6","author":"Chippaux","year":"2012","journal-title":"Drug Des. Devel Ther."},{"key":"ref_4","first-page":"1","article-title":"Trends in Scorpion Diversity and Richness in Morocco","volume":"42","author":"Laghzaoui","year":"2021","journal-title":"Uttar Pradesh J. Zool."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.toxicon.2007.12.012","article-title":"New Analysis of the Toxic Compounds from the Androctonus mauretanicus mauretanicus Scorpion Venom","volume":"51","author":"Oukkache","year":"2008","journal-title":"Toxicon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"277","DOI":"10.4269\/ajtmh.2000.62.277","article-title":"Scorpion Envenomation and Serotherapy in Morocco","volume":"62","author":"Ghalim","year":"2000","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_7","first-page":"115","article-title":"M\u00e9ta-Analyse des Donn\u00e9es des Envenimations Scorpioniques Au Maroc","volume":"1","author":"Abbassi","year":"2018","journal-title":"SMETox J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"875","DOI":"10.5962\/bhl.part.80218","article-title":"Compl\u00e9ments \u00e0 La Faune de Scorpions (Arachnida) de l\u2019Afrique du Nord, Avec des Consid\u00e9rations Sur Le Genre Buthus Leach, 1815","volume":"110","year":"2003","journal-title":"Rev. Suisse Zool."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"299","DOI":"10.12980\/jclm.4.2016J6-22","article-title":"Epidemiological and Spatial Analysis of Scorpion Stings in Two Regions of Morocco: Marrakesh-Tensift-Al Haouz and Souss-Massa-Draa","volume":"4","author":"Touloun","year":"2016","journal-title":"J. Coast. Life Med."},{"key":"ref_10","first-page":"38","article-title":"Scorpion envenomation in the region of Marrakesh Tensift Alhaouz (Morocco): Epidemiological characterization and therapeutic approaches","volume":"13","author":"Touloun","year":"2012","journal-title":"Serket"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s13149-012-0234-4","article-title":"Donn\u00e9es \u00c9pid\u00e9miologiques Sur l\u2019envenimation Scorpionique En Alg\u00e9rie","volume":"105","author":"Hellal","year":"2012","journal-title":"Bull. De La Soci\u00e9t\u00e9 De Pathol. Exot."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.wem.2017.09.011","article-title":"Update on the Epidemiology of Scorpion Envenomation in the South of Tunisia","volume":"29","author":"Karray","year":"2018","journal-title":"Wilderness Environ. Med."},{"key":"ref_13","first-page":"712","article-title":"Lutte Anti-Scorpionique Dans Le Gouvernorat de Sidi Bouzid (Tunisie)","volume":"77","author":"Jeddi","year":"1984","journal-title":"Bull. De La Soci\u00e9t\u00e9 De Pathol. Exot."},{"key":"ref_14","first-page":"773","article-title":"Scorpion Venom: A Poison or a Medicine-Mini Review","volume":"47","author":"Shah","year":"2018","journal-title":"Indian J. Geomarine Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40409-015-0028-5","article-title":"Arachnids of Medical Importance in Brazil: Main Active Compounds Present in Scorpion and Spider Venoms and Tick Saliva","volume":"21","author":"Cordeiro","year":"2015","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_16","first-page":"214","article-title":"Les Envenimations Scorpioniques Graves: Physiopathologie et R\u00f4le de l\u2019inflammation Dans La D\u00e9faillance Multivisc\u00e9rale","volume":"27","author":"Bahloul","year":"2017","journal-title":"Med. Sante Trop."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"096032712110728","DOI":"10.1177\/09603271211072872","article-title":"Induced Pathophysiological Alterations by the Venoms of the Most Dangerous Moroccan Scorpions Androctonus Mauretanicus and Buthus Occitanus: A Comparative Pathophysiological and Toxic-Symptoms Study","volume":"41","author":"Darkaoui","year":"2022","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_18","first-page":"48","article-title":"Modifications Histopathologiques Apr\u00e8s Envenimation Scorpionique Exp\u00e9rimentale Chez La Souris","volume":"53","author":"Oukkache","year":"2009","journal-title":"La Rev. M\u00e8dicopharmaceutique N\u00b0 53-4\u00e8me Trimest."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00134-020-05924-8","article-title":"Scorpion Envenomation: State of the Art","volume":"46","author":"Abroug","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0041-0101(02)00393-8","article-title":"Report of a WHO Workshop on the Standardization and Control of Antivenoms","volume":"41","author":"Theakston","year":"2003","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1002\/2211-5463.13143","article-title":"Mass Spectrometry-based Top-down and Bottom-up Approaches for Proteomic Analysis of the Moroccan Buthus occitanus Scorpion Venom","volume":"11","author":"Daoudi","year":"2021","journal-title":"FEBS Open Bio"},{"key":"ref_22","unstructured":"B\u00e9raud, J. (2001). Le Technicien d\u2019analyses Biologiques: Guide Th\u00e9orique et Pratique, \u00c9d Tec and Doc."},{"key":"ref_23","unstructured":"Amitai, Y. (2017). Critical Care Toxicology, Springer International Publishing."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1081\/CLT-120021114","article-title":"Antivenom Treatment in Arachnidism","volume":"41","author":"Isbister","year":"2003","journal-title":"J. Toxicol. Clin. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.3390\/toxins6061873","article-title":"Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes","volume":"6","author":"Oukkache","year":"2014","journal-title":"Toxins"},{"key":"ref_26","first-page":"317","article-title":"Chemistry and Pharmacology of Buthinae Scorpion Venoms","volume":"48","author":"Zlotkin","year":"1978","journal-title":"Arthropod Venoms"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/B978-0-12-138903-1.50020-X","article-title":"Scorpionism in the Old World","volume":"3","author":"Balozet","year":"1971","journal-title":"Venom. Anim. Their Venoms"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1590\/S1678-91992006000300004","article-title":"Optimization of Antiscorpion Venom Production","volume":"12","author":"Ozkan","year":"2006","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.toxicon.2011.09.010","article-title":"Heminecrolysin, a Potential Immunogen for Monospecific Antivenom Production against Hemiscorpius lepturus Scorpion","volume":"58","author":"Borchani","year":"2011","journal-title":"Toxicon"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ledsgaard, L., Jenkins, T., Davidsen, K., Krause, K., Martos-Esteban, A., Engmark, M., R\u00f8rdam Andersen, M., Lund, O., and Laustsen, A. (2018). Antibody Cross-Reactivity in Antivenom Research. Toxins, 10.","DOI":"10.3390\/toxins10100393"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1016\/j.intimp.2008.05.011","article-title":"Combination of Two Antibody Fragments F(Ab\u2032)2\/Fab: An Alternative for Scorpion Envenoming Treatment","volume":"8","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.toxicon.2011.11.004","article-title":"Amelioration of Cardio-Respiratory Perturbations following Mesobuthus eupeus Envenomation in Anesthetized Rabbits with Commercial Polyvalent F(Ab\u2032)2 Antivenom","volume":"59","author":"Zayerzadeh","year":"2012","journal-title":"Toxicon"},{"key":"ref_33","first-page":"110","article-title":"Effet de l\u2019immunoth\u00e9rapie Sur Les Modifications M\u00e9taboliques et Histopathologiques Apr\u00e8s Envenimation Scorpionique Exp\u00e9rimentale","volume":"96","author":"Bessalem","year":"2003","journal-title":"Bull. Soci\u00e9t\u00e9 Pathol. Exot."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/0041-0101(96)00074-8","article-title":"Body Distribution of Tityus serrulatus Scorpion Venom in Mice and Effects of Scorpion Antivenom","volume":"34","author":"Revelo","year":"1996","journal-title":"Toxicon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.toxicon.2004.08.021","article-title":"Histophatological Changes and Inflammatory Response Induced by Tityus discrepans Scorpion Venom in Rams","volume":"44","author":"Salazar","year":"2004","journal-title":"Toxicon"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Darkaoui, B., Aksim, M., Aarab, A., Lafnoune, A., Khourcha, S., Cadi, R., Filali, O.A., and Oukkache, N. (2023). Neutralization Capacity of Tissue Alterations Caused by the Venoms of the Most Dangerous Scorpions in North Africa Using a Selective Antivenom. Toxins, 16.","DOI":"10.3390\/toxins16010016"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1056\/NEJMoa0808455","article-title":"Antivenom for Critically Ill Children with Neurotoxicity from Scorpion Stings","volume":"360","author":"Boyer","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/archdischild-2013-305483","article-title":"Efficacy of Scorpion Antivenom plus Prazosin versus Prazosin Alone for Mesobuthus tamulus Scorpion Sting Envenomation in Children: A Randomised Controlled Trial","volume":"99","author":"Pandi","year":"2014","journal-title":"Arch. Dis. Child."},{"key":"ref_39","first-page":"50","article-title":"The Determination of Acute Lethal Dose-50 (LD50) Levels of Venom in Mice, Obtained by Different Methods from Scorpions, Androctonus crassicauda (Oliver 1807)","volume":"28","author":"Filazi","year":"2004","journal-title":"Acta Parasitol. Turc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0076-6879(57)03413-8","article-title":"Spectrophotometric and Turbidimetric Methods for Measuring Proteins","volume":"3","author":"Layne","year":"1957","journal-title":"Methods Enzym."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/0076-6879(90)82008-P","article-title":"Quantitation of Protein","volume":"182","author":"Stoscheck","year":"1990","journal-title":"Methods Enzym."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_43","unstructured":"World Health Organization (1981). Progress in the Characterization of Venoms and Standardization of Antivenoms, WHO Offset Publication."},{"key":"ref_44","unstructured":"Finney, D. (1971). Probit Analysis, Cambridge University Press. [3rd ed.]."},{"key":"ref_45","first-page":"30","article-title":"Diffusion-In-Gel Methods for Immunological Analysis II (Part 1 of 4)","volume":"Volume 6","author":"Ouchterlony","year":"1962","journal-title":"Progress in Allergy"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0003-2697(74)90139-0","article-title":"A Simplified Method for Cyanogen Bromide Activation of Agarose for Affinity Chromatography","volume":"60","author":"March","year":"1974","journal-title":"Anal. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1073\/pnas.76.9.4350","article-title":"Electrophoretic Transfer of Proteins from Polyacrylamide Gels to Nitrocellulose Sheets: Procedure and Some Applications","volume":"76","author":"Towbin","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.4081\/ejh.2016.2639","article-title":"Histological and Histochemical Methods\u2014Theory and Practice","volume":"60","author":"Malatesta","year":"2016","journal-title":"Eur. J. Histochem."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/5\/214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:39:41Z","timestamp":1760107181000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/5\/214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,4]]},"references-count":49,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["toxins16050214"],"URL":"https:\/\/doi.org\/10.3390\/toxins16050214","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,4]]}}}