Clinical effects of immunization, bleeding, and albumin-based fluid therapy in horses used as immunoglobulin source to produce a polyspecific antivenom (Echitab-plus-ICP) towards venoms of African snakes.
Abstract: During the production of snake antivenoms, the animals used as immunoglobulin source are subjected to processes that could deteriorate their physical condition. Therefore, these conditions must be carefully designed and validated. In this work, the immunization and bleeding protocols applied to horses used to produce the African polyspecific antivenom EchiTAb-plus-ICP were evaluated regarding their effects on the horses' health. The study focused on horses that had been previously immunized with venoms and then received periodic booster venom injections for antivenom production. It was found that the periodic immunization with 5 mg of a mixture of venoms of , , and did not induce systemic signs of envenomation, and only caused mild swelling at the injection site, which did not evolve to abscesses, fistulas, or fibrosis. Three consecutive days of bleeding, collecting 6-8 L of blood per day, and self-transfusing the red blood cells (RBC) in the second and third days, did not induce evident cardiorespiratory alterations. However, this procedure caused significant reductions in RBC, hematocrit, hemoglobin, and total plasma protein values. Seven weeks after bleeding, these parameters were recovered, and horses were ready for the next immunization/bleeding cycle. The intravenous administration of equine albumin, at a dose of 2 g/kg body weight, increased the apparent plasma volume and the albumin concentration. However, this procedure induced early adverse reactions and transient alterations of the serum levels of the enzyme gamma-glutamyl transferase (GGT), thus suggesting some degree of hepatic injury. It was concluded that immunization and bleeding as described in this work do not cause significant clinical alterations in the horse's health, except for a transient drop in some hematological parameters. The albumin-based fluid therapy used does not hasten the recovery after bleeding but instead induces adverse events in the animals.
© 2023 The Authors.
Publication Date: 2023-04-17 PubMed ID: 37180815PubMed Central: PMC10172988DOI: 10.1016/j.toxcx.2023.100158Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research focuses on the welfare of the horses used in producing antivenoms. It analyses the effect of immunization, bleeding, and albumin-based fluid therapy on the health of the horses. The study concluded that the process did not cause serious health issues for the horses aside from temporary drops in certain hematological parameters.
Overview of the Research
- The research aimed to investigate the effects of immunization and bleeding protocols on horses used as a source of immunoglobulins to produce an African polyspecific antivenom named EchiTAb-plus-ICP.
- The study was centered on horses that received venoms for immunization regularly and underwent bleeding for antivenom production.
- The study noted that these protocols must be carefully monitored to ensure that they do not harm the horses’ health.
Findings of the Research
- Immunizing the horses with a mixture of different venoms did not cause systemic signs of venom poisoning, but only mild swelling at the injection site. There was no development of abscesses, fistulas, or fibrosis due to the immunization.
- The process of bleeding the animals over three days, with reinfusion of red blood cells on the second and third days, led to no clear cardiorespiratory changes. However, this procedure did cause significant drops in red blood cell count, hematocrit, hemoglobin, and total plasma protein values.
- Seven weeks after bleeding, these parameters were back to normal, and the horses were ready for the next immunization/bleeding cycle.
- The albumin-based fluid therapy treatment didn’t hasten the recovery after bleeding but instead caused adverse reactions and temporary changes in the levels of the enzyme from the liver known as gamma-glutamyl transferase (GGT), indicating potential liver injury.
Conclusions of the Research
- The immunization and bleeding procedures used in the study did not cause substantial clinical changes in the horse’s health, apart from a transient decrease in some parameters related to the blood.
- The albumin-based fluid therapy used after bleeding did not accelerate recovery but instead resulted in adverse reactions in the horses.
Cite This Article
APA
Huertas RM, Arguedas M, Estrada JM, Moscoso E, Umaña D, Solano G, Vargas M, Segura Á, Sánchez A, Herrera M, Villalta M, Arroyo-Portilla C, Gutiérrez JM, León G.
(2023).
Clinical effects of immunization, bleeding, and albumin-based fluid therapy in horses used as immunoglobulin source to produce a polyspecific antivenom (Echitab-plus-ICP) towards venoms of African snakes.
Toxicon X, 18, 100158.
https://doi.org/10.1016/j.toxcx.2023.100158 Publication
Researcher Affiliations
- Laboratorio de Análisis Clínicos, Escuela de Medicina Veterinaria, Universidad Nacional de Costa Rica, Heredia, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Hospital de Equinos, Especies Mayores y Terapias Regenerativas, Escuela de Medicina Veterinaria, Universidad Nacional de Costa Rica, Heredia, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Departamento de Análisis Clínicos, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
- Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Conflict of Interest Statement
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guillermo Leon Montero reports financial support was provided by Wellcome Trust.
References
This article includes 35 references
- Angulo Y, Estrada R, Gutiérrez JM. Clinical and laboratory alterations in horses during immunization with snake venoms for the production of polyvalent (Crotalinae) antivenom.. Toxicon 1997 Jan;35(1):81-90.
- Angulo Y, Estrada R, Gutiérrez JM. Effects of bleeding in horses immunized with snake venoms for antivenom production.. Rev. Biol. Trop. 1997;45:1215–1221.
- Arguedas M, Umaña D, Moscoso E, García A, Pereira C, Sánchez A, Durán G, Cordero D, Sánchez A, Segura Á, Vargas M, Herrera M, Villalta M, Gómez A, Salas C, Díaz C, María Gutiérrez J, León G. Comparison of adjuvant emulsions for their safety and ability to enhance the antibody response in horses immunized with African snake venoms.. Vaccine X 2022 Dec;12:100233.
- Chotwiwatthanakun C, Pratanaphon R, Akesowan S, Sriprapat S, Ratanabanangkoon K. Production of potent polyvalent antivenom against three elapid venoms using a low dose, low volume, multi-site immunization protocol.. Toxicon 2001 Oct;39(10):1487-94.
- . CIOMS International Guiding Principles for Biomedical Research Involving Animals.. Altern Lab Anim 1985 Jun;12(4):ii-.
- da Silva WD, Tambourgi DV. The humoral immune response induced by snake venom toxins.. Inflamm Allergy Drug Targets 2011 Oct;10(5):343-57.
- Estrada R, Chaves F, Robles A, Rojas E, Segura E, Gutiérrez JM. [Hematologic values and serum enzymes in horses inoculated with snake venoms for the production of antivenins in Costa Rica].. Rev Biol Trop 1992 Apr;40(1):95-9.
- Feige K, Ehrat FB, Kästner SB, Wampfler B. The effects of automated plasmapheresis on clinical, haematological, biochemical and coagulation variables in horses.. Vet J 2005 Jan;169(1):102-7.
- . How much plasma, relative to his body weight, can a donor give over a certain period without a continuous deviation of his plasma protein metabolism in the direction of plasma protein deficiency?. Vox Sang 1984;47(6):435-48.
- Fukanoki S, Iwakura T, Iwaki S, Matsumoto K, Takeda R, Ikeda K, Shi Z, Mori H. Safety and efficacy of water-in-oil-in-water emulsion vaccines containing Newcastle disease virus haemagglutinin-neuraminidase glycoprotein.. Avian Pathol 2001 Oct;30(5):509-16.
- Gómez A, Sánchez A, Durán G, Cordero D, Segura Á, Vargas M, Solano D, Herrera M, Chaves-Araya S, Villalta M, Sánchez M, Arguedas M, Díaz C, Gutiérrez JM, León G. Intrageneric cross-reactivity of monospecific rabbit antisera against venoms of the medically most important Bitis spp. and Echis spp. African snakes.. PLoS Negl Trop Dis 2022 Aug;16(8):e0010643.
- GORNALL AG, BARDAWILL CJ, DAVID MM. Determination of serum proteins by means of the biuret reaction.. J Biol Chem 1949 Feb;177(2):751-66.
- Gutiérrez JM, Rojas E, Quesada L, León G, Núñez J, Laing GD, Sasa M, Renjifo JM, Nasidi A, Warrell DA, Theakston RD, Rojas G. Pan-African polyspecific antivenom produced by caprylic acid purification of horse IgG: an alternative to the antivenom crisis in Africa.. Trans R Soc Trop Med Hyg 2005 Jun;99(6):468-75.
- Jansen T, Hofmans MP, Theelen MJ, Manders FG, Schijns VE. Dose and timing requirements for immunogenicity of viral poultry vaccine antigen: investigations of emulsion-based depot function.. Avian Pathol 2007 Oct;36(5):361-5.
- León G, Estrada R, Chaves F, Rojas G, Ovadia M, Gutiérrez JM. Inhibition by CaNa2EDTA of local tissue damage induced by Bothrops asper (terciopelo) venom: application in horse immunization for antivenom production.. Toxicon 1998 Feb;36(2):321-31.
- León G, Sánchez L, Hernández A, Villalta M, Herrera M, Segura A, Estrada R, Gutiérrez JM. Immune response towards snake venoms.. Inflamm Allergy Drug Targets 2011 Oct;10(5):381-98.
- León G, Vargas M, Segura Á, Herrera M, Villalta M, Sánchez A, Solano G, Gómez A, Sánchez M, Estrada R, Gutiérrez JM. Current technology for the industrial manufacture of snake antivenoms.. Toxicon 2018 Sep 1;151:63-73.
- Magdesian KG, Brook D, Wickler SJ. Temporal effects of plasmapheresis on serum proteins in horses.. Am J Vet Res 1992 Jul;53(7):1149-53.
- Malikides N, Hodgson JL, Rose RJ, Hodgson DR. Cardiovascular, haematological and biochemical responses after large volume blood collection in horses.. Vet J 2001 Jul;162(1):44-55.
- Mann S, Ramsay JD, Wakshlag JJ, Stokol T, Reed S, Divers TJ. Investigating the pathogenesis of high-serum gamma-glutamyl transferase activity in Thoroughbred racehorses: A series of case-control studies.. Equine Vet J 2022 Jan;54(1):39-51.
- Mazzachi BC, Peake MJ, Ehrhardt V. Reference range and method comparison studies for enzymatic and Jaffé creatinine assays in plasma and serum and early morning urine.. Clin Lab 2000;46(1-2):53-5.
- Merlot AM, Kalinowski DS, Richardson DR. Unraveling the mysteries of serum albumin-more than just a serum protein.. Front Physiol 2014;5:299.
- RODKEY FL. DIRECT SPECTROPHOTOMETRIC DETERMINATION OF ALBUMIN IN HUMAN SERUM.. Clin Chem 1965 Apr;11:478-87.
- Schmotzer WB, Riebold TW, Porter SL, Blauvelt SR. Time saving techniques for the collection, storage, and administration of equine blood and plasma.. Vet. Med. 1985;80:89–94.
- Segura A, Villalta M, Herrera M, León G, Harrison R, Durfa N, Nasidi A, Calvete JJ, Theakston RD, Warrell DA, Gutiérrez JM. Preclinical assessment of the efficacy of a new antivenom (EchiTAb-Plus-ICP) for the treatment of viper envenoming in sub-Saharan Africa.. Toxicon 2010 Feb-Mar;55(2-3):369-74.
- Stockham SL. Interpretation of equine serum biochemical profile results.. Vet Clin North Am Equine Pract 1995 Dec;11(3):391-414.
- Szasz G. A kinetic photometric method for serum gamma-glutamyl transpeptidase.. Clin Chem 1969 Feb;15(2):124-36.
- TALKE H, SCHUBERT GE. [ENZYMATIC UREA DETERMINATION IN THE BLOOD AND SERUM IN THE WARBURG OPTICAL TEST].. Klin Wochenschr 1965 Feb 1;43:174-5.
- Theakston RD, Warrell DA, Griffiths E. Report of a WHO workshop on the standardization and control of antivenoms.. Toxicon 2003 Apr;41(5):541-57.
- Udroiu I. Storage of blood in the mammalian spleen: an evolutionary perspective.. J. Mamm. Evol. 2017;24:243–260.
- Vargas M, Segura Á, Villalta M, Herrera M, Gutiérrez JM, León G. Purification of equine whole IgG snake antivenom by using an aqueous two phase system as a primary purification step.. Biologicals 2015 Jan;43(1):37-46.
- Vaz E, Araujo P. Da sangria de animais de imunização.. Mem. Inst. Butantan (Sao Paulo) 1949;21:275–298.
- Waghmare AB, Salvi NC, Deopurkar RL, Shenoy PA, Sonpetkar JM. Evaluation of health status of horses immunized with snake venom and montanide adjuvants, IMS 3012 (nanoparticle), ISA 206 and ISA 35 (emulsion based) during polyvalent snake antivenom production: hematological and biochemical assessment.. Toxicon 2014 May;82:83-92.
- Welch-Huston B, Durward-Akhurst S, Norton E, Ellingson L, Rendahl A, McCue M. Comparison between smartphone electrocardiography and standard three-lead base apex electrocardiography in healthy horses.. Vet Rec 2020 Oct 31;187(9):e70.
- . Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins.. .
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
