Skip to main content
SpringerLink
Log in

Production and Utilization of Snake Antivenoms in South America

  • Living reference work entry
  • First Online:
Toxins and Drug Discovery

Part of the book series: Toxinology ((TOXI))

Abstract

Venomous snakebites represent an important public health issue in many parts of the world, including South America, causing high morbidity and mortality. In this continent, antivenoms are currently manufactured in Argentina, Bolivia, Brazil, Colombia, Peru, and Venezuela, and by more than one laboratory in some of these countries. Eight of them are public laboratories (three in Brazil) that produce specific mono- and polyvalent antivenoms, derived from the antibodies produced mostly by horses immunized with either one or a pool of venoms from snakes, spiders, scorpions, and caterpillars of medical importance. F(ab’)2 fragments or whole IgG are purified from plasmas of immunized horses. Studies on the cross-neutralization between antivenoms and venoms from different species countries, as well as clinical trials confirming the efficacy and safety of antivenoms may improve the antivenom availability at a regional level.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Araujo HP, Bourgnong SC, Boller MAA, Diasa AASO, Lucas EPR, Santos IC, Delgado IF. Potency evaluation of antivenoms in Brazil: the national control laboratory experience between 2000 and 2006. Toxicon. 2000;51:502–14.

    Article  Google Scholar 

  • Argentina. Ministerio de Salud. Guía de Prevención, Diagnóstico, Tratamiento y Vigilancia Epidemiológica de los Envenenamientos Ofidicos. Buenos Aires: Ministerio de Salud; 2007.

    Google Scholar 

  • Argentina. Ministerio de Salud. Guía de Centros Antiponzoñosos de la República Argentina. Buenos Aires: Ministerio de Salud; 2011.

    Google Scholar 

  • Brazil V. Contribuição ao estudo do veneno ofídico: tratamento das mordeduras de cobras. Rev Med São Paulo. 1903;13:265–78.

    Google Scholar 

  • Brazil. Agência Nacional de Vigilância Sanitária. Farmacopeia Brasileira. Brasilia; 2010.

    Google Scholar 

  • Brazil. Ministerio da Saude. Manual de Diagnóstico e Tratamento dos Acidentes por Animais Peçonhentos. Brasilia, 2001.

    Google Scholar 

  • Bucaretchi F, Douglas JL, Fonseca MR, Zambrone FA, Vieira RJ. Snake bites in children: antivenom early reaction frequency in patients pretreated with histamine antagonists H1 and H2 and hydrocortisone. Rev Inst Med Trop Sao Paulo. 1994;36(5):451–7.

    Article  CAS  PubMed  Google Scholar 

  • Bucaretchi F, Herrera SR, Hyslop S, Baracat EC, Vieira RJ. Snakebites by Bothrops spp in children in Campinas, Sao Paulo, Brazil. Rev Inst Med Trop Sao Paulo. 2001;43(6):329–33.

    Article  CAS  PubMed  Google Scholar 

  • Bucaretchi F, Herrera SR, Hyslop S, Baracat EC, Vieira RJ. Snakebites by Crotalus durissus ssp in children in Campinas, Sao Paulo, Brazil. Rev Inst Med Trop Sao Paulo. 2002;44(3):133–8.

    Article  PubMed  Google Scholar 

  • Calvete JJ, Sanz L, Pérez A, Borges A, Vargas AM, Lomonte B, et al. Snake population venomics and antivenomics of Bothrops atrox: Paedomorphism along its transamazonian dispersal and implications of geographic venom variability on snakebite management. J Proteomics. 2011;74(4):510–27.

    Article  CAS  PubMed  Google Scholar 

  • Cardoso JL, Fan HW, Franca FO, Jorge MT, Leite RP, Nishioka SA, et al. Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in Sao Paulo. Brazil Q J Med. 1993;86(5):315–25.

    CAS  PubMed  Google Scholar 

  • Caricati CP, Oliveira-Nascimento L, Yoshida JT, Caricati AT, Raw I, Stephano MA. Safety of snake antivenom immunoglobulins: efficacy of viral inactivation in a complete downstream process. Biotechnol Prog. 2013;29(4):972–9.

    Article  CAS  PubMed  Google Scholar 

  • Centro de Biotecnologia de la Universidad Central de Venezuela. Suero antiofídico polivalente – Available online: http://www.biotecfar.com.ve/biotecfar/pdf/suero_antiofidico_polivalente.pdf. Accessed 5 Sep 2016.

  • Colombia. Ministerio de la Protección Social. Guías para el Manejo de Urgencias Toxicológicas. Bogotá, 2008.

    Google Scholar 

  • De Franco M, Kalil J. The Butantan Institute: history and future perspectives. PLoS Negl Trop Dis. 2014;8(7), e2862.

    Article  PubMed  PubMed Central  Google Scholar 

  • de Roodt A, Dolab JA, Fernandez T, Segre L, Hajos SE. Cross-reactivity and heterologous neutralization of crotaline antivenoms used in Argentina. Toxicon. 1998;36(7):1025–38.

    Article  PubMed  Google Scholar 

  • da Silva Dias W, Guidolin R, Raw I, Higashi HG, Caricati CP, Morais JF, et al. Cross-reactivity of horse monovalente antivenoms to venoms of tem Bothrops species. Mem Inst Butantan. 1989;51(4):153–68.

    Google Scholar 

  • Ecuador. Ministerio de Salud Pública. Manual de Normas y Procedimientos sobre Prevención y Tratamiento de Accidentes Ocasionados por Mordeduras de Serpientes. Guayaquil; 2008.

    Google Scholar 

  • Fan HW, Marcopito LF, Cardoso JL, Franca FO, Malaque CM, Ferrari RA, et al. Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites. BMJ. 1999;318(7196):1451–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feitosa ES, Sampaio V, Sachett J, Castro DB, Noronha M, Lozano JL, et al. Snakebites as a largely neglected problem in the Brazilian Amazon: highlights of the epidemiological trends in the State of Amazonas. Rev Soc Bras Med Trop. 2015;48 Suppl 1:34–41.

    Article  PubMed  Google Scholar 

  • Fernandez GP, Segura A, Herrera M, Velasco W, Solano G, Gutierrez JM, et al. Neutralization of Bothrops mattogrossensis snake venom from Bolivia: experimental evaluation of llama and donkey antivenoms produced by caprylic acid precipitation. Toxicon. 2010;55(2–3):642–5.

    Article  CAS  PubMed  Google Scholar 

  • Furtado MF, Cardoso ST, Soares OE, Pereira AP, Fernandes D, Tambourgi DV, et al. Antigenic cross-reactivity and immungoenicity of Bothrops venoms from snakes of the Amazon region. Toxicon. 2010;55(4):881–7.

    Article  CAS  Google Scholar 

  • Gutierrez JM. Improving antivenom availability and accessibility: science, technology, and beyond. Toxicon. 2012;60(4):676–87.

    Article  CAS  PubMed  Google Scholar 

  • Gutierrez JM, Higashi HG, Wen FH, Burnouf T. Strengthening antivenom production in Central and South American public laboratories: report of a workshop. Toxicon. 2007;49(1):30–5.

    Article  CAS  PubMed  Google Scholar 

  • Gutierrez JM, Fan HW, Silvera CL, Angulo Y. Stability, distribution and use of antivenoms for snakebite envenomation in Latin America: report of a workshop. Toxicon. 2009;53(6):625–30.

    Article  CAS  PubMed  Google Scholar 

  • Higashi HG, Guidolin R, Caricati CP, Fernandes I, Marcelino JR, et al. Antigenic cross-reactivity among components of Brazilian Elapidae snake venoms. Braz J Med Biol Res. 1995;28(7):767–71.

    CAS  PubMed  Google Scholar 

  • Instituto Biológico Dr. Tomás Perón, Argentina. Suero antibotrópico. Available on line: http://www.ms.gba.gov.ar/sitios/laboratorio/files/2012/06/SueroAntibotropico.pdf. Accessed 5 Sep 2016.

  • Instituto Nacional de Productos Biológicos, Argentina. Suero antibotrópico. Available on line: http://www.anlis.gov.ar/inpb/?page_id=522. Accessed 5 Sep 2016.

  • Instituto Nacional de Salud, Colombia. Suero antiofídico polivalente. Available on line: http://www.ins.gov.co/lineas-de-accion/Produccion/Paginas/suero-antiofidico-polivalente.aspx. Accessed 5 Sep 2016.

  • Instituto Nacional de Salud, Peru. Suero antibotrópico polivalente. Available on line: http://www.ins.gob.pe/insvirtual/hdetprod.aspx?1653. Accessed 5 Sep 2016.

  • Instituto Nacional de Salud, Peru. Suero antilachésico monovalente. Available on line: http://www.ins.gob.pe/insvirtual/hdetprod.aspx?1559. Accessed 5 Sep 2016.

  • Instituto Nacional de Salud, Peru. Suero crotálico monovalente. Available on line: http://www.ins.gob.pe/insvirtual/hdetprod.aspx?1654. Accessed 5 Sep 2016.

  • Jorge MT, Ribeiro LA. Antivenom serum doses in the treatment of poisoning by a venomous snake of the genus Bothrops. Rev Assoc Med Bras. 1997;43(1):74–6.

    Article  CAS  PubMed  Google Scholar 

  • Jorge MT, Cardoso JL, Castro SC, Ribeiro L, Franca FO, de Almeida ME, et al. A randomized ‘blinded’ comparison of two doses of antivenom in the treatment of Bothrops envenoming in Sao Paulo, Brazil. Trans R Soc Trop Med Hyg. 1995;89(1):111–4.

    Article  CAS  PubMed  Google Scholar 

  • Laing GD, Yarleque A, Marcelo A, Rodriguez E, Warrell DA, Theakston RD. Preclinical testing of three South American antivenoms against the venoms of five medically-important Peruvian snake venoms. Toxicon. 2004;44(1):103–6.

    Article  CAS  PubMed  Google Scholar 

  • Leon G, Monge M, Rojas E, Lomonte B, Gutierrez JM. Comparison between IgG and F(ab')2 polyvalent antivenoms: neutralization of systemic effects induced by Bothrops asper venom in mice, extravasion to muscle tissue, and potential for induction of adverse reactions. Toxicon. 2001;39(6):793–801.

    Article  CAS  PubMed  Google Scholar 

  • Leon G, Segura A, Herrera M, Otero R, Franca FO, Barbaro KC, et al. Human heterophilic antibodies against equine immunoglobulins: assessment of their role in the early adverse reactions to antivenom administration. Trans R Soc Trop Med Hyg. 2008;102(11):1115–9.

    Article  PubMed  Google Scholar 

  • Leon G, Herrera M, Segura A, Villalta M, Vargas M, Gutierrez JM. Pathogenic mechanisms underlying adverse reactions induced by intravenous administration of snake antivenoms. Toxicon. 2013;76:63–76.

    Article  CAS  PubMed  Google Scholar 

  • Menezes MC, Furtado MF, Travaglia-Cardoso SR, Camargo AC, Serrano SM. Sex-based individual variation of snake venom proteome among eighteen Bothrops jararaca siblings. Toxicon. 2006;47(3):304–12.

    Article  CAS  PubMed  Google Scholar 

  • Morais V, Negrin A, Tortorella MN, Massaldi H. Evolution of venom antigenaemia and antivenom concentration in patients bitten by snakes in Uruguay. Toxicon. 2012;60(6):990–4.

    Article  CAS  PubMed  Google Scholar 

  • Nunez V, Cid P, Sanz L, De La Torre P, Angulo Y, Lomonte B, et al. Snake venomics and antivenomics of Bothrops atrox venoms from Colombia and the Amazon regions of Brazil, Peru and Ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism. J Proteomics. 2009;73(1):57–78.

    Article  CAS  PubMed  Google Scholar 

  • Otero R, Gutierrez JM, Nunez V, Robles A, Estrada R, Segura E, et al. A randomized double-blind clinical trial of two antivenoms in patients bitten by Bothrops atrox in Colombia. The Regional Group on Antivenom Therapy Research (REGATHER). Trans R Soc Trop Med Hyg. 1996;90(6):696–700.

    Article  CAS  PubMed  Google Scholar 

  • Otero R, Gutierrez JM, Rojas G, Nunez V, Diaz A, Miranda E, et al. A randomized blinded clinical trial of two antivenoms, prepared by caprylic acid or ammonium sulphate fractionation of IgG, in Bothrops and Porthidium snake bites in Colombia: correlation between safety and biochemical characteristics of antivenoms. Toxicon. 1999;37(6):895–908.

    Article  CAS  PubMed  Google Scholar 

  • Otero R, Leon G, Gutierrez JM, Rojas G, Toro MF, Barona J, et al. Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without beta-propiolactone, in the treatment of Bothrops asper bites in Colombia. Trans R Soc Trop Med Hyg. 2006;100(12):1173–82.

    Article  CAS  PubMed  Google Scholar 

  • Otero-Patino R. Epidemiological, clinical and therapeutic aspects of Bothrops asper bites. Toxicon. 2009;54(7):998–1011.

    Article  CAS  PubMed  Google Scholar 

  • Otero-Patino R, Cardoso JL, Higashi HG, Nunez V, Diaz A, Toro MF, et al. A randomized, blinded, comparative trial of one pepsin-digested and two whole IgG antivenoms for Bothrops snake bites in Uraba, Colombia. The Regional Group on Antivenom Therapy Research (REGATHER). Am J Trop Med Hyg. 1998;58(2):183–9.

    CAS  PubMed  Google Scholar 

  • Otero-Patino R, Segura A, Herrera M, Angulo Y, Leon G, Gutierrez JM, et al. Comparative study of the efficacy and safety of two polyvalent, caprylic acid fractionated [IgG and F(ab')2] antivenoms, in Bothrops asper bites in Colombia. Toxicon. 2012;59(2):344–55.

    Article  CAS  PubMed  Google Scholar 

  • Paraguay. Ministerio de Salud Publica y Bienestar Social. Manual de Procedimiento sobre Accidentes Ofidicos. Assuncion, 2008p.

    Google Scholar 

  • Pardal PP, Souza SM, Monteiro MR, Fan HW, Cardoso JL, Franca FO, et al. Clinical trial of two antivenoms for the treatment of Bothrops and Lachesis bites in the north eastern Amazon region of Brazil. Trans R Soc Trop Med Hyg. 2004;98(1):28–42.

    Article  CAS  PubMed  Google Scholar 

  • Peru. Ministerio de Salud. Norma Técnica sobre Prevención y Tratamiento de Accidentes por Animales Ponzoñosos. Lima, 2004, 58p.

    Google Scholar 

  • Pidde-Queiroz G, Furtado Mde F, Filgueiras CF, Pessoa LA, Spadafora-Ferreira M, van den Berg CW, et al. Human complement activation and anaphylatoxins generation induced by snake venom toxins from Bothrops genus. Mol Immunol. 2010;47(16):2537–44.

    Article  CAS  PubMed  Google Scholar 

  • Ponte CF. Vacinação, controle de qualidade e produção de vacinas no Brasil a partir de 1960’. Hist Cien Saúde Manguinhos. 2003;10(2):619–53.

    Article  Google Scholar 

  • Raw I, Guidolin R, Higashi HG, Kelen EMA. Antivenins in Brazil: preparation. In: Tu AT, editor. Reptile venoms and toxins, vol. 5. New York: Marcel Dekker; 1991. p. 557–81.

    Google Scholar 

  • Saldarriaga MM, Otero R, Nunez V, Toro MF, Diaz A, Gutierrez JM. Ontogenetic variability of Bothrops atrox and Bothrops asper snake venoms from Colombia. Toxicon. 2003;42(4):405–11.

    Article  CAS  PubMed  Google Scholar 

  • Sano-Martins IS, Santoro ML, Castro SC, Fan HW, Cardoso JL, Theakston RD. Platelet aggregation in patients bitten by the Brazilian snake Bothrops jararaca. Thromb Res. 1997;87(2):183–95.

    Article  CAS  PubMed  Google Scholar 

  • Sano-Martins IS, Tomy SC, Campolina D, Dias MB, de Castro SC, de Sousa-e-Silva MC, et al. Coagulopathy following lethal and non-lethal envenoming of humans by the South American rattlesnake (Crotalus durissus) in Brazil. QJM. 2001;94(10):551–9.

    Article  CAS  PubMed  Google Scholar 

  • Santoro ML, Sano-Martins IS, Fan HW, Cardoso JL, Theakston RD, Warrell DA, et al. Haematological evaluation of patients bitten by the jararaca, Bothrops jararaca, in Brazil. Toxicon. 2008;51(8):1440–8.

    Article  CAS  PubMed  Google Scholar 

  • Segura A, Castillo MC, Nuñez V, Yarlequé A, Gonçalves LRC, Villalta M, et al. Preclinical assessment of the neutralizing capacity of antivenoms produced in six Latin American countries against medically-relevant Bothrops snake venoms. Toxicon. 2010;56(6):980–9.

    Article  CAS  PubMed  Google Scholar 

  • Smalligan R, Cole J, Brito N, Laing GD, Mertz BL, Manock S, et al. Crotaline snake bite in the Ecuadorian Amazon: randomised double blind comparative trial of three South American polyspecific antivenoms. BMJ. 2004;329(7475):1129.

    Article  PubMed  PubMed Central  Google Scholar 

  • Squaiella-Baptistão CC, Marcelino JR, Ribeiro da Cunha LE, Gutierrez JM, Tambourgi DV. Anticomplementary activity of horse IgG and F(ab')2 antivenoms. Am J Trop Med Hyg. 2014;90(3):574–84.

    Article  PubMed  PubMed Central  Google Scholar 

  • Stephano MA, Guidolin R, Higashi HG, Tambourgi DV, Sant'Anna OA. The improvement of the therapeutic anti-Lachesis muta serum production in horses. Toxicon. 2005;45(4):467–73.

    Article  CAS  PubMed  Google Scholar 

  • Tanaka GD, Pidde-Queiroz G, de Fatima DFM, van den Berg C, Tambourgi DV. Micrurus snake venoms activate human complement system and generate anaphylatoxins. BMC Immunol. 2012;13:4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tanaka GD, Sant'Anna OA, Marcelino JR, Lustoza da Luz AC, Teixeira da Rocha MM, et al. Micrurus snake species: venom immunogenicity, antiserum cross-reactivity and neutralization potential. Toxicon. 2016;117:59–68.

    Article  CAS  PubMed  Google Scholar 

  • Theakston RD, Fan HW, Warrell DA, Da Silva WD, Ward SA, Higashi HG. Use of enzyme immunoassays to compare the effect and assess the dosage regimens of three Brazilian Bothrops antivenoms. The Butantan Institute Antivenom Study Group (BIASG). Am J Trop Med Hyg. 1992;47(5):593–604.

    CAS  PubMed  Google Scholar 

  • Toro GH, Hernandez CA, Raad J. Instituto Nacional de Salud 1917–1997, Una historia, un compromiso. Bogotá: Instituto Nacional de Salud; 1998.

    Google Scholar 

  • Waghmare A, Deopurkar RL, Salvi N, Khadilkar M, Kalolikar M, Gade SK. Comparison of Montanide adjuvants, IMS 3012 (Nanoparticle), ISA 206 and ISA 35 (Emulsion based) along with incomplete Freund's adjuvant for hyperimmunization of equines used for production of polyvalent snake antivenom. Vaccine. 2009;27(7):1067–72.

    Article  CAS  PubMed  Google Scholar 

  • 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;82:83–92.

    Article  CAS  PubMed  Google Scholar 

  • WHO. Rabies and envenomings: a neglected public health issue. Geneva: WHO; 2007.

    Google Scholar 

  • WHO. Guidelines for the production, control and regulation of snake antivenom immunoglobulins. Geneva: WHO; 2010.

    Google Scholar 

  • Zelanis A, Tashima AK, Rocha MM, Furtado MF, Camargo AC, Ho PL, Serrano SM. Analysis of the ontogenetic variation in the venom proteome/peptidome of Bothrops jararaca reveals different strategies to deal with prey. J Proteome Res. 2010;9(5):2278–91.

    Article  CAS  PubMed  Google Scholar 

  • Zelanis A, Andrade-Silva D, Rocha MM, Furtado MF, Serrano SM, Junqueira-de-Azevedo IL, et al. A transcriptomic view of the proteome variability of newborn and adult Bothrops jararaca snake venoms. PLoS Negl Trop Dis. 2012;6(3), e1554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Instituto Butantan, São Paulo, Brazil

    Jorge Kalil & Hui Wen Fan

Authors
  1. Jorge Kalil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hui Wen Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jorge Kalil .

Editor information

Editors and Affiliations

  1. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media B.V.

About this entry

Cite this entry

Kalil, J., Fan, H.W. (2016). Production and Utilization of Snake Antivenoms in South America. In: Gopalakrishnakone, P. (eds) Toxins and Drug Discovery. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6726-3_26-1

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-6726-3_26-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-6726-3

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation