Antivenoms for snakebite envenomings

Inflammation and Allergy - Drug Targets

Volumn 10, Issue 5, 2011, Pages 369-380

  Gutiérrez, José María ^a   León, Guillermo ^a   Lomonte, Bruno ^a   Angulo, Yamileth ^a  

^a UNIVERSIDAD DE COSTA RICA   (Costa Rica)

Author keywords

Adverse reactions; Antivenom; Envenoming; Fractionation; Neglected tropical disease; Pharmacokinetics; Quality control; Snakebite; Viral safety

Indexed keywords

IMMUNOGLOBULIN F(AB')2 FRAGMENT; IMMUNOGLOBULIN F(AB) FRAGMENT; IMMUNOGLOBULIN G; PAPAIN; PEPSIN A; PLACEBO; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; SNAKE VENOM; SNAKE VENOM ANTISERUM;

ANTIBODY RESPONSE; ARTICLE; DNA IMMUNIZATION; DRUG CLEARANCE; DRUG CONTAMINATION; DRUG COST; DRUG CROSS REACTIVITY; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG STORAGE; DRUG SYNTHESIS; ENVENOMATION; IMMUNIZATION; NONHUMAN; SERUM SICKNESS; SNAKEBITE;

EID: 80052828103     PISSN: 18715281     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152811797200669     Document Type: Article

References (123)

1. Bon, C. Serum Therapy was Discovered 100 Years Ago. In: Envenomings and Their Treatments; Bon, C., Goyffon, M., Eds.; Fondation Marcel Mérieux: Lyon, 1996; pp. 3-9.
2. Vital-Brazil, O. History of the primordia of snake-bite accident serotherapy. Mem. Inst. Butantan., 1987, 49, 7-20.
3. Winkel, K.D.; Mirtschin, P.; Pearn, J. Twentieth century toxinology and antivenom development in Australia. Toxicon, 2006, 48, 738-754.
4. Zhang, Y.; Cremer, P.S. Interactions between macromolecules and ions: the Hofmeister series. Curr. Op. Chem. Biol., 2006, 10, 158-163.
5. Pope, C.G. The action of proteolytic enzymes on the antitoxins and proteins in immune sera. I. True digestion of the proteins. Br. J. Exp. Pathol., 1939, 20, 132-149.
6. Pope, C.G. The action of proteolytic enzymes on the antitoxins and proteins in immune sera. II. Heat denaturation after partial enzyme action. Br. J. Exp. Pathol., 1939, 20, 201-212.
7. Gutiérrez, J.M.; León, G. Snake Antivenoms. Technological, Clinical and Public Health Issues. In: Animal Toxins: State of the Art. Perspectives in Health and Biotechnology; de Lima, M.E., Pimenta, A.M.C., Martin-Euclaire, M.F., Zingali, R.B., Rochat, H., Eds,; Editora UFMG: Belo Horizonte, 2009; pp. 393-421.
8. Dos Santos, M.C.; D'Imperio Lima, M.R.; Furtado, G.C.; Colletto, G.M.; Kipnis, T.L.; Dias da Silva, W. Purification of F(ab')2 antisnake venom by caprylic acid: a fast method for obtaining IgG fragments with high neutralization activity, purity and yield. Toxicon, 1989, 27, 297-303.
9. Rojas, G.; Jiménez, J.M.; Gutiérrez, J.M. Caprylic acid fractionation of hyperimmune horse plasma: description of a simple procedure for antivenom production. Toxicon, 1994, 32, 351-63.
10. Grandgeorge, M.; Véron, J.L.; Lutsch, C.; Makula, M.F.; Riffard, P.; Pépin, S.; Scherrmann, J.M. Preparation of Improved F(ab')2 Antivenoms. An Example: New Polyvalent European Viper Antivenom (Equine). In: Envenomings and Their Treatments; Bon, C., Goyffon, M., Eds,; Fondation Marcel Mérieux: Lyon, 1996; pp. 161-172.
11. Al-Abdulla, I.; Garnvwa, J.M.; Rawat, S.; Smith, D.S.; Landon, J.; Nasidi, A. Formulation of a liquid ovine Fab-based antivenom for the treatment of envenomation by the Nigerian carpet viper (Echis ocellatus). Toxicon 2003, 42, 399-404.
12. Theakston, R.D.G.; Warrell, D.A.; Griffiths, E. Report of a WHO workshop on the standardization and control of antivenoms. Toxicon, 2003, 41, 541-557.
13. Gutiérrez, J.M.; Theakston, R.D.G.; Warrell, D.A. Confronting the neglected problem of snake bite envenoming: the need for a global partnership. PLoS Med., 2006, 3, e412.
14. World Health Organization. Rabies and Envenomigs. A Neglected Public Health Issue; World Health Organization: Geneva, 2007, pp. 1-32.
15. Meier, J. Commercially Available Antivenoms ("Hyperimune Sera", "Antivenins", "Antisera") for Antivenom Treatment. In: Handbook of Clinical Toxicology of Animal Venoms and Poisons; Meier, J.; White, J., Eds,; CRC Press: Boca Raton, 1995; pp. 689-721.
16. Lalloo, D.G.; Theakston, R.D.G. Snake antivenoms. J. Toxicol. Clin. Toxicol., 2003, 41, 317-327.
17. Gutiérrez, J.M.; Higashi, H.G.; Wen, F.H.; Burnouf, T. Strengthening antivenom production in Central and South American public laboratories: report of a workshop. Toxicon, 2007, 49, 30-35.
18. Fernández, G.P.; Segura, A.; Herrera, M.; Velasco, W.; Solano, G.; Gutiérrez, J.M.; León, G. Neutralization of Bothrops mattogrossensis snake venom from Bolivia: Experimental evaluation of llama and donkey antivenoms produced by caprylic acid precipitation. Toxicon, 2010, 55, 642-645.
19. World Health Organization. WHO Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins; World Health Organization: Geneva, 2010.
20. Gutiérrez, J.M.; Rojas, G.; Bogarín, G.; Lomonte, B. Evaluation of the Neutralizing Ability of Antivenoms for the Treatment of Snake Bite Envenoming in Central America. In: Envenomings and Their Treatments; Bon, C.; Goyffon, M., Eds,; Fondation Marcel Mérieux: Lyon, 1996; pp. 223-231.
21. Gutiérrez, J.M.; Lomonte, B.; León, G.; Alape-Girón, A.; Flores-Díaz, M.; Sanz, L.; Angulo, Y.; Calvete, J.J. Snake venomics and antivenomics: Proteomic tools in the design and control of antivenoms for the treatment of snakebite envenoming. J. Proteomics, 2009, 165-182.
22. Calvete, J.J.; Sanz, L.; Angulo, Y.; Lomonte, B.; Gutiérrez, J.M. Venoms, venomics, antivenomics. FEBS Lett. 2009, 583, 1736-1743.
23. Fan, H.W.; Cardoso, J.L. Clinical Toxicology of Snake Bites in South America. In: Handbook of Clinical Toxicology of Animal Venoms and Poisons; Meier, J.; White, J., Eds.; CRC Press: Boca Raton, 1995; pp. 667-688.
24. Warrell, D.A. Epidemiology, Clinical Features and Management of Snakebites in Central and South America In: The Venomous Reptiles of the Western Hemisphere; Campbell, J.A.; Lamar, W.W., Eds.; Cornell University Press: Ithaca and London, 2004; Vol. 1, pp. 709-761.
25. Bolaños, R.; Cerdas, L.; Abalos, J.W. Venoms of coral snakes (Micrurus spp): report of a multivalent antivenin for the Americas. Bull. Pan Am. Health Org., 1978, 12, 23-27.
26. Ismail, M.; Al-Ahaidib, M.S.; Abdoon, N.; Abd-Elsalam, M.A. Preparation of a novel antivenom against Atractaspis and Walterinnesia venoms. Toxicon, 2007, 49, 8-18.
27. Ariaratnam, C.A.; Thuraisingam, V.; Kularatne, S.A.; Sheriff, M.H.; Theakstomn, R.D.G.; de Silva, A.; Warrell, D.A. Frequent and potentially fatal envenoming by hump-nosed pit vipers (Hypnale hypnale and H. nepa) in Sri Lanka: lack of effective antivenom. Trans. R. Soc. Trop. Med. Hyg., 2008, 102, 1120-1126.
28. Chippaux, J.P.; Williams, V.; White, J. Snake venom variability: methods of study, results and interpretation. Toxicon, 1991, 29, 1279-1303.
29. Alape-Girón, A.; Sanz, L.; Escolano, J.; Flores-Díaz, M.; Madrigal, M.; Sasa, M.; Calvete, J.J. Snake venomics of the lancehead pitviper Bothrops asper: geographic, individual and ontogenetic variations. J. Proteome Res., 2008, 7, 3556-3571.
30. Barlow, A.; Pook, C.E.; Harrison, R.A.; Wüster, W. Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution. Proc. Biol. Sci., 2009, 276, 1443-1449.
31. Chotwiwatthanakun, C.; Pratapaphon, 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, 39, 1487-1494.
32. Christensen, P.A. 1955. South African Snake Venoms and Antivenoms. The South African Institute for Medical Research: Johannesburg, 1955, 129 p.
33. Sriprapat, S.; Aeksowan, S.; Sapsutthipas, S.; Chotwiwatthanakun, C.; Suttijitpaisal, P.; Pratanaphon, R.; Khow, O.; Sitprija, V.; Ratanabanangkoon, K. The impact of a low dose, low volume, multi-site immunization on the production of therapeutic antivenoms in Thailand. Toxicon, 2003, 41, 57-64.
34. Gutiérrez, J.M.; Rojas, E.; Quesada, L.; León, G.; Núñez, J.; Laing, G.D.; Sasa, M.; Renjifo, J.M.; Nasidi, A.; Warrell, D.A.; Theakston, R.D.G.; 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, 99, 468-475.
35. Cardoso, D.F.; Mota, I. Effect of Crotalus venom on the humoral and cellular immune response. Toxicon, 1997, 35, 607-612.
36. Stephano, M.A.; Guidolin, R.; Higashi, H.G.; Tambourgi, D.V.; Sant'Anna, O.A. The improvement of the therapeutic anti-Lachesis muta serum production in horses. Toxicon, 2005, 45, 467-473.
37. Angulo, Y.; Estrada, R.; Gutiérrez, J.M. Clinical and laboratory alterations in horses during immunization with snake venoms for the production of polyvalent (Crotalinae) antivenom. Toxicon, 1997, 35, 81-90.
38. Fernandes, I.; Lima, E.X.; Takehara, H.A.; Moura-da-Silva, A.M.; Tanjoni, I.; Gutiérrez, J.M. Horse IgG isotypes and crossneutralization of two snake antivenoms produced in Brazil and Costa Rica. Toxicon 2000, 38, 633-644.
39. Steinbach, F.; Deeg, C.; Mauel, S.; Wagner, B. Equine immunology: offspring of the serum horse. Trends Immunol., 2002, 23, 223-225.
40. Bolaños, R. Antivenenos. In: Manual de Procedimientos. Producción y Pruebas de Control en la Preparación de Antisueros Diftérico, Tetánico, Botulínico, Antivenenos y de la Gangrena Gaseosa; Organización Panamericana de la Salud: Washington, D.C., 1977; pp. 104-141.
41. Otero, R.; Gutiérrez, J.M.; Rojas, G.; Núñez, V.; Díaz, A.; Miranda, E.; Uribe, A.F.; Silva, J.F.; Ospina, J.G.; Medina, Y.; Toro, M.F.; García, M.E.; León, G.; García, M.; Lizano, S.; De La Torre, J.; Márquez, J.; Mena, Y.; González, N.; Arenas, L.C.; Puzón, A.; Blanco, N.; Sierra, A.; Espinal, M.E.; Arboleda, M.; Jiménez, J.C.; Ramírez, P.; Díaz, M.; Guzmán, M.C.; Barros, J.; Henao, S.; Ramírez, A.; Macea, U.; Lozano, R.; 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, 895-908.
42. Raw, I.; Guidolin, R.; Higashi, H.G.; Kelen, E.M.A. Antivenins in Brazil: Preparation. In: Handbook of Natural Toxins, Reptile Venoms and Toxins; Tu, A.T., Ed.; Marcel Dekker: New York, 1991, Vol 5, pp. 557-581.
43. Jadhav, S.S.; Kapre, S.V. Antivenom production in India. In: Handbook of Natural Toxins. Reptile Venoms and Toxins; Tu, A.T., Ed.; Marcel Dekker: New York, 1991, Vol 5, 583-610.
44. Jones, R.G.A.; Landon, J. A protocol for 'enhanced pepsin digestion': a step by step method for obtaining pure antibody fragments in high yield from serum. J. Immunol. Meth., 2003, 275, 239-250.
45. Scherrmann, J.M. Antibody treatment of toxin poisoning-recent advances. J. Toxicol. Clin. Toxicol., 1994, 32, 363-375.
46. Gutiérrez, J.M.; León, G.; Lomonte, B. Pharmacokineticpharmacodynamic relationships of immunoglobulin therapy for envenomation. Clin. Pharmacokinet., 2003, 42, 721-741.
47. Covell, D.G.; Barbet, J.; Holton, O.D.; Black, C.D.; Parker, R.J.; Weinstein, J.N. Pharmacokinetics of monoclonal immunoglobulin G1, F(ab')2, and Fab' in mice. Cancer Res., 1986. 46, 3969-3978.
48. Ariaratnam, C.A.; Meyer, W.P.; Perera, G.; Eddleston, M.; Kuleratne, S.A.; Attapattu, W.; Sheriff, R.; Richards, A.M.; Theakston, R.D.G.; Warrell, D.A. A new monospecific ovine Fab fragment antivenom for treatment of envenoming by the Sri Lankan Russell's viper (Daboia russelii russelli): a preliminary dose-finding and pharmacokinetic study. Am. J. Trop. Med. Hyg., 1999, 61, 259-65.
49. Boyer, L.V.; Seifert, S.A.; Clark, R.F.; Williams, S.R.; Nordt, S.P.; Walter, F.G.; Dart, R.C. Recurrent and persistent coagulopathy following pit viper envenomation. Arch. Intern. Med., 1999, 159, 706-710.
50. Gutiérrez, J.M.; Lomonte, B.; León, G.; Rucavado, A.; Chaves, F.; Angulo, Y. Trends in snakebite envenomation therapy: scientific, technological and public health considerations. Curr. Pharm. Des., 2007, 13, 2935-2950.
51. Olvera, A.; Ramos-Cerrillo, B.; Estévez, J.; Clement, H.; de Roodt, A.; Paniagua-Solís, J.; Vázquez, H.; Zavaleta, A.; Arruz, M.S.; Stock, R.P.; Alagón, A. North and South American Loxosceles spiders: development of a polyvalent antivenom with recombinant sphingomyelinases D as antigens. Toxicon, 2006, 48, 64-74.
52. Azevedo-Marques, M.M.; Hering, S.E.; Cupo, P. Acidente Crotálico. In: Animais Peçonhentos no Brasil. Biologia, Clínica e Terapêutica dos Acidentes; Cardoso, J.L.C.; França, F.O.S.; Wen, F.H.; Málaque, C.M.S.; Haddad, V., Eds.; Sarvier: Sao Paulo, 2003; pp. 91-98.
53. Harrison, R.A. Development of venom toxin-specific antibodies by DNA immunization: rationale and strategies to improve therapy of viper envenoming. Vaccine 2004, 22, 1648-1655.
54. Wagstaff, S.C.; Laing, G.D.; Theakston, R.D.G.; Papaspyridis, C.; Harrison, R.A. Bioinformatics and multiepitope DNA immunization to design rational snake antivenom. PLoS Med., 2006, 3, e184.
55. Wang, L.; Sun, X.; Ghosh, R. Purification of equine IgG using membrane based enhanced hybrid bioseparation technique: a potential method for manufacturing hyperimmune antibody. Biotechnol. Bioeng., 2008, 99, 625-633.
56. Burnouf, T.; Radosevich, M. Nanofiltration of plasma-derived biopharmaceutical products. Haemophilia, 2003, 9, 24-37.
57. Segura A.; León, G.; Su, C.Y.; Gutiérrez, J.M.; Burnouf, T. Assessment of the impact of solvent/detergent treatment on the quality and potency of a whole IgG equine antivenom. Biologicals, 2009, 37, 306-312.
58. Ménez, A. Molecular immunology of snake toxins. Pharmac. Ther., 1985, 30, 91-113.
59. Serrano, S.M.T.; Shannon, J.D.; Wang, D.; Camargo, A.C.; Fox, J.W. A multifaceted analysis of viperid snake venoms by twodimensional gel electrophoresis: an approach to understanding venom proteomics. Proteomics, 2005, 5, 501-510.
60. Calvete, J.J.; Juárez, P.; Sanz, L. Snake venomics. Strategy and applications. J. Mass Spectrom., 2007, 42, 1405-1414.
61. Cardoso, D.F.; Yamaguchi, I.K.; Moura da Silva, A.M. Produção de Soros Antitoxinas e Perspectivas de Modernização por Técnicas de Biologia Molecular. In: Animais Peçonhentos no Brasil. Biologia, Clínica e Terapêutica dos Acidentes; Cardoso, J.L.C.; França, F.O.S.; Wen, F.H.; Málaque, C.M.S.; Haddad, V., Eds.; Sarvier: Sao Paulo, 2003, pp. 367-379.
62. Selisko, B.; Cosio, G.; García, C.; Becerril, B.; Possani, L.D.; Horjales, E. Bacterial expression, purification and functional characterization of a recombinant chimeric Fab derived from murine mAb BCF2 that neutralizes the venom of the scorpion Centruroides noxius Hoffmann. Toxicon, 2004, 43, 43-51.
63. Vaughan, T.J.; Williams, A.J.; Pritchard, K.; Osbourn, J.K.; Pope, A.R.; Earnshaw, J.C.; McCafferty, J.; Hodits, R.A.; Wilton, J.; Johnson, K.S. Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nature Biotechnol., 1996, 14, 309-314,
64. Lafaye, P.; Choumet, V.; Demangel, C.; Bon, C.; Mazié, J.C. Biologically active human anti-crotoxin scFv isolated from a semisynthetic phage library. Immunotechnology, 1997, 3, 117-125.
65. Stewart, C.S.; MacKenzie, C.R.; Hall, J.C. Isolation, characterization and pentamerization of0020-αcobrotoxin specific single-domain antibodies from a naïve phage display library: preliminary findings for antivenom development. Toxicon, 2007, 49, 699-709.
66. Juárez-González, V.R.; Riaño-Umbarila, L.; Quintero-Hernández, V.; Olamendi-Portugal, T.; Ortiz-León, M.; Possani, L.D.; Becerril, B. Directed evolution, phage display and combination of evolved mutants: a strategy to recover the neutralization properties of the scFv version of BCF2 a neutralizing monoclonal antibody specific to scorpion toxin Cn2. J. Mol. Biol., 2005, 346, 1287-297.
67. Kulkeaw, K.; Sakolvaree, Y.; Srimanote, P.; Tongtawe, P.; Maneewatch, S.; Sookrung, N.; Tungtrongchitr, A.; Tapchaisri, P.; Kurazono, H.; Chaicumpa, W. Human monoclonal scFv neutralize lethal Thai cobra, Naja kaouthia, neurotoxin. J. Proteomics, 2009, 72, 270-282.
68. Lauwereys, M.; Gharoudi, M.A.; Desmyter, A.; Kinne, J.; Hölzer, W.; De Genst, E.; Wyns, L.; Muyldermans, S. Potent enzyme inhibitors derived from dromedary heavy-chain antibodies. EMBO J, 1998, 17, 3512-20.
69. Omidfar, K.; Rasaee, M.J.; Moditahedi, H.; Forouzandeh, M.; Taghikhani, M.; Golmakani, N. Production of a novel camel singledomain antibody specific for the type III mutant EGFR. Tumor Biol., 2004, 25, 296-305.
70. Rodrigues-Silva, R.; Antunes, G.F.; Velarde, D.T.; Santoro, M.M. Thermal stability studies of hyperimmune horse antivenoms. Toxicon, 1999, 37, 33-45.
71. Segura, A.; Herrera, M.; González, E.; Vargas, M.; Solano, G.; Gutiérrez, J.M.; León, G. Stability of equine IgG antivenoms obtained by caprylic acid precipitation: towards a liquid formulation stable at tropical room temperature. Toxicon, 2009, 53, 609-615.
72. Maria, W.S.; Pacheco, B.G.; Barbosa, C.F.; Velarde, D.T.; Chavez-Olórtegui, C. Determination of the neutralizing potency of horse antibothropic and anticrotalic antivenoms in blood samples collected on filter paper. Toxicon, 2001, 39, 1607-1609.
73. Rial, A.; Morais, V.; Rossi, S.; Massaldi, H. A new ELISA for determination of potency in snake antivenoms. Toxicon, 2006, 48, 462-466.
74. Gutiérrez, J.M.; Avila, C.; Rojas, G.; Cerdas L. An alternative in vitro method for testing the potency of the polyvalent antivenom produced in Costa Rica. Toxicon, 1988, 26, 411-413.
75. Sells, P.G.; Laing, G.D.; Theakston, R.D.G. An in vivo but insensate model for the evaluation of antivenoms (ED50) using fertile hens' eggs. Toxicon, 2001, 39, 665-668.
76. World Health Organization. Progress in the Characterization of Venoms and Standardization of Antivenoms. World Health Organization: Geneva, 1981; pp. 1-43.
77. Bogarín, G.; Morais, J.F.; Yamaguchi, I.K.; Stephano, M.A.; Marcelino, J.R.; Nishikawa, A.K.; Guidolin, R.; Rojas, G.; Higashi, H.G.; Gutiérrez, J.M. Neutralization of crotaline snake venoms from Central and South America by antivenoms produced in Brazil and Costa Rica. Toxicon, 2000, 38, 1429-1441.
78. Araújo, H.P.; Bourguignon, S.C.; Boller, M.A.; Dias, A.A.; Lucas, E.P.; Santos, I.C.; Delgado, I.F. Potency evaluation of antivenoms in Brazil: the national control laboratory experience between 2000 and 2006. Toxicon, 2008, 51, 502-514.
79. Gutiérrez, J.M.; Rojas, G.; Cerdas, L. Ability of a polyvalent antivenom to neutralize the venom of Lachesis muta melanocephala, a new Costa Rican subspecies of the bushmaster. Toxicon, 1987, 25, 713-20.
80. Theakston, R.D.G.; Reid, H.A. Development of simple standard assay procedures for the characterization of snake venom. Bull. World Health Organ., 1983, 61, 949-956.
81. Instituto Clodomiro Picado. Determinación de Actividades Tóxicas de Venenos de Serpientes y su Neutralización por Antivenenos. Manual de Métodos de Laboratorio. Instituto Clodomiro Picado: San José, 2008, pp. 1-31.
82. Gutiérrez, J.M.; Chaves, F.; Rojas, E.; Elizondo, J.; Avila, C.; Cerdas, L. Production of monovalent anti-Bothrops asper antivenom: development of immune response in horses and neutralizing ability. Rev. Biol. Trop., 1988, 36, 511-517.
83. Colombini, M.; Fernandes, I.; Cardoso, D.F.; Moura-da-Silva, A.M. Lachesis muta muta venom: immunological differences compared with Bothrops atrox venom and importance of specific antivenom therapy. Toxicon, 2001, 39, 711-719.
84. Theakston, R.D.G.; Laing, G.D.; Fielding, C.M.; Lascano, A.F.; Touzet, J.M.; Vallejo, F.; Guderian, R.H.; Nelson, S.J.; Wüster, W., Richards, A.M. Treatment of snake bites by Bothrops species and Lachesis muta in Ecuador: laboratory screening of candidate antivenoms. Trans. R. Soc. Trop. Med. Hyg., 1995, 89, 550-554.
85. Gutiérrez, J.M.; Gené, J.A.; Rojas, G.; Cerdas, L. Neutralization of proteolytic and hemorrhagic activities of Costa Rican snake venoms by a polyvalent antivenom. Toxicon, 1985, 23, 887-893.
86. De Roodt, A.; Dolab, J.A.; Fernández, T.; Segre, L.; Hajos, S.E. Cross-reactivity and heterologous neutralization of crotaline antivenoms used in Argentina. Toxicon, 1998, 36, 1025-38.
87. ®) for the treatment of viper envenoming in sub-Saharan Africa. Toxicon, 2010, 55, 369-374
88. Lomonte, B.; León, G.; Angulo, Y.; Rucavado, A.; Núñez, V. Neutralization of Bothrops asper venom by antibodies, natural products, and synthetic drugs: contributions to understanding snakebite envenomings and their treatment. Toxicon 2009, 54, 1012-1028.
89. Meyer, W.P.; Habib, A.G.; Onayade, A.A.; Yakubu, A.; Smith, D.C.; Nasidi, A.; Daudu, I.J.; Warrell, D.A.; Theakston, R.D.G. First clinical experiences with a new ovine Fab Echis ocellatus snake bite antivenom in Nigeria: randomized comparative trial with Institute Pasteur Serum (IPSER) Africa antivenom. Am. J. Trop. Med. Hyg., 1997, 56, 291-300.
90. Warrell, D.A.; Davidson, N.M.; Omerod, L.D.; Pope, H.M.; Watkins, B.J.; Greenwood, B.M.; Reid, H.A. Bites by the sawscaled or carpet viper (Echis carinatus): trial of two specific antivenoms. Br. Med. J., 1974, 4, 437-440.
91. Cardoso, J.L.C.; Fan, H.W.; França, F.O.S.; Jorge, M.T.; Leite, R.P.; Nishioka, S.A.; Ávila, A.; Sano-Martins, I.S.; Tomy, S.C.; Santoro, M.L.; Chudzinski, A.M.; Castro, S.C.B.; Kamiguti, A.S.; Kelen, E.M.A.; Hirata, M.H.; Mirnadola, R.M.S.; Theakston, R.D.G.; Warrell, D.A. Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in São Paulo, Brazil. Q. J. Med., 1993, 86, 315-325.
92. Smalligan, R.; Cole, J.; Brito, N.; Laing, G.D.; Mertz, B.L.; Manock, S.; Maudlin, J.; Quist, B.; Holland, G.; Nelson, S.; Lalloo, D.G.; Rivadeneira, G.; Barragan, M.E.; Dolley, D.; Eddleston, M.; Warrell, D.A.; Theakston, R.D.G. Crotaline snake bite in the Ecuadorian Amazon: randomized double blind comparative trial of three South American polyspecific antivenoms. Br. Med. J., 2004, 329, 1129-1135.
93. Otero, R.; León, G.; Gutiérrez, J.M.; Rojas, G.; Toro, M.F.; Barona, J.; Rodríguez, V.; Díaz, A.; Núñez, V.; Quintana, J.C.; Ayala, S.; Mosquera, D.; Conrado, L.L.; Fernández, D.; Arroyo, Y.; Paniagua, C.A.; López, M.; Ospina, C.E.; Alzate, C.; Fernández, J.; Meza, J.J.; Silva, J.F.; Ramírez, P.; Fabra, P.E.; Ramírez, E.; Córdoba, E.; Arrieta, A.B.; Warrell, D.A.; Theakston, R.D.G. Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without β-propiolactone, in the treatment of Bothrops asper bites in Colombia. Trans. R. Soc. Trop. Med. Hyg., 2006, 100, 1173-1182.
94. Chippaux, J.P.; Massougbodji, A.; Stock, R.; Alagón, A. Clinical trial of an F(ab')2 polyvalent antivenom for African snake bites in Benin. Am. J. Trop. Med. Hyg., 2007, 77, 538-546.
95. Warrell, D.A. Clinical Features of Envenoming from Snake Bites. In: Envenomings and Their Treatments; Bon, C.; Goyffon, M., Eds.; Fondation Marcel Mérieux: Lyon, 1996, pp. 63-76.
96. Gutiérrez, J.M.; León, G.; Rojas, G.; Lomonte, B.; Rucavado, A.; Chaves, F. Neutralization of local tissue damage induced by Bothrops asper (terciopelo) snake venom. Toxicon, 1998, 36, 1529-1538.
97. Warrell, D.A. Clinical Toxicology of Snakebite in Africa and the Middle East/Arabian Peninsula. In: Handbook of Clinical Toxicology of Animal Venoms and Poisons; Meier, J.; White, J., Eds.; CRC Press: Boca Raton, 1995; pp. 433-492.
98. Fan, H.W. Soroterapia. In: Animais Peçonhentos no Brasil. Biologia, Clínica e Terapêutica dos Acidentes; Cardoso, J.L.C.; França, F.O.S.; Wen, F.H.; Málaque, C.M.S.; Haddad, V., Eds.; Sarvier: Sao Paulo, 2003; pp. 380-393.
99. Chippaux, J.P.; Lang, J.; Eddine, S.A.; Fagot, P.; Rage, V.; eyrieux, J.C.; Le Mener, V. Clinical safety of a polyvalent F(ab')2 equine antivenom in 223 African snake envenomations: a field trial in Cameroon. Trans. R. Soc. Trop. Med. Hyg., 1998, 92, 657-62.
100. Otero-Patiño, R.; Cardoso, J.L.C.; Higashi, H.G.; Núñez, V.; Díaz, A.; Toro, M.F.; García, M.E.; Sierra, A.; García, L.F.; Moreno, A.M.; Medina, M.C.; Castañeda, N.; Silva-Díaz, J.F.; Murcia, M.; Cárdenas, S.Y.; Dias da Silva, W.D. A randomized, blinded, comparative trial of one pepsin-digested and two whole IgG antivenoms for Bothrops snake bites in Urabá, Colombia. Am. J. Trop. Med. Hyg., 1998, 58, 183-189.
101. Moran, N.F.; Newman, W.J.; Theakston, R.D.G.; Warrell, D.A.; Wilkinson, D. High incidence of early anaphylactoid reaction to SAIMR polyvalent snake antivenom. Trans. R. Soc. Trop. Med. yg., 1998, 92, 69-70.
102. Warrell, D.A. WHO/SEARO Guidelines for the clinical management of snake bites in the Southeast Asian region. Southeast Asian J. Trop. Med. Public Health, 1999, 30 (Suppl 1), 1-85.
103. Sutherland, S.K. Serum reactions. An analysis of commercial antivenoms and the possible role of anticomplementary activity in de-novo reactions to antivenoms and antitoxins. Med. J. Aust., 1977, 1, 613-615.
104. León, G.; Monge, M.; Rojas, E.; Lomonte, B.; Gutiérrez, J.M. Comparison between IgG and F(ab')2 polyvalent antivenoms: neutralization of systemic effects produced by Bothrops asper venom in mice, extravasation to muscle tissue, and potential for induction of adverse reactions. Toxicon, 2001, 39, 793-801.
105. Herrera, M.; León, G.; Segura, A.; Meneses, F.; Lomonte, B.; Chippaux, J.P.; Gutiérrez, J.M. Factors associated with adverse reactions induced by caprylic acid-fractionated whole IgG preparations: comparison between horse, sheep and camel IgGs. Toxicon, 2005, 46, 775-81.
106. Malasit, P.; Warrell, D.A.; Chanthavanich P.; Viravan, C.; Mongkolsapaya, J.; Singhthong, B.; Supich, C. Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites. Br. Med. J., 1986, 292, 17-20.
107. Morais, J.F.; de Freitas, M.C.; Yamaguchi, I.K.; Dos Santos, M.C.; Dias da Silva, W. Snake antivenoms from hyperimmunized horses: comparison of the antivenom activity and biological properties of their whole IgG and F(ab')2 fragments. Toxicon, 1994, 32, 725-734.
108. ®, un antiveneno polivalente producido en México. Iatreia, 2007, 20, 244-262.
109. García, M.; Monge, M.; León, G.; Lizano, S.; Segura, E.; Solano, G.; Rojas, G.; Gutiérrez, J.M. Effect of preservatives on IgG aggregation, complement-activating effect and hypotensive activity of horse polyvalent antivenom used in snakebite envenomation. Biologicals, 2002, 30, 143-151.
110. León, G.; Rodríguez, M.A.; Rucavado, A.; Lomonte, B.; Gutiérrez, J.M. Anti-human erythrocyte antibodies in horse-derived antivenoms used in the treatment of snakebite envenomations. Biologicals, 2007, 35, 5-11.
111. Ayuso, R.; Lehrer, S.B.; López, M.; Reese, G.; Ibáñez, M.D.; Esteban, M.M.; Ownby, D.R.; Schwartz, H. Identification of bovine IgG as a major cross-reactive vertebrate meat allergen. Allergy, 2000, 55, 348-354.
112. Hunter, W.M.; Budd, P.S. Circulating antibodies to ovine and bovine immunoglobulin in healthy subjects: a hazard for immunoassays. Lancet, 1980, 1136.
113. Bernhisel-Broadbent, J.; Yolken, R.H.; Sampson, H.A. Allergenicity of orally administered immunoglobulin preparations in food-allergic children. Pediatrics, 1991, 87, 208-214.
114. León, G.; Segura, A.; Herrera, M.; Otero, R.; França, F.O.; Barbaro, K.C.; Cardoso, J.L.; Wen, F.H.; de Medeiros, C.R.; Prado, J.C.; Málaque, C.M.; Lomonte, B.; Gutiérrez, J.M. Human heterophylic antibodies against equine immunoglobulins: assessment of their role in the early adverse reactions to antivenom administration. Trans. R. Soc. Trop. Med. Hyg., 2008, 102, 1115-1119.
115. Corrigan, P.; Russell, F.E.; Wainschel, J. Clinical reactions to antivenin. In: Toxins: Animal, Plant and Microbial; Rosenberg, P., Ed.; Pergamon Press: Oxford, 1978; pp. 457-65.
116. LoVecchio, F.; Klemens, J.; Roundy, E.B.; Klemens, A. Serum sickness following administration of Antivenin (Crotalidae) Polyvalent in 181 cases of presumed rattlesnake envenomation. Wilderness Environ. Med., 2003, 14, 220-221.
117. Burnouf, T.; Griffiths, E.; Padilla, A.; Seddik, S.; Stephano, M.A.; Gutiérrez, J.M. Assessment of the viral safety of antivenoms fractionated from equine plasma. Biologicals, 2004, 32, 115-128.
118. Burnouf, T.; Terpstra, F.; Habib, G.; Seddik, S. Assessment of viral inactivation during pH 3.3 pepsin digestion and caprylic acid treatment of antivenoms. Biologicals, 2007, 35, 329-334.
119. Williams, D.; Gutiérrez, J.M.; Harrison, R.; Warrell, D.A.; White, J.; Winkel, K.D.; Gopalakrishnakone, P. An antidote for snake bite: the global snake bite initiative. Lancet, 2010, 375, 89-91.
120. Gutiérrez, J.M.; Williams, D.; Fan, H.W.; Warrell, D.A. Snakebite envenoming from a global perspective: towards an integrated approach. Toxicon, 2010, 56, 1223-1235.
121. Leynaud, G.C.; Reati, G.J. Identificación de las zonas de riesgo ofídico en Córdoba, Argentina, mediante el programa SIGEpi. Rev. Panam. Salud Pública, 2009, 26, 64-69.
122. Gutiérrez, J.M.; Fan, H.W.; Silvera, C.L.; Angulo, Y. Stability, distribution and use of antivenoms for snakebite envenomation in Latin America: report of a workshop. Toxicon, 2009, 53, 625-630.
123. Han, S.K.; Yoon, E.T.; Scott, D.L.; Sigler, P.B.; Cho, W. Structural aspects of interfacial adsorption. A crystallographic and sitedirected mutagenesis study of the phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus. J. Biol. Chem., 1997, 272, 3573-3582.