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Gómez Cardona, J. P. ., Gómez Cabal, C. ., & Gómez Cabal, M. L. . (2017). Anti-ophidic sera in Colombia: analysis of production, supply, and recommendations for the improvement of the production network. Biosalud, 16(2), 96–116. https://doi.org/10.17151/biosa.2017.16.2.9
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Abstract
Ophidiotoxicosis or snake accident is a recurring event in Colombia. There are two snake families of epidemiological and clinical importance in the country, vipers and coral snakes. For the snake poisoning treatment, the use of anti-poisonous therapy is mandatory. The sera are manufactured with horse immunoglobulins. Even though these products were discovered more than 100 years ago, still today are constantly changing. Today its industry in Colombia requires a high technification, with processes of efficiency, safety, and high-quality standards. The anti snake sera are not chemical-pharmaceutical products; they are biological products. Therefore, they are not characterized by their chemical composition, but by their therapeutic properties. They are classified as monovalent and polyvalent that, depending on their physical composition, allow neutralizing different kinds of poisons. There are two domestic producers in Colombia (Instituto Nacional De Salud and Probiol Laboratories), and imports are done with a producer from Mexico (Bioclon). The neutralizing capacity and quality vary depending on their composition and manufacturing process associated with some proteins and aggregates, which will influence the type and number of adverse reactions to the medicine. This article intends to contextualize the reader in the manufacturing process, in the problem of scarcity and quality of anti-snake sera in Colombia, providing a valuation to concepts and presenting theoretical foundations that contribute to this issue, and besides, commenting on the current situation of the country because of the shortage of this product.
Keywords:
References
1. Otero R. Manual de diagnóstico y tratamiento del accidente ofídico. Medellin, Colombia: Universidad de Antioquia; 1994. 81 p.
2. Chippaux JP, Goyffon M. Venoms, antivenoms and immunotherapy. Toxicon. 1998; 36(6):823-46.
3. Warrell DA. Venomous Bites, Stings, and Poisoning. Infectious Disease Clinics of North America 2012; 26(2):207-23.
4. Gutiérrez JM, Lomonte B, Rojas G, Gené JA, Chaves F, Estrada R, et al. El suero antiofídico polivalente producido en Costa Rica: estabilidad y capacidad neutralizante. Rev Cost Cienc Méd. 1988; 9(2):155- 69.
5. Ferreira Cardoso D, Yamaguchi IK, Maura Da Silva AM. Produção de Soros Antitoxinas e Perspectivas de Modernização por Técnicas de Biologia Molecular. Animais peçonhentos no Brasil: biologia, clínica e terapêutica dos acidentes. São Paulo: SARVIER; 2003. p. 376-9.
6. Espino-Solis GP, Riaño-Umbarila L, Becerril B, Possani LD. Antidotes against venomous animals: State of the art and prospectives. Journal of Proteomics 2009; 72(2):183-99.
7. 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.
8. Calvete JJ, Sanz L, Angulo Y, Lomonte B, Gutiérrez JM. Venoms, venomics, antivenomics. FEBS Letters. 2009; 583 (1873-3468 (Electronic)):1736 - 43.
9. Otero-Patino R. Epidemiological, clinical, and therapeutic aspects of Bothrops asper bites. Toxicon. 2009; 54(7):998-1011.
10. Gutiérrez JM, Williams D, Fan HW, Warrell DA. Snakebite envenoming from a global perspective: Towards an integrated approach. Toxicon. 2010;56(7):1223-35.
11. Gutiérrez JM, Burnouf T, Harrison RA, Calvete JJ, Kuch U, Warrell DA, et al. A multicomponent strategy to improve the availability of antivenom for treating snakebite envenoming. Bulletin of the World Health Organization 2014; 92(7):526-32.
12. Núñez Rangel V, Fernández Culma M, Rey-Suárez P, Pereañez JA. Development of a sensitive enzyme immunoassay (ELISA) for specific identification of Lachesis acrochorda venom. Journal of Venomous Animals and Toxins including Tropical Diseases. 2012; 18:173-9.
13. Campbell JA, Lamar WW. The Venomous Reptiles of the Western Hemisphere. Volume I. Cornell University Press ed: Cornell University Press; 2004.
14. Otero R, Gutiérrez JM, Estrada R, Osorio RG, Del-Valle G, Valderrama R, et al. Neutralizing capacity of a new monovalent anti-Bothrops atrox antivenom: comparison with two commercial antivenoms. Brazilian Journal of Medical and Biological Research 1997; 30(1):375-9.
15. Gómez J. Accidente ofídico, Seminario de accidente por animales venenosos. Universidad San Martin, Facultad de Medicina, Medelín. 2015.
16. Hui Wen F. Soroterapia. Animais peçonhentos no Brasil: biologia, clínica e terapêutica dos acidentes. São Paulo: SARVIER; 2003. p. 380-93.
17. Calvete JJ, Sanz L, Perez A, Borges A, Vargas AM, Lomonte B, et al. Snake population venomics and antivenomics of Bothropsatrox: Paedomorphism along its transamazonian dispersal and implications of geographic venom variability on snakebite management. Journal of Proteomics 2011; 74(4):510-27.
18. Gutiérrez JM. Envenenamientos por mordeduras de serpientes en América Latina y el Caribe: Una visión integral de carácter regional. Bol Mal Salud Amb. 2011; 51(1):1-16.
19. Santoro ML, Sousa-E-Silva MCC, Gonçalves LRC, Almeida-Santos SM, Cardoso DF, Laporta-Ferreira IL, et al. Comparison of the biological activities in venoms from three subspecies of the South American rattlesnake (Crotalusduris susterrificus, C. durissus cascavella and C. durissus collilineatus). Comparative Biochemistry and Physiology - C Pharmacology Toxicology and Endocrinology. 1999; 122(1):61-73.
20. Faure G, Bon C. Crotoxin, a phospholipase A2 neurotoxin from the South American rattlesnake Crotalus durissus terrificus: purification of several isoforms and comparison of their molecular structure and of their biological activities. Biochemistry 1988; 26(2):730- 8.
21. Otero R. Primer Simposio Colombiano de Toxinología. Medellín 12-14 de marzo. Seroterapia y tratamiento del accidente ofídico en Antioquia y Chocó; Medellín: Universidad de Antioquia; 1998.
22. Otero-Patiño R. Epidemiological, clinical and therapeutic aspects of Bothrops asper bites. Toxicon. 2009; 54(7):998-1011.
23. Lomonte B. Venenos de serpiente: de la investigación al tratamiento. Acta Médica Costarricense 2012; 54:86-96.
24. Chavez-Olortegui C, Lopes CS, Cordeiro FD, Granier C, Diniz CR. An enzyme linked immunosorbent assay (ELISA) that discriminates between Bothrops atrox and Lachesis muta muta venoms.
Toxicon. 1993; 31(4):417-26.
25. Alves Araújo FA, Santalúcia M, Cabral RF. Epidemiologia dos Acidentes por Animais Peçonhentos. In: Cardoso JLC, França Fods, Wen FH, Malaque CMSA, Haddad Junior V, editors. Animais peçonhentos no Brasil: biologia, clínica e terapêutica dos acidentes. São Paulo: Salvier; 2003. p. 6-13.
26. Ministério da Saúde. Fundação Nacional de Saúde. Manual de diagnóstico e tratamento de acidentes por animais peçonhentos. 2ª ed. Brasília (Brasil): Fundação Nacional de Saúde; 2001. 112
p.
27. Cuesta T. JD, Restrepo H. AM. Accidente ofídico bothrópico. In: Peña A. L, Arroyabe H. C, editors. Fundamentos de medicina: Toxicología clínica. Medellín, Colombia: CIB; 2010.
28. Caron EJ, Manock SR, Maudlin J, Koleski J, Theakston RDG, Warrell DA, et al. Apparent marked reduction in early antivenom reactions compared to historical controls: Was it prophylaxis or method of administration? Toxicon. 2009; 54(6):779-83.
29. Otero-Patiño R, Segura Á, Herrera M, Angulo Y, León G, Gutiérrez 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.
30. León G, Stiles B Fau - Alape A, Alape A Fau - Rojas G, Rojas G Fau - Gutiérrez JM, Gutiérrez JM. Comparative study on the ability of IgG and F(ab’)2antivenoms to neutralize lethal and myotoxic effects induced by Micrurus nigrocinctus (coral snake) venom. Am J Trop Med Hyg. 1999; 61(2):266–71.
31. Otero-Patiño R, Silva-Haad JJ, Barona Acevedo MJ, Toro Castaño MF, Quintana Castillo JC, Díaz Cadavid A, et al. Accidente bothrópico en Colombia: estudio multicéntrico de la eficacia seguridad de Antivipmyn-Tri®, un antiveneno polivalente producido en México. IATREIA 2007; 20(3):244-62.
32. de Roodt AR, Litwin S, Estévez J, Gould EG, Dolab JA, Gould J. Comparación entre dos métodos de producción para la elaboración de antivenenos ofídicos. Acta Toxicológica Argentina 2010; 18(1):10- 20.
33. Litwin S, Isabettini AO, Calderón L, Varni LM. Optimización en la recuperación de inmunoglobulinas, como molécula entera y fragmento F(ab´)2 , en la producción de antivenenos. ActaToxicol Argent. 2014; 22(2):82-9.
34. Theakston RDG, Laing GD, Fielding CM, Lascano AF, Touzet JM, Vallejo F, et al. Treatment of snake bites by Bothrops species and Lachesis muta in Ecuador: laboratory screening of candidate antivenoms. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1995; 89(5):550-4.
35. Otero R, Gutiérrez JM, Rojas G, Núñez V, Dı́az 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.
36. Ávila L, De Marco M, Fingermann M, Temprano G, Iácono R, Dokmetjian C, et al. Antivenenos ofídicos: comparación del desempeño de dos métodos de obtención. Rev Argent Salud Pública. 2013; 4(14):12-7.
37. Otero R, Núñez V, Barona J, Díaz A, Saldarriaga M. Características bioquímicas y capacidad neutralizante de cuatro antivenenos polivalentes frente a los efectos farmacológicos y enzimáticos del veneno de Bothrops Asper y Porthidium nasutum de Antioquia y Chocó. IATREIA. 2002; 15(1):5-15.
38. Gutiérrez JM, León G, Burnouf T. Antivenoms for the treatment of snakebite envenomings: The road ahead. Biologicals. 2011; 39(3):129-42.
39. Araceli D, Cheroni P. Producción de suero antiofídico en Uruguay. Rev Med Uruguay. 1994; 10:147- 54.
40. World Health Organization W. Guidelines for the Production, Control and Regulation of Snake Antivenenos ofídicos: comparación del desempeño de dos métodos de . WHO Press ed. Switzerland 2010.
41. Abd-Elsalam MA, Abdoon N, Al-Ahaidib MS. What is the optimum concentration of m-cresol in antivenoms? Journal of Venomous Animals and Toxins including Tropical Diseases. 2011; 17(1):12-22.
42. Zambrano ÁM. Accidente ofídico como evento de interés en salud pública en Colombia: aportes al diseño de estrategias de gestión. Bogotá, D.C., Colombia: Universidad Nacional de Colombia; 2012.
43. World Health Organization W. Rabies and envenomings: a neglected public health issue: report of a Consultative Meeting. Geneva- Italy: World Health Organization; 2007. 32 p.
44. Ayerbe S. Primer simposio Colombiano de Toxinología. Medellín 12-14 de marzo. In: Antioquia. Ud, editor. Seroterapia y tratamiento del ofidismo departamento del cauca, 1993 – 1997;
Medellín.1998.
45. Otero R, Callejas ME, Gutiérrez J, Lotero GJ, Rodríguez O, Villa NH, et al. Necesidades reales de antivenenos en Colombia. Características de los productos y del mercado. Revista Epidemiológica de Antioquia. 2001; 26:49-59.
46. Rodríguez-Vargas AL. Comportamiento general de los accidentes provocados por animales venenosos en Colombia, 2006-2010. Rev salud pública. 2012; 14(6):1001-9.
47. Rodríguez Vargas AL. Comportamiento general de los accidentes provocados por animales venenosos en Colombia entre 2006 y 2010, atendidos en el Centro de Investigación, Gestión e Información Toxicológica de la Universidad Nacional de Colombia. Bogotá, Colombia: Universidad Nacional de Colombia; 2012.
48. Gómez C. Seminario de accidente ofídico en Colombia. Bogotá D.C. 2015.
49. INS. Suero Antiofídico Polivalente, Ficha técnica. 2015. p. 1.
50. PROBIOL LSA. Suero Polivalente Antiviperido “Ficha Técnica”. In: PROBIOL L, editor. 2015. p. 2. From: http://www.probiol.com/images/pdf/probiolsueropolivalente.pdf
51. BIOCLON L. AntivipmynTri, Ficha Técnica. 2015. p. 1. From: http://www.medicalkit.org/index.php?option=com_content&view=article&id=50&Itemid=63
52. Rey-Suárez P, Núñez V, Fernández J, Lomonte B. Integrative characterization of the venom of the coral snake Micrurus dumerilii (Elapidae) from Colombia: Proteome, toxicity, and cross-neutralization by antivenom. Journal of Proteomics 2016; 136:262-73.
53. Castillo MC. Memorias: III Congreso Nacional de Investigación e Innovación en Salud Pública. 5 – 8 Octubre del 2015. Desarrollo de un antiveneno micrúrico polivalente en el Instituto Nacional de Salud; Bogotá: Instituto Nacional de Salud; 2015. p. 41.
54. Suero AntiCoral. [Internet]. 2014. Disponible en: www.icp.ucr.ac.cr/recursos/docs/sueros/INSERTO_ACLQ.pdf.
55. Monje Belmonte S. Determinación de la dosis letal media (Dl50), de cinco especies de género Micrurus en estado de cautiverio en Nilo-Cundinamarca (Colombia). Florencia - Caquetá: Universidad de la Amazonia; 2007. Tesis.
2. Chippaux JP, Goyffon M. Venoms, antivenoms and immunotherapy. Toxicon. 1998; 36(6):823-46.
3. Warrell DA. Venomous Bites, Stings, and Poisoning. Infectious Disease Clinics of North America 2012; 26(2):207-23.
4. Gutiérrez JM, Lomonte B, Rojas G, Gené JA, Chaves F, Estrada R, et al. El suero antiofídico polivalente producido en Costa Rica: estabilidad y capacidad neutralizante. Rev Cost Cienc Méd. 1988; 9(2):155- 69.
5. Ferreira Cardoso D, Yamaguchi IK, Maura Da Silva AM. Produção de Soros Antitoxinas e Perspectivas de Modernização por Técnicas de Biologia Molecular. Animais peçonhentos no Brasil: biologia, clínica e terapêutica dos acidentes. São Paulo: SARVIER; 2003. p. 376-9.
6. Espino-Solis GP, Riaño-Umbarila L, Becerril B, Possani LD. Antidotes against venomous animals: State of the art and prospectives. Journal of Proteomics 2009; 72(2):183-99.
7. 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.
8. Calvete JJ, Sanz L, Angulo Y, Lomonte B, Gutiérrez JM. Venoms, venomics, antivenomics. FEBS Letters. 2009; 583 (1873-3468 (Electronic)):1736 - 43.
9. Otero-Patino R. Epidemiological, clinical, and therapeutic aspects of Bothrops asper bites. Toxicon. 2009; 54(7):998-1011.
10. Gutiérrez JM, Williams D, Fan HW, Warrell DA. Snakebite envenoming from a global perspective: Towards an integrated approach. Toxicon. 2010;56(7):1223-35.
11. Gutiérrez JM, Burnouf T, Harrison RA, Calvete JJ, Kuch U, Warrell DA, et al. A multicomponent strategy to improve the availability of antivenom for treating snakebite envenoming. Bulletin of the World Health Organization 2014; 92(7):526-32.
12. Núñez Rangel V, Fernández Culma M, Rey-Suárez P, Pereañez JA. Development of a sensitive enzyme immunoassay (ELISA) for specific identification of Lachesis acrochorda venom. Journal of Venomous Animals and Toxins including Tropical Diseases. 2012; 18:173-9.
13. Campbell JA, Lamar WW. The Venomous Reptiles of the Western Hemisphere. Volume I. Cornell University Press ed: Cornell University Press; 2004.
14. Otero R, Gutiérrez JM, Estrada R, Osorio RG, Del-Valle G, Valderrama R, et al. Neutralizing capacity of a new monovalent anti-Bothrops atrox antivenom: comparison with two commercial antivenoms. Brazilian Journal of Medical and Biological Research 1997; 30(1):375-9.
15. Gómez J. Accidente ofídico, Seminario de accidente por animales venenosos. Universidad San Martin, Facultad de Medicina, Medelín. 2015.
16. Hui Wen F. Soroterapia. Animais peçonhentos no Brasil: biologia, clínica e terapêutica dos acidentes. São Paulo: SARVIER; 2003. p. 380-93.
17. Calvete JJ, Sanz L, Perez A, Borges A, Vargas AM, Lomonte B, et al. Snake population venomics and antivenomics of Bothropsatrox: Paedomorphism along its transamazonian dispersal and implications of geographic venom variability on snakebite management. Journal of Proteomics 2011; 74(4):510-27.
18. Gutiérrez JM. Envenenamientos por mordeduras de serpientes en América Latina y el Caribe: Una visión integral de carácter regional. Bol Mal Salud Amb. 2011; 51(1):1-16.
19. Santoro ML, Sousa-E-Silva MCC, Gonçalves LRC, Almeida-Santos SM, Cardoso DF, Laporta-Ferreira IL, et al. Comparison of the biological activities in venoms from three subspecies of the South American rattlesnake (Crotalusduris susterrificus, C. durissus cascavella and C. durissus collilineatus). Comparative Biochemistry and Physiology - C Pharmacology Toxicology and Endocrinology. 1999; 122(1):61-73.
20. Faure G, Bon C. Crotoxin, a phospholipase A2 neurotoxin from the South American rattlesnake Crotalus durissus terrificus: purification of several isoforms and comparison of their molecular structure and of their biological activities. Biochemistry 1988; 26(2):730- 8.
21. Otero R. Primer Simposio Colombiano de Toxinología. Medellín 12-14 de marzo. Seroterapia y tratamiento del accidente ofídico en Antioquia y Chocó; Medellín: Universidad de Antioquia; 1998.
22. Otero-Patiño R. Epidemiological, clinical and therapeutic aspects of Bothrops asper bites. Toxicon. 2009; 54(7):998-1011.
23. Lomonte B. Venenos de serpiente: de la investigación al tratamiento. Acta Médica Costarricense 2012; 54:86-96.
24. Chavez-Olortegui C, Lopes CS, Cordeiro FD, Granier C, Diniz CR. An enzyme linked immunosorbent assay (ELISA) that discriminates between Bothrops atrox and Lachesis muta muta venoms.
Toxicon. 1993; 31(4):417-26.
25. Alves Araújo FA, Santalúcia M, Cabral RF. Epidemiologia dos Acidentes por Animais Peçonhentos. In: Cardoso JLC, França Fods, Wen FH, Malaque CMSA, Haddad Junior V, editors. Animais peçonhentos no Brasil: biologia, clínica e terapêutica dos acidentes. São Paulo: Salvier; 2003. p. 6-13.
26. Ministério da Saúde. Fundação Nacional de Saúde. Manual de diagnóstico e tratamento de acidentes por animais peçonhentos. 2ª ed. Brasília (Brasil): Fundação Nacional de Saúde; 2001. 112
p.
27. Cuesta T. JD, Restrepo H. AM. Accidente ofídico bothrópico. In: Peña A. L, Arroyabe H. C, editors. Fundamentos de medicina: Toxicología clínica. Medellín, Colombia: CIB; 2010.
28. Caron EJ, Manock SR, Maudlin J, Koleski J, Theakston RDG, Warrell DA, et al. Apparent marked reduction in early antivenom reactions compared to historical controls: Was it prophylaxis or method of administration? Toxicon. 2009; 54(6):779-83.
29. Otero-Patiño R, Segura Á, Herrera M, Angulo Y, León G, Gutiérrez 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.
30. León G, Stiles B Fau - Alape A, Alape A Fau - Rojas G, Rojas G Fau - Gutiérrez JM, Gutiérrez JM. Comparative study on the ability of IgG and F(ab’)2antivenoms to neutralize lethal and myotoxic effects induced by Micrurus nigrocinctus (coral snake) venom. Am J Trop Med Hyg. 1999; 61(2):266–71.
31. Otero-Patiño R, Silva-Haad JJ, Barona Acevedo MJ, Toro Castaño MF, Quintana Castillo JC, Díaz Cadavid A, et al. Accidente bothrópico en Colombia: estudio multicéntrico de la eficacia seguridad de Antivipmyn-Tri®, un antiveneno polivalente producido en México. IATREIA 2007; 20(3):244-62.
32. de Roodt AR, Litwin S, Estévez J, Gould EG, Dolab JA, Gould J. Comparación entre dos métodos de producción para la elaboración de antivenenos ofídicos. Acta Toxicológica Argentina 2010; 18(1):10- 20.
33. Litwin S, Isabettini AO, Calderón L, Varni LM. Optimización en la recuperación de inmunoglobulinas, como molécula entera y fragmento F(ab´)2 , en la producción de antivenenos. ActaToxicol Argent. 2014; 22(2):82-9.
34. Theakston RDG, Laing GD, Fielding CM, Lascano AF, Touzet JM, Vallejo F, et al. Treatment of snake bites by Bothrops species and Lachesis muta in Ecuador: laboratory screening of candidate antivenoms. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1995; 89(5):550-4.
35. Otero R, Gutiérrez JM, Rojas G, Núñez V, Dı́az 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.
36. Ávila L, De Marco M, Fingermann M, Temprano G, Iácono R, Dokmetjian C, et al. Antivenenos ofídicos: comparación del desempeño de dos métodos de obtención. Rev Argent Salud Pública. 2013; 4(14):12-7.
37. Otero R, Núñez V, Barona J, Díaz A, Saldarriaga M. Características bioquímicas y capacidad neutralizante de cuatro antivenenos polivalentes frente a los efectos farmacológicos y enzimáticos del veneno de Bothrops Asper y Porthidium nasutum de Antioquia y Chocó. IATREIA. 2002; 15(1):5-15.
38. Gutiérrez JM, León G, Burnouf T. Antivenoms for the treatment of snakebite envenomings: The road ahead. Biologicals. 2011; 39(3):129-42.
39. Araceli D, Cheroni P. Producción de suero antiofídico en Uruguay. Rev Med Uruguay. 1994; 10:147- 54.
40. World Health Organization W. Guidelines for the Production, Control and Regulation of Snake Antivenenos ofídicos: comparación del desempeño de dos métodos de . WHO Press ed. Switzerland 2010.
41. Abd-Elsalam MA, Abdoon N, Al-Ahaidib MS. What is the optimum concentration of m-cresol in antivenoms? Journal of Venomous Animals and Toxins including Tropical Diseases. 2011; 17(1):12-22.
42. Zambrano ÁM. Accidente ofídico como evento de interés en salud pública en Colombia: aportes al diseño de estrategias de gestión. Bogotá, D.C., Colombia: Universidad Nacional de Colombia; 2012.
43. World Health Organization W. Rabies and envenomings: a neglected public health issue: report of a Consultative Meeting. Geneva- Italy: World Health Organization; 2007. 32 p.
44. Ayerbe S. Primer simposio Colombiano de Toxinología. Medellín 12-14 de marzo. In: Antioquia. Ud, editor. Seroterapia y tratamiento del ofidismo departamento del cauca, 1993 – 1997;
Medellín.1998.
45. Otero R, Callejas ME, Gutiérrez J, Lotero GJ, Rodríguez O, Villa NH, et al. Necesidades reales de antivenenos en Colombia. Características de los productos y del mercado. Revista Epidemiológica de Antioquia. 2001; 26:49-59.
46. Rodríguez-Vargas AL. Comportamiento general de los accidentes provocados por animales venenosos en Colombia, 2006-2010. Rev salud pública. 2012; 14(6):1001-9.
47. Rodríguez Vargas AL. Comportamiento general de los accidentes provocados por animales venenosos en Colombia entre 2006 y 2010, atendidos en el Centro de Investigación, Gestión e Información Toxicológica de la Universidad Nacional de Colombia. Bogotá, Colombia: Universidad Nacional de Colombia; 2012.
48. Gómez C. Seminario de accidente ofídico en Colombia. Bogotá D.C. 2015.
49. INS. Suero Antiofídico Polivalente, Ficha técnica. 2015. p. 1.
50. PROBIOL LSA. Suero Polivalente Antiviperido “Ficha Técnica”. In: PROBIOL L, editor. 2015. p. 2. From: http://www.probiol.com/images/pdf/probiolsueropolivalente.pdf
51. BIOCLON L. AntivipmynTri, Ficha Técnica. 2015. p. 1. From: http://www.medicalkit.org/index.php?option=com_content&view=article&id=50&Itemid=63
52. Rey-Suárez P, Núñez V, Fernández J, Lomonte B. Integrative characterization of the venom of the coral snake Micrurus dumerilii (Elapidae) from Colombia: Proteome, toxicity, and cross-neutralization by antivenom. Journal of Proteomics 2016; 136:262-73.
53. Castillo MC. Memorias: III Congreso Nacional de Investigación e Innovación en Salud Pública. 5 – 8 Octubre del 2015. Desarrollo de un antiveneno micrúrico polivalente en el Instituto Nacional de Salud; Bogotá: Instituto Nacional de Salud; 2015. p. 41.
54. Suero AntiCoral. [Internet]. 2014. Disponible en: www.icp.ucr.ac.cr/recursos/docs/sueros/INSERTO_ACLQ.pdf.
55. Monje Belmonte S. Determinación de la dosis letal media (Dl50), de cinco especies de género Micrurus en estado de cautiverio en Nilo-Cundinamarca (Colombia). Florencia - Caquetá: Universidad de la Amazonia; 2007. Tesis.
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