title: Preclinical evaluation of caprylic acid-fractionated IgG antivenom for the treatment of Taipan (Oxyuranus scutellatus) envenoming in Papua New Guinea.
abstract: BACKGROUND
  Snake bite is a common medical emergency in Papua New Guinea (PNG). The taipan, Oxyuranus scutellatus, inflicts a large number of bites that, in the absence of antivenom therapy, result in high mortality. Parenteral administration of antivenoms manufactured in Australia is the current treatment of choice for these envenomings. However, the price of these products is high and has increased over the last 25 years; consequently the country can no longer afford all the antivenom it needs. This situation prompted an international collaborative project aimed at generating a new, low-cost antivenom against O. scutellatus for PNG.
  
  
  RESULTS
  A new monospecific equine whole IgG antivenom, obtained by caprylic acid fractionation of plasma, was prepared by immunising horses with the venom of O. scutellatus from PNG. This antivenom was compared with the currently used F(ab')(2) monospecific taipan antivenom manufactured by CSL Limited, Australia. The comparison included physicochemical properties and the preclinical assessment of the neutralisation of lethal neurotoxicity and the myotoxic, coagulant and phospholipase A(2) activities of the venom of O. scutellatus from PNG. The F(ab')(2) antivenom had a higher protein concentration than whole IgG antivenom. Both antivenoms effectively neutralised, and had similar potency, against the lethal neurotoxic effect (both by intraperitoneal and intravenous routes of injection), myotoxicity, and phospholipase A(2) activity of O. scutellatus venom. However, the whole IgG antivenom showed a higher potency than the F(ab')(2) antivenom in the neutralisation of the coagulant activity of O. scutellatus venom from PNG.
  
  
  CONCLUSIONS
  The new whole IgG taipan antivenom described in this study compares favourably with the currently used F(ab')(2) antivenom, both in terms of physicochemical characteristics and neutralising potency. Therefore, it should be considered as a promising low-cost candidate for the treatment of envenomings by O. scutellatus in PNG, and is ready to be tested in clinical trials.
authors: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors: Mariángela
authors: M
authors: Vargas
authors: Alvaro
authors: A
authors: Segura
authors: María
authors: M
authors: Herrera
authors: Mauren
authors: M
authors: Villalta
authors: Ricardo
authors: R
authors: Estrada
authors: Maykel
authors: M
authors: Cerdas
authors: Owen
authors: O
authors: Paiva
authors: Teatulohi
authors: T
authors: Matainaho
authors: Simon D
authors: SD
authors: Jensen
authors: Kenneth D
authors: KD
authors: Winkel
authors: Guillermo
authors: G
authors: León
authors: José María
authors: JM
authors: Gutiérrez
authors: David J
authors: DJ
authors: Williams
references: Mol Phylogenet Evol. 2005 Jan;34(1):1-14
references: 15579378
references: Nature. 1970 Aug 15;227(5259):680-5
references: 5432063
references: PLoS Negl Trop Dis. 2010 Jul 27;4(7):e767
references: 20668549
references: Trans R Soc Trop Med Hyg. 1995 Jul-Aug;89(4):415-7
references: 7570884
references: Toxicon. 1989;27(8):841-8
references: 2781583
references: P N G Med J. 1988 Sep;31(3):195-8
references: 3245338
references: Toxicon. 1990;28(10):1127-9; author reply 1129-32
references: 2264065
references: Biologicals. 2009 Aug;37(4):230-4
references: 19375941
references: WHO Offset Publ. 1981;(58):1-44
references: 7245916
references: Med J Aust. 1991 Feb 18;154(4):266-8
references: 1994203
references: Pharmacol Ther. 1985;31(1-2):79-102
references: 2882528
references: Exp Neurol. 2000 Feb;161(2):517-26
references: 10686073
references: Circ Res. 1987 Oct;61(4 Pt 2):I6-9
references: 2443275
references: Trans R Soc Trop Med Hyg. 1995 Jul-Aug;89(4):444-6
references: 7570895
references: Trans R Soc Trop Med Hyg. 1995 May-Jun;89(3):322-5
references: 7660450
references: Neurochem Res. 1991 Jun;16(6):651-8
references: 1791912
references: Toxicon. 2003 Dec 15;42(8):915-31
references: 15019491
references: Toxicon. 1999 Jun;37(6):895-908
references: 10340829
references: J Immunol Methods. 2003 Nov;282(1-2):63-72
references: 14604541
references: Ann Neurol. 1995 Dec;38(6):916-20
references: 8526464
references: Acta Trop. 2005 Jan;93(1):85-95
references: 15589801
references: Eur J Biochem. 1976 Sep 15;68(2):457-69
references: 976268
references: Trans R Soc Trop Med Hyg. 2008 May;102(5):397-9
references: 18359053
references: J Biol Chem. 1986 Oct 5;261(28):13258-67
references: 3531198
references: Am J Trop Med Hyg. 1995 Jun;52(6):525-31
references: 7611559
references: J Pharmacol Toxicol Methods. 2010 Jan-Feb;61(1):27-31
references: 19615454
references: Cell Mol Life Sci. 2008 Sep;65(18):2897-912
references: 18563294
references: J Neurochem. 2009 Nov;111(3):737-44
references: 19712054
references: Am J Trop Med Hyg. 1998 Feb;58(2):183-9
references: 9580075
references: Blood Coagul Fibrinolysis. 1995 Feb;6(1):65-72
references: 7540879
references: Med J Aust. 2004 Dec 6-20;181(11-12):687-91
references: 15588214
references: Trans R Soc Trop Med Hyg. 2006 Dec;100(12):1173-82
references: 16698053
references: Biochemistry. 1980 Mar 4;19(5):1020-3
references: 6986908
references: Pathophysiol Haemost Thromb. 2005;34(4-5):200-4
references: 16707928
references: Neurotoxicology. 2010 Mar;31(2):239-43
references: 20036687
references: Bull World Health Organ. 1983;61(6):949-56
references: 6609011
references: Biochemistry. 2006 May 9;45(18):5800-16
references: 16669624
references: Toxicon. 1992 Nov;30(11):1343-64
references: 1485334
references: Br J Pharmacol. 1982 May;76(1):61-75
references: 7082907
references: Toxicon. 1979;17(6):661-4
references: 524395
references: Comp Biochem Physiol C Comp Pharmacol Toxicol. 1986;84(1):159-64
references: 2873948
references: Toxicon. 1999 Dec;37(12):1771-8
references: 10519654
references: J Pharmacol Exp Ther. 2005 Dec;315(3):1196-202
references: 16135698
references: Pathology. 1981 Oct;13(4):705-15
references: 7335377
references: Toxicon. 2010 Aug 1;56(1):75-85
references: 20338189
references: J Biol Chem. 1989 Jul 5;264(19):11503-10
references: 2544597
references: Toxicon. 1994 Mar;32(3):351-63
references: 8016856
references: Toxicon. 1989;27(3):297-303
references: 2728022
references: Trans R Soc Trop Med Hyg. 1997 Jan-Feb;91(1):53-6
references: 9093629