Preclinical Evaluation of Caprylic Acid-fractionated IgG Antivenom for the Treatment of Taipan (Oxyuranus Scutellatus) Envenoming in Papua New Guinea

Overview

Journal PLoS Negl Trop Dis

Specialties Infectious Diseases
Tropical Medicine

Date 2011 May 26

PMID 21610854

Citations 21

Authors

Mariangela Vargas

Alvaro Segura

Maria Herrera

Mauren Villalta

Ricardo Estrada

Maykel Cerdas

Owen Paiva

Teatulohi Matainaho

Simon D Jensen

Kenneth D Winkel

Guillermo Leon

Jose Maria Gutierrez

David J Williams

Affiliations

Soon will be listed here.

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.

Methodology/principal Findings: 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/significance: 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.

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References

Wuster W, Dumbrell A, Hay C, Pook C, Williams D, Fry B . Snakes across the Strait: trans-Torresian phylogeographic relationships in three genera of Australasian snakes (Serpentes: Elapidae: Acanthophis, Oxyuranus, and Pseudechis). Mol Phylogenet Evol. 2004; 34(1):1-14. DOI: 10.1016/j.ympev.2004.08.018. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Abubakar I, Abubakar S, Habib A, Nasidi A, Durfa N, Yusuf P . Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria. PLoS Negl Trop Dis. 2010; 4(7):e767. PMC: 2910709. DOI: 10.1371/journal.pntd.0000767. View

Trevett A, Lalloo D, Nwokolo N, Naraqi S, Kevau I, Theakston R . Electrophysiological findings in patients envenomed following the bite of a Papuan taipan (Oxyuranus scutellatus canni). Trans R Soc Trop Med Hyg. 1995; 89(4):415-7. DOI: 10.1016/0035-9203(95)90035-7. View

Gene J, Roy A, Rojas G, Gutierrez J, Cerdas L . Comparative study on coagulant, defibrinating, fibrinolytic and fibrinogenolytic activities of Costa Rican crotaline snake venoms and their neutralization by a polyvalent antivenom. Toxicon. 1989; 27(8):841-8. DOI: 10.1016/0041-0101(89)90096-2. View

Currie B, Vince J, Naraqi S . Snake bite in Papua New Guinea. P N G Med J. 1988; 31(3):195-8. View

Gutierrez J, Rojas G, Lomonte B, Gene J, Chaves F, Alvarado J . Standardization of assays for testing the neutralizing ability of antivenoms. Toxicon. 1990; 28(10):1127-9; author reply 1129-32. DOI: 10.1016/0041-0101(90)90110-s. View

Herrera M, Meneses F, Gutierrez J, Leon G . Development and validation of a reverse phase HPLC method for the determination of caprylic acid in formulations of therapeutic immunoglobulins and its application to antivenom production. Biologicals. 2009; 37(4):230-4. DOI: 10.1016/j.biologicals.2009.02.020. View

. Progress in the characterization of venoms and standardization of antivenoms. WHO Offset Publ. 1981; (58):1-44. View

10.

Currie B, Sutherland S, Hudson B, Smith A . An epidemiological study of snake bite envenomation in Papua New Guinea. Med J Aust. 1991; 154(4):266-8. DOI: 10.5694/j.1326-5377.1991.tb121088.x. View

11.

Harris J . Phospholipases in snake venoms and their effects on nerve and muscle. Pharmacol Ther. 1985; 31(1-2):79-102. DOI: 10.1016/0163-7258(85)90038-5. View

12.

Harris J, Grubb B, Maltin C, Dixon R . The neurotoxicity of the venom phospholipases A(2), notexin and taipoxin. Exp Neurol. 2000; 161(2):517-26. DOI: 10.1006/exnr.1999.7275. View

13.

Brown A, Yatani A, Lacerda A, Gurrola G, Possani L . Neurotoxins that act selectively on voltage-dependent cardiac calcium channels. Circ Res. 1987; 61(4 Pt 2):I6-9. View

14.

Trevett A, Lalloo D, Nwokolo N, Naraqi S, Kevau I, Theakston R . Failure of 3,4-diaminopyridine and edrophonium to produce significant clinical benefit in neurotoxicity following the bite of Papuan taipan (Oxyuranus scutellatus canni). Trans R Soc Trop Med Hyg. 1995; 89(4):444-6. DOI: 10.1016/0035-9203(95)90051-9. View

15.

Trevett A, Lalloo D, Nwokolo N, Naraqi S, Kevau I, Theakston R . The efficacy of antivenom in the treatment of bites by the Papuan taipan (Oxyuranus scutellatus canni). Trans R Soc Trop Med Hyg. 1995; 89(3):322-5. DOI: 10.1016/0035-9203(95)90562-6. View

16.

Lambeau G, Lazdunski M, Barhanin J . Properties of receptors for neurotoxic phospholipases A2 in different tissues. Neurochem Res. 1991; 16(6):651-8. DOI: 10.1007/BF00965551. View

17.

Gutierrez J, Ownby C . Skeletal muscle degeneration induced by venom phospholipases A2: insights into the mechanisms of local and systemic myotoxicity. Toxicon. 2004; 42(8):915-31. DOI: 10.1016/j.toxicon.2003.11.005. View

18.

Otero R, Gutierrez J, Rojas G, Nunez V, Diaz A, Miranda E . 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. DOI: 10.1016/s0041-0101(98)00220-7. View

19.

Raweerith R, Ratanabanangkoon K . Fractionation of equine antivenom using caprylic acid precipitation in combination with cationic ion-exchange chromatography. J Immunol Methods. 2003; 282(1-2):63-72. DOI: 10.1016/j.jim.2003.07.014. View

20.

Connolly S, Trevett A, Nwokolo N, Lalloo D, Naraqi S, Mantle D . Neuromuscular effects of Papuan Taipan snake venom. Ann Neurol. 1995; 38(6):916-20. DOI: 10.1002/ana.410380612. View