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).

Abstract

The therapeutic efficacy and the incidence of early antivenom reactions (EARs) were compared in a clinical trial performed in 79 patients bitten by Bothrops sp. in Urabá, Colombia. Patients were randomized into three groups according to the antivenom administered: A (n ϭ 30, Butantan polyspecific, pepsin-digested Bothrops antivenom); B (n ϭ 27, Butantan polyspecific, whole IgG Bothrops antivenom); and C (n ϭ 22, Colombian commercial, monovalent, whole IgG Bothrops antivenom). The groups were comparable in all clinical and epidemiologic aspects; 33 patients had mild, 22 moderate, and 24 severe envenoming. At the doses used (two, four, and six vials [10 ml/vial] for mild, moderate, and severe envenomings, respectively) there were no differences between the antivenoms in restoring normal hemostatic parameters within 24 hr. The evolution of local envenoming was comparable in the three groups. Serum venom/antivenom kinetics determined by ELISA showed a complete clearance of venom levels 1 hr after treatment in mild/moderate envenomings. In severe cases, venom levels remained detectable up to 24 hr and recurrence of antigenemia was observed in some cases. Antivenom concentrations remained at high levels up to 24 hr of treatment. The incidence of EARs was significantly different in the groups: A (36.7%), B (11.1.%), and C (81.8%). There were no life-threatening anaphylactic reactions. We conclude that the efficacy of the three antivenoms was similar in neutralizing human Bothrops envenomings and that the production of whole IgG antivenoms by caprylic acid fractionation is a good alternative for reducing the incidence of EARs.

What is the optimum concentration of m-cresol in antivenoms?

“…Segura et al (6) observed that the reduction of phenol to a concentration of 0.15 g% maintains the physical stability of antivenoms and decreases their liability of forming aggregates (6). Other researchers corroborate such finding, especially if the protein content is elevated, which may lead to loss of antivenom activity and to adverse reactions due to activation of the immune response (4,21,(26)(27)(28)(29)(30). At the same time, the decrease of m-cresol concentrations may diminish antivenom toxicity to humans, particularly in certain circumstances in which high doses are required, such as in the two cases mentioned by Buntain (31) and Ganthavorn (32) (750 to 1150 mL of antivenom).…”

Anticomplementary Activity of Horse IgG and F(ab')2 Antivenoms

“…7,8 However, various studies have shown that both types of antivenoms can activate the complement system in vitro 9,10 and induce EARs in patients. 11,12 Some data highlight the impact of the fractionation protocol on the induction of EARs. It was shown that IgG antivenom precipitated by ammonium sulphate had more aggregates and induced a higher incidence of EARs than IgG antivenom precipitated by caprylic acid.…”

Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Colombia

“…In several experimental and clinical trials it has been demonstrated that antivenoms are of limited value to stop edema progression within the first 12-24 h of treatment, while they are highly efficient in restoring blood coagulation status within the same time interval (7,22,23).…”

“…The antivenoms commonly used for the serotherapy of snakebites show a very limited efficacy in the neutralization of edema, not only due to the variety of components inducing this alteration, but also due to its rapid onset (6)(7)(8). Defibrinating (in vivo) and coagulant (in vitro) effects are produced by thrombin-like toxins present in the venom which induce fibrinogen consumption and incoagulable blood that may favor systemic bleeding (9).…”