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

Abstract

The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05).

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

“…However, clinical trials using IgG antivenoms produced at the Clodomiro Picado Institute found that severe EARs were infrequent. 13,30 A study comparing the concentrations of anaphylatoxins and other inflammatory mediators in plasma from Sri Lanka snakebite victims before and after antivenom therapy was recently published. 31 Sri Lankan snake envenoming induced complement activation and release of inflammatory mediators, and antivenom therapy further increased the levels of these mediators but not anaphylatoxins.…”

Effectiveness of Rapid Transport of Victims and Community Health Education on Snake Bite Fatalities in Rural Nepal

“…8 Previous studies investigated other strategies to reduce snake bite mortality, such as improvement of antivenom efficacy and safety, [15][16][17] and development of better first-aid methods and treatment protocols. [18][19][20][21] We demonstrated the efficacy of an innovative approach, i.e., promoting rapid transport of victims by motorcycle to a specialized snake bite center.…”

Snake antivenoms: adverse reactions and production technology

“…Recently, Otero et al (65) reported a clinical trial that compared two antivenoms composed of IgG processed by caprylic acid purification, with similar aggregate concentration. One of which was treated with β-propiolactone, known to inhibit the complement activation (66).…”