The Improvement and Standardization of Antivenom Production in Developing Countries: Comparing Antivenom Quality, Therapeutical Efficiency, and Cost

Abstract

The first antivenom was prepared by Calmette in 1894. More than a century later, it is still the only specific treatment for envenoming. The methods currently used by almost all antivenom producers worldwide to isolate and concentrate antivenom antibodies and their enzymatically derived fragments are improvements of those originally developed by Pope in 1938. Several new alternatives have been proposed to produce F(ab')2 or Fab antivenoms to improve their purity, neutralizing potency, and safety and to overcome the problems encountered in the production protocols based on ammonium sulfate precipitation of equine immunoglobulin. These include complete or partial modifications in the antivenom production regarding animal producers (ovine, laying hens...), immunization protocols, crude serum preparation and/or purification procedures concerning antibody extraction (PEG, caprylic acid, ion-exchange chromatography or immunoaffinity chromatography), and cleavage conditions (pepsin, papain...). In Tunisia, antivenom has been produced since the 1950's. Constant improvements and standardization of all the steps involved in antivenom production, purification, and quality control have resulted in a pure, safe, and efficient F(ab')2 product with no side effects when used intravenously, and with a high seroneutralization yield, as a result of the high toxin specific F(ab')2 concentration. The real impact of the new or modified procedures is a substantial increase in the cost of an antivenom dose. The quality is similar to that of the old procedure when its production was accurately standardized, optimized, correctly conducted and controlled. In addition, severe side effects have been reported after application of either equine F(ab')2 or ovine Fab antivenoms purified by the new methods (i.e. ion-exchange chromatography and immunoaffinity chromatography). Consequently, the introduction of these methods in developing countries still needs justification

In vivo pharmacological study on the effectiveness of available polyclonal antivenom against Hemiscorpius lepturus venom

“…For example, in a study performed on rats envenomed by Androctonus australis hector scorpion, cardiovascular and pulmonary effects were neutralized by this route of administration (31). However, in another experiment, IM administration of antivenom in envenomed patients by Buthus tunetanus occitanus did not show significant therapeutic effects (32). Subcutaneous envenomation by H. lepturus venom produced hyperglycemia and augmentation in serum LDH in rabbits (4).…”

Optimization of purification procedure for horse F(ab´)2 antivenom against <i>Androctonus crassicauda</i> (Scorpion) venom

“…In addition, it can precipitate all the immunoglobulin (IgG, IgM and IgA) from serum and leave the albumin in the supernatant. Some albumin molecules are trapped within the immunoglobulin precipitate based on the conventional method [23]. The results indicated that 4.8 was regarded as the best pH for inhibiting enzyme activity due to isoelectric pH of albumin leading to the higher removal of albumin and impure proteins.…”

Appropriate antivenom doses for six types of envenomations caused by snakes in taiwan

“…Although improvements in the production and standardization of antivenom have occurred over the years, and resulted in highly efficient treatments, these changes have increased production costs, and several authors believe that the overall quality is similar to those from older methods when properly conducted (13). Additionally, new assay systems allow a very accurate assessment of antivenom efficacy, apart from changes in a patient clinical status (15).…”