The first advance on crude filtered immune serum or plasma for treating systemically envenomed bite victims was the use of IgG (predominantly equine) precipitated by salt treatment. This was followed by the development of F(ab')(2) antivenoms, prepared using pepsin digestion to remove both the highly reactive and nonspecific Fc part of the IgG molecule and also other non-antibody proteins from the material. Within normal limitations, both monospecific (raised against the venom of a single species) and polyspecific (raised against a mixture of venoms of different species) F(ab')(2) antivenoms have proved to be generally effective. Many preparations are poor for a wide range of reasons often not related to the method of preparation. The main problem associated with them is the high reaction rate in patients caused by complement-mediated anaphylactic reactions. The most significant recent development in immunotherapy has been the production of ovine Fab antivenoms prepared by replacing pepsin digestion with papain digestion. Theoretically, these possess advantages over F(ab')(2) antivenoms, such as a greater volume of distribution and more rapid kinetics. A major disadvantage of Fab antivenoms is, however, their shorter clearance time, which may result in inadequate blood antivenom concentrations for neutralising venom entering the system late from a venom depot at the bite site. Affinity purification of both Fab and F(ab')(2) antivenoms also results in a major increase in specific activity when compared with the original serum source, but this adds greatly to the cost of production, rendering its use prohibitive in the rural tropics where bites and stings are a major problem. The use of sheep as opposed to horses for immunisation also results in a cheaper product, due to the lower cost of animal maintenance; theoretically, sheep preparations should also be safer, causing fewer sensitivity reactions, due to the nature of ovine as opposed to equine protein. Additionally, it is a great advantage in the rural tropics to have a lyophilised, as opposed to a liquid, antivenom because of the longer shelf-life of the former at ambient tropical temperatures. However, lyophilisation does add considerably to the cost of production, involves additional testing and has also in the past been reported to result in some decrease in neutralising potency. There may well be a case for the development of a combined ovine Fab/F(ab')(2) antivenom which combines the advantages of each product. Alternatives to conventional antivenoms should also be explored in the future.
