The first advance on crude filtered immune serum or plasma for treatin
g systemically envenomed bite victims was the use of IgG (predominantl
y equine) precipitated by salt treatment. This was followed by the dev
elopment of F(ab')(2) antivenoms, prepared using pepsin digestion to r
emove both the highly reactive and nonspecific Fc part of the Ige mole
cule and also other non-antibody proteins from the material. Within no
rmal limitations, both monospecific (raised against the venom of a sin
gle species) and polyspecific (raised against a mixture of venoms of d
ifferent species) F(ab')2 antivenoms have proved to be generally effec
tive. Many preparations are poor for a wide range of reasons often not
related to the method of preparation. The main problem associated wit
h them is the high reaction rate in patients caused by complement-medi
ated anaphylactic reactions, The most significant recent development i
n immunotherapy has been the production of ovine Fab antivenoms prepar
ed 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. Af
finity purification of both Fab and F(ab')(2) antivenoms also results
in a major increase in specific activity when compared with the origin
al serum source, but this adds greatly to the cost of production, rend
ering its use prohibitive in the rural tropics where bites and stings
are a major problem. The use of sheep as opposed to horses for immunis
ation also results in a cheaper product, due to the lower cost of anim
al maintenance; theoretically, sheep preparations should also be safer
, causing fewer sensitivity reactions, due to the nature of ovine as o
pposed to equine protein. Additionally, it is a great advantage in the
rural tropics to have a lyophilised, as opposed to a liquid, antiveno
m because of the longer shelf-life of the former at ambient tropical t
emperatures. However, lyophilisation does add considerably to the cost
of production, involves additional testing and has also in the past b
een 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. Alternati
ves to conventional antivenoms should also be explored in the future.