*Perspective Chapter: Diagnostic and Antivenom Immunotherapeutic Approaches… DOI: http://dx.doi.org/10.5772/intechopen.112147*

Antivenom in its liquid form requires, in addition to preservatives, and more challengingly, the need for refrigeration at 4–6°C in order to ensure that its potency is maintained. Although freeze-dried or lyophilized antivenom products are also available, the liquid form is distributed in order to cut down cost and maximize its use [32]. Also, the incidence of adverse reactions is believed to be increased by the formation of protein aggregates, particularly in liquid antivenom, a phenomenon triggered by high temperatures [33]. Owing to the poor stability, antivenoms are sold with dates of expiration, while also warning users to avoid those that have undergone several cycles of freeze-thawing, even though a handful of the available evidence suggests that the efficacy of an antivenom is not significantly affected by either of these two [34].

## *3.4.1.3 Adverse effects/reactions associated with antivenom therapy*

Antivenoms by their architecture contain antigenic proteins, which cause the immune system to be activated, thereby leading to adverse reactions. These reactions are classified as acute (anaphylactic or pyrogenic) and delayed "plasma" sickness (given that most antivenoms are made from plasma), with the latter still been referred to as late "serum" sickness [35]. The early type reactions are characterized by mild symptoms such as headaches, coughing, nausea, vomiting, and diarrhea, and others may be sparked immediately, although symptoms can start after about 1 hour. Severe anaphylactic reactions are also capable of developing and may be associated among other symptoms with angioedema, hypotension, and bronchospasm [23]. Endotoxins, occurring as a result of bacterial contamination, may give rise to pyrogenic reactions associated with symptoms such as fever, reduced blood pressure, chills, and vasodilation. On the other hand, late-type reactions mostly show up a number of days following administration of the initial dose and may be characterized by the same symptoms not only as happens with the early reactions but also other symptoms including joint pains, albuminuria, adenopathy, and occasionally encephalopathy. Prophylactic drugs, including hydrocortisone and adrenaline, are used to frequently treat anaphylactic reactions successfully [36]. How frequently adverse reactions occur and their nature depends partly on the level of purification of the antivenom. While in about 54% of patients, adverse reactions have been reported to be caused by crude firstgeneration antivenoms and second-generation antivenoms, which are obtained by affinity chromatography, and contain only intact IgGs without plasma proteins, have been reported to decrease adverse side effects to below 25% of victims. Thirdgeneration antivenoms are generated by the enzymatic digestion of antibodies with either pepsin or papain leading to the removal of Fc regions, which are believed to cause fewer adverse side effects. In the midst of all these purification processes, however, the full neutralization effect of antivenoms is hardly achieved [15].

#### *3.4.1.4 Cost of antivenoms*

The cost of maintaining animals coupled with increasing immunoglobulin purification procedures are thought to account for the rise in treatment costs. In the developed world, more effective and expensive generations of antivenoms are available for use, where cost may not be an issue. However, in the developing world with rampant snakebites, such exorbitant antivenoms have the potential to cripple victims both financially and physically following a snakebite, with most of the time friends and family having to share in the financial burden. Treatment cost in India is estimated around \$5000, a cost which is more than 2-fold the per capita GDP of India, and

represents in excess of 10 years financial entitlements (in terms of salary) of a normal farm worker [37]. In the United States, there are reports of extremely high treatment costs (with antivenom inclusive) of about \$153,000, with the possibility of even costlier treatments taking place [38]. In the face of this, however, inexpensive antivenoms are still possible to produce. At a treatment cost of just about \$40, this is regarded as one of the most cost-effective antivenom treatments anywhere in the world, developed from a collaboration between Nigeria and the UK [30]. According to [38], treatment costs in some countries can go as high as 1000 times the cost involved in producing a vial of antivenom after considering expenses from clinical trials and hospital charges.
