**3. Snakebite envenoming**

Snake envenoming is a major health issue worldwide and often considered a rationalization for morbidity and mortality (morbi-mortality) and a variety of losses, both socially and economically. Conservative estimates of the global incidence of snakebite cases suggest that approximately 5.5 million incidents are reported each year [19]. Snakebite envenoming is a potentially fatal disease that normally occurs as a result of the injection of venom following the bite of a venomous snake. Snakebite envenoming can also be caused by the spraying of venom into a person's eyes by particular snake species that are capable of spitting venom as a defense measure. Envenoming results from an estimated 50–55% of all snakebites. Snakebite envenoming in humans and animals affects multiple organ systems based on the specific snake species and the groups of toxins present in the venom and can cause *inter alia* neuromuscular paralysis, hemorrhage and protracted disruption of hemostasis, cardiotoxicity, tissue necrosis, thrombosis, and myolysis (muscle degeneration) [1, 2].

Taxonomically, snakes are carnivorous in nature, classified as reptiles and may be elapids, vipers, colubrids, boids, or pythons. Whereas the majority of bites occur when snakes are inadvertently stepped on by barefooted or unprotected victims, others may be instigated by alcohol intoxication and malevolence. In terms of classification, more than 3500 snake species are believed to exist, with venomous species accounting for approximately 600 (15–17%) [19].

#### **3.1 Epidemiology of snakebite envenoming**

Available epidemiological data on the control of snakebite envenoming has largely been fragmented, and for that matter inaccurate, a problem attributable to inadequate control efforts or measures. Rather than seeking help from health centers or hospitals, many snakebite victims resort to traditional remedies, a practice which further reduces the accuracy of existing data. Internationally, data available on snakebite reports is generally limited. Particularly, in developing countries, nearly all snakebites and the consequent deaths go unreported. In countries with poor infrastructure in rural areas, the extent of under-reporting is believed to be in excess of 70%. In spite of this, of the estimated 4.5–5.4 million snakebites yearly, close to half (1.8–2.7 million) result in clinical illness, with about 81,000–138,000 deaths due to complications. Globally, snakebites tend to affect rural populations of low socioeconomic status disproportionately, especially with groups considered as high risk including farmers or agricultural workers, hunters, fishermen, herders, occupants of poorly developed houses, working children, and people with little or no access to healthcare and

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

education. High-case fatalities are more common among children, while young people are more frequently affected in terms of morbidities and mortalities. In addition, access to medical care is quite challenging for women from certain cultural backgrounds, with pregnant women being exceedingly vulnerable. Across the world, snakebite envenoming and its associated deaths are unevenly distributed, with the highest cases in Asia (South and South-East) and sub-Saharan Africa. A majority of the world's population is thought to live in these areas, a phenomenon that brings about human-snake conflicts. On the other hand, Australia, Europe, and together with North America have the lowest cases of envenoming [2, 20].

#### **3.2 Mechanism and pathogenesis of snakebite envenoming**

Snake venom is produced and stored in a dedicated gland. During a bite, the venom is released through a compressor muscle-mediated action in which muscle surrounds the venom gland. Through the help of a duct, the venom is delivered to the fangs, which is then delivered into the tissues of a victim. Subsequent to snakebite envenoming, the venom toxins may act on different parts of the body systems. The venom of snakes is delivered or injected *via* a specialized delivery system. In elapids, viperids, and lamprophiids, the system is composed of a group of fangs located anterior to the maxillary bones. However, in colubrids with no front fangs, the fangs are positioned posteriorly. The injection of snake venom may either be subcutaneous or intramuscular based on the size of the fangs. Following envenoming, certain toxic components of the venom evoke pathological effects localized within the surrounding tissues, while some other toxins exert their effects on various organs as a result of their systemic distribution through the blood vessels and lymphatic system [21]. Following bites from vipers and certain cobras, local swelling is detected in a space of 2–4 hours with the potential of extending rapidly to reach its peak 2 or 3 days later. Within 2– 12 hours of the bite, blistering develops and tissue necrosis becomes evident on the first day. In the subsequent weeks or month, the necrotic tissue undergoes sloughing while secondary infections such as osteomyelitis develops. Swelling of the bitten limb may be completely resolved, and normal function restored only after some weeks. Systemic envenoming may be indicated by syncope or vomiting occurring within minutes of the bite. A few hours after the bite, coagulopathy and bleeding set in and can persevere for two or more weeks without treatment. Signs of neurotoxicity can advance to widespread flaccid paralysis and respiratory arrest within half an hour to a few hours [22, 23]. Paralysis resulting from elapid bites including mambas, cobras, and kraits may be reversed if treated with specific antivenoms or acetylcholinesterase inhibitors, with recovery over a period of time in all instances, so long as respiration is supported sufficiently. Occasionally, drowsiness may also be observed with other local symptoms such as moderate or no pain, local swelling (mostly devoid of blisters or necrosis), and paraesthesia [22, 23], In addition, envenomings from non-front-fanged colubrids including boomslangs of African origin and vine snakes are usually typified by bruising (also called ecchymosis), which tends to evolve late or slowly, coagulopathy, systemic bleeding, and severe injury to the kidney, even when envenoming is minimal [24].

#### **3.3 Diagnosis of snakebites**

Snakebite envenoming is an emergency that presents clinical and diagnostic challenges due to the potentially rapid lethal effect. Decision-making can be complicated

by the doubts surrounding the identity of a snake species, the amount of venom injected during a bite, and the composition therein, which may vary depending on the age of the snake and intra-species within its location. Nurses and health assistants are the personnel who manage most cases of snakebites in health posts, dispensaries, clinics, as well as district and rural-level hospitals. Sometimes, it is possible to refer cases to tertiary-level facilities with laboratories, specialists, and intensive care units [1].

#### *3.3.1 Clinical diagnosis*

The clinical diagnosis of snakebite envenoming relies on identifying specific signs in the patient. These include local signs such as swelling, blistering, and local necrosis. For the purposes of accurate diagnosis, systemic signs such as characteristic of viper bites, while signs of neurotoxicity and muscle damage (rhabdomyolysis) are primarily common with elapid bites and sea snake bites, respectively. There may, however, be some exceptions to these observations pertaining to snakebites. For instance, bites from some viper snakes, such as the tropical rattlesnake and berg adder, exhibit signs of neurotoxicity in patients with systemic envenomation. Following the bite of vipers particularly, localized effects including necrosis may occur; however, necrosis tends to manifest slightly later on and therefore may not necessarily be of diagnostic value. Also, in addition to neurotoxicity, certain Australian elapids can cause incoagulable blood and hemorrhage. In a similar way, certain cobras that have the capacity to spit venom into the eyes can cause serious localized painful conjunctivitis together with swelling. Whether or not fang marks are present cannot be used as a basis for diagnosis albeit the distance between the fang marks may offer a clue about the size of the snake implicated in the bite. Nonetheless, the identification of fang marks does not form sufficient basis to suggest that venom has indeed been introduced because in close to 50% of bites, no venom is injected [14].

#### *3.3.2 Laboratory and other diagnostic methods*

The diagnosis of snakebites in the laboratory operates on the basis of the changes, which take place following envenomation in victims. Such changes may include detecting irregular changes in blood parameters [such as incoagulable blood assessable using the 20-minute whole blood clotting test (WBCT20), dramatic drop in platelet count, and changes in white and red blood cell counts], changes in some enzyme levels (e.g. creatine phosphokinase), and presence or absence of myoglobinuria, as well as detecting specific venom antigens in the blood of envenomed individuals (biodetection techniques using immunologically based methods) [14].

Severe hemorrhage may be indicated by a low hematocrit value, while a high hematocrit value may be indicative of haemoconcentration, which occurs when plasma leaks into the tissues due to an increase in capillary permeability. Systemic envenoming by viperids, non-front-fanged colubrids, and oceanic elapids are mainly characterized by incoagulable blood. The 20-minute whole-blood clotting test (WBCT20) is a simple test that involves collecting a few milliliters (normally 2 mL) of venous blood into a new, clean, and dry glass tube, allowing it to stand undisturbed for 20 minutes at room temperature and then tilting the tube to see if it has clotted [25]. The absence of clotting is an indication of a venom that is anticoagulant or severe consumption coagulopathy [23]. Generalized fibrinolysis and intravascular coagulation may be detected by more sensitive laboratory tests including prothrombin and
