Kamis, 25 Agustus 2011

RABIES AND ENVENOMINGS: neglected diseases

Rabies and envenomings are diseases that result from bites by rabid mammals or bites and stings by venomous animals, especially snakes and scorpions. In all cases, appropri-ate early treatment, including therapeutic antisera, can prevent life-threatening systemic spread of the virus or venom toxins.

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RABIES

In most parts of the world, rabies is endemic (Figure 1). Rabies virus, a rhabdovirus present in infected animal's saliva is inoculated into the bite wounds (Figure 2a), enters peripheral nerves and spreads to the central nervous system where it causes a lethal encephalomyelitis (Figure 2b). Once clinically established, rabies encephalomyelitis is almost invariably fatal, but the disease is entirely preventable provided that complete post-exposure prophylaxis is implemented promptly (2).

The regimen of post-exposure prophylaxis for people bitten by rabid mammals that is currently recommended by WHO consists of a combination of wound cleaning, active immu-nization with a tissue culture rabies vaccine and passive immunization with equine (or, rarely, human) rabies immunoglobulin (3). This has proved highly effective in preventing infection. Inclusion of rabies immunoglobulin in the post-exposure regimen is regarded as mandatory for WHO “category 3” exposures (bites or scratches that break the skin and contamination of mucosae with saliva) which constitute about 60% of all cases. The effi cacy of equine rabies

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immunoglobulin was established by studies of Iranian patients who had been attacked by rabid wolves (4,5). Rabies immunoglobulin is infi ltrated around the bite wounds and any residual immunoglobulin solution is injected intramuscularly.

SNAKE BITES

Envenomings by snake bite create medical emergencies that involve different organs and tissues, depending on the species responsible for the bite. Most severe cases result from bites by members of the families Viperidae (pit vipers and true vipers) and Elapidae (cobras, kraits, mambas, coral snakes, Australasian species and sea snakes). Venomous snakes are widely distributed throughout the world (Figure 3) except for a few islands, frozen environments and high altitudes (6,7,8).

Life-threatening effects of snake bite envenoming include shock, spontaneous systemic bleeding, paralysis involving respiratory muscles, generalized break down of skeletal muscle (rhabdomyolysis), acute renal failure and infection of necrotic tissue at the site of the bite (Fig-ure 4a,b). Viperid snake venoms cause local extravasation of plasma and blood into the bitten limb, infl ammation and tissue damage, due to the action of toxins on muscle, skin and blood vessels, resulting in pain, oedema, blistering, bleeding and necrosis of skin, subcutaneous tissues and muscle. Some elapid snake venoms (e.g. African spitting cobras and some Asian cobras) can also cause extensive local necrosis. Viperid snake venoms induce spontaneous systemic haemorrhage (e.g. into the brain or gastrointestinal tract), secondary to microvascular damage, coagulopathy and platelet dysfunction, together with cardiovascular shock and renal failure. Elapid snake venoms usually cause neurotoxicity, in particular descending paralysis that may lead to respiratory failure. Some venoms provoke systemic myotoxicity, associated with myoglobinuria, hyperkalaemia and acute renal failure.

Since these local pathological effects develop rapidly and irreversibly after venom injection, those who survive snake bite may suffer permanent sequelae including the results of the locally necrotic effects of viper and some elapid venoms, requiring amputation of digits or limbs

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RABIES AND ENVENOMINGS

(Figure 5a,b) and causing contractures (Figure 6a), tendon damage, arthrodeses and chronic infected ulcers and osteomyelitis that may cause malignant transformation (squamous cellcarcinoma) (Figure 6b). Chronic renal failure, chronic pituitary-adrenal failure and neurological sequelae from haemorrhagic strokes also occur.

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The clinical management of snake bite envenoming is centred on the intravenous adminstration of antivenom, together with a series of ancillary interventions that may include entilatory support for neurotoxic envenoming, fl uid replacement for hypovolaemic shock, ialysis for acute renal failure, tetanus prophylaxis and antibiotics for local wound infection and urgical debridement of necrotic tissue, followed by rehabilitation to restore full function in the itten limb. Because of the large inter- and intra- specifi c variation in venom composition and mmunogenicity, antivenoms are manufactured using the venoms that are most relevant for given geographical region. They are therefore specifi c for snake species of a given region, nd are usually ineffective in other regions inhabited by different species of snakes

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SCORPION STINGS

Envenomings by scorpion stings are also an impor tant, yet neglected, health issue in many parts of the world, particularly in the extreme Northern and Southern parts of Africa, the Middle East, Southern states of USA, Mexico and parts of South America, and the Indian sub-continent. Scorpion venoms, which are especially lethal in young children, release autonomic nervous system mediators causing myocardial damage, cardiac arrhythmias, pulmonary oedema, shock, paralysis, muscle spasms and pancreatitis. Early administra-tion of antivenom is highly ef fective, together with intensive care support in severe cases. However, the rapid tissue distribution of scorpion venom toxins and their ability to cause early death especially in young children, demands early treatment with antivenom and full cardio-respiratory support.

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