Antivenom


Antivenom, also known as antivenin, venom antiserum, and antivenom immunoglobulin, is a medication made from antibodies that is used to treat certain venomous bites and stings. Antivenoms are recommended only if there is significant toxicity or a high risk of toxicity. The specific antivenom needed depends on the species involved. It is given by injection.
Side effects may be severe. They include serum sickness, shortness of breath, and allergic reactions including anaphylaxis. Antivenom is made by collecting venom from the relevant animal and injecting small amounts of it into a domestic animal. The antibodies that form are then collected from the domestic animal's blood and purified. Versions are available for spider bites, snake bites, fish stings, and scorpion stings.
Antivenom was first developed in the late 19th century and came into common use in the 1950s. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Antivenom is used to treat certain venomous bites and stings. They are recommended only if there is significant toxicity or a high risk of toxicity. The specific antivenom needed depends on the species involved.
In the US, approved antivenom, including for pit viper snakebite, is based on a purified product made in sheep known as CroFab. It was approved by the FDA in October, 2000. U.S. coral snake antivenom is no longer manufactured, and remaining stocks of in-date antivenom for coral snakebite expired in the Fall of 2009, leaving the U.S. without a coral snake antivenom. Efforts are being made to obtain approval for a coral snake antivenom produced in Mexico which would work against U.S. coral snakebite, but such approval remains speculative.
As an alternative when conventional antivenom is not available, hospitals sometimes use an intravenous version of the antiparalytic drug neostigmine to delay the effects of neurotoxic envenomation through snakebite. Some promising research results have also been reported for administering the drug nasally as a "universal antivenom" for neurotoxic snakebite treatment.
Antivenoms can be classified into monovalent or polyvalent.
The majority of antivenoms are administered intravenously; however, stonefish and redback spider antivenoms are given intramuscularly. The intramuscular route has been questioned in some situations as not uniformly effective.
Antivenoms bind to and neutralize the venom, halting further damage, but do not reverse damage already done. Thus, they should be given as soon as possible after the venom has been injected, but are of some benefit as long as venom is present in the body. Since the advent of antivenoms, some bites which were previously invariably fatal have become only rarely fatal provided that the antivenom is given soon enough.

Side effects

Antivenoms are purified by several processes but will still contain other serum proteins that can act as antigens. Some individuals may react to the antivenom with an immediate hypersensitivity reaction or a delayed hypersensitivity reaction and antivenom should, therefore, be used with caution. Although rare, severe hypersensitivity reactions including anaphylaxis to antivenin are possible. Despite this caution, antivenom is typically the sole effective treatment for a life-threatening condition, and once the precautions for managing these reactions are in place, an anaphylactoid reaction is not grounds to refuse to give antivenom if otherwise indicated. Although it is a popular myth that a person allergic to horses "cannot" be given antivenom, the side effects are manageable, and antivenom should be given as rapidly as the side effects can be managed.

Mechanism

Antivenoms act by binding to and neutralizing venoms. The principle of antivenom is based on that of vaccines, developed by Edward Jenner; however, instead of inducing immunity in the person directly, it is induced in a host animal and the hyperimmunized serum is transfused into the person. The host animals may include horses, donkeys, goats, sheep, rabbits, chickens, llamas, and camels. In addition, opossums are being studied for antivenom production. Antivenoms for medical use are often preserved as freeze-dried ampoules, but some are available only in liquid form and must be kept refrigerated. They are not immediately inactivated by heat, however, so a minor gap in the cold chain is not disastrous.
Some ophiophagic animals produce natural antidotes that render them immune to certain snake venoms. No human is immune to animal venom, but some individuals may be more or less susceptible to its effects.
A person can build up immunity to a particular venom through frequent low and increasing doses, but this immunity is only in effect while he or she is undergoing the dose regime. According to Greek history, King Mithridates did this in order to protect himself against attempts of poisoning, therefore this procedure is often called mithridatism. However, cytotoxic venom causes injury even at low doses meant to build resistance and the long-term effects of venom dosing in general have not been studied. Thus, there is no practical purpose or favorable cost/benefit ratio for this, except for people like zoo handlers, researchers, and circus artists who deal closely with venomous animals. Mithridatism has been tried with success in Australia and Brazil and total immunity has been achieved even to multiple bites of extremely venomous cobras and pit vipers.
Because neurotoxic venoms must travel farther in the body to do harm and are produced in smaller quantities, it is easier to develop resistance to them than directly cytotoxic venoms that are injected in large quantity and damage immediately upon injection.

History

Surgeon-Major Edward Nicholson wrote in the November 1870 Madras Medical Journal that he had witnessed a Burmese snake-catcher inoculating himself with cobra venom. However, the snake-catcher was unsure whether this was actually effective and therefore continued to treat his snakes with care. Nicholson, along with other Britons, began to consider that venom might provide its own cure. Although Scottish surgeon, Patrick Russell, had noted in the late 18th century that snakes were not affected by their own venom, it was not until the late 19th century that Joseph Frayer, Lawrence Waddell, and others began to consider venom-based remedies again. However, they and other naturalists working in India did not have the funding to fully develop their theories. Not until 1895 did Sir Thomas Fraser, Professor of Medicine at the University of Edinburgh, pick up Fayrer and Waddell's research to produce a serum to act against cobra venom. His 'Antivenin' was effective, but failed to make an impact as the public were focused on contemporary Pasteurian discoveries.
Another anti-ophidic serum was developed by Albert Calmette, a French scientist of the Pasteur Institute working at its Indochine branch in 1895, to treat the bites of the Indian Cobra.
In 1901, Vital Brazil, working at the Instituto Butantan in São Paulo, Brazil, developed the first monovalent and polyvalent antivenoms for Central and South American Crotalus and Bothrops genera, as well as for certain species of venomous spiders, scorpions, and frogs.
In Australia, the Commonwealth Serum Laboratories began antivenom research in the 1920s. CSL has developed antivenoms for the redback spider, funnel-web spiders and all deadly Australian snakes.

Availability

There is an overall shortage of antivenom to treat snakebites. Because of this shortage, clinical researchers are considering whether lower doses may be as effective as higher doses in severe neurotoxic snake envenoming.
Snake antivenom is complicated and expensive for manufacturers to produce. When weighed against profitability, the result is that many snake antivenoms, world-wide, are very expensive. Availability, from region to region, also varies.
Internationally, antivenoms must conform to the standards of pharmacopoeia and the World Health Organization. Antivenoms have been developed for the venoms associated with the following animals:

Spiders

Acarids

Insects

Scorpions

Marine animals

Snakes

AntivenomSpeciesCountry
PANAF PREMIUM Purified lyophilized enzyme refined Equine ImmunoglobulinsEchis ocellatus, Echis leucogaster, Echis carinatus, Bitis arietans, Bitis rhinoceros, Bitis nasicornis, Bitis gabonica, Dendroaspis polylepis, Dendroaspis viridis, Dendroaspis angusticeps, Dendroaspis jamesoni, Naja nigricollis, Naja melanoleuca and Naja hajeIndia
Snake Venom Antiserum Purified lyophilized enzyme refined Equine ImmunoglobulinsNaja naja, Vipera russelii and Echis carinatusIndia
INOSERP MENA Bitis arietans, Cerastes cerastes, Cerastes gasperettii,Cerastes vipera, Daboia deserti, Daboia mauritanica, Daboia palaestinae, Echis carinatus sochureki, Echis coloratus, Echis khosatzkii, Echis leucogaster, Echis megalocephalus, Echis omanensis, Echis pyramidum, Macrovipera lebetina obtusa, Macrovipera lebetina transmediterranea, Macrovipera lebetina turanica, Montivipera bornmuelleri, Montivipera raddei kurdistanica, Pseuocerastes fieldi, Pseudocerastes persicus, Vipera latastei, Naja haje, Naja nubiae, Naja pallida and Walterinnesia aegyptiaSpain
INOSERP PAN-AFRICA Echis ocellatus, Bitis arietans, Dendroaspis polylepis and Naja nigricollisSpain
EchiTAbG Echis ocellatus, Echis pyramidumWales, UK
Polyvalent snake antivenomSouth American rattlesnake Crotalus durissus and fer-de-lance Bothrops asperMexico ; South America
Polyvalent snake antivenomSaw-scaled viper Echis carinatus, Russell's viper Daboia russelli, spectacled cobra Naja naja, common krait Bungarus caeruleusIndia
Death adder antivenomDeath adderAustralia
Taipan antivenomTaipanAustralia
Black snake antivenomPseudechis spp.Australia
Tiger snake antivenomAustralian copperheads, tiger snakes, Pseudechis spp., rough-scaled snakeAustralia
Brown snake antivenomBrown snakesAustralia
Polyvalent snake antivenomAustralian snakes as listed aboveAustralia
Sea snake antivenomSea snakesAustralia
Vipera tabVipera spp.UK
Polyvalent crotalid antivenin North American pit vipers North America
Soro antibotropicocrotalicoPit vipers and rattlesnakesBrazil
AntielapidicoCoral snakesBrazil
SAIMR polyvalent antivenomMambas, cobras, Rinkhalses, puff adders South Africa
SAIMR echis antivenomSaw-scaled vipersSouth Africa
SAIMR Boomslang antivenomBoomslangSouth Africa
Panamerican serumCoral snakesCosta Rica
AnticoralCoral snakesCosta Rica
Anti-mipartitus antivenomCoral snakesCosta Rica
Anticoral monovalentCoral snakesCosta Rica
AntimicrurusCoral snakesArgentina
CoralmynCoral snakesMexico
Anti-micruricoscoralesCoral snakesColombia

Terminology

The name "antivenin" comes from the French word, meaning venom, which in turn was derived from Latin, meaning poison.
Historically, the term antivenin was predominant around the world, its first published use being in 1895. In 1981, the World Health Organization decided that the preferred terminology in the English language would be venom and antivenom rather than venin and antivenin or venen and antivenene.