Antivenom

For the Marvel Comics character, see Anti-Venom (comics).

Milking a snake for the production of antivenom.

Antivenom (or antivenin or antivenene) is a biological product used in the treatment of venomous bites or stings. Antivenom is created by milking venom from the desired snake, spider or insect. The venom is then diluted and injected into a horse, sheep, goat or cat. The subject animal will undergo an immune response to the venom, producing antibodies against the venom's active molecule which can then be harvested from the animal's blood and used to treat envenomation. Internationally, antivenoms must conform to the standards of Pharmacopoeia and the World Health Organization (WHO).

Terminology

The name "antivenin" comes from the French word "venin", meaning venom, and historically "antivenin" was predominant around the world. In 1981, the World Health Organization decided that the preferred terminology in the English language would be "venom" and "antivenom" rather than "venin/antivenin" or "venen/antivenene".

Therapeutic use

The principle of antivenom is based on that of vaccines, developed by Edward Jenner; however, instead of inducing immunity in the patient directly, it is induced in a host animal and the hyperimmunized serum is transfused into the patient.

Antivenoms can be classified into monovalent (when they are effective against a given species' venom) or polyvalent (when they are effective against a range of species, or several different species at the same time). The first antivenom for snakes (called an anti-ophidic serum) was developed by Albert Calmette, a French scientist of the Pasteur Institute working at its Indochine branch in 1895, against the Indian Cobra (Naja naja). Vital Brazil, a Brazilian scientist, developed in 1901 the first monovalent and polyvalent antivenoms for Central and South American Crotalus, Bothrops and Elaps genera, as well as for certain species of venomous spiders, scorpions, and frogs. They were all developed in a Brazilian institution, the Instituto Butantan, located in São Paulo, Brazil.

Antivenoms for therapeutic 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, so a minor gap in the cold chain is not disastrous.) The majority of antivenoms (including all snake 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 administered 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 inevitably fatal have become only rarely fatal provided that the antivenom is administered soon enough.

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 (anaphylaxis) or a delayed hypersensitivity (serum sickness) reaction and antivenom should, therefore, be used with caution. 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.

Sheep are generally used in preference over horses now, however, as the potential for adverse immunological responses in humans from sheep-derived antibodies is generally somewhat less than that from horse-derived antibodies. The use of horses to raise antibodies - in Australia at least, where much antivenom research has been undertaken (by Sutherland and others for example) - has been attributed to the research base originally having been a large number of veterinary officers. These vets had, in many cases, returned from taking part in the Boer and First World Wars and were generally experienced with horses due to working with cavalry. The large animal vets were similarly oriented given the use of horses as a prime source of motive power and transport, especially in the rural setting. The overall experience with horses naturally made them the preferred subject in which to raise antibodies. It was not until later that the immuno-reactivity of certain horse serum proteins was assessed to be sufficiently problematic that alternatives in which to raise antibodies were investigated.

In the U.S. the only approved antivenom for pit viper (rattlesnake, copperhead and water moccasin) 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. In the absence of antivenom, all coral snakebite should be treated in a hospital by elective endotracheal intubation and mechanical ventilation until the effects of coral snake neurotoxins abate. It is important to remember that respiratory paralysis in coral snakebite can occur suddenly, often up to 12 or more hours after the bite, so intubation and ventilation should be employed in anticipation of respiratory failure and not after it occurs, when it may be too late.

Veterinary Antivenom

The United States Department of Agriculture (USDA) regulates veterinary antibody and antivenom products based on the Virus Serum Toxin Act. Currently, Fort Dodge Animal Health has received a United States Veterinary License Number for an equine derived antivenom labeled for canine use. Animal Health Consulting, LLC is coordinating the trials for a new pit viper antivenom for veterinary medicine [1].

Natural and acquired immunity

Although individuals can vary in their physiopathological response and sensitivity to animal venoms, there is no natural immunity to them in humans. Some ophiophagic animals are immune to the venoms produced by some species of venomous snakes, by the presence of antihemorrhagic and antineurotoxic factors in their blood. These animals include King snakes, opossums, mongooses, and hedgehogs.

It is quite possible to immunize a person directly with small and graded doses of venom rather than an animal. According to Greek history, King Mithridates did this in order to protect himself against attempts of poisoning, therefore this procedure is often called mithridatization. However, unlike a vaccination against disease which must only produce a latent immunity that can be roused in case of infection, to neutralize a sudden and large dose of venom requires maintaining a high level of circulating antibody (a hyperimmunized state), through repeated venom injections (typically every 21 days). The long-term health effects of this process have not been studied. For some large snakes, the total amount of antibody it is possible to maintain in one human being is not enough to neutralize one envenomation. Further, cytotoxic venom components can cause pain and minor scarring at the immunization site. Finally, the resistance is specific to the particular venom used; maintaining resistance to a variety of venoms requires multiple monthly venom injections. 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. Mithridatization 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. Starting in 1950, Bill Haast successfully immunized himself to the venoms of Cape, Indian and King cobras.

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 (such as those of most vipers) that are injected in large quantity and do damage immediately upon injection.

Availability of antivenoms

Antivenoms have been developed for the venoms associated with the following animals:

Spiders

antivenom	Species	Country
Funnel web spider antivenom	Sydney funnel-web spider	Australia
Soro antiaracnidico	Brazilian wandering spider	Brazil
Soro antiloxoscelico	Recluse spider	Brazil
Suero antiloxoscelico	Chilean recluse	Peru
Aracmyn	All species of Loxosceles and Latrodectus	Mexico
Redback spider antivenom	Redback spider	Australia
Black widow antivenom	Black Widow spider	North America
SAIMR Spider antivenom	Button spider	South Africa
Anti Latrodectus antivenom	Black Widow spider	Argentina

Acarids

Antivenom	Species	Country
Tick antivenom	Paralysis tick	Australia

Insects

Antivenom	Species	Country
Soro antilonomico	Lonomia oblique caterpillar	Brazil

Scorpions

Antivenom	Species	Country
Alacramyn	Centruroides limpidus, C. noxius, C. suffusus	Mexico
Suero Antialacran	Centruroides limpidus, C. noxius, C. suffusus	Mexico
Tunisian polyvalent antivenom	All Iranian scorpions	Tunisia
Anti-Scorpion Venom Serum I.P.(AScVS)	Indian red scorpion	India
Anti-scorpionique	Androctonus spp., Buthus spp.	Algeria
Scorpion antivenom	Black scorpion, Buthus occitanus	Morocco
Soro antiescorpionico	Tityus spp.	Brazil
SAIMR scorpion antivenom	Parabuthus spp.	South Africa
Purified polyvalent Anti-Scorpion Serum(equine)	Leiurus spp.& Androctons scorpions	Egypt

Marine animals

Antivenom	Species	Country
CSL box jellyfish antivenom	Box jellyfish	Australia
CSL stonefish antivenom	Stonefish	Australia

Snakes

Antivenom	Species	Country
Polyvalent snake antivenom	South American Rattlesnake Crotalus durissus and fer-de-lance Bothrops asper	South America
Polyvalent snake antivenom	Saw-scaled Viper Echis carinatus, Russell's Viper Daboia russelli, Spectacled Cobra Naja naja, Common Krait Bungarus caeruleus	India
Death adder antivenom	Death adder	Australia
Taipan antivenom	Taipan	Australia
Black snake antivenom	Pseudechis spp.	Australia
Tiger snake antivenom	Australian copperheads, Tiger snakes, Pseudechis spp., Rough scaled snake	Australia
Brown snake antivenom	Brown snakes	Australia
Polyvalent snake antivenom	Many Australian snakes	Australia
Sea snake antivenom	Sea snakes	Australia
Vipera tab	Vipera spp.	USA
Polyvalent crotalid antivenin (CroFab - Crotalidae Polyvalent Immune Fab (Ovine))	North American pit vipers (all rattlesnakes, copperheads, and cottonmouths)	North America
Soro antibotropicocrotalico	Pit vipers and rattlesnakes	Brazil
Antielapidico	Coral snakes	Brazil
Soro anti-elapidico	Coral snakes	Brazil
SAIMR polyvalent antivenom	Mambas, Cobras, Rinkhalses, Puff adders (Unsuitable small adders: B. worthingtoni, B. atropos, B. caudalis, B. cornuta, B. heraldica, B. inornata, B. peringueyi, B. schneideri, B. xeropaga)	South Africa
SAIMR echis antivenom	Saw-scaled vipers	South Africa
SAIMR Boomslang antivenom	Boomslang	South Africa
Panamerican serum	Coral snakes	Costa Rica
Anticoral	Coral snakes	Costa Rica
Anti-mipartitus antivenom	Coral snakes	Costa Rica
Anticoral monovalent	Coral snakes	Costa Rica
Antimicrurus	Coral snakes	Argentina
Coralmyn	Coral snakes	Mexico
Anti-micruricoscorales	Coral snakes	Colombia

Antivenom sources

The following groups assist in locating antivenoms:

• Africa: South African Institute for Medical Research, Johannesburg, Republic of South Africa.
• Asia: Haffkine Biopharmaceutical Corporation, Parel, Mumbai, India.
• Australia: CSL Limited, Parkville, Victoria.
• Brazil: Instituto Butantan, São Paulo
• Costa Rica: Instituto Clodomiro Picado, San José
• Mexico: Instituto Bioclon
• USA, The Antivenom Index is a joint project of the Association of Zoos and Aquariums and the American Association of Poison Control Centers: They maintain a website to help locate rare antivenoms.[2]
• USA, Colorado: Poisindex central office in Denver, Colorado, USA (1-800-332-3073).
• USA, Miami, Florida: The Miami-Dade Fire Rescue Antivenom Bank: Emergency: 1-786-336-6600 available 24 hours. A list of available antivenoms and more information about the bank is available at [3]
• Pakistan: National Institute of Health (NIH), Islamabad. Produces polyvalent antivenom

External links

• Snakebite. eMedicine.
• New antivenom could save more snakebite victims