Antivenin

Antivenin (or antivenom or antivenene) is a biological product used in the treatment of venomous bites or stings. The name comes from the French word venin meaning venom, and historically the word antivenin was predominant around the world. For the English language the World Health Organization decided in 1981 that the preferred terminology in the English language would be "venom" and "antivenom" rather than "venin/antivenin" or "venen/antivenene". [cite book |last= World Health Organization| first= |title=Progress in the characterization of venoms and standardization of antivenoms |publisher=WHO Offset Publications | location=Geneva |year=1981|pages=5| isbn=9241700580] However, it is still called antivenin or antivenene by many organizations today.

Antivenin is created by injecting a small amount of the targeted venom into an animal such as a horse, sheep, goat, or rabbit; the subject animal will suffer 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 in others. Internationally, antivenins must carefully meet the standards of Pharmacopoeia and the World Health Organization (WHO). [cite journal |author=Theakston RD, Warrell DA, Griffiths E |title=Report of a WHO workshop on the standardization and control of antivenoms |journal=Toxicon |volume=41 |issue=5 |pages=541–57 |year=2003 |month=April |pmid=12676433 |doi= 10.1016/S0041-0101(02)00393-8 |url=http://linkinghub.elsevier.com/retrieve/pii/S0041010102003938 |issn=]

Therapeutic use

The principle of antivenin is based on that of vaccines, developed by Louis Pasteur, 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.

Antivenins 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 antivenin 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 antivenins 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.

Antivenins 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 antivenins (including all snake antivenins) are administered intravenously, however stonefish and redback spider antivenins are given intramuscularly. The intramuscular route has been questioned in some situations as not uniformly effective.cite journal | author=Isbister GK. | title=Failure of intramuscular antivenom in Redback spider envenoming | journal=Emerg Med (Fremantle) | year=2002 | pages=436–9 | volume=14 | issue=4 | pmid=12534488]

Antivenins 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 antivenins, some bites which were previously inevitably fatal have become only rarely fatal provided that the antivenin is administered soon enough.

Antivenins are purified by several processes but will still contain other serum proteins that can act as antigens. Some individuals may react to the antivenin with an immediate hypersensitivity reaction (anaphylaxis) or a delayed hypersensitivity (serum sickness) reaction and antivenin should, therefore, be used with caution. Despite this caution, antivenin 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 antivenin if otherwise indicated. Although it is a popular myth that a person allergic to horses "cannot" be given antivenin, the side effects are manageable, and antivenin should be given as rapidly as the side effects can be managed. [See, for example, the Antivenin Precautions paragraph of the Medication section of cite web
url=http://www.emedicine.com/emerg/topic543.htm#section~medication
title=Snake Envenomations, Sea
author=James Forster, MD, MS
date=2006-03-14
work=eMedicine Emergency Medicine (environmental)
accessdate=2006-06-25]

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 antivenin research has been undertaken (by Sutherland and others for example) - has been attributed to the research base originally having been comprised of 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 (eg: 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.Fact|date=February 2007

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 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 antivenins

Antivenins have been developed for the venoms associated with the following animals:cite journal |author= |title=Appendix: Antivenom Tables |journal=Clinical Toxicology |volume=41 |issue=3 |pages=317–27 |year=2003|doi=10.1081/CLT-120021117 ]

piders

corpions

Marine animals

nakes

* 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), USA
* 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 AfricaSpawls S, Branch B. 1995. The Dangerous Snakes of Africa. Ralph Curtis Books. Dubai: Oriental Press. 192 pp. ISBN 0-88359-029-8.]
* SAIMR echis antivenom: Saw-scaled vipers, South Africa
* SAIMR Boomslang antivenom: Boomslang, South Africa
* Panamerican serum: anticoral polyvalent 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

Antivenin sources

The following groups assist in locating antivenins:
* 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
* 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 antivenins. [http://www.aza.org/ai/]
* 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 antivenins is available at [http://www.miami-dadefirerescue.com/modules/AMS/article.php?storyid=13] . More information about the bank is available at [http://www.venomone.com]

Footnotes

External links

* [http://www.emedicine.com/med/topic2143.htm Snakebite] . eMedicine.
* [http://www.newscientist.com/article.ns?id=dn9277&feedId=online-news_rss20 New antivenom could save more snakebite victims]