Antivenom

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Antivenin (or antivenene or antivenom) is a biological product used in the treatment of venomous bites or stings. It 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, Snake Venom Antitoxin must carefully meet the standards of Pharmacopoeia and the World Health Organization (WHO). [2]

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. 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 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). 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 red-back spider antivenins are given intramuscularly. The intramuscular route has been questioned in some situations as not uniformly effective.

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.

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.

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 mythology, 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 Cobra, Indian Cobra 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:

Spiders

• 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: Red-back spider, Australia
• Black widow antivenin: Black widow spider, USA
• SAIMR Spider antivenom: Button spider, South Africa
• Anti Latrodectus antivenom: Black widow spider, Argentina

Acarids

• Tick antivenom: Ixodes holocyclus (Paralysis tick), Australia

Insects

• Soro antilonomico: Lonomia (Lonomia oblique) caterpillar, Brazil

Scorpions

• 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

• CSL box jellyfish antivenom: Box jellyfish, Australia
• CSL stonefish antivenom Stonefish, Australia

Snakes

• Polyvalent snake antivenom: Saw-scaled Viper Echis carinatus, Russell's Viper Daboia 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|Pseudechis spp.]] Australia.
• Tiger snake antivenom: Austrelaps|Australian copperheads]], Tiger snakes, Pseudechis spp., Rough scaled snake. Australia
• Brown snake antivenom: Pseudonaja|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, Bitis atropos, Bitis caudalis, Bitis cornuta, Bitis heraldica, Bitis inornata, Bitis peringueyi, Bitis schneideri, Bitis xeropaga), South Africa
• 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:

• 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 [3]. More information about the bank is available at [4]
• USA, The Antivenom Index is a joint project of the The American Zoo and Aquarium Association and the American Association of Poison Control Centers: They maintain a website to help locate rare antivenins.[5]
• USA, Colorado: Poisindex central office in Denver, Colorado, USA (1-800-332-3073).
• Australia]]: CSL Limited, Parkville, Victoria, Victoria (Australia).
• Asia: Haffkine Biopharmaceutical Corporation, Parel, Bombay, India.
• Africa: South African Institute for Medical Research, Johannesburg, Republic of South Africa.
• Brazil: Instituto Butantan, São Paulo

External links

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

Acknowledgements

The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.