Antivenom

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, rabbit, or goat. 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).[1]

Terminology

The name "antivenin" comes from the French word venin, meaning venom, which in turn was derived from Latin venenum, meaning poison.

Historically, the term antivenin was predominant around the world, its first published use being in 1895.[2] 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.[3]

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 single 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). 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.

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, however, 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.[4]

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 invariably 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.[5]

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.[6] 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.

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.

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. Further, cytotoxic venom components can cause pain and 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.

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:[7]

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 Chile
Aracmyn All species of Loxosceles and Latrodectus Mexico
Redback spider antivenom Redback spider Australia
Black widow antivenom Black widow spider United States
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
zoro antilonomico Lonomia obliqua 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 antiscorpionico Tityus spp. Brazil
SAIMR scorpion antivenin Parabuthus spp. South Africa
Purified prevalent Anti-Scorpion Serum(equine) Leiurus spp.& Androctonus 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 Mexico (Instituto Bioclon)
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. UK
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
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[8]
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:

References

  1. ↑ Theakston RD, Warrell DA, Griffiths E (April 2003). "Report of a WHO workshop on the standardization and control of antivenoms". Toxicon 41 (5): 541–57. doi:10.1016/S0041-0101(02)00393-8. PMID 12676433.
  2. ↑ Merriam-Webster Dictionary Antivenin
  3. ↑ World Health Organization (1981). Progress in the characterization of venoms and standardization of antivenoms. Geneva: WHO Offset Publications. p. 5. ISBN 92-4-170058-0.
  4. ↑ Isbister GK. (2002). "Failure of intramuscular antivenom in Redback spider envenoming". Emerg Med (Fremantle) 14 (4): 436–9. doi:10.1046/j.1442-2026.2002.00356.x. PMID 12534488.
  5. ↑ See, for example, the Antivenom Precautions paragraph of the Medication section of James Forster, MD, MS (2006-03-14). "Snake Envenomations, Sea". eMedicine Emergency Medicine (environmental). Archived from the original on 26 June 2006. Retrieved 2006-06-25.
  6. ↑ http://www.savagelabs.com/Products/CroFab/Home/crofab_frame.htm Link to PDF for full prescribing information, retrieved 11/11/12
  7. ↑ "Appendix: Antivenom Tables". Clinical Toxicology 41 (3): 317–27. 2003. doi:10.1081/CLT-120021117.
  8. ↑ Spawls, S; Branch B (1995). The Dangerous Snakes of Africa. Ralph Curtis Books. Dubai: Oriental Press. p. 192. ISBN 0-88359-029-8.

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