Milking a snake for the production of antivenom
Antivenom, also known as antivenin, venom antiserum and antivenom immunoglobulin, is a medication made from antibodies which 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. 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 1800s and came into common use in the 1950s. They are on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Depending on the type, the wholesale cost in the developing world is 9.00 to 118.80 USD per vial. In the United States the wholesale cost is as high as 2,300 USD per dose.
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).
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.
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. 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.
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.
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 act by binding to and neutralizing venoms.
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.
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. In Australia, the Commonwealth Serum Laboratories (CSL) began antivenom research in the 1920s. CSL has developed antivenoms for the redback spider, funnel-web spiders and all deadly Australian snakes.
There is an overall shortage of antivenom to treat snakebites. Because of this shortage, clinical researchers are looking at seeing if low doses can be as effective in severe neurotoxic snake envenoming.
Internationally, antivenoms must conform to the standards of pharmacopoeia and the World Health Organization (WHO). Antivenoms have been developed for the venoms associated with the following animals:
|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 spider (Latrodectus Mactans) antivenin (equine origin)||Southern Black widow spider||United States|
|SAIMR Spider antivenom||Button spider||South Africa|
|Anti Latrodectus antivenom||Black Widow spider||Argentina|
|Tick antivenom||Paralysis tick||Australia|
|zoro antilonomico||Lonomia obliqua caterpillar||Brazil|
|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|
|INOSCORPI MENA (Middle East and North Africa)||Androctonus australis Hector, Androctonus mauritanicus, Androctonus australis garzoni, Buthus occitanus mardochei, Buthus occitanus occitanus, Leiurus quinquestriatus quinquestriatus, Leiurus quinquestriatus hebreus" and related species.||Spain|
|CSL box jellyfish antivenom||Box jellyfish||Australia|
|CSL stonefish antivenom||Stonefish||Australia|
|Polyvalent snake antivenom||South American rattlesnake Crotalus durissus and fer-de-lance Bothrops asper||Mexico (Instituto Bioclon); South America|
|INOSERP MENA||Bitis arietans, Cerastes cerastes, Naja haje, Macrovipera lebetina obtusa, Vipera palestinae, Naja pallida, Naja nigricollis, Walterinnesia aegyptia, Echis leucogaster, Macrovipera deserti, Cerastes vipera, Cerastes gasperettii, Echis coloratus, Echis pyrramidum, Echis khosatzkii, Echis sochureki, Echis megalocephalus, Echis omanensis, Echis carinatus sochureki; Macrovipera lebetina transmediterranea, Macrovipera lebetina turanica, Macrovipera mauritanica, Naja nubiae, Pseudocerastes persicus fieldi, Pseudocerastes persicus persicus, Vipera bornmuelleri, Vipera latastei, Vipera raddei kurdistanica||Spain|
|INOSERP Pan-Africa (Sub-Sahara)||Naja nigricollis, Dendroaspis polylepis, Echis ocellatus, Bitis arietans, Echis leucogaster, Echis pyramidum, Echis coloratus, Bitis gabonica, Bitis gabonica rhinoceros, Dendroaspis viridis, Dendroaspis angusticeps, Dendroaspis jamesoni, Naja haje, Naja pallida, Naja melanoleuca||Spain|
|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|
|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|
|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|
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.
- WHO Model Formulary 2008 (PDF). World Health Organization. 2009. pp. 396–397. ISBN 9789241547659. Archived (PDF) from the original on 13 December 2016. Retrieved 8 January 2017.
- Dart, Richard C. (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 250–251. ISBN 9780781728454. Archived from the original on 2017-01-09.
- British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 43. ISBN 9780857111562.
- Gad, Shayne Cox (2007). Handbook of Pharmaceutical Biotechnology. John Wiley & Sons. p. 692. ISBN 9780470117101. Archived from the original on 2017-01-09.
- "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
- "Antivenom Serum". International Drug Price Indicator Guide. Archived from the original on 27 February 2017. Retrieved 8 December 2016.
- Lewis, Danny (11 September 2015). "Why A Single Vial Of Antivenom Can Cost $14,000". Smithsonian. Retrieved 9 January 2017.
- "One step closer to cheaper antivenom". ScienceDaily. 3 September 2015. Archived from the original on 9 January 2017. Retrieved 9 January 2017.
- 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.
- Bhoite RR, Bhoite GR, Bagdure DN, Bawaskar HS (2015). "Anaphylaxis to scorpion antivenin and its management following envenomation by Indian red scorpion, Mesobuthus tamulus". Indian Journal of Critical Care Medicine. 19 (9): 547–549. doi:10.4103/0972-5229.164807.
- See, for example, the Antivenom Precautions paragraph of the Medication section of James Forster (2006-03-14). "Snake Envenomations, Sea". eMedicine Emergency Medicine (environmental). Archived from the original on 26 June 2006. Retrieved 2006-06-25.
- "Archived copy". Archived from the original on 2016-03-03. Retrieved 2016-02-08. Link to PDF for full prescribing information, retrieved 11/11/12
- Franklin, Deborah, "Potential Treatment For Snakebites Leads To A Paralyzing Test Archived 2014-08-09 at the Wayback Machine.", NPR.org, July 31, 2013.
- "Universal antidote for snakebite: Experimental trial represents promising step Archived 2014-07-07 at the Wayback Machine.", California Academy of Sciences via Science Daily, May 28, 2014.
- "CSL antivenoms 1956". Power House Museum. Archived from the original on 7 August 2016. Retrieved 24 February 2017.
- Agarwal, R; Aggarwal, AN; Gupta, D; Behera, D; Jindal, SK (June 2005). "Low dose of snake antivenom is as effective as high dose in patients with severe neurotoxic snake envenoming". Emergency medicine journal : EMJ. 22 (6): 397–9. doi:10.1136/emj.2004.020727. PMC 1726801. PMID 15911942.
- 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.
- "Appendix: Antivenom Tables". Clinical Toxicology. 41 (3): 317–27. 2003. doi:10.1081/CLT-120021117.
- Spawls, S; Branch B (1995). The Dangerous Snakes of Africa. Ralph Curtis Books. Dubai: Oriental Press. p. 192. ISBN 0-88359-029-8.
- "Antivenin". Merriam-Webster Dictionary.
- 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.