Antivenom

Antivenom, also known as antivenin, venom antiserum, and antivenom immunoglobulin, is a medication made from antibodies that is used to treat certain venomous bites and stings.[1] Antivenoms are recommended only if there is significant toxicity or a high risk of toxicity.[1] The specific antivenom needed depends on the species involved.[1] It is given by injection.[1]

For the comics character, see Anti-Venom.

Antivenom

Milking a snake for the production of antivenom
Clinical data
Other names	antivenin, antivenene
AHFS/Drugs.com	Monograph
Routes of administration	injection
ATC code	J06
Identifiers
ChemSpider	none

Side effects may be severe.[1] They include serum sickness, shortness of breath, and allergic reactions including anaphylaxis.[1] Antivenom is made by collecting venom from the relevant animal and injecting small amounts of it into a domestic animal.[2] The antibodies that form are then collected from the domestic animal's blood and purified.[2] Versions are available for spider bites, snake bites, fish stings, and scorpion stings.[3]

Antivenom was first developed in the late 19th century and came into common use in the 1950s.[2][4] It is on the World Health Organization's List of Essential Medicines.[5]

Medical uses

Antivenom is used to treat certain venomous bites and stings.[1] They are recommended only if there is significant toxicity or a high risk of toxicity.[1] The specific antivenom needed depends on the species involved.[1]

In the US, approved antivenom, including 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.[7][8]

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.[9] Some promising research results have also been reported for administering the drug nasally as a "universal antivenom" for neurotoxic snakebite treatment.[10]

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 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.[11]

Antivenoms bind to and neutralize the venom, halting further damage, but do not reverse damage already done. Thus, they should be given 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 given soon enough.

Side effects

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.[12] 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.[13]

Mechanism

Antivenoms act by binding to and neutralizing venoms. The principle of antivenom is based on that of vaccines, developed by Edward Jenner; however, instead of inducing immunity in the person directly, it is induced in a host animal and the hyperimmunized serum is transfused into the person.[14] The host animals may include horses, donkeys, goats, sheep, rabbits, chickens, llamas, and camels.[15] In addition, opossums are being studied for antivenom production.[16] Antivenoms for medical 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.

Some ophiophagic animals produce natural antidotes that render them immune to certain snake venoms. No human is immune to animal venom, but some individuals may be more or less susceptible to its effects.[17]

A person can build up immunity to a particular venom through frequent low and increasing doses (about every 21 days), but this immunity is only in effect while he or she is undergoing the dose regime.[17] According to Greek history, King Mithridates did this in order to protect himself against attempts of poisoning, therefore this procedure is often called mithridatism. However, cytotoxic venom causes injury even at low doses meant to build resistance and the long-term effects of venom dosing in general have not been studied.[17] 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. Mithridatism 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 damage immediately upon injection.

History

Surgeon-Major Edward Nicholson wrote in the November 1870 Madras Medical Journal that he had witnessed a Burmese snake-catcher inoculating himself with cobra venom. However, the snake-catcher was unsure whether this was actually effective and therefore continued to treat his snakes with care. Nicholson, along with other Britons, began to consider that venom might provide its own cure. Although Scottish surgeon, Patrick Russell, had noted in the late 18th century that snakes were not affected by their own venom,[18] it was not until the late 19th century that Joseph Frayer, Lawrence Waddell, and others began to consider venom-based remedies again. However, they and other naturalists working in India did not have the funding to fully develop their theories. Not until 1895 did Sir Thomas Fraser, Professor of Medicine at the University of Edinburgh, pick up Fayrer and Waddell's research to produce a serum to act against cobra venom. His 'Antivenin' was effective, but failed to make an impact as the public were focused on contemporary Pasteurian discoveries.[19]

Another anti-ophidic serum was developed by Albert Calmette, a French scientist of the Pasteur Institute working at its Indochine branch in 1895, to treat the bites of the Indian Cobra (Naja naja).[20]

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,[21] 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.[22]

Availability

There is an overall shortage of antivenom to treat snakebites. Because of this shortage, clinical researchers are considering whether lower doses may be as effective as higher doses in severe neurotoxic snake envenoming.[23]

Snake antivenom is complicated and expensive for manufacturers to produce.[24] When weighed against profitability (especially for sale in poorer regions), the result is that many snake antivenoms, world-wide, are very expensive. Availability, from region to region, also varies.[25]

Internationally, antivenoms must conform to the standards of pharmacopoeia and the World Health Organization (WHO).[15][26] Antivenoms have been developed for the venoms associated with the following animals:[27]

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 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

Acarids

Antivenom	Species	Country
Tick antivenom	Paralysis tick	Australia

Insects

Antivenom	Species	Country
soro antilonomico	Lonomia obliqua caterpillar	Brazil

Scorpions

Antivenom	Species	Country
Scorpion Venom Anti Serum (India) Purified lyophilized enzyme refined Equine Immunoglobulins	Buthus tamulus	India
ANTISCORP - Premium (Scorpion Venom Antiserum North Africa) Purified lyophilized enzyme refined Equine Immunoglobulins	Androctonus amoerexi and Leiurus quinquestraiatus	India
INOSCORPI MENA (Middle East and North Africa)	Androctonus australis, Androctonus mauritanicus, Androctonus crassicauda, Buthus occitanus mardochei, Buthus occitanus occitanus, Leiurus quinquestriatus quinquestriatus, Leiurus quinquestriatus hebreus	Spain
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 source)	Leiurus spp. and Androctonus scorpions	Egypt

Marine animals

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

Snakes

Antivenom	Species	Country
PANAF PREMIUM (Sub-Sahara Africa) Purified lyophilized enzyme refined Equine Immunoglobulins [28]	Echis ocellatus, Echis leucogaster, Echis carinatus, Bitis arietans, Bitis rhinoceros, Bitis nasicornis, Bitis gabonica, Dendroaspis polylepis, Dendroaspis viridis, Dendroaspis angusticeps, Dendroaspis jamesoni, Naja nigricollis, Naja melanoleuca and Naja haje	India
Snake Venom Antiserum (India) Purified lyophilized enzyme refined Equine Immunoglobulins	Naja naja, Vipera russelii and Echis carinatus	India
INOSERP MENA (Middle East and North Africa)	Bitis arietans, Cerastes cerastes, Cerastes gasperettii,Cerastes vipera, Daboia deserti, Daboia mauritanica, Daboia palaestinae, Echis carinatus sochureki, Echis coloratus, Echis khosatzkii, Echis leucogaster, Echis megalocephalus, Echis omanensis, Echis pyramidum, Macrovipera lebetina obtusa, Macrovipera lebetina transmediterranea, Macrovipera lebetina turanica, Montivipera bornmuelleri, Montivipera raddei kurdistanica, Pseuocerastes fieldi, Pseudocerastes persicus, Vipera latastei, Naja haje, Naja nubiae, Naja pallida and Walterinnesia aegyptia	Spain
INOSERP PAN-AFRICA (Sub-Sahara Africa)	Echis ocellatus, Bitis arietans, Dendroaspis polylepis and Naja nigricollis	Spain
EchiTAbG (Sub-Sahara Africa)[29]	Echis ocellatus, Echis pyramidum	Wales, UK
Polyvalent snake antivenom	South American rattlesnake Crotalus durissus and fer-de-lance Bothrops asper	Mexico (Instituto Bioclon); 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	Australian snakes as listed above	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[30]
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

Terminology

The name "antivenin" comes from the French word venin, meaning venom, which in turn was derived from Latin venenum, meaning poison.[31]

Historically, the term antivenin was predominant around the world, its first published use being in 1895.[32] 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.[33]

References

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2. Dart, Richard C. (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 250–251. ISBN 9780781728454. Archived from the original on 2017-01-09.
3. British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 43. ISBN 9780857111562.
4. Gad, Shayne Cox (2007). Handbook of Pharmaceutical Biotechnology. John Wiley & Sons. p. 692. ISBN 9780470117101. Archived from the original on 2017-01-09.
5. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
6. "Archived copy". Archived from the original on 2016-03-03. Retrieved 2016-02-08.CS1 maint: archived copy as title (link) Link to PDF for full prescribing information, retrieved 11/11/12
7. "CORAL SNAKE & ANTIVENOM FAQ's". Florida Poison Information Center - Tampa. May 2017. Retrieved October 31, 2019.
8. "North American Micrurus (Coral Snake Venoms)". Toxnet: Toxicology Data Network. September 15, 2015. Retrieved October 31, 2019.
9. Franklin, Deborah, "Potential Treatment For Snakebites Leads To A Paralyzing Test Archived 2014-08-09 at the Wayback Machine", NPR.org, July 31, 2013.
10. "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.
11. Isbister GK. (2002). "Failure of intramuscular antivenom in Redback spider envenoming". Emerg Med. 14 (4): 436–9. doi:10.1046/j.1442-2026.2002.00356.x. PMID 12534488.
12. 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. PMC 4578200. PMID 26430342.
13. 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.
14. Gad, Shayne. Handbook of Pharmaceutical Biotechnology. p. 692.
15. "Guidelines for the production, control and regulation of snake antivenom immunoglobulins" (PDF). WHO Technical Series No, 1004. WHO. 2017. Retrieved 15 January 2020.
16. "Opossum Compounds Isolated to Help Make Antivenom". Scientific American. 2015-03-30. Retrieved 2020-02-01.
17. Kalyan kumar, B. (October 4, 2014). "ANTISNAKE VENOM SERUM (ASVS)". International Journal on Pharmaceutical and Biomedical Research(IJPBR). 1 (3): 77 – via documents.pub.
18. Bhaumik, Rahul (2018-11-01). "Colonial Encounter on Indian Snakes and their Venoms: The Transmission and Transformation of Western Ophiological Knowledge in British India, 1780s-1910s" (PDF). Indian Journal of History of Science. 53 (4). doi:10.16943/ijhs/2018/v53i4/49536. ISSN 0019-5235.
19. Bhaumik, Rahul (2018-11-01). "Colonial Encounter on Indian Snakes and their Venoms: The Transmission and Transformation of Western Ophiological Knowledge in British India, 1780s-1910s" (PDF). Indian Journal of History of Science. 53 (4). doi:10.16943/ijhs/2018/v53i4/49536. ISSN 0019-5235.
20. Bochner, Rosany (8 June 2016). "Paths to the discovery of antivenom serotherapy in France". Journal of Venomous Animals and Toxins Including Tropical Diseases. 22 (20): 20. doi:10.1186/s40409-016-0074-7. PMC 4898362. PMID 27279829.
21. De Franco, Marcelo; Kalil, Jorge (3 July 2014). "The Butantan Institute: History and Future Perspectives". PLoS Neglected Tropical Diseases. 8 (7): e2862. doi:10.1371/journal.pntd.0002862. ISSN 1935-2727. PMC 4080994. PMID 24992341.
22. "CSL antivenoms 1956". Power House Museum. Archived from the original on 7 August 2016. Retrieved 24 February 2017.
23. 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. 22 (6): 397–9. doi:10.1136/emj.2004.020727. PMC 1726801. PMID 15911942.
24. Lewis, Danny (11 September 2015). "Why A Single Vial Of Antivenom Can Cost $14,000". Smithsonian. Retrieved 9 January 2017.
25. "Antivenom Supply for Snake bites". www.pharmaceutical-technology.com.
26. 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.
27. "Appendix: Antivenom Tables". Clinical Toxicology. 41 (3): 317–27. 2003. doi:10.1081/CLT-120021117.
28. Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead, Elsevier, 1 September 2016, retrieved 1 September 2016
29. Snake Antivenom for Sub – Sharan Africa EchiTAbG (PDF), World Health Organization, 20 June 2019, retrieved 14 December 2019
30. Spawls, S; Branch B (1995). The Dangerous Snakes of Africa. Ralph Curtis Books. Dubai: Oriental Press. p. 192. ISBN 0-88359-029-8.
31. Weinstein, Scott A. (1 September 2015). "Snake venoms: A brief treatise on etymology, origins of terminology, and definitions". Toxicon. Elsevier. 103: 188–195. doi:10.1016/j.toxicon.2015.07.005. PMID 26166305.
32. "Antivenin". Merriam-Webster Dictionary.
33. 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.

External links

• Antivenom Index, a joint project of the Association of Zoos and Aquariums and the American Association of Poison Control Centers which helps locate rare antivenoms
• Venom Response Program of the Miami-Dade Fire Rescue service