Snake antivenom
Encyclopedia
Snake antivenom, is a biological product that typically consists of venom neutralizing antibodies derived from a host animal, such as a horse or sheep. The host animal is hyperimmunized to one or more snake venoms, a process which creates an immunological response that produces large numbers of neutralizing antibodies against various components (toxins) of the venom. The antibodies are then collected from the host animal, and further processed into snake antivenom for the treatment of envenomation
Envenomation
Envenomation is the process by which venom is injected into some animal by the bite of a venomous animal. Many kinds of animals, including mammals , reptiles , spiders , insects , employ venom for hunting and for self defense...

. Internationally, snake antivenoms must conform to the standards of Pharmacopoeia
Pharmacopoeia
Pharmacopoeia, pharmacopeia, or pharmacopoea, , in its modern technical sense, is a book containing directions for the identification of samples and the preparation of compound medicines, and published by the authority of a government or a medical or pharmaceutical society.In a broader sense it is...

 and the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (WHO).

Snake Venom

Snake venoms are used in the production of snake antivenom as hyperimmunizing antigens. Snake venoms are complex substances that, depending on the species, can contain a variety of toxins. Toxin components can include proteases, nucleases, phosphodiesterases, and other enzymes which disrupt physiological processes and cellular integrity. The venom toxins are largely classified as neurotoxins, cytotoxins, myotoxins, and cardiotoxins. Venomous snake bites may cause a variety of symptoms, including pain, swelling, tissue necrosis, hypotension, neuromuscular collapse, blood clotting dysfunction, respiratory paralysis, kidney failure, coma and death.

Manufacturing and Production

Antivenoms are typically produced using a donor animal, such as a horse or sheep. The donor animal is hyperimmunized with non-lethal doses of one or more venoms to produce a neutralizing antibody response. Then, at certain intervals, the blood from the donor animal is collected and neutralizing antibodies are purified from the blood to produce an antivenom.

Regulations

  • Human Medicine: In the United States, antivenom production and distribution is regulated by the Food and Drug Administration
    Food and Drug Administration
    The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

    .
  • Veterinary Medicine
    Veterinary medicine
    Veterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...

    : In the United States, antivenom production and distribution is regulated by the United States Department of Agriculture
    United States Department of Agriculture
    The United States Department of Agriculture is the United States federal executive department responsible for developing and executing U.S. federal government policy on farming, agriculture, and food...

    's Center for Veterinary Biologics.

Monovalent vs. Polyvalent

Snake antivenom can be classified by which antigens (venoms) were used in the production process. If the hyperimmunizing venom is obtained from a single species, then it is considered a monovalent
Monovalent
Monovalent may refer to:*In chemistry, valence is a measure of the number of chemical bonds formed by the atoms of a given element. Monovalent is a synonym of univalent.*Monovalent ions contain one valence electron....

 antivenom. If the antivenom contains neutralizing antibodies raised against two or more species of snakes, then the composition is considered polyvalent
Polyvalent
In chemistry, polyvalence or multivalence refers to species that are not restricted to a distinct number of valence bonds....

.

Antibody Composition

Compositions of the antivenom can be classified as whole IgG, or fragments of IgG. Whole antibody products consist of the entire antibody molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

, often immunoglobulin G
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...

 (IgG), whereas antibody fragments are derived by digesting the whole IgG into Fab
Fab
-Commerce:*Fab , a frozen confectionery*Fab, a detergent marketed by Colgate-Palmolive-Culture:* F.A.B., a radio acknowledgment used in the Thunderbirds TV series...

 (monomeric binding) or F(ab')2 (dimeric binding). The fragment antigen binding
Fragment antigen binding
The fragment antigen-binding is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. These domains shape the paratope — the antigen-binding site — at the amino terminal end of the monomer...

, or Fab, is the selective antigen binding region. An antibody, such as IgG, can be digested by papain
Papain
Papain, also known as papaya proteinase I, is a cysteine protease enzyme present in papaya and mountain papaya .-Papain family:...

 to produce three fragments: two Fab fragments and one Fc fragment. An antibody can also be digested by pepsin
Pepsin
Pepsin is an enzyme whose precursor form is released by the chief cells in the stomach and that degrades food proteins into peptides. It was discovered in 1836 by Theodor Schwann who also coined its name from the Greek word pepsis, meaning digestion...

 to produce two fragments: a F(ab')2 fragment and a pFc' fragment]]
The fragment antigen-binding (Fab fragment) is a region on an antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 that binds to antigens, such as venoms. The molecular size of Fab is approximately 50kDa, making it smaller than F(ab')2 which is approximately 110kDa. These size differences greatly affect the tissue distribution and rates of elimination.

Cross Neutralization Properties

Antivenoms may also have some cross protection against a variety of venom
Venom
Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting...

s from snakes within the same family or genera
Genera
Genera is a commercial operating system and development environment for Lisp machines developed by Symbolics. It is essentially a fork of an earlier operating system originating on the MIT AI Lab's Lisp machines which Symbolics had used in common with LMI and Texas Instruments...

. For instance, Antivipmyn (Instituto Bioclon) is made from the venoms of Crotalus durissus
Crotalus durissus
Crotalus durissus is a venomous pitviper species found in South America. The most widely distributed member of its genus, this species poses a serious medical problem in many parts of its range...

 and Bothrops asper
Bothrops asper
Bothrops asper is a venomous pit viper species ranging from southern Mexico to northern South America. Sometimes referred to as the "ultimate pit viper," these snakes are found in a wide range of lowland habitats, often near human habitations. This species is the main cause of snakebite incidents...

. Antivipmyn has been shown to cross neutralize the venoms from all North American pit vipers. Cross neutralization affords antivenom manufacturers the ability to hyperimmunize with fewer venom types to produce geographically suitable antivenoms.

Families of venomous snakes

Over 600 species are known to be venomous—about a quarter of all snake species. The following table lists some major species.
Family Description
Atractaspididae
Atractaspididae
The Atractaspididae are a family of snakes found in Africa and the Middle East. Currently, 12 genera are recognized.-Description:This family includes many genera formerly classed in other families, on the basis of fang type. It includes fangless , rear-fanged , fixed-fanged , and viper-like species...

 (atractaspidids)
Burrowing asps, mole vipers, stiletto snakes.
Colubridae (colubrids) Most are harmless, but others have toxic saliva and at least five species, including the boomslang (Dispholidus typus), have caused human fatalities.
Elapidae
Elapidae
Elapidae is a family of venomous snakes found in tropical and subtropical regions around the world, terrestrially in Asia, Australia, Africa, North America and South America and aquatically in the Pacific and Indian Oceans...

 (elapids)
Sea snakes, Taipans, Brown snakes
Pseudonaja
Pseudonaja is a genus of venomous elapid snakes native to Australia. Members are known commonly as brown snakes and are considered to be one of the most dangerous snakes in the country; even young snakes are capable of delivering a fatal envenomation to a human.- Species :* Dugite or Spotted...

, Coral snakes, Kraits
Bungarus
Bungarus, commonly referred to as kraits , is a genus of venomous elapid snakes found in South and South-East Asia. There are 12 species and 5 subspecies recognized.- Distribution :...

, King Cobra, Mambas, Cobras
Naja
Naja is a genus of venomous elapid snakes. Although there are several other genera that share the common name, Naja are the most recognized and most widespread group of snakes commonly known as cobras. The genus Naja consists of 20 to 22 species, but has undergone several taxonomic revisions in...

.
Viperidae
Viperidae
The Viperidae are a family of venomous snakes found all over the world, except in Antarctica, Australia, Ireland, Madagascar, Hawaii, various other isolated islands, and above the Arctic Circle. All have relatively long, hinged fangs that permit deep penetration and injection of venom. Four...

 (viperids)
True vipers
Viperinae
The Viperinae, or viperines, are a subfamily of venomous vipers found in Europe, Asia and Africa. They are distinguished by their lack of the heat-sensing pit organs that characterize their sister group, the Crotalinae. Currently, 12 genera and 66 species are recognized...

 and pit vipers
Crotalinae
The Crotalinae, commonly known as "pit vipers" or crotaline snakes, are a subfamily of venomous vipers found in Asia and the Americas. They are distinguished by the presence of a heat-sensing pit organ located between the eye and the nostril on either side of the head...

, including rattlesnakes
Crotalus
Crotalus is a genus of venomous pit vipers found only in the Americas from southern Canada to northern Argentina. The name is derived from the Greek word krotalon, which means "rattle" or "castanet", and refers to the rattle on the end of the tail which makes this group so distinctive...

 and copperheads and cottonmouths
Agkistrodon
Agkistrodon is a genus of venomous pit vipers found in North America from the United States south to northern Costa Rica. The name is derived from the Greek words ἄγκιστρον 'fishhook' and ὁδοὐς 'tooth', and is likely a reference to the fangs...

.

Snake Antivenom Manufacturers and Research Institutions

Bioclon Institute (Instituto Bioclon)
Calzada de Tlalpan no. 4687, Col. Toriello Guerra. C.P. 14050, Mexico D.F.
Tel: +52 5 5665 4111

BioVeteria Life Sciences, LLC 1042 Willow Creek Rd: A101-482, Prescott, AZ 86301 USA
Tel: 928 776-1813

BTG International Ltd
5 Fleet Place, London EC4M 7RD, UK
Tel: + 44 (0)20 7575 0000

Butantan Institute
Av. Vital Brasil, 1500 - Butantãn - 05503-900, São Paulo, SP, Brasil
Tel.: +55 11 3726 7222

CSL
Poplar Road 45, 3052 Victoria Parkville
Tel:+61-3-93891911,

Clodomiro Picado Institute
Faculdad de Microbiología, Universidad de Costa Rica, San Jose, Costa Rica
Tel: +506 299 0344

Central Research Institute
173204 Kasauli (H.P.), India
Tel:+91-1-792-72114

Institut Pasteur du Tunis
13 Place Pasteur, B.P. 74, Tunis, Tunisia
Tel:+21-61-283022

National Antivenom and Vaccine Production Centre
P.O. Box 22490, 11426 Riyadh, Saudi Arabia
Tel:+966-1-252-0088

Sanofi Pasteur SA
Avenue Pont Pasteur 2, cedex 07, 69367 Lyon, France

Types of snake antivenom

Antivenom Species Country
Polyvalent snake antivenom South American Rattlesnake Crotalus durissus
Crotalus durissus
Crotalus durissus is a venomous pitviper species found in South America. The most widely distributed member of its genus, this species poses a serious medical problem in many parts of its range...

and fer-de-lance Bothrops asper
Bothrops asper
Bothrops asper is a venomous pit viper species ranging from southern Mexico to northern South America. Sometimes referred to as the "ultimate pit viper," these snakes are found in a wide range of lowland habitats, often near human habitations. This species is the main cause of snakebite incidents...

Mexico (Instituto Bioclon)
Polyvalent snake antivenom South American Rattlesnake Crotalus durissus
Crotalus durissus
Crotalus durissus is a venomous pitviper species found in South America. The most widely distributed member of its genus, this species poses a serious medical problem in many parts of its range...

and fer-de-lance Bothrops asper
Bothrops asper
Bothrops asper is a venomous pit viper species ranging from southern Mexico to northern South America. Sometimes referred to as the "ultimate pit viper," these snakes are found in a wide range of lowland habitats, often near human habitations. This species is the main cause of snakebite incidents...

South America
Polyvalent snake antivenom Saw-scaled Viper Echis carinatus
Echis carinatus
Echis carinatus is a venomous viper species found in parts of the Middle East and Central Asia, and especially the Indian subcontinent. It is the smallest member of the Big Four snakes...

, Russell's Viper Daboia russelli
Daboia
Daboia is a monotypic genus of venomous Old World viper. The single species, D. russelii, is found in Asia throughout the Indian subcontinent, much of Southeast Asia, southern China and Taiwan...

, Spectacled Cobra Naja naja, Common Krait Bungarus caeruleus
India
Death adder antivenom Death adder
Death adder
Death adder may refer to:In herpetology:* All members of the genus Acanthophis, a group of highly venomous elapids found in Australia and New Guinea* Agkistrodon contortrix, a.k.a...

Australia
Taipan antivenom Taipan
Taipan
The taipans are a genus of large, fast, highly venomous Australasian snakes of the elapid family.-Overview:The taipan was named by Donald Thomson after the word used by the Wik-Mungkan Aboriginal people of central Cape York Peninsula, Queensland, Australia.There are three known species: the coastal...

Australia
Black snake antivenom Pseudechis spp.
Pseudechis
The genus Pseudechis contains the group of elapids commonly referred to as the Black Snakes. These snakes are found in every Australian state with the exception of Tasmania and some species are found in Papua New Guinea....

Australia
Tiger snake antivenom Australian copperheads
Austrelaps
Austrelaps is a genus of venomous elapid snakes native to the relatively fertile temperate southern and eastern part of the Australian continent. Three species are currently recognized, of which there are no subspecies. They are commonly called copperheads or Australian copperheads...

, Tiger snakes, Pseudechis spp., Rough scaled snake
Australia
Brown snake antivenom Brown snakes
Pseudonaja
Pseudonaja is a genus of venomous elapid snakes native to Australia. Members are known commonly as brown snakes and are considered to be one of the most dangerous snakes in the country; even young snakes are capable of delivering a fatal envenomation to a human.- Species :* Dugite or Spotted...

Australia
Polyvalent snake antivenom Many Australian snakes Australia
Sea snake antivenom Sea snakes Australia
Vipera tab Vipera
Vipera
Vipera is a genus of venomous vipers. It has a very wide range, being found from North Africa to just within the Arctic Circle and from Great Britain to Pacific Asia. The name is possibly derived from the Latin words vivus and pario, meaning "alive" and "bear" or "bring forth"; likely a reference...

 spp.
USA
Polyvalent crotalid antivenin (CroFab
CroFab
CroFab is the commercial name for a Crotalidae Polyvalent Immune Fab snake antivenom, indicated for minimal or moderate North American Crotalid snake envenomation. It is developed and manufactured by BTG plc , and distributed in the US by Nycomed Inc...

 - Crotalidae Polyvalent Immune Fab (Ovine))
North American pit vipers (all rattlesnake
Rattlesnake
Rattlesnakes are a group of venomous snakes of the genera Crotalus and Sistrurus of the subfamily Crotalinae . There are 32 known species of rattlesnake, with between 65-70 subspecies, all native to the Americas, ranging from southern Alberta and southern British Columbia in Canada to Central...

s, copperhead
Agkistrodon contortrix
Agkistrodon contortrix is a species of venomous snake found in North America, a member of the Crotalinae subfamily. The more common name for the species is "copperhead". The behavior of Agkistrodon contortrix may lead to accidental encounters with humans...

s, and cottonmouth
Cottonmouth
Cottonmouth may refer to:Snakes* Agkistrodon piscivorus, a.k.a. the water moccasin, a venomous and semiaquatic pitviper found in the US* Agkistrodon contortrix mokasen, a.k.a...

s)
North America
Soro antibotropicocrotalico Pit vipers
Crotalinae
The Crotalinae, commonly known as "pit vipers" or crotaline snakes, are a subfamily of venomous vipers found in Asia and the Americas. They are distinguished by the presence of a heat-sensing pit organ located between the eye and the nostril on either side of the head...

 and rattlesnakes
Brazil
Antielapidico Coral snake
Coral snake
The coral snakes are a large group of elapid snakes that can be subdivided into two distinct groups, Old World coral snakes and New World coral snakes...

s
Brazil
SAIMR polyvalent antivenom Mamba
Mamba
Mambas, of the genus Dendroaspis , are a group of highly venomous, fast-moving land-dwelling snakes of Africa. They belong to the family of Elapidae which includes cobras, coral snakes, taipans, brown snakes, tiger snakes, death adders, kraits and, debatably, sea snakes...

s, Cobras
Naja
Naja is a genus of venomous elapid snakes. Although there are several other genera that share the common name, Naja are the most recognized and most widespread group of snakes commonly known as cobras. The genus Naja consists of 20 to 22 species, but has undergone several taxonomic revisions in...

, Rinkhals
Rinkhals
The Rinkhals also called the Ringhals or Ring-necked Spitting Cobra is a venomous elapid species found in parts of southern Africa...

es, Puff adders
Bitis
Bitis is a genus of venomous vipers found in Africa and the southern Arabian Peninsula. It includes the largest and the smallest vipers in the world. Members are known for their characteristic threat displays that involves inflating and deflating their bodies while hissing and puffing loudly. The...

 (Unsuitable small adders: B. worthingtoni, B. atropos
Bitis atropos
Bitis atropos is a venomous viper species found only in mountainous regions in southern Africa. A small species. No subspecies are currently recognized.-Description:...

, B. caudalis
Bitis caudalis
Bitis caudalis is a venomous viper species found in the arid region of south-west Africa. Easily distinguished by the presence of a single, large horn-like scale over each eye. No subspecies are currently recognized.-Description:...

, B. cornuta
Bitis cornuta
Bitis cornuta is a venomous viper species found in certain rocky desert areas, mostly along the Atlantic coast of southern Africa. They have a characteristic tuft of horns above each eye. Two subspecies are currently recognized, including the nominate subspecies described here.-Description: Small...

, B. heraldica
Bitis heraldica
Bitis heraldica is a venomous viper species found only in Angola. Easily distinguished from B. caudalis by its heavily speckled belly and lack of any supraocular horns. No subspecies are currently recognized.-Geographic range:...

, B. inornata
Bitis inornata
Bitis inornata is a venomous viper species found only in Cape Province, South Africa. No subspecies are currently recognized.-Geographic range:...

, B. peringueyi
Bitis peringueyi
Bitis peringueyi is a venomous viper species found in Namibia and southern Angola. No subspecies are currently recognized.-Description:A small snake with an average length of 20–25 cm and a maximum recorded length of 32 cm....

, B. schneideri
Bitis schneideri
Bitis schneideri is a venomous viper species found in a small coastal region that straddles the border between Namibia and South Africa. This is the smallest species in the genus Bitis and possibly the world's smallest viperid...

, B. xeropaga
Bitis xeropaga
Bitis xeropaga is a venomous viper species found in southern Namibia and north-western Cape Province in South Africa. No subspecies are currently recognized.-Description:Adults average 40–50 cm in length, with a maximum of 61 cm for a female....

)
South Africa
SAIMR echis antivenom Saw-scaled vipers
Echis
Echis is a genus of venomous vipers found in the dry regions of Africa, the Middle East, Pakistan, India and Sri Lanka. They have a characteristic threat display, rubbing sections of their body together to produce a "sizzling" warning sound...

South Africa
SAIMR Boomslang antivenom Boomslang
Boomslang
The boomslang is a large venomous colubrid snake.-Taxonomy & etymology:It is currently the only species in its genus, although several species and subspecies have been described in the past...

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
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