Antivenom
Antivenom, also known as antivenin, venom antiserum, and antivenom immunoglobulin, is a specific treatment for envenomation. It is composed of antibodies and used to treat certain venomous bites and stings.[1] Antivenoms 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.[1] Antivenom is traditionally 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. Due to the high cost of producing antibody-based antivenoms and their short shelf lives when not refrigerated, alternative methods of production of antivenoms are being actively explored. One such different method of production involves production from bacteria.[5] Another approach is to develop targeted drugs (which, unlike antibodies, are usually synthetic and easier to manufacture at scale).
Antivenom was first developed in the late 19th century and came into common use in the 1950s.
Antivenoms
Snakebite envenoming
For more than 100 years, the mainstay of primary treatment for snakebite has been the administration of antivenoms. Antivenoms work by boosting our immune response after a snakebite. They are made by immunizing donor animals such as horses or sheep with snake venoms. These animals have robust immune systems and produce powerful antibodies that can bind to snake venom components, enabling our own immune defences to eliminate these toxins.
Antivenoms are obtained by harvesting and then purifying the antibodies from plasma produced by the donor animal. Good-quality antivenoms can literally make a difference between life and death. Bufo Bufo Venom for Sale
However, the potential of antivenom treatment to significantly contribute to effectively controlling the burden of snakebite morbidity, disability and mortality have been limited by a number of factors:
Poor regulatory frameworks for antivenoms, an absence of appropriate reference standards, and a lack of expertise and capacity within national drug control laboratories;
Inadequate investment in research and development that would lead to improved product safety, efficacy and clinical effectiveness;
Absence of minimum specifications for neutralization of overall lethality and specific toxic activities of antivenoms that reflect clinical effectiveness definitions in defined markets;
Traditional belief systems that associate snakebite envenoming with supernatural, rather than health-related events;
Sustained erosion of confidence in antivenom products due to poor training of health workers, marketing of poor quality, unsafe or ineffective products, and other factors;
Health system weaknesses, inadequate infrastructure and inefficient distribution of antivenoms;
A cycle of consequences driven by low investment in procurement, poor quality and specificity of some antivenoms which erodes sales, drives down production, curtails profitability, drives up prices and drives down accessibility – which perpetuates the market decline and drives manufacturers out of the antivenom supply sector.
The consequence of these and other issues has been most dramatic in Sub-Saharan Africa, where local manufacturing of antivenoms has always been inadequate to the needs of the continent. Major multinational antivenom producers have cited competition from inferior (and sometimes less expensive) products as the reason for their abandonment of production in Sub-Saharan Africa.
The loss of effective products and their replacement with both poor quality products, and products that have not been adequately evaluated prior to market penetration, has compounded the collapse of confidence in the use of antivenoms among health workers.
Furthermore, poor data on the number and type of snake bites, and difficulty in accurately establishing forward needs assessments for specific antivenom products in each country, further discourage the participation of mainstream pharmaceutical manufacturers.
Medical uses
Antivenom is used to treat certain venomous bites and stings. They are recommended only if there is significant toxicity or a high risk of toxicity.[1] The specific antivenom needed depends on the venomous species involved.
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. It was approved by the FDA in October 2000. U.S. coral snake antivenom is no longer manufactured, and the 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.
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.[12] Some promising research results have also been reported for administering the drug nasally as a “universal antivenom” for neurotoxic snakebite treatment.
A monovalent antivenom is specific for one toxin or species, while a polyvalent one is effective against multiple toxins or species.
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 the 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.
WHO responds to some venom issues:
A structured comprehensive assessment of antivenom products intended for use in Sub-Saharan Africa commenced in 2016 and will culminate in the release of a report and specific procurement recommendations in late 2017. The key outcome of this will be an evidence-based list of WHO-recommended antivenom products that are suitable for procurement by Sub-Saharan African Member States and other stakeholders.
Updating of the WHO Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins in order to provide manufacturers with strong guidance on high-quality antivenom design, production, quality control, preclinical and clinical testing, and national regulatory agencies with framework guidance to ensure that products which they license meet the highest standards.
Further reform of antivenom production and regulatory governance is still required, and WHO will develop strategies to introduce programmes for further improvement in the quality and safety of antivenom products, as well as address some of the other constraints. Some of the approaches that may be taken include:
Facilitation of technical support services to drive the improvement of current production and quality control technologies;
Creation of a pathway for the entry of antivenom products into the WHO Prequalification Programme as a direct means of assuring the supply of safe, effective and affordable antivenoms to markets in Sub-Saharan Africa and Asia;
Delivery of guidance and technical support to Member State drug regulators and Ministries of Health on the regulation and control of antivenom products.
Establishment of a stockpile of WHO-recommended antivenoms to generate stability of supply and demand and stimulate production growth in a manner that translates into increased access to effective treatments for the victims of snakebite envenoming.
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, 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 was focused on contemporary Pasteurian discoveries.
Another anti-ophitic 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).
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.
Side effects
Antivenoms are purified from animal serum by several processes and may contain other serum proteins that can act as immunogens. 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 antivenom 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 rapidly as the side effects can be managed.
