Instruct: Given a question, retrieve documents that answer the question.
Query: Does Botulinum toxin cause botulism?
Botulinum toxin produced by "Clostridium botulinum" is the cause of botulism. Humans most commonly ingest the toxin from eating improperly-canned foods in which "C. botulinum" has grown. However, the toxin can also be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin within the intestine and can cause a condition known as floppy baby syndrome. In all cases, the toxin can then spread, blocking nerves and muscle function. In severe cases, the toxin can block nerves controlling the respiratory system or heart, resulting in death.
A few strains from organisms genetically identified as other "Clostridium" species have caused human botulism: "C. butyricum" has produced type E toxin and "C. baratii" had produced type F toxin. The ability of "C. botulinum" to naturally transfer neurotoxin genes to other clostridia is concerning, especially in the food industry, where preservation systems are designed to destroy or inhibit only "C. botulinum" but not other "Clostridium" species.
In 1895 (seventy-five years later), Émile van Ermengem, professor of bacteriology and a student of Robert Koch, correctly described "Clostridium botulinum" as the bacterial source of the toxin. Thirty-four attendees at a funeral were poisoned by eating partially salted ham, an extract of which was found to cause botulism-like paralysis in laboratory animals. Van Ermengem isolated and grew the bacterium, and described its toxin, which was later purified by P Tessmer Snipe and Hermann Sommer.
In 1820, Justinus Kerner, a small-town German medical officer and romantic poet, gave the first complete description of clinical botulism based on extensive clinical observations of so-called “sausage poisoning”. Following experiments on animals and on himself, he concluded that the toxin acts by interrupting signal transmission in the somatic and autonomic motor systems, without affecting sensory signals or mental functions. He observed that the toxin develops under anaerobic conditions, and can be lethal in minute doses. His prescience in suggesting that the toxin might be used therapeutically earned him recognition as the pioneer of modern botulinum toxin therapy.
With the outbreak of World War II, weaponization of botulinum toxin was investigated at Fort Detrick in Maryland. Carl Lamanna and James Duff developed the concentration and crystallization techniques that Edward J. Schantz used to create the first clinical product. When the Army’s Chemical Corps was disbanded, Schantz moved to the Food Research Institute in Wisconsin, where he manufactured toxin for experimental use and generously provided it to the academic community.
Richard Clark, a plastic surgeon from Sacramento (CA), was the first to document a cosmetic use for botulinum toxin. He treated forehead asymmetry caused by left sided forehead nerve paralysis that occurred during a cosmetic facelift. Since the injured nerve could possibly regenerate by 24 months, a two-year waiting period was necessary before definitive surgical treatment could be done. Clark realized that botulinum toxin, which had been previously used only for cross eyed babies and facial tics, could also be injected to smooth the wrinkles of the right forehead to match her paralyzed left. He received FDA approval for this cosmetic application of the toxin and successfully treated the person and published the case study in 1989.
Botulinum toxin therapy of strabismus is a medical technique used sometimes in the management of strabismus, in which botulinum toxin is injected into selected extraocular muscles in order to reduce the misalignment of the eyes. The injection of the toxin to treat strabismus, reported upon in 1981, is considered to be the first ever use of botulinum toxin for therapeutic purposes. Today, the injection of botulinum toxin into the muscles that surround the eyes is one of the available options in the management of strabismus. Other options for strabismus management are vision therapy and occlusion therapy, corrective glasses (or contact lenses) and prism glasses, and strabismus surgery.
On July 29, 2016, Food and Drug Administration (FDA), of the United States of America approved abobotulinumtoxinA for injection for the treatment of lower limb spasticity in pediatric patients two years of age and older. AbobotulinumtoxinA is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity. In the United States of America, the FDA approves the text of the labels of prescription medicines. The FDA approves which medical conditions the drug manufacturer may sell the drug for. However, those approved by the FDA to prescribe these drugs may freely prescribe them for any condition they wish, called off-label use. Botulinum toxins have been used off-label for several pediatric conditions, including infantile esotropia.
In the 1970's, Scott started to experiment with Botox as a therapy for strabismus, due to its muscle relaxing features. In 1978, he received permission from the FDA to test Botox in clinical trials with humans, which was at that time groundbreaking, as Botox in higher dosages could paralyze and ultimately kill humans. After successful clinical trials on patients, the treatment received FDA approval in 1989. Two years later he sold the patent to Allergen for $9M. Allergen which changed the name for Oculinum to Botox. Its 1991 revenue amounted to $13M, as it was solely used for medical treatments. As Allergen conducted further studies with Botox for its cosmetic wrinkle reducing quality, it received FDA approval in 2002. Today, Botox annual revenue is estimated to be more than $2.5B. Scott has published numerous articles on the subject of strabismus. He founded the Strabismus Research Foundation in San Francisco, and continues to conduct research on strabismus and related topics together with Joel M. Miller and Talita Malta e Cunha.
"O. tsutsugamushi" causes a complex and dangerous infection scrub typhus. Infection starts when chiggers bite on the skin during their feeding. The bacteria are deposited at the site of feeding (inoculation), where they multiply. They cause progressive tissue damage (necrosis). Necrosis progresses to inflammation of the blood vessels called vasculitis. This in turn causes inflammation of the lymph nodes, called lymphadenopathy. Within a few days, vasculitis extends to various organs including liver, brain, kidney, meninges and the lung. The disease is responsible for nearly a quarter of all the febrile (high fever) illness in endemic areas. Mortality in severe case or due to improper treatment or misdiagnosis may be as high as 30-70%. About 6% of infected people die untreated, and 1.4% of the patients die even with medical treatment. Moreover, death rate can be as high as 13% where medical treatment is not properly handled. In cases of misdiagnosis and failure of treatment, systemic complications rapidly develop including acute respiratory distress syndrome, acute kidney failure, encephalitis, gastrointestinal bleeding, hepatitis, meningitis, myocarditis, pancreatitis, pneumonia, septic shock, sub-acute thyroiditis, and multi-organ dysfunctions. Harmful symptoms involving multiple organ failure and neurological impairment are difficult to treat, and can be lifelong debilitation or directly fatal. The central nervous system is often affected and result in various complications including cerebellitis, cranial nerve palsies, meningoencephalitis, plexopathy, transverse myelitis, neuroleptic malignant syndrome, and Guillan-Barré syndrome. Death rates due to complications can be up to 14% in brain infections, and 24% with multiple organ failure. It is the major cause of acute encephalitis syndrome in India, where viral infection Japanese encephalitis has been regarded as the main factor.
The cosmetic effect of BTX-A on wrinkles was originally documented by a plastic surgeon from Sacramento, California, Richard Clark, and published in the journal "Plastic and Reconstructive Surgery" in 1989. Canadian husband and wife ophthalmologist and dermatologist physicians, JD and JA Carruthers, were the first to publish a study on BTX-A for the treatment of glabellar frown lines in 1992. Similar effects had reportedly been observed by a number of independent groups (Brin, and the Columbia University group under Monte Keen.) After formal trials, on April 12, 2002, the FDA announced regulatory approval of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines). Subsequently, cosmetic use of botulinum toxin type A has become widespread. The results of Botox Cosmetic can last up to four months and may vary with each patient. The US Food and Drug Administration approved an alternative product-safety testing method in response to increasing public concern that LD50 testing was required for each batch sold in the market.
An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacteria. Although they are most effective in neutralizing toxins, they can kill bacteria and other microorganisms. Antitoxins are made within organisms, but can be injected into other organisms, including humans. This procedure involves injecting an animal with a safe amount of a particular toxin. Then, the animal’s body makes the antitoxin needed to neutralize the toxin. Later, the blood is withdrawn from the animal. When the antitoxin is obtained from the blood, it is purified and injected into a human or other animal, inducing passive immunity. To prevent serum sickness, it is often best to use antitoxin generated from the same species (e.g. use human antitoxin to treat humans).
The toxin has been implicated in cases of respiratory irritation, inflammation of the eye and severe contact dermatitis in fishermen. Antillatoxin is a very potent neurotoxin, although exact toxicity differs between species. The lethal concentration LC is about 0.1 µM for goldfish, making it the most potent toxin known for goldfish after brevetoxin. It can be cytotoxic to single cerebellar granule cells at concentrations as low as 20 nM in rats but more typically at 50 nM.
Khalaf Bushara and David Park were the first to demonstrate a nonmuscular use of BTX-A while treating patients with hemifacial spasm in England in 1993, showing that botulinum toxin injections inhibit sweating, and so are useful in treating hyperhidrosis (excessive sweating). BTX-A has since been approved for the treatment of severe primary axillary hyperhidrosis (excessive underarm sweating of unknown cause), which cannot be managed by topical agents.
In 1986, Scott's micromanufacturer and distributor of Botox was no longer able to supply the drug because of an inability to obtain product liability insurance. Patients became desperate, as supplies of Botox were gradually consumed, forcing him to abandon patients who would have been due for their next injection. For a period of four months, American blepharospasm patients had to arrange to have their injections performed by participating doctors at Canadian eye centers until the liability issues could be resolved.
Organophosphate pesticides are one of the top causes of poisoning worldwide, with an annual incidence of poisonings among agricultural workers varying from 3-10% per country.
Mosquito-borne diseases or mosquito-borne illnesses are diseases caused by bacteria, viruses or parasites transmitted by mosquitoes. They can transmit disease without being affected themselves. Nearly 700 million people get a mosquito-borne illness each year resulting in over one million deaths.
Based on data from thousands of patients collected by 240 investigators, Allergan received FDA approval in 1989 to market Oculinum for clinical use in the United States to treat adult strabismus and blepharospasm, using the trademark Botox. This was under the 1983 US Orphan Drug Act.
On January 15, 2010, Johnson & Johnson announced a voluntary recall of several hundred batches of popular medicines, including Benadryl, Motrin, Rolaids, Simply Sleep, St. Joseph Aspirin and Tylenol. The recall was due to complaints of a musty smell suspected to be due to contamination of the packaging with the chemical 2,4,6-tribromoanisole. The full health effects of 2,4,6-tribromoanisole are not known but no serious events have been documented in medical literature. The recall came 20 months after McNeil first began receiving and investigating consumer complaints about moldy-smelling bottles of Tylenol Arthritis Relief caplets, according to the United States Food and Drug Administration (FDA). The recall included 53 million bottles of over-the-counter products including Tylenol, Motrin and Rolaids, Benadryl and St. Joseph's Aspirin, involving lots in the Americas, the United Arab Emirates and Fiji.
Interest in melioidosis has been expressed because it has the potential to be developed as a biological weapon. It is classed by the US Centers for Disease Control (CDC) as a category B agent. "B. pseudomallei", like "B. mallei" which causes glanders, was studied by the US as a potential biological warfare agent, but never weaponized. The Soviet Union was reported to have also experimented with "B. pseudomallei" as a biological warfare agent.
Bovine spongiform encephalopathy (BSE), commonly known as "mad cow disease", is a fatal, neurodegenerative disease of cattle, which infects by a mechanism that surprised biologists upon its discovery in the late 20th century. In the UK, the country worst affected, 179,000 cattle were infected and 4.4 million killed as a precaution. The disease can be transmitted to human beings who eat or inhale material from infected carcasses. In humans, it is known as new variant Creutzfeldt–Jakob disease (vCJD or nvCJD), and by June 2007, it had killed 165 people in Britain, and six elsewhere with the number expected to rise because of the disease's long incubation period. Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989.
"C. botulinum" is responsible for foodborne botulism (ingestion of preformed toxin), infant botulism (intestinal infection with toxin-forming "C. botulinum"), and wound botulism (infection of a wound with "C. botulinum"). "C. botulinum" produces heat-resistant endospores that are commonly found in soil and are able to survive under adverse conditions.
Botulinum toxin (BTX) is a neurotoxic protein produced by the bacterium "Clostridium botulinum" and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis. Infection with the bacterium causes the disease botulism. The toxin is also used commercially in medicine, cosmetics and research.
Botulinum is the most acutely lethal toxin known, with an estimated human median lethal dose (LD) of 1.3–2.1 ng/kg intravenously or intramuscularly and 10–13 ng/kg when inhaled.
Foodborne botulism results from contaminated foodstuffs in which "C. botulinum" spores have been allowed to germinate and produce botulism toxin, and this typically occurs in canned non-acidic food substances that have not received a strong enough thermal heat treatment. "C. botulinum" prefers low oxygen environments and is a poor competitor to other bacteria, but its spores are resistant to thermal treatments. When a canned food is sterilized insufficiently, most other bacteria besides the "C. botulinum" spores are killed, and the spores can germinate and produce botulism toxin. Botulism is a rare but serious paralytic illness, leading to paralysis that typically starts with the muscles of the face and then spreads towards the limbs. The botulinum toxin is extremely dangerous because it cannot be detected by sight or smell, and ingestion of even a small amount of the toxin can be deadly. In severe forms, it leads to paralysis of the breathing muscles and causes respiratory failure. In view of this life-threatening complication, all suspected cases of botulism are treated as medical emergencies, and public health officials are usually involved to prevent further cases from the same source.
"Clostridium botulinum" is an anaerobic, Gram positive, spore-forming rod. Botulinum toxin is one of the most powerful known toxins: about one microgram is lethal to humans when inhaled. It acts by blocking nerve function (neuromuscular blockade) through inhibition of the excitatory neurotransmitter acetylcholine's release from the presynaptic membrane of neuromuscular junctions in the somatic nervous system. This causes paralysis. Advanced botulism can cause respiratory failure by paralysing the muscles of the chest; this can progress to respiratory arrest. Furthermore, acetylcholine release from the presynaptic membranes of muscarinic nerve synapses is blocked. This can lead to a variety of autonomic signs and symptoms described above.