Botulism
Encyclopedia
Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin
which is metabolic waste produced under anaerobic conditions by the bacterium Clostridium botulinum
, and affecting a wide range of mammals, birds and fish.
The toxin enters the human body
in one of three ways: by colonization of the digestive tract by the bacterium in children (infant botulism) or adults (adult intestinal toxemia), by ingestion of toxin from foods (foodborne botulism) or by contamination of a wound by the bacterium (wound botulism). Person to person transmission of botulism does not occur.
All forms lead to paralysis
that typically starts with the muscles of the face and then spreads towards the limbs. In severe forms, it leads to paralysis of the breathing muscles and causes respiratory failure
. In light 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.
Botulism can be prevented by killing the spores by pressure cooking or autoclaving at 121 °C (249.8 °F) for 3 minutes or providing conditions that prevent the spores from growing. The toxin itself is destroyed by normal cooking processes - that is, boiling for a few minutes. Additional precautions for infants include not feeding them honey
.
. A group of twelve nerves controls eye movements, the facial muscles
and the muscles controlling chewing and swallowing
. Double vision
, drooping of both eyelids
, loss of facial expression and swallowing problems may therefore occur, as well as difficulty with talking
. The weakness then spreads to the arms (starting in the shoulders and proceeding to the forearms) and legs (again from the thighs down to the feet). Severe botulism leads to reduced movement of the muscles of respiration
, and hence problems with gas exchange
. This may be experienced as dyspnea
(difficulty breathing), but when severe can lead to respiratory failure
, due to the buildup of unexhaled carbon dioxide
and its resultant depressant effect on the brain. This may lead to coma
and eventually death if untreated.
In addition to affecting the voluntary muscles
, it can also cause disruptions in the autonomic nervous system
. This is experienced as a dry mouth and throat
(due to decreased production of saliva), postural hypotension (decreased blood pressure on standing, with resultant lightheadedness and risk of blackouts), and eventually constipation
(due to decreased peristalsis
). Some of the toxins (B and E) also precipitate nausea
and vomiting
.
Clinicians frequently think of the symptoms of botulism in terms of a classic triad: bulbar palsy
and descending paralysis, lack of fever, and clear senses and mental status ("clear sensorium").
spores, and subsequent colonization of the small intestine. The infant gut may be colonized when the composition of the intestinal microflora
(normal flora) is insufficient to competitively inhibit the growth of C. botulinum
. Medical science does not yet completely understand all factors that make an infant susceptible to C. botulinum
colonization. The growth of the spores releases botulinum toxin
, which is then absorbed into the bloodstream and taken throughout the body, causing paralysis by blocking the release of acetylcholine at the neuromuscular junction
. Typical symptoms of infant botulism include constipation, lethargy, weakness, difficulty feeding and an altered cry, often progressing to a complete descending flaccid paralysis
. Although constipation is usually the first symptom of infant botulism, it is commonly overlooked.
Honey
is the only known dietary reservoir of C. botulinum
spores linked to infant botulism. For this reason honey should not be fed to infants less than one year of age. Due to the success of this public health message, fewer than 5% of recent infant botulism cases have been exposed to honey. The remaining 95% of infant botulism cases are thought to have acquired the spores from the natural environment. Clostridium botulinum
is a ubiquitous soil-dwelling bacterium. Many infant botulism patients have been demonstrated to live near a construction site or an area of soil disturbance.
Infant botulism has been reported in 49 of 50 US states, and cases have been recognized in 26 countries on five continents.
rate is less than 1% for hospitalized infants with botulism.
Botulism can result in death due to respiratory
failure. However, in the past 50 years, the proportion of patients with botulism who die has fallen from about 50% to 8% due to improved supportive care. A patient with severe botulism may require a breathing machine as well as intensive medical and nursing care for several months. Patients who survive an episode of botulism poisoning may
have fatigue
and shortness of breath for years and long-term therapy may be needed to aid their recovery.
, Gram positive, spore-forming rod. Botulin toxin is one of the most powerful known toxins: about one microgram
is lethal to humans. It acts by blocking nerve
function and leads to respiratory
and musculoskeletal paralysis
.
In all cases illness is caused by the toxin made by C. botulinum, not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that are firing more often.
Specifically, the toxin acts by blocking the production or release of acetylcholine
at synapses and neuromuscular junctions. Death occurs due to respiratory failure.
Four main modes of entry for the toxin are known. The most common form in Western countries is infant botulism. This occurs in small children who are colonized
with the bacterium during the early stages of their lives. The bacterium then releases the toxin into the intestine, which is absorbed into the bloodstream. The consumption of honey
during the first year of life has been identified as a risk factor for infant botulism; it is a factor in a fifth of all cases. The adult form of infant botulism is termed adult intestinal toxemia, and is exceedingly rare.
Foodborne botulism results from contaminated foodstuffs in which C. botulinum spores have been allowed to germinate in anaerobic conditions. This typically occurs in home-canned food substances and fermented uncooked dishes. Given that multiple people often consume food from the same source, it is common for more than a single person to be affected simultaneously. Symptoms usually appear 12–36 hours after eating, but can also appear within 6 hours to 10 days.
Wound botulism results from the contamination of a wound with the bacteria, which then secrete the toxin into the bloodstream. This has become more common in intravenous drug users since the 1990s, especially people using black tar heroin
and those injecting heroin into the skin
rather than the veins.
Isolated cases of botulism have been described after inhalation
by laboratory workers and after cosmetic use of inappropriate strengths of Botox
.
.
Physicians may consider diagnosing botulism if the patient's history and physical examination suggest botulism. However, these clues are often not enough to allow a diagnosis. Other diseases such as Guillain-Barré syndrome
, stroke
, and myasthenia gravis
can appear similar to botulism, and special tests may be needed to exclude these other conditions. These tests may include a brain scan, cerebrospinal fluid
examination, nerve conduction test (electromyography
, or EMG), and an edrophonium
chloride (Tensilon) test for myasthenia gravis. A definite diagnosis can be made if botulinum toxin is identified in the food, stomach or intestinal contents, vomit or feces. The toxin is occasionally found in the blood in peracute cases. Botulinum toxin can be detected by a variety of techniques, including enzyme-linked immunosorbent assays (ELISAs), electrochemiluminescent (ECL) tests and mouse inoculation or feeding trials. The toxins can be typed with neutralization tests in mice. In toxicoinfectious botulism, the organism can be cultured from tissues. On egg yolk medium, toxin-producing colonies usually display surface iridescence that extends beyond the colony.
In cattle, the symptoms may include drooling, restlessness, uncoordination, urine retention, dysphagia, and sternal recumbency. Laterally recumbent animals are usually very close to death. In sheep, the symptoms may include drooling, a serous nasal discharge, stiffness, and incoordination. Abdominal respiration may be observed and the tail may switch on the side. As the disease progresses, the limbs may become paralyzed and death may occur.
Phosphorus-deficient cattle, especially in southern Africa, are inclined to ingest bones and carrion containing clostridial toxins and consequently suffer lame sickness or lamsiekte.
The clinical signs in horses are similar to cattle. The muscle paralysis is progressive; it usually begins at the hindquarters and gradually moves to the front limbs, neck, and head. Death generally occurs 24 to 72 hours after initial symptoms and results from respiratory paralysis. Some foals are found dead without other clinical signs.
Pigs are relatively resistant to botulism. Reported symptoms include anorexia, refusal to drink, vomiting, pupillary dilation, and muscle paralysis.
In poultry and wild birds, flaccid paralysis
is usually seen in the legs, wings, neck and eyelids. Broiler chickens with the toxicoinfectious form may also have diarrhea with excess urates.
A recommended prevention measure for infant botulism is to avoid feeding honey to infants less than 12 months of age. In older children and adults the normal intestinal bacteria suppress development of C. botulinum.
While commercially canned goods are required to undergo a "botulinum cook" in a pressure cooker at 121 °C (249.8 °F) for 3 minutes, and so rarely cause botulism, there have been notable exceptions such as the 1978 Alaskan salmon outbreak and the 2007 Castleberry's Food Company
outbreak. Foodborne botulism is the rarest form though, accounting for only around 15% of cases (US) and has more frequently been from home-canned
foods with low acid content, such as carrot juice
, asparagus, green bean
s, beet
s, and corn
. However, outbreaks of botulism have resulted from more unusual sources. In July, 2002, fourteen Alaska
ns ate muktuk (whale meat
) from a beached whale
, and eight of them developed symptoms of botulism, two of them requiring mechanical ventilation
. Other, but much rarer sources of infection (about every decade in the US) include garlic
or herbs stored covered in oil
without acidification, chilli peppers
, improperly handled baked potatoes wrapped in aluminium
foil, tomatoes, and home-canned or fermented fish
. Persons who do home canning should follow strict hygienic
procedures to reduce contamination of foods. Oils infused with fresh garlic or herbs should be acidified and refrigerated. Potatoes which have been baked while wrapped in aluminum foil should be kept hot until served or refrigerated. Because the botulism toxin is destroyed by high temperatures, home-canned foods are best boiled for 10 minutes before eating. Metal cans containing food in which bacteria, possibly botulinum, are growing may bulge outwards due to gas production from bacterial growth; such cans should be discarded. Any container of food which has been heat-treated and then assumed to be airtight which shows signs of not being so, e.g., metal cans with pinprick holes from rust or mechanical damage, should also be discarded. Contamination of a canned food solely with C. botulinum may not cause any visual defects (e.g. bulging). Only sufficient thermal processing during production should be used as a food safety control.
Wound botulism can be prevented by promptly seeking medical care for infected wounds, and by avoiding punctures by unsterile things such as needles used for street drug injections. It is currently being researched at USAMRIID under BSL-434.
The respiratory failure and paralysis that occur with severe botulism may require a patient to be on a ventilator for weeks, plus intensive medical and nursing care. After several weeks, the paralysis
slowly improves. If diagnosed early, foodborne and wound botulism can be treated by inducing passive immunity
with a horse-derived antitoxin
, which blocks the action of toxin circulating in the blood. This can prevent patients from worsening, but recovery still takes many weeks. Physicians may try to remove contaminated food still in the gut by inducing vomiting or by using enema
s. Wounds should be treated, usually surgically, to remove the source of the toxin-producing bacteria. Good supportive care in a hospital is the mainstay of therapy for all forms of botulism.
Furthermore each case of food-borne botulism is a potential public health emergency in that it is necessary to identify the source of the outbreak and ensure that all persons who have been exposed to the toxin have been identified, and that no contaminated food remains.
There are two primary Botulinum Antitoxins available for treatment of wound and foodborne botulism. Trivalent (A,B,E) Botulinum Antitoxin is derived from equine sources utilizing whole antibodies (Fab & Fc portions). This antitoxin is available from the local health department via the CDC. The second antitoxin is heptavalent (A,B,C,D,E,F,G) Botulinum Antitoxin which is derived from "despeciated" equine IgG antibodies which have had the Fc portion cleaved off leaving the F(ab')2 portions. This is a less immunogenic antitoxin that is effective against all known strains of botulism where not contraindicated. This is available from the US Army. On 1 June 2006 the US Department of Health and Human Services awarded a $363 million contract with Cangene Corporation for 200,000 doses of Heptavalent Botulinum Antitoxin over five years for delivery into the Strategic National Stockpile
beginning in 2007.
rate is less than 1% for hospitalized infants with botulism.
Between 1910 and 1919 the death rate from botulism was 70% in the United States, dropping to 9% in the 1980s and 2% in the early 1990s, mainly because of the development of artificial respirators. Up to 60% of botulism cases are fatal if left untreated.
The World Health Organization
(WHO) reports that the current mortality rate is 5% (type B) to 10% (type A). Other sources report that, in the U.S., the overall mortality rate is about 7.5%, but the mortality rate among adults over 60 is 30%. The mortality rate for wound botulism is about 10%. The infant botulism mortality rate is about 1.3%.
Death from botulism is common in waterfowl; an estimated 10,000 to 100,000 birds die of botulism annually. In some large outbreaks, a million or more birds may die. Ducks appear to be affected most often. Botulism also affects commercially raised poultry. In chickens, the mortality rate varies from a few birds to 40% of the flock. Some affected birds may recover without treatment.
Botulism seems to be relatively uncommon in domestic mammals; however, in some parts of the world, epidemics with up to 65% mortality are seen in cattle. The prognosis is poor in large animals that are recumbent. Most dogs with botulism recover within 2 weeks.
The number of cases of food borne and infant botulism has changed little in recent years, but wound botulism has increased because of the use of black tar heroin
, especially in California
.
in its Augusta, Georgia
plant. It was later identified that the Castleberry's plant had serious production issues on a specific line of retorts that had under-processed the cans of food. These issues included broken cooking alarms, leaking water valves and inaccurate temperature devices, all the result of poor management of the company.
All of the victims were hospitalized and placed on mechanical ventilation. The Castleberry's Food Company outbreak was the first instance of botulism in commercial canned foods in the United States in over 30 years.
soup.
and invertebrates
are reports are not just limited to humans, rats, mouse, chicken, frogs, toads, goldfish, aplysia, squid, crayfish, drosophila, leech etc.
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...
which is metabolic waste produced under anaerobic conditions by the bacterium Clostridium botulinum
Clostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...
, and affecting a wide range of mammals, birds and fish.
The toxin enters the human body
Human body
The human body is the entire structure of a human organism, and consists of a head, neck, torso, two arms and two legs.By the time the human reaches adulthood, the body consists of close to 100 trillion cells, the basic unit of life...
in one of three ways: by colonization of the digestive tract by the bacterium in children (infant botulism) or adults (adult intestinal toxemia), by ingestion of toxin from foods (foodborne botulism) or by contamination of a wound by the bacterium (wound botulism). Person to person transmission of botulism does not occur.
All forms lead to paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
that typically starts with the muscles of the face and then spreads towards the limbs. In severe forms, it leads to paralysis of the breathing muscles and causes respiratory failure
Respiratory failure
The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
. In light of this life-threatening complication, all suspected cases of botulism are treated as medical emergencies
Medical emergency
A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...
, and public health
Public health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals" . It is concerned with threats to health based on population health...
officials are usually involved to prevent further cases from the same source.
Botulism can be prevented by killing the spores by pressure cooking or autoclaving at 121 °C (249.8 °F) for 3 minutes or providing conditions that prevent the spores from growing. The toxin itself is destroyed by normal cooking processes - that is, boiling for a few minutes. Additional precautions for infants include not feeding them honey
Honey
Honey is a sweet food made by bees using nectar from flowers. The variety produced by honey bees is the one most commonly referred to and is the type of honey collected by beekeepers and consumed by humans...
.
Signs and symptoms
The muscle weakness of botulism characteristically starts in the muscles supplied by the cranial nervesCranial nerves
Cranial nerves are nerves that emerge directly from the brain, in contrast to spinal nerves, which emerge from segments of the spinal cord. In humans, there are traditionally twelve pairs of cranial nerves...
. A group of twelve nerves controls eye movements, the facial muscles
Facial muscles
The facial muscles are a group of striated muscles innervated by the facial nerve that, among other things, control facial expression. These muscles are also called mimetic muscles.-Structure:...
and the muscles controlling chewing and swallowing
Swallowing
Swallowing, known scientifically as deglutition, is the process in the human or animal body that makes something pass from the mouth, to the pharynx, and into the esophagus, while shutting the epiglottis. If this fails and the object goes through the trachea, then choking or pulmonary aspiration...
. Double vision
Diplopia
Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...
, drooping of both eyelids
Ptosis (eyelid)
Ptosis is a drooping of the upper or lower eyelid. The drooping may be worse after being awake longer, when the individual's muscles are tired. This condition is sometimes called "lazy eye", but that term normally refers to amblyopia...
, loss of facial expression and swallowing problems may therefore occur, as well as difficulty with talking
Dysarthria
Dysarthria is a motor speech disorder resulting from neurological injury of the motor component of the motor-speech system and is characterized by poor articulation of phonemes...
. The weakness then spreads to the arms (starting in the shoulders and proceeding to the forearms) and legs (again from the thighs down to the feet). Severe botulism leads to reduced movement of the muscles of respiration
Muscles of respiration
The various muscles of respiration aid in both inspiration and expiration, which require changes in the pressure within the thoracic cavity. The respiratory muscles work to achieve this by changing the dimensions of the thoracic cavity....
, and hence problems with gas exchange
Gas exchange
Gas exchange is a process in biology where gases contained in an organism and atmosphere transfer or exchange. In human gas-exchange, gases contained in the blood of human bodies exchange with gases contained in the atmosphere. Human gas-exchange occurs in the lungs...
. This may be experienced as dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
(difficulty breathing), but when severe can lead to respiratory failure
Respiratory failure
The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
, due to the buildup of unexhaled carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
and its resultant depressant effect on the brain. This may lead to coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
and eventually death if untreated.
In addition to affecting the voluntary muscles
Somatic nervous system
The somatic nervous system is the part of the peripheral nervous system associated with the voluntary control of body movements via skeletal muscles...
, it can also cause disruptions in the autonomic nervous system
Dysautonomia
Dysautonomia is a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome , inappropriate sinus tachycardia , vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic...
. This is experienced as a dry mouth and throat
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
(due to decreased production of saliva), postural hypotension (decreased blood pressure on standing, with resultant lightheadedness and risk of blackouts), and eventually constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
(due to decreased peristalsis
Peristalsis
Peristalsis is a radially symmetrical contraction and relaxation of muscles which propagates in a wave down the muscular tube, in an anterograde fashion. In humans, peristalsis is found in the contraction of smooth muscles to propel contents through the digestive tract. Earthworms use a similar...
). Some of the toxins (B and E) also precipitate nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
.
Clinicians frequently think of the symptoms of botulism in terms of a classic triad: bulbar palsy
Bulbar palsy
Bulbar palsy refers to impairment of function of the cranial nerves IX, X, XI and XII, which occurs due to a lower motor neuron lesion either at nuclear or fascicular level in the medulla oblongata or from lesions of the lower cranial nerves outside the brainstem.In contrast, pseudobulbar palsy...
and descending paralysis, lack of fever, and clear senses and mental status ("clear sensorium").
Infant botulism
Infant botulism was first recognized in 1976, and is the most common form of botulism in the United States. There are 80 - 100 diagnosed cases of infant botulism in the United States each year. Infants are susceptible to infant botulism in the first year of life, with more than 90% of cases occurring in infants younger than six months. Infant botulism results from the ingestion of the C. botulinumClostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...
spores, and subsequent colonization of the small intestine. The infant gut may be colonized when the composition of the intestinal microflora
Gut flora
Gut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora....
(normal flora) is insufficient to competitively inhibit the growth of C. botulinum
Clostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...
. Medical science does not yet completely understand all factors that make an infant susceptible to C. botulinum
Clostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...
colonization. The growth of the spores releases botulinum toxin
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...
, which is then absorbed into the bloodstream and taken throughout the body, causing paralysis by blocking the release of acetylcholine at the neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
. Typical symptoms of infant botulism include constipation, lethargy, weakness, difficulty feeding and an altered cry, often progressing to a complete descending flaccid paralysis
Flaccid paralysis
Flaccid paralysis is a clinical manifestation characterized by weakness or paralysis and reduced muscle tone without other obvious cause .-Polio:...
. Although constipation is usually the first symptom of infant botulism, it is commonly overlooked.
Honey
Honey
Honey is a sweet food made by bees using nectar from flowers. The variety produced by honey bees is the one most commonly referred to and is the type of honey collected by beekeepers and consumed by humans...
is the only known dietary reservoir of C. botulinum
Clostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...
spores linked to infant botulism. For this reason honey should not be fed to infants less than one year of age. Due to the success of this public health message, fewer than 5% of recent infant botulism cases have been exposed to honey. The remaining 95% of infant botulism cases are thought to have acquired the spores from the natural environment. Clostridium botulinum
Clostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...
is a ubiquitous soil-dwelling bacterium. Many infant botulism patients have been demonstrated to live near a construction site or an area of soil disturbance.
Infant botulism has been reported in 49 of 50 US states, and cases have been recognized in 26 countries on five continents.
Complications
Infant botulism has no long-term side effects, but can be complicated by nosocomial adverse events. The case fatalityCase fatality
In epidemiology, case fatality or fatality rate, is the ratio of deaths within a designated population of people with a particular condition, over a certain period of time. An example of a fatality rate would be 9 deaths per 10,000 people at risk per year...
rate is less than 1% for hospitalized infants with botulism.
Botulism can result in death due to respiratory
Respiration (physiology)
'In physiology, respiration is defined as the transport of oxygen from the outside air to the cells within tissues, and the transport of carbon dioxide in the opposite direction...
failure. However, in the past 50 years, the proportion of patients with botulism who die has fallen from about 50% to 8% due to improved supportive care. A patient with severe botulism may require a breathing machine as well as intensive medical and nursing care for several months. Patients who survive an episode of botulism poisoning may
have fatigue
Fatigue (physical)
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
and shortness of breath for years and long-term therapy may be needed to aid their recovery.
Cause
C. botulinum is an anaerobicAnaerobic organism
An anaerobic organism or anaerobe is any organism that does not require oxygen for growth. It could possibly react negatively and may even die if oxygen is present...
, Gram positive, spore-forming rod. Botulin toxin is one of the most powerful known toxins: about one microgram
Microgram
In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...
is lethal to humans. It acts by blocking nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
function and leads to respiratory
Respiratory system
The respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles...
and musculoskeletal paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
.
In all cases illness is caused by the toxin made by C. botulinum, not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that are firing more often.
Specifically, the toxin acts by blocking the production or release of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
at synapses and neuromuscular junctions. Death occurs due to respiratory failure.
Four main modes of entry for the toxin are known. The most common form in Western countries is infant botulism. This occurs in small children who are colonized
Colonisation (biology)
Colonisation is the process in biology by which a species spreads into new areas, regions, and continents. It is sometimes also referred to as immigration, but colonisation often refers to successful immigration with integration to a community, having resisted initial local extinction.One classic...
with the bacterium during the early stages of their lives. The bacterium then releases the toxin into the intestine, which is absorbed into the bloodstream. The consumption of honey
Honey
Honey is a sweet food made by bees using nectar from flowers. The variety produced by honey bees is the one most commonly referred to and is the type of honey collected by beekeepers and consumed by humans...
during the first year of life has been identified as a risk factor for infant botulism; it is a factor in a fifth of all cases. The adult form of infant botulism is termed adult intestinal toxemia, and is exceedingly rare.
Foodborne botulism results from contaminated foodstuffs in which C. botulinum spores have been allowed to germinate in anaerobic conditions. This typically occurs in home-canned food substances and fermented uncooked dishes. Given that multiple people often consume food from the same source, it is common for more than a single person to be affected simultaneously. Symptoms usually appear 12–36 hours after eating, but can also appear within 6 hours to 10 days.
Wound botulism results from the contamination of a wound with the bacteria, which then secrete the toxin into the bloodstream. This has become more common in intravenous drug users since the 1990s, especially people using black tar heroin
Black tar heroin
Black tar heroin is a type of illicit opiate narcotic drug formed from the incomplete acetylation of morphine. It is also called brown.Black tar can contain a variable percentage of heroin, but despite the name, what makes Black Tar specific as a type is not actually its heroin content, but rather...
and those injecting heroin into the skin
Skin popping
Skin popping is a method of administration for the use of drugs by injecting or placing the substance or drug under the skin. It can include subcutaneous placement or intradermal placement though is also rarely used to mean intramuscular injection. It is however as a term distinct from the meaning...
rather than the veins.
Isolated cases of botulism have been described after inhalation
Inhalation
Inhalation is the movement of air from the external environment, through the air ways, and into the alveoli....
by laboratory workers and after cosmetic use of inappropriate strengths of Botox
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...
.
Diagnosis
For infant botulism, diagnosis should be made on clinical grounds. Confirmation of the diagnosis is made by testing of a stool or enema specimen with the mouse bioassayBioassay
Bioassay , or biological standardization is a type of scientific experiment. Bioassays are typically conducted to measure the effects of a substance on a living organism and are essential in the development of new drugs and in monitoring environmental pollutants...
.
Physicians may consider diagnosing botulism if the patient's history and physical examination suggest botulism. However, these clues are often not enough to allow a diagnosis. Other diseases such as Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, and myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
can appear similar to botulism, and special tests may be needed to exclude these other conditions. These tests may include a brain scan, cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
examination, nerve conduction test (electromyography
Electromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
, or EMG), and an edrophonium
Edrophonium
Edrophonium is a readily reversible acetylcholinesterase inhibitor. It prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting the enzyme acetylcholinesterase, mainly at the neuromuscular junction...
chloride (Tensilon) test for myasthenia gravis. A definite diagnosis can be made if botulinum toxin is identified in the food, stomach or intestinal contents, vomit or feces. The toxin is occasionally found in the blood in peracute cases. Botulinum toxin can be detected by a variety of techniques, including enzyme-linked immunosorbent assays (ELISAs), electrochemiluminescent (ECL) tests and mouse inoculation or feeding trials. The toxins can be typed with neutralization tests in mice. In toxicoinfectious botulism, the organism can be cultured from tissues. On egg yolk medium, toxin-producing colonies usually display surface iridescence that extends beyond the colony.
In cattle, the symptoms may include drooling, restlessness, uncoordination, urine retention, dysphagia, and sternal recumbency. Laterally recumbent animals are usually very close to death. In sheep, the symptoms may include drooling, a serous nasal discharge, stiffness, and incoordination. Abdominal respiration may be observed and the tail may switch on the side. As the disease progresses, the limbs may become paralyzed and death may occur.
Phosphorus-deficient cattle, especially in southern Africa, are inclined to ingest bones and carrion containing clostridial toxins and consequently suffer lame sickness or lamsiekte.
The clinical signs in horses are similar to cattle. The muscle paralysis is progressive; it usually begins at the hindquarters and gradually moves to the front limbs, neck, and head. Death generally occurs 24 to 72 hours after initial symptoms and results from respiratory paralysis. Some foals are found dead without other clinical signs.
Pigs are relatively resistant to botulism. Reported symptoms include anorexia, refusal to drink, vomiting, pupillary dilation, and muscle paralysis.
In poultry and wild birds, flaccid paralysis
Flaccid paralysis
Flaccid paralysis is a clinical manifestation characterized by weakness or paralysis and reduced muscle tone without other obvious cause .-Polio:...
is usually seen in the legs, wings, neck and eyelids. Broiler chickens with the toxicoinfectious form may also have diarrhea with excess urates.
Prevention
Although the botulinum toxin is destroyed by thorough cooking over the course of a few minutes, the spore itself is not killed by the temperatures reached with normal sea-level-pressure boiling, leaving it free to grow and again produce the toxin when conditions are right.A recommended prevention measure for infant botulism is to avoid feeding honey to infants less than 12 months of age. In older children and adults the normal intestinal bacteria suppress development of C. botulinum.
While commercially canned goods are required to undergo a "botulinum cook" in a pressure cooker at 121 °C (249.8 °F) for 3 minutes, and so rarely cause botulism, there have been notable exceptions such as the 1978 Alaskan salmon outbreak and the 2007 Castleberry's Food Company
Castleberry's Food Company
Castleberry's Food Company was an Augusta, Georgia-based canned food company founded in the 1920s by Clement Stewart Castleberry with the help of his father Clement Lamar Castleberry and closed permanently in March 2008 by the United States Food and Drug Administration.The company grew from a...
outbreak. Foodborne botulism is the rarest form though, accounting for only around 15% of cases (US) and has more frequently been from home-canned
Home canning
Home canning or bottling, also known colloquially as putting up or processing, is the process of preserving foods, in particular, fruits, vegetables, and meats, by packing them into glass jars and then heating the jars to kill the organisms that would create spoilage.- North America :In North...
foods with low acid content, such as carrot juice
Carrot juice
Carrot juice is juice produced from carrots, often consumed as a health drink. Carrot juice has a particularly high content of β-carotene, a source of vitamin A, but it is also high in B complex vitamins like folate, and many minerals including calcium, copper, magnesium, potassium, phosphorus, and...
, asparagus, green bean
Bean
Bean is a common name for large plant seeds of several genera of the family Fabaceae used for human food or animal feed....
s, beet
Beet
The beet is a plant in the Chenopodiaceae family which is now included in Amaranthaceae family. It is best known in its numerous cultivated varieties, the most well known of which is the purple root vegetable known as the beetroot or garden beet...
s, and corn
Maize
Maize known in many English-speaking countries as corn or mielie/mealie, is a grain domesticated by indigenous peoples in Mesoamerica in prehistoric times. The leafy stalk produces ears which contain seeds called kernels. Though technically a grain, maize kernels are used in cooking as a vegetable...
. However, outbreaks of botulism have resulted from more unusual sources. In July, 2002, fourteen Alaska
Alaska
Alaska is the largest state in the United States by area. It is situated in the northwest extremity of the North American continent, with Canada to the east, the Arctic Ocean to the north, and the Pacific Ocean to the west and south, with Russia further west across the Bering Strait...
ns ate muktuk (whale meat
Whale meat
Whale meat is the flesh of whales used for consumption by humans or other animals. It is prepared in various ways, and is historically part of the diet and cuisine of various communities that live near an ocean, including those of Japan, Norway, Iceland, and the Arctic...
) from a beached whale
Beached whale
A beached whale is a whale that has stranded itself on land, usually on a beach. Beached whales often die due to dehydration, the body collapsing under its own weight, or drowning when high tide covers the blowhole.-Species:...
, and eight of them developed symptoms of botulism, two of them requiring mechanical ventilation
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...
. Other, but much rarer sources of infection (about every decade in the US) include garlic
Garlic
Allium sativum, commonly known as garlic, is a species in the onion genus, Allium. Its close relatives include the onion, shallot, leek, chive, and rakkyo. Dating back over 6,000 years, garlic is native to central Asia, and has long been a staple in the Mediterranean region, as well as a frequent...
or herbs stored covered in oil
Cooking oil
Cooking oil is purified fat of plant origin, which is usually liquid at room temperature ....
without acidification, chilli peppers
Capsicum
Capsicum is a genus of flowering plants in the nightshade family, Solanaceae. Its species are native to the Americas where they have been cultivated for thousands of years, but they are now also cultivated worldwide, used as spices, vegetables, and medicines - and have become are a key element in...
, improperly handled baked potatoes wrapped in aluminium
Aluminium
Aluminium or aluminum is a silvery white member of the boron group of chemical elements. It has the symbol Al, and its atomic number is 13. It is not soluble in water under normal circumstances....
foil, tomatoes, and home-canned or fermented fish
Fermented fish
Fermented fish is an Eskimo food that is eaten raw and frozen. It is a staple part of the diet in many Yup'ik communities of the Yukon-Kuskokwim Delta.- Preparation :Fermented fish is prepared by first digging a hole about two feet in the ground...
. Persons who do home canning should follow strict hygienic
Hygiene
Hygiene refers to the set of practices perceived by a community to be associated with the preservation of health and healthy living. While in modern medical sciences there is a set of standards of hygiene recommended for different situations, what is considered hygienic or not can vary between...
procedures to reduce contamination of foods. Oils infused with fresh garlic or herbs should be acidified and refrigerated. Potatoes which have been baked while wrapped in aluminum foil should be kept hot until served or refrigerated. Because the botulism toxin is destroyed by high temperatures, home-canned foods are best boiled for 10 minutes before eating. Metal cans containing food in which bacteria, possibly botulinum, are growing may bulge outwards due to gas production from bacterial growth; such cans should be discarded. Any container of food which has been heat-treated and then assumed to be airtight which shows signs of not being so, e.g., metal cans with pinprick holes from rust or mechanical damage, should also be discarded. Contamination of a canned food solely with C. botulinum may not cause any visual defects (e.g. bulging). Only sufficient thermal processing during production should be used as a food safety control.
Wound botulism can be prevented by promptly seeking medical care for infected wounds, and by avoiding punctures by unsterile things such as needles used for street drug injections. It is currently being researched at USAMRIID under BSL-434.
Treatment
Most infant botulism patients require supportive care in a hospital setting. The only drug currently available to treat infant botulism is Botulism Immune Globulin Intravenous-Human (BIG-IV or BabyBIG). BabyBIG was developed by the Infant Botulism Treatment and Prevention Program at the California Department of Public Health.The respiratory failure and paralysis that occur with severe botulism may require a patient to be on a ventilator for weeks, plus intensive medical and nursing care. After several weeks, the paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
slowly improves. If diagnosed early, foodborne and wound botulism can be treated by inducing passive immunity
Passive immunity
Passive immunity is the transfer of active humoral immunity in the form of readymade antibodies, from one individual to another. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and can also be induced artificially, when high levels...
with a horse-derived antitoxin
Antitoxin
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...
, which blocks the action of toxin circulating in the blood. This can prevent patients from worsening, but recovery still takes many weeks. Physicians may try to remove contaminated food still in the gut by inducing vomiting or by using enema
Enema
An enema is the procedure of introducing liquids into the rectum and colon via the anus. The increasing volume of the liquid causes rapid expansion of the lower intestinal tract, often resulting in very uncomfortable bloating, cramping, powerful peristalsis, a feeling of extreme urgency and...
s. Wounds should be treated, usually surgically, to remove the source of the toxin-producing bacteria. Good supportive care in a hospital is the mainstay of therapy for all forms of botulism.
Furthermore each case of food-borne botulism is a potential public health emergency in that it is necessary to identify the source of the outbreak and ensure that all persons who have been exposed to the toxin have been identified, and that no contaminated food remains.
There are two primary Botulinum Antitoxins available for treatment of wound and foodborne botulism. Trivalent (A,B,E) Botulinum Antitoxin is derived from equine sources utilizing whole antibodies (Fab & Fc portions). This antitoxin is available from the local health department via the CDC. The second antitoxin is heptavalent (A,B,C,D,E,F,G) Botulinum Antitoxin which is derived from "despeciated" equine IgG antibodies which have had the Fc portion cleaved off leaving the F(ab')2 portions. This is a less immunogenic antitoxin that is effective against all known strains of botulism where not contraindicated. This is available from the US Army. On 1 June 2006 the US Department of Health and Human Services awarded a $363 million contract with Cangene Corporation for 200,000 doses of Heptavalent Botulinum Antitoxin over five years for delivery into the Strategic National Stockpile
Strategic National Stockpile
The Strategic National Stockpile is the United States' national repository of antibiotics, vaccines, chemical antidotes, antitoxins and other critical medical equipment and supplies...
beginning in 2007.
Prognosis
Infant botulism has no long-term side effects, but can be complicated by nosocomial adverse events. The case fatalityCase fatality
In epidemiology, case fatality or fatality rate, is the ratio of deaths within a designated population of people with a particular condition, over a certain period of time. An example of a fatality rate would be 9 deaths per 10,000 people at risk per year...
rate is less than 1% for hospitalized infants with botulism.
Between 1910 and 1919 the death rate from botulism was 70% in the United States, dropping to 9% in the 1980s and 2% in the early 1990s, mainly because of the development of artificial respirators. Up to 60% of botulism cases are fatal if left untreated.
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) reports that the current mortality rate is 5% (type B) to 10% (type A). Other sources report that, in the U.S., the overall mortality rate is about 7.5%, but the mortality rate among adults over 60 is 30%. The mortality rate for wound botulism is about 10%. The infant botulism mortality rate is about 1.3%.
Death from botulism is common in waterfowl; an estimated 10,000 to 100,000 birds die of botulism annually. In some large outbreaks, a million or more birds may die. Ducks appear to be affected most often. Botulism also affects commercially raised poultry. In chickens, the mortality rate varies from a few birds to 40% of the flock. Some affected birds may recover without treatment.
Botulism seems to be relatively uncommon in domestic mammals; however, in some parts of the world, epidemics with up to 65% mortality are seen in cattle. The prognosis is poor in large animals that are recumbent. Most dogs with botulism recover within 2 weeks.
Epidemiology
Between 1990 and 2000, the Centers for Disease Control reported 263 individual 'cases' from 160 foodborne botulism 'events' in the United States with a case-fatality rate of 4%. Thirty-nine percent (103 cases and 58 events) occurred in Alaska, all of which were attributable to traditional Alaska aboriginal foods. In the lower 49 states, home-canned food was implicated in 70 (91%) events with canned asparagus being the most numerous cause. Two restaurant-associated outbreaks affected 25 persons. The median number of cases per year was 23 (range 17–43), the median number of events per year was 14 (range 9–24). The highest incidence rates occurred in Alaska, Idaho, Washington, and Oregon. All other states had an incidence rate of 1 case per ten million people or less.The number of cases of food borne and infant botulism has changed little in recent years, but wound botulism has increased because of the use of black tar heroin
Black tar heroin
Black tar heroin is a type of illicit opiate narcotic drug formed from the incomplete acetylation of morphine. It is also called brown.Black tar can contain a variable percentage of heroin, but despite the name, what makes Black Tar specific as a type is not actually its heroin content, but rather...
, especially in California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
.
Castleberry's Food Company Outbreak
Beginning in late June 2007, 8 people contracted botulism poisoning by eating canned food products produced by Castleberry's Food CompanyCastleberry's Food Company
Castleberry's Food Company was an Augusta, Georgia-based canned food company founded in the 1920s by Clement Stewart Castleberry with the help of his father Clement Lamar Castleberry and closed permanently in March 2008 by the United States Food and Drug Administration.The company grew from a...
in its Augusta, Georgia
Augusta, Georgia
Augusta is a consolidated city in the U.S. state of Georgia, located along the Savannah River. As of the 2010 census, the Augusta–Richmond County population was 195,844 not counting the unconsolidated cities of Hephzibah and Blythe.Augusta is the principal city of the Augusta-Richmond County...
plant. It was later identified that the Castleberry's plant had serious production issues on a specific line of retorts that had under-processed the cans of food. These issues included broken cooking alarms, leaking water valves and inaccurate temperature devices, all the result of poor management of the company.
All of the victims were hospitalized and placed on mechanical ventilation. The Castleberry's Food Company outbreak was the first instance of botulism in commercial canned foods in the United States in over 30 years.
Bon Vivant incident
On July 2, 1971, the U.S. Food and Drug Administration (FDA) released a public warning after learning that a New York man had died and his wife had become seriously ill due to botulism after eating a can of Bon Vivant vichyssoiseVichyssoise
Vichyssoise is a thick soup made of puréed leeks, onions, potatoes, cream, and chicken stock. It is traditionally served cold, but can also be eaten hot.-Origin:...
soup.
In other species
Botulism can occur in many vertebratesVertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
and invertebrates
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
are reports are not just limited to humans, rats, mouse, chicken, frogs, toads, goldfish, aplysia, squid, crayfish, drosophila, leech etc.
See also
- Botox
- Centers for Disease Control and PreventionCenters for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC) - List of foodborne illness outbreaks
External links
- Agent Fact Sheet: Botulism, Center for BiosecurityCenter for BiosecurityThe Center for Biosecurity is an independent, nonprofit organization of the University of Pittsburgh Medical Center that is dedicated to improving the country’s resilience to major biological threats.-Mission statement:...
- Botulism (Technical information from the CDCCenters for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
) - Infant Botulism Treatment and Prevention Program
- Clostridium Botulinum (FDAFood and Drug AdministrationThe 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...
/CFSAN) - Botulism (WHOWhoWho may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
) - Avian Botulism
- Clostridium botulinum genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID