Botulism (Latin, botulus, "sausage") also known as botulinus intoxication is a rare but serious

paralytic illness caused by botulinum toxin, which is produced by the bacterium Clostridium
botulinum under anaerobic conditions.

The toxin enters the 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).[1]

All forms lead to paralysis that typically starts with the muscles of the face and then spreads
towards the limbs.[1] 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.[1]

Botulism can be prevented by killing the spores by cooking at 121 °C (250 °F) for 3 minutes or
providing conditions that prevent the spores from growing. Additional precautions for infants
include not feeding them honey.

The muscle weakness of botulism characteristically starts in the muscles supplied by the cranial
nerves. 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).[1] 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.[1]

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).
[1]
Some of the toxins (B and E) also precipitate nausea and vomiting.[1]

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").[2]

[edit] Mode of acquisition

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 life. The bacterium then releases the toxin into the intestine, which is
absorbed into the bloodstream. While 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.[1] The adult
form of infant botulism is termed adult intestinal toxemia, and is exceedingly rare.[1]

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. It
takes 3–5 days for the symptoms to become apparent.[1]

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.[1]

Isolated cases of botulism have been described after inhalation by laboratory workers and after
cosmetic use of inappropriate strengths of Botox.[1]

[edit] 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.[3] Infant botulism results from the ingestion
of the C. botulinum 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.[citation needed] 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,[3] and cases have been recognized in 26
countries on five continents.[4]
[edit] Complications

Infant botulism has no long-term side effects, but can be complicated by nosocomial adverse
events. The case fatality 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.

[edit] Mechanism
C. botulinum is an anaerobic, 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.[5]
Specifically, the toxin acts by blocking the production or release of acetylcholine at synapses and
neuromuscular junctions. Death occurs due to respiratory failure.

[edit] 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 bioassay.

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.[6]

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.

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.[7]

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.

[edit] 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 produce the toxin when conditions are right.

The only known prevention measure for infant botulism is to avoid feeding honey to infants less
than 12 months of age.

While commercially canned goods are required to undergo a "botulinum cook" at 121 °C
(250 °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 has more frequently been from home-canned foods with low acid content,
such as carrot juice, asparagus, green beans, beets, and corn. However, outbreaks of botulism
have resulted from more unusual sources. In July, 2002, fourteen Alaskans ate muktuk (whale
meat) from a beached whale, and eight of them developed symptoms of botulism, two of them
requiring mechanical ventilation.[8] Other sources of infection include garlic or herbs[9] stored
covered in oil without acidification,[10] chilli peppers,[11] improperly handled baked potatoes
wrapped in aluminium foil,[11] tomatoes,[11] and home-canned or fermented fish. Persons who do
home canning should follow strict hygienic procedures to reduce contamination of foods. Oils
infused with 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 20
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.

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-4.
[edit] 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.[12]

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.[13] 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 enemas. 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.[14]

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.[15]

[edit] Prognosis
This article may be confusing or unclear to readers. Please help clarify the article;
suggestions may be found on the talk page. (February 2009)

Infant botulism has no long-term side effects, but can be complicated by nosocomial adverse
events. The case fatality 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 to 100 thousand 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.

[edit] 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 Native foods. In the lower 49 states, home-canned food was implicated in 70 (91%)
events with Asparagus being the worst culprit. 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.[16]

The number of cases of foodborne 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

Clostridium botulinum is a gram-positive, rod-shaped bacterium that produces neurotoxins known as

botulinum neurotoxins types A-G, which causes flaccid muscular paralysis seen in botulism, and is also
the main paralytic agent in botox. It is an anaerobic spore-former, which produces oval, subterminal
endospores and is commonly found in soil.

Clostridium botulinum is a rod-shaped microorganism. It is an obligate anaerobe, meaning that

oxygen is poisonous to the cells. However, C. botulinum tolerates traces of oxygen due to the
enzyme called superoxide dismutase (SOD) which is an important antioxidant defense in nearly
all cells exposed to oxygen.[1] C. botulinum is only able to produce the neurotoxin during
sporulation, which can only happen in an anaerobic environment. Other bacterial species produce
spores in an unfavorable growth environment to preserve the organism's viability and permit
survival in a dormant state until the spores are exposed to favorable conditions.
In the laboratory Clostridium botulinum is usually isolated in tryptose sulfite cycloserine (TSC)
growth media in an anaerobic environment with less than 2% of oxygen. This can be achieved by
several commercial kits that use a chemical reaction to replace O2 with CO2 (E.J. GasPak
System). C. botulinum is a lipase negative microorganism that grows between pH of 4.8 and 7
and it can't use lactose as a primary carbon source, characteristics important during a
biochemical identification.[2]

[edit] Taxonomy history

Clostridium botulinum was first recognized and isolated in 1895 by Emile van Ermengem from
home cured ham implicated in a botulism outbreak.[3] The isolate was originally named Bacillus
botulinus. However, isolates from subsequent outbreaks were always found to be anaerobic spore
formers, so Bengston proposed that the organism be placed into the genus Clostridium as the
Bacillus genus was restricted to aerobic spore-forming rods.[4]

Since 1959 all species producing the botulinum neurotoxins (types A-G) have been designated
C. botulinum. Substantial phenotypic and genotypic evidence exists to demonstrate heterogeneity
within the species. This has led to the reclassification of C. botulinum type G strains as a new
species Clostridium argentinense.[5]

Clostridium botulinum strains that do not produce a botulin toxin are referred to as Clostridium
sporogenes.[6]

The complete genome of C. botulinum has been sequenced Sanger.

[edit] Phenotypes
The current nomenclature for C. botulinum recognises four physiological groups (I-IV). The
classification is based on the ability of the organism to digest complex proteins.[7][8] Studies at the
DNA and rRNA level support the subdivision of the species into groups I-IV. Most outbreaks of
human botulism are caused by group I (proteolytic) or II (non-proteolytic) C. botulinum. Group
III organisms mainly cause diseases in animals. There has been no record of Group IV C.
botulinum causing human or animal disease.

[edit] Pathology
Botulism poisoning can occur due to improperly preserved or home canned low-acid food that
was not processed using correct preservation times and/or pressure.

[edit] Neurotoxin types

Neurotoxin production is the unifying feature of the species C. botulinum. Seven types of toxins
have been identified and allocated a letter (A-G). Most strains produce one type of neurotoxin
but strains producing multiple toxins have been described. Clostridium botulinum producing B
and F toxin types have been isolated from human botulism cases in New Mexico and California.
[9]
The toxin type has been designated Bf as the type B toxin was found in excess to the type F.
Similarly, strains producing Ab and Af toxins have been reported. There is evidence that the
neurotoxin genes have been the subject of horizontal gene transfer, possibly from a viral source.
This theory is supported by the presence of integration sites flanking the toxin in some strains of
C. botulinum. However, these integrations sites are degraded indicating that the C. botulinum
acquired the toxin genes quite far into the evolutionary past.

Only types A, B, E, and F cause disease in humans while types C and D cause disease in cows,
birds, and other animals but not in humans. The "gold standard" for determining toxin type is a
mouse bioassay, but the genes for types A, B, E, and F can now be readily differentiated using
Real-time polymerase chain reaction (PCR).[10]

Organisms genetically as they identified as other Clostridium species have caused human
botulism; Clostridium butyricum producing type E toxin[11] and Clostridium baratii producing
type F toxin.[12][13] 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.

Phenotypic groups of Clostridium botulinum

Properties Group I Group II Group III Group IV
Toxin Types A, B, F B, E, F C, D G
Proteolysis + - weak -
Saccharolysis - + - -
Disease host human human animal -
Toxin gene chromosome chromosome bacteriophage plasmid
Close C. sporogenes, C. C. butyricum, C. C. haemolyticum, C. C. subterminale, C.
relatives putrificum beijerinickii novyi type A haemolyticum

[edit] Clostridium botulinum in different geographical

locations
A number of quantitative surveys for C. botulinum spores in the environment have suggested a
prevalence of specific toxin types in given geographic areas, which remain unexplained.

[edit] North America

Type A C. botulinum predominates the soil samples from the western regions while type B is the
major type found in eastern areas.[14] The type B organisms were of the proteolytic type I.
Sediments from the Great Lake regions were surveyed after outbreaks of botulism among
commercially reared fish and only type E spores were detected.[15][16][17] It has been noted in a
survey that type A strains were isolated from soils that were neutral to alkaline (average pH 7.5)
while type B strains were isolated from slightly acidic soils (average pH 6.25).
[edit] Europe

Clostridium botulinum type E is prevalent in aquatic sediments in Norway and Sweden,[18]

Denmark,[19] the Netherlands, the Baltic coast of Poland and Russia.[14] It was then suggested that
the type E C. botulinum is a true aquatic organism, which was indicated by the correlation
between the level of type E contamination and flooding of the land with seawater. As the land
dried, the level of type E decreased and type B became dominant.

In soil and sediment from the United Kingdom, C. botulinum type B predominates. In general,
the incidence is usually lower in soil than in sediment. In Italy, a survey was conducted in the
vicinity of Rome, and a low level of contamination was found; all strains were proteolytic C.
botulinum type A or B.[20]

[edit] Australia

Clostridium botulinum type A was found to be present in soil samples from mountain areas of
Victoria.[21] Type B organisms were detected in marine mud from Tasmania.[22] Type A C.
botulinum have been found in Sydney suburbs and types A and B were isolated from urban
areas. In a well defined area of the Darling-Downs region of Queensland, a study showed the
prevalence and persistence of C. botulinum type B after many cases of botulism in horses.

[edit] Other
A "mouse protection" or "mouse bioassay" test determines the type of C. botulinum present using
monoclonal antibodies. This can now also be accomplished using real-time PCR.[10]

Clostridium botulinum is also used to prepare the medicaments Botox, Dysport, Xeomin, and
Neurobloc used to selectively paralyze muscles to temporarily relieve muscle function. It has
other "off-label" medical purposes, such as treating severe facial pain, such as that caused by
trigeminal neuralgia.

Botulin toxin produced by C. botulinum is often believed to be a potential bioweapon as it is so

potent that it takes about 75 nanograms to kill a person (LD50 of 1 ng/kg,[23] assuming an average
person weighs ~75 kg); 500 grams of it would be enough to kill half of the entire human
population.

Clostridium botulinum is a soil bacterium. The spores can survive in most environments and are
very hard to kill. They can survive the temperature of boiling water at sea level, thus many foods
are canned with a pressurized boil that achieves an even higher temperature, sufficient to kill the
spores.

Growth of the bacterium can be prevented by high acidity, high ratio of dissolved sugar, high
levels of oxygen, very low levels of moisture or storage at temperatures below 3°C (38°F) for
type A. For example in a low acid, canned vegetable such as green beans that are not heated hot
enough to kill the spores (i.e., a pressurized environment) may provide an oxygen free medium
for the spores to grow and produce the toxin. On the other hand, pickles are sufficiently acidic to
prevent growth; even if the spores are present, they pose no danger to the consumer. Honey, corn
syrup, and other sweeteners may contain spores but the spores cannot grow in a highly
concentrated sugar solution; however, when a sweetener is diluted in the low oxygen, low acid
digestive system of an infant, the spores can grow and produce toxin. As soon as infants begin
eating solid food, the digestive juices become too acidic for the bacterium to grow.