Botulism

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Botulism
Botulism1and2.JPG
A 14-year-old with botulism, characterised by weakness of the eye muscles and the drooping eyelids shown in the left image, and dilated and non-moving pupils shown in the right image. This youth was fully conscious.
Pronunciation
Specialty Infectious disease, gastroenterology
Symptoms Weakness, trouble seeing, feeling tired, trouble speaking
Complications Respiratory failure
Usual onset12 to 72 hours
DurationVariable
Causes Clostridium botulinum
Diagnostic method Finding the bacteria or their toxin
Differential diagnosis Myasthenia gravis, Guillain–Barré syndrome, Amyotrophic lateral sclerosis, Lambert Eaton syndrome
PreventionProper food preparation, no honey for children younger than one
Treatment Antitoxin, antibiotics, mechanical ventilation
Prognosis ~7.5% risk of death

Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium Clostridium botulinum . The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakness of the arms, chest muscles, and legs. Vomiting, swelling of the abdomen, and diarrhea may also occur. The disease does not usually affect consciousness or cause a fever.

Contents

Botulism can occur in several ways. The bacterial spores which cause it are common in both soil and water and are very resistant. They produce the botulinum toxin when exposed to low oxygen levels and certain temperatures. Foodborne botulism happens when food containing the toxin is eaten. Infant botulism instead happens when the bacterium develops in the intestines and releases the toxin. This typically only occurs in children less than one year old, as protective mechanisms against development of the bacterium develop after that age. Wound botulism is found most often among those who inject street drugs. In this situation, spores enter a wound, and in the absence of oxygen, release the toxin. The disease is not passed directly between people. Its diagnosis is confirmed by finding the toxin or bacteria in the person in question.

Prevention is primarily by proper food preparation. The toxin, though not the spores, are destroyed by heating it to more than 85 °C (185 °F) for longer than five minutes. The clostridial spores can be destroyed in the autoclave with moist heat (120°C/ 250°F for at least 15 minutes) or dry heat (160°C for 2 hours) or by irradiation. The spores of group I strains are inactivated by heating at 121°C (250°F) for 3 minutes during commercial canning. Spores of group II strains are less heat-resistant, and they are often damaged by 90°C (194°F) for 10 minutes, 85°C for 52 minutes, or 80°C for 270 minutes; however, these treatments may not be sufficient in some foods. [1] Honey can contain the organism, and for this reason, honey should not be fed to children under 12 months. Treatment is with an antitoxin. In those who lose their ability to breathe on their own, mechanical ventilation may be necessary for months. Antibiotics may be used for wound botulism. Death occurs in 5 to 10% of people. Botulism also affects many other animals. The word is from Latin botulus, meaning 'sausage'.

Signs and symptoms

The muscle weakness of botulism characteristically starts in the muscles supplied by the cranial nerves—a group of twelve nerves that control 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. 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 forward movement of intestinal contents). [2] Some of the toxins (B and E) also precipitate nausea, vomiting, [2] and 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). [2]

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 respiratory compromise and death if untreated. [2]

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"). [3]

Infant botulism

An infant with botulism. Despite not being asleep or sedated, he cannot open his eyes or move; he also has a weak cry. Infant botulism patient.jpeg
An infant with botulism. Despite not being asleep or sedated, he cannot open his eyes or move; he also has a weak cry.

Infant botulism (also referred to as floppy baby syndrome) was first recognized in 1976, and is the most common form of botulism in the United States. 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. [4] 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 and levels of bile acids (which normally inhibit clostridial growth) are lower than later in life. [5]

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. [6]

Honey is a known dietary reservoir of C. botulinum spores and has been linked to infant botulism. For this reason, honey is not recommended for infants less than one year of age. [5] Most cases of infant botulism, however, are thought to be caused by acquiring 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. [7]

Infant botulism has been reported in 49 of 50 US states (all save for Rhode Island), [4] and cases have been recognized in 26 countries on five continents. [8]

Complications

Infant botulism has no long-term side effects.[ citation needed ]

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 7% due to improved supportive care. A patient with severe botulism may require mechanical ventilation (breathing support through a ventilator) as well as intensive medical and nursing care, sometimes for several months. The person may require rehabilitation therapy after leaving the hospital. [9]

Cause

A photomicrograph of Clostridium botulinum bacteria. Clostridium botulinum.jpg
A photomicrograph of Clostridium botulinum bacteria.

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. [10] 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. [11] 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.[ citation needed ]

In all cases, illness is caused by the botulinum toxin which the bacterium C. botulinum produces in anaerobic conditions and not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that fire (depolarize) at a higher frequency first. [12]

Mechanisms of entry into the human body for botulinum toxin are described below.[ citation needed ]

Colonization of the gut

The most common form in Western countries is infant botulism. This occurs in infants who are colonized with the bacterium in the small intestine during the early stages of their lives. The bacterium then produces the toxin, 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. [2] The adult form of infant botulism is termed adult intestinal toxemia, and is exceedingly rare. [2]

Food

Toxin that is produced by the bacterium in containers of food that have been improperly preserved is the most common cause of food-borne botulism. Fish that has been pickled without the salinity or acidity of brine that contains acetic acid and high sodium levels, as well as smoked fish stored at too high a temperature, presents a risk, as does improperly canned food.[ citation needed ]

Food-borne botulism results from contaminated food in which C. botulinum spores have been allowed to germinate in low-oxygen conditions. This typically occurs in improperly prepared home-canned food substances and fermented dishes without adequate salt or acidity. [13] 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. [14]

No withdrawal periods have been established for cows affected by Botulism. Lactating cows injected with various doses of Botulinum toxin C have not resulted in detectable Botulinum neurotoxin in milk produced. [15] Using mouse bioassays and immunostick ELISA tests, botulinum toxin was detected in whole blood and serum but not in milk samples, suggesting that botulinum type C toxin does not enter milk in detectable concentrations. [16] Cooking and pasteurization denatures botulinum toxin but does not necessarily eliminate spores. Botulinum spores or toxins can find their way into the dairy production chain from the environment. [17] Despite the low risk of milk and meat contamination, the protocol for fatal bovine botulism cases appears to be incineration of carcasses and withholding any potentially contaminated milk from human consumption. It is also advised that raw milk from affected cows should not be consumed by humans or fed to calves. [18]

Wound

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. [2] Wound botulism accounts for 29% of cases.[ citation needed ]

Inhalation

Isolated cases of botulism have been described after inhalation by laboratory workers. [19]

Injection

Symptoms of botulism may occur away from the injection site of botulinum toxin. [20] This may include loss of strength, blurred vision, change of voice, or trouble breathing which can result in death. [20] Onset can be hours to weeks after an injection. [20] This generally only occurs with inappropriate strengths of botulinum toxin for cosmetic use or due to the larger doses used to treat movement disorders. [2] Following a 2008 review the FDA added these concerns as a boxed warning. [21]

Mechanism

The toxin is the protein botulinum toxin produced under anaerobic conditions (where there is no oxygen) [22] by the bacterium Clostridium botulinum . [23]

Clostridium botulinum is a large anaerobic Gram-positive bacillus that forms subterminal endospores. [24]

There are eight serological varieties of the bacterium denoted by the letters A to H. The toxin from all of these acts in the same way and produces similar symptoms: the motor nerve endings are prevented from releasing acetylcholine, causing flaccid paralysis and symptoms of blurred vision, ptosis, nausea, vomiting, diarrhea or constipation, cramps, and respiratory difficulty.[ citation needed ]

Botulinum toxin is broken into eight neurotoxins (labeled as types A, B, C [C1, C2], D, E, F, and G), which are antigenically and serologically distinct but structurally similar. Human botulism is caused mainly by types A, B, E, and (rarely) F. Types C and D cause toxicity only in other animals. [25]

In October 2013, scientists released news of the discovery of type H, the first new botulism neurotoxin found in forty years. However, further studies showed type H to be a chimeric toxin composed of parts of types F and A (FA). [26]

Some types produce a characteristic putrefactive smell and digest meat (types A and some of B and F); these are said to be proteolytic; type E and some types of B, C, D and F are nonproteolytic and can go undetected because there is no strong odor associated with them. [24]

When the bacteria are under stress, they develop spores, which are inert. Their natural habitats are in the soil, in the silt that comprises the bottom sediment of streams, lakes, and coastal waters and ocean, while some types are natural inhabitants of the intestinal tracts of mammals (e.g., horses, cattle, humans), and are present in their excreta. The spores can survive in their inert form for many years. [27]

Toxin is produced by the bacteria when environmental conditions are favourable for the spores to replicate and grow, but the gene that encodes for the toxin protein is actually carried by a virus or phage that infects the bacteria. Little is known about the natural factors that control phage infection and replication within the bacteria. [28]

The spores require warm temperatures, a protein source, an anaerobic environment, and moisture in order to become active and produce toxin. In the wild, decomposing vegetation and invertebrates combined with warm temperatures can provide ideal conditions for the botulism bacteria to activate and produce toxin that may affect feeding birds and other animals. Spores are not killed by boiling, but botulism is uncommon because special, rarely obtained conditions are necessary for botulinum toxin production from C. botulinum spores, including an anaerobic, low-salt, low-acid, low-sugar environment at ambient temperatures. [29]

Botulinum inhibits the release within the nervous system of acetylcholine, a neurotransmitter, responsible for communication between motor neurons and muscle cells. All forms of botulism lead to paralysis that typically starts with the muscles of the face and then spreads towards the limbs. [2] In severe forms, botulism 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 identify the source and take steps to prevent further cases from occurring. [2]

Botulinum toxin A, C, and E cleave the SNAP-25, ultimately leading to paralysis.[ citation needed ]

Diagnosis

For botulism in babies, diagnosis should be made on signs and symptoms. Confirmation of the diagnosis is made by testing of a stool or enema specimen with the mouse bioassay.

In people whose history and physical examination suggest botulism, 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. [30]

Prevention

Although the vegetative form of the bacteria is destroyed by boiling, [31] [32] 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. [33] [34] [35]

A recommended prevention measure for infant botulism is to avoid giving honey to infants less than 12 months of age, as botulinum spores are often present. In older children and adults the normal intestinal bacteria suppress development of C. botulinum. [36]

While commercially canned goods are required to undergo a "botulinum cook" in a pressure cooker at 121 °C (250 °F) for 3 minutes,[ citation needed ] and thus rarely cause botulism, there have been notable exceptions. Two were the 1978 Alaskan salmon outbreak and the 2007 Castleberry's Food Company outbreak. Foodborne botulism is the rarest form, accounting for only around 15% of cases (US) [37] and has more frequently resulted 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. [38]

Other, much rarer sources of infection (about every decade in the US [37] ) include garlic or herbs [39] stored covered in oil without acidification, [40] chili peppers, [37] improperly handled baked potatoes wrapped in aluminum foil, [37] tomatoes, [37] and home-canned or fermented fish.

When canning or preserving food at home, attention should be paid to hygiene, pressure, temperature, refrigeration and storage. When making home preserves, only acidic fruit such as apples, pears, stone fruits and berries should be used. Tropical fruit and tomatoes are low in acidity and must have some acidity added before they are canned. [41]

Low-acid foods have pH values higher than 4.6. They include red meats, seafood, poultry, milk, and all fresh vegetables except for most tomatoes. Most mixtures of low-acid and acid foods also have pH values above 4.6 unless their recipes include enough lemon juice, citric acid, or vinegar to make them acidic. Acid foods have a pH of 4.6 or lower. They include fruits, pickles, sauerkraut, jams, jellies, marmalades, and fruit butters. [42]

Although tomatoes usually are considered an acid food, some are now known to have pH values slightly above 4.6. Figs also have pH values slightly above 4.6. Therefore, if they are to be canned as acid foods, these products must be acidified to a pH of 4.6 or lower with lemon juice or citric acid. Properly acidified tomatoes and figs are acid foods and can be safely processed in a boiling-water canner. [42]

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. [43] Metal cans containing food in which bacteria are growing may bulge outwards due to gas production from bacterial growth or the food inside may be foamy or have a bad odor; cans with any of these signs should be discarded. [44] [45]

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 be discarded. Contamination of a canned food solely with C. botulinum may not cause any visual defects to the container, such as bulging. Only assurance of sufficient thermal processing during production, and absence of a route for subsequent contamination, should be used as indicators of food safety.

The addition of nitrites and nitrates to processed meats such as ham, bacon, and sausages reduces growth and toxin production of C. botulinum. [46] [47]

Vaccine

Vaccines are under development, but they have disadvantages. [48] [ clarification needed ] As of 2017 work to develop a better vaccine was being carried out, but the US FDA had not approved any vaccine against botulism. [49] [50]

Treatment

Botulism is generally treated with botulism antitoxin and supportive care. [48]

Supportive care for botulism includes monitoring of respiratory function. Respiratory failure due to paralysis may require mechanical ventilation for 2 to 8 weeks, plus intensive medical and nursing care. After this time, paralysis generally improves as new neuromuscular connections are formed. [51]

In some abdominal cases, physicians may try to remove contaminated food still in the digestive tract by inducing vomiting or using enemas. Wounds should be treated, usually surgically, to remove the source of the toxin-producing bacteria. [52]

Antitoxin

Botulinum antitoxin consists of antibodies that neutralize botulinum toxin in the circulatory system by passive immunization. [53] This prevents additional toxin from binding to the neuromuscular junction, but does not reverse any already inflicted paralysis. [53]

In adults, a trivalent antitoxin containing antibodies raised against botulinum toxin types A, B, and E is used most commonly; however, a heptavalent botulism antitoxin has also been developed and was approved by the U.S. FDA in 2013. [11] [54] In infants, horse-derived antitoxin is sometimes avoided for fear of infants developing serum sickness or lasting hypersensitivity to horse-derived proteins. [55] To avoid this, a human-derived antitoxin has been developed and approved by the U.S. FDA in 2003 for the treatment of infant botulism. [56] This human-derived antitoxin has been shown to be both safe and effective for the treatment of infant botulism. [56] [57] However, the danger of equine-derived antitoxin to infants has not been clearly established, and one study showed the equine-derived antitoxin to be both safe and effective for the treatment of infant botulism. [55]

Trivalent (A,B,E) botulinum antitoxin is derived from equine sources utilizing whole antibodies (Fab and Fc portions). In the United States, this antitoxin is available from the local health department via the CDC. The second antitoxin, heptavalent (A,B,C,D,E,F,G) botulinum antitoxin, is derived from "despeciated" equine IgG antibodies which have had the Fc portion cleaved off leaving the F(ab')2 portions. This less immunogenic antitoxin is effective against all known strains of botulism where not contraindicated. [58]

Prognosis

The paralysis caused by botulism can persist for two to eight weeks, during which supportive care and ventilation may be necessary to keep the patient alive. [51] Botulism can be fatal in five to ten percent of people who are affected. [48] However, if left untreated, botulism is fatal in 40 to 50 percent of cases. [57]

Infant botulism typically has no long-term side effects but can be complicated by treatment-associated adverse events. The case fatality rate is less than two percent for hospitalized babies. [59]

Epidemiology

Globally, botulism is fairly rare, [48] with approximately 1,000 identified cases yearly. [60]

United States

In the United States an average of 145 cases are reported each year. Of these, roughly 65% are infant botulism, 20% are wound botulism, and 15% are foodborne. [61] Infant botulism is predominantly sporadic and not associated with epidemics, but great geographic variability exists. From 1974 to 1996, for example, 47% of all infant botulism cases reported in the U.S. occurred in California. [61]

Between 1990 and 2000, the Centers for Disease Control and Prevention reported 263 individual foodborne cases from 160 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 events (~69%) with canned asparagus being the most frequent cause. Two restaurant-associated outbreaks affected 25 people. 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. [62]

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. [63]

All data regarding botulism antitoxin releases and laboratory confirmation of cases in the US are recorded annually by the Centers for Disease Control and Prevention and published on their website. [61]

United Kingdom

The largest recorded outbreak of foodborne botulism in the United Kingdom occurred in June 1989. A total of 27 patients were affected; one patient died. Twenty-five of the patients had eaten one brand of hazelnut yogurt in the week before the onset of symptoms. Control measures included the cessation of all yogurt production by the implicated producer, the withdrawal of the firm's yogurts from sale, the recall of cans of the hazelnut conserve, and advice to the general public to avoid the consumption of all hazelnut yogurts. [70]

China

From 1958 to 1983 there were 986 outbreaks of botulism in China involving 4,377 people with 548 deaths. [71]

Qapqal disease

After the Chinese Communist Revolution in 1949, a mysterious plague (named Qapqal disease) was noticed to be affecting several Sibe villages in Qapqal Xibe Autonomous County. It was endemic with distinctive epidemic patterns, yet the underlying cause remained unknown for a long period of time. [72] It caused a number of deaths and forced some people to leave the place. [73]

In 1958, a team of experts were sent to the area by the Ministry of Health to investigate the cases. The epidemic survey conducted proved that the disease was primarily type A botulism, [74] with several cases of type B. [72] The team also discovered that the source of the botulinum was local fermented grain and beans, as well as a raw meat food called mi song hu hu. [73] They promoted the improvement of fermentation techniques among local residents, and thus eliminated the disease.

Canada

From 1985 to 2005 there were outbreaks causing 91 confirmed cases of foodborne botulism in Canada, 85% of which were in Inuit communities, especially Nunavik, as well as First Nations of the coast of British Columbia, following consumption of traditionally prepared marine mammal and fish products. [75]

Ukraine

In 2017, there were 70 cases of botulism with 8 deaths in Ukraine. The previous year there were 115 cases with 12 deaths. Most cases were the result of dried fish, a common local drinking snack. [76]

Vietnam

In 2020, several cases of botulism were reported in Vietnam. All of them were related to a product containing contaminated vegetarian pâté. Some patients were put on life support. [77] [78]

Other susceptible species

Botulism can occur in many vertebrates and invertebrates. Botulism has been reported in such species as rats, mice, chicken, frogs, toads, goldfish, aplysia, squid, crayfish, drosophila and leeches. [79]

Death from botulism is common in waterfowl; an estimated 10,000 to 100,000 birds die of botulism annually. The disease is commonly called "limberneck". In some large outbreaks, a million or more birds may die. Ducks appear to be affected most often. An enzootic form of duck botulism in the Western US and Canada is known as "western duck sickness". [80] Botulism also affects commercially raised poultry. In chickens, the mortality rate varies from a few birds to 40% of the flock.

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.

In cattle, the symptoms may include drooling, restlessness, incoordination, 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 develop 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.

Clostridium botulinum type C toxin has been incriminated as the cause of grass sickness, a condition in horses which occurs in rainy and hot summers in Northern Europe. The main symptom is pharynx paralysis. [81]

Domestic dogs may develop systemic toxemia after consuming C. botulinum type C exotoxin or spores within bird carcasses or other infected meat [82] but are generally resistant to the more severe effects of C. botulinum type C. Symptoms include flaccid muscle paralysis, which can lead to death due to cardiac and respiratory arrest. [83]

Pigs are relatively resistant to botulism. Reported symptoms include anorexia, refusal to drink, vomiting, pupillary dilation, and muscle paralysis. [84]

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.

Prevention in non-human species

One of the main routes of exposure for botulism is through the consumption of food contaminated with C. botulinum. Food-borne botulism can be prevented in domestic animals through careful inspection of the feed, purchasing high quality feed from reliable sources, and ensuring proper storage. Poultry litter and animal carcasses are places in which C. botulinum spores are able to germinate so it is advised to avoid spreading poultry litter or any carcass containing materials on fields producing feed materials due to their potential for supporting C. botulinum growth. [85] Additionally, water sources should be checked for dead or dying animals, and fields should be checked for animal remains prior to mowing for hay or silage. Correcting any dietary deficiencies can also prevent animals from consuming contaminated materials such as bones or carcasses. [86] Raw materials used for silage or feed mixed on site should be checked for any sign of mold or rotten appearance. Acidification of animal feed can reduce, but will not eliminate, the risk of toxin formation, especially in carcasses that remain whole. [87]

Vaccines in animals

Vaccines have been developed for use in animals to prevent botulism. The availability and approval of these vaccines varies depending on the location, with places experiencing more cases generally having more vaccines available and routine vaccination is more common. [87]

A variety of vaccines have been developed for the prevention of botulism in livestock. Most initial vaccinations require multiple doses at intervals from 2–6 weeks, however, some newer vaccines require only one shot. This mainly depends on the type of vaccine and manufacturers recommendations. All vaccines require annual boosters to maintain immunity. Many of these vaccines can be used on multiple species including cattle, sheep, and goats with some labeled for use in horses and mules as well as separate vaccines for mink. Additionally, vaccination during an outbreak is as beneficial as therapeutic treatment in cattle, and this method is also used in horses and pheasants. [87]

The use of region specific toxoids to immunize animals has been shown to be effective. Toxoid types C and D used to immunize cattle is a useful vaccination method in South Africa and Australia. Toxoid has also been shown to be an appropriate method of immunizing minks and pheasants. In endemic areas, for example Kentucky, vaccination with type B toxoid appears to be effective. [86]

Use in biological warfare and terrorism

United States

Based on CIA research in Fort Detrick on biological warfare, anthrax and botulism were widely regarded as the two most effective options. [88] During the 1950s, a highly lethal strain was discovered during the biological warfare program. [88] The CIA continued to hold 5 grams of Clostridium botulinum , even after Nixon's ban on biological warfare in 1969. [88] During the Gulf War, when the United States were concerned with a potential biowarfare attack, the efforts around botulism turned to prevention. [88] However, the only way to make antitoxin in America until the 1990s was by drawing antibodies from a single horse named First Flight, raising much concern from Pentagon health officials. [88] [89]

Iraq

Iraq has historically possessed many types of germs, including botulism. [88] The American Type Culture Collection sold 5 variants of botulinum to the University of Baghdad in May 1986. [88] 1991 CIA reports also show Iraqis filled shells, warheads, and bombs with biological agents like botulinum (though none have been deployed). [88] The Iraqi air force used the code name "tea" to refer to botulinum, and it was also referred to as bioweapon "A." [88]

Japan

A Japanese cult called Aum Shinrikyo created laboratories that produced biological weapons, specifically botulinum, anthrax, and Q fever. [88] From 1990 to 1995, the cult staged numerous unsuccessful bioterrorism attacks on civilians. [88] They sprayed botulinum toxin from a truck in downtown Tokyo and in the Narita airport, but there are no reported cases of botulism as a result. [88]

See also

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Clostridium botulinum is a gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce botulinum toxin, which is a neurotoxin.

<span class="mw-page-title-main">Tetanus</span> Bacterial infection characterized by muscle spasms

Tetanus, also known as lockjaw, is a bacterial infection caused by Clostridium tetani and characterized by muscle spasms. In the most common type, the spasms begin in the jaw, and then progress to the rest of the body. Each spasm usually lasts for a few minutes. Spasms occur frequently for three to four weeks. Some spasms may be severe enough to fracture bones. Other symptoms of tetanus may include fever, sweating, headache, trouble swallowing, high blood pressure, and a fast heart rate. Onset of symptoms is typically 3 to 21 days following infection. Recovery may take months; about 10% of cases prove to be fatal.

<span class="mw-page-title-main">Diphtheria</span> Bacterial disease

Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks, the mortality rate approaches 10%. Signs and symptoms may vary from mild to severe, and usually start two to five days after exposure. Symptoms often develop gradually, beginning with a sore throat and fever. In severe cases, a grey or white patch develops in the throat, which can block the airway, and create a barking cough similar to what is observed in croup. The neck may also swell, in part due to the enlargement of the facial lymph nodes. Diphtheria can also involve the skin, eyes, or genitals, and can cause complications, including myocarditis, inflammation of nerves, kidney problems, and bleeding problems due to low levels of platelets.

<i>Clostridioides difficile</i> infection Disease caused by C. difficile bacteria

Clostridioides difficile infection , also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.

<i>Clostridium perfringens</i> Species of bacterium

Clostridium perfringens is a Gram-positive, bacillus (rod-shaped), anaerobic, spore-forming pathogenic bacterium of the genus Clostridium. C. perfringens is ever-present in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates, insects, and soil. It has the shortest reported generation time of any organism at 6.3 minutes in thioglycolate medium.

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.

<span class="mw-page-title-main">Foodborne illness</span> Illness from eating spoiled food

Foodborne illness is any illness resulting from the contamination of food by pathogenic bacteria, viruses, or parasites, as well as prions, and toxins such as aflatoxins in peanuts, poisonous mushrooms, and various species of beans that have not been boiled for at least 10 minutes.

Exogenous bacteria are microorganisms introduced to closed biological systems from the external world. They exist in aquatic and terrestrial environments, as well as the atmosphere. Microorganisms in the external environment have existed on Earth for 3.5 billion years. Exogenous bacteria can be either benign or pathogenic. Pathogenic exogenous bacteria can enter a closed biological system and cause disease such as Cholera, which is induced by a waterborne microbe that infects the human intestine. Exogenous bacteria can be introduced into a closed ecosystem as well, and have mutualistic benefits for both the microbe and the host. A prominent example of this concept is bacterial flora, which consists of exogenous bacteria ingested and endogenously colonized during the early stages of life. Bacteria that are part of normal internal ecosystems, also known as bacterial flora, are called Endogenous Bacteria. A significant amount of prominent diseases are induced by exogenous bacteria such as gonorrhea, meningitis, tetanus, and syphilis. Pathogenic exogenous bacteria can enter a host via cutaneous transmission, inhalation, and consumption.

In immunology, passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.

Flaccid paralysis is a neurological condition characterized by weakness or paralysis and reduced muscle tone without other obvious cause. This abnormal condition may be caused by disease or by trauma affecting the nerves associated with the involved muscles. For example, if the somatic nerves to a skeletal muscle are severed, then the muscle will exhibit flaccid paralysis. When muscles enter this state, they become limp and cannot contract. This condition can become fatal if it affects the respiratory muscles, posing the threat of suffocation. It also occurs in the spinal shock stage in complete transection of the spinal cord occurring in injuries such as gunshot wounds.

<i>Clostridium tetani</i> Common soil bacterium and the causative agent of tetanus

Clostridium tetani is a common soil bacterium and the causative agent of tetanus. Vegetative cells of Clostridium tetani are usually rod-shaped and up to 2.5 μm long, but they become enlarged and tennis racket- or drumstick-shaped when forming spores. C. tetani spores are extremely hardy and can be found globally in soil or in the gastrointestinal tract of animals. If inoculated into a wound, C. tetani can grow and produce a potent toxin, tetanospasmin, which interferes with motor neurons, causing tetanus. The toxin's action can be prevented with tetanus toxoid vaccines, which are often administered to children worldwide.

<span class="mw-page-title-main">Castleberry's Food Company</span>

Castleberry's Food Company is 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 in March 2008 by the United States Food and Drug Administration until Hanover Foods bought the rights to Castleberry's food and name.

Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

Clostridium baratii is an anaerobic, motile, gram-positive bacterium. It is a rare cause of infant botulism, in which newborns or infants lose their muscle tone, and develop trouble feeding due to a difficulty in breathing, which can be fatal. Newborns can recover spontaneously or as in two known cases improve with injected botulism antitoxin. As of 2015, the environmental source of this bacterium is unknown, despite extensive investigations when cases have occurred. It is named after Barat who is a French bacteriologist.

The Botulism Antitoxin Heptavalent - (Equine), made by Emergent BioSolutions Canada Inc. – is a licensed, commercially available botulism anti-toxin that effectively neutralizes all seven known botulinum nerve toxin serotypes. It is indicated for sporadic cases of life-threatening botulism and is also stockpiled for the eventuality of botulinum nerve toxins being used in a future bioterrorist attack.

Avian Botulism is a strain of botulism that affects wild and captive bird populations, most notably waterfowl. This is a paralytic disease brought on by the Botulinum neurotoxin (BoNt) of the bacterium Clostridium botulinum. C. botulinum can fall into one of 7 different types which are strains A through G. Type C BoNt is most frequently associated with waterfowl mortality. The Type E strain is also commonly associated with avian outbreaks and is frequently found in fish species which is why most outbreaks occur in piscivorous birds.

<i>Clostridioides difficile</i> Species of bacteria

Clostridioides difficile is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.

First Flight was a thoroughbred horse used in the production of the first botulism antitoxin. The horse was used as a research animal between 1978 and 1993 to produce antitoxin for military and civilian personnel. Until the 1990s, serum derived from First Flight was the only source of the antitoxin in the United States.

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