botulism.pdf

Botulism Importance Botulism is caused by botulinum toxins, neurotoxins produced by Clostridium botulinum and a few other clostridial species. By binding to nerve endings, these toxins Shaker Foal Synd...

Botulism Importance Botulism is caused by botulinum toxins, neurotoxins produced by Clostridium botulinum and a few other clostridial species. By binding to nerve endings, these toxins Shaker Foal Syndrome, cause progressive flaccid paralysis in humans and animals. Many untreated cases end Limberneck, in death from paralysis of the respiratory muscles. C. botulinum spores are common in Western Duck Sickness, the environment, but they can germinate and grow only under certain anaerobic Bulbar Paralysis, conditions. Foodborne botulism results from the ingestion of preformed toxins after the Loin Disease, organism has grown in food or other organic matter. Foodborne outbreaks may be Lamziekte extensive in some animals, especially farmed mink or foxes and wild waterfowl. Losses that may threaten survival of the species have been reported in endangered wild birds. Sporadic cases of botulism also occur when botulinum-producing organisms grow inside the body, particularly in the immature gastrointestinal tracts of human infants Last Updated: January 2018 and foals, or in anaerobic wounds. Botulism can be treated successfully, but human or animal patients may require weeks or months of intensive care, sometimes including mechanical ventilation, while the nerve endings regenerate. Treatment may be impractical in adult livestock unless the case is mild. The potential for botulinum toxins to be used in bioterrorism is an additional concern. Etiology Botulism is caused by botulinum toxin, a potent neurotoxin produced by Clostridium botulinum, a few strains of C. baratii and C. butyricum, and C. argentinense. All of these organisms are anaerobic, Gram-positive, spore-forming rods. C. botulinum is currently divided into three genotypically and phenotypically distinct groups, I through III. Groups I and II, which are the usual causes of botulism in humans, differ in heat resistance, optimal growth temperatures and other characteristics that can influence the types of foods where they tend to grow. The former group IV C. botulinum has been reclassified as C. argentinense. Seven types of botulinum toxins, A through G, and a few mosaics of these toxins are currently recognized. Mosaic toxins include C-D and D-C, detected during outbreaks in birds and ruminants, respectively, and an A-F toxin from a human infant, which was initially reported as a novel "type H." All toxin types cause the same clinical signs, but some tend to result in more severe illnesses. Knowing the toxin type is important in treatment, as the antiserum produced against one type is not protective against others. An apparently novel toxin (“type X”) was described in 2017 and caused clinical signs in experimentally intoxicated mice. It is still uncertain whether this toxin is ever expressed in nature. Some C. botulinum strains produce additional types of toxins, including enterotoxins that can cause gastrointestinal signs. Most of the clostridia that cause botulism produce one type of botulinum toxin, although they may contain genes for others. Human illnesses can be caused by group I or group II C. botulinum, which may produce toxins A, B, E or F; C. butyricum, which also produces type E toxin; and C. baratii, which produces type F. Toxin types A, B and E are found most often in people, while type F is uncommon. Type G toxin has been implicated very rarely in human disease. Illnesses that appeared to be caused by this toxin included one case of wound botulism and several sudden deaths, some of which might have resulted from foodborne botulism. Group III organisms, which make toxin types C, D and their mosaics, are usually associated with botulism in animals. However, members of groups I/II can be more prominent in some animal species or locations. For instance, type B toxin causes most cases of botulism in horses in the midwestern and mid-Atlantic states of the U.S., while type A is usually responsible for equine cases in the western states. Rare reports of human botulism were attributed to type C and D toxins in the 1950s; however, the virulence of these types for people has since been questioned. Species Affected Botulism is known to affect mammals, birds, reptiles and fish, although some species seem to be more susceptible than others. This disease is reported regularly in horses, domesticated ruminants, ranched mink, poultry, wild birds in aquatic. www.cfsph.iastate.edu © 2003-2018 page 1 of 13  Botulism environments, and game birds (pheasants), and occasionally suggesting that this may be rare in some species or locations in other species such as ferrets, farmed foxes, captive except during outbreaks. wildlife (e.g., nonhuman primates, sea lions) and free-living Botulism is not transmitted between animals or people wild mammals. Cases also occur in dogs and pigs, but are by casual contact; however, it can be acquired by ingesting uncommon, while botulism has been reported very rarely in contaminated tissues. If an animal dies of botulism, any cats. Outbreaks have been seen in farmed rainbow trout spores in its intestinal tract (e.g., from contaminated food) (Oncorhynchus mykiss), and other species of fish were can germinate and grow. This may result in high levels of shown to be susceptible in experiments. Clinical cases have toxin in decomposing carcasses. Such carcasses can help also been documented in turtles. Amphibians are susceptible perpetuate and amplify outbreaks in poultry and mammals to experimental intoxication. through carnivory. Particularly high levels of toxin are reported to develop in dead tortoises. Invertebrates such as Zoonotic potential snails, earthworms, maggots, darkling beetles in poultry Botulism is usually acquired from the environment and houses, and nematodes are unaffected by botulinum toxin, not directly from animals. However, at least two recent cases but they can accumulate these toxins and cause botulism in of infant botulism caused by C. butyricum (type E toxin) animals that feed on them. were linked to healthy pet yellow-bellied terrapins (Trachemys scripta scripta) and/or their environments. Sources of botulism for humans Whether terrapins regularly carry this organism is not yet Foodborne botulism occurs when people ingest clear; some animals were probably infected in contaminated preformed toxins. C. botulinum spores can survive cooking, feed. then germinate and grow in the food if the conditions are appropriate. Some clinical cases have occurred when baked Geographic Distribution foods were left at room temperature or in a warm oven C. botulinum occurs worldwide, but the predominant overnight. Most often, botulism is associated with home- toxin types can differ between areas. Type E-producing C. canned, low acid foods; meat products such as sausages, pate botulinum strains tend to occur in northern regions, where and ham; and salted, pickled or fermented fish, seal and they are associated with coastal areas and other aquatic whale meat. However, it has also been caused by products as environments. In North America, type A strains predominate diverse as traditional long-fermented yogurt, soft cheeses, west of the Missouri River, while type B strains are more garlic oil and foil-wrapped baked potatoes. While the amount common to its east. C. argentinense has, to date, been of toxin in the tissues of freshly-dead animals is uncertain, reported from humans in Europe and North America, as well some clinical cases resulted from eating raw tissues from as from soil samples in South America. whale carcasses. Transmission Wound botulism occurs when botulinum-producing clostridia contaminate and grow in an anaerobic wound. It is Botulism usually occurs when people or animals ingest particularly common in injecting drug abusers, especially preformed botulinum toxins in food or water, or when those who inject “black tar” heroin into the subcutaneous clostridial spores germinate in anaerobic tissues within the tissues. body and produce toxins as they grow. Botulinum toxins do Infant botulism is seen in children less than a year of not pass through intact skin, but they can cross mucous age, when organisms germinate and grow in their intestines. membranes and broken skin. Infants are thought to be susceptible because the intestinal C. botulinum can grow in a wide variety of organic tract, particularly the normal flora, is still immature. Honey matter, but it requires anaerobic conditions, a relatively high has been associated with some cases, but spores can also be water content, pH > 4.6 (Group III type C toxin-producing found in many other sources including dust. Some babies strains are inhibited by pH < 5.1-5.4), and the absence of with infant botulism can shed C. botulinum for up to 7 inhibitory concentrations of salt or other preservatives. The months, long after they have recovered clinically. Spores optimal, minimal and maximal temperatures for growth from the environment can be ingested by most older differ between organisms. In particular, type E-producing C. children and adults without harm; they simply pass through botulinum are able to survive and grow at lower temperatures the intestines without germinating. However, there are rare than the strains that produce types A or B. C. botulinum does cases of intestinal colonization botulism in people who not compete well with other bacteria and fungi, and it have altered intestinal conditions from procedures and proliferates more readily if they have been killed or inhibited. diseases such as gastrointestinal surgery, intensive Clostridial spores are highly resistant to inactivation, antibiotic therapy or abnormalities such as achlorhydria. and they can survive for many years in the environment until Botulism can also occur after laboratory accidents (e.g., favorable conditions allow them to germinate and grow. C. by inhalation or accidental injection of toxin), and rare botulinum spores are common in soils, and they also occur in iatrogenic cases have been reported after therapeutic or sediments in lakes, streams and coastal waters. Spores have cosmetic use. In a bioterrorist attack, botulinum toxin could been found in the intestinal tracts of healthy mammals, be delivered by aerosols, or in food or water. Person-to- poultry, wild birds and fish; however, there are reports person transmission of botulism has not been reported. www.cfsph.iastate.edu © 2003-2018 page 2 of 13  Botulism Botulism in animals Botulism in Animals Some sources of preformed toxins for animals include decaying vegetable matter (grass, hay, haylage, grain, Incubation Period spoiled silage) or high protein garbage, animal tissues Reported incubation periods in animals range from 2 (including fish), invertebrates (e.g., maggots that have fed hours to approximately 2 weeks. In many foodborne cases, on carcasses) and contaminated water. Feed for herbivores the clinical signs appear about 12 to 48 hours after ingesting is often thought to have been contaminated by the carcass botulinum toxin. of a bird or small mammal. Ruminants have developed botulism after eating contaminated poultry litter that was Clinical Signs used as bedding or feed or spread on nearby fields. Cattle Botulism is characterized by progressive motor in phosphorus-deficient areas may develop pica and chew paralysis. In animals, it usually appears as an ascending bones and scraps of attached meat; a gram of dried flesh paralysis that affects the hind legs first. Autonomic may contain enough botulinum toxin to kill a cow. Similar dysfunction, difficulties in chewing and swallowing, visual cases have been reported from Australia when protein- disturbances, and generalized weakness and incoordination deficient sheep ate the carcasses of small animals. may also be apparent. Loss of muscle tone around the eyes Botulism in young foals (the shaker foal syndrome) is and mouth may result in an appearance of lethargy or mostly thought to be caused by the growth of C. botulinum in somnolence, with drooping of the eyelids, dilation of the the gastrointestinal tract, similarly to infant botulism in pupils and slow pupillary reflexes. Sensory defects are humans, although wound botulism has been implicated in a absent. Death usually results from paralysis of the respiratory few cases. Toxicoinfectious botulism is also suspected to occur muscles. Mildly affected animals may recover with minimal in the intestinal tracts of chickens (e.g., broilers intensively treatment. reared on litter) and possibly other species such as cattle. Ruminants Whether toxin can be shed in the milk of animals Ascending muscle weakness and incoordination, suffering from botulism is uncertain; however, one paper progressing to paralysis, is the most apparent sign in cattle. reports having found it in milk samples from some cattle, The head may be held abnormally low. Other clinical signs and experimentally infected, axenic (germ-free) rats with may include difficulty chewing and swallowing, excessive toxicoinfectious botulism shed it in milk. C. botulinum has salivation, protrusion of the tongue, constipation and urine been detected on eggshells during outbreaks in poultry, but retention. The tongue test, which evaluates an animal’s it was not found in the egg contents. In one instance, ability to resist or retract the tongue when it is pulled laterally contamination was detected on eggs laid 5 months after an from the mouth, often reveals compromised function. In outbreak. cattle that become recumbent, the head is often turned toward Disinfection/Inactivation the flank, similarly to a cow with hypocalcemia. Complications such as aspiration pneumonia and pressure Botulinum toxins are large, easily denatured proteins, and sores are common in cattle that are impaired by botulism for toxins exposed to sunlight are inactivated within a few hours. a prolonged period. Laterally recumbent animals are usually They can also be destroyed by treating with 0.1% sodium very close to death. Some animals may be found dead hypochlorite or 0.1 N NaOH, or by heating to 80°C (176°F) without preceding clinical signs. Atypical presentations with for 20 minutes or > 85°C (185°F) for at least 5 minutes. Their gastrointestinal signs (diarrhea, regurgitation, vomiting and heat resistance varies with composition of the food or other profuse salivation) have been reported in a few outbreaks. medium, and the concentration of the toxin. Reports suggest that HTST pasteurization (72°C/162°F for 15 seconds) is The clinical signs are similar in small ruminants, but the likely to inactivate most or all of the toxin in contaminated effects on mastication and swallowing are reported to be less milk, while conventional pasteurization at 63°C/145°F for 30 apparent. An arched back, accompanied by drooping of the minutes seems to be less effective. Chlorine and other agents head, neck and tail, is a common presentation in these can destroy botulinum toxins in water. species, and an unusual stilted gait has been reported during the early stages of botulism in sheep. The vegetative cells of C. botulinum are susceptible to many disinfectants, including 1% sodium hypochlorite and Visceral botulism 70% ethanol, but clostridial spores are very resistant to Some authors have proposed that toxicoinfectious inactivation. They can be destroyed in the autoclave with botulism and/or chronic exposure to botulinum toxins causes moist heat (120°C/ 250°F for at least 15 minutes) or dry heat a syndrome called “visceral botulism” in cattle. Clinical (160°C for 2 hours) or by irradiation. The spores of group I signs reported in affected herds have included lethargy, strains are inactivated by heating at 121°C (250°F) for 3 decreased milk production, constipation alternating with minutes during commercial canning. Spores of group II strains diarrhea, dependent edema, non-infectious chronic laminitis, are less heat-resistant, and they are often damaged by 90°C ataxia, paralysis, engorged veins, forced respiration, a (194°F) for 10 minutes, 85°C for 52 minutes, or 80°C for 270 retracted abdomen, emaciation and unexpected deaths. A minutes; however, these treatments may not be sufficient in more recent report described a herd with locomotor some foods. abnormalities, swollen joints, regurgitation, viscous saliva, a www.cfsph.iastate.edu © 2003-2018 page 3 of 13  Botulism drooping head and tail, suppuration of skin wounds, poor breeding gave birth to an apparently healthy litter, despite suckling in calves and death after a few weeks. Most cases being hospitalized for 5 days during the illness and having are reported to occur during the peripartum period. Whether some residual defects for < 1 month. visceral botulism is a real syndrome is controversial. A In the single outbreak described in cats, anorexia and mild recent case-control study could not substantiate a link to depression were the first signs, followed by ascending flaccid botulism on some farms with visceral botulism signs. paralysis, and in some cases, dyspnea. Some severely affected Horses cats died, others recovered spontaneously and rapidly. The signs of intoxication by botulinum toxin in adult Marine mammals horses resemble those in ruminants. Inactivity and dysphagia, followed in some cases by Toxicoinfectious botulism in foals (the shaker foal unexpected deaths, were reported in sea lions. Although syndrome) is typically characterized by weakness, a stilted some animals appeared to be hungry, chewing fish and gait, muscle tremors and dysphagia. Affected foals are often attempting to swallow, they eventually released the partially unable to stand for more than a few minutes. Constipation, chewed fish from their mouths. reduced eyelid, tongue and tail tone, mydriasis, frequent Birds urination and other signs of motor or autonomic dysfunction may also be seen. Without treatment, death from respiratory Reluctance to move and dullness may be the initial signs paralysis generally occurs 24 to 72 hours after the initial observed in poultry. Botulism usually affects the legs of signs. Some foals may be found dead. poultry and waterfowl first, followed by the wings and neck. Milder cases may be limited to paresis or paralysis of the Equine grass sickness legs. In gulls, the toxin’s effects on the wing muscles may be Equine grass sickness is a neurodegenerative disease observed initially, with delayed or uncoordinated flight. seen in grazing equids. This disease, which is often fatal, has Mildly affected gulls are able to stand and run, but not fly. both acute and chronic presentations. It is characterized by Birds with botulism may have diarrhea with excess urates, as dysfunction of the autonomic nervous system, and signs of well as additional neurological signs such as paralysis of the intestinal dysmotility are prominent. Weight loss and nictitating membrane. The feathers of chickens may be progressive myasthenia are common in chronic cases. ruffled, and they may be shed easily when the birds are Equine grass sickness tends to be seen in young adult horses handled. Birds may die from respiratory dysfunction, and and is most common in the spring. Its cause is still uncertain. waterfowl with paralyzed necks may drown. Egg production There is some evidence for a link to type III C. botulinum; and quality do not seem to be significantly decreased in layer however, it is possible that this is a coincidence or that chickens with botulism. intestinal dysfunction predisposes these animals to the growth of clostridia in the intestinal tract. Reptiles Loss of equilibrium and flaccid paralysis of the legs, Pigs followed by drowning, have been reported in green sea Pigs are relatively resistant to botulism. Reported turtles (Chelonia mydas). clinical signs include anorexia, refusal to drink, vomiting, pupillary dilation and muscle paralysis. Fish Loss of equilibrium and erratic swimming have been Foxes, mink and ferrets reported in fish with botulism. Some fish may attempt to Clinical signs in theses species resemble those in other swim in a head up/ tail down orientation, with breaching of animals. During outbreaks of botulism in mink, many the water surface. Increased swimming bursts were the first animals may be found dead, while others have various sign in experimentally exposed rainbow trout. degrees of flaccid paralysis and dyspnea. In some mildly Hyperpigmentation was also seen in some experimentally affected foxes, only the hind legs are paralyzed. These infected fish, including round goby (Neogobius animals may sit and drag the hind part of their bodies. melanostomas), yellow perch (Perca flavescens), and some Dogs and cats members of the carp family (Cyprinidae). Abnormal swimming behavior was not observed in these goby until the Limited studies in dogs suggest that this species is late stages of hyperpigmentation. Like other vertebrates, fish relatively insensitive to the ingestion of botulinum toxin. usually die from respiratory compromise. They are usually Reported clinical signs include vomiting and anterior immobile at this stage. A few fish with mild clinical signs abdominal pain, in addition to neurological signs (e.g., such as slight loss of equilibrium and increased swimming salivation, incoordination, ascending weakness of the legs, bursts may recover completely. inability to urinate, diminished reflexes). Congestion of the mucous membranes of the mouth, fetid brownish saliva, Post Mortem Lesions Click to view images cheilitis and an unusual hoarse, suppressed bark or whine There are no pathognomonic lesions in animals that die of were reported in some experimentally exposed dogs. Some botulism; any lesions are usually the result of muscle paralysis, dogs have recovered, but others died of respiratory failure. debilitation, the inability to eat and drink, or other secondary One pregnant bitch that contracted botulism soon after www.cfsph.iastate.edu © 2003-2018 page 4 of 13  Botulism effects. Congestion may be noted in a variety of tissues, and Serology is not usually helpful in diagnosis, but respiratory paralysis may cause nonspecific signs in the lungs. antibodies to botulinum toxin have been reported in some Some strains of C. botulinum also produce an enterotoxin that animals that recovered, including horses, cattle and a dog. In may cause diffuse intestinal hemorrhages. Edema of the head the dog, paired serum samples revealed a fourfold increase and neck, probably associated with lowered head carriage, is in titer. Repetitive nerve stimulation studies have been used reported to be a prominent but inconsistent finding in horses. to help diagnose botulism in foals. In shaker foal syndrome, the most consistent lesions are excess pericardial fluid with strands of fibrin, pulmonary edema and Treatment congestion. The binding of botulinum toxins to the endplates of neurons cannot be reversed; however, the endplates can Diagnostic Tests regenerate if the patient can be kept alive. Mechanical A definitive diagnosis can be made if botulinum toxin is ventilation has significantly reduced the death rate in foals, identified in environmental samples (e.g., feed), serum, but it is impractical and/or unavailable for some animals such gastrointestinal contents (stomach, crop or intestines), as adult livestock. Gastric lavage, emetics, cathartics and/or wounds, vomitus, feces or tissues such as the liver. Fecal enemas may be used to eliminate some of the toxin from the samples are more likely to be diagnostic than serum, which gastrointestinal tract, and activated charcoal or other usually contains this toxin only in the early stages of the substances may help prevent absorption. Where the water disease and is rarely positive in some livestock. Repeated supply has high salinity, giving fresh water to prairie fecal sampling may improve detection. Low levels of toxin wildfowl can improve their condition. The supraorbital gland can be difficult to detect, and a presumptive diagnosis in in these birds, which functions in osmoregulation, is highly sensitive species (e.g., cattle and horses) must innervated by nerves affected by the toxin. sometimes be based on the clinical signs and the exclusion Antitoxins can neutralize circulating botulinum toxins in of diseases with similar signs. birds and mammals, provided the antibodies match the toxin Botulinum toxin is usually identified with a mouse type. Decisions on antitoxin treatment must often be made bioassay (the mouse neutralization test), which can take up to before the results from typing are available. In some cases, an 4 days, but ELISAs and PCR assays may be available in some educated guess may be made, based on the most common laboratories. Because ELISAs detect both active and toxin types in that species and location. Antitoxins that inactivated toxins, false positives are possible with this test. neutralize more than one toxin type, including pentavalent PCR tests may, likewise, amplify some “silent” botulinum antitoxins (types A through E), are available in some countries. toxin genes. Only active toxins are detected in mice. Pre- Early administration of antitoxin, while the animal is still incubating samples under anaerobic conditions can improve standing, has been associated with improved survival in the sensitivity of both ELISAs and PCR. One recent study horses. If feasible, this should be considered before a horse is reported that storing samples at room temperature or 5°C referred for intensive care. Economic considerations may limit (41°F), rather than at -18°C (0°F), reduced the sensitivity of a the use of antitoxins in some species. However, treatment was C. botulinum PCR test, even when the samples were stored for reported to be cost effective in one group of birds due to their only 48 hours. Other types of assays are also in development, small size. Guanidine hydrochloride has also been used in with the goal of replacing the mouse bioassay. Some measure efforts to mitigate the neuromuscular blockade, especially in the toxin’s activity on synthetic peptides that mimic its targets. the past when antitoxins were less readily available. Botulinum toxins can be typed during the mouse Antibiotics are not needed in foodborne botulism, as the neutralization test or with genetic techniques. organisms are not growing in the body. They have sometimes Botulism can also be diagnosed by recovering toxin- been used in the treatment of poultry, with varying success. In producing clostridia from clinical samples and/or the foals, antibiotics are primarily used to prevent secondary suspected source of the intoxication. C. botulinum can be complications such as aspiration pneumonia. Whether they cultured on various solid and liquid media, including blood could have any role in eliminating the organism from the or egg yolk agar, but anaerobic conditions are required. Heat intestines of foals is unclear; the treatment of this condition is and/or ethanol treatment, which destroy competing mostly extrapolated from human infant botulism, where microorganisms but not clostridial spores, may aid recovery antibiotics are avoided. Drugs that have neuromuscular in highly contaminated samples such as food or feces. blocking properties, such as aminoglycosides, should be Biochemical tests, morphology and the detection of volatile avoided. metabolic products, using gas-liquid chromatography, are Some animals with mild disease can survive with helpful in identification. The metabolic patterns and other minimal treatment, or recover on their own. characteristics vary with the strain/ group. Definitive identification is by the demonstration of botulinum toxin. Control Molecular techniques such as multi-locus sequence typing Disease reporting (MLST) or variable number tandem repeat (VNTR) analysis can help determine the source of an outbreak. Veterinarians who encounter or suspect botulism should follow their national and/or local guidelines for disease www.cfsph.iastate.edu © 2003-2018 page 5 of 13  Botulism reporting. In the U.S., botulism appears on the reportable horses during outbreaks. However, the case fatality rate among disease lists for many, but not all, states. hospitalized horses was 50% at one referral hospital, with a high survival rate (95%) in animals that were able to stand Prevention throughout their stay. Nearly 80% of the horses in this study Feed for mink and other ranched animals may be heat received antitoxin. The shaker foal syndrome had a case processed and/or acidified to reduce the risk of botulism. fatality rate of 90% at one time, but the use of intensive care, Carcasses should not be allowed to contaminate feed for mechanical ventilation and antitoxin has significantly herbivores, and silage should be monitored for proper improved survival. Approximately 88% of the mechanically acidification. Re-using broiler litter on ruminant farms, as ventilated foals in one study and 96% of the treated foals in feed or bedding, increases the risk of botulism. When broiler another study (some of which did not require respiratory litter is spread on fields, it should be plowed in immediately. support) recovered. Ruminants should be given feed supplements to reduce the Carnivores and pigs are thought to be relatively resistant incidence of pica when dietary deficiencies exist. Vaccines to botulism; nevertheless, they can become ill if they may be available for horses, cattle, sheep, goats, mink and/or consume sufficient doses of the toxin. Contaminated feed has birds in some countries. Vaccination of the dam decreases sometimes resulted in outbreaks affecting hundreds or the risk of foal botulism. A vaccine against one toxin type thousands of unvaccinated farmed mink, ferrets and (rarely) does not protect animals against other types. foxes. During one large outbreak, more than 50,000 ranched Other measures may help control outbreaks once they foxes and other species died of botulism. Most of the animals begin. Carcasses should be collected promptly to prevent affected in this outbreak were blue foxes (Alopex lagopus) cannibalism of toxic carcasses, while fly control helps and shadow foxes, a color variant of this species. Mortality prevent the occurrence of “toxic” maggots (maggots that was low (< 4%) in silver foxes and blue silver foxes, which have ingested botulinum toxin). If possible, the litter should are color variants of Vulpes vulpes. Cats and dogs were be removed from poultry houses. If this cannot be done, relatively resistant to the ingestion of botulinum toxin in a disinfectants or other treatments may help suppress the limited number of laboratory experiments. In one study, dogs growth of clostridia in litter. Cleaning and disinfection of the did not become ill unless food was withheld for 48 hours environment is also recommended. Some farms may remain before they were exposed to the toxin. In the only outbreak persistently contaminated after an outbreak despite this reported in cats, they had eaten tissues from a dead pelican measure. Controlling outbreaks in wild birds can be difficult. that contained very high levels of botulinum toxin. Four of Methods that have been attempted include discouraging the eight cats died, but the surviving cats recovered quickly. birds from using contaminated areas, making environmental Surviving a case of botulism is not thought to result in modifications that reduce the proliferation of C. botulinum immunity to this disease. (e.g., reducing decaying anaerobic vegetable matter), and There is relatively little information about botulism in collecting bird carcasses. One recent study suggested that fish. The mortality rates in fish administered various oral meticulous collection of wild bird carcasses might not be doses of toxin were 92-100% in round goby, 83-92% in able to significantly impact the course of an outbreak. walleye (Sander vitreus), 42-92% in rainbow trout, and 25- Morbidity and Mortality 67% in yellow perch. Yellow perch also survived significantly longer than the other three species. In poultry, botulism tends to be most common during the summer. Most outbreaks occur in broiler chickens, especially in intensively reared flocks between 2 and 8 weeks of age. Botulism in Humans Chickens are reported to become less susceptible as they mature, and botulism is infrequently seen in layers. In turkeys, Incubation Period this disease seems to occur most often in 6 to 16 week-old The reported incubation period for foodborne botulism birds. Flock mortality rates of 1-40% are common in poultry, ranges from a few hours to 16 days, with many severe cases but higher mortality rates have been documented. Botulism is becoming symptomatic in 12-36 hours. Inhalation of reported to be especially severe in pen-reared pheasants, and botulinum toxin often becomes apparent in 12-36 hours as more than 80% of the flock may die. Outbreaks of botulism well, although some cases may take up to a few days. The are seen regularly in wild waterfowl and shorebirds, first signs of wound botulism can appear within a few days sometimes affecting up to a million or more birds. Dabbling and up to 2 weeks after exposure. There seems to be little ducks, coots and gulls are among the most commonly affected definitive information about the incubation period for species. Vultures seem to be resistant to botulism. infant botulism, probably because the moment of exposure Among domesticated mammals, horses and ruminants is often unknown and the symptoms can be insidious. are reported to be particularly susceptible to botulinum toxin. Clinical Signs The case fatality rate is often around 90% in cattle, as effective treatment and supportive care is not generally The neurological signs are similar in all forms of available and/or economically feasible in this species. botulism, although additional symptoms may be seen in Mortality rates up to 70-90% have also been described in adult some forms. Rare cases in pregnant woman suggest that the fetus is not affected. www.cfsph.iastate.edu © 2003-2018 page 6 of 13  Botulism Foodborne botulism Intestinal colonization botulism in adults Gastrointestinal disturbances such as nausea, vomiting Intestinal colonization botulism resembles foodborne and abdominal pain are common in the early stages of botulism, but the course of the disease may be prolonged and foodborne botulism. Botulinum toxin causes constipation, relapses can occur. The initial signs may include lassitude, but some contaminated foods can result in diarrhea. As the weakness and vertigo. As the disease progresses, patients may disease progresses, a descending flaccid paralysis develops experience blurred or double vision, progressive difficulty in the motor and autonomic nerves. The effects are usually speaking and swallowing, descending flaccid paralysis, and symmetrical; however, asymmetrical signs have other symptoms characteristic of botulism. Abdominal occasionally been noted, such as during the initial stages of distention and constipation may also be seen. a case of wound botulism on the head. Common symptoms Inhalational botulism of botulism include blurred or double vision, photophobia, drooping eyelids, an expressionless face, slurred speech, Inhalational botulism was reported in laboratory dysphagia, dysuria, reduced lacrimation, a dry mouth, workers in 1962. It resembled foodborne botulism. somnolence and muscle weakness. There are also reports of Chronic botulism mild cases that were primarily characterized by One survey of farmers whose cattle herds had been gastrointestinal signs, with or without mild cranial nerve involvement. Fever is usually absent, and cognitive diagnosed with “visceral botulism” found that many of them function and the senses are almost always unaffected. self-reported various nonspecific signs such as weakness, dizziness, nausea, dry mouth, speech problems, blurred Untreated cases may progress to descending paralysis of vision and respiratory difficulties. The researchers found the respiratory muscles, arms and legs. Fatal respiratory botulinum toxins in the feces of some farmers, and have paralysis can occur within 24 hours in severe cases. The proposed the existence of “chronic botulism” resulting from pharynx may collapse from cranial nerve paralysis, resulting persistent exposure to botulinum toxins. However, no in dyspnea even if the respiratory muscles are not affected. systematic diagnostic investigation of the farmers’ Death is usually caused by respiratory compromise. symptoms has been reported, and the botulinum toxins found Recovery typically takes weeks to months, although some in their feces often differed from the toxin types in their patients begin improving within days. Some survivors cattle. experience fatigue and shortness of breath for up to a year after recovery. Diagnostic Tests Wound botulism Most, but not all, cases of botulism in people can be diagnosed by detecting toxins and/or organisms in feces, Wound botulism is very similar to the foodborne form; other clinical samples (e.g., serum, vomitus, gastric however, gastrointestinal signs are uncommon and patients aspirates, wound samples) or food, as in animals. Botulinum may have a wound exudate or develop a fever. In other cases, toxin may disappear sooner from the feces than the spores the abscess can be minor (e.g., a small furuncle or mild ingested in contaminated food, and assays to detect both are cellulitis) or clinically inapparent. recommended. In a minority of cases, the toxin or organism Infant botulism cannot be found, and a presumptive diagnosis is based on Most cases of infant botulism occur before the age of 6 clinical signs and the exclusion of diseases with similar months, but babies up to a year of age are susceptible. The symptoms. Nerve conduction studies and electromyography onset may be insidious or sudden, and the symptoms and may be helpful in supporting the diagnosis or excluding other severity can vary considerably. The first sign is usually causes of flaccid paralysis. constipation, which can persist for several days before Treatment neurological signs develop. Lethargy, weakness, excessively long sleep periods, difficulty suckling and swallowing, People with botulism can recover if they receive diminished gag reflexes, dysphagia with drooling, drooping supportive treatment until the endplates of the neurons eyelids and poor pupillary light reflexes may also be regenerate. Depending on the severity of the illness, the apparent. Some babies have a weak or altered cry. In respiratory system may need to be sustained with progressive cases, the infant may develop flaccid paralysis; supplemental oxygen, intubation to keep the airway open a “floppy head” is typical. In severe cases, respiratory and/or mechanical ventilation. Supportive care may be dysfunction or arrest is possible. A rare syndrome caused by necessary for several weeks or months in some cases. type F toxin is characterized by rapid progression and severe Botulinum antitoxin neutralizes toxins that have not yet signs in very young infants, and constipation is reported to bound to the nerve endings. It can prevent the disease from be less common than with other toxin types. Botulism might progressing and decrease the duration of the illness. It should also be responsible for some sudden deaths. Supportive care be given as soon as possible, preferably within the first 24 may be needed for several weeks to months in some hours. How late antitoxin administration should be hospitalized infants; however, mildly affected babies can considered is uncertain, but some reports suggest that it is recover quickly. Relapses are occasionally seen after the still beneficial when given after 48 hours. Equine source symptoms have resolved. antitoxin, which may contain antibodies against one or more www.cfsph.iastate.edu © 2003-2018 page 7 of 13  Botulism toxin types, is used in adults. One recent formulation is a Person-to-person transmission of botulinum has never heptavalent antitoxin that can neutralize all known toxin been described, but precautions should be taken to avoid types (A to G). Human-derived antitoxin, usually employed exposure to toxins in body fluids and feces, and anyone who only in infants, is available from the California Department has been exposed should remain alert for the onset of of Public Health’s Infant Botulism Treatment and Prevention symptoms. Babies may shed C. botulinum in the feces for Program. This unit accepts international requests as well as several months after recovery from infant botulism. those from the U.S. Most sources do not recommend the use of equine source antitoxins in infants, due to concerns about Morbidity and Mortality side effects and the possibility of lifelong sensitization to Botulism tends to occur as sporadic cases and small equid proteins. However, a review of infants treated with outbreaks affecting a few people; however, large outbreaks these products in Argentina suggested that they might be are possible, especially when commercially prepared foods considered in some cases where human-source antitoxin is are involved. Wound botulism, which was once very rare, unavailable. has been increasing with certain types of drug abuse. The Additional treatments depend on the form of botulism. severity of botulism can be influenced by the dose of the Agents that bind or eliminate any remaining toxins in the toxin, the toxin type and concurrent illnesses. Cases caused gastrointestinal tract may be employed in foodborne by type B toxin tend to be milder than those caused by type botulism. Treatment for wound botulism includes surgical A. The physical and chemical characteristics of a food, as debridement of the wound and antibiotics, which are well as the conditions under which it is held, can affect the generally started after antitoxin has been administered. amount of toxin produced. Aerobic conditions may be induced in the wound with Untreated botulism is often fatal, but supportive care has hydrogen peroxide or hyperbaric oxygen therapy. a high success rate when the disease is diagnosed in time. Antibiotics are not recommended in infant botulism because The case fatality rate for foodborne botulism was the death of the causative organisms might release additional approximately 60-70% before 1950, but it has now dropped toxins, and antibiotics might alter the intestinal flora, to about 5-10% in developed countries. The case fatality rate potentially enhancing the organism’s growth. In addition, for infant botulism is estimated to be less than 1-2%, while attempts to eradicate botulinum-producing clostridia from wound botulism is reported to kill approximately 10-15% of infants’ intestines with antibiotics were unsuccessful in the patients, even with aggressive treatment. People who past. If antibiotics are used to treat secondary infections in survive botulism do not become immune to this disease. patients with botulism, drugs that have neuromuscular blocking properties should be avoided. Internet Resources Prevention California Department of Public Health Infant Botulism Commercial canning processes are designed to destroy C. Treatment and Prevention Program botulinum spores, but some common home canning Centers for Disease Control and Prevention (CDC). techniques are ineffective and should not be used with non- Botulism acidic foods. The risk of botulism in foods can also be reduced by acidification, reductions in the amount of moisture, and eMedicine.com. Botulism treatment with salt or other compounds known to inhibit eMedicine.com. Pediatric Botulism clostridial germination and/or growth. Refrigeration can inhibit the growth of group I strains, but some nonproteolytic European Centre for Disease Control and Prevention. group II strains may grow at 3-4°C (37-39°F). Preformed Botulism toxins in foods can be destroyed by heating the food before serving. Food safety guidelines generally recommend heating Food and Drug Administration (FDA). Bacteriological canned foods to 80°C for 30 minutes or to 100°C (212°F) for Analytical Manual Online 10 minutes. Some C. botulinum strains can break down sugars Public Health Agency of Canada. Pathogen Safety and ferment proteins, and foods with “off” odors or flavors Data Sheets should not be eaten; however, other strains grow without changing the food’s flavor, odor or appearance. The Merck Manual Honey should not be fed to infants less than a year of The Merck Veterinary Manual age, as some batches contain C. botulinum spores. Tissues World Health Organization from animals with botulism, including meat and milk, should not be eaten. In laboratories, C. botulinum must be handled under BSL-2 conditions or greater, with BSL-3 precautions Acknowledgements recommended for some procedures. A vaccine was used to This factsheet was written by Anna Rovid Spickler, DVM, help protect laboratory workers in the U.S. at one time, but it PhD, Veterinary Specialist from the Center for Food was withdrawn due to concerns about its efficacy. New Security and Public Health. The U.S. Department of vaccines are in development. Agriculture Animal and Plant Health Inspection Service www.cfsph.iastate.edu © 2003-2018 page 8 of 13  Botulism (USDA APHIS) provided funding for this factsheet through Caya JG, Agni R, Miller JE. Clostridium botulinum and the a series of cooperative agreements related to the clinical laboratorian: a detailed review of botulism, including development of resources for initial accreditation training. biological warfare ramifications of botulinum toxin. Arch Pathol Lab Med. 2004;128(6):653-62. The following format can be used to cite this factsheet. Centers for Disease Control and Prevention (CDC). Botulism Spickler, Anna Rovid. 2018. Botulism. Retrieved from [website online]. CDC; 2017 Oct. Available at: http://www.cfsph.iastate.edu/DiseaseInfo/factsheets.php. https://www.cdc.gov/botulism/. Accessed 20 Jan 2018. Center for Food Safety and Applied Nutrition (CFSAN). References Foodborne Pathogenic Microorganisms and Natural Toxins Handbook. 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