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BOTULISM
 Botulism is a disease caused by the neurotoxins of Clostridium botulinum.
 This microorganism is:
o spore-forming,
o gram-positive,
o anaerobic bacillus,
 Botulism spp. may exist in soil or marine sediments throughout the world.
 Clostridial spores are highly heat resistant and can survive up to 2 hours at 100° C with inactivation requiring
exposure to a temperature of 120° C.
 Foodborne botulism is a severe type of food poisoning caused by the ingestion of foods containing the potent
neurotoxin formed during growth of the botulism organism in anaerobic condition.
 High-risk foods include:
o home-canned or home-processed low-acid fruits and vegetables;
o home-canned or home-processed fish and fish products; and condiments, such as relish and chili peppers.
 The neurotoxin causes a paralytic disease with blockade of neuromuscular conduction.
 Toxin types A, B, E, and, in rare cases F, cause human disease;
 The toxin is heat labile and can be destroyed if heated at 80°-100°C for 10 minutes or longer.
Pathophysiology:
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The toxin causes blockade of neuromuscular conduction by binding to receptor sites on presynaptic motor nerve
terminals, entering the nerve terminal, and inhibiting the release of acetylcholine by proteolysis of components of the
neurotransmitter exocytosis apparatus.
Blockade of neurotransmitter release at the nerve terminal is considered permanent. Evidence exists that the axon
may sprout new terminals and allow recovery of neurotransmission.
The peripheral cholinergic nerve terminals involved include neuromuscular junctions, cholinergic parasympathetic
nerve endings, and some peripheral ganglia.
History:
Botulism generally is seen in 3 clinical scenarios, based on the mode of acquisition.
 Food poisoning: This follows the ingestion of preformed toxins in food contaminated with C botulinum (conserve
food).
 Wound infection: Infection of wounds by C botulinum most commonly occurs where wounds are contaminated
heavily with soil or water. Spores may germinate into toxin-producing vegetative microorganisms.
 Infant botulism: C. botulinum can colonize the gastrointestinal tract of an infant less than 1 year of age. C. botulinum
spores in honey used to sweeten infants milk or water, when ingested, geminate in the infants intestinal tract,
colonize it and produce toxin in vivo. Constipation is the first sign of disease; the same neurological signs seen in the
adult follow the constipation. Antibiotics are generally not effective and may exacerbate the illness by elimination of
normal flora. Therapy is the same as for adult botulism except that antitoxin is generally not used because the disease
is milder in children.
Food poisoning:
 The incubation period is generally 18-36 hours (ranges from 4 hours to 8 days).
 The onset of symptoms can be abrupt or can evolve over several days.
 Typically, patients are afebrile
 Patients generally remain alert and responsive.
1. Ophtalmoplegia syndrome - lesion of the III (oculomotor), IV (trochlear), VI (abbducent) nerve
o Accommodation paresis, with blurred vision – lesion of the central nucleus of the III nerve, that regulate the
configuration of the crystalline lens
o Blepharoptosis - lesion of the III nerve
o Mydriasis - pupil dysfunction with poorly reactive pupils, lesion of the nn.ciliares breves
o Anisocoria - lesion of the nn.ciliares breves
o Diplopia (double vision)
o Divergence strabismus – predominant lesion of III nerve
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Convergence strabismus - predominant lesion of VI nerve
Nystagmus may be noted
Decreased corneal reflexes
Dry eye symptoms with impairment of lacrimation (anticholinergic effects of the neurotoxins)
2. Pharyngal neuropathic syndrome
 impairment of salivary secretion,
 dysphagia - impairment of swallowing and drinking
 gag reflex may be suppressed
 impairment of the palatinate reflex
3. Glottal neuropathic syndrome
 dysphonia,
 hoarse voice
 slurry speach
4. Respiratory difficulties
 intercostal and diaphragmatic weakness
 dispnea, tahypnea
5. Haemodinamic impairment
 tahicardia
 paleness
 cyanosis
 high or low arterial pressure, orthostatic hypotension
6. Muscular (miastenia) syndrome
 Muscle weakness
 A generally symmetric descending flaccid paralysis occurs, with involvement of neck, arms, thorax, and legs
 Paralytic ileus advancing to severe constipation and urinary retention.
 Gastric dilation
7. Gastrointestinal syndrome
 Abdominal pain, with nausea and vomiting may precede or follow paralysis.
 Reduced salivation
Wound infection
o Wound botulism is the rarest form of botulism.
o The incubation period is 4-14 days. Wound botulism may occur in any wound contaminated by soil or water.
o Symptoms are generally the same as those seen in food-borne botulism, except gastrointestinal symptoms are absent.
o The source wound may appear relatively benign. Since 1994, the number of patients with WB and a history of
chronic intravenous drug abuse has increased dramatically.
o No gastrointestinal symptoms are involved with WB
o Patients may be febrile, but this is more likely due to the wound infection rather than the WB syndrome.
o Often, the wound appears quite benign.
Infant botulism
o The incubation period varies from 3-30 days. In this form of botulism, the severity ranges from mild illness with
failure to thrive to severe paralysis with respiratory failure.
o About 90 percent of infants with botulism are younger than six months.
o The first sign of the disease may be constipation. Other features include lethargy, hypotonia with poor head control,
poor feeding, with difficulty in sucking and swallowing, and pooled oral secretions. Respiratory failure occurs in up
to one half of diagnosed infants.
o The identification of contaminated honey as a source of spores has lead to the recommendation that honey should not
be given to infants younger than 1 year. Susceptibility decreases with age as the normal intestinal flora develops.
Lab Studies:
 The diagnosis of botulism requires a high degree of clinical suspicion.
o The diagnosis must be considered in an afebrile patient with progressive descending paralysis, especially
in the presence of gastrointestinal symptoms.
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Serum toxin bioassay:
 The demonstration of toxin in serum involves a bioassay in mice. The identification of the toxin type is
performed by a mouse toxin neutralization test.
o Aliquots of serum from a patient are mixed with the following antitoxins: polyvalent antitoxin ABE,
monovalent antitoxin A, monovalent antitoxin B, monovalent antitoxin E and buffer control (without
antitoxin). Each test mixture is then injected intraperitoneally into a pair of Swiss white mice using 0.5
mL per mouse. The mice are observed for a period of up to 4 days. If any of the botulinum toxins is
present in sufficient quantities to be detected, all mice will die from respiratory failure except those
receiving the specific antitoxin. For example, if a patient has type E toxin in the serum, the two pairs of
mice that receive antitoxin ABE and antitoxin E test mixtures will survive, but the three pairs that
receive antitoxin A, antitoxin B and buffer control test mixtures will die.
Treatment
o Stomach and intestinal irrigation.
 Magnesium salts, citrate, or sulfate, should not be administered because magnesium can potentiate the toxininduced neuromuscular blockade.
o Wound infection requires incision and thorough debridement of the infected wound
o Ventilatory support:
 In adults, ventilatory support will be needed in as many as one third of cases.
 Pulse oximetry, arterial blood gas analysis, and spirometry should be monitored.
 Mechanical ventilation is considered when vital capacity is less than 30% of predicted.
 The average duration of pulmonary support for those requiring mechanical ventilation is 6-8 weeks. Some
patients experience residual weakness and autonomic dysfunction for as long as 1 year.
o Parenteral nutrition may be required in view of gastrointestinal disturbance.
o Urinary catheterization may be required for urinary retention
o Stress ulcer prophylaxis also is a standard component of intensive care management.
 If an ileus is present, nasogastric suction and intravenous hyperalimentation are very helpful supportive
measures. If no ileus is present, tube feeding can be used for nutritional supplementation.
Antitoxin:
Botulism antitoxin -- Intravenous administration of one vial of botulism antitoxin results in serum levels of type
A, B, and E antibodies capable of neutralizing serum toxin concentrations in excess of those reported for
botulism patients. Circulating antitoxins have a half-life of 5-8 days.
Adult Dose: 2 vials of 10,000 IU IV (each vial contains approximately 100 times more antitoxin than needed to
neutralize toxin)
Pediatric Dose: Administer as in adults; however, equine antitoxin rarely has been used in infant botulism
because of lack of evidence of benefit and risks of hypersensitivity
Contraindications Documented hypersensitivity to equine antitoxin
Pregnancy Safety for use during pregnancy has not been established.
Precautions Prior to administration of the antitoxin, perform skin testing to test for sensitivity to serum or
antitoxin; approximately 9% of persons treated experience hypersensitivity reactions
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An antitoxin may be beneficial, even when provided several wk after toxin ingestion because circulating toxin
has been detected in serum as long as 30 d later.
Antitoxin will not neutralize toxin already bound to neuromuscular junctions.
The antitoxin should be given as soon as possible, prior to receiving laboratory confirmation of diagnosis.
Although antitoxin can slow disease progression, it has no effect on established neurologic deficits.
In food-borne illness, trivalent (types A, B, and E) equine antitoxin should be administered.
In Moldova:
o 1 polyvalent equine botulism antitoxin serum dose contain: Tape A – 10.000 IU, tape B – 5.000 IU, tape
E - 10.000 IU
o The dose of polyvalent serum in admission department:
 non-severe botulism 1-2 doses
 moderate severe botulism 3-4 doses
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 severe botulism 5-6 doses
The dose of serum during the hole course of treatment:
 non-severe botulism 1-2 doses
 moderate severe botulism 2-10 doses
 severe botulism 15-17 doses
USA. There are two primary Botulinum Antitoxins available for treatment of wound and foodborne
botulism:
o Trivalent (A,B,E) Botulinum Antitoxin is derived from equine sources. This antitoxin is
available from the local health department via the CDC.
o The second antitoxin is heptavalent (A,B,C,D,E,F,G) Botulinum Antitoxin. This is a less
immunogenic antitoxin that is effective against all known strains of botulism where not
contraindicated. This is available from the US Army
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Human botulism immune globulin (HBIG - human botulinum immune globulin, sometimes referred to as "BabyBIG") is benefical for infant botulism
Botulism (infant and wound) should be treated with penicillin or metronidazole to stop toxigenesis.
o Penicillin G (Pfizerpen) 20-30 million U/kg/d IV in 6 divided doses
o Chloramphenicol (Chloromycetin) -- Alternate to penicillin. 50 mg/kg/d IV
o Clindamycin (Cleocin) 600 mg IV q8h
Remember that aminoglycoside antibiotics and tetracyclines may increase neuromuscular blockade by impairment of
neuronal calcium entry.
Pentavalent (ABCDE) botulinum toxoid is a combination of aluminum phosphate-adsorbed toxoid derived from
formalin-inactivated type A,B,C,D and E botulinum toxins. The toxoid is used to protect individuals from accidental
exposure to botulinum toxins. It should be administered only to individuals working in high risk laboratories who are
actively working or expect to be working with cultures of Clostridium botulinum or the toxins. The vaccine induces
immunity over several months.
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