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Botulism
Adult Intestinal Toxin-Mediated Botulism

Botulism is an intoxication caused by botulinum toxin produced by the bacterium Clostridium botulinum.

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Presentation

In all forms of botulism, the signs and symptoms are similar. However, in the food borne variety, gastrointestinal symptoms like vomiting and diarrhea may be present.

The most common presentation is the characteristic weakness of the muscles supplied by cranial nerves. Muscle paralysis starts from the face which manifests as loss of facial expressions, ptosis, diplopia, dyspnea, dysphagia and difficulty in talking [4].

The paralysis then symmetrically descends to involve the limbs causing weakness of the arms and legs. There may also be a diminishing or even a total absence of the reflexes. As the disease progresses, it may also cause paralysis of the muscles of respiration leading to respiratory arrest which can be life threatening.

Constipation is an early symptom in infant botulism which is most likely to be missed.

Entire Body System

  • Malaise

    Vomiting Dysphagia Diplopia Dilated/fixed pupils Extremely dry mouth unrelieved by drinking fluids Generally, botulism progresses as follows: Preceding or following the onset of paralysis are nonspecific findings such as nausea, vomiting, abdominal pain, malaise [emedicine.medscape.com]

    Generally, botulism progresses as follows:Preceding or following the onset of paralysis are nonspecific findings such as nausea, vomiting, abdominal pain, malaise, dizziness, dry mouth, dry throat, and, occasionally, sore throat. [slideshare.net]

Respiratoric

  • Dyspnea

    Description HPO Frequency Orphanet Frequency HPO Source Accession 1 ptosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000508 2 diplopia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000651 3 diarrhea 59 32 frequent (33%) Frequent (79-30%) HP:0002014 4 dyspnea [malacards.org]

    […] stool, serum, food or other specimen; Scope: Global Signs & Symptoms: dizziness; fatigue; pharyngitis; abdominal pain; constipation; diarrhea; nausea, vomiting; deep tendon reflexes, reduced; dysphagia; speech, impaired; weakness; vision, impaired; dyspnea [web.archive.org]

    Muscle paralysis starts from the face which manifests as loss of facial expressions, ptosis, diplopia, dyspnea, dysphagia and difficulty in talking. [symptoma.com]

  • Stridor

    Patient B presented with shortness of breath, vomiting, and stridor. [ncbi.nlm.nih.gov]

Gastrointestinal

  • Constipation

    Botulism is a potentially fatal infection characterized by progressive muscle weakness, bulbar paralysis, constipation and other autonomic dysfunctions. [ncbi.nlm.nih.gov]

    In foodborne botulism, constipation, diarrhea, and/or vomiting may occur. In intestinal botulism, infants are weak, constipated, and "floppy" with loss of head control. Patients die from respiratory paralysis. [web.archive.org]

  • Vomiting

    In foodborne botulism, constipation, diarrhea, and/or vomiting may occur. In intestinal botulism, infants are weak, constipated, and "floppy" with loss of head control. Patients die from respiratory paralysis. [web.archive.org]

    Symptoms often begin with blurred vision and difficulty in swallowing and speaking, but sometimes diarrhoea and vomiting can occur. The disease can go on to lead to further problems with vision, and paralysis. [patient.info]

    Therefore, the classical diagnostic pentad of botulism (dry mouth, nausea, vomiting, dysphagia, diplopia, fixed dilated pupils) may be of limited sensitivity in single cases. [ncbi.nlm.nih.gov]

    In foodborne botulism, there may also be diarrhoea and vomiting. The disease can progress to a more generalised paralysis that includes the arms, legs, trunk and respiratory muscles. [gov.uk]

  • Nausea

    Therefore, the classical diagnostic pentad of botulism (dry mouth, nausea, vomiting, dysphagia, diplopia, fixed dilated pupils) may be of limited sensitivity in single cases. [ncbi.nlm.nih.gov]

    Findings that distinguish botulism from myasthenia gravis: nausea/vomiting, poorly reactive pupils, and paralysis of accommodation. [Purvin V, Kawasaki A. Neuro-Ophthalmic Emergencies for the Neurologist. Neurologist. 2005 Jul;11(4):195-233.] [web.archive.org]

    The clinical symptoms of wound botulism are similar to those of foodborne botulism except that gastrointestinal symptoms (including nausea, vomiting, diarrhea) are uncommon. [emedicine.medscape.com]

    Bacillus cereus B. cereus food poisoning 10-16 hrs Abdominal cramps, watery diarrhea, nausea 24-48 hours Meats, stews, gravies, vanilla sauce Campylobacter jejuni Campylobacteriosis 2-5 days Diarrhea, cramps, fever, and vomiting; diarrhea may be bloody [fda.gov]

  • Dysphagia

    The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia. [ncbi.nlm.nih.gov]

  • Dysphagia

    The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia. [ncbi.nlm.nih.gov]

Cardiovascular

  • Orthostatic Hypotension

    Prominent features of cardiovascular failure were high resting heart rate, supine hypertension, orthostatic hypotension, and impaired baroreflex function. Three patients reported inability to keep up with their routine amount of physical work. [ncbi.nlm.nih.gov]

    Orthostatic hypotension Botulism is a rare but important suspicion in acute or predominant isolated autonomic dysfunction. Heart failure with diastolic dysfunction also has been reported. [medicaljoyworks.com]

    hypotension Reduced salivation Reduced lacrimation Other neurologic findings include the following: Changes in deep tendon reflexes, which may be either intact or diminished Incoordination due to muscle weakness Absence of pathologic reflexes and normal [emedicine.medscape.com]

  • Tachycardia

    Symptoms of botulism include: Blurred vision/double vision Drooping Eyelids; other signs of facial nerve paralysis Slurred speech Nausea and vomiting Difficulty swallowing, dry mouth and throat Tachycardia Respiratory paralysis Constipation, problems [commonsensehome.com]

    Over the next 24 hours, she had a decreased level of consciousness, a depressed Glasgow coma scale score, tachycardia, and difficulty breathing, with eventual respiratory failure requiring ventilation support. [ncbi.nlm.nih.gov]

Eyes

  • Blurred Vision

    They present ileus and acute cranial nerve dysfunction including dysphagia and blurred vision. One of them had severe neurologic impairment and required mechanical ventilatory support. [ncbi.nlm.nih.gov]

    Maaring makabulag ito kung hindi maaagapan (If left untreated, these bacteria could cause paralysis, blurred vision, or even cause blindness)," he said. [youtube.com]

    Symptoms include double or blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness. Treatment may include antitoxins, intensive medical care, or surgery of infected wounds. [fpnotebook.com]

    vision and diplopia; botulism may be classified into several subtypes such as food borne, infant, wound, and others 005.1 Excludes Applies To Botulism NOS Food poisoning due to Clostridium botulinum ICD-9-CM Volume 2 Index entries containing back-references [icd9data.com]

  • Diplopia

    Therefore, the classical diagnostic pentad of botulism (dry mouth, nausea, vomiting, dysphagia, diplopia, fixed dilated pupils) may be of limited sensitivity in single cases. [ncbi.nlm.nih.gov]

    Affiliated tissues include colon, and related phenotypes are ptosis and diplopia Human phenotypes related to Adult Intestinal Botulism: 59 32 (show all 9) # Description HPO Frequency Orphanet Frequency HPO Source Accession 1 ptosis 59 32 hallmark (90% [malacards.org]

    Visual blurring maybe interpreted as diplopia by the patient, it is important to assess the vision accurately. Is a manifestation of cranial neuropathy affecting occulomotor (CN III), trochlear (CN IV) and abducens (CNVI) nerves. [medicaljoyworks.com]

    […] caused by potent protein neurotoxins produced by clostridium botulinum, which interfere with the presynaptic release of acetylcholine at the neuromuscular junction; clinical features include abdominal pain, vomiting, acute paralysis, blurred vision and diplopia [icd9data.com]

  • Blepharoptosis

    Blepharoptosis. It is the result of dysfunction of the levator palpebrae superioris which is innervated by the superior division of third cranial nerve and the Mueller muscle of the eyelid. [medicaljoyworks.com]

Musculoskeletal

  • Muscle Weakness

    By history, the most common symptoms were dysphagia (66%), proximal muscle weakness of upper and lower extremity (60%), neck flexor muscle weakness (33%), ophthalmoplegia (53%), bilateral ptosis (46%), dysarthria (53%), double vision (40%), blurred vision [ncbi.nlm.nih.gov]

    Incoordination of muscles. It is due to muscle weakness in neuromuscular junction toxicity in botuoinum. Incoordination of muscles. It is due to muscle weakness in neuromuscular junction toxicity in botuoinum. [medicaljoyworks.com]

    Symptoms of botulism include difficulty in focusing the eyes, double vision, difficulty in swallowing, drooping eyelids, dry mouth, muscle weakness, and/or slurred speech. [businessdictionary.com]

    On discharge 3 months after admission he still had muscle weakness and required feeding by a nasogastric tube. [poison.org]

  • Muscle Hypotonia

    Infant botulism presents a broad spectrum of severity ranging from mild muscle hypotonia, manageable on an outpatient basis, to sudden death caused by respiratory arrest ( 3 ). [doi.org]

Urogenital

  • Urinary Retention

    Urinary retention with bladder distension It is due to autonomic toxic neuropathy in botulism, when the suspected patients present with abdominal distention and abdominal pain, urinary retention has to be suspected., Urinary retention with bladder distension [medicaljoyworks.com]

    Initial symptoms include blurry vision (accommodation defects, diplopia) with bilateral ptosis, followed by dysautonomic symptoms (dry mouth and eyes, mydriasis, dysphagia, dysarthria, urinary retention and constipation). [orpha.net]

    Other symptoms after ingestion may include dry mouth, abdominal distention, urinary retention, postural hypotension, and paralysis of extraocular muscles. Symptoms progress over several days to respiratory paralysis. [web.archive.org]

    Later complications include paralytic ileus, severe constipation, and urinary retention. Wound botulism results when wounds are contaminated with C botulinum spores. [emedicine.medscape.com]

  • Bladder Distention

    distention advancing to urinary retention Orthostatic hypotension Reduced salivation Reduced lacrimation Other neurologic findings include the following: Changes in deep tendon reflexes, which may be either intact or diminished Incoordination due to [emedicine.medscape.com]

    The autonomic nervous system is also involved.Manifestations of this include the following:1 Paralytic ileus advancing to severe constipation2 Gastric dilatation3 Bladder distention advancing to urinary retention4 Orthostatic hypotension5 Reduced salivation6 [slideshare.net]

Neurologic

  • Flaccid Paralysis

    Abstract Botulism is the acute, flaccid paralysis caused by a neurotoxin produced by Clostridium botulinum. [ncbi.nlm.nih.gov]

  • Guillain-Barré Syndrome

    Both botulism and Miller-Fisher variant of Guillain-Barré syndrome were initial diagnostic considerations, and she was treated with intravenous immunoglobulin and botulinum antitoxin. [ncbi.nlm.nih.gov]

    Differential diagnosis Differential diagnosis, depending on the disease form, in adults or infants, includes myasthenia, Guillain-Barré syndrome (and Miller Fisher syndrome), Lambert-Eaton syndrome (see these terms), bacterial and chemical food poisoning [orpha.net]

    Physicians must be careful when diagnosing botulism because it may cause symptoms similar to diseases such as Guillain-Barré syndrome, myasthenia gravis, Lambert-Eaton syndrome, and strokes. [aanem.org]

  • Stroke

    Physicians must be careful when diagnosing botulism because it may cause symptoms similar to diseases such as Guillain-Barré syndrome, myasthenia gravis, Lambert-Eaton syndrome, and strokes. [aanem.org]

    At first, hospital staff thought she had suffered a stroke because of her slurred speech and muscle weakness. The doctor did ask her if she had eaten any spoiled food lately, however. Too weak to speak, Mrs. [web.archive.org]

    Diagnosis Botulism is a rare disease and diagnosis may be blurred by other similar disease such as Guillain-Barre syndrome, stroke and myasthenia gravis. [health.hawaii.gov]

    Botulism is diagnosed through a combined assessment of the patient’s symptoms and history and specialized tests to rule out other diseases that can appear as botulism, such as stroke, myasthenia gravis and Guillain-Barré syndrome. [tbdhu.com]

  • Dysarthria

    A 60-year-old man was hospitalized with blurred vision, diplopia, and dysarthria. On hospital day 2, the patient was transferred to the intensive care unit for progressive fatigable weakness with ptosis, dysphagia, dysarthria, and nausea. [ncbi.nlm.nih.gov]

  • Dizziness

    On January 28, 2011, an Ohio resident, aged 29 years, was hospitalized after 5 days of progressive dizziness, blurred vision, dysphagia, and difficulty breathing. The patient required mechanical ventilation and botulism antitoxin. [ncbi.nlm.nih.gov]

    These long-term effects most often include fatigue, weakness, dizziness, dry mouth, and difficulty performing strenuous tasks. Patients also report a generally less happy and peaceful psychological state than before their illness. [foodborneillness.com]

    Diagnostic: Clinical; Detection of toxin in stool, serum, food or other specimen; Scope: Global Signs & Symptoms: dizziness; fatigue; pharyngitis; abdominal pain; constipation; diarrhea; nausea, vomiting; deep tendon reflexes, reduced; dysphagia; speech [web.archive.org]

Workup

Most of the cases of infant botulism should be diagnosed on clinical grounds. Confirmation can be made by stool or enema specimen with the mouse bioassay.

In all other forms, the diagnosis of botulism can be based on the patient’s history and physical examination; however, the signs and symptoms may mimic other diseases like Guillain-Barré syndrome, stroke and myasthenia gravis [5].

Confirmation of diagnosis can be made if botulinum toxin is identified in the food, stomach contents, vomitus and/or feces of the patient. In peracute cases, the toxin can be found in blood as well. The detection of toxin in various specimens can be carried out by different tests such as:

  • Enzyme-linked Immunosorbent Assays (ELISA)
  • Electrochemiluminiscence (ECL) [6]
  • Mouse inoculation tests

Treatment

The primary treatment consists of administration of antitoxin and the provision of supportive care [7].

In case of respiratory paralysis, the patient may require a ventilator for weeks or months. Food borne and wound botulism, if diagnosed early, can be treated with passive immunity and antibiotics [8].

Two types of antitoxins are available:

  • trivalent antitoxin (effective against the toxin types A, B and E) [9]
  • heptavalent antitoxin (effective against all the toxin types from A to G) [10]

Infant botulism is harder to manage. Currently, a drug named Botulism Immune Globulin Intravenous (Human) is the only suitable option to manage this form of botulism.

Prognosis

Untreated botulism may be fatal in as many as 60% of the cases. However, if diagnosed early, the disease can be successfully treated with no complications.

The recovery however, may still take some weeks. Before the development of artificial respirators, mortality due to botulism was very high, but in 1990s it dropped to as low as 2%.

Etiology

Botulism is caused by the toxin produced by the bacterium Clostridium botulinum and not by infection with the bacterium itself. The organism produces toxin in anaerobic conditions. The toxin enters the bloodstream and acts on the nervous system causing flaccid paralysis of voluntary muscles which may progress to paralysis of respiratory muscles leading to respiratory arrest.

The disease in humans in mostly caused by three toxin types A, B and E. The lethal doses for causing disease in a man of 70 kg weight are estimated to be 0.09 to 0.15 micrograms intravenously, 0.80 to 0.90 micrograms through inhalation and 70 micrograms orally.

Food borne Botulism

This form of botulism occurs when food containing botulinum toxin is consumed. In conditions of environmental stress, the bacteria form spores which are resistant to cooking. Later, when they receive a favorable environment (e.g. one that has an alkaline pH and a low salt & sugar content), they produce botulinum toxin. This mostly occurs in improperly preserved foods.Symptoms appear 12 to 36 hours after eating such contaminated food.

Infant Botulism

This is the type of botulism which occurs due to colonization of the bacteria in the intestines. The bacteria produce toxins which are absorbed from the intestinal wall into the bloodstream. It most commonly occurs in infants of the ages of 2 to 3 months. This is because by that age, their normal intestinal flora have not been fully established. Normally, the intestinal flora compete with Clostrodium botulinum, preventing it from actively colonizing the intestine. Honey consumption in infants is regarded as the most common cause of infant botulism [2].
Adult form of infant botulism is termed as adult intestinal toxemia but it is exceedingly rare.

Wound Botulism

Wound botulism occurs as a result of contamination of a wound by either the bacteria or its spores. The toxin produced by them then enters the bloodstream. Nowadays, intravenous drug use is a very common cause of this form of botulism [3].

Inhalation Botulism

It is a very rare kind of botulism. Some cases have been reported due to the accidental inhalation of Clostridium botulinum spores by laboratory workers.

Epidemiology

Globally, botulism is not a very common disease. Most of the cases are sporadic, although sometimes outbreaks have occurred in certain areas of the United States and the United Kingdom.

The Centers for Disease Control USA has documented 263 individual cases during the years 1990 to 2000; 163 of which happened to be of the food borne variety. The average number of cases of food borne botulism in the United States is estimated to be 24 cases per year - most of which occur in Alaska [1].

There are about 80 to 100 cases of infant botulism annually in United States, making it the most common form of botulism. About 20% of these occur due to the consumption of honey in children below one year of age.The largest incidence of infant botulism has been found to be in Philadelphia and Pennsylvania.

Wound botulism occurs due to trauma and its incidence is on the rise since 1990s due to increased use of intravenous drugs and skin popping.

Pathophysiology

The bacterium Clostridium botulinum produces eight types of toxins (A, B, C1, C2, D, E, F, and G). These toxins are serologically different but produce similar symptoms in the patients. The toxin types A, B and E cause disease in humans.

In all forms of botulism the toxin affects the nervous system. Once it is absorbed in the bloodstream it is carried to the peripheral cholinergic synapses specially that of the neuromuscular junctions where it inhibits the release of acetylcholine from the nerve terminals by irreversibly binding to the acetylcholine receptors.

This neurotransmitter produces a bridge between synapses where dendrites and axons connect with each other. The toxin enzymatically blocks acetylcholine release from the motor nerve endings which results in paralysis.

Prevention

There are no guidelines for prevention of Botulism.

Summary

Botulism is a rare but potentially lethal condition caused by a spore-producing gram positive bacterium Clostridium botulinum that naturally occurs in the soil. The organism produces botulinum toxin which causes neuromuscular flaccid paralysis.

Depending upon the route of entry of the bacteria or its toxin, botulism can be divided into several types; namely food-borne botulism, infant botulism, wound botulism, and the less common, inhalation botulism.

The disease begins with fatigue, blurring of vision and diplopia followed by the weakness of motor function throughout the body and difficulty in breathing.

If diagnosed early, it can be treated by providing passive immunity, although complete recovery may take weeks to months.

Patient Information

Botulism is a rare but fatal disease caused by a bacterium that is normally found in the soil. It is characterized by paralysis of the muscles of the face, arms, legs and chest (including the muscles required for breathing).

It usually results from eating food that is contaminated with the toxin. This condition is treated by the injection of appropriate antitoxins. In cases that are diagnosed early, the prognosis is quite good.

References

  1. Shaffer N, Wainwright, RB, Middaugh, JP, et al. Botulism among Alaska Natives. The role of changing food preparation and consumption practices. West J Med. 1990;153(4):393-393.
  2. Grant KA, McLauchlin J, Amar C. Infant botulism: advice on avoiding feeding honey to babies and other possible risk factors. Community practitioner : the journal of the Community Practitioners' & Health Visitors' Association. Jul 2013;86(7):44-46.
  3. Passaro DJ, Werner SB, McGee J, Mac Kenzie WR, Vugia DJ. Wound botulism associated with black tar heroin among injecting drug users. JAMA : the journal of the American Medical Association. Mar 18 1998;279(11):859-863.
  4. Khakshoor H, Moghaddam AA, Vejdani AH, Armstrong BK, Moshirfar M. Diplopia as the primary presentation of foodborne botulism. Oman journal of ophthalmology. May 2012;5(2):109-111.
  5. Forss N, Ramstad R, Backlund T, Lindstrom M, Kolho E. Difficulties in diagnosing food-borne botulism. Case reports in neurology. May 2012;4(2):113-115.
  6. Sachdeva A, Singh AK, Sharma SK. An electrochemiluminescence assay for the detection of bio threat agents in selected food matrices and in the screening of Clostridium botulinum outbreak strains associated with type A botulism. Journal of the science of food and agriculture. Mar 15 2014;94(4):707-712.
  7. Werner SB, Chin J. Botulism--diagnosis, management and public health considerations. California medicine. May 1973;118(5):84-88.
  8. Chalk CH, Benstead TJ, Keezer M. Medical treatment for botulism. The Cochrane database of systematic reviews. Feb 20 2014;2:CD008123.
  9. Alizadeh AM, Zamani N. Treatment of foodborne botulism in current clinical toxicology. Pediatric reports. Apr 2 2012;4(2):e22.
  10. Hill SE, Iqbal R, Cadiz CL, Le J. Foodborne botulism treated with heptavalent botulism antitoxin. The Annals of pharmacotherapy. Feb 2013;47(2):e12.
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