Botulism

Original Editors - Elliot Mattingly from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Elliot Mattingly, Lucinda hampton, Admin, Elaine Lonnemann, Wendy Walker, WikiSysop and Kim Jackson  

Introduction

Botulism is a neuroparalytic syndrome that results from the systemic effects of an exo neurotoxin produced by the rod-shaped, spore-forming, anaerobic bacterium Clostridium botulinum.

• Botulinum toxins are one of the most lethal substances known that can block nerve functions and can lead to respiratory and muscular paralysis.
• Human botulism may allude to foodborne botulism, infant botulism, wound botulism, and inhalation botulism or other types of intoxication.
• Foodborne botulism, caused by consumption of improperly processed food, is a rare but potentially fatal diseasethat requires rapid diagnosis and antitoxin treatment. Homemade canned, preserved or fermented foodstuffs are a common source of foodborne botulism and their preparation requires extra caution.

Etiology

Botulinum toxins are neurotoxic and therefore affect the nervous system. Botulinum neurotoxin is considered the deadliest toxin known due to its high potency and lethality, with a lethal dose of 1 ng to 3 nanograms of toxin per kilogram of body mass. The flaccid paralysis of botulism results from the irreversible inhibition of acetylcholine release at the presynaptic nerve terminal of the neuromuscular junctions.

Spores produced by the bacteria Clostridium botulinum, being heat-resistant and existing widely in the environment, freely germinate grow and then excrete toxins in anaerobic conditions . There are 7 distinct forms of botulinum toxin, types A–G. Four of these (types A, B, E and rarely F) cause human botulism. Types C, D and E cause illness in other mammals, birds and fish.

Botulinum toxins are ingested through improperly processed food where bacteria or the spores survive, then increase in number and produce the toxins. Though mainly a foodborne intoxication, human botulism can also be caused by intestinal infection with C. botulinum in infants, wound infections, and by inhalation.

Transmission

There are three common forms of botulism.

1. Intestinal botulism (most common form). Caused by eating food, or swallowing dust or soil that contains the bacteria, Clostridium botulinum. Infants under the age of 12 months are most at risk, however adults who have certain gastrointestinal problems also at risk. The bacteria multiply inside the gut and produce toxins. Healthy adults have natural defences in their gut that prevent the bacteria from multiplying usually.
2. Food-borne botulism: Caused by eating food contaminated with toxins. Symptoms generally occur between 12 and 36 hours after eating the contaminated food. This form of botulism can be severe and may lead to death.
3. Wound botulism (rare form): Caused by bacteria (often in soil or gravel) entering the body through a wound or IV drug use. Symptoms can occur up to two weeks after the wound.

Epidemiolgy

Botulism outbreaks are rare, however thay are public health emergencies requiring rapid recognition to identify the disease source, distinguish outbreak types (between natural, accidental or potentially deliberate), prevent more cases and successfully manage treatment to affected patients.

• In 2014, 123 cases of botulism were reported by 16 EU/EEA countries, including 91 cases reported as confirmed. Thirteen countries notified zero cases.
• In Australia, there is typically only one case of botulism reported per year.
• In the United states, 5 years from 2011 through 2015, an average of 162 annual cases of botulism was reported. 

'Botox'

C. botulinum is the bacterium used to produce Botox, a product predominantly injected for clinical and cosmetic use (a purified and heavily diluted botulinum neurotoxin type A).      

Characteristics/Clinical Presentation

Symptoms in adults may include:

• blurred or double vision
• difficulty in speaking, swallowing and breathing
• nausea and vomiting
• dry mouth
• increasing weakness, fatigue and ultimately paralysis

File:Infant botulism2.JPG

Infant with extreme floppiness/weakness

Symptoms in infants may include:

• constipation
• weak, feeble cry
• loss of head control
• loss of appetite (poor sucking and feeding)
• breathing difficulties, choking and gagging
• reduced movement of limbs and increased weakness and floppiness, paralysis

Paralysis of breathing muscles may cause loss of respiratory failure and death unless mechanical ventilation is provided.

Medications

Antitoxin therapy,:

• This is the only specific treatment for botulism. 
• The antitoxin can stop the progression of paralysis and decrease the duration of paralysis and dependence on mechanical ventilation.
• Ideally should be given within 24 hours of onset of symptoms.
• In the past the treatment dose was 2-4 times more than it is at this time. Less than 1% of individuals have serious reactions.
• The prognosis is excellent for infants who received the human derived antitoxin. There is a case fatality rate of less than 2%.
• Recovery results from the regeneration of nerve terminals and motor endplates.
• There are two different types of antitoxin. The trivalent antitoxin is effective against three C. Botulinum neurotoxins, A, B, E. This version of the antitoxin is given by the CDC from quarantine stations. The heptavalent antitoxin is effective against seven neurotoxins, A, B, C, D, E, F, and G. This is only available through the Army or FEMA.

Human Botulism Immune Globulin

• Treatment for Infant Botulism
• As compared with the control group in the randomized trial, infants treated with BIG-IV had a reduction in the mean length of the hospital stay, the primary efficacy outcome measure, from 5.7 weeks to 2.6 weeks
• No serious adverse effects
• In the open-label study, infants treated with BIG-IV within seven days of admission had a mean length of hospital stay of 2.2 weeks, and early treatment with BIG-IV shortened the mean length of stay significantly more than did later treatment

Diagnostic Tests/Lab Tests/Lab Values

Primary Diagnostic Tool

• Confirmed with the "demonstration of the toxin in specimens of patient serum, gastric secretions, or stool or in a food sample." If the organism Clostridium botulinum is found in the patient's stool or in a wound (found through a culture) then a diagnosis of a botulism syndrome can be confidently used. 
• This test is confirmed using a bioassay, which measures the amount of concentration in a sample. 
• The test was standardized through the use of mice injected with the organism. 
• For food botulism the samples taken for testing include: gastric secretions, vomitus, stool samples, as well as suspected foods.  For wound botulism a sample of serum and anaerobic wound material is needed.  For infant botulism, the preferred sample is a stool sample.
• The laboratory tests have had sensitivities reported as low as 33-44% but can vary with time of onset of symptoms. If a sample is taken more than one week after an ingestion of the organism the toxin may not be present in serum.  However, it may be present in the patient's stool.

EMG Evaluation of Suspected Cases of Infant Botulism

• Motor and sensory nerve conduction velocity in one arm and one leg
• Diagnostic triad for infant botulism: 1) Compound muscle action potentials of decreased amplitude in at least two muscle groups. 2) Tetanic and post-tetanic facilitation defined by an amplitude of more than 120 percent of baseline. 3) Prolonged post-tetanic facilitation of more than 120 seconds and absence of post-tetanic exhaustion.
• The EMG evaluation is used to assist in the primary tests mentioned above.

                              

Different Causes of Botulism

1) Food Borne Botulism: This is caused by the ingestion of foods contaminated with botulinum toxin. Home canned foods as well as a number of Alaska Native dishes (dishes that are fermented and consumed without cooking) are the main reasons for intoxication of individuals in the U.S.

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File:Wound botulism2.JPG

Wound Botulsim

2) Wound Botulism: This type is caused by the contamination of the wound with the organism's spores from the environment as well as the subsequent germination of the spores as well as production of the toxin in the perfect environment of an abscess. This type of botulism has been increasing in incidence since the early 1990's specifically due injection drug users. The injection drug associated individuals with botulism used a specific type of preparation of heroin.  This was called "black tar heroin."As well as the different preparation, the patient injected the drug subcutaneously.                                                 

                                               

                                                                      

3) Infant Botulism: This results from ingested spores that germinate and colonize in the infant's GI tract, initially at the cecum.  At this point the ileocecal valve might allow the colonizing bacteria to extend into the ileum.  After colonization the toxin is produced and absorbed throughout the intestines. At this point the toxin begins it's block on the neruomuscular junctions inhibiting contractions. The only identified food associated with infantile botulism is honey.  It only accounts for a handful of the cases, but because of the correllation shown the FDA and CDC reccomends that you do not give honey to your chile under the age of one.

4) Adult Intestinal Toxemia Botulism: Results from absorption of toxin produced by rarely occurring intestinal colonization in a few adults by botulinum toxin producing Clostridia. This is also associated with anatomical or functional bowel abnormalities in the individual. This type of botulism is considered sporadic, meaning the symptoms come and go.

5) Inhalational Botulism: This is one of the non naturally occurring types of botulism. Symptoms resemble food borne botulism.  Deliberate spraying of this toxin could cause an outbreak of the disease.

6) Iatrogentic Botulism: Caused by the injection of botulinum toxin for cosmetic or medical treatments.  Most of the time cosmetic doses are too low, but high doses are used for disorders such as cerebral palsy.

Systemic Involvement

Cadiovascular:

• Most cases are accompanied by normal vital signs and blood pressure.
• The normal blood pressure is a result of a vagal blockade as well as extensive peripheral vasodilation which are both caused by the toxin.
• In some cases the individuals will present with hypotension.

Neuromuscular:

• Cranial nerve palsies mentioned above
• Paralysis starting from proximal to distal
• Progressive disappearance of deep tendon reflexes
• Loss of muscle tone

Gastrointestinal:

• Constipation almost always occurs in individuals with botulism

Urinary:

• Individual may have the inability to urinate

Respiratory:

• Paralysis of diaphragm and accessory breathing muscles possibly leading to respiratory arrest.

Central Nervous System:

• Infants occasionaly have seizures

Medical Management (current best evidence)

Supportive Intensive Care,:

• Development of modern intensive care helped decrease the mortality rate among patients from 60-70% early in the 1900's to the current rate of 3-5%
• Patients diagnosed with botulism should be placed immediately in the ICU.
• Patient may need mechanical ventilation in a further progressed case.
• Frequent monitoring of vital capacity is also necessary
• Patient may need a nasogastric feeding tube
• Physical and Occupational Therapy while in supportive care

Antitoxin Therapy:

• The antitoxin is administered as soon as possible leading to a very promising rate of success
• The antitoxin can prevent the disorder from worsening but it still may take many weeks for a full recovery.
• Side effects include anaphylaxis, hypersensitivity reactions, and serum sickness 

Isolation and Infection Control:

• Standard precautions should be taken when evaluating and treating patients.
• While Botulinum Toxin cannot be absorbed through intact skin, it can be absorbed through the eye, mucosal surfaces, and non intact skin.
• Following a food history taken by the physician, it is necessary to contact the appropriate authorities

Surgical Intervention:

• Surgical debridement should be performed on a wound infected with the C. botulinum spores.
• Following the debridement, the wound should be cleaned and appropriate antimicrobial therapy should be provided.

Physical Therapy Management (current best evidence)

Physical therapists will be a part of the supportive care team that is required for individuals with botulism. Their recovery will be dependent on the administering of the antitoxin as well as the help of the supporting staff to get the individual back to their normal selves. Some interventions are listed below, but the physical therapy management of a patient with botulism could be handled many different ways. 

Breathing Exercises:

• Since respiratory failure is the primary cause for death in individuals with botulism it is very important to try to maintain controlled breathing as long as possible.
• Diaphragmatic controlled breathing will be important to try to maintain quality control of the respiratory cycle.
• Pursed lip breathing will be beneficial as well. The goal of this exercise will be to improve gas mixing at rest, decrease the mechanical disadvantage the individual might develop during the progression of botulism, and finally pursed lip breathing can reduce premature collapse of airways.

ROM Exercises:

• It is important for the patient to keep their joints moving as much as possible during their time in the hospital. ROM will begin as active until the patient loses function. The exercises will need to be continued passively if the individual has developed paralysis of the extremities.

Strengthening Exercises:

• Immobilization can do a lot of damage to the muscles of the body and it is the job of the physical therapist to keep the individual working on strengthening those muscles. In a patient with botulism it will be important to try to maintain the function as long as possible. While this is a progressive disease when the antitoxin is not administered, having the patient perform isometric exercises in their hospital bed can only help maintain that control and activation of the muscles until they finally fall to the toxin.
• Some exercises that would be effective include: Quad sets, Glut Sets, Short Arc Quads, Abduction at shoulders, bicep curls, etc.
• The hypotonicity associated with botulism needs the attention from the physical therapist from day one. The individuals will benefit from manual facilitation, verbal cueing, and numerous repetitions of motions. One would assume that a lot of the treatments would be similar to that of guillain barre syndrome.  Both of these diseases can expect a good recovery when the appropriate measures are taken and physical therapy is a key ingredient to the patient's success.

Other Important Items:

• It is very important for the physical therapist to continue with communication to the patient in any way possible. In a progressed stage of botulism, communication may only be made through the movement of a single toe, but the patient will still be cognitively intact. It will be necessary to assess the patient's status before administering PT. This will not only help the therapist with thier treatments, they will be able to educate the individual and their family.
  

Differential Diagnosis

• Guillain-Barré Syndrome
• Myasthenia Gravis
• Stroke Syndromes
• Eaton-Lambert syndrome
• Tick Paralysis
• Tetrodotoxin
• Shellfish Poisoning

Case Reports/ Case Studies

1. Manfredi M, Scoditti U, Angelini M, de Giampaulis P, Borrini BM, Macaluso GM, Pavesi G, Vescovi P. Dry mouth as an initial sign of food borne botulism: a case report and review of the literature. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, And Endodontics. 2011 Apr; Vol. 111 (4), 15-18. Available at: 
   http://ck8zf4yc8t.search.serialssolutions.com.libproxy.bellarmine.edu/?genre=article&isbn=&issn=1528395X&title=Oral+Surgery%2c+Oral+Medicine%2c+Oral+Pathology%2c+Oral+Radiology%2c+And+Endodontics&volume=111&issue=4&date=20110401&atitle=Dry+mouth+as+an+initial+sign+of+food-borne+botulism%3a+a+case+report+and+review+of+the+literature.&aulast=Manfredi+M&spage=e15&sid=EBSCO:MEDLINE&pid=
2. Pujar T, Spinello IM. Chest. A 38-year-old woman with heroin addiction, ptosis, respiratory failure, and proximal myopathy. 2008 Oct;134(4):867-70.Pujar T, Spinello IM. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18842921
3. Barash JR, Tang T, Arnon S. First case of infant botulism caused by Clostridium baratii type F in California. J Clin Microbiol. 2005 August; 43(8): 4280–4282. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1233924/
4. Bhatia K, Münchau A, Thompson P, Houser M, Chauhan V, Hutchinson M, Shapira A, Marsden C. Generalised muscular weakness after botulinum toxin injections for dystonia: a report of three cases. J Neurol Neurosurg Psychiatry 1999;67:90–93. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1736426/pdf/v067p00090.pdf
5. Fenicia L, Ferrini AM, Aureli P, Pocecco M. A case of infant botulism associated with honey feeding in Italy. Eur. J. Epidemiol. November 1993. 671-673. Available at: http://ck8zf4yc8t.scholar.serialssolutions.com/?sid=google&auinit=L&aulast=Fenicia&atitle=A+case+of+infant+botulism+associated+with+honey+feeding+in+Italy&id=doi:10.1007/BF00211445&title=European+journal+of+epidemiology&volume=9&issue=6&date=1993&spage=671&issn=0393-2990

Resources

1. World Health Organization: http://www.who.int/mediacentre/factsheets/fs270/en/
2. Center for Disease Control and Prevention: http://www.cdc.gov/ncidod/dbmd/diseaseinfo/files/botulism_manual.htm
3. Journey to Perplexity: Botulism: http://iamyouasheisme.wordpress.com/2010/02/10/botulism/
4. Phil Strandwitz: Botulism: http://bioweb.uwlax.edu/bio203/s2008/strandwi_phil/new_page_1.htm
5. Pub Med: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001624/