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[Health Department Name] [Unit Name] [Street] [City, State, Zip Code] Phone: [insert number] Fax: [insert number] [Email Address], [Website] [Insert Logo] BOTULISM HEALTH ALERT [INSERT DATE] [Insert short description why Health Alert is being released (e.g., Two cases of botulism have been identified)]. This Health Alert is posted on the [insert website name] at [insert web link]. ACTIONS REQUESTED OF ALL CLINICIANS: 1. Be alert for cases of botulism. 2. Report suspect cases to [insert unit/department name] at [insert phone number]. [Insert party responsible for testing and release of antitoxin] can facilitate testing and release of antitoxin. 3. Consider Neurology and Infectious Disease consultation. 4. Obtain serum for toxin assays (in serum separator tubes). INCIDENT SUMMARY [Insert event-specific background information (e.g., Suspected aerosol release of botulism toxin)]. DESCRIPTION Botulism is a muscle-paralyzing disease caused by a toxin made by a bacterium called Clostridium botulinum. There are seven serotypes of the toxin, labeled A-G. Types A, B, and E (and rarely, F) cause natural diseases in humans. C. botulinum can also release spores that are resistant to chemicals, heat, and drying, which allows them to remain persistent in the environment even under the most unfavorable conditions. These spores can later produce growing cells that are capable of making the botulism toxin. There are three naturally occurring forms of botulism: Foodborne botulism: Occurs when a person ingests pre-formed toxin that leads to illness within a few hours or a few days. Wound botulism: Occurs when wounds are infected with C. botulinum that secretes the toxin. Since 1988 it has been predominantly associated with subcutaneous or intramuscular black tar heroin use. Intestinal botulism: Occurs in a small number of susceptible infants per year who harbor C. botulinum in their intestinal tract. Rarely occurs in adults. Additionally, there is a man-made form of botulism: Inhalation botulism: Results from the aerosolized botulism toxin, has been demonstrated experimentally in primates, and has been attempted by bioterrorists. Botulism toxin is considered a bioweapon because of its extreme potency, lethality, and the need for prolonged intensive care among infected persons. This health alert focuses on foodborne and inhalational botulism because they are the forms most likely to occur following a botulism release. Categories of urgency levels Health Alert: Conveys the highest level of importance; warrants immediate action or attention. Health Advisory: Provides important information for a specific incident or situation; may not require immediate action. Health Update: Provides updated information regarding an incident or situation; unlikely to require immediate action. [Insert Health Department Name] CASE DEFINITION The following definitions should be used to identify exposed persons and cases. Testing, treatment, and implementation of infection control measures should be based upon these definitions. BOTULISM: CASE DEFINITION (Excluding Intestinal Botulism) Categorization Definition Foodborne 1. Potentially Exposed Person 2. Probable Case 4. Confirmed Case Inhalation A person who [insert type of food consumed A person in the proximity of [insert /location present] during [insert timeframe event/place] during [insert timeframe (note: (note: incubation period is usually within 8 incubation period for aerosol release is days)] usually within 36 hours)]. Meets: 1) Potentially exposed person case definition; AND 2) Has clinical symptoms compatible with botulism: Diplopia Blurred vision Bulbar weakness Symmetric paralysis, which may progress rapidly 1) Clinical symptoms compatible with botulism; AND 1) Clinical symptoms compatible with botulism; AND 2a) Laboratory-confirmed Detection of botulinum toxin in serum, stool, or patient's food, or Isolation of C. botulinum from stool OR 2b) Occurs among persons who [ate the same food/had the same exposure (insert specific food or exposure)]as persons who have laboratory-confirmed botulism. 2a) Laboratory-confirmed: Detection of botulinum toxin in clinical specimen Isolation of C. botulinum from clinical specimen OR 2b) Occurs among persons [who had the same exposure(insert exposure)] as persons who have laboratory-confirmed botulism. CLINICAL FEATURES The disease manifestations of botulism are similar, regardless of botulism type. Botulism may be recognized by its classic triad: 1) Symmetric descending flaccid paralysis with prominent bulbar palsies (diplopia, dysarthria, dysphagia, and dysphonia), in 2) An afebrile patient, with 3) A clear sensorium The following clinical features should be noted for suspected cases of botulism: Last revised: 5/4/2017 Page 2 of 6 [Insert Health Department Name] BOTULISM: CLINICAL FEATURES Incubation Period§ Transmission FOODBORNE INHALATION 2 hours – 72 hours (range 2 hrs – 8 days) 24-36 hours (aerosol*) Ingestion of preformed toxin Inhalation of preformed toxin Early Presentation – cranial nerve abnormalities • Dysarthria • Blurred and/or double vision • Dry mouth • Ptosis • Symptoms may be slow in onset or rapidly progressive (dosedependent) Later Presentation – descending paralysis Dysphonia, dysphagia Symmetrical, descending progressive muscular weakness Dilated or fixed pupils Decreased gag reflex Signs & Respiratory failure Symptoms Autonomic nerve dysfunction; may include urinary retention, orthostasis Normal mental status, though may appear lethargic and have difficulty with communication Normal sensory nerve function Afebrile unless there is complicating infection Normal CSF glucose, protein, cell count Normal CBC Normal imaging of brain and spine (CT scan or MRI) Laboratory Characteristic EMG findings include: Findings Incremental response (facilitation) to repetitive stimulation at 50 Hz Short duration of motor unit potentials Normal sensory nerve function Normal nerve conduction velocity * Time to onset of inhalational botulism cannot be stated with certainty because so few cases are known. Monkeys showed signs of botulism in 12-80 hours, and the 3 known human cases had an onset of symptoms at approximately 72 hours. § Incubation period is dose-dependent Differential Diagnosis Botulism is frequently misdiagnosed, most often as a polyradiculoneuropathy (Guillain-Barré or Miller-Fisher syndrome), myasthenia gravis, or disease of the central nervous system. Botulism differs from other flaccid paralyses in its prominent cranial nerve palsies disproportionate to milder weakness and hypotonia below the neck, in its symmetry, and in its absence of sensory nerve damage. Note: A careful travel, activity, and dietary history should be taken in any suspected botulism outbreak. Patients should also be asked if they know others with similar symptoms. Last revised: 5/4/2017 Page 3 of 6 [Insert Health Department Name] REPORTING Immediately report all cases of botulism (including suspect cases) to your facility’s infection control practitioner AND to [Insert Unit/Department Name]: [Insert Phone Number]. The health department can authorize and facilitate testing, and will initiate the public health response as needed. Please either ask family members and close contacts of patients for their telephone contact information, or ask these individuals to stay at the hospital for public health interview and potential intervention. INFECTION CONTROL Infection Control for Caregivers Person-to-person transmission does not occur in botulism. Standard Precautions are adequate for the care of patients with botulism. Patients do not require isolation. See http://www.sfcdcp.org/document.html?id=317 for key features of standard infection control precautions. Decontamination Botulism toxin is easily destroyed. Heating to an internal temperature of 85ºC for at least 5 minutes will detoxify any contaminated food or drink. All suspected food or drink should be promptly removed from potential consumers and submitted to public health authorities for testing. It is estimated that in the case of aerosolized botulism, substantial inactivation of the toxin occurs by 2 days after aerosolization (although this is dependent upon specific atmospheric conditions and particle size of the aerosol). Clothing and skin should be washed with soap and water after exposure to botulism toxin. Contaminated objects or surfaces should be cleaned with a 0.1% hypochlorite bleach solution if they cannot be avoided for the hours or days required for natural degradation. Spores are hardy, resistant to desiccation, heat, UV light, and alcohols, and can survive boiling up to 4 hours. They are, however, readily killed by chlorine solutions. LABORATORY & DIAGNOSTIC TESTING Consider testing symptomatic persons. Asymptomatic persons need not be tested. If you are testing or considering testing for botulism: 1. Immediately notify: a. [Insert Unit/Department Name]: [Insert Phone Number]. The health department can authorize and facilitate testing and will initiate the public health response as needed; AND b. Your hospital laboratory and infection control practitioner that botulism is under suspicion; AND 2. If testing is deemed necessary: a. Use appropriate precautions when obtaining diagnostic specimens. b. Specimens to be obtained should include: i. Serum (Preferred specimen for food borne, wound botulism and intentional release): Collect 30 cc whole blood as soon as possible after symptom onset and before antitoxin administration). Do not ship whole blood, which tends to become hemolyzed during transit. Notify testing lab if patient has received "stigmine drugs" or a Tensilon test. Keep specimen refrigerated at all times. ii. Food: Generally, public health officials will obtain food specimens. Clinicians can facilitate testing by asking patients not to throw away food from recent meals or to empty garbage containing food items. Potentially contaminated food samples may be collected (10-50 gm), sealed, and transported under refrigeration. Last revised: 5/4/2017 Page 4 of 6 [Insert Health Department Name] iii. Stool: Stool specimens are rarely used and should only be collected if advised by your health department. c. Submit specimens to your hospital laboratory, and notify them to test for botulism. If needed, your lab will submit specimens to the public health laboratory for testing. i. Transport specimens at 4ºC immediately to the laboratory. *Note: Diagnosis and appropriate treatment primarily depends on the basis of clinical presentation. Laboratory confirmation often requires 1-4 days to complete and is performed only at reference laboratories. Test results may be negative if the samples were collected late or the quantity of toxin is small; thus lack of detection of botulinum toxin does not necessarily rule out the diagnosis of botulism. TREATMENT AND PROPHYLAXIS Supportive care is the mainstay of care for botulism, including: Timely administration of botulinum antitoxin Mechanical ventilation Parenteral nutrition Ventilatory support may be required for several weeks or more Note: Aminoglycosides and clindamycin are contraindicated for treatment of secondary infections since they may exacerbate the neuromuscular blockade. Botulism Antitoxin Treatment Botulinum toxin binds to cholergenic neurons and blocks acetylcholine release, which causes the affiliated muscle to become paralyzed. Normal functioning resumes slowly, either through production of new synapses or turnover of proteins, which can take up to a few months. Botulism antitoxin only binds to toxin circulating in the blood, and does not affect toxin that has already bound to the neuron or reverse existing paralysis. To obtain antitoxin, phone [Insert Health Department/Unit Name]: [Insert 24 hour phone number]. If the clinical picture is compatible with botulism, antitoxin may be released emergently (within 12 hours). Antitoxin is most effective when given within 24 hours after symptom onset. Antitoxin cannot reverse any existing paralysis, but can slow progression of further disease and potentially decrease the duration of ventilatory support and increase the likelihood of survival. The supply of antitoxin is very limited. Decisions to release antitoxin will be made in consultation with local and state public health authorities. Antitoxin Type and Dose: The currently available formulation is botulinum antitoxin bivalent for types A and B (licensed by FDA). Botulinum antitoxin type E is investigational. A trivalent preparation (types A, B, E) has been discontinued. The military is testing a heptavalent antitoxin (type A through G). One 10-ml vial of each preparation of antitoxin is sufficient to neutralize circulating toxin from most naturally occurring intoxications. A repeat dose is not usually necessary. Antitoxin Hypersensitivity: Since antitoxin is of equine origin, hypersensitivity reactions, including anaphylaxis, serum sickness, and febrile reactions have occurred in up to 9% of patients receiving antitoxin. Skin testing for hypersensitivity should be performed in all patients before administering antitoxin. If skin testing is positive, the patient can be desensitized over several hours before the full dose of antitoxin is administered. Diphenhydramine and epinephrine should be available during administration. Last revised: 5/4/2017 Page 5 of 6 [Insert Health Department Name] No Prophylaxis of Exposed, Asymptomatic Persons There is currently no available post exposure prophylaxis for asymptomatic exposed persons. Such persons should be: 1. Educated regarding the signs and symptoms of clinical botulism 2. Instructed to seek medical care immediately if symptoms occur Exposed persons and their families may experience anxiety and/or somatic symptoms that may include neurologic symptoms. These patients should be carefully assessed. Antitoxin supplies are limited, and therapy will be reserved for patients with compatible neurological findings. Pre-exposure immunization with botulinum toxoid is restricted to certain laboratory and military personnel. Supplies are extremely limited and would not be available for the public. ADDITIONAL RESOURCES [Add your health department name and link.] CDC Emergency Preparedness & Response Bioterrorism Site: www.bt.cdc.gov/bioterrorism Working Group on Civilian Biodefense: http://jama.ama-assn.org/cgi/content/abstract/285/8/1059 Health Protection Agency Deliberate Release: www.hpa.org.uk/infections/topics_az/deliberate_release/menu.htm REFERENCES Arnon SS et al, for the Working Group on Civilian Biodefense. Botulinum toxin as a biological weapon: medical and public health management. JAMA 2001;285(8):1059-81. CIDRAP. Botulism: Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment, and prophylaxis. June 16, 2005.(www.cidrap.umn.edu/cidrap/content/bt). CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(RR10):1-55 http://www.cdc.gov/mmwr/preview/mmwrhtml/00047449.htm. CDC. Biosafety in microbiological and biomedical laboratories (BMBL). Ed 4, Apr 1999. Section VIIA: Bacterial agents: Clostridium botulinum. Last revised: 5/4/2017 Page 6 of 6