BOTULISM (SAUSAGE POISON) CA: Botulinum toxin derived from Clostridium botulinum IP: 2 hrs to 8 days MOT: foodborne

Inhalational: manmade aerosolized form can be used as weapon of bioterrorism Ss

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: Classic triad of botulism: 1. acute, symmetric, descending flaccid paralysis with prominent bulbar palsies 2. no fever 3. clear sensorium Features of bulbar palsy present in >90% patients: diplopia , dysarthria, dysphonia, dysphagia (difficulty with seeing, speaking and swallowing) Blurry vision with ptosis, diplopia, enlarged pupils with sluggish reactions Flaccid paralysis progresses in descending manner- loss of head control, generalized weakness and hypotonia, loss of deep tendon reflexes (in days), airway obstruction and respiratory muscle paralysis requiring ventilatory support Death results from airway obstruction and respiratory muscle paralysis Gastrointestinal symptoms present in foodborne botulism- abdominal cramps, nausea, vomiting, diarrhea

Dx:
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based on clinical features for initial management EMG (electromyography) may helpful in establishing diagnosis: o normal NCV (nerve conduction velocity) and sensory nerve function o a pattern of brief small amplitude motor potentials o a repetitive nerve stimulation at 20-50 Hz may show a characteristic incremental response. Laboratory diagnosis: Botulinum toxin is identified by mouse bioassay, which can detect as little as 0.03ng of the toxin. o Botulinum toxin assay is available in CDC and state labs o samples of serum, gastrointestinal content and suspected source (e.g. food) should be collected and tested for botulinum toxin o Fecal and gastric samples can also be cultured anaerobically. Takes 7-10 days (range 520 days). o Acceptable specimens (for testing at higher-level LRN laboratories)  Clinical specimens: gastric contents, exudates, tissues, serum, etc.  Postmortem specimens  Culture/isolate  Food samples (solid or liquid)  Environmental samples: soil, water o Precautions

These procedures should be performed in microbiology laboratories that use Biological Safety Level-2 practices.  Level A Laboratories should not attempt to culture, identify the organism, or attempt to perform toxin analysis. Enzyme linked immunosorbent assay from nasal mucosa taken within 24 hours of exposure has been used by military for detection of aerosolized toxin [5]. Alternative in vitro assays, amplified ELISA and PCR are under development [9,10,16]. CSF remains normal but may be useful to differentiate from other CNS causes.


Treatment:
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Passive immunization: o Botulinum antitoxin is an equine antitoxin available from CDC via state and local health departments in USA. It contains neutralizing antibodies against A, B and E. o A heptavalent (A-G) investigational antitoxin is held by US Army. o A human antitoxin (Human Botulism Immune Globulin, HBIG) is available as an investigational agent for infant botulism (California Department of Public Health) [15] o Each 10ml vial of trivalent equine antitoxin (ABE) contains 5500-8500 IU of antibodies of each type, and is administered IV after diluting 1:10 with 0.9% saline. o Administer as soon as possible after clinical diagnosis to minimize neurological progression. It does not reverse existent paralysis. o One vial of antitoxin is generally enough for food borne botulism. o In case of intentional exposure, adequacy can be confirmed by retesting serum for toxin after administering usual dose of antitoxin. o Children, pregnant women and immunocompromized group have been treated with equine antitoxin safely. o Side effects: serum sickness (2%), urticaria (9%), mild hypersensitivity (18%), anaphylaxis (2%). Skin test followed by desensitization in patients with wheal and flare should be done by administering incremental doses over 3-4 hours. [3] Supportive care o reverse trendelenberg positioning (20-250) for airway protection and improved respiration o assisted ventilation required in 20% adults and 60% infant botulism o fluid and nutritional support o treatment of complications including secondary infections Role of antibiotics in treatment of botulism remains unclear, but penicillin G has been recommended to treat wound botulism. Antibiotics are also useful in treatment of secondary infections. Aminoglycosides and clindamycin are contraindicated because of their ability to exacerbate neuromuscular blockade.

Prevention:
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Botulinum toxoid o a pentavalent (ABCDE), investigational vaccine is available for high risk laboratory personnel and military. Its efficacy tested during Gulf war showed good immunogenic response with a second booster (28% with first, 97% with booster). [12]

A tetravalent vaccine (ABEF) tested in Japan seems to need 3 or more doses [13]. A candidate vaccine against botulinum neurotoxin serotype A (BoNT/A) developed by using Venezuelan equine encephalitis (VEE) virus vector is also being tested [17] Postexposure prophylaxis o Early treatment with antitoxin after exposure to botulinum toxin has been shown to reduce neurological manifestations. o To balance between the need of scarce equine antitoxin with its potential side effects and the advantages of early treatment after an intentional or unintentional outbreak, it has been suggested to closely observe exposed patients and administer antitoxin when early signs appear. o CDC maintains US Botulism Surveillance System and releases antitoxin through its network within United States. CDC also provides antitoxin to other countries of Western Hemisphere through its contract with PAHO (Pan American Health Organization) with exception of Canada. Canada has its own supply of botulinum antitoxin. [11] Decontamination: o Botulinum toxin can be destroyed by heating food and drink to core temperature of 850 C for 5 minutes, but all suspected food should be removed and sent to Public Health Department for testing. o wash exposed clothes and skin with soap and water o clean objects and surfaces with 0.1% hypochlorite bleach solution o covering mouth and nose with clothing provides some protection from aerosolized toxin Infection Control: standard precautions only
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