North Central District Health Department Botulism A Bioterrorism Agent Presented by: Donna Anderson, RN Staff Epidemiologist North Central District Health Department April 6, 2006 Botulinum toxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. An outbreak of botulism constitutes a medical emergency that requires prompt provision of botulinum antitoxin and, often, mechanical ventilation, and it constitutes a public health emergency that requires immediate intervention to prevent additional cases. Timely recognition of a botulism outbreak begins with an astute clinician who quickly notifies public health officials.

What is Botulism The Illness The Germ Clostridium botulinum Therapeutic use of botulinum toxin How common is botulism Illness in US Incidence<200 annual cases all forms Disease: Botulinum toxin is a remarkably poisonous substance. While it has a variety of medical uses, it is also of interest and concern to physicians because of its involvement in food poisoning and its potential use as an agent of bioterrorism. Agent: Botulinum toxin is an enzyme produced by Clostridium botulinum, a spore-forming bacillus. One gram of crystalline botulinum toxin is enough to kill 1 million people. The toxin blocks the neuromuscular junction which results in flaccid paralysis of muscles. Source: Botulism is worldwide in distribution. The spores are ubiquitous; are found in soils, airborne dust, surfaces of raw fruits and vegetables and seafood throughout the world. Hardy and heat resistant. Discovered bacterium in 1895 Belgium but the first complete description of the botulism was published in the mid 1800’s Germany, the toxin was linked to consumption of smoked sausage. It was named botulus, which means sausage in latin. Therapeutic use of botulinum toxin: Botox frown lines. Packaged in dilute preparations so not feasible to weaponize Focal dystonias – involuntary, sustained, or spasmodic patterned muscle activity Spasticity – velocity-dependent increase in muscle tone Nondystonic disorders of involuntary muscle activity Strabismus (disorder of conjugate eye movement) and nystagmus Disorders of localized muscle spasms and pain Cosmetic use Sweating disorders Sporadic cases, outbreaks in families, and general outbreaks occur when food products are not prepared or preserved using proper methods. An average of 9 or 10 outbreaks occur each year in the United States. US Largest 20th Century outbreak of food-borne botulism. Michigan 1977 59 cases from home-preserved jalapeno peppers at a restaurant Approx 9 annual outbreaks of food-borne with average of 24 cases Mortality 25% prior to 1960 6% during the 90’s

Categories of Botulism Foodborne botulism Intestinal botulism (infant and child/adult) Wound botulism Inhalation botulism Foodborne botulism Caused by eating foods that contain botulism toxin Intestinal botulism (infant and child/adult) Caused by ingesting spores of the bacteria which germinate and produce toxin in the intestines Wound botulism C. botulinum spores germinate in the wound Inhalation botulism Aerosolized toxin is inhaled Does not occur naturally and may be indicative of bioterrorism

Usually Seen Following…. Home-canned goods (foodborne) Particularly low-acid foods such as asparagus, beets, and corn Honey (ingestion) Can contain C. botulinum spores Not recommended for infants <12 month old Crush injuries, injection drug use (wound)

Botulism Prevention Proper Canning Proper heating of home canned foods No honey for < 1 year olds Seek medical care for wounds Avoid injectable street drugs Botulism vaccine

Botulism: As a Weapon Weaponized by several nations including the U.S., Japan, and Soviet Union, beginning in the 1930’s Iraq (1980’s) produced 19,000 L of concentrated botulism toxin Japan (1990’s) Aum Shinrikyo cult

What Makes Botulism Toxin a Good Weapon? Extreme potency and lethality Ease of production Difficult to distinguish intentional exposures Expensive, long-term care needed for recovery Botulism toxin is the most poisonous substance known High lethality: 1 aerosolized gram could potentially kill 1 million people Isolated fairly easily from soil Could be released as an aerosol or as a contaminant in the food supply Ease of transport

What causes illness Incubation period varies with type of poisoning Toxin enters bloodstream from mucosal surface or wound Binds to peripheral nerve endings Preventing muscles from contracting Incubation period Depends on inoculated dose Ingestion: unknown Foodborne: 6 hours – 8 days Wound: 4 – 14 days Inhalation: (estimated) 24 – 36 hours Toxin enters bloodstream from mucosal surface (gut or lungs) or wound (break in skin) Intact skin not penetrated Binds to peripheral cholinergic nerve endings Inhibits release of acetylcholine, preventing muscles from contracting All forms of disease lead to same process

And then……. Symmetrical, descending paralysis occurs beginning with cranial nerves and progressing downward Can result from airway obstruction or paralysis of respiratory muscles Secondary complications related to prolonged ventilatory support and intensive care Symmetrical: Lose head control Lose gag- require intubation Lose diaphragm- require mechanical ventilation Loss of deep tendon reflexes Gastrointestinal/Urinary: N/V/D Abd pain, Intestinal ileus, urinary retention Neurologic : Dry mouth, blurry vision, diplopia,dilated or unreactive pupils dysphagia, decreased gag reflex Muscular: Symmetrical skeletal muscle weakness, respiratory muscle paralysis, fatigue, dyspnea

Classic symptoms of botulism poisoning include: Blurred/double vision Muscle weakness Drooping eyelids Slurred speech Difficulty swallowing Patient is afebrile and alert Infants with botulism will present with: Weak cry Poor feeding Constipation Poor muscle tone, “floppy” baby syndrome

How is it Diagnoses? Toxin neutralization mouse bioassay Serum, stool, gastric aspirate, suspect foods Isolation of C. botulinum or toxin Feces, wound, tissue Collect samples for diagnostic testing Serum, vomit, gastric aspirate, suspect food , stool Collect serum before antitoxin is given If enema required, use sterile water Refrigerate samples and suspect foods Confirmation takes 1-4 days Available at CEC and State Labs Culture results in 7-10 days

Botulism Treatment Closely monitor known/suspected exposed Treat with antitoxin at first sign of disease Elimination Induced vomiting High enemas Supportive care Mechanical ventilation Body positioning Parenteral nutrition Antitoxin adverse effects Serum sickness (2-9%),anaphylaxis (2 %) Recovery takes weeks Special groups-same treatment : children, pg. women, immunocompromised

Botulism Antitoxin Equine antitoxin Effective in the treatment of foodborne, intestinal, and wound botulism Effectiveness for inhalation botulism has not been proven Does not reverse current paralysis, but may limit progression and prevent nerve damage if administered early Trivalent and bivalent antitoxins available through the CDC Licensed trivalent antitoxin neutralizes type A, B, and E botulism toxins

Call North Central District Health What do I do now? Immediately Call North Central District Health if during office hours (208) 799-3100 or State Communications Public Health Paging System (24/7) Public Health will be paged 1 800 632-8000 What to do at first suspicion of a case Immediately notify Public Health Acquire therapeutic antitoxin Get medication list to rule out anticholinsterases

Botulism Infection Control Botulism cannot be transmitted person-to-person Standard precautions should be taken when caring for botulism patients

Decontamination Aerosolized toxin viability Inactivate by 2 days in optimal conditions Re-aerosolization a theoretical concern Mask over the face may be protective Exposed clothing and surfaces Wash with 1:10 hypochlorite solution

Botulism Talk Takeaways Disease caused by C. botulinum toxin Most toxic substance ever identified Known to be weaponized Classic Signs and Symptoms Symmetric, descending flaccid paralysis No fever Alert

Botulism Talk Takeaways Clinical diagnosis Report to State/Local Health Department ASAP Start antitoxin ASAP Supportive care Recovery may take weeks