and potential as a bioweapon
is a major threat as a bioweapon due to its extreme potency and ability to cause
death, its ease of production and transport, and the need for prolonged intensive
care among survivors. Botulinum toxin is the most poisonous substance known
to man. A single gram of crystalline botulinum toxin, evenly dispersed and inhaled,
could kill more than 1 million people. It is 15,000 to 100,000 times more toxic
than sarin, the destructive nerve agent used in the Tokyo subway system.
already been several attempts by terrorists to use botulinum toxin as a bioweapon.
Botulinum aerosols were dispersed at multiple sites in Japan, including U.S.
military installations, on at least 3 occasions between 1990 and 1995, by the
Japanese cult Aum Shinrikyo. Fortunately, the attacks failed due to inadequate
microbiological technique, deficient aerosolized generating equipment, or internal
sabotage. The cult members obtained their botulism spores from soil collected
in northern Japan. Botulinum toxin was also used in the 1930s, during
the Japanese occupation of Manchuria. Although the 1972 Biological and Toxin
Weapons Convention prohibited offensive research and production of biological
weapons, at least four of the countries listed by the U.S. government as state
sponsors of terrorism Iran, Iraq, North Korea, and Syria, have developed,
or are believed to be developing, botulinum toxin as a weapon. After the 1991
Persian Gulf War, Iraq admitted to the United Nations inspection team that they
produced 19,000 liters of concentrated botulinum toxin, of which approximately
10,000 liters were loaded onto military weapons. These 19,000 liters of concentrated
toxin are not fully accounted for and constitute approximately 3 times the amount
needed to kill the current human population by inhalation.
The neurotoxic agent sarin is the most poisonous substance known.
effects of a potent neurotoxin produced from Clostridium botulinum create botulism,
an anaerobic, spore forming bacterium whose natural habitat is soil. There are
seven recognized types of botulinum neurotoxins. Human botulism is caused by
strains of botulism that produce toxin types A, B, and E. Botulinum toxin blocks
the transmission of acetylcholine across the junction between nerves and muscles,
producing muscle paralysis, including paralysis of respiratory muscles. The
picture shows a six month old suffering extreme flaccid paralysis produced by
botulinum toxin. Note the lack of muscle tone, especially at the neck.
of naturally occurring human botulism exist: foodborne, wound, and intestinal.
Fewer than 200 cases of all forms of botulism are reported annually in the U.S.
All forms of botulism result due to absorption of botulinum toxin into the circulation
either from a mucosal surface such as the intestine or lung, or from a wound.
Botulinum toxin does not penetrate intact skin. Inhalational botulism is a man-made
form that results from manufacturing botulinum toxin in an aerosol form and
distributing it among an unsuspecting population.
is colorless, odorless, and tasteless. The toxin is readily inactivated by heat;
thus, foodborne botulism is always transmitted by foods that are not heated,
or heated thoroughly before eating. The most commonly implicated foods in the
U.S. are home canned or home processed vegetables, meats, fish, fermented or
salted fish products, whale or seal products, relish, chili peppers, and salsa.
Foil wrapped baked potatoes kept at room temperature for long periods of time
after baking have also been the source of botulism in restaurants. Garlic cooked
in oil, sautéed onions kept in butter sauce, and cheese sauces have also
been implicated in outbreaks of foodborne botulism.
begin with cranial nerve dysfunction affecting the muscles of the head and neck.
The first symptoms include difficulty seeing, speaking, and/or swallowing. Prominent
neurological findings include ptosis or drooping eyelids, diplopia or double
vision, blurred vision, often enlarged or sluggishly reactive pupils, and difficulty
speaking and swallowing. Sensory changes do not occur except for hyperventilation
as the patient becomes frightened by the onset of paralysis. The rapidity of
onset and severity of botulism depend on the rate and amount of toxin absorption
into the circulation. Typically, patients who have foodborne botulism begin
to experience symptoms between 12 and 72 hours after the contaminated meal.
be recognized by a classic diagnostic triad
that includes symmetric, descending flaccid paralysis with prominent bulbar
palsies in an afebrile patient with a clear sensorium. Bulbar palsies refer
to weakness or paralysis of muscles of the head and neck needed for normal speech
and swallowing. The prominent bulbar palsies associated with botulism are also
known as the 4 Ds diplopia (double vision), dysarthria (difficulty
moving facial muscles to pronounce words). dysphonia (difficulty speaking),
and dysphagia (difficulty swallowing). As paralysis extends beyond bulbar musculature,
loss of head control, weakened muscle tone, and generalized weakness become
prominent. Dysphagia and loss of a protective gag reflex may require intubation
and mechanical ventilation. In untreated persons, death results from airway
obstruction due to pharyngeal and upper airway muscle paralysis and inadequate
tidal volume due to paralysis of the diaphragm and accessory muscles of respiration.
Botulism is frequently misdiagnosed, most often as Gullain-Barre syndrome, stroke, or myasthenia gravis. Botulism differs from other conditions causing flaccid paralysis in that its primary effects are:
Clinical diagnosis of botulism
is confirmed by specialized laboratory testing that often takes days to complete.
Routine lab tests are usually unremarkable. Therefore, clinical diagnosis is
the foundation for early recognition of and response to a bioterrorist attack
with botulinum toxin. Botulism and botulinum toxin are not contagious and cannot
be transmitted from person to person.
botulism consists of supportive care and passive immunization with botulism
antitoxin. Antibiotics have no effect on botulinum toxin. Administration of
antitoxin will minimize subsequent nerve damage and the severity of the disease,
but does not reverse already existing paralysis. Use of botulism antitoxin for
post exposure prophylaxis is limited by its scarcity and potential complications.
There are also few published data on the safety of botulism antitoxin. Due to
the potential risks of equine antitoxin therapy, it is less certain how to best
care for persons who have been exposed to botulinum toxin but who are not yet
require supportive care that includes feeding by enteral tube or parenteral
nutrition, intensive care, mechanical ventilation, and treatment of secondary
infections. Patients with suspected botulism should be carefully monitored for
impending respiratory failure. Botulism patients should be assessed for the
adequacy of their ability to gag and cough, ability to control oropharyngeal
secretions, and indicators of respiratory function such as oxygen saturation,
vital capacity, and inspiratory force. The proportion of patients with botulism
who require mechanical ventilation ranges from 20% to 60%. A reverse Trendelenburg
position may postpone or avoid the need for mechanical ventilation in mildly
affected patients because of improved respiratory mechanics and airway protection.
With this position, the patient is placed on a flat mattress tilted at 20 degrees.
A tightly rolled cloth can be used to support the cervical vertebrae and bumpers
can be used at the foot of the bed to prevent the patient from sliding downward.
For those patients who survive, eventual recovery from botulism results from
new motor axon twigs that sprout to reinnervate paralyzed muscle fibers, a process
that may take weeks or months to complete. In a large outbreak of botulism affecting
a major metropolitan area, the need for mechanical ventilators, critical care
beds, and skilled personnel might quickly exceed local capacity and persist
for weeks or months.
Recognition of a covert intentional release of finely aerosolized botulinum toxin would probably occur too late to prevent additional exposures. When exposure is anticipated, covering the mouth and nose with clothing such as a handkerchief, scarf, or shirt may provide some protection. Features of an outbreak that would suggest a deliberate release of botulinum toxin include:
An outbreak of a large number of cases of acute flaccid paralysis with prominent bulbar palsies.
An outbreak with an unusual botulinum toxin type.
An outbreak with a common geographic factor among cases (e.g., air travel, work location), but without a common dietary exposure.
Multiple simultaneous outbreaks with no common source.