Botulism

NATIA SHAVGULIDZE , INFECTIOUS DISEASE SPECIALIST, M.D

N.KIPSHIDZE CENTRAL UNIVERSITY CLINIC OF TBILISI STATE MEDICAL UNIVERISTY
KUTAISI STATE UNIVERSITY AFTER AK. TSERETELI , MEDICAL FACULTY
Botulism

 Botulism is an acute
neurologic disorder that
causes potentially life-
threatening neuroparalysis
due to a neurotoxin
produced by Clostridium
botulinum.
 Botulism is a paralytic disease
caused by the neurotoxins of
Clostridium botulinum and, in rare
cases, C butyricum and C baratii.
These gram-positive spore-forming
anaerobes can be found in soil
samples and marine sediments
throughout the world. With a lethal
dose to humans of less than 1 mcg,
botulinum toxins are the most
poisonous substances known and
pose a great threat as an
agent of biological warfare.
 Botulinum toxin is classified by the Centers for Disease Control
and Prevention (CDC) as one of the six highest-risk threat agents
for bioterrorism because of the high lethality, ease of production
and transport, and need for prolonged intensive care treatment.
 Investigations of Clostridium neurotoxin as a biological weapon
have been carried out by various nations. The Japanese in World
War II carried out human experiments on prisoners in
Manchuria. Also in World War II, the British secretly used a
botulism-impregnated grenade in the assassination of a German
Gestapo officer
 The United States studied botulinum toxin as a military bioweapon
until President Nixon signed the Biological and Toxin Weapons
Convention in 1972, ending all US biotoxin weapons research. Iraq and
the Soviet Union stockpiled neurotoxin, with Iraq admitting to
weaponizing thousands of liters of toxin in warheads after the 1991
Gulf War. An attempt at terrorist use of Clostridium toxin in the early
1990s by the Japanese Aum Shinrikyo cult against American military
targets was unsuccessful.
 The term botulus is derived from the Latin word for
"sausage." An outbreak of clostridial "sausage poisoning" in
Europe in the late 1700s was responsible for many deaths. A
German physician, Dr. Justinus Kerner, published the first
case descriptions of botulism in 1822, with experiments
conducted on himself and laboratory animals. Investigation
and confirmation of poor canning practices as the cause of
outbreaks of food-borne botulism occurred in the 1920s.
 Classification

• Food-borne botulism

• Wound botulism

• Infant botulism

• Adult intestinal colonization botulism

• Injection-related botulism

• Inhalational botulism
 Infant botulism is caused by ingested C botulinum spores that
germinate in the intestine and produce toxin. These spores
typically come from bee honey or the environment. The
attributed infant mortality rate is less than 1%.
 Wound botulism results from contamination of a wound with
toxin-producing organisms inhabiting wounds.
 Foodborne botulism and wound botulism occur predominantly
in adults. Food-borne botulism follows the ingestion of preformed
toxin in foods that have not been canned or preserved properlყ.
 Adult intestinal colonization botulism is similar in pathogenesis to infant
botulism. This form occurs in older children and adults with abnormal
intestinal function or anatomy, such as colitis, intestinal bypass procedures, or
other conditions that may create local or widespread disruption in the normal
intestinal flora.

 Injection-related botulism is a result of inadvertent misadventures with

injection of therapeutic pharmaceutical botulinum toxin.

 Inhalational botulism has recently been described. To date, the only human
cases have been the result of inadvertent Inhalation of toxin by laboratory
workers. However, aerosolization and inhalation of botulinum toxin is
considered a likely method for poison delivery in a bioterrorist attack.
 Pathogenesis
 C botulinum is an anaerobic gram-positive rod that
survives in soil and marine sediment by forming spores.
Under anaerobic conditions that permit germination, it
synthesizes and releases a potent exotoxin
 Blocks neurotransmitter release at peripheral cholinergic
nerve terminals .
 Binding to receptors on unmyelinated presynaptic
membrane
 Uptake of toxin into nerve terminals by endocytosis
 Translocation across endosome membrane

 Inhibition of transmitter exocytosis from presynaptic

terminal
toxins
Eight antigenically distinct C botulinum toxins are known, including A,
B, C (alpha), C (beta), D, E, F, and G.
Each strain of C botulinum can produce only a single toxin type. Types A, B,
E, and, rarely, F cause human disease:
 Toxins A and B are the most potent, and the consumption of small
amounts of food contaminated with these types has resulted in full-blown
disease. ( During the last 20 years, toxin A has been the most common cause
of foodborne outbreaks; toxins B and E follow in frequency)
 Toxins C and D cause disease in various animals.
 Type G toxin has been associated with sudden death but not with
neuroparalytic illness. It was isolated from autopsy material from 5 patients in
Switzerland in 1977
In 15% of C botulinum infection outbreaks, the toxin type is not
determined..
Clinical manifestation
Food born botulism :
o Incubation period 18-36 h
o Descending paralysis ( up to resp. failure, death… )
o Cranial nerve involment : dislopia , dysarthria , dysphonia , dysphagia
o Weakness
o Nausea, vomiting,
o Abdominal pain
o Dizzines
o Blurred vision
o Dry mouth
o Ptosis
o Urinary retention
o Severe constipation
Wound Botulism

o Incubation Period up to 10 days

o No gastrointestinal syptoms
o Fever
Wound botulism has increased in recent decades in people who inject heroin,
which can contain spores of the bacteria. In fact, this type of botulism is most
common in people who inject black tar heroin.
diagnose
 Initial diagnosis is based on clinical symptoms . Treatment should
not wait for laboratory confirmation
 Laboratory confirmation is done by demonstrating the presence of
toxin in serum, stool, or food, or by culturing C. botulinum from
stool, a wound or food.
 Laboratory testing may take hours or days. Initial diagnosis and
appropriate treatment depend on clinical diagnosis through a
thorough history and physical examination.
Laboratory Confirmation
 It is done by bioanalyses of laboratory mouse . A
sample from patient’s serum, gastric secretion or stool
will be injected into lab.mouse ‘s peritoneal area . After
this, mouse is monitored about botulism clinical signs.
This kind of test can be made with potentially
contaminated food particles , also.
This bioanalyze can be done only special
laboratories: according to the botulin toxin toxicity – it’s
mandatory to have at least 2nd level biosafety laboratories
or even more
Laboratory confirmation

 Stool, gastric secret or potentially poisoned food particle’s

culturing
 Culturing method can be done, only if the suspect is about
foodborne botulism, infant’s botulism or wound botulism
 It can’t be done , if the suspect is inhaled or iatrogenic botulism ,
because they are caused with the toxin’s isolates (so we can’t
catch the bacteria into no any culture samples )
 Nowadays , there is going work about detection of
botulin toxin into poisoned food with ELISE method
 Although , it’s use can be restricted into endogenic
proteinase containing food products , such as egg hearts
and milk
 Also it’s use restricted for clinical samples : serum or
stool
Differential Diagnosis for Adults
 Guillain-Barre syndrome : 95% cases starts with ascending paralyses
Laboratory : CSF analyses shows elevated protein level , while for botulism it’s
normal

 Myasthenia gravis- such patients devlop autonomic(vegetative system) no

stability . To all such patients have antibodies against acetylcholine receptors

 Tick bite paralyses – Dermacentor

Mainly is diagnosed and distinguished with patient’s examination and anamnesis .
After bite , tick stays fixed on humans body sites , so it can be easily found if you check
patient’s body carefully (especially : hairy parts : head , axila..)
Paralises is always ascending , not descending !!
 Chemical intoxication (e.g. poisoning by Phosphate organic
toxins, Magnium intoxication )

Poisoning by Phosphate organic toxins : Characterizes with cholinergic

symptoms :Bradycardia , hypersalivation, tear off , broncho spasm ,
urination, nausea, vomiting
Similarly to botulism, here can be : neck muscles weakness, deep
tendon reflex decrease , cranial nerves pathology , muscles proximal
weakness –likehood botulism signs
Lab. Tests : erythrocyte’s acethylcholinesterase activity checking (if
laboratory affordable ) or plasma cholinestherase activity analyse .
 Magnum intoxication
 Itcan cause muscle paralyses or deep tendon reflex
disappearance
 Smooth muscle’s disfunction : manifested with respiratory
disorders :superficial breathing up to apnea
 Somnolence
 Lab. Findings : Elevated magnum concnetration
 Spinal muscle atrophy
 Genetic, inherited disease , with several types : can be as in
adults as in infants
 Compare to botulism weakness is much more longitudinal
and not such severe
 Infantsspinal muscle atrophy – characterizes with no eye
and anal muscle’s weakness, as it happens in occasion of
botulism
 Lab.checking : genetic mutagenic tests, specific for spinal
muscle atrophy
Poliomyelitis

 Poliomyelitis- probable case of polio is defined as an acute onset of flaccid

paralysis of one or more limbs with decreased or absent tendon reflexes in the
affected limbs, without other apparent cause, and without sensory or cognitive
loss. Paralysis usually begins in the arm or leg on one side of the body
(asymmetric) and then moves towards the end of the arm or leg (progresses to
involve distal muscle groups). This is described as descending paralysis. Many
patients with AFP will have a lumbar puncture and analysis of cerebrospinal
fluid (CSF) performed as part of their evaluation. Detection of poliovirus in
CSF from confirmed polio cases is uncommon, and a negative CSF test result
cannot be used to rule out polio.
 Consider polio in patients with polio-like symptoms, especially if the person is
unvaccinated and recently traveled abroad to a place where polio still occurs,
or was exposed to a person who recently traveled to one of these areas.
Cerebrovascular accident (CVA)
• Sudden numbness or weakness in the face, arm, or leg,
especially on one side of the body.
• Sudden confusion, trouble speaking, or difficulty
understanding speech.
• Sudden trouble seeing in one or both eyes.
• Sudden trouble walking, dizziness, loss of balance, or
lack of coordination.
• Sudden severe headache with no known cause.
Differential Diagnosis for Infants

Sepsis
Meningitis
Electrolyte-mineral imbalance
Reye’s syndrome
Congential myopathy
Werdnig-Hoffman disease
Leigh disease
Treatment
 Botulinum antitoxin should be administered as soon as possible. Antitoxin does not
reverse paralysis but arrests its progression
 Before administration of antitoxin, skin testing should be performed for sensitivety to
serum or antitoxin.
 After skin testing, administration of one vial of antitoxin IV is recommended. There is
no need to re-administer the antitoxin since the circulating antitoxins have a half-life
of 5-8 days.
 Based on limited information, there is no indication that treatment of children from the
age of 12 month , pregnant women, or immunocompromised persons with botulism
should differ from standard therapy.
 For infants , under age of 12 month – botulism immunoglobulin should be
administered - BabyBIG
Other care options :

 Meticulous intensive care should be exercised, including

monitoring of respiratory function and when required, artificial
ventilation.
 Recovery follows the regeneration of new neuromuscular
connections.
 2-8 weeks duration of ventilatory support may be required in
more severe cases.
Bioterrorism weapon
 Botulinum toxin may be used to immobilize the opponent in military action. It has
been estimated that if used as a point source aerosol in a densely populated area, it
could incapacitate or kill 10% of the population within 0.5 km downwind. In
addition, it could be used to deliberately contaminate food.[
 A careful dietary, activity, and travel history is of almost importance in any
suspected botulism outbreak. Patients should also be asked whether they know of
anyone else with similar symptoms. An outbreak resulting in a large number of
cases of acute flaccid paralysis with prominent bulbar palsies should raise
suspicion of a deliberate release of the toxin.
 Outbreaks consisting of cases with a common geographic factor, but without a
common dietary exposure, should raise suspicion of a possible aerosol attack.
Summery –Botulism main aspects

 Paralytic disease - caused by neurotoxin , produced by Clostridium

botulinum : which is thick , anaerobic , gram-positive bacteria . It
exists mainly in spore forms
 Clinical symptoms develop when botulin toxin spreads into the blood
stream
 Toxin action manifests like : cranial nerve paralyses , oculo-bulbar
weakness , descending , symmetric , slow paralyses –without fever ,
without sensor deficiency
 Diagnoses is mainly clinical and can be confirmed by the detection
toxin into the clinical specimens
Thank you for attention !