CLOSTRIDIAL INFECTIONS

TETANUS, BOTULISM,
GAS GANGRENE
WTetanushat is Tetanus?

 An infectious disease caused by

contamination of wounds from the
bacteria Clostridium tetani, or the
spores they produce that live in the
soil, and animal feces

 Greek words -“tetanosand teinein”,

meaning rigid and stretched, which
describe the condition of the
muscles affected by the toxin,
tetanospasmin, produced
by Clostridium tetani
Sporulated Vegetative
Causes
 Tetanus spores are found throughout the
environment, usually in soil, dust, and animal waste.

 Tetanus is acquired through contact with the

environment; it is not transmitted from person to
person.
 The usual locations for the bacteria to
Causes
enter the body:

 Puncture wounds (such as those

caused by rusty nails, splinters,
or insect bites.)
 Burns, any break in the skin, and IV
drug access sites are also potential
entryways for the bacteria.
 Epidemiology

Tetanus is an international health problem, as

spores are ubiquitous. The disease occurs almost
exclusively in persons who are unvaccinated or
inadequately immunized.
Tetanus occurs worldwide but is more common in
hot, damp climates with soil rich in organic matter.
More common in developing and under developing
countries.
More prevalent in industrial establishment, where
agricultures workers are employed.
Tetanus neonatorum is common due to lack of MCH
care.
Incubation Period

 Varies from 1 day to several months. It

is defined as the time from injury to
the first symptom.
Period of onset

 It is the time from first symptoms to the

reflex spasm.

 An incubation period of 4 days or less

or
 A period of onset of less than 48 hr is
associated with the development of severe
tetanus.
Pathogenesis
 1. C. tetani enters 2. Stays in sporulated
body from through form until anaerobic
wound. conditions are presented.

3. Germinates under 4. Tetnospasmin spreads

using blood and lymphatic
anaerobic conditions and system, and binds to motor
begins to multiply and neurons.
produce tetanospasmin.

5. Travels along the 6. Binds to sites responsible

axons to the spinal for inhibiting skeletal
cord. muscle contraction.
•Initially binds to
peripheral nerve
terminals
•Transported within
the axon and across
synaptic junctions until
it reaches the central
nervous system.
•Becomes rapidly fixed
to gangliosides at the
presynaptic inhibitory
motor nerve endings,
then taken up into the
axon by endocytosis.
How the toxin acts?
Blocks the release of inhibitory
neurotransmitters (glycine and gamma-amino
butyric acid) across the synaptic cleft, which
is required to check the nervous impulse.
If nervous impulses cannot be checked by
normal inhibitory mechanisms, it leads to
unopposed muscular contraction and spasms
that are characteristic of tetanus.
Tetanus prone wound

 A wound sustained more than 6 hr before

surgical treatment.
 A wound sustained at any interval after
injury which is puncture type or shows
much devitalised tissue or is septic or is
contaminated with soil or manure.
Clinical features
 Risus sardonicus: Contraction of the muscles
at the angle of mouth and frontalis
 Trismus (Lock Jaw): Spasm of Masseter
muscles.
 Opisthotonus: Spasm of extensor of the neck,
back and legs to form a backward curvature.
 Muscle spasticity
 Prolonged muscular action causes sudden,
powerful, and painful contractions of muscle
groups. This is called tetany. These episodes
can cause fractures and muscle tears.
 If respiratory muscle is involved – apnoea.
Signs and Symptoms

Other symptoms include:

 Drooling
 Excessive sweating
 Fever
 Hand or foot spasms
 Irritability
 Swallowing difficulty
 Uncontrolled urination or defecation
Diagnosis
 There are currently no blood tests that
can be used to diagnose tetanus. Diagnosis
is done clinically.
Differential Diagnosis
 Masseter muscle spasm due to dental
abscess
 Dystonic reaction to phenothiazine
 Rabies
 Hysteria
Principle of Treatment

 1. Neutralization of unbound toxin with

Human tetanus immunoglobulin
 2. Prevention of further toxin
production by
-Wound debridement
-Antibiotics (Metronidazole)
 3. Control of spasm
- Nursing in quiet environment
- Avoid unnecessary stimuli
- Protecting the airway
 4. Supportive care
- Adequate hydration
- Nutrition
- Treatment of secondary infection
- Prevention of bed sores.
If spasms occur, antispasmodic drugs
should be used and respiration
maintained by ventilator if necessary.
Prevention

 Tetanus is completely preventable

by active tetanus immunization.

 Immunization is thought to provide

protection for 10 years.

 Begins in infancy with the DTP

series of shots. The DTP vaccine is a
"3-in-1" vaccine that protects
against diphtheria, pertussis, and
tetanus.
Prevention
 Can be achieved by active immunization by
tetanus toxoid (beginnig in third month)

 Older teenagers and adults who have

sustained injuries, especially puncture-type
wounds, should receive booster immunization
for tetanus if more than 10 years have
passed since the last booster.

 Clinical tetanus does not produce immunity to

further attacks. Therefore, even after
recovery patients must receive a full course
of tetanus toxoid.
BOTULISM
History
 Disease – botulism
 Agent – botulinum toxin
 Source of toxin - Clostridium botulinum
 Discovered in 1895
 United States
 Largest 20th Century outbreak of food-
borne botulism
 Michigan 1977
 59 cases from home-preserved jalapeno
peppers at a restaurant
History

 Therapeutic use of botulinum toxin

 FDA approved for neuromuscular disorders
 Blepharospasm
 Strabismus
 Torticollis
 Many other unapproved uses
 Packaged in dilute preparations
 Not feasible to use licensed toxin for weapon
Bioweapon Potential

 Botulinum toxin a major threat because

 Extreme potency and lethality
 Ease of production
 Ease of transport
 Need for prolonged intensive care
 Top 6 potential biological warfare
agents
 Listed as Category A agent: High
priority
Clinical presentation

 Naturally occurring botulism

 Foodborne (preserved or non-preserved)
 Wound
 Intestinal
 Bioterrorism routes of intoxication
 Aerosol (inhaled into lungs)
 Foodborne
 Food-borne botulism
 Foods that have higher pH
 corn, pepper, carrots, beans,
 Contaminated condiments
 Commercial foods
 Difficult to distinguish intentional
 Inhalational exposure
 One documented accidental outbreak
 Germany 1962
 3 laboratory workers
 Exposed to re-aerosolized toxin type A
 Confirms that aerosol route is effective
means of intoxication
Epidemiology

 U.S. incidence
 < 200 annual cases of all forms
 Approx 9 annual outbreaks of food-borne
 median of 24 cases
 Recent trend toward restaurant rather than
home-preserved foods
 All ages and genders equally
susceptible
 Mortality
 25% prior to 1960
 6% during 1990’s
Epidemiology

 Incubation period
 Depends on inoculated dose
 Inhalational
 12-18 hours in primate studies
 72 hours in 3 known inhalational cases
 True incubation period is unknown
 Foodborne
 6 hours to 8 days
 Wound
 7.5 days (range 4-18 days) after injury
Microbiology

 C. botulinum
 Gram-positive obligate anaerobic bacillus
 Spore-forming
 Produces botulinum toxin
 Heat sensitive as bacillus
 Prefers low acid environment

Inglesby, T. The Washington Post

Wednesday, December 9, 1998; Page H01
Microbiology
WuDunn S, Miller J, Broad WJ.
How Japan germ terror alerted world.
New York Times.
May 26, 1998:A1, A10.

 C. botulinum spores
 Ubiquitous
 Soil
 Airborne dust
 Surfaces of raw fruits and vegetables
 Seafood
 Heat resistant

Tucker JB, ed. Toxic Terror: Assessing the Terrorist Use of Chemical
and Biological Weapons. Cambridge, Mass: MIT Press; 2000.
Microbiology

 Botulinum toxins
 Consist of light and heavy chains
 Light chain – zinc endopeptidase
 The bioactive component
 Colorless, odorless
 Environmental survival
 Inactivated by heat >85ºC for 5 min
 pH <4.5
Neurotoxins

 Seven different types: A through G

 Different types affect different species
 All cause flaccid paralysis
 Only a few nanograms can cause illness
 Irreversibly binds neuromuscular junctions
– flaccid paralysis
 Toxin: Destroyed by boiling
 Spores: Higher temperatures to be
inactivated
Center for Food Security and Public Health Iowa State University 2004
Neurotoxins

Neurotoxin A B C D E F G
Human X X X X
Horses X X
Cattle X X X
Sheep X
Dogs X X
Avian X X
Mink & Ferret X X X

Center for Food Security and Public Health Iowa State University 2004
Pathogenesis

 Possible routes of exposure

 Inhalation of toxin (in a biological
attack)
 Food or water toxin contamination
 Wound infected with C. botulinum
Pathogenesis

 Estimated lethal human dose

 crystalline type A toxin
 0.09-0.15 g given iv or im
 0.70-0.90 g inhalationally
 70 g given po
Pathogenesis
 Toxin must enter body
 Direct toxin absorption from mucosal
surface
 Gut – foodborne
 Lungs – inhalational
 Via toxin produced by infection with
C.botulinum
 Skin breaks – wound botulism after trauma, IV
drugs
 Gut – intestinal botulism
 Does not penetrate intact skin
Pathogenesis

Wound Botulism from a heroin user.

Jermann M, Hiersemenzel LP, Waespe W Drug-dependent patient with multiple
cutaneous abscesses and wound botulism
Schweiz Med Wochenschr 1999;129:1467
Pathogenesis
 All forms of disease lead to same
process
 Toxin absorbed into bloodstream
 Irreversibly binds peripheral cholinergic
synapses
 Cleaves fusion proteins used by neuronal
vesicles to release acetylcholine into
neuromuscular junction
 Blocks Acetylcholine release permanently
 Results in paralysis of that muscle
 Reinnervation via regeneration of axon twigs
 Takes weeks to months
Pathogenesis

JAMA. 2001;285:1059-1070
Pathogenesis

JAMA. 2001;285:1059-1070
Clinical Features

 Symptoms
 All forms same neuro symptoms
 Diplopia / blurred vision (Dilated or
unreactive pupils)
 Ptosis
 Slurred speech
 Dysphagia / dry mouth
 Muscle weakness
Clinical Features

 Infant botulism specifically

 Appears lethargic
 Feeds poorly
 Constipated
 Weak cry
 Poor muscle tone
Clinical Features

 Classic Triad
 Symmetric, descending flaccid paralysis
with prominent bulbar palsies
 Afebrile
 Clear sensorium
 Bulbar palsies summarized as "4 Ds"
 Diplopia, dysarthria, dysphonia, dysphagia
 Dilated or unreactive pupils
Clinical Features

Patient at rest, Requested to perform

bilateral mild ptosis, max. smile. Ptosis,
disconjugate gaze, disconjugate gaze, mild
symmetric facial asymmetric smile.
muscles. JAMA. 2001;285:1059-1070
Clinical Features

 Symptom progression
 Descending paralysis
 Lose head control
 Lose gag – require intubation
 Lose diaphragm – mechanical ventilation
 Loss of deep tendon reflexes
Clinical Features
Gastrointestinal/ Neurologic Muscular
Urinary
Nausea Dry Mouth Symmetrical
sceletal
Muscle weakness
Vomiting Blurred vision Respiratory
muscle
paralysis
Diarrhea Diplopia Fatigue
Abdominal Pain Dilated or Dyspnea
unreactive
pupils
Intestinal ileus Dysphagia

Urinary retention Decreased gag

reflex
Clinical Features

 4 clinical forms of botulism

 Food-borne (first described in 1897)
 Wound (1943)
 Infant (1976)
 Indeterminate (1977)
Clinical Features

 Infant
 Occurs in children < one year old
 Ingests spores, grows in bowel & release
toxin
 Intestinal colonization of organisms
 Normal intestinal flora not developed
Clinical Features

 Indeterminate
 No specific food or wound source identified
 Similar to infant but occurs only in adults
 Risk factor: surgical alterations of the GI
tract and/or antibiotic therapy
 Leads to colonization
Diagnosis

 Clinical diagnosis
 Diagnostic tests help confirm
 Toxin neutralization mouse bioassay
 Serum, stool, or suspect foods
 Infant botulism
 C botulinum organism or toxin in feces
Diagnosis

 What to do at first suspicion of a

case
 Immediately notify public health dept
 Acquire therapeutic antitoxin
 Send samples for diagnostic testing
 Serum, vomit, gastric aspirate, suspect
food, stool
 Collect serum before antitoxin given
 If enema required, use sterile water
 Refrigerate samples and suspect foods
 Get medication list to rule out
anticholinesterases
Diagnosis
 Confirmation
 Takes 1-4 days
 Available only at CDC and state public health
labs
 Mouse Bioassay
 Type-specific antitoxin protects vs. toxin in
sample
 The assay can detect at minimal 0.03ng of
toxin.
 Culture
 Fecal and gastric specimens cultured
anaerobically
 Results in 7 to 10 days
Diagnosis

 Differential diagnosis
 Guillain-Barre, myasthenia gravis
 Unique features to help in diagnosis
 Disproportionate cranial nerve palsies
 More hyptonia in facial muscles than below
neck
 Lack of sensory changes
Treatment

 Supportive care
 Enteral tube feeding or parenteral
nutrition
 Mechanical ventilation
 Treatment of secondary infections
 Avoid aminoglycosides and clindamycin
 Worsens neuromuscular blockade
Treatment
 Passive immunization - equine
antitoxin
 Antibodies to Types A, B and E toxins
 Binds and inactivates circulating toxin
 Stops further damage but doesn’t
reverse
 Administer ASAP for best outcome
 Dose per package insert
 Heptavalent antitoxin
 Investigational
 Effective against all toxins
Treatment

 Antitoxin action
 Food-borne botulism
 Neutralizing antibody levels exceed toxin
levels
 Single dose adequate
 Large exposure (e.g. biological weapon)
 can confirm adequacy of neutralization
 recheck toxin levels after treatment
 Antitoxin adverse effects
 Serum sickness (2-9%), anaphylaxis (2%)
Treatment

 Recovery takes weeks

 Until motor axon twigs regenerate
 Special groups - same treatment
strategy
 Children
 Pregnant women
 Immunocompromised
Prevention

 Natural disease
 Boil home-canned foods 10 minutes
 Follow USDA instructions on home-canning
 Restrict honey from < 1 year old
 Seek medical care for wounds
 Avoid injectable street drugs
Prevention

 Vaccine
 Botulinum pentavalent toxoid
 Not available to general public
 Limited supply provided by CDC
 In use for laboratory workers, military
 Protects vs. types A-E
 Long-lasting immunity
 Prohibits future therapeutic use of toxin
 Onset too slow to be effective PEP
GAS GANGRENE
 It is a rapidly progressive, potentially fatal
condition characterized by widespread necrosis
of the muscles and subsequent soft-tissue
destruction.

 This is a dreaded consequence of inadequately

treated missile wounds, crushing injuries and
high-voltage electrical injuries.
Causative agent

 Clostridium species – spore forming, Gram +

C.septicum

C.novyi
C.perfringens
(mostly)
• They are present in the
soil and have also been
isolated from the human
gastrointestinal tract
and female genital tract.

• Non-clostridial gas-
producing organisms
such as coliforms have
also been isolated in 60–
85% of cases of gas
gangrene.
 Vegetative
cells multiply
Spores Carbohydrates
germinate Fermentation

Anaerobic
PATHOGENESIS Gas production
In tissues
environment Incubation period is
1-7 days

Distension of
Toxemia and tissues
death Interfering
Blood supply
Ischemia/
gangrene
Pathogenesis

- Bacteria - The toxins - Examples of enzyme:

enters the (lecithinase) colagenases, proteases
and enzyme and lipases
broken skin are produced
or wound
- These enzymes will kill
- The bacteria are other host cell and extend
- Spores
are grow and ferment the anaerobic environment
produced the muscle
carbohydrate - Produce gases (nitrogen,
hydrogen sulphide and
- The bacteria carbon dioxide)
present in - The anaerobic - Crepitant tissue
circulation
tissue present ( destroyed tissue)
system
Epidemiology

 The persons at risk those with Diabetes

Mellitus, blood vessel disease and colon
cancer

 Contact with contaminated cloth and other

foreign material

 Trauma or recent surgical wound

 Symptoms
• High fever
• Shock
• Massive tissue destruction
• Blackening of skin
• Severe pain around a skin of wound
• Blisters with gas bubbles form near the
infected area,
• The heartbeat and breathing become
rapid.
 Presentation
Crepitation in tissues,
sickly sweet odor discharge,
rapidly progressing necrosis,
fever, hemolysis, toxemia,
shock,
renal failure, and death
Lab. Investigations

Culture and susceptibility

Storming fermentation
Lecithinase test
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Prevention
 Cleaning the wound
 Avoid the contaminated material
 improve circulation in
patients with poor circulation
 antitoxin
 Prevention
(1) Do a thorough wound toilet.
(2) In high risk wounds give the patient
penicillin 1.5 MU every 4 hourly,
or tetracycline
Treatment

 High doses of antibiotics: Penicillin

 The dead tissue is removed or limbs are

amputated

 No vaccine
10 megaunits of benzyl penicillin daily
for 5 days as four 6 hourly doses.

Or
Tetracycline 0.5 g intravenously
or 1 g orally every 6 hours.

Clostridia not sensitive to

metronidazole,
some other anaerobic bacteria are,
so give it.
Myonecrosis of right leg
Myonecrosis of left foot
Stump of above knee amputation
 Patients should be admitted to ICU and
treated aggressively with careful
monitoring.
 The role of HBO is not as clear as in
necrotising fasciitis but it is recommended
in severe cases if the facilities are
available.
 increases the normal oxygen saturation in the
infected wounds by 1000-fold leading to
 Bacteriocidal effect,
 Improves neutrophil function,
 Enhanced wound healing
Thank You For Your Attention