Transcript Tetanus & Rabies - Cleveland Clinic Hospital Locations

Tetanus & Rabies
Chapt. 146-147
January 12, 2005
Dr. Kiss
slides by
Scott Gunderson PGY-2
Tetanus – Epidemiology

Uncommon in the US but not worldwide

1 million cases worldwide per year

Mortality rate of 20-50%

Highest prevalence in developing countries
Epidemiology

Fewer than 50 cases per year in the US

Majority of cases in temperate climates (Texas,
California, and Florida)

Mortality rate of 11%

Most who develop it have an inadequate immunization
history

Only 27% of Americans older than age 70 have
adequate immunity to tetanus
Pathophysiology

Wound contamination with Clostridium
tetani


Motile, nonencapsulated, anaerobic, gram
positive rod
Spore forming and ubiquitous in soil and
animal feces
Pathophysiology



Usually introduced in the spore forming state,
then germinates to the toxin producing
vegetative form
Requires decreased tissue oxygen tension to
germinate
Vegetative state produces two exotoxins


Tetanolysin
Tetanospasmin
Toxins

Tetanolysin – clinically insignificant

Tetanospasmin
Neurotoxin responsible for the clinical
manifestations of tetanus
 Reaches peripheral nerves by hematogenous
spread and retrograde intraneuronal transport
 Does not cross blood brain barrier
 Reaches CNS by retrograde transport

Tetanospasmin


Acts on the motor end plates of skeletal
muscle, in the spinal cord, and in the
sympathetic nervous system
Prevents release of inhibitory
neurotransmitters glycine and gammaaminobutyric acid (GABA)
Clinical Features



Tetanospasmin responsible for generalized
muscular rigidity, violent muscular contractions,
and instability of the ANS.
Typical wound is a puncture, but no wound is
identified in up to 10%
Other routes are surgical procedures, otitis
media, abortion, umbilical stump and drug
abusers
Four Clinical Forms

Local

Generalized

Cephalic

Neonatal
Local Tetanus



Rigidity of the muscles in proximity to the
site of injury
Usually resolves completely in weeks to
months
May develop into generalized
Generalized Tetanus



Most common form
Most common presenting complaint is pain
and stiffness of the masseter muscles
(Lockjaw)
Short axon nerves affected initially
therefore starts in the face, then neck,
trunk, and extremities
Generalized Tetanus



Muscle stiffness leads to rigidity
Trismus and characteristic sardonic smile
develops (risus sardonicus)
Reflex convulsive spasms and tonic muscle
contraction create dysphasia, opisthotonos
(arching of back and neck), flexing arms,
clenching fists, and lower extremity extension
Trismus and Sardonic Smile
Opisthotonos
Generalized Tetanus

Autonomic nervous system
Hypersympathetic state
 Usually in the second week

Tachycardia
 HTN
 Diaphoresis
 Increased urinary catecholamines


Significant morbidity and mortality
Cephalic Tetanus



Results from an injury to the head or otitis
media
Cranial nerves affected most commonly
the seventh
Poor prognosis
Neonatal Tetanus



400,000 worldwide deaths annually
Results from inadequately immunized
mothers
Frequent after unsterile treatment of the
cord stump
Neonatal Tetanus


Signs

Weakness

Irritability

Inability to suck
Presents in the 2nd week of life
Diagnosis

Clinical diagnosis

No laboratory confirmatory tests


Wound cultures not very useful as C. tetani may
be recovered without tetanus
Immunization history usually unknown or
inadequate
Tetanus Ddx

Strychnine poisoning

Peritonitis

Dystonic reaction

Meningeal irritation

Hypocalcemic tetany

Rabies

Peritonsillar abscess

TMJ
Treatment


Admit to ICU
Be prepared for intubation with neuromuscular
blockade as respiratory compromise may
develop

Minimal environmental stimuli to avoid reflex
convulsive spasms

Initial wound debridement to improve
oxygenation
Treatment

Tetanus Immunoglobulin (TIG)
Neutralizes wound and circulating
tetanospasmin
 Does not neutralize toxin already bound to the
nervous system
 Does not improve clinical symptoms
 Decreases mortality

Treatment

TIG
Usual dose is 3,000 to 6,000 units
 Administered IM opposite side as Td given
 Give before wound debridement

Treatment

Antibiotics
Questionable utility but usually given
 Metronidazole



antibiotic of choice
Avoid penicillin

it is a GABAA antagonist and may worse symptoms
Treatment

Muscle relaxants

Tetanospasmin


Midazolam


prevents neurotransmitter release at inhibitory
interneurons and therapy of tetanus is aimed at
restoring balance
preferred agent as it is water soluble
Baclofen

specific GABAB agonist that has also been used
Treatment

Neuromuscular blockade
Blockade often required to allow respiration
and to prevent fractures and rhabdomyolysis
 Succinylcholine



recommended for initial airway management
Vecuronium

treatment of choice for long term blockade
Treatment

ANS dysfunction treatment

Labetalol


Magnesium sulfate


useful for treatment due to combined alpha and
beta activity
inhibits the release of epinephrine and
norepinephrine from the adrenal glands
Clonidine

central alpha receptor agonist for cardiac stability
Immunization


Disease does not confer immunity so those that
recover must undergo immunization
Tetanus toxoid



0.5 cc IM at presentation, 6 weeks, and 6 months
Local reactions are common
Less common serous reactions include urticaria,
anaphylaxis, or neurologic complications
Immunization and TIG
guide
Clean, Minor
wounds
History of Td
Doses
Unknown or < 3
Three or more



Td
Yes
No
TIG
No
No
Td dose: 0.5cc IM
TIG dose: 250 U IM
DPT given if under 7, Td given if over 7
All other
wounds
Td
Yes
Yes
TIG
Yes
No
Rabies
Rabies



Rabies ranks number 10 worldwide as a
cause of mortality
50,000 – 60,000 deaths annually
worldwide
Rare human cases in US but 35,000
people provided prophylaxis annually
Microbiology

Lyssavirus genus prototype


Single-stranded, negative-sense,
nonsegmented RNA
7 rabies groups in genus
Classic rabies virus – common rabies
 6 others with less than 10 reported human
cases of disease

Pathophysiology

Virus course
Initial uptake of virus by monocytes in 48-96
hours
 Crosses motor end-plate to travel up the axon
to the dorsal root ganglia to the spinal cord
and the CNS
 Then spreads outward via peripheral nerves
to infect almost all tissue of the body

Pathophysiology

Histologically resembles other encephalitis


Monocellular infiltration with focal hemorrhage
Demyelination




Perivascular gray matter
Basal ganglia
Spinal cord
Negri bodies



Eosinophilic intracellular lesions in cerebral neurons
Highly specific for rabies
Present in 75% of rabies cases
Negri bodies
Epidemiology



Primarily a disease of animals
Human cases reflect the prevalence in animals
and degree of human contact with them
Major vectors include







Dogs
Foxes
Raccoons
Skunks
Coyotes
Mongooses
bats
Epidemiology
7,369 cases of animal rabies in the US in 2000

Wild animals (93%)





Raccoons (37.7%)
Skunks (30.2%)
Bats (16.8%)
Foxes (6.2%)
Others (2.2%)

Domestic animals
(7%)
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



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Cats (3.4%)
Dogs (1.6%)
Cattle (1.1%)
Horses, donkeys, mules
(0.71%)
Sheep, goats, camels
(0.15%)
Others and ferrets
(0.06%)
http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm
http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm
Epidemiology

Dogs



Less than 5% of animal cases in US, Canada and
Europe
Greater than 90% of animal cases in developing
countries
Very rare documented rabies in:


Squirrels, hamsters, guinea pigs, gerbils, chipmunks,
rats, mice, domesticated rabbits and other small
rodents
Almost never requires post exposure prophylaxis
Epidemiology

Transmission
Saliva though bite of an rabid animal most
common
 Aerosolized in bat caves
 Mucus membrane transmission also reported


Bites and scratches

Risk of developing rabies dependant on the
location injury, depth, an number of bites
Infection Risk

Risk of infection
Multiple bites around the face
80-100%
Single bite
15-40%
Superficial bite on the extremity
5-10%
Contamination of open wound by
saliva
Transmission via fomites (e.g. tree
branch, or animal)
0.1%
0%
Epidemiology

32 cases reported from 1980 to 1996 in
the US

7 had a known animal bite
6 dog bites in a foreign country
 1 bat bite


Animal contact identified in 12
8
2
1
1


with
with
with
with
a
a
a
a
bat
dog
cow
cat
No identifiable source in the other 13
Preexposure Prophylaxis

Prophylaxis
Individuals with occupations or recreation that
place them at risk should receive the series
 4 shot series with booster shots required
 Does not eliminate need for postexposure
prophylaxis


No need for HRIG and less doses of vaccine
Postexposure Prophylaxis

Indicated for all persons possibly exposed to a
rabid animal



Exposure is a bite, scratch, abrasion, open wounds, or
mucous membrane exposure
Contact alone, and contact with blood, urine, or feces
does not constitute and exposure
Cleansing wound with 20% soap and water has
been show in experimental animals to markedly
reduce the rate of infection
Bats



Increasingly important wildlife vectors of
transmission of rabies
All cases of possible bat bites the bat
should be collected and tested for rabies
Bat unavailable

Begin postexposure prophylaxis
Dogs, Cats, and Ferrets

Observation
CDC recommends 10 days of observation of a
healthy dog, cat, or ferret after a bite
 Normal behavior



No action needed
Unusual behavior

Sacrifice animal, test for rabies, and initiate HRIG
and vaccine


Positive – Complete course of vaccine
Negative – Discontinue course
Possible animal exposure
Carnivore, bat or
salivary exposure
Bird, reptile, rodent or
nonsalivary exposure
Bat, skunk, raccoon, cow,
bobcat, coyote, or fox
Dog or cat
Captured
No Vaccine needed
Captured and quarantined
Sacrifice and test
Initiate vaccine +HRIG
Normal behavior 10 days
Rabid
Vaccine +HRIG
No vaccine needed
Not Rabid
Discontinue vaccine
Strange behavior
Sacrifice, initiate
vaccine and HRIG
Escaped
Rabid
Vaccine + HRIG
Not Rabid
Discontinue vaccine
Escaped
No epidemiologic
prevalence in area
No vaccine needed
Epidemiologic prevalence
Vaccine +HRIG
Vaccine + HRIG
Bat, skunk, raccoon, cow,
bobcat, coyote, or fox
Captured and quarantined
Escaped
Sacrifice and test
Initiate vaccine +HRIG
Rabid
Vaccine +HRIG
Not Rabid
Discontinue vaccine
Vaccine + HRIG
Dog or cat
Captured
Escaped
Normal behavior
10days
No epidemiologic
prevalence in area
No vaccine needed
No vaccine needed
Epidemiologic
prevalence
Strange behavior
Sacrifice, initiate
vaccine and HRIG
Rabid
Vaccine + HRIG
Not Rabid
Discontinue vaccine
Vaccine +HRIG
Postexposure Prophylaxis

Course

HRIG (human rabies immune globulin)
One dose initially
 May be given up to 7 days after an exposure
 Infiltrate as much as possible around wound
 Give on the opposite side as the vaccine


Vaccine

5 doses over 28 days
Postexposure Prophylaxis

Vaccine reactions

Minor reaction
Erythema, swelling, pain
 30-74%


Systemic reaction
Headache, nausea, abdominal pain, muscle aches
 5-40%


Anaphylaxis and neurological symptoms


Rarely reported
Vaccine should not be stopped for minor
or systemic reactions
Special Circumstances

Prior rabies immunization
Either prior preexposure course or full
postexposure course
 No HRIG
 Course shortened to 2 doses

One dose on presentation
 One dose three days later

Special Circumstances

Immunocompromised patient
HRIG and vaccine usual course
 Safe


Vaccine is inactivated so no danger of contracting
Stop all immunosuppressives if possible
 Measure antibody titers to assure appropriate
response

Special Circumstances

Travelers

Preexposure prophylaxis
Recommended if prevalence and possible exposure
 Veterinarians, animal handlers, spelunkers, certain
lab workers


Non-FDA postexposure prophylaxis

If initiated in another country contact health
department for recommendations
Special Circumstances

Pregnancy
No adverse effects of the vaccine or HRIG
 Follow usual course in pregnancy if indicated

Special Circumstances

Children

Vaccine


Same dose and same course
HRIG
Dose is based on weight
 If quantity of HRIG not sufficient to infiltrate all
wounds may be diluted with saline

Clinical Disease

Incubation period




20 to 90 days
4 days up to 19 years have been reported
Greater than 1 year is well documented
Prodrome



Fever, sore throat, chills malaise, headache, N/V,
weakness
May report limb pain, weakness, and paresthesias
Nonspecific neurologic conditions such as anxiety,
agitation, irritability or psychiatric disturbances
Clinical Disease

Acute neurologic phase

Furious – 80%
Hyperactivity, disorientation, hallucinations, bizarre
behavior
 Symptoms may alternate with calm
 Autonomic dysfunction
 Hydrophobia with pharynx spasms in 50%


Paralytic – 20%
Paralysis in the extremity, diffuse or ascending
 Fever and nuchal rigidity

Clinical Disease

Coma


Almost always present within 10 days
Death
Occurs from complications such as pituitary
dysfunction, seizures, respiratory dysfunction,
cardiac dysfunction, ANS dysfunction, ARF, or
infection
 Outcome almost always fatal
 No person without post-exposure prophylaxis
in the US has survived since 1980

Diagnosis


Rabies should be in the differential of any
acute encephalitis
May be confused with poliomyelitis,
Guillain-Barre syndrome, transverse
myelitis, postvaccinial encephalomyelitis,
CVA, atropine-like poisoning, other viral
encephalitis
Diagnosis

Lab testing
No one test is completely informative
 Test serum, CSF, and skin for antibodies in a
non-vacinated person
 Nuchal skin biopsy most sensitive early
 PCR from saliva also useful

Treatment

Limited
No specific treatment exists for clinical course
 Treatment directed at the clinical
complications

References


Tintinalli, Judith E., Emergency Medicine a Comprehensive Study Guide.
Sixth edition. McGrw-Hill Companies, Inc. 2004. Chapter 146-147. Tetanus
and Rabies. Pages 943-953.
Centers for Disease Control.
http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm,
Accessed January 5, 2005.
Questions
1.
2.
The majority of elderly patients have adequate
immunity to tetanus. (T/F)
A patient with previous tetanus immunization
(3 or greater) presents with a puncture wound
by a dirty nail. Appropriate tetanus
prophylaxis includes:
a)
b)
c)
d)
Td and TIG IM
Td only
TIG only
None as he was previously vaccinated
Questions
3.
4.
Negri bodies are always present in Rabies. (T
or F)
Which is not considered to be a vector of
rabies:
a)
b)
c)
d)
e)
Dogs
Fox
Bat
Squirrel
Raccoon
Questions
5.
A stay dog bit a child. The dog was not seen
by anyone else and escaped and is unavailable
for capture. There is no epidemiologic
evidence of rabies in dogs in your area.
Rabies prophylaxis includes:
a)
b)
c)
d)
Initiate rabies vaccine and administer HRIG
Initiate vaccine only
Administer HRIG only
No prophylaxis initiated, observation.
Answers: 1-F, 2-B, 3-F, 4-D, 5-D