Tetanus Rabies

7/27/2019 Tetanus Rabies

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Tetanus & RabiesChapt. 146-147

January 12, 2005

Dr. Kiss

slides by

Scott Gunderson PGY-2


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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


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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 immunizationhistory

Only 27% of Americans older than age 70 haveadequate immunity to tetanus


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Pathophysiology

Wound contamination with Clostridiumtetani

Motile, nonencapsulated, anaerobic, grampositive rod

Spore forming and ubiquitous in soil andanimal feces


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Pathophysiology

Usually introduced in the spore forming state,then germinates to the toxin producingvegetative form

Requires decreased tissue oxygen tension togerminate

Vegetative state produces two exotoxins Tetanolysin

Tetanospasmin


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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


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Tetanospasmin

Acts on the motor end plates of skeletalmuscle, in the spinal cord, and in thesympathetic nervous system

Prevents release of inhibitoryneurotransmitters glycine and gamma-aminobutyric acid (GABA)


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Clinical Features

Tetanospasmin responsible for generalizedmuscular rigidity, violent muscular contractions,and instability of the ANS.

Typical wound is a puncture, but no wound isidentified in up to 10%

Other routes are surgical procedures, otitismedia, abortion, umbilical stump and drugabusers


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Four Clinical Forms

Local

Generalized

Cephalic

Neonatal


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Local Tetanus

Rigidity of the muscles in proximity to thesite of injury

Usually resolves completely in weeks tomonths

May develop into generalized


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Generalized Tetanus

Most common form

Most common presenting complaint is painand stiffness of the masseter muscles(Lockjaw)

Short axon nerves affected initiallytherefore starts in the face, then neck,trunk, and extremities


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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


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Trismus and Sardonic Smile


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Opisthotonos


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Generalized Tetanus

Autonomic nervous system

Hypersympathetic state

Usually in the second week

Tachycardia

HTN

Diaphoresis

Increased urinary catecholamines Significant morbidity and mortality


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Cephalic Tetanus

Results from an injury to the head or otitismedia

Cranial nerves affected most commonlythe seventh

Poor prognosis


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Neonatal Tetanus

400,000 worldwide deaths annually

Results from inadequately immunizedmothers

Frequent after unsterile treatment of thecord stump


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Diagnosis

Clinical diagnosis

No laboratory confirmatory tests

Wound cultures not very useful as C. tetanimaybe recovered without tetanus

Immunization history usually unknown orinadequate


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Tetanus Ddx

Strychnine poisoning

Dystonic reaction

Hypocalcemic tetany

Peritonsillar abscess

Peritonitis

Meningeal irritation

Rabies

TMJ


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Treatment

Admit to ICU

Be prepared for intubation with neuromuscularblockade as respiratory compromise maydevelop

Minimal environmental stimuli to avoid reflexconvulsive spasms

Initial wound debridement to improveoxygenation


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Treatment

Tetanus Immunoglobulin (TIG)

Neutralizes wound and circulatingtetanospasmin

Does not neutralize toxin already bound tothe nervous system

Does not improve clinical symptoms

Decreases mortality


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Treatment

TIG

Usual dose is 3,000 to 6,000 units

Administered IM opposite side as Td given

Give before wound debridement


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Treatment

Antibiotics

Questionable utility but usually given

Metronidazole

antibiotic of choice

Avoid penicillin

it is a GABAA antagonist and may worse symptoms


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Treatment

Muscle relaxants

Tetanospasmin

prevents neurotransmitter release at inhibitory

interneurons and therapy of tetanus is aimed atrestoring balance

Midazolam

preferred agent as it is water soluble

Baclofen

specific GABAB agonist that has also been used


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Treatment

Neuromuscular blockade

Blockade often required to allow respirationand to prevent fractures and rhabdomyolysis

Succinylcholine recommended for initial airway management

Vecuronium

treatment of choice for long term blockade


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Treatment

ANS dysfunction treatment

Labetalol

useful for treatment due to combined alpha and

beta activity

Magnesium sulfate

inhibits the release of epinephrine andnorepinephrine from the adrenal glands

Clonidine

central alpha receptor agonist for cardiac stability


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Immunization

Disease does not confer immunity so those thatrecover 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


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Immunization and TIGguide

Td dose: 0.5cc IM TIG dose: 250 U IM DPT given if under 7, Td given if over 7

Clean, Minor

wounds

All other

wounds

History of TdDoses Td TIG Td TIG

Unknown or < 3 Yes No Yes Yes

Three or more No No Yes No


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Rabies


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Rabies

Rabies ranks number 10 worldwide as acause of mortality

50,000 60,000 deaths annuallyworldwide

Rare human cases in US but 35,000people provided prophylaxis annually


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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 humancases of disease


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Pathophysiology

Virus course

Initial uptake of virus by monocytes in 48-96hours

Crosses motor end-plate to travel up the axonto the dorsal root ganglia to the spinal cordand the CNS

Then spreads outward via peripheral nervesto infect almost all tissue of the body


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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


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Negri bodies


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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


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Epidemiology

Wild animals (93%)

Raccoons (37.7%)

Skunks (30.2%)

Bats (16.8%)

Foxes (6.2%)

Others (2.2%)

Domestic animals(7%)

Cats (3.4%)

Dogs (1.6%)

Cattle (1.1%)

Horses, donkeys, mules(0.71%)

Sheep, goats, camels(0.15%)

Others and ferrets0.06%

7,369 cases of animal rabies in the US in 2000


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http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm


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http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm


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Epidemiology

Dogs

Less than 5% of animal cases in US, Canada andEurope

Greater than 90% of animal cases in developingcountries

Very rare documented rabies in:

Squirrels, hamsters, guinea pigs, gerbils, chipmunks,

rats, mice, domesticated rabbits and other smallrodents

Almost never requires post exposure prophylaxis


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Epidemiology

Transmission

Saliva though bite of an rabid animal mostcommon

Aerosolized in bat caves

Mucus membrane transmission also reported

Bites and scratches

Risk of developing rabies dependant on thelocation injury, depth, an number of bites


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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

0.1%

Transmission via fomites (e.g. treebranch, or animal)

0%


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Epidemiology

32 cases reported from 1980 to 1996 inthe US 7 had a known animal bite

6 dog bites in a foreign country 1 bat bite

Animal contact identified in 12 8 with a bat

2 with a dog 1 with a cow

1 with a cat

No identifiable source in the other 13


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Preexposure Prophylaxis

Prophylaxis

Individuals with occupations or recreation thatplace them at risk should receive the series

4 shot series with booster shots required

Does not eliminate need for postexposureprophylaxis

No need for HRIG and less doses of vaccine


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Postexposure Prophylaxis

Indicated for all persons possibly exposed to arabid 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 hasbeen show in experimental animals to markedlyreduce the rate of infection


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Bats

Increasingly important wildlife vectors oftransmission of rabies

All cases of possible bat bites the batshould be collected and tested for rabies

Bat unavailable

Begin postexposure prophylaxis


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Dogs, Cats, and Ferrets

Observation

CDC recommends 10 days of observation of ahealthy dog, cat, or ferret after a bite

Normal behavior No action needed

Unusual behavior

Sacrifice animal, test for rabies, and initiate HRIGand vaccine

Positive Complete course of vaccine

Negative Discontinue course

Possible animal exposure


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Carnivore, bat or

salivary exposure

Bird, reptile, rodent or

nonsalivary exposure

Dog or catBat, skunk, raccoon, cow,

bobcat, coyote, or fox

Captured and quarantined

Escaped

Vaccine + HRIG

Sacrifice and test

Initiate vaccine +HRIG

Rabid

Vaccine +HRIG

Not Rabid

Discontinue vaccine

Captured

Escaped

No epidemiologic

prevalence in area

No vaccine needed

Epidemiologic prevalence

Vaccine +HRIG

Normal behavior 10 days

No vaccine needed

Strange behavior

Sacrifice, initiate

vaccine and HRIG

Rabid

Vaccine + HRIG

Not Rabid

Discontinue vaccine

No Vaccine needed

Bat skunk raccoon cow


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Bat, skunk, raccoon, cow,

bobcat, coyote, or fox

Captured and quarantined Escaped

Vaccine + HRIGSacrifice and testInitiate vaccine +HRIG

Rabid

Vaccine +HRIG

Not Rabid

Discontinue vaccine

Dog or cat


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g

Captured Escaped

No epidemiologic

prevalence in area

No vaccine needed

Epidemiologic

prevalence

Vaccine +HRIG

Normal behavior

10days

No vaccine needed

Strange behavior

Sacrifice, initiate

vaccine and HRIG

Rabid

Vaccine + HRIG

Not RabidDiscontinue vaccine


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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


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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 minoror systemic reactions


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Special Circumstances

Prior rabies immunization

Either prior preexposure course or fullpostexposure course

No HRIG

Course shortened to 2 doses

One dose on presentation

One dose three days later


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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


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Travelers

Preexposure prophylaxis

Recommended if prevalence and possible exposure

Veterinarians, animal handlers, spelunkers, certainlab workers

Non-FDA postexposure prophylaxis

If initiated in another country contact health

department for recommendations


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Pregnancy

No adverse effects of the vaccine or HRIG

Follow usual course in pregnancy if indicated


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Children

Vaccine

Same dose and same course

HRIG Dose is based on weight

If quantity of HRIG not sufficient to infiltrate allwounds may be diluted with saline


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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


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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


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Clinical Disease

ComaAlmost always present within 10 days

Death Occurs from complications such as pituitary

dysfunction, seizures, respiratory dysfunction,cardiac dysfunction, ANS dysfunction, ARF, orinfection

Outcome almost always fatal No person without post-exposure prophylaxis

in the US has survived since 1980


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Diagnosis

Rabies should be in the differential of anyacute encephalitis

May be confused with poliomyelitis,Guillain-Barre syndrome, transversemyelitis, postvaccinial encephalomyelitis,

CVA, atropine-like poisoning, other viralencephalitis


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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


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Treatment

Limited

No specific treatment exists for clinical course

Treatment directed at the clinical

complications


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References

Tintinalli, Judith E., Emergency Medicine a Comprehensive Study Guide.Sixth edition. McGrw-Hill Companies, Inc. 2004. Chapter 146-147. Tetanusand Rabies. Pages 943-953.

Centers for Disease Control.http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm,

Accessed January 5, 2005.
http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htmhttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm


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Questions

3. Negri bodies are always present in Rabies. (Tor F)

4. Which is not considered to be a vector of

rabies:a) Dogs

b) Fox

c) Bat

d) Squirrel

e) Raccoon


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Questions

5. A stay dog bit a child. The dog was not seenby anyone else and escaped and is unavailablefor capture. There is no epidemiologicevidence of rabies in dogs in your area.

Rabies prophylaxis includes:a) Initiate rabies vaccine and administer HRIG

b) Initiate vaccine only

c) Administer HRIG only

d) No prophylaxis initiated, observation.

Answers: 1-F, 2-B, 3-F, 4-D, 5-D

Tetanus Rabies

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