Tetanus & Rabies

April 1, 2008

Anwar Wardy W

FKK UMJ
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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 immunization history Only 27% of Americans older than age 70 have adequate immunity to tetanus

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Pathophysiology

Wound contamination with Clostridium

tetani

Motile, nonencapsulated, anaerobic, gram positive rod Spore forming and ubiquitous in soil and animal feces

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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

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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 skeletal muscle, in the spinal cord, and in the sympathetic nervous system Prevents release of inhibitory neurotransmitters glycine and gammaaminobutyric acid (GABA)

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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

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Four Clinical Forms

Local Generalized Cephalic Neonatal

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Local Tetanus

Rigidity of the muscles in proximity to the site of injury Usually resolves completely in weeks to months

May develop into generalized

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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

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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 otitis media Cranial nerves affected most commonly the seventh

Poor prognosis

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Neonatal Tetanus

400,000 worldwide deaths annually Results from inadequately immunized mothers Frequent after unsterile treatment of the cord stump

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Neonatal Tetanus

Signs

Weakness
Irritability Inability to suck

Presents in the 2nd week of life

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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

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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 neuromuscular blockade as respiratory compromise may develop Minimal environmental stimuli to avoid reflex convulsive spasms Initial wound debridement to improve oxygenation

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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

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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 it is a GABAA antagonist and may worse symptoms

Avoid penicillin

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Treatment

Muscle relaxants

Tetanospasmin

prevents neurotransmitter release at inhibitory interneurons and therapy of tetanus is aimed at restoring balance preferred agent as it is water soluble specific GABAB agonist that has also been used

Midazolam

Baclofen

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Treatment

Neuromuscular blockade

Blockade often required to allow respiration and to prevent fractures and rhabdomyolysis Succinylcholine

recommended for initial airway management

treatment of choice for long term blockade

Vecuronium

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Treatment

ANS dysfunction treatment

Labetalol

useful for treatment due to combined alpha and beta activity inhibits the release of epinephrine and norepinephrine from the adrenal glands central alpha receptor agonist for cardiac stability

Magnesium sulfate

Clonidine

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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

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Immunization and TIG guide

Clean, Minor wounds History of Td Doses Unknown or < 3 Three or more All other wounds

Td Yes No

TIG No No

Td Yes Yes

TIG Yes No

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

Rabies

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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

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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 human cases of disease

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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

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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
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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Cats (3.4%) Dogs (1.6%) Cattle (1.1%) Horses, donkeys, mules (0.71%) Sheep, goats, camels (0.15%) Others and ferrets (0.06%)

Epidemiology

Dogs

Less than 5% of animal cases in US, Canada and Europe Greater than 90% of animal cases in developing countries
Squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, domesticated rabbits and other small rodents Almost never requires post exposure prophylaxis

Very rare documented rabies in:

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Epidemiology

Transmission

Saliva though bite of an rabid animal most common Aerosolized in bat caves Mucus membrane transmission also reported
Risk of developing rabies dependant on the location injury, depth, an number of bites

Bites and scratches

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Infection Risk

Risk of infection Multiple bites around the face 80-100%

Single bite Superficial bite on the extremity Contamination of open wound by saliva Transmission via fomites (e.g. tree branch, or animal)
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15-40% 5-10% 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 8 2 1 1 with with with with a a a a bat dog cow cat

Animal contact identified in 12

No identifiable source in the other 13

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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

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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

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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

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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 Sacrifice animal, test for rabies, and initiate HRIG and vaccine

Unusual behavior

Positive Complete course of vaccine Negative Discontinue course

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Possible animal exposure Carnivore, bat or salivary exposure Bird, reptile, rodent or nonsalivary exposure Bat, skunk, raccoon, cow, bobcat, coyote, or fox Captured No Vaccine needed

Dog or cat

Captured and quarantined Sacrifice and test Initiate vaccine +HRIG

Normal behavior 10 days

No vaccine needed

Rabid Vaccine +HRIG Not Rabid Discontinue vaccine

Strange behavior Sacrifice, initiate vaccine and HRIG Rabid Vaccine + HRIG Not Rabid Discontinue vaccine Escaped No epidemiologic prevalence in area No vaccine needed

Escaped

Vaccine + HRIG

Epidemiologic prevalence

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Vaccine +HRIG

Bat, skunk, raccoon, cow, bobcat, coyote, or fox

Captured and quarantined

Escaped

Sacrifice and test Initiate vaccine +HRIG

Vaccine + HRIG

Rabid Vaccine +HRIG

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Not Rabid Discontinue vaccine

Dog or cat

Captured Normal behavior 10days

Escaped No epidemiologic prevalence in area

No vaccine needed

No vaccine needed
Epidemiologic prevalence

Strange behavior Sacrifice, initiate vaccine and HRIG

Vaccine +HRIG

Rabid Vaccine + HRIG Not Rabid Discontinue vaccine

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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

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Postexposure Prophylaxis

Vaccine reactions

Minor reaction

Erythema, swelling, pain 30-74% Headache, nausea, abdominal pain, muscle aches 5-40% Rarely reported

Systemic reaction

Anaphylaxis and neurological symptoms

Vaccine should not be stopped for minor or systemic reactions

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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

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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

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Special Circumstances

Travelers

Preexposure prophylaxis

Recommended if prevalence and possible exposure Veterinarians, animal handlers, spelunkers, certain lab workers If initiated in another country contact health department for recommendations

Non-FDA postexposure prophylaxis

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Special Circumstances

Pregnancy

No adverse effects of the vaccine or HRIG Follow usual course in pregnancy if indicated

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Special Circumstances

Children

Vaccine

Same dose and same course Dose is based on weight If quantity of HRIG not sufficient to infiltrate all wounds may be diluted with saline

HRIG

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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
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

Prodrome

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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% Paralysis in the extremity, diffuse or ascending Fever and nuchal rigidity

Paralytic 20%

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Clinical Disease

Coma

Almost always present within 10 days

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

Death

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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

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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

Emergency Medicine a Comprehensive Study Guide. Sixth edition. McGrwHill 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,

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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

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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

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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

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