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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.

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Tetanus rabies l.jpg

Tetanus & Rabies

Chapt. 146-147

January 12, 2005

Dr. Kiss

slides by

Scott Gunderson PGY-2


Tetanus epidemiology l.jpg
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 l.jpg
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


Tetanospasmin l.jpg
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 gamma-aminobutyric 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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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


Tetanus ddx l.jpg

Strychnine poisoning

Dystonic reaction

Hypocalcemic tetany

Peritonsillar abscess

Peritonitis

Meningeal irritation

Rabies

TMJ

Tetanus Ddx


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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


Treatment23 l.jpg
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 at restoring balance

    • Midazolam

      • preferred agent as it is water soluble

    • Baclofen

      • specific GABAB agonist that has also been used


Treatment26 l.jpg
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


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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 and norepinephrine from the adrenal glands

    • Clonidine

      • central alpha receptor agonist for cardiac stability


Immunization l.jpg
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

  • Td dose: 0.5cc IM

  • TIG dose: 250 U IM

  • DPT given if under 7, Td given if over 7



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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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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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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 ferrets (0.06%)

Epidemiology

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


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


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


Epidemiology40 l.jpg
Epidemiologyhttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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


Epidemiology41 l.jpg
Epidemiologyhttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 l.jpg
Infection Riskhttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • Risk of infection


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

  • 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 with a bat

      • 2 with a dog

      • 1 with a cow

      • 1 with a cat

    • No identifiable source in the other 13


Preexposure prophylaxis l.jpg
Preexposure Prophylaxishttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 l.jpg
Postexposure Prophylaxishttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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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Batshttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 Ferretshttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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


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Postexposure Prophylaxishttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 prophylaxis52 l.jpg
Postexposure Prophylaxishttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 l.jpg
Special Circumstanceshttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 Circumstanceshttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 Circumstanceshttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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


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Special Circumstanceshttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • Pregnancy

    • No adverse effects of the vaccine or HRIG

    • Follow usual course in pregnancy if indicated


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Special Circumstanceshttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 l.jpg
Clinical Diseasehttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 disease59 l.jpg
Clinical Diseasehttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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 Diseasehttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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


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

  • 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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Diagnosishttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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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Treatmenthttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • Limited

    • No specific treatment exists for clinical course

    • Treatment directed at the clinical complications


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

  • 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 l.jpg
Questionshttp://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm

  • 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:

    • Td and TIG IM

    • Td only

    • TIG only

    • None as he was previously vaccinated


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

  • Negri bodies are always present in Rabies. (T or F)

  • Which is not considered to be a vector of rabies:

    • Dogs

    • Fox

    • Bat

    • Squirrel

    • Raccoon


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

  • 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:

    • 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