1. Tetanus & Rabies Dr. Kiss Chapt. 146-147 January 12, 2005 slides by
Scott Gunderson PGY-2

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

3. 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

4. Pathophysiology Wound contamination with Clostridium tetani
Motile, nonencapsulated, anaerobic, gram positive rod
Spore forming and ubiquitous in soil and animal feces

5. 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

6. 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

7. 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)

8. 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

9. Four Clinical Forms
Local
Generalized
Cephalic
Neonatal

10. Local Tetanus
Rigidity of the muscles in proximity to the site of injury
Usually resolves completely in weeks to months
May develop into generalized

11. 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

12. 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

13. Trismus and Sardonic Smile

14. Opisthotonos

15. Generalized Tetanus Autonomic nervous system Hypersympathetic state
Usually in the second week
Tachycardia
HTN
Diaphoresis
Increased urinary catecholamines
Significant morbidity and mortality

16. Cephalic Tetanus Results from an injury to the head or otitis media
Cranial nerves affected most commonly the seventh
Poor prognosis

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

18. Neonatal Tetanus Signs Presents in the 2nd week of life Weakness
Irritability
Inability to suck
Presents in the 2nd week of life

19. 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

20. Tetanus Ddx Strychnine poisoning Dystonic reaction Hypocalcemic tetany
Peritonsillar abscess
Peritonitis
Meningeal irritation
Rabies
TMJ

21. 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

22. 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

23. Treatment TIG Usual dose is 3,000 to 6,000 units
Administered IM opposite side as Td given
Give before wound debridement

24. Treatment Antibiotics Questionable utility but usually given
Metronidazole
antibiotic of choice
Avoid penicillin
it is a GABAA antagonist and may worse symptoms

25. Treatment Muscle relaxants Tetanospasmin Midazolam Baclofen
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

26. 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

27. Treatment ANS dysfunction treatment Labetalol Magnesium sulfate
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

28. 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

29. Immunization and TIG guide
Clean, Minor
wounds
All other
History of Td Doses Td
TIG
Unknown or < 3
Yes No
Three or more
Td dose: 0.5cc IM
TIG dose: 250 U IM
DPT given if under 7, Td given if over 7

30. Rabies

31. 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

32. Microbiology Lyssavirus genus prototype 7 rabies groups in genus
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

33. Pathophysiology Virus course
Initial uptake of virus by monocytes in 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

34. 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

35. Negri bodies

36. 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

37. 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%)
Cats (3.4%)
Dogs (1.6%)
Cattle (1.1%)
Horses, donkeys, mules (0.71%)
Sheep, goats, camels (0.15%)
Others and ferrets (0.06%)

40. Epidemiology Dogs Very rare documented rabies in:
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

41. Epidemiology Transmission Bites and scratches
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

42. 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. tree branch, or animal) 0%

43. 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 with a bat
2 with a dog
1 with a cow
1 with a cat
No identifiable source in the other 13

44. Preexposure 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

45. 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

46. 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

47. 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

51. 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

52. 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

53. 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

54. 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

55. 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

56. Special Circumstances
Pregnancy
No adverse effects of the vaccine or HRIG
Follow usual course in pregnancy if indicated

57. 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

58. Clinical Disease Incubation period Prodrome 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

59. Clinical Disease Acute neurologic phase Furious – 80% Paralytic – 20%
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

60. Clinical Disease Coma Death 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

61. 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

62. 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

63. Treatment Limited No specific treatment exists for clinical course
Treatment directed at the clinical complications

64. References
Tintinalli, Judith E., Emergency Medicine a Comprehensive Study Guide. Sixth edition. McGrw-Hill Companies, Inc Chapter Tetanus and Rabies. Pages
Centers for Disease Control. Accessed January 5, 2005.

65. Questions
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

66. Questions 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

67. Questions
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