Tetanus & Rabies

1. Tetanus & Rabies Chapt. 146-147 January 12, 2005 Dr. Kiss 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 • 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. Strychnine poisoning Dystonic reaction Hypocalcemic tetany Peritonsillar abscess Peritonitis Meningeal irritation Rabies TMJ Tetanus Ddx

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 • 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 • 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 • 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 • 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 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

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. 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

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

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

40. 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

41. 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

42. Infection Risk • Risk of infection

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 • 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