Tetanus & Rabies Dr. Kiss Chapt. 146-147 January 12, 2005 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 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

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

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

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 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)

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

Four Clinical Forms Local Generalized Cephalic Neonatal

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

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

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

Trismus and Sardonic Smile

Opisthotonos

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

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

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

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

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 Strychnine poisoning Dystonic reaction Hypocalcemic tetany Peritonsillar abscess Peritonitis Meningeal irritation Rabies TMJ

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

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

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

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

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

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

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

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

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

Rabies

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

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

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

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

Negri bodies

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

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%)

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

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

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

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

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%

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

References 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 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

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

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