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Tetanus Mary & Victoria Tetanus •What is Tetanus? •The Biology: Clostridium tetani •Prevention by Vaccination •Treatment WHAT IS TETANUS? Bacterial disease Affects the nervous system Often caused by infection to cuts/wounds, especially when they are deep Other causes: Burns Abortion Frostbite IV drug abuse Oposthotonus, by Sir Charles Bell (1809). Source: http://www.brown.edu/Courses/Bio_160/Projects2004/pertussis/diphther. htm WHAT IS TETANUS? Continual excitatory discharge of the motor and autonomic nervous system –Lockjaw –Suffocation –Muscle rigidity/spasms –Stiffness –Bell’s Palsy –Dysphagia Uncontrollable muscle spasms may lead to respiratory or cardiac arrest, and severe BP changes WHAT IS TETANUS? Generalized Tetanus Most common Symptoms may progress in a descending pattern Frequent muscle spasms lasting several minutes Localized Tetanus Uncommon Affects a specific area of the body Same area as the infection site May be a precursor to generalized tetanus WHAT IS TETANUS? Neonatal Tetanus Affects newborns without passive immunity from their mother Usually due to infected umbilical stump Rare in U.S., but prevalent in underdeveloped Neonatal Tetanus ID# 6374 (1995). Source: Center for countries Disease Control--Public Health Image Library WHAT IS TETANUS? Cephalic Tetanus Rare form Mainly involving the facial nerves Sometimes occurs with ear infections, or after head injury Man with Cephalic Tetanus ID# 1657 (1965). Source: Center for Disease Control--Public Health Image Library INCIDENCE OF TETANUS Decreased prevalence in industrialized nations Tetanus is rare in the U.S. due to immunizations and improved wound care Approximately 5 deaths per year In the U.S. it affects mostly older people Gardening during retirement years Mortality rate in the elderly: >50% INCIDENCE OF TETANUS Worldwide public health issue Ninth most common cause of death due to infectious disease Approximately 250,000 deaths per year Global fatality rate: 30-50% Neonatal tetanus Mortality rate: 90% THE BIOLOGY: CLOSTRIDIUM TETANI Obligate anaerobe Bacillus About 0.3-1.1µm by 3-12µm Gram-positive Mesophile Endospores “drum-stick” shape Motile Some may produce flagella 3-4 times it’s length Gram Stain of Clostridium tetani –ID#6372 (1995). Source: Center for Disease Control--Public Health Image Library THE BIOLOGY: CLOSTRIDIUM TETANI Clostridium tetani Produces two exotoxins: Tetanospasmin—neurotoxin that causes muscle spasms Tetanolysin—no known clinical significance Incubation period = 3 - 14 days Produces spores Extremely resilient to temperature, moisture, chemicals, and even 10-15 minutes of autoclaving (121˚C) Germination occurs when exposed to anaerobic conditions such as wounds and tissue necrosis THE BIOLOGY: CLOSTRIDIUM TETANI Commonly found in: Soil Manure/human & animal feces Dust Rust Noncommunicable THE BIOLOGY: CLOSTRIDIUM TETANI Tetanospasmin: Excreted into the bloodstream Travels through nerves or by lymphocytes to CNS Attach to presynaptic inhibitory nerve endings Blocks the release of inhibitor neurotransmitters, causing muscle spasms One of the most potent toxins known Lethal dose: 175 nanograms for a 154lb/70kg person (That’s 0.000175 miligrams!!) PREVENTION BY VACCINATION The best way to prevent Tetanus is by vaccination Virtually 100% efficacy rate in properly immunized people Girl Receives Vaccine–ID#9297 (2006). Source: Center for Disease Control--Public Health Image Library PREVENTION BY VACCINATION Three types of Vaccines: DTaP vaccine (Diphtheria, Tetanus, Pertussis) DT vaccine (Diphtheria, Tetanus) Td Vaccine (Tetanus, Diphtheria) PREVENTION BY VACCINATION DTaP: “3-in-1” Recommended for childhood immunization Protects against Diphtheria, Tetanus, and Pertussis Given 5 doses (2 months, 4 months, 6 months, 15-18 months, 4-6 years) Only for children under age 7 PREVENTION BY VACCINATION DT “2-in-1” For children less than 7 years old. If a child has an allergic reaction to the Pertussis vaccine in DTaP. PREVENTION BY VACCINATION Td “2-in1” Adult vaccine Slightly differs in dosage of Diphtheria vaccine than in DT. Anyone over the age of 7 Injected, usually in arm PREVENTION BY VACCINATION T Vaccine: A vaccine for Tetanus by itself can be given (Tetanus Immune Globulin/HTIG) -Injected into arm -Made from blood of person or animal containing antibodies against Tetanus Typically for an adult who is having a dirty wound/injury taken care of TREATMENT Although immunization is available, Tetanus is not eradicated. TREATMENT Those at risk: Lack of immunization Partial Immunization Fully immunized patients have still been documented to contract the disease Very rare TREATMENT Main Goals: Use a method of attacking the anaerobic, sporeforming bacillus Find a way around the actions of the nervous system caused by the Tetanus toxin TREATMENT Recognition of Tetanus Vital to the victim Stabilize and Resuscitate Neutralize Tetanus Toxin Clean wound with antibiotics Treat any muscle spasms Control Pain TREATMENT Resuscitation Most common cause of death in Tetanus is due to respiratory failure. Can be a general complication of the disease, failure to treat spasms quickly enough, or as a side effect of medications. Tracheotomy is performed as precaution. Helps to prevent a stimulus from causing another spasm. TREATMENT Class Drug Indication Benzodiazepines 1. Diazepam 2. Midazolam Spasm Control and Sedation GABA-B Agonist 1. Inthrathecal baclofen Spasm Control Refractory to BZ Muscle Relaxant 1. Dantrolene Spasm Control Alternative Neuromuscular blocking agents 1. Vecuronium 2. Pancuronium 3. Succinylcholine Spasm Control Refractory to BZ, Minimize Sedation Antibiotics 1. Metronidazole 2. Benzyl Penicillin 3. Benzathine Penicillin Elimination of C. Tetani Toxin Alpha and Beta Blocker 1. Labetalol Control of Autonomic Dysfunction Alpha 2 Agonist 1. Clonidine Control of Autonomic Dysfunction Opioid 1. Morphine Sulfate Control of Pain and Peripheral Vasodilatation Detoxified Exotoxin 1. DTaP 2. Tetanus Toxoid Active Immunization Human Immunoglobin 1. HTIG Passive Immunization, Neutralizes Free Exotoxin, Treatment of Tetanus, Post exposure TREATMENT HTIG (immune globulin) Tetanus toxin binds to nerve endings that normally calm the muscle, blocking the inhibitory signals. HTIG neutralizes the free form tetanospasmin toxin by binding to it, prohibiting it from blocking signals Frees the neurotoxin without crossing blood brain barrier TREATMENT Administration of Td Contracting the disease does not ensure immunity Injected simultaneously with HTIG Enhances short-term (passive) immunity and longterm (active) immunity. TREATMENT Eliminating the toxin: Excision – Surgical removal of the toxin producing organisms. Creates an aerobic environment, hindering the growth of C. tetani spores Only to be done after Td is given to the patient due to the release of tetanospasmin during the procedure TREATMENT Antibiotic mode of action depends on which antibiotic is used Metronidazole is used most often for tetanus Works by inhibiting nucleic acid synthesis QUESTIONS??