TETANUS Manvi gupta rabiezahran@hotmail.com 1 Introduction. Definition Tetanus is an acute , often fatal disease caused by an exotoxin produced by the bacterium Clostridium tetani. But prevented by immunization with tetanus toxoid. It is characterized by generalized rigidity and convulsive spasms of skeletal muscles . The muscle stiffness usually involves the jaw (lockjaw)and neck and then becomes generalized. rabiezahran@hotmail.com 2 Introduction (con ). History: • Tetanus was first described in Egypt over 3000 years ago(Edwin smith papyrus). • It was again described by Hippocrates •Carle and Rattone in 1884 who first noticed tetanus in animals by injecting them with pus from a fatal human tetanus case. •During the same year , Nicolaier produced tetanus in animals by injecting them with samples of soil. rabiezahran@hotmail.com 3 Introduction(con). History: •In 1889,Kitasato isolated the organism from a human victim,showed that it produced disease when injected into animals,and reported that the toxin could be neutralized by specific antibodies. •Nocard demonstrated the protective effect of passively transferred antitoxin,and passive immunization in humans •Passive immunization and prophylaxis for tetanus during World War I •Tetanus Toxoid was first widely used during world war II rabiezahran@hotmail.com 4 Causative Organism Clostridium tetani Acridine orange stain of characteristic C tetani with endospores wider than the characteristic drumstick shape. rabiezahran@hotmail.com 5 Clostridium tetani • C.tetani is : * a slender gram-positive, anaerobic rod that may develop a terminal spore giving it a drumstick appearance. * It is sensitive to heat and cannot survive in the presence of oxygen. • It produces two exotoxins : 1) tetanolysin . its function of is not known with certainty. 2) tetanospasmin is a neurotoxin and causes the clinical manifestations of tetanus. Tetanospasmin estimated Human lethal dose is 2.5 ng/kg ((a nanogram is one billionth of a gram) rabiezahran@hotmail.com 6 Courtesy : Google Image on tetanus rabiezahran@hotmail.com 7 Spores: *very resistant to heat and the usual antiseptics. •They can not survive autoclaving at (121 °C)for 20 minutes. • relatively resistant to phenol & other chemical agents. • widely distributed in soil and in the intestines and faces of horses, sheep, cattle , dogs , cats , rats, guinea pigs , and chickens. Manure-treated soil may contain large numbers of spores. Spores may persist for months to years. rabiezahran@hotmail.com 8 rabiezahran@hotmail.com 9 Epidemiology: a:Occurrence. b:Reservoir . c:Mode of Transmission d:Communicability rabiezahran@hotmail.com Source : CDC.,google pictures 10 Epidemiology: • Tetanus - Greek Word -- Tetanos -to Contract • Tetanus Remains a Major Public Health Problem in the Developing World and Is Still Encountered in the Developed World. • There Are about 800 000 : 1 Million Deaths Due to Tetanus Each Year.80% of These Deaths Occur in Africa and South East Asia and It Remains Endemic in 90 Countries World Wide. • 1998 - U.K,USA 7 Cases, 41 Cases Including One Neonate rabiezahran@hotmail.com 11 Epidemiology(con): •Occurrence: Tetanus occurs worldwide but is most frequently encountered in densely populated regions in hot , damp climates with soil rich in organic matter. •Reservoir : Organisms are found primarily in the soil and intestinal tracts of animals and humans. •Mode of Transmission: is primarily by: * contaminated wounds, *Tissue injury( surgery , burns , deep puncture wounds , crush wounds , Otitis media ,dental infection , animal bites, abortion , and pregnancy). rabiezahran@hotmail.com 12 Epidemiology (contu ): •Communicability Tetanus is not contagious from person to person .It is the only vaccinepreventable disease that is : “infectious but not contagious”. Temporal pattern : Peak in winter and summer season. Incubation Period: 8 DAYS ( 3-21 DAYS) rabiezahran@hotmail.com Source : CDC.,google pictures 13 Host Factors : • Age : I t is the disease of active age (5-40 years), New born baby, female during delivery or abortion • Sex : males > females • Occupation : Agricultural workers are at higher risk • Rural > Urban areas . • Immunity : Herd immunity(community immunity) does not protect the individual. • Environmental and social factors: Unhygienic custom habits , Unhygienic delivery practices. rabiezahran@hotmail.com 14 Pathogenesis . rabiezahran@hotmail.com 15 Pathogenesis *C. tetani usually enters the body through a wound. *In the presence of anaerobic conditions, the spores germinate and start to produce toxin and disseminated via blood and lymphatics. *Toxin reaches the CNS . by passing along the motor nerves to the anterior horn cells of the spinal cord . (The shortest peripheral nerves are the first to deliver the toxin to the CNS, which leads to the early symptoms of facial distortion and back and neck stiffness.) *Toxins act at several sites within the central nervous system, including : 1) peripheral motor end plates, 2) spinal cord, 3) brain, 4) sympathetic nervous system. rabiezahran@hotmail.com 16 How tetanospasmin reaches the CNS . • Tetanospasmin is taken up by motor neurons in the peripheral nerve endings through endocytosis. It then travels along the axons until it reaches the motor neuron cell bodies in the spinal cord, by fast rabiezahran@hotmail.com retrograde transport. 17 Speed of toxin transport: The toxin travels via intra axonal transport at a rate of 75 -250 mm/day . A process which takes 2 -14 days to reach the CNS. rabiezahran@hotmail.com 18 Pathogenesis (con ) The typical clinical manifestations of tetanus are caused when tetanus toxin interferes with release of neurotransmitters blocking inhibitory impulses. This leads to unopposed muscle contraction and spasm. Seizures may occur, and the autonomic nervous system may also be affected. rabiezahran@hotmail.com 19 Mechanism of Action of Tetanus Toxin rabiezahran@hotmail.com 20 Clinical Features rabiezahran@hotmail.com 21 Incubation period : I P. ranges from 3 to 21 days, usually about 8 days. In general : *The further the injury site is from the CNS, the longer the I P. *The shorter the I P, the higher the chance of death. * In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days. rabiezahran@hotmail.com 22 Types of tetanus: (On the basis of clinical findings, three different forms of tetanus have been described). 1) Local tetanus is an uncommon form of the disease,in which patients have persistent contraction of muscles in the same anatomic area of the injury. Local tetanus may precede the onset of generalized tetanus but is generally milder .Only about 1%of cases are fatal. rabiezahran@hotmail.com Source : CDC. 23 Types of tetanus(con) 2)Cephalic tetanus is a rare form of the disease, occasionally occurring with otitis media(ear infections)in which C. tetani is present in the flora of the middle ear , or following injuries to the head . There is involvement of the cranial nerves, especially in the facial area. rabiezahran@hotmail.com 24 Types of tetanus(contu) 3) generalized tetanus It is The most common type (about 80%)of reported tetanus .The disease usually presents with a descending pattern. Neonatal tetanus is a form of generalized tetanus rabiezahran@hotmail.com 25 Sequence of events Lock Jaw Stiff Neck Difficulty Swallowing Muscle Rigidity Spasms rabiezahran@hotmail.com 26 rabiezahran@hotmail.com 27 Risus Sardonicus in Tetanus Patient A person suffering from tetanus undergoes convulsive muscle rabiezahran@hotmail.com 28 contractions of the jaw--called LOCKJAW Opisthotonos in Tetanus Patient The contractions by the muscles of the back and extremities may become so violent rabiezahran@hotmail.com 29 and strong that bone fractures may occur Opisthotonos in Tetanus Patient rabiezahran@hotmail.com 30 Oposotinus postion in tetanus rabiezahran@hotmail.com 31 Neck rigidity & retraction. rabiezahran@hotmail.com 32 Unfortunately, the affected individual is conscious throughout the illness, but cannot stop these contractions rabiezahran@hotmail.com 33 Rusty nail may cause prick & transmit tetanus rabiezahran@hotmail.com 34 Traumatic T. Puerperal T. Type of Otogenic T. Tetanus Idiopathic T. T. Neonatorum rabiezahran@hotmail.com 35 Complications . rabiezahran@hotmail.com 36 rabiezahran@hotmail.com 37 Diagnosis rabiezahran@hotmail.com 38 Laboratory diagnosis *There are no laboratory findings characteristic of tetanus. *The diagnosis is entirely clinical and does not depend upon bacteriologic confirmation. •C. tetani is recovered from the wound in only 30% of cases and can be isolated from patients who do not have tetanus. •Laboratory identification of the organism depends most importantly on the demonstration of toxin production in mice. rabiezahran@hotmail.com 39 Clinically it is confirmed by noticing the following features: 1. Risus sardonicus or fixed sneer. 2. Lock jaw. 3. Opisthotonos (extension of lower extremities, flexion of upper extremities and arching of the back. The examiners hand can be passed under the back of the patient when he lies on the bed in supine position.) 4. Neck rigidity rabiezahran@hotmail.com 40 Diagnostic tests for tetanus: Spatula Test : Apet and Kamad discribe a simple bedside test to diagnose tetanus : the posterior pharyngeal wall is touched with a spatula and a reflex spasm of the masseters indicates a +ve.test. This test shows 94 % sensitivity . and 100 % specificity. The altered whistle : This explained as an early effect of tone in facial muscles which causes the classic R . sardonicus rabiezahran@hotmail.com 41 scale for the severity and the prognosis of tetanus: Score : One point for each of the following 7 items: •I P. < 7 days (period between injury and 1st.symptom.) •Period of onset < 48 hours (period between 1st. Symptom and 1st. Spasm. ) •Acquired from burns, surgical wounds, compound fractures, or septic abortion . •Addiction (Narcotics) •Generalized tetanus •Temperature greater than 104°F (40°C) •Tachycardia greater than 120 beats per minute (>150 rabiezahran@hotmail.com 42 beats per min in neonates) Total score indicates the severity and the prognosis as follows: Score Severity Prognosis (mortality rate) 0 -1 mild < 10 % 2 -3 moderate 10 : 20 % 4 severe 20 : 40 % 5:6 very severe > 50 % rabiezahran@hotmail.com 43 1) Medical Management . 2) Wound Management . rabiezahran@hotmail.com 44 Medical Management Aim of TTT: (1) provide supportive care (until the tetanospasmin that is fixed in tissue has been metabolized ) by: • a: treatment of muscle spasm, • b: prevention of respiratory complications. • c: prevention of metabolic complications. (2)neutralization of circulating toxin to prevent the continued spread. (3) elimination of the source of toxin. rabiezahran@hotmail.com 45 How to treat : 1: Admit patients with severe: to the (ICU). For risk of reflex spasms . 2: maintain a dark and quiet room for the patient. 3: Avoid unnecessary procedures . 4: Seriously consider prophylactic intubation with succinylcholine in all patients with moderateto-severe clinical manifestations. Intubation and ventilation are required in 67% of patients. rabiezahran@hotmail.com 46 How to treat : 5:Perform tracheostomy in patients requiring intubation for more than 10 days. Tracheostomy has also been recommended after onset of the first generalized seizure. 7:Tetanus immune globulin (TIG)(passive immunization) is recommended for treatment of tetanus. TIG can only help remove unbound tetanus toxin, but it cannot affect toxin bound to nerve endings. A single IM. dose of 3000-5000 units is generally recommended for children and adults, with part of the dose infiltrated around the wound if it can be identified. rabiezahran@hotmail.com 47 How to treat : Recovered individuals : do not necessarily develop “natural Immunity” against the infection--because of extreme potency of the toxin and very small amount produced during the infection, It does not elicit a strong , protective immune response which would produce enough antibodies against future re-infection. rabiezahran@hotmail.com 48 How to treat : SO Active immunization with tetanus toxoid should begin or continue as soon as the person’s condition has stabilized. rabiezahran@hotmail.com 49 Drugs: 1) Penicillin G: Adult 10-24 million U/d. ( IV/IM/6h. ) Pediatric 100,000-250,000 U/kg/d. (IV/IM/6h. ) ( 10- to 14-d course of treatment is recommended.) rabiezahran@hotmail.com 50 Drugs: 2) Metronidazole : *considered as a drug of choice by many. * has a better safety profile, better tissue penetrability and negligible CNS excitability. (penicillin can cause seizures at high doses). It can also be given rectally Adult 500 mg orally/6h or 1 g IV /12h; not to exceed 4 g/d Pediatric 15-30 mg/kg/d IV divided /8-12h; not to exceed 2 g/d rabiezahran@hotmail.com ( 10- to 14-d course of treatment is recommended.) 51 Drugs: 3)Doxycycline : Used when there is contraindication to penicillin or metronidazol. Adult 100 mg orally/IV /12h Pediatric <8 years: Not recommended <45 kg : 4.4 mg/kg/d) PO/IV divided bid > 45 kg: Administer as in adults rabiezahran@hotmail.com 52 Drugs: Anticonvulsants: Sedative-hypnotic agents are the mainstays of tetanus treatment. 1) Diazepam (Valium): Depresses all levels of CNS, including limbic and reticular formation, possibly by increasing activity of GABA(γ-Amino-butyric acid ), a major inhibitory neurotransmitter. Adult Mild spasms: 5-10 mg PO /4-6h Moderate spasms: 5-10 mg IV(diluted in 8 ml glucose 5% or saline ) Severe spasms: Mix 50-100 mg in 500 mL D5W and infuse at 40 mg/h Pediatric Mild spasms: 0.1-0.8 mg/kg/d PO divided tid/qid Moderate or severe spasms: 0.1-0.3 mg/kg IV q4-8h rabiezahran@hotmail.com 53 2) Phenobarbital: used to * prolong effects of diazepam. * treat severe muscle spasms. Adult 1 mg/kg IM q4-6h; not to exceed 400 mg/d Pediatric 5 mg/kg/d IV/IM divided tid/qid rabiezahran@hotmail.com 54 Skeletal muscle relaxants These agents can inhibit both monosynaptic and polysynaptic reflexes at spinal level, possibly by hyperpolarization of afferent terminals. * Baclofen (Lioresal) a physiological GABA agonist Adult <55 years: 1000 mcg IT(intrathecal) >55 years: 800 mcg IT Pediatric <16 years: 500 mcg IT >16 years: Administer as inrabiezahran@hotmail.com adults 55 Differential Diagnoses Other Problems to Be Considered Mandible dislocations, Stroke , Encephalitis Subarachnoid Hemorrhage Hypocalcemia Dystonic Reactions Meningitis Peri-tonsillar Abscess Rabies Intraoral disease Odontogenic infections Globus hystericus Hepatic encephalopathy Hysteria Strychnine poisoning rabiezahran@hotmail.com 56 Wound Management . rabiezahran@hotmail.com 57 All wounds should be cleaned with H2O2&antiseptic. Necrotic tissue and foreign material should be removed. Passive immunization. Active immunization. Or Both. rabiezahran@hotmail.com 58 PREVENTION rabiezahran@hotmail.com 59 PREVENTION How to kill spores : Spores are extremely stable ,but killed by: • Immersion in boiling water for 15 minutes. • Autoclaving for 15-20 minutes at 121°c. • Sterilization by dry heat for 1 -3 hrs at 160 °C. • Ethylene oxide sterilization is sporocid. rabiezahran@hotmail.com 60 PREVENTION Fumigation • Sterilization of operation theatre by : * 500 ml of formalin , 200gms of Potpermanganate/30 cu . meters of space *All windows and doors are closed except one . *Fissures between the panels of the doors and windows are closed with adhesive tape *After 12 hours the doors and windows are opened and the theatre is aired for 24 hours before decommissioning it. rabiezahran@hotmail.com 61 Active Immunization by using tetanus toxoid rabiezahran@hotmail.com 62 TETANUS TOXOID • Tetanus toxoid was developed by Descombey in 1924, • Tetanus toxoid immunizations were used extensively in the armed services during World War II. • Tetanus toxoid consists of a formaldehyde-treated toxin. • There are two types of toxoid available — 1)adsorbed (aluminum salt precipitated)toxoid 2) fluid toxoid. • Although the rates of seroconversion are about equal,the adsorbed toxoid is preferred because the antitoxin response reaches higher titers and is longer lasting than that following the fluid toxoid. rabiezahran@hotmail.com 63 rabiezahran@hotmail.com 64 Passive Immunization rabiezahran@hotmail.com 65 Passive Immunization 1. ATS(equine)I g. 1500 IU/s.c after sensitivity test (or) 2. ATS(human)I g. 250-500 IU, no anaphylactic shock, very safe and costly. rabiezahran@hotmail.com 66 Tetanus Neonatorum. rabiezahran@hotmail.com 67 Newborn showing risus sardonicus and generalized spasticity rabiezahran@hotmail.com 68 rabiezahran@hotmail.com 69 THANK YOU rabiezahran@hotmail.com 70