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Tetanus: the Forgotten Disease Kansas Journal of Medicine 2007 Tetanus: The Forgotten Disease Tetanus: The Forgotten Disease 1 Boutros El-Haddad, M.D. 1 Jill Hanrahan, M.D. Maha Assi, M.D. 1,2 1University of Kansas School of Medicine – Wichita Department of Internal Medicine 2Infectious Disease Consultants, Wichita, KS Introduction Tetanus was well known to the ancient tetanus immunoglobulin were given physicians of Egypt and Greece, but since intramuscularly and active immunization institution of the active immunization in was started. Although there was no active 1940, it has become an old forgotten disease wound infection, the patient was started on in developed countries. 1 Tetanus is a intravenous metronidazole. Muscle spasms nervous system disorder characterized by and rigidity were controlled with a prolonged contraction of the skeletal scheduled dose of intravenous diazepam. muscles. The disease is caused by Over the next three weeks, the patient’s tetanospasmin, a neurotoxin produced by the symptoms gradually improved, and she was anaerobic bacterium Clostridium tetani. discharged to a skilled nursing facility. Case Report Epidemiology A 74-year-old Caucasian female The incidence of tetanus in developed presented to the emergency department countries dropped dramatically since 1940 complaining of trismus. The patient had not mainly due to the widespread use of active been evaluated by a physician for several immunization. 1 Better hygiene and wound years. Her symptoms started 10 days prior care also have played a major role. The with difficulty opening her mouth, annual incidence of tetanus in the US has generalized muscle stiffness, and episodic fallen from 4 to 0.2 per million since 1947. 1 muscle spasms. She denied fever and chills, The decline in incidence was accompanied was not taking any medications, and had no by a decrease in mortality from 50 to 30%. history of alcohol or illicit drug use. She did Between 1998 and 2000, the annual not remember ever receiving tetanus incidence of tetanus was 0.16 cases/million vaccination. representing an average of 43 cases per On physical examination, the patient was year. 2 The majority of cases were in patients unable to open her mouth more than 1 cm older than 60 years, reflecting the waning of and the masseter muscle was contracted. immunity with age or inadequate She had a generalized increase in muscle immunization of the elderly. 1 Injection drug tone and episodic painful muscle spasms abuse and the increase of non-immunized involving the entire body. Multiple scars immigrants are responsible for most cases of in different healing stages over the lower tetanus in younger individuals aged 25 to 59. extremities had been caused by scratches According to the CDC 2, 15% of cases of from her 13 cats. tetanus in the US occurred in intravenous The diagnosis of generalized tetanus was drug users. suspected. Five hundred units of human 9 Kansas Journal of Medicine 2007 Tetanus: The Forgotten Disease Acute injuries account for 70 to 80% of increased muscle tone and painful spasm. US cases; 23% of cases are associated with The autonomic nervous system also is chronic decubitus ulcers, gangrene, burns affected, manifested by a hypersympathetic and abcesses. 1 About 7% of cases have no state due to failure to inhibit the adrenal apparent source. Neonatal tetanus is rare in release of catecholamine. Tetanospasmin the US. 1,2 interferes with pre-synaptic acetylcholine Tetanus is common in developing release at the neuromuscular junction and countries. The worldwide incidence is about disinhibits sympathetic reflexes at the spinal 1,000,000 cases per year. 3,4 It is a major level.1 The inhibitory effect of cause of death especially in neonates. tetanospasmin is irreversible. Recovery Tetanus accounted for 300,000 deaths in requires the growth of new axonal nerve 2000, including 200,000 neonatal deaths.5 terminals in 4 to 6 weeks. Clostridium tetani produces another toxin called tetanolysin Pathogenesis and Pathology that apparently has no pathogenic role. 1 Clostridium tetani is an obligatory gram positive anaerobic bacillus. The bacteria are Clinical Features usually found in contaminated soil and The incubation period of tetanus usually animal gut in the sporiform phase. When lasts between 3 and 21 days with a range of these spores contaminate a wound, they one day to several months. 1 A correlation germinate under anaerobic conditions, exists between the distance of the injury transform into a rod-shaped bacterium, and from the CNS and the duration of the produce tetanospasmin. Tetanospasmin is incubation period.1,5 The closer the distance, an exotoxin produced by mature bacteria, the shorter the incubation period. Both the then cleaved intracellularly into light and incubation period and the time of onset heavy chains before exocytosis. The heavy (time from the first symptom to the first chain appears to mediate binding to cell generalized spasm) inversely correlate with surface and transport proteins, while the prognosis.1 light chain is responsible for the clinical Tetanus has four clinical forms: manifestations of tetanus. 1 generalized, localized, cephalic, and After its excretion, tetanospasmin gains neonatal. Generalized tetanus is the most entry into the central nervous system (CNS), common and severe. The generalized form both locally and distally, via the presynaptic typically starts with spasm of the masseter terminals of lower motor neurons. muscles, causing trismus or “lockjaw” and Tetanospasmin is transported intra-axonally increased tone of the orbicularis oris in a retrograde fashion to the cell body, the resulting in the characteristic “risus ventral horns of the spinal cord, and to the sardonicus”. The patient experiences diffuse motor nuclei of the cranial nerves where it spasms involving muscle groups in the neck, exerts its major pathogenic action. After back, abdomen, and extremities. These reaching the spinal cord and the brain stem, spasms are painful, intermittent, and tetanospasmin binds tightly and irreversibly unpredictable. They often are triggered by to specific receptors, inhibiting the release noise and light. of inhibitory neurotransmitters (glycine and Patients with generalized tetanus γ-amino-butyric acid) from presynaptic typically have symptoms of autonomic inhibitory neurons. overactivity that manifest as sweating, The net effect is the disinhibition of tachycardia, cardiac arrhythmia, labile motor excitatory neurons resulting in hypertension or hypotension, and fever. 10 Kansas Journal of Medicine 2007 Tetanus: The Forgotten Disease Respiratory muscles also are affected Differential Diagnosis causing periods of apnea. During Strychnine poisoning may produce a generalized tetanic spasms, patients clinical syndrome similar to tetanus. characteristically clench their fists, arch their Toxicologic screen of urine and blood back, flex their arms while extending their should be performed if a suspicious injection legs, and become apneic. 1 Death is due to is suspected or the history is not typical for respiratory failure or to autonomic tetanus (e.g., no injury or adequate dysfunction. Recurrent tetanus may occur if immunization). The treatment of tetanus the patient is not immunized since the and strychnine poisoning is similar. infection does not confer immunity. Trismus due to dental infection may be Recovery is typically 2 to 6 weeks. confused with cephalic tetanus. Drug Localized tetanus is usually a prodrome induced dystonia and malignant neuroleptic of the generalized form. It presents with syndrome can mimic tetanus. localized rigidity and spasm of a muscle group near the site of injury. Subsequently, Treatment patients develop generalized tetanus. In The treatment of patients with tetanus some cases, localized disease reflects partial requires a multidisciplinary approach in the immunity with resolution of the spasms intensive care unit.1 The mainstay of without generalization. 6 Cephalic tetanus is treatment consists of eliminating the source a form of localized tetanus involving the of toxin production, neutralizing unbound cranial nerves in a patient with head and toxin, and managing symptoms and neck injuries. 1 complications. Neonatal tetanus is related to the inadequate use of aseptic techniques in non- Halting toxin production immunized mothers. It usually occurs Wound debridement is important to within 14 days after birth. 1,7 Infants present eliminate the source of toxin production. with generalized weakness and failure to All foreign bodies, including spores and nurse, followed by rigidity and spasms. necrotic tissue, should be removed. Mortality exceeds 90%. Apnea and sepsis Metronidazole and penicillin G are the drugs are the leading causes of death. of choice, but studies have shown better outcomes with metronidazole. 1,8 Intravenous Diagnosis metronidazole should be given initially at a The diagnosis of tetanus is based on dose of 15mg/kg followed by 20 to 30 clinical symptoms and a high index of mg/kg/day intravenously for 7 to 14 days or suspicion in susceptible individuals.1 until there is no visible sign of active local Anaerobic cultures from the wound are infection.1 Alternatives include cefazolin, usually negative. A positive culture does cefuroxime, and ceftriaxone. not confirm the diagnosis. Anti-tetanus antibodies are undetectable in the majority Neutralizing of unbound toxin of patients with tetanus. However, the Tetanospasmin is bound irreversibly to presence of antibodies at low titer does not tissues and only unbound toxin is available
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