Clostridia are variable genera of anaerobic organisms made up of at least 209 species and five subspecies. Clostridium tetani is one of the 4 most well-known exotoxin producing pathogens within this category and the sole causative organism for the disease process known as tetanus. Although widespread vaccination efforts have reduced the public health threat, tetanus is a potentially fatal condition. Thus, it is important to recognize the typical clinical presentation, immediate management, and treatment of C. tetani infection.
C. tetani is part of a genus of obligate anaerobic, saprophytic, gram-positive organisms. Other notable organisms within this genus include Clostridium perfringens which can cause gangrene, Clostridium difficile which leads to infectious colitis, and Clostridium botulinum which is responsible for botulism. C. tetani is well known for its toxin-producing ability making it one of the most dangerous of its genus. C. tetani is a spore-forming organism that cannot be eliminated from the environment and can withstand extreme temperature conditions in both indoor and outdoor environments. Thus, vaccination is required for prevention.
Most cases of tetanus take place in developing countries where immunity is rare, globally, and particularly in areas where natural disasters have occurred. The spores of C. tetani are present in the environment irrespective of geographical location. The spores reside in the soil and can enter through open, contaminated skin. All ages are susceptible to infection, and the case-fatality rate can approach 100% if immediate medical intervention is not available. Neonates are at increased risk in under-developed areas of the world when non-sterilized medical equipment is used to cut the umbilical cord. World Health Organization (WHO) estimates that in 2015, approximately 34,000 neonates died from neonatal tetanus. Tetanus is a vaccine-preventable disease for which tetanus toxoid-containing vaccines (TTCV) is included in the routine childhood immunization schedule. The average annual incidence in the United States from 2001 to 2008 was 0.01 per 100,000 population per WHO. The age groups at highest risk are children and the elderly likely secondary to reduced immunity thus highlighting the importance of booster vaccinations to maintain protection. Tetanus toxin vaccine was first produced in 1924 and used extensively for the first time among soldiers during World War II. Currently, the pentavalent vaccine, which protects against diphtheria, tetanus, pertussis, Hib and hepatitis B (DTP-Hib-HepB), is the most commonly used childhood vaccine worldwide.
Tetanus is a disease process that is characterized by severe, diffuse muscle contractions. The muscular rigidity and spasms of tetanus are caused by tetanus toxin (tetanospasmin). The transmission of C. tetani is through exposure of a deep tissue wound to the spores which are present in soil or fecal matter from animals or humans. Given that C. tetani is an obligate anaerobe, the anaerobic tissue wound provides an ideal environment for replication and growth of C. tetani. Following extensive bacterial replication at the wound site, an expression of the genes encoding the 2 toxins, tetanospasmin and tetanolysin, occur. Tetanospasmin is taken up at the nerve terminals of the peripheral nervous system and can interfere with the vesicular release of acetylcholine at the neuromuscular junction. Thus, an initial presenting symptom of tetanus is flaccid paralysis which can resemble the effects of C. botulinum. However, the toxin is transported in a retrograde fashion toward the central nervous system (CNS) and eventually reaching the spinal cord or brainstem. It is here that the tetanus toxin produces its characteristic satellite of symptoms. The toxin causes inhibition of the release of GABA and glycine inside inhibitory nerve terminals that control the activity of the lower motor neurons. Thus, this action causes a hyperactivity effect leading to involuntary contraction of the skeletal muscles.
Tetanus is categorized into 4 categories: generalized, neonatal, local, and cephalic. Neonatal is defined as a generalized form in children less than 1 month, and cephalic is localized to the head region. The incubation period of tetanus is approximately 8 days but ranges from 3 to 21 days; however, in neonatal tetanus; it is typically shorter. Generalized tetanus is the most recognizable and well-known form and is characterized by specific clinical findings including stiff neck, opisthotonus (backward arching of the head, neck, and spine), Risus sardonicus (sustained spasm of facial muscles that resembles a grin), and/or rigid abdomen. Patients can also experience airway compromise presenting as dysphagia and eventually apnea and airway obstruction. The clinical presentation of tetanus can sometimes have an early phase that includes symptoms of autonomic over-activity, i.e., irritability, restlessness, sweating, and tachycardia. Local tetanus is somewhat rare and presents with muscle contractions in a specific body region. Cephalic tetanus is a form of local tetanus that can present as dysphagia, trismus, and focal cranial neuropathies and sometimes mistaken for a cerebrovascular accident. The severity of the illness is dependent on the amount of toxin that reaches the CNS.
Diagnosis of tetanus is usually based on physical exam, immunization history, and clinical presentation while less emphasis is placed on laboratory testing. Infection with C. tetani has a varied list of differential diagnoses which includes strychnine poisoning, neuroleptic malignant syndrome, meningitis, and drug-induced dystonias amongst others. Of this group, strychnine poisoning appears the most like tetanus. Strychnine is a colorless, bitter, crystalline alkaloid typically used as a pesticide; however, it can be found mixed in with heroin and cocaine. Poisoning with this substance can, like tetanus, cause trismus, opisthotonus, painful muscular spasms, and rigidity. Differentiating tests include blood, urine, and tissue assays.
The focus of acute tetanus management should center around toxin mitigation and aggressive symptom management including airway protection. Thus, patients should be admitted to the intensive care unit for initial evaluation. All patients with tetanus, if exposed because of an open wound, should undergo immediate debridement to eradicate spores and avoid further spread of the toxin from tissue to the bloodstream. Regarding mitigation of the toxin, tetanus toxin binds irreversibly to tissue, and so the focus of neutralization is the unbound toxin. Per current recommendations, human tetanus immune globulin should be given as soon as tetanus is suspected at a dose of 3000 to 6000 units. Antimicrobial therapy is typically metronidazole as the preferred treatment for tetanus with penicillin G as an option for second-line therapy with a treatment duration of 1 week to 10 days. It is important to note that antimicrobial therapy plays a relatively minor role in the management of tetanus and of primary importance is wound debridement and toxin mitigation. Symptom management is also of the utmost importance. Muscular spasms in the setting of tetanus are life-threatening and can lead to respiratory compromise, aspiration, and exhaustion. Benzodiazepines can be used in controlling the rigidity and spasms associated with tetanus. In situations where sedation is not sufficient, neuromuscular blocking agents such as pancuronium or vecuronium can be used. It should be noted that infection with C. tetani does not provide immunity, and thus, all patients with the diagnosis of tetanus should receive immunization immediately with three doses of tetanus and diphtheria toxoid.
The key to preventing tetanus is patient education. All healthcare workers should educate the patient on the importance of childhood tetanus vaccination. Healthcare workers should develop aseptic techniques when doing procedures and emergency room personnel should always ask patients if they have had tetanus immunization.
The prognosis of patients infected with C.Tetani depends on the time of presentation, the inoculation dose and the time to the first tetanic spasm. Overall, patients who develop tetanus quickly have a poor prognosis. For those who survive tetanus, they may have some residual deficits but the life span is not reduced. However, some patients may have hypotonia for life. Finally, despite the infection, no one develops active immunity and these patients need active immunization to prevent a recurrence. (Level V)