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.
Tetanus is a serious life-threatening disorder that presents with painful muscular spasms and hypertonia. Despite widespread vaccination in the US, the disorder still occurs. Tetanus is classified into the following categories:
Patients with generalized tetanus often present with trismus, dysphagia and nuchal rigidity. As the disorder progresses, the individual will develop systemic rigidity and tonic contractions. The patient often develops excruciating pain from these contractions which can result in tendo rupture, fractures, and acute respiratory failure.
Individuals with localized tetanus often have localized muscle rigidity and have low mortality and morbidity.
Those with cephalic tetanus may present with cranial nerve paralysis. These cases are rare and may occur after an ear infection or head trauma.
Neonatal tetanus still remains a major cause of death in developing countries. It is often due to unsterile transection of the umbilical cord following delivery, in addition to a lack of maternal vaccination. Within the first 7 days, the infant is irritable, develop severe rigidity and has a poor outcome.
The key to tetanus infection is to prevent it in the first place with vaccination.
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.It is well known that tetanus spores can survive in the environment for many years and are often resistant to heat and disinfectants. The source of infection in most people is a wound or a recent injury; the injury is often mild. In others, tetanus may develop from a burn injury abscess, following a surgical procedure, IV drug abuse or gangrene. In many cases, the patients are either under-immunized or have not been vaccinated.
Neonatal tetanus is often the result of home delivery and unsanitary excision of the umbilical cord. In most people, the immunity from tetanus vaccine declines with advancing age. Thus, vaccination or booster shots are 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 the 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.
One can perform the spatula test; this involves touching the oropharynx with a tongue blade and determining if the patient has a gag reflex. If tetanus is present the patient will attempt to bite down on the blade; normal people will immediately gag and expel the spatula.
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.
Admission to the ICU is highly recommended. Unnecessary procedures and manipulations should be avoided. The patient should be in a quiet room with low traffic. Some patients may even require mechanical ventilation.
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.
Autonomic complications may require management with magnesium sulfate in combination with a benzodiazepine. If magnesium is administered intravenously, the patellar reflex should be monitored. If areflexia occurs, the dose of magnesium should be lowered. Morphine can also be used to manage pain and other autonomic symptoms but it can cause hypotension. Patients with bradycardia may need a temporary pacemaker.
The prognosis following tetanus depends on time to symptoms or incubation period. In general, a short incubation period usually indicates severe disease. Negative prognostic factors including an incubation period of fewer than 48 hours, addiction to narcotics, generalized tetanus, high fever (greater than 104F), acquiring tetanus from surgery, burns, IV drug abuse or a septic abortion. Both cephalic and neonatal tetanus have poor outcomes.
Recovery in most patients is slow but can take months or years for full recovery. Unfortunately some patients may remain hypotonic for life. Since tetanus does not provide any immunity, those who survive should be actively immunized.
Tetanus is administered through vaccination with DTP at ages 2, 4, 6 12-18 months and at 4 years. Pregnancy is not a contraindication to vaccination in the 2nd or 3rd trimester.
Secondary prevention is done by thorough wound cleaning, debridement, and administration of tetanus toxoid. It is not always necessary to wait for 10 years to get the adult Tdap dose after the last dose.
Tetanus is a serious life-threatening infection that is associated with high morbidity and mortality. The best way to manage tetanus is to prevent it in the first place. Public health nurses, pharmacists, and primary care clinicians need to educate patients on the importance of childhood tetanus vaccination. Patients should be educated about how tetanus is acquired and when they should seek medical assistance. The key is to see a clinician as soon as possible. Healthcare workers should develop aseptic techniques when doing procedures and emergency room personnel should always ask patients if they have had tetanus immunization. Anytime a nurse manages a wound, he or she should always ask the patient if he or she is up to date with tetanus vaccination. Only through open communication and creating awareness of the morbidity of tetanus can the outcomes be improved. 
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)
|||Sharma DS,Shah MB, A Rare Case of Localized Tetanus. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2018 Sep [PubMed PMID: 30294137]|
|||Avila L,Cascone O,Biscoglio M,Fingermann M, An effective, simple and low-cost pretreatment for culture clarification in tetanus toxoid production. Preparative biochemistry [PubMed PMID: 30265189]|
|||Bae C,Bourget D, Tetanus null. 2018 Jan [PubMed PMID: 29083804]|
|||Tadele H, Clinical Profile and Outcome of Pediatrics Tetanus: The Experience of a Tertiary Hospital in Ethiopia. Ethiopian journal of health sciences. 2017 Sep [PubMed PMID: 29217961]|
|||Finkelstein P,Teisch L,Allen CJ,Ruiz G, Tetanus: A Potential Public Health Threat in Times of Disaster. Prehospital and disaster medicine. 2017 Jun [PubMed PMID: 28215195]|
|||Stock I, [Tetanus and Clostridium tetani--a brief review]. Medizinische Monatsschrift fur Pharmazeuten. 2015 Feb [PubMed PMID: 26376540]|
|||Alshanqiti FM,Al-Masaudi SB,Al-Hejin AM,Redwan EM, Adjuvants for Clostridium tetani and Clostridium diphtheriae vaccines updating. Human antibodies. 2017 [PubMed PMID: 27858706]|
|||Toker I,Kılıc TY,Kose S,Yesilaras M,Calıskan F,Atilla OD,Unek O,Hacar S,Kılınc Toker A, Tetanus immunity status among adult trauma patients in an ED. Turkish journal of emergency medicine. 2017 Sep [PubMed PMID: 28971156]|
|||Tetanus vaccines: WHO position paper – February 2017. Releve epidemiologique hebdomadaire. 2017 Feb 10 [PubMed PMID: 28185446]|
|||Uleanya ND, Achieving neonatal tetanus elimination in Nigeria: undisclosed challenges and prospects. Tropical doctor. 2018 Jan [PubMed PMID: 28147895]|
|||N'Diaye DS,Schwarzinger M,Obach D,Poissy J,Matheron S,Casalino E,Yazdanpanah Y, Effectiveness and cost of quick diagnostic tests to determine tetanus immunity in patients with a wound in French emergency departments. BMC infectious diseases. 2014 Nov 19 [PubMed PMID: 25407690]|
|||Tetanus surveillance --- United States, 2001-2008. MMWR. Morbidity and mortality weekly report. 2011 Apr 1 [PubMed PMID: 21451446]|