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TETANUS INFECTION (CAUSED BY CLOSTRIDIUM
TETANI)
Babajanova Gulchekhra Bakhtiyorovna
Assistant at the Medical faculty of Alfraganus University Email: gulchexra197129@gmail.com https://doi.org/10.5281/zenodo.13959310
ABSTRACT
This educational activity equips clinicians with comprehensive knowledge of tetanus, covering its microbiological foundation, diagnostic techniques, treatment protocols, and preventive measures. Mastery of this information is essential for improving clinical skills and optimizing patient outcomes in cases of tetanus.
immunoglobulin.
Continuing Education Activity
Clostridium tetani is an anaerobic, spore-forming bacterium responsible for causing muscle stiffness and heightened sympathetic activity, leading to tetanus. With an estimated 1 million cases annually, tetanus predominantly affects regions with limited resources and unvaccinated populations. The tetanus toxin disrupts neurotransmitter release in the brainstem and spinal cord. While wound contamination is the most common mode of entry, occasionally, no clear site of inoculation is identified. Diagnosis is largely clinical, as laboratory tests have limited value in confirming the condition. Effective treatment requires a multifaceted approach, including airway management, benzodiazepines, human tetanus immunoglobulin, and tetanus toxoid, with specific measures to address sympathetic overactivity. Tetanus is preventable through immunization with tetanus toxoid. Objectives:
• Distinguish the clinical signs of tetanus from other neuromuscular disorders to ensure timely and accurate diagnosis.
• Implement preventive strategies, such as tetanus toxoid vaccinations, with a focus on their importance for high-risk groups.
• Choose appropriate treatment options, including airway management, benzodiazepines, and immunoglobulin administration, based on the clinical presentation of tetanus.
• Collaborate effectively with multidisciplinary teams, including clinical microbiologists, infectious disease specialists, intensivists, and public health officials, to manage tetanus cases promptly.
Introduction
ARTICLE INFO
Received: 14th October 2024 Accepted: 20th October 2024 Online: 21th October 2024
KEYWORDS Clostridium tetani, anaerobic, benzodiazepines, human tetanus immunoglobulin, human tetanus
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Clostridium tetani is the bacterium responsible for causing tetanus [1]. The spores and bacilli of C. tetani are widespread in the environment, and infections from neurotoxin-producing strains have plagued humanity since ancient times. Fortunately, the development of highly effective vaccines has nearly eradicated tetanus globally. However, tetanus remains a major health issue in resource-limited regions where public health initiatives may be insufficient. In contrast, in resource-rich countries where vaccines are readily accessible, tetanus is rare, and many clinicians may have limited experience diagnosing and treating it. This rarity can sometimes result in delays in identifying and managing tetanus in clinical settings [2].
It is therefore critical to identify risk factors, recognize common clinical symptoms, and understand the immediate management and treatment of C. tetani infection [3][4][5][6]. Tetanus is a potentially fatal condition characterized by painful muscle spasms, hypertonia, and autonomic nervous system dysfunction. Despite widespread vaccination programs in the U.S., cases of tetanus continue to occur [7].
Tetanus is categorized into four types:
• Generalized
• Localized
• Cephalic
• Neonatal
Mortality rates are highest in individuals at the extremes of age, where diminished immunity and the presence of comorbidities are more common. Ideally, patients with tetanus should receive care from a multidisciplinary team in a critical care setting. Unfortunately, such optimal care environments are often unavailable in regions where they are most needed. In resource-limited areas, neonatal tetanus remains a significant cause of death.
The management of tetanus is based on the collective experience reported in case studies. Due to the low incidence of tetanus and its potentially lethal nature, there are no large-scale randomized, placebo-controlled trials comparing treatment strategies [6]. Nonetheless, treatment protocols have been well established through anecdotal evidence, case series, and smaller clinical studies [8].
Etiology
Clostridium tetani are obligate anaerobic, gram-positive, spore-forming bacilli that are found widely in the environment, including soil, feces from both humans and domestic animals, dust, and the gastrointestinal tract [1]. While they initially appear gram-positive in fresh cultures, they may appear gram-variable in mature cultures. The mature bacteria possess terminal spores, giving them a characteristic "tennis racket" or "squash racket" shape [9]. A useful mnemonic to recall this feature is associating the sound similarity between "tetanus" and "tennis" when interpreting micrographic images of the bacilli.
These spores, which persist in the environment, germinate into active bacteria when introduced into injured tissue. They are incredibly resilient and can withstand exposure to common disinfectants such as formalin, ethanol, and household cleaners, as well as boiling and freezing. However, iodine, hydrogen peroxide, glutaraldehyde, and autoclaving at high temperatures and pressure can inactivate them. In clinical practice, culturing C. tetani provides limited diagnostic value due to the difficulty in culturing the organism [10]. A
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positive culture may reflect the presence of non-toxigenic strains, and even individuals who have been immunized may still have positive cultures without developing the disease.
In most cases, tetanus is associated with traumatic wounds, but it can also result from burn injuries, surgical abscesses, intravenous drug use, circumcision, or gangrene. Occasionally, no source of infection can be identified. Incomplete or lack of immunization is often linked to tetanus cases.
Neonatal tetanus is commonly caused by unsanitary practices during home deliveries, particularly when cutting the umbilical cord [11]. Immunity conferred by the tetanus vaccine tends to wane with age, making routine vaccinations or booster doses essential for continued protection [1][3][10][12].
Epidemiology
Most cases of tetanus occur in developing countries where immunity is inadequate, particularly in regions affected by natural disasters [12]. In wealthier nations, the primary groups at risk include unvaccinated individuals and those whose vaccine-induced immunity has waned. Surveillance data reveals that people who inject drugs and those with insulin-dependent diabetes are particularly vulnerable [7].
Clostridium tetani spores are ubiquitous in the environment, found in soil and capable of entering the body through skin wounds. Wounds with devitalized tissue are at the highest risk of infection, making all age groups susceptible. Without high-quality medical care, the fatality rate can approach 100%, though with optimal treatment, mortality decreases to 10%-20% [3]. Neonates are at heightened risk in low-resource regions, especially when unsanitary birth practices are used, such as cutting the umbilical cord with non-sterilized instruments or applying contaminated dressings to the umbilical stump [11]. In 2015, the World Health Organization (WHO) estimated that approximately 34,000 neonates died from neonatal tetanus [13].
Tetanus is preventable with vaccines, and tetanus toxoid-containing vaccines (TTCV) are part of the routine childhood immunization schedule. Between 2001 and 2008, the average annual incidence of tetanus in the U.S. was 0.01 per 100,000 population [7]. From 2009 to 2015, 197 cases of tetanus were reported in the U.S., resulting in 16 deaths [14]. The age groups most at risk are newborns and the elderly. The tetanus toxoid vaccine was first produced in 1924 and was widely used during World War II. Today, the pentavalent vaccine, which protects against diphtheria, tetanus, pertussis, Hib, and hepatitis B (DTP-Hib-HepB), is the most commonly used childhood vaccine worldwide [3]. It's important to note that infection with C. tetani does not confer immunity, and tetanus is not transmitted from person to person.
Pathophysiology
When Clostridium tetani spores enter a wound, they germinate into bacilli, which produce two toxins: tetanospasmin (the tetanus toxin) and tetanolysin. Tetanospasmin spreads through the lymphatic system and bloodstream, binding to receptors in the peripheral nervous system at neuromuscular junctions. It is then taken up by nerve cells and retrogradely transported along peripheral nerve axons to inhibitory interneurons within the central nervous system (CNS). In the CNS, tetanospasmin inhibits the release of gamma-aminobutyric acid (GABA) and glycine—key inhibitory neurotransmitters in the spinal cord
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and brainstem. Additionally, it blocks the release of inhibitory neurotransmitters in the sympathetic nervous system. The lack of inhibitory signaling leads to unchecked activity of excitatory neurotransmitters, causing muscle spasms and hypersympathetic activity. The precise role of tetanolysin in tetanus pathogenesis is still unclear. However, the excessive release of excitatory neurotransmitters is responsible for the characteristic involuntary muscle spasms seen in tetanus [15].
The uninhibited release of catecholamines from the adrenal glands leads to heightened sympathetic activity [16]. Once tetanospasmin binds at the neuromuscular junction, it cannot be reversed.
History and Physical
In many tetanus cases, a history of deep penetrating wounds that result in devitalized tissue is often present, although not always. Other causes include minor trauma, post-surgical infections, injection drug use, intramuscular injections, compound fractures, decubitus ulcers, or even cases with no identifiable wound [15][17]. In neonates born to unvaccinated mothers, tetanus may develop due to contamination of the umbilical stump [11].
The incubation period for tetanus ranges from one day to several months following wound contamination. A shorter incubation period is associated with more severe disease, which is likely influenced by the size of the bacterial load and the proximity of the inoculation site to the central nervous system. Tetanus typically lasts for about two weeks, though full recovery may take several months as new nerve terminals grow to replace damaged ones.
Generalized tetanus is the most common form of the disease. It often begins with trismus (lockjaw) and rigidity of the orbicularis oris muscles (risus sardonicus), followed by painful, generalized muscle contractions. Hyperextension of the back and legs, along with flexion of the arms (opisthotonus), can resemble decorticate posturing. Difficulty swallowing (dysphagia), caused by pharyngeal muscle spasms, is a common initial complaint [18][2]. Airway obstruction can result from spasms of the neck muscles and diaphragm. Muscle spasms, which can be triggered by noise, touch, or simple nursing care, may persist for weeks due to the persistence of toxins in the nerve axons. Additionally, hypersympathetic activity and autonomic dysfunction can manifest as fluctuating blood pressure and cardiac arrhythmias. Despite these symptoms, mental clarity remains intact in the absence of brain dysfunction. The severity of the disease, including morbidity and mortality, is often influenced by comorbidities and complications that arise from prolonged hospitalization.
Localized tetanus is a rarer form of the disease, typically confined to the body part where the injury occurred. Although localized, it can progress to generalized tetanus. When localized tetanus results from injuries to the face or scalp, it may develop into cephalic tetanus, which affects the cranial nerves.
Cephalic tetanus involves cranial nerve dysfunction and may present symptoms similar to a stroke [5]. This form can also progress to generalized tetanus.
Neonatal tetanus typically develops from contamination of the umbilical stump in infants born to unvaccinated mothers [11]. The incubation period is usually around seven days. Affected infants exhibit symptoms like difficulty suckling, followed by generalized muscle rigidity, often leading to opisthotonus. Mortality rates are high due to complications like apnea and sepsis.
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Evaluation
The diagnosis of tetanus is primarily based on clinical presentation, as diagnostic tools such as radiology, hematology, clinical chemistry, and microbiology are typically insufficient for confirmation [1][4][12][15]. Gathering information about the patient's immunization history and any recent traumatic wounds is crucial, though obtaining reliable details may sometimes be difficult [19]. In neonatal tetanus cases, the mother's immunization status is a key factor, and the possibility of unsanitary delivery practices should also be considered.
Treatment / Management
Effective treatment of tetanus requires a collaborative approach involving infectious disease specialists and critical care intensivists. Management focuses on mitigating the effects of the tetanus toxin and providing aggressive symptomatic care [6][20]. Immediate wound cleansing and debridement are crucial to remove C. tetani spores and prevent the toxin from spreading to the bloodstream. Patients exhibiting tetanus symptoms should be closely monitored, ideally in an intensive care unit (ICU), where noise, bright light, and tactile stimuli should be minimized to reduce triggers for spasms. Airway compromise is a significant risk, and intubation should be anticipated if needed [21].
Given the rarity of tetanus, much of the treatment is based on case reports and small studies, with few large randomized trials. Variations in disease severity across reports can also confound treatment data.
Since tetanospasmin binds irreversibly at the neuromuscular junction, treatment aims to neutralize any circulating unbound toxins. Passive immunization with human tetanus immune globulin (HTIG) should be administered as soon as tetanus is suspected, as it has been shown to reduce disease severity and duration.
In resource-limited areas where HTIG is unavailable, equine antitetanus serum can be used intravenously, although it carries the risk of anaphylaxis. Skin testing is advised before administration. The role of intrathecal administration of antisera remains unclear, with conflicting data preventing a definitive recommendation [8][20]. If neither human nor equine antitetanus serum is available, pooled human immunoglobulin can be considered.
Managing muscle spasms and hypersympathetic activity is critical. Benzodiazepines, which provide sedative, muscle relaxant, and anxiolytic effects, are commonly used, though care must be taken to avoid oversedation, respiratory suppression, or coma. Neuromuscular blocking agents such as vecuronium may be necessary in severe cases where benzodiazepines are insufficient [21].
Although data on the use of intravenous magnesium sulfate for tetanus treatment is limited, it has shown promise in controlling spasms and catecholamine release, especially in milder cases. However, the optimal dosing and duration of magnesium sulfate infusion remain unclear [6][20].
Intrathecal baclofen has also been used to control tetanic spasms with some success, though its use can lead to respiratory depression and cardiac instability, necessitating administration in an ICU setting [20].
Antibiotic therapy, typically with metronidazole or penicillin, is administered for 7 to 10 days to eliminate C. tetani from the wound, though there is no clear consensus on the optimal duration of therapy. These antibiotics target the wound infection but do not alleviate muscle
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spasms or autonomic dysfunction. Broader-spectrum antibiotics may be necessary for wounds infected with mixed flora. There is some concern that high-dose intravenous penicillin could interfere with inhibitory neurotransmitters [20].
Comparative studies on metronidazole and penicillin for tetanus-associated wound management are limited and inconclusive regarding the superiority of one antibiotic over the other in this context.
Differential Diagnosis
Tetanus has a limited differential diagnosis, as outlined below. However, due to its rarity, many clinicians may struggle to identify the condition promptly or may even miss the diagnosis entirely, which can have fatal consequences [2][4][5][17][18]. The differential diagnoses include:
1. Oropharyngeal abscess: Depending on the size and location of the abscess, patients may present with dysphagia and trismus.
2. Stroke: Both ischemic and hemorrhagic strokes can cause cranial nerve palsies.
3. Meningitis: Inflammation of the meninges can lead to muscle rigidity, although tetanuslike spasms are not present. A common early sign is neck stiffness.
4. Strychnine poisoning: This can cause similar muscle spasms but typically lacks the autonomic dysfunction seen in tetanus. Strychnine poisoning may result from intentional ingestion or accidental poisoning, particularly from adulterated substances like cocaine and heroin [22][23].
5. Botulism: Caused by Clostridium botulinum toxin, this condition manifests with symptoms such as dysphagia and cranial nerve palsies followed by flaccid paralysis. Unlike tetanus, botulism does not produce muscle spasms or hypertonia.
6. Hypocalcemia: Low calcium levels may lead to muscle spasms, but the autonomic features typical of tetanus are usually absent.
7. Neuroleptic malignant syndrome: A drug-induced disorder characterized by hyperthermia, altered mental status, and muscle rigidity. It is distinguished from tetanus by the patient's clinical history.
Prognosis
The prognosis for tetanus largely depends on the incubation period or the time between exposure and the onset of symptoms. A shorter incubation period generally indicates a more severe form of the disease. Poor prognostic factors include an incubation period of fewer than 48 hours, narcotic addiction, generalized tetanus, high fevers exceeding 104°F, and cases arising from surgical procedures, burns, intravenous drug use, or septic abortion. Cephalic and neonatal tetanus are particularly associated with worse outcomes.
In contrast, individuals with localized tetanus tend to have lower rates of mortality and morbidity. While recovery is typically slow, it can take months or even years for a full recovery. Importantly, surviving tetanus does not confer immunity, so individuals must undergo active immunization following recovery. Enhancing Healthcare Team Outcomes
The elimination of tetanus begins with public health efforts focused on educating communities about the critical importance of immunizations. In some regions, overcoming cultural barriers to vaccination may be necessary. Neonatal tetanus remains the leading cause
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of tetanus worldwide, and despite ongoing efforts to eradicate it through maternal and neonatal vaccination programs, the goal has not yet been fully reached [27].
An equally important challenge is educating the public about proper wound care and the importance of seeking medical attention for tetanus-prone injuries. Clinicians in primary care and emergency medicine must stay informed about current tetanus immunization schedules. Due to the rarity of tetanus in modern clinical practice, some healthcare providers may be unfamiliar with its symptoms. Early tetanus cases may first be seen by dentists, otolaryngologists, primary care doctors, or neurologists, many of whom may have never encountered a tetanus case before. While tetanus has distinctive features and a narrow differential diagnosis, its rarity can cause delays in recognition and treatment. Furthermore, reliance on radiologic and laboratory tests offers limited diagnostic value.
Treating tetanus requires a multidisciplinary approach, ideally involving infectious disease specialists and critical care teams. The scarcity of tetanus cases means that large randomized clinical trials to establish definitive management guidelines are lacking. Instead, treatment recommendations are derived from small randomized studies, case series, and expert opinion [6][8][10][13].
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