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TETANUS - Complete Notes
DEFINITION & OVERVIEW
- Acute disease caused by skeletal muscle spasm and autonomic nervous system disturbance
- Caused by a powerful neurotoxin produced by Clostridium tetani (gram-positive, anaerobic, spore-forming rod)
- Completely preventable by vaccination
- In developed countries: seen occasionally in incompletely vaccinated individuals
- In developing countries: vaccination coverage is low; severe disease with high mortality
DEFINITION (CDC/WHO)
- CDC: Probable tetanus = "an acute illness with muscle spasms or hypertonia in the absence of a more likely diagnosis"
- Neonatal tetanus (WHO): "An illness occurring in a child who has the normal ability to suck and cry in the first 2 days of life but who loses this ability between days 3 and 28 of life and becomes rigid and has spasms"
- Maternal tetanus (WHO): Tetanus occurring during pregnancy or within 6 weeks after conclusion of pregnancy (whether with birth, miscarriage, or abortion)
ETIOLOGY
- Spores are highly resilient; survive in the environment worldwide
- Spores resist boiling and many disinfectants
- In addition to wounds, tetanus spores and bacilli survive in the intestinal systems of many animals; fecal carriage is common
- Spores enter the body through abrasions, wounds, or the umbilical stump in neonates
- Once in a suitable anaerobic environment, organisms multiply and release toxin
- Very low concentrations of toxin can result in tetanus (minimal lethal human dose: 2.5 ng/kg)
EPIDEMIOLOGY
- Rare in developed world: Only 2 cases of neonatal tetanus reported in the US since 2009; in 2018, 23 cases total reported to the US national surveillance system (almost all in adults)
- Most cases in incompletely vaccinated or unvaccinated individuals
- Vaccination status known in 25% of US cases (2009-2015): 20% had received 3+ doses of tetanus toxoid-containing vaccine
- Persons >60 years are at greater risk (antibody levels decrease over time)
- ~25% of recent US cases in persons >65 years; diabetes is an associated risk
- ~13% of all cases and 25% of deaths (2009-2015) were in injection-drug users
- ~6% of cases (2009-2015) were in injection-drug users
- Global incidence has significantly reduced following WHO, UNICEF, UNFPA elimination programs
- In 2015, estimated 30,000-62,000 deaths from tetanus in older children and adults
PATHOGENESIS
- Genome sequencing identified several exotoxins and virulence factors
- Only tetanospasmin causes tetanus
- Closely related to botulinum toxins in structure and mode of action
- Tetanospasmin undergoes retrograde transport into the CNS → presynaptic inhibitory interneuron terminals
- The light chain is a zinc-dependent endopeptidase that cleaves VAMP (vesicle-associated membrane protein 2), also known as synaptobrevin
- VAMP is necessary for presynaptic binding and release of neurotransmitters
- Toxin blocks inhibitory interneuron discharge → unregulated motor neuron activity
- Similar action in the autonomic nervous system → cardiovascular complications
- Tetanus toxin can interact with several different pH-dependent conformations → can access neuronal trafficking systems and evade degradation
Toxin as a 150-kDa protein:
- Heavy chain (100 kDa): binds to specific membrane components in presynaptic motor terminals; evidence of binding to polysialogangliosides and membrane proteins → toxin internalization and uptake into motor neurons
- Once inside the motor neuron: undergoes retrograde transport proximally to the motor neuron body
- Then travels across the synapse to reach presynaptic inhibitory interneuron terminals
CLINICAL AND PATHOLOGIC PROGRESSION (Figure 152-1)
| Stage | Timing | Features |
|---|---|---|
| Wound infection with C. tetani | Day 0 | - |
| No symptoms (incubation) | 7-10 days | - |
| Initial symptoms | After incubation | Muscle aches, trismus (lockjaw), myalgia |
| Toxin uptake into nervous system + VAMP cleavage in GABA inhibitory neurons | 24-72 hours | - |
| Widespread disinhibition of motor and autonomic nervous system | After 24-72 hrs | - |
| Muscle spasm | During illness | Local and generalized |
| Cardiovascular instability | During illness | Labile BP, tachy- or bradycardia |
| Pyrexia, increased respiratory and GI secretions | During illness | - |
| Toxin degradation | 4-6 weeks | - |
| Resolution | 4-6 weeks | Cessation of spasms, restoration of normal muscle tone, cardiovascular and autonomic control |
APPROACH TO THE PATIENT / CLINICAL MANIFESTATIONS
- Clinical manifestations occur only after tetanus toxin has reached presynaptic inhibitory nerves
- Management: neutralize remaining unbound toxin, support vital functions until toxin effects wear off
Clinical Features - Broadly Divided:
1. Local Tetanus: Only isolated areas of the body affected; mild form
2. Generalized Tetanus (most common):
- Muscles of face and jaw affected first (shorter distances toxin must travel)
- Neonatal tetanus: toxin must travel up motor nerves to reach presynaptic terminals; neonates typically present with inability to suck
- Common initial symptoms: trismus (lockjaw), muscle stiffness, neck pain, difficulty in feeding
- As disease progresses: muscle spasm develops; generalized muscle spasm can be very painful
- Laryngeal muscles involved early/or severely → complete airway obstruction (life-threatening event)
- Respiratory failure = most common cause of death in tetanus
- Autonomic disturbance: maximal during the second week; cardiovascular events become the major risk (death due to cardiovascular events); labile blood pressure, tachycardia, bradycardia and heart block
- Gastrointestinal stasis, sweating, increased tracheal secretions, acute (often high-output) renal failure
Assessing prognosis:
- Incubation period (wound to first symptom) and period of onset (first symptom to first generalized spasm) - shorter = worse outcome
- Neonatal tetanus: younger infant when symptoms occur = worse prognosis
DIAGNOSIS
- Based on clinical findings; treatment should not be delayed while laboratory tests are conducted
- Culture: C. tetani from a wound provides supportive evidence
- Serum anti-tetanus immunoglobulin G: measured in a sample taken before administration of antitoxin/immunoglobulin; levels >0.1 IU/mL (by standard ELISA) are deemed protective and do not support the diagnosis
- Polymerase chain reaction (PCR) may be helpful but a negative result does not exclude the diagnosis; these levels are not generally performed
Differential Diagnosis:
- Conditions mimicking generalized tetanus: strychnine poisoning, dystonic reactions to antidopaminergic drugs
- Abdominal muscle rigidity is characteristically continuous in tetanus but episodic in latter two conditions
- Cephalic tetanus: confused with trismus of other etiologies such as oropharyngeal infection
- Hypocalcemia and meningoencephalitis are in the differential for neonatal tetanus
TREATMENT
1. Wound Care
- If possible: identify, clean, and debride the entry wound to remove anaerobic foci of infection and prevent further toxin production
2. Antibiotics
- Metronidazole 400 mg rectally or 500 mg IV every 6h for 7 days - preferred
- Alternative: penicillin (100,000-200,000 IU/kg per day) - theoretically may exacerbate spasms and in one study was associated with increased mortality
- Failure to remove pockets of ongoing infection may result in recurrent or prolonged tetanus
3. Antitoxin
- Given early to deactivate any circulating toxin and prevent its uptake into the nervous system
- Two preparations available:
- Human TIG (Tetanus Immune Globulin) - preparation of choice (less likely to cause anaphylactoid reactions); dose = single IM 500-5,000 IU with a portion injected around the wound
- Equine antitoxin - widely available, used in low-income countries; after hypersensitivity testing, 10,000-20,000 IU IM as a single dose or divided doses
- Some evidence that intrathecal administration of TIG (50-1,500 IU) inhibits disease progression and leads to better outcomes; meta-analysis supports this for both adults and neonates with doses of 50-1,500 IU; however most preparations are not licensed for intrathecal use
4. Controlling Spasms
- Heavy sedation with benzodiazepines (chlorpromazine and phenobarbital also used worldwide)
- IV magnesium sulfate: used as a muscle relaxant; plasma concentration target 2-4 mmol/L or titrated against disappearance of patellar reflex
- Morphine, fentanyl, or other sedatives may also be used
- Short-acting drugs that allow rapid titration preferred; longer-acting beta antagonists should be used with caution as their use has been associated with hypotensive cardiac arrest
- Propofol infusions: used successfully to control spasms and provide sedation
- Problem: doses needed to control spasms also cause respiratory depression; in resource-limited settings without ventilators, controlling spasms while maintaining ventilation is problematic
5. Airway Management
- Establish a secure airway early in severe tetanus
- Nurse in calm, quiet environments (light and noise can trigger spasms)
- Tracheal secretions increased + dysphagia due to pharyngeal involvement + hyperactivity of laryngeal muscles → endotracheal intubation difficult
- Tracheostomy is the usual method of securing the airway in severe tetanus; patients may need ventilator support for several weeks
6. Cardiovascular Instability
- Rapid fluctuations in BP and HR are notoriously difficult to treat
- Improved by increasing sedation + IV magnesium sulfate
- Drugs acting on the cardiovascular system: esmolol, calcium antagonists, inotropes
- Short-acting drugs preferred; caution with longer-acting beta antagonists (risk of hypotensive cardiac arrest)
7. Complications
- Thrombophlebitis (from diazepam injection)
- Ventilator-associated pneumonia
- Central-line infections
- Septicemia
- Prophylaxis against deep-vein thrombosis and thromboembolism is routine
8. Recovery
- Takes 4-6 weeks
- Patients must be given a full primary course of immunization as tetanus toxin is poorly immunogenic and the immune response following natural infection is inadequate
PROGNOSIS & POOR PROGNOSTIC FACTORS
TABLE 152-1: Factors Associated with Poor Prognosis
| Adult Tetanus | Neonatal Tetanus |
|---|---|
| Age >70 years | Younger age, premature birth |
| Incubation period <7 days | Incubation period <6 days |
| Short time from first symptom to admission | Delay in hospital admission |
| Puerperal, IV, postsurgery, burn entry site | Grass used to cut cord |
| Period of onset <48 h | Low birth weight |
| Heart rate >140 beats/min | Fever on admission |
| Systolic blood pressure >140 mmHg | |
| Severe disease or spasms | |
| Temperature >38.5°C |
Time from first symptom to first generalized spasm. At hospital admission.
- Rapid development of tetanus is associated with more severe disease and poorer outcome
- In many adults, particularly the elderly: surviving tetanus associated with reduced long-term functional outcome measures
- Studies of children and neonates: higher incidence of neurologic sequelae; may be at increased risk of learning disabilities, behavioral problems, cerebral palsy, and deafness
PREVENTION
- Tetanus is prevented by good wound care and immunization
- In neonates: use of safe, clean delivery and cord-care practices + maternal vaccination are essential
- WHO guidelines: primary course of 3 doses in infancy; boosters at 4-7 years and 12-15 years; one booster in adulthood
- CDC (US): additional dose at 15-18 months with booster at 11-12 years and every 10 years thereafter
- Incomplete vaccination: 3-dose primary course with 4 weeks between first two doses, followed by booster 6-12 months later; catch-up schedules under 7 years = 4 doses if child <12 months at first dose, or 3 doses for >12 months
- Standard WHO recommendations: 2 doses of tetanus toxoid at least 4 weeks apart for previously unimmunized pregnant women; third dose ≥6 months later; one dose in subsequent pregnancies (or ≥1 year intervals), total of 5 doses for long-term immunity
- Tetanus-prone wounds in individuals with incomplete/unknown vaccination or last booster >10 years ago: should undergo passive immunization with TIG
- Tetanus toxoid given in conjunction with diphtheria toxoid (DTaP for <7 years, Td for 7-9 years, Tdap for >9 years old)
Global Burden:
- In 1989, World Health Assembly resolved to eliminate neonatal tetanus by year 2000 (defined as <1 case/1,000 live births in every district in every country)
- By 1999: elimination was still to be achieved in 57 countries
- 2005 deadline extended with additional target of eliminating maternal tetanus
- As of December 2020, 12 countries have yet to achieve this goal
- 47 countries have achieved maternal and neonatal tetanus elimination (including China, India, Indonesia)
- Worldwide, deaths from neonatal tetanus fell by 96% between 1990 and 2015; in 2015, 72% of mothers received at least 2 doses of tetanus toxoid-containing vaccine and an estimated 34,000 neonatal tetanus deaths, mainly in Africa and Southeast Asia
- Primary vaccination coverage in infancy (3 doses of DTP) is 86%, but rates for subsequent boosters necessary for long-term protection are unknown
BOTULISM (Chapter 153 - Brief Introduction)
- Rare, life-threatening disease characterized by cranial nerve palsies and symmetric descending flaccid paralysis
- 4 forms of naturally occurring botulism:
- Foodborne botulism
- Infant botulism
- Wound botulism
- Adult intestinal colonization/toxemia
- Other forms: iatrogenic botulism, inhalational botulism
- Effective treatment depends on early clinical diagnosis
Etiology and Pathogenesis:
- Caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum
- Rare strains of C. baratii and C. butyricum can also produce BoNTs
- 7 distinct serotypes of BoNT (A through G) are well characterized; serotypes A, B, E, and F require cause disease in humans; novel serotypes BoNT/FA (H or HA), BoNT/En, and BoNT/X also proposed
- Foodborne botulism: by ingestion of foods contaminated with BoNT; wound botulism occurs when spores of BoNT-producing Clostridium contaminate a wound and germinate, multiply, and produce toxin
- Infant botulism: caused by BoNT-producing species of Clostridium colonizing the intestinal tract of infants ≤1 year of age
- Adult intestinal toxemia: similar to infant botulism but affects persons >1 year
- Iatrogenic botulism: occurs when a patient is given more BoNT than they can tolerate
Source: Harrison's Principles of Internal Medicine, Chapter 152 (Tetanus) and Chapter 153 (Botulism)
Can u simplified it lil bit
TETANUS - Simplified Notes
WHAT IS IT?
- Disease causing muscle spasms + autonomic disturbance
- Caused by toxin from Clostridium tetani (a bacteria)
- Completely preventable by vaccination
- High mortality in developing countries
HOW IT CAUSES DISEASE (Simple)
- Bacteria enters through a wound
- Produces tetanospasmin toxin
- Toxin travels up nerves to the spinal cord
- Blocks inhibitory neurons (the "brakes" on muscles)
- Result: uncontrolled muscle contractions
TIMELINE
| Time | What Happens |
|---|---|
| Day 0 | Wound infection |
| 7-10 days | No symptoms (incubation) |
| After incubation | Muscle aches, jaw stiffness (trismus) |
| 24-72 hrs later | Widespread muscle spasms |
| Week 2 | Worst cardiovascular instability |
| 4-6 weeks | Recovery begins |
SYMPTOMS
- Trismus (lockjaw) - hallmark symptom
- Muscle stiffness progressing to painful spasms
- Respiratory failure - #1 cause of death
- Labile blood pressure, fast/slow heart rate
- Sweating, fever, difficulty swallowing
DIAGNOSIS
- Mainly clinical - don't wait for tests to start treatment
- Serum anti-tetanus IgG >0.1 IU/mL = protective (makes tetanus unlikely)
- Culture of wound provides supportive evidence
TREATMENT (Easy to Remember)
| Step | What to Do |
|---|---|
| 1. Wound | Clean and debride |
| 2. Antibiotics | Metronidazole 500 mg IV q6h x 7 days |
| 3. Antitoxin | Human TIG (preferred) or equine antitoxin |
| 4. Spasms | Benzodiazepines (heavy sedation) |
| 5. Airway | Tracheostomy in severe cases |
| 6. Heart | Magnesium sulfate + sedation |
| 7. After recovery | Full vaccination course |
Key point: Recovery takes 4-6 weeks. Must vaccinate after recovery (natural infection gives NO immunity)
POOR PROGNOSIS SIGNS
Adults: Age >70, heart rate >140, short incubation (<7 days), high BP, high temp, severe spasms
Neonates: Very young/premature, incubation <6 days, low birth weight, fever on admission
PREVENTION
- Vaccine: DTP series in childhood; booster every 10 years
- Pregnant women: 2 doses of tetanus toxoid (at least 4 weeks apart)
- Wound + incomplete vaccination: Give TIG immediately
- Neonates: Clean delivery, sterile cord cutting
BOTULISM (Brief - Chapter 153)
- Also caused by Clostridium toxin (BoNT)
- Causes descending flaccid paralysis (opposite pattern to tetanus)
- 4 types: Foodborne, Infant, Wound, Adult intestinal
- Diagnosis must be made early for effective treatment
Tetanus vs Botulism quick memory trick:
- Tetanus = spastic (too much muscle tone - spasms)
- Botulism = flaccid (too little muscle tone - paralysis)
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