How the tetanus vaccine works
Dispelling myths about tetanus and the vaccine
Tetanus, also known as lockjaw, is unique among vaccine preventable diseases in that it is not infectious from person to person. Thus, herd immunity does not provide protection for those who are unvaccinated. According to the CDC, almost all reported cases of tetanus occur in people who have either never been vaccinated, or who completed a primary series but have not had a booster in more than 10 years.
There are an estimated 800,000 to 1,000,000 deaths from tetanus each year [1], and roughly 50% of these are attributed to neonatal tetanus. This article aims to dispel current myths around the causes, treatment and prevention of the disease.
1) The bacterium and its spores
Before discussing tetanus it’s important to distinguish between the vegetative and spore state of the bacterium Clostridium tetani:
1) In a vegetative state, Clostridium tetani is anaerobic and produces the toxins that cause tetanus infection. In this state, the bacterium is sensitive to heat and dies if exposed to oxygen.
2) By contrast, the spore state of C tetani is ubiquitous and extremely hardy. Spores consist of a core that contains only the bare essentials necessary to initiate bacterial growth, surrounded by a tough and highly impermeable coating that is made up of several layers. Spores essentially protect the bacterium from harmful environmental conditions that would otherwise kill the vegetative form of the bacterium [2]. While the vegetative form of C tetani is sensitive to heat and oxygen, its spores can survive oxygenated environments, boiling and disinfectants. [2] From what we know to date, spores can only be killed by placing in a solution of carbolic acid, formalin, chloramine or hydrogen hyperoxidates for 15–24 hours, or by heating to 120°C for 15–20 minutes. [3]
If C tetani spores come in contact with a favorable anaerobic or hypo-aerobic environment (such as dead or injured tissue surrounding a wound), the spores germinate to the vegetative form that releases toxins.
Spores of C tetani are ubiquitous and are found in the soil (approximately 30% of soil samples in the US according to one survey [4]), as well as the intestinal flora of humans and animals, in feces, on human skin and on teeth [5]. Spores have also been detected in street dust, and the dust and air of operating theatres. [6] [7] All of these environments are continually exposed to oxygen and heat. To recap:
2) How tetanus spores enter the body
Tetanus spores are harmless if inhaled or ingested as they require an anaerobic environment to germinate [5].
By contrast, if spores enter the body through a wound and locate dead or injured tissue surrounding the wound, this anaerobic environment gives rise to the vegetative form of C tetani [5] [8] that releases dangerous toxins.
Deep-tissue wounds contaminated with soil, fecal matter or rusty metal are typical causes of tetanus. However, spores can also enter the body via the following means: [5] [9] [10]
- Animal bites
- Burns
- Childbirth or abortion related infections of the uterus
- Chronic dermatitis
- Chronic middle ear infections
- Compound fractures
- Necrotic tumours
- Non-sterile acupuncture or body piercings
- Non-sterile intravenous or muscular injections
- Splinters
- Surgery or dental extractions
- Ulcers
While severe wounds are common causes of tetanus, the infection can also follow trivial injuries. In fact, up to 50% of tetanus cases occur after indoor injuries or injuries not considered serious enough to seek medical treatment. In 15–25% of cases, there is no evidence of a recent wound [1][9].
3) Incubation period
The incubation period (the time from injury to the onset of the first symptom) can be as short as 24 hours and as long as many months. [10] The average time period is 7–10 days. Typically, the further the injury from the central nervous system, the longer the incubation period. [5]
4) How the tetanus infection works
Under anaerobic conditions found in dead or infected tissue, tetanus spores mature to the vegetative form of C tetani, multiply and secrete two toxins — tetanospasmin and tetanolysin:
1) Tetanolysin damages otherwise viable tissue surrounding the infection and optimizes the conditions for bacterial multiplication.
2) Tetanospasmin is a neurotoxin that leads to the clinical manifestations of tetanus. It is the second most potent toxin in the world, after botulinus toxin. The entire global population can be annihilated with 250 grams of tetanus toxin.
The released tetanospasmin (also called tetanus toxin) spreads to underlying muscle tissue. As the toxin load grows, it spreads via the following means:
- A minute amount of toxin may enter nerve terminals at the site of injury, from where it moves to the central nervous system. [8] [10] This may be insufficient to cause the clinical manifestations of tetanus.
- The vast majority of tetanus toxin, however, is transported via the lymphatic system to the blood stream, from where it diffuses to bind to nerve terminals throughout the body [8] [10] [11] [12]. (Here, antibodies in the blood stream can neutralize the toxin.)
Once the tetanus toxin reaches the central nervous system, it leads to intense muscular rigidity and spasms. Over time, these spasms become more violent, intensely painful and can lead to spinal fractures, muscle tears and tendon rupture. [8] Muscles of the jaw, face, and head are often involved first (known as “lockjaw”) because of their shorter nerve pathways. Spasms in the trunk of the body and limbs then follow. [1]
5) Cause of death
Death from tetanus is usually due to:
- Intense spams that lead to respiratory failure, if no access to mechanical ventilation is available, or
- Cardiac failure linked to autonomic dysfunction
Before the invention of ICU, 80% of tetanus patients died as a result of acute respiratory failure. [1] In some regions, tetanus mortality was 100%. [13] With access to modern healthcare facilities, the mortality rate ranges from 10-40%. [5]
6) Treatment of tetanus
Although the treatment of tetanus has greatly improved in the last few decades, tetanus remains a severe, costly and lengthy disease to treat. The direct cost of treating a tetanus patient in the US can exceed $ 150,000. [39]
If a patient already exhibits the clinical manifestations of tetanus (such as muscular spasms and lockjaw), it is too late to vaccinate and treatment usually involves three principles:
1) Removing the source of infection — this involves cleaning the wound, removing unhealthy tissue surgically and killing the tetanus bacteria via antibiotics to prevent further toxin release.
2) Neutralizing the unbound toxin — TIG (tetanus immune globulin), which contains tetanus antibodies from donated blood, can be injected into the body to neutralize toxin that is still outside the central nervous system.
3) Minimizing the effects of the toxin already in the central nervous system — Nothing can be done to discharge the toxin already bound to nerves [5]. Neuronal binding of toxin is irreversible and recovery requires the growth of new nerve terminals which can take several weeks. [1]
While waiting for nerve terminals to regrow, the symptoms of tetanus can be managed via sedation with drugs, anticonvulsants, neuromuscular blocking agents and mechanical ventilation. [1] Additional drugs may be needed to counter hypertension and cardiac problems. [8]
Severe cases of tetanus usually require ICU admission for 3–5 weeks and additional months of hospitalization. Patients can fully recover however some follow-up studies in survivors have pointed to long term physical and psychological complications. [1] Neonatal tetanus can lead to intellectual disability. [14]
7) Complications
Short term complications of tetanus infection can include pulmonary embolism, bed sores, hospital acquired pneumonia, catheter-association infections and contractures. Survivors can also be left with long term complications such as:
- prolonged muscle fatigue
- hyperostoses (thickening of bone tissue)
- osteoarthritis (a form of arthritis involving sore or stiff joints)
- difficulties with speech, memory and mental capacity [15] [16] [17]
Survivors can be left with long term complications such as difficulties with speech, memory and mental capacity.
8) Natural immunity?
Tetanus infection does not induce natural immunity. This is because tetanospasmin is so potent that even a lethal dose is insufficient to provoke an immune response — by contrast, the tetanus vaccine contains a much larger amount of inactivated toxoid which stimulates protective antibody levels.
Lack of natural immunity is evident in animal studies, as well as case reports of relapsing [30] [32] [33] and recurrent tetanus infection in humans. [5] [31]
The tetanus vaccine, by contrast, contains enough immunogens to produce high levels of antibody that last 10 years or more.
9) How the preventative vaccine works
The tetanus toxoid vaccine became commercially available in the US in 1938 but was not widely used until the military introduced routine vaccination in 1941. [3]
The tetanus vaccine contains inactivated tetanus toxoid. This is prepared by treating tetanus toxin chemically (usually by formaldehyde) to render it nontoxic without losing its immunogenic properties. The toxoid is concentrated, purified and absorbed onto a suitable adjuvant. [5]
Immunization with tetanus toxoid stimulates the body to create protective antibodies to the tetanus toxin.
The amount of antibody produced is measured in International Units (IU/ml). Based on animal studies it has been estimated that toxin antibody levels higher than 0.01 IU/ml are sufficient to protect against tetanus. This estimate has been confirmed in clinical reports. [5]
After receiving primary doses of the vaccine, antibody levels greatly exceed the protective levels of 0.1 IU/mL. However, antibodies decrease over time, and the CDC recommends a booster every 10 years. It is also recommended that anyone who receives a wound that is neither clean nor minor and has not had a booster in more than five years should receive one [18].
The vaccine is nearly 100% effective in preventing tetanus [8] [18] and almost all reported cases of tetanus are in persons who have either never been vaccinated, or who completed a primary series but have not had a booster in the preceding 10 years. [18]
10) Proof of vaccine effectiveness
The following studies and historical reviews shed light on vaccine effectiveness:
- A double blind, randomized, controlled trial in rural Colombia showed that tetanus toxoid administered to women of childbearing age reduced neonatal tetanus cases by 100% compared to controls. [19] [20] [21] Similar studies report 70% to 100% vaccine effectiveness in preventing neonatal tetanus. [22] [23] [24]
- In 1942, German scientists Wolters and Dehmel immunized themselves with tetanus toxoid and achieved protective antibody levels up to 0.01 IU/ml. They then injected themselves with “two or three fatal doses” of tetanus toxin, without problems. [25]
- Tetanus mortality in US troops was drastically reduced in World War II compared to World War I due to routine tetanus immunization of soldiers before World War II. In World War I, 70 out of 520,000 wounded US soldiers contracted tetanus (13.4 per 100,00). In World War II, the figure reduced to only 12 cases of tetanus among 2.73 million wounded US soldiers (0.44 per 100,000). Only 4 of the 12 cases had been vaccinated. [26] A similar experience was reported in the British army. [27] By contrast, the German army had not been immunized against tetanus and spies reported 80 cases of tetanus among German troops during the Normandy invasion alone. [28] That figure may be highly conservative as there were 53 cases of tetanus among American-held German prisoners of war in the United Kingdom during the period 7 September to 2 October 1944. [29]
The tetanus vaccine was added to the routine childhood immunization schedule in 1944 due to:
- the success of tetanus immunization campaigns in the military
- wide C tetani spore distribution
- high tetanus case-fatality rates
- frequent, severe reactions to tetanus antitoxin as a form of treatment, which also had limited efficacy
Duration of vaccine-induced immunity
Even though a tetanus booster is recommended every 10 years, vaccine-induced immunity may last longer than 10 years. Studies in Denmark indicated that a three-dose primary series of tetanus immunization led to protective levels of antitoxin for more than 25 years in 72% of recipients. [35] [36] [37] These studies have suggested that a 20 year booster may be sufficient to maintain immunity. Other studies have suggested that no further assessment of tetanus immunity is needed until individuals reach 50 years of age. [38]
Serosurveys on tetanus antibodies suggest that susceptibility to tetanus increases with age as a result of lack of booster doses. [3] The age distribution of tetanus in developed countries reflects this. A survey in the US from 1998 to 2000 found that 75% of tetanus deaths occurred in persons 60 years or old. [34]
The immune response to the tetanus vaccine is not compromised by the presence of passively acquired antibodies. [3]
11) Debunking current anti-vaccine myths
Myth 1: You cannot get tetanus from a wound that bleeds
This is incorrect. Tetanus spores can survive in highly oxygenated environments (they live in the soil and intestines for example). Once they enter the body through a wound and find a favourable anaerobic environment in dead or injured tissue, they germinate, mature to the vegetative form of C tetani (which is anaerobic) and release toxins. One of the toxins produced, tetanolysin further damages the surrounding tissue and aids in maintaining an anaerobic environment for spore germination.
Myth 2: If I just clean my child’s wounds, he will be fine.
Wound cleaning is always a good idea. However:
- Wounds start healing within 20 minutes of an injury. C tetani may be lodged deep within a wound while the exterior of the wound has started healing and clsoing. Wound cleaning may not reach all affected tissue.
- The spore format of C tetani is very hardy. It can only be inactivated by placing in a solution of carbolic acid, formalin, chloramine or hydrogen hyperoxidates for 15–24 hours, or by heating to 120°C for 15–20 minutes. [3] Only once spores have germinated and matured to the vegetative form of C tetani, does the bacterium become sensitive to heat and light.
- Up to 50% of tetanus cases occur after indoor injuries or injuries not considered serious enough to seek medical treatment. In 15–25% of cases, there is no evidence of a recent wound [1][9].
Myth 3: I can always give my child the TIG shot if he develops tetanus. Treatment with TIG is preferrable to the tetanus vaccine.
TIG (tetanus immune globuline) contains tetanus antibodies derived from donated human or animal blood, and is used in the treatment of tetanus (as described in section 6 above). However, TIG is only recommended in life-threatening conditions as it has the following disadvantages:
- As a blood product, TIG can lead to severe allergic reactions including anaphylactic shock [5]. TIG derived from animal blood often leads to allergic side effects such as anaphylaxis and serum sickness.
- TIG carries the risk of transmitting other infectious agents such as hepatitis and HIV. Donor screening has reduced but not completely eliminated this risk:
“Because TIG is prepared from pooled human plasma, it may carry a risk of transmitting infectious agents, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD). Improved donor screening, viral-inactivation procedures (e.g., solvent/detergent treatment), and/or filtration procedures have reduced, but not completely eliminated, risk of pathogen transmission with plasma-derived preparations. The manufacturing process for TIG includes certain chemical (solvent/detergent) treatment procedures and/or heat-treatment procedures to reduce viral infectious potential. Because no purification method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge which may not be inactivated by the manufacturing process or the chemical (solvent/detergent) treatment procedures currently used, administer TIG only when a benefit is expected.” [Source]
- Protection via donated antibodies is short-lived. TIG produced from animal serum lasts 2 days whereas TIG from human serum lasts 24–30 days. [10] Thus the TIG shot would need to be re-done for each and every suspected tetanus injury. Protection via the tetanus shot, by contrast, lasts 10 years or more.
Myth 4: There is no evidence the vaccine works
The vaccine is nearly 100% effective in preventing tetanus [8] [18] and almost all reported cases of tetanus are in unvaccinated individuals, or individuals who lapsed on boosters. [18] Please see section 10 above for studies on vaccine effectiveness.
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