Tetanus is now a rare disease in the United States due to the effectiveness and nation-wide implementation of tetanus toxoid vaccines (Td). However, tetanus remains a constant threat because its vaccine does not confer herd immunity, and clinical disease does not bestow individual immunity. Protection from this severe disease comes only in the forms of primary and secondary prevention. Unfortunately, these two measures are often erroneously hybridized and thereby misunderstood. In Talan’s series of 1988 patients presenting to US Emergency Departments, none of the 504 patients most in need of secondary prophylaxis were treated correctly. In Abbate’s survey of Italian Emergency Departments, only 1.5% of the physicians correctly adhered to tetanus prophylaxis practices in wound management.
Primary Prevention – Tetanus Toxoid Vaccine
Primary prevention refers to measures that decrease the likelihood of disease in the absence of exposure. Clostridum tetani spores are widely distributed in soil, intestines of most animals, skin surfaces, and contaminated heroin. They can survive extreme heat – including that of autoclaving – as well as antiseptics. The widespread reservoir and resilience of this pathogen makes eradication unfeasible. Thus, the principal means of primary prophylaxis falls to vaccination, which is administered as the primary series and boosters.
The primary series educates a naive immune system to recognize tetanus toxoid and to produce a basal level of neutralizing immunoglobulins. The usual schedule is four doses at 2, 4, 6, and 15-18 months of age with a booster at 11-12 years old. Essentially all recipients of the primary series have serum antitoxin levels greater than the protective level of 0.1 IU/mL.But serum antitoxin levels wane with time and tetanospasmin is amongst the most potent of toxins (lethal dose 2.5ng/kg), capable of producing disease without stimulating the immune system. Thus, tetanus boosters are recommended every 10 years to stimulate production of anti-toxoid antibodies.
The clinical efficacy of Td in primary prevention is dramatic. After its introduction to military personnel in Sept 1914, a significant decrease in tetanus cases was noted by December.
Tetanus toxoid vaccine became part of routine childhood immunization in the late 1940s, which heralded a steady decline in tetanus cases.
Secondary Prevention – The Futility of Tetanus Toxoid
Secondary prevention refers to measures that decrease the likelihood of disease after the fact to a potential exposure. Unlike primary prophylaxis, tetanus toxoid vaccine has a very limited role in preventing disease after sustaining a wound. Clinical tetanus has incubation periods as short as three days. However, serum antitoxin levels does not demonstrate significant response at 4 days after injection with tetanus booster.
Tetanus booster alone likely provides no protection in patients inoculated with tetanus spores. Thus, the oft asked question of “when was your last tetanus shot” has little, if any, relevance to wound management. Furthermore, the answer to this question has been shown to be notoriously unreliable. A third of patients incorrectly recalled that they were not up-to-date on their vaccination. A quarter of patients wrongly recalled that they were up-to-date on their vaccinations. This topic has been so frustrating that McVicar (2013) proposed simply testing tetanus titres in the Emergency Department and not rely on the patient’s history at all. Her study concluded that if vaccination were based on recall status, 38.8% of patients would receive incorrect treatment.
Unfortunately, antibody titres and immunity are not in full agreement as evidenced by several case reports of patients who developed clinical tetanus with protective titres. More importantly, tetanus vaccine is a primary preventative measure, beneficial only if given prior to the exposure. The question of tetanus vaccination status should be ideally inquired when the presenting complaint is not wound-related for the sole goal of ensuring adequate immunization rather wound-treatment. This is currently not practiced. To reconcile, CDC recommends giving tetanus booster to patients with wounds if more than 5 years have elapsed since their last dose. The overlap helps cover our current, imperfect vaccination practices.
Secondary Prevention – Tetanus Immunoglobulins
The correct treatment for clinical tetanus or secondary prevention of tetanus is tetanus immunoglobulin (TIG). It was first used in 1897 by Nocard for treatment and prophylaxis in WWI. CDC recommends TIG for patients who fulfill two criteria: 1) received less than three primary tetanus toxoids and 2) have a wound that is anything but clean and simple.
1) Incomplete Primary Series (< 3)
The vast majority of tetanus cases did not complete their primary series. Only one patient from Filia’s Italian series of 343 patients with known vaccination status developed clinical tetanus.
Thus, completion of the primary series is the most important question to answer in wound-related complaints. In Talan’s series, this was documented in less than 20% of wound-related visits to the ED.
2) Wound that is Anything but Clean and Simple
Multiple organizations over the years have formulated many descriptors for tetanus prone wounds:
- contaminated with dirt, feces, soil, or saliva; puncture wound; avulsions; and resulting from missiles, crushing, burns, and frostbite
- sustained more than six hours before surgical management; with significant devitalized tissue; punctures; in contact with soil or manure; or associated with sepsis.
- wounds or burns requiring surgical intervention delayed by > 6h, with significant devitalized tissue, puncture, soil/manure, with foreign body, with compound fractures, or with sepsis.
Unexpectedly, several reported cases of tetanus involved trivial wounds, sterile surgical procedures, or nontraumatic conditions. Given the wide prevalence of tetanus spores, even clean wounds can be at risk for secondary infection. Reported cases to the CDC from 2001 to 2008 revealed that only 72% of cases had acute wounds preceding illness, 20% of which had wounds not traditionally thought to be associated with tetanus. The remainder reported a chronic wound (diabetic ulcers, dental abscesses) or reported no wounds. The majority of the latter group had a history of IV drug use.
The CDC no longer stipulates definitions for tetanus prone wounds given the heterogeneity of the wounds in tetanus cases. The criteria of anything but clean and simple should be interpreted as constant vigilance for a rare but still severe disease.
Other Risk Factors
There is debate as to the correct course of action for patients who have completed their primary series but are not up to date on their tetanus boosters. The CDC recommends not utilizing TIG given that most patients still have protective titers even without boosters. Porter et al. (1992) demonstrated that 5/31 patients who have completed the primary series had low antitoxin titres, though the clinical significance of this is unclear. Vaccine failure or waning immunity may be rather common, especially in older patients. Thus, the United Kingdom recommends using of TIG irrespective of immunization history of patient if the wound is tetanus prone and high risk for contamination.
The data from CDC’s 2001-2008 series suggests that boosters are indeed important, and even fully up to date individuals can still contract the disease. Talan’s series shows that 4.7% of adequately immunized individuals still had low tetanus titers while 13.7% of inadequately immunized individuals had low tetanus titers.
Age has been a frequently identified risk factor, particularly because immunity tends to wane with time.
Diabetes and IV drug use have also been shown to be risk factors. Diabetics represented 15% of tetanus cases in USA between 2001-2008. IV drug use also represented 15% of the same population. Quinine, used to dilute heroin, may support the growth of C. tetani.
Tetanus was among one of the many scourges that fell to obscurity with public vaccination practices. But unlike the other pathogens, tetanus is as ubiquitous today as it was a century ago and there is no herd immunity to provide mass protection. The falling rates of tetanus disease can lend false reassurance to medical care providers. The threat of disease is ever-present and the onus is on each individual to obtain adequate protection through appropriate primary and secondary prevention practices.
Edsall labelled tetanus as the inexcusable disease in 1976.
— From CDC —
If a person gets a puncture wound or laceration on Friday night, does the person need to receive tetanus wound management that night or can it wait until Monday?
ACIP has not addressed this issue specifically. Puncture wounds, however, should be attended to as soon as possible. The decision to delay a booster dose of tetanus toxoid-containing vaccine following an injury should be based on the nature of the injury and likelihood that the injured person is susceptible to tetanus. The more likely the person is to be susceptible, the more quickly that tetanus prophylaxis should be administered. A person with a tetanus-prone wound (e.g., punctures, wounds contaminated with soil or fecal material) and who has no history of tetanus immunization must be vaccinated and given tetanus immune globulin (TIG) as soon as possible. A person with a documented series of at least three tetanus toxoid-containing products, with a booster dose within the previous 10 years ago is less likely to be susceptible to tetanus, and the need for a booster dose is not as urgent, particularly if the wound can be thoroughly cleaned. The more likely a person is to be completely susceptible to tetanus (i.e., unvaccinated or incompletely vaccinated), the sooner that TIG and Td/Tdap should be administered, even if it means a trip to the emergency department.
When should tetanus immune globulin (TIG) be administered as part of wound management?
TIG is recommended for any wound other than a clean minor wound if the person’s vaccination history is either unknown, or s/he has had less than a full series of 3 doses of Td vaccine. TIG should be given as soon as possible after the injury.
How long after a wound occurs is tetanus immune globulin no longer recommended?
In the opinion of the tetanus experts at the CDC, for a person who has been vaccinated but is not up to date, there is probably little benefit in giving TIG more than a week or so after the injury. For a person believed to be completely unvaccinated, it is suggested to increase this interval to 3 weeks (i.e., up to day 21 post injury). Td or Tdap should be given concurrently.