Tetanus Prophylaxis

Etiology

Tetanus is a disease caused by Clostridium tetani, a toxin-producing obligate anaerobe, which is found in the soil and gut of mammals. The spores cannot be eliminated from the environment. They may enter the body through compromises in the skin barrier or mucous membranes. Once inoculated, C. tetani transforms into a vegetative bacterium which then travels to the spinal cord and brainstem via the motor neurons. It then produces neurotoxin tetanospasmin, which interferes with the nervous system inhibitory neurotransmitters.[4] C. tetani also produce tetanolysin, which has hemolytic properties and causes membrane damage, but its role is unknown.

Epidemiology

Since the 1940s, due to universal vaccinations of children in developed nations, the incidence has dropped dramatically and steadily. According to the Center for Disease Control and Prevention, between 2009 to 2017, there were 264 cases reported. 23% of those cases were age more than 65 years old, and 13% were less than 20 years old. Mortality was about 7%, and all deaths were more than 55 years old. The highest risk for both tetanus and death is more than 65 years old.[5] Age plays a significant factor due to waning immunity. Similar data are reported worldwide in developed nations.

Prior to the widespread vaccination with tetanus toxoid in the late 1940s, there were approximately 600 cases of tetanus per year in the United States.[6] Since then, the tetanus vaccine has achieved near-universal coverage in the United States, which has resulted in a 96% reduction in the incidence of tetanus cases and the elimination of neonatal tetanus.[7] Presently, the incidence in the United States is 0.01 per 100,000.[1] Most patients who develop tetanus do not have a complete tetanus immunization or received inappropriate prophylaxis after a wound.

Unfortunately, tetanus continues to cause significant mortality in undeveloped nations. Worldwide, an estimated 1 million cases per year of tetanus with 200,000 deaths annually, with most cases and deaths occurring in Southeast Asia and Africa.[8] These areas have no resources for mass immunization programs, vaccines, or proper wound or traumatic injuries treatment. The World Health Organization fears that individuals affected by tetanus are dramatically low due to unreported cases. Many undeveloped nations do not even have reporting and surveillance systems in place.

Pathophysiology

C. tetani enter the body through a break in the skin or mucous membranes. Once within the body and in anaerobic conditions, the bacteria travel to the spinal cord and brainstem within the motor neuron. It then produces highly potent neurotoxin tetanospasmin. The toxin enters inhibitory interneurons and blocks neurotransmission at the synapses.[4] There is then inactivation of inhibitory neurotransmission that normally modulates anterior horn cells and muscle contraction. Loss of inhibition of anterior horn cells will cause increased muscle tone and painful spasms. Loss of inhibition of autonomic neurons will cause widespread autonomic instability, mainly manifests as sweating, tachycardia, and hypertension.[9][10] These effects are long-lasting, and recovery requires the growth of a new nerve terminal.

In healthy tissues, C. tetani will not grow. The incubation period for tetanus ranges from three days to 21 days but usually starts about 8 days. Predisposing factors must be present with the absence of inadequate vaccination plus the following: penetrating or devitalizing type injuries, polymicrobial infections, missed foreign body in wounds or injuries, and any blood flow compromise. Approximately 25% with tetanus has no identifiable causes. Tetanus rarely occurs in patients who are timely and properly receive immunizations.[8]

Toxicokinetics

Tetanus vaccine is a type of artificial active immunity. This type of immunity produces antibodies when a dead or weakened version of C. tetani is inoculated. Thereby, when there is actual exposure, the immune system will recognize the antigen and will rapidly produce antibodies. Antibodies wane over time, so periodic vaccines will be needed to boost the production of antibodies.

History and Physical

A thorough medical history should be obtained. Focus on previous immunization or completion thereof and any previous complications of vaccination. Be wary of patients from other countries, especially those coming from undeveloped nations. Ask about signs and symptoms of muscle spasms, stiffness, and pain. Ask if there is a history of wound or traumatic injuries, then ask about the mechanism of injury, timing, and any predisposing factors. 

A thorough physical exam should be done. Look for muscle rigidity, tone, and spasm. If there is a wound, then note the size and depth of the wound, state of wound tissue, look for foreign body, and any sign of decreased blood flow. 

Do not forget to ask and look for autonomic instability signs and symptoms such as profuse sweating, tachycardia, and labile hypertension or hypotension.

Evaluation

Tetanus should be suspected when there is a history of tetanus prone to injury and inadequate immunization. Evaluation of a patient at risk for tetanus is based on a thorough history and physical examination. Tetanus is a clinical diagnosis. Laboratory tests are not helpful. No diagnostic studies are needed other than to rule out other mimics of tetanus, such as dental abscess or meningitis. There are differences in the diagnosis of adults and neonates, described by the WHO (World Health Organization). For adults, WHO guidelines require clinical evidence of a history of an injury or wound and at least one of the following: painful muscular contractions, trismus, and risus sardonicus. In neonatal tetanus, an infant who in the first 2 days of life and able to cry and suck and then loses that ability in days 3 to 28 and develops spasms or becomes rigid, tetanus is suspected.[11] 

Trismus is caused by intense painful spasms of the masseter muscles with the inability to open the mouth. A clinical test with 100% specificity and 94% sensitivity is the "spatula test," which can be performed to help aid in the diagnosis of tetanus in the clinical setting. This is performed by touching the posterior wall of the oropharynx with a dull instrument, causing reflex jaw spam if tetanus is present.

Treatment / Management

Tetanus prophylaxis is determined by previous immunization and classifying low versus high-risk wound(s): unimmunized (less than 3 doses or unknown) versus immunized (greater than 3 doses), low risk (clean and minor) versus high risk (contaminated, puncture, avulsions, or resulting from missiles, crushing, burns, animal or human bites, or frostbite). In an unimmunized individual with a low-risk wound, the tetanus vaccine is indicated; if high risk, then both vaccine and human tetanus immune globulin (HTIG) are also indicated. In immunized individuals with low-risk wounds, the tetanus vaccine is indicated only if the last dose was given more than 10 years ago. If high risk, then the vaccine is indicated more if the last booster was more than 5 years ago. Prophylaxis should be administered as soon as a possible following wound or traumatic injury and even upon delayed presentation due to the long and variable incubation period of tetanus. Of note, HTIG can be given up to 21 days for unvaccinated individuals if indicated.[2][11][12] Tetanus toxin is irreversibly bound to tissues, therefore only unbound toxin is available for neutralization. The use of passive immunization such as HTIG to neutralize unbound toxin is associated with improved survival, and it is considered to be a standard treatment. In undeveloped nations where HTIG is unavailable, anti-tetanus horse serum can be used but with great adverse effects. If HTIG is indicated and used, part of the dose needs to be injected around the wound or site of a traumatic injury.

All tetanus prophylaxis should be used in conjunction with timely cleaning and debridement of wounds. Patients should receive immediate surgical treatment if indicated. Tetanus-prone wounds may be left open to avoid anaerobic conditions. 

In pregnancy, it is a category C vaccine and is indicated to give Tdap in 27 to 36 weeks and every pregnancy regardless of the last dose. If unvaccinated, then a series of three will be given 4 weeks apart.

In patients with HIV/AIDS, HTIG is indicated regardless of immunization status or wound classification.

Differential Diagnosis

• Drug-induced dystonias
• Strychnine poisoning (rat poison)
• Malignant neuroleptic syndrome
• Stiff-person syndrome 
• Dental infection with trismus
• Meningitis
• Encephalitis
• Hepatic encephalopathy
• Status epilepticus
• Malignant hyperthermia
• Black widow spider envenomation

Treatment Planning

There is no cure for tetanus. Treatment is supportive as best. Prevention is the best strategy by following immunization guidelines with a booster every 10 years and proper identification and prophylaxis of wounds and traumatic injuries. Vaccinations do give lifelong immunity if such guidelines and recommendations are followed.

Toxicity and Adverse Effect Management

 Common side effects are fever, redness, swelling, and pain at the injection site, which are usually the deltoid and thigh regions. Fever is more common in routine vaccinations when administered with concurrent vaccines.[13] Anaphylaxis, urticaria, angioedema, and neurologic complications have been reported following tetanus vaccine administration but rare. Contraindications are an anaphylactic reaction to the previous dose and encephalopathy not attributed to other causes within 7 days of the previously given dose. Precautions should be considered for GBS within 6 weeks of previous dose, history of Arthus-type reaction, or underlying neurologic conditions.

Prognosis

Tetanus continues to cause significant mortality in the developing world. Approximately 2 out of every 10 individuals who develop the disease will not survive. Tetanus does not provide any immunity; those who survive should be actively immunized. Cephalic and neonatal tetanus have poor outcomes. Complete recovery may take months due to the requirement of new nerve terminal growth, which is usually 4 to 6 weeks.

Complications

Although rare in developed nations, complications arise from unvaccinated, missed booster vaccines, and improper treatment of wounds and traumatic injuries. Once tetanus is diagnosed, it is only supportive care and often too late with high morbidity and mortality.