Tetanus

The agent responsible for tetanus is a toxin produced by the Gram-positive bacterium Clostridium tetani, which belongs to the Clostridiaceae family. The bacillus grows optimally in an anaerobic, i.e., oxygen-free, environment and has flagella on its surface that make it mobile.
The bacterium's natural reservoir is the gastrointestinal tract of herbivores, which have become regular hosts. The bacterium, in order to cope with adverse environmental conditions, turns into spores and is then eliminated by feces that infect the soil. The spores take on a "drumstick"-like shape and are resistant to drying, boiling and some disinfectants such as ethanol. Under favorable conditions, the spores geminate releasing the vegetative form of the bacterium that will produce two forms of toxins:
- tetanolysin, which has no pathological effect on humans and has little clinical value;
- tetanospasmin, also called tetanus toxin. It is a very potent neurotoxin and is responsible for the clinical manifestations as it affects the nervous system, first the peripheral then the central, causing the classic symptoms of the disease.

Tetanus is not transmitted from person to person. There are a large number of animals in nature that serve as reservoirs of the pathogen. Therefore, vaccination coverage is not so much important to stop the spread of the infectious agent as to defend as many individuals as possible.
Contagion is direct: infection mostly follows penetration of the spores through skin and mucous wounds (or burns, sores, animal bites, stings, injections). Cases of surgical tetanus are now exceptional; those secondary to obstetrical maneuvers and drug use are less infrequent.
Contamination of wounds or mucous lesions with tetanic spores does not necessarily lead to disease: in fact, spores require much less oxygen tension to germinate than is normally present in tissues. The tetanic spore can survive in the body months or years and give rise to infection only when local conditions are changed even as a result of minor trauma.
Tissue necrosis, foreign bodies, and intercurrent infections often localized to wound sites promote spore germination and production of the exotoxin responsible for symptomatology.

Tetanus is a sporadic disease that occurs particularly in rural areas, while in industrialized countries it is considered a rare disease due to vaccination coverage. The mortality rate can vary from 10% to 70% depending on health treatment, the age of the individual and the patient's general health condition. In the absence of treatment, the mortality rate is about 100%. According to data provided by the European Center for Disease Control and Prevention, there were 117 reported cases of tetanus in Europe in 2015 in 26 countries, an increase of 20 cases from the previous year. Italy reported 48 cases with a 41 percent share of all cases, the highest in Europe. France and Poland followed with 12 cases. The most affected age group is the elderly, with a rate of 0.11 cases per 100000 inhabitants, accounting for 72% of cases with a prevalence in the female sex. Most cases were reported during the warmer months from May to October, peaking in July. This increase generally is associated with the activities people engage in outdoors. However, Clostridium tetani is widespread in the environment worldwide and cannot be eradicated. To reduce the number of tetanus cases, efforts focus on prevention through vaccination and post-exposure wound care.

The incubation period of the disease is 3 to 21 days (average of 7 days). Following lysis of the bacterium, which is present at the wound site, tetanospasmin is released. Through the bloodstream, it reaches the nerves, blocking the release of inhibitory motor neurons (glycinergic and GABAergic) from synapses causing continuous stimulation of skeletal muscles causing continuous and painful muscle spasms.

Four different forms of tetanus can be distinguished:

- Generalized tetanus: about 80% of cases manifest generalized tetanus, the first symptom generally being facial trismus due to contraction of the masseter muscle giving the face the characteristic appearance called "sardonic laughter." After this stage there are symptoms such as; neck stiffness, difficulty swallowing and abdominal muscle rigidity. In some cases, symptoms such as fever, tachycardia or arrhythmias may also occur. There remains opisthotonos (i.e., a state of severe hyperextension and spasticity in which an individual's head, neck and spine enter a completely "bowed" or "bridged" position. This symptom is the most noticeable of tetanus, caused by the contraction of skeletal muscles, which in turn results in hyperextension of the trunk, lower and flexion of the upper limbs.
- Neonatal tetanus: This form occurs in infants from generally immunized mothers; infection occurs during cord cutting through the use of nonsterile instruments. Symptoms arise on average in the first two weeks of life with rigidity, spasms, and poor feeding. Surviving infants may suffer from bilateral deafness.
- Local tetanus: this is the least severe form, is seen in partially immunized individuals, and symptoms are localized exclusively in the muscles near the wound.
- Cephalic tetanus: is a special form of localized tetanus, occurring following a facial wound affecting the cranial nerves.

The diagnosis of tetanus of is based purely on the patient's clinical history. Evaluation of tetanus symptoms and signs is essential, especially when the patient presents with sudden unexplained stiffness and muscle spasms associated with a history of recent injury. In addition, the patient's immune status may point toward the diagnosis.
In some cases, tetanus is confused with meningo-encephalitis caused by viruses or bacteria, but the diagnosis is positive for tetanus in combinations of three factors: an intact sensor, unaltered cerebrospinal fluid, and muscle spasms.

Once tetanus disease is diagnosed, the patient should be admitted to the intensive care unit to make sure that steps are taken to maintain adequate ventilation if respiratory muscles are involved. A tracheotomy may be provided in very severe cases.
In addition, neutralization of circulating toxins with the administration of human antitetanus immunoglobulins, known as active prophylaxis, is provided. Thorough cleansing of the wound with oxidant-acting disinfectants and eventual removal of necrotic tissue is essential.
To prevent further muscle spasm and to prevent the production of new tetanospasms, Clostridium tetani-sensitive antibiotics are to be administered. Penicillin G in this case represents the drug of choice. To control spasms, treatment relies on the administration of muscle relaxant drugs such as intravenous benzodiazepines or barbiturates.
Once tetanus disease is diagnosed, the patient should be admitted to the intensive care unit to make sure that steps are taken to maintain adequate ventilation if respiratory muscles are involved. A tracheotomy may be provided in very severe cases.
In addition, provision is made for neutralization of circulating (unfixed) toxins by administration of human tetanus immunoglobulin, the so-called active prophylaxis. Thorough cleansing of the wound with oxidant-acting disinfectants and eventual removal of necrotic tissue is essential.
To prevent further muscle spasms and to prevent the production of new tetanospasms, Clostridium tetani-sensitive antibiotics are to be administered, penicillin G being the drug of choice in this case. To control spasms, treatment relies on the administration of muscle relaxant drugs such as intravenous benzodiazepines or barbiturates.

Prevention is the cornerstone for avoiding tetanus complications, and thanks to vaccination, tetanus is now considered a rare disease in industrialized countries. In Africa, tetanus cases, especially in children, are still high due to poor vaccine offerings. WHO (the World Health Organization) continues to reiterate the importance of having high vaccination coverage throughout the population, as it is the only form of prevention of the disease. The vaccine contains purified tetanus anatoxin, thus rendered non-pathogenic but able to stimulate the immune system to produce protective antibodies against possible infection. Although very effective, tetanus vaccination does not confer permanent immunity over time, which is why a vaccine booster is recommended every 10 years. In Italy, in the first year of infants' lives, the basic tetanus antitetanus cycle is administered in combination with that against diphtheria, pertussis, poliomyelitis, hepatitis B and heamophilus influenzae type B. The cycle is based on three doses, at months 3, 5, and 11. An additional booster is given at 5/6 years and around 15/16 years. A booster is needed every 10 years to preserve immunity.