Tetanus

Tetanus is a severe neurological disorder with a generally fatal outcome, caused by exposure to the spores of the Clostridium tetani bacteria.

These toxins damage the nervous system, which can lead to paralysis and tonic contractures (spasms) of skeletal muscles, and can often fatal. The disease is common all over the world and is caused by injury or direct contact of broken skin with contaminated objects.

Fortunately, with the introduction of a vaccine, cases have decreased dramatically, but the disease does still occur, affecting all age groups, with a higher prevalence among the over-60s.

The microorganism lives in the intestines of herbivorous animals (particularly horses and cattle), and are excreted in the faeces in the form of spores. This can subsequently contaminate the territory where they can remain for years.

CAUSES

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., an oxygen-free) environment, and has various flagella on its surface that make it mobile.

The natural reservoir of the bacteria is the gastrointestinal tract of herbivores, which have become the habitual hosts. In order to cope with adverse environmental conditions, the bacteria transforms into spores that are successively eliminated in the faeces, which contaminate the soil. The spores have a "drumstick"-like appearance and are resistant to dehydration, boiling and some disinfectants, such as ethanol. Under the right conditions, the spores geminate releasing the vegetative form of the bacteria that produces two types of toxins:

• tetanolysin, which has no pathological effect on humans and is of little clinical value;
• tetanospasmin, also known as tetanus toxin (TeNT). TeNT is a very potent neurotoxin and is responsible for the clinical symptoms, as it affects the nervous system: first the peripheral nervous system, then the central nervous system, which causes the classic symptoms of the disease.

TRANSMISSION

Tetanus cannot be transmitted from person to person. There are a large number of animals in nature that act as reservoirs of the pathogen. This is why vaccination coverage is not directed so much at stopping the spread of the infectious agent but more at protecting as many people as possible.

Contagion is direct: infection mostly follows the penetration of the spores into skin and mucosal wounds (e.g. burns, sores, animal bites, stings, injections, etc.,). Cases of surgical tetanus are now very rare, however, secondary infections due to obstetrical manoeuvrers and drug use are more frequent.

Contamination of wounds or mucous lesions with tetanus spores does not necessarily lead to disease: in fact, in order to germinate, the spores require a much lower oxygen tension than is normally found in tissue. Tetanus spores can survive in the body for months or years and can give rise to an infection only when local conditions are changed, even as a result of minor trauma.

Tissue necrosis, foreign bodies, and intercurrent localised infections, often in the wound site, promote spore germination and the production of the exotoxin responsible for the disease symptoms.

GEOGRAPHICAL DISTRIBUTION

Tetanus is a sporadic disease that is particularly common in rural areas, whereas, in industrialised countries it is considered a rare disease due to vaccination coverage. The mortality rate can range from 10% to 70%, depending on the health care treatment provided, the age of the individual, and the patient's overall health. In the absence of treatment, mortality is approximately 100%.

According to data provided by the European Center for Disease Control and Prevention, there were 117 notified cases of tetanus in Europe in 2015, in 26 countries, an increase of 20 cases compared to the previous year.

Italy reported the highest incidence in Europe, with 48 cases, equivalent to 41% of all cases. This is followed by France and Poland, with 12 cases. The most affected age group are the elderly, with a rate of 0.11 cases per 100,000 population, accounting for 72% of cases, with a higher prevalence in females.

Most cases were reported during the warmer months, from May to October, with a peak in July. This increase is generally associated with people engaging in more outdoor activities.

However, Clostridium tetani is widespread in the environment worldwide and cannot be eradicated. To reduce the number of tetanus cases, prevention efforts focus on vaccination and post-exposure wound care.

SYMPTOMS

The incubation period of the disease is 3 to 21 days (average of 7 days). Following lysis at the wound site, the bacteria releases tetanospasmin. The bacteria travels through the bloodstream, reaching the nerves, blocking the release of inhibitory motor neurons (glycinergic and GABAergic) by the synapses, causing continuous stimulation of skeletal muscles which leads to constant and painful muscle spasms.

There are 4 different forms of tetanus:

• Generalised tetanus: approximately 80% of cases present with generalised tetanus. The first symptom is usually facial trismus (lockjaw), due to the contraction of the jaw and facial muscles, which gives the face the typical “Risus sardonicus” (or rictus grin). After this stage, symptoms such as; neck stiffness, difficulty swallowing, and abdominal muscle stiffness occur. In some cases, there may also be symptoms of fever, tachycardia, or arrhythmias. That leaves opisthotonos (i.e., a state of severe hyperextension and abnormal posturing), in which an individual's head, neck, and spine form a completely "bowed" or "bridged" position. This is one of the most noticeable symptoms of tetanus, and is caused by the contraction of skeletal muscles, which in turn results in hyperextension in the trunk, lower limbs, and flexion of the upper limbs.
• Neonatal tetanus: This form occurs in infants of generally immunised mothers; the infection is caused when the umbilical cord is cut using a non-sterile instruments. On average, symptom onset usually occurs in the first two weeks after birth, with stiffness, spasms, and reduced ability to feed. Babies that survive may suffer from bilateral deafness.
• Local tetanus: this is the least severe form, and can be observed in partially immunised individuals, in which symptoms are localised exclusively to the muscles near the wound.
• Cephalic tetanus: is a rare form of localised tetanus, which occurs as a result of facial injury affecting the cranial nerves.

DIAGNOSIS

The diagnosis of tetanus di 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 also point towards diagnosis.

In some cases tetanus can be confused with viral or bacterial meningoencephalitis, but the diagnosis can be considered positive for tetanus in combination with three factors: an intact sensor, unaltered cerebrospinal fluid, and muscle spasms.

TREATMENT

Once tetanus has been diagnosed, the patient should be admitted to an intensive care unit to ensure the necessary measures are taken to maintain adequate ventilation, in case of respiratory muscle involvement. A tracheotomy may be required in very severe cases.

In addition, neutralisation of circulating toxins is expected with the administration of human anti-tetanus immunoglobulins, the so-called active prophylaxis. Thorough cleansing of the wound with oxidising disinfectants and eventual removal of necrotic tissue is essential.

To prevent further muscle spasms and the production of new tetanospasmins, Clostridium tetani-sensitive antibiotics should also be administered. In this case, Penicillin G is the drug of choice. To control spasms, treatment relies on the administration of muscle relaxant drugs, such as intravenous benzodiazepines or barbiturates.

Once tetanus has been diagnosed, the patient should be admitted to an intensive care unit to ensure the necessary measures are taken to maintain adequate ventilation, in case of respiratory muscle involvement. A tracheotomy may be required in very severe cases.

In addition, neutralisation of circulating toxins (non-fixed) is expected with the administration of human anti-tetanus immunoglobulins, the so-called active prophylaxis. Thorough cleansing of the wound with oxidising disinfectants and eventual removal of necrotic tissue is essential.

To prevent further muscle spasms and the production of new tetanospasmins, Clostridium tetani-sensitive antibiotics should also be administered. In this case, Penicillin G is the drug of choice. To control spasms, treatment relies on the administration of muscle relaxant drugs, such as intravenous benzodiazepines or barbiturates.

PREVENTION

Prevention is key in avoiding tetanus complications. Thanks to vaccination, tetanus disease is now considered a rare disease in industrialised countries.

Tetanus cases, especially in children, are still high in Africa due to lack of vaccination. WHO (the World Health Organization) continues to reiterate the importance of having high vaccination coverage throughout the population, as it is the only way to prevent the disease.

The vaccine contains purified tetanus anatoxin, which has been inactivated but still able to stimulate the immune system to produce protective antibodies against possible infection. Although very effective, tetanus vaccination does not provide life-long immunity, so a vaccine booster is recommended every 10 years.

In Italy, the basic course of tetanus anti-tetanus is administered with the combined diphtheria, pertussis, poliomyelitis, hepatitis B and haemophilus influenzae type B vaccine in the first year of life.

The cycle consists of three doses, administered at 3, 5 and 11 months of age. An additional booster is given at age 5-6 and around 15-16 years of age. A booster is required every 10 years to maintain immunity.

 

Bibliography & Sitography

Hmwe H. Kyu , John Everett Mumford, Jeffrey D. Stanaway, Ryan M. Barber, Jamie R. Hancock, Theo Vos, Christopher J. L. Murray and Mohsen Naghavi. Mortality from tetanus between 1990 and 2015: findings from the global burden of disease study 2015. BMC Public Health, 2017.

Moroni M., Spinello A., Vullo V. Manuale di Malattie Infettive. Edra LSWR, Masson, 2018.

Bartolozzi G. Vaccini e Vaccinazioni, Seconda Edizione. Masson 2005.

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De Grazia S., Ferrero D., Giammanco G. Microbiologia e Microbiologia Clinica per infermieri, 2012.

Enciclopedia Treccani: www.treccani.it

Epicentro, il portale dell’epidemiologia per la sanità pubblica: www.epicentro.iss.it

Istituto Superiore di Sanità: www.iss.it

Ministero della Salute: www.salute.gov.it

VaccinarSi, informazioni sulle vaccinazioni. Portale di informazione medica scientifica sulle vaccinazioni a cura della SITI (Società Italiana di Igiene): www.vaccinarsi.org

CDC Centers for Disease Center: https://www.cdc.gov