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Tetanus is an infection characterized by a state of generalized hypertonia that manifests in the form of painful muscle spasms of the jaw and neck caused by the toxin-producing anaerobe *Clostridium tetani* found mainly in the soil. We will cover pathogenesis, risk factors, clinical presentation, management and complications associated with tetanus.

Clinical presen­tation patterns

Genera­lized tetanus
Neonatal tetanus
Localized tetanus
Cerebral tetanus
Since C. tetani spores cannot be eliminated from the enviro­nment, immuni­zation and proper treatment of wounds and traumatic injuries are crucial for tetanus preven­tion.

Etiology

Tetanus is due to infection from the bacterium Clost­ridium tetani a gram-p­osi­tive, spore-­for­ming, obligate anaerobic bacillus. This bacteria and its spores are frequently found in hot and wet climates where the soil is rich with organic matter.
C. tetani may enter the human body through wound puncture, lacera­tion, skin breaks, or inocul­ation with an infected syringe or insect bites.
High-risk popula­tions include those that have not been vaccin­ated, intrav­enous drug users, and those who are immuno­sup­pre­ssed. Other causes of infection are through surgical proced­ures, intram­uscular inject­ions, compound fractures, dental infect­ions, and dog bites.
Tetanus can also develop as a conseq­uence of chronic conditions such as abscesses and gangrene. Burn patients and patients undergoing surgery can also acquire the infection.

pathop­hys­iology

C. tetani secretes the toxins, tetano­spa­smin, and tetano­lysin. Tetano­spasmin enters the presyn­aptic terminals in the neurom­uscular endplate of motor neurons and inhibits neurot­ran­smitter release of glycine and GABA.
The incubation period can last from one to 60 days but is, on average, around 7 to 10 days.

Clinical features

Genera­lized Tetanus
typically have symptoms of autonomic over-a­cti­vity. Tonic and periodic spastic muscular contra­ctions are respon­sible for most of the classic clinical findings of tetanus such as: ●Stiff neck ●Opist­hotonus ●Risus sardonicus (sardonic smile) ●A board-like rigid abdomen ●Periods of apnea and/or upper airway obstru­ction due to vise-like contra­ction of the thoracic muscles and/or glottal or pharyngeal muscle contra­ction, respec­tively ●Dysphagia
Duration of illness
Tetanus toxin-­induced effects are long lasting because recovery is believed to require the growth of new axonal nerve terminals. The usual duration of clinical tetanus is four to six weeks.
The severity is related to the incubation period of the illness and the interval from the onset of symptoms to the appearance of spasms, the longer the interval, the milder the clinical features of tetanus. More severe illness is seen in those with deep penetr­ating wounds

Risk factors for neonatal tetanus

1. Unvacc­inated mother
2. Home delivery
3. Septic cutting of the umbilical cord
4. Neonatal tetanus in a previous child
5. Infectious substances applied to the umbilical stump, such as animal dung, mud
Tetanus usually occurs in persons who are not immunized, partially immunized or fully immunized but lacking adequate booster doses.

Treatment and Management

Treatment modality
Advantages and Disadv­antage
Summary of findings and level of confidence
Recomm­end­ation
Halting toxin production
Wound management
Eliminate conditions ideal for spore germin­ation
 
All patients with tetanus should undergo wound debrid­ement to eradicate spores and necrotic tissue
Antimi­crobial therapy
Metron­idazole use has a theore­tical advantage over penicillin use as the latter can potent­ially facilitate tetano­spasmin activity
The first study to compare penicillin and metron­idazole found a greater reduction in mortality in the metron­idazole group. However, in three subsequent studies, there was no difference in mortality in patients treated with penicillin and those treated with metron­ida­zole. In one of the former studies, patients receiving metron­idazole required fewer muscle relaxants and sedatives. Level of confidence B
Metron­idazole (500 mg intrav­enously [IV] every six to eight hours) is the preferred treatment for tetanus, but penicillin G (2 to 4 million units IV every four to six hours) is a safe and effective altern­ative. Suggested treatment duration of 7 to 10 days
Neutra­liz­ation of unbound toxin
Admini­str­ation of immuno­glo­bulins
Admini­str­ation of immuno­glo­bulins is benefi­cial. The best route of admini­str­ation (intra­mus­cular alone versus intrat­hecal plus intram­usc­ular) is debatable
Evidence from two meta-a­nalyses are confli­cting
Human tetanus immune globulin (HTIG) is the prepar­ation of choice. recommend a single dose of 500 units intram­usc­ularly. The previously recomm­ended dose range was 3000 to 6000 units. Given as soon as the diagnosis of tetanus is consid­ered, with part of the dose infilt­rated around the wound
Control of muscle spasms
Benzod­iaz­epines and other sedatives
Advant­ages: combined sedative, antico­nvu­lsant and muscle relaxant effects Disadv­ant­ages: prolonged duration of action with long-a­cting drugs.
Used as standard therapy
Usual starting dose of diazepam for an adult is 10 to 30 mg IV and repeated as needed every 1 to 4 hours.
Neurom­uscular blocking agents
Used when sedation alone is inadeq­uate. Pancur­onium, a long-a­cting agent, has been tradit­ionally used, but it may worsen autonomic instab­ility because it is an inhibitor of catech­olamine reuptake
Evidence is limited to a few case series (level of evidence C)
Vecuronium or other cardio­vas­cular inert neurom­uscular blockers are preferred. Intrat­hecal baclofen given as an initial bolus in a dose ranging from 40 to 200 mcg followed by a continuous infusion of 20 mcg/hour was found to control spasms and rigidity
Autonomic dysfun­ction
Magnesium sulphate
Advant­ages: readily available in resour­ce-­limited settings, has antico­nvu­lsant, muscle relaxant proper­ties, Disadv­ant­ages: needs close monito­ring, Risk of hypoca­lca­emia, Less effective in severe disease
Meta-a­nalysis shows no mortality benefit (level of evidence A)
Magnesium sulfate (loading dose 40 mg/kg over 30 minutes, followed by continuous infusion of either 2 g per hour for patients over 45 kg or 1.5 g per hour for patients ≤45 kg). During magnesium infusion, the patellar reflex needs to be monitored
Beta blockade
Labetalol has frequently been admini­stered because of its dual alpha- and betabl­ocking proper­ties. Beta blockade alone (propr­ano­lol­)should be avoided because of reports of sudden death
Evidence limited to case reports and few case series (level of evidence C)
Use may be reasonable on a case by case basis Labetalol (0.25 to 1 mg/min) Morphine sulfate (0.5 to 1 mg/kg per hour by continuous intrav­enous infusion)
Level of eviden­ce:A, data derived from multiple randomized clinical trials or meta-a­nal­ysis; B, data derived from a single randomized trial or non-ra­ndo­mized trials; C, only consensus opinion of experts, case studies or standard of care.
GABA antagonist effect of penici­llins and third-­gen­eration cephal­osp­orins, may lead to central nervous system (CNS) excita­bility thus not recomm­ended during treatment.

Supportive management

Prophy­lactic treatment with sucralfate or protein pump inhibitors may be used to prevent gastro­eso­phageal hemorrhage from stress ulceration
Prophy­laxis of thromb­oem­bolism with heparin, low molecular weight heparin, or other antico­agu­lants should be admini­stered early
Physical therapy should be started as soon as spasms have ceased, since tetanus patients often are left with disability from prolonged muscle wasting and contra­ctures
All patients require full tetanus toxoid immuni­zation at recovery; having the infection does not give future immunity
HTIG should be admini­stered at different sites than tetanus toxoid.
Intrav­enous immune globulin may be admini­stered as an altern­ative if HTIG is not available

Prognosis

An establ­ished scale can be used to predict the prognosis of tetanus. One point is given for each of the following:
- Incubation - shorter than 7 days
- Onset - less than 48 hours
- Causes of tetanus - burns, surgical wounds, septic abortion, umbilical stump, compound fractures, or intram­uscular injection
- Addiction to opiates
- Genera­lized tetanus
- Temper­ature - more than 104 F (40 C)
- Tachyc­ardia - more than 120/min (150/min in neonates)

The total score indicates disease severity:

0-1 - mortality of less than 10%
2-3 - mortality of 10-20%
4 - mortality of 20-40%
5-6 - mortality of more than 50%.
Some patients develop hypotonia and autonomic dysfun­ction that lasts for months or years. Even those who survive, need tetanus toxoid as the infection does not confer immunity.

Differ­ential diagnosis

1. Drug-i­nduced dystonias such as those due to phenot­hia­zines
2. Trismus due to dental infection
3. Strychnine poisoning due to ingestion of rat poison
4. Malignant neurol­eptic syndrome
5. Stiff-­person syndrome
The only condition that mimics tetanus the most is strychnine poisoning. One of the typical symptoms of tetanus is trismus which may be present in many other condit­ions.

Compli­cations

Vocal cord paralysis leading to respir­atory distress
Hysteria
Neoplasms
Malignant hypert­hermia
Autonomic dysfun­ction- leading to hypert­ension
Asphyxia
Long bone fractures
Paralytic ileus
Joint disloc­ation
Aspiration pneumonia
Pressure sores
Stress ulcers
Coma
Nerve palsy
Urine retention
Seizures
Sympat­hetic overac­tivity is the most signif­icant cause of tetanu­s-a­sso­ciated mortality in critical patients

References

Bae C, Bourget D. Tetanus. [Updated 2020 Feb 28]. In: StatPearls [Inter­net]. Treasure Island (FL): StatPearls Publis­hing; 2020 Jan-. Available from: https:­//w­ww.n­cb­i.n­lm.n­ih.go­v/b­ook­s/N­BK4­59217/
Centers for Disease Control and Preven­tion. Tetanus. https:­//w­ww.c­dc.go­v/v­acc­ine­s/p­ubs­/su­rv-­man­ual­/ch­pt1­6-t­eta­nus.html (Accessed on February 24, 2020).
Kyu HH, Mumford JE, Stanaway JD, et al. Mortality from tetanus between 1990 and 2015: findings from the global burden of disease study 2015. BMC Public Health 2017; 17:179.
Rodrigo C, Fernando D, Rajapakse S. Pharma­col­ogical management of tetanus: an eviden­ce-­based review. Crit Care 2014; 18:217.
Yen LM, Dao LM, Day NPJ. Management of tetanus: a comparison of penicillin and metron­ida­zole. Symposium of antimi­crobial resistance in southern Viet Nam, 1997.
Thwaites CL, Yen LM, Loan HT, et al. Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial. Lancet 2006; 368:1436.
Buchanan N, Smit L, Cane RD, De Andrade M. Sympat­hetic overac­tivity in tetanus: fatality associated with propra­nolol. Br Med J 1978; 2:254.

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