Case of the Month

July 2017

Sandra D. Ngongang, Tom Boyles, Division of Infectious Diseases & HIV Medicine, Groote Schuur Hospital, Cape Town

A 49-year old man presented to Groote Schuur Hospital casualty with a 2-day history of difficulty opening and closing his mouth, and neck stiffness. Five days earlier he had stepped on a rusty nail. The patient reported a low-grade fever, pain of the left foot and rigid lower limbs. He had type 2diabetes mellitus, poorly controlled on metformin with diabetic retinopathy. His vaccination status was unknown.

On examination, he was conscious, had a temperature of 37.5°C, the pulse rate was 83 beats per minute, the blood pressure 120/70mmHg and the respiratory rate 20 breaths per minute. The patient had marked trismus, a stiff neck, and an infected wound on the left foot. He developed generalized spasms a few minutes after admission with airway obstruction, necessitating intubation and admission in ICU.

Question 1 - What is your differential diagnosis?

Answer to Question 1

The differential diagnosis includes tetanus, strychnine poisoning (history of ingestion of rat poison), drugs induced dystonia, malignant neuroleptic syndrome, stiff person syndrome and dental infection. In this case the history of trauma with a rusty nail and an infected wound, with no history of drug or poison ingestion strongly suggests the diagnosis of tetanus.

Question 2: Describe the etiology, epidemiology and clinical manifestations of tetanus
Answer to Question 2

Tetanus is caused by Clostridium tetani, a ubiquitous spore forming anaerobic Gram-positive bacillus. It is found in soil and the wider environment throughout the world. About one million cases of tetanus occur worldwide every year. In 2015, there were 56743 deaths due to tetanus worldwide, with about 20 000 occurring in the neonatal period. About 36% of non-neonatal tetanus deaths occurred in sub-Saharan Africa. In South Africa, 19 non-neonatal tetanus deaths were reported in 2015 with a mortality rate of 0.04 per 100 000 people.

Risk factors for tetanus include absence of appropriate vaccination, advanced age (>65years old), diabetes mellitus (diabetic foot) and intravenous drugs use.

Infection outside the neonatal period usually results from a penetrating injury. Newborns can become infected through contaminated instruments used to cut the umbilical cord or by inappropriate handling of the umbilical stump. Some cases have been reported after a circumcision campaign for HIV prevention in 14 countries of eastern and southern Africa.

Clinical manifestations are due to the release of tetanospasmine which is a neurotoxin produced by C.tetani. The neurotoxin enters the nervous system and inhibits presynaptic neurotransmission resulting in increased muscle tone, spasms and autonomic instability.

Tetanus has 4 main clinical presentations:
  1. Generalized tetanus is the most recognized form with risus sardonicus, trismus (lockjaw) and generalized spasms. The patient is conscious during spasms and experiences severe pain.
  2. Localized tetanus where only the muscles around the inoculation site are involved.
  3. Cephalic tetanus which is characterized by cranial nerve involvement.
  4. Neonatal tetanus which is defined by the WHO as an illness occurring in a child who has the normal ability to suck and cry in the first 2 days of life but who loses this ability between days 3 and 28 of life, becomes rigid and has spasms.
Question 3 -What is the prognosis of tetanus
Answer to Question 3

The mortality rate in mild and or moderate tetanus is about 6%. In severe forms, mortality may reach 60% even in expert ICU centers. Short incubation periods are associated with severe disease and mortality. Other factors associated with poor prognosis include: short period of onset (time from the first symptom to the first generalized spasm <48h), autonomic dysfunctions (systolic blood pressure> 140, heart rate >140, fever, sweating), some portals of entry (e.g. compound fractures). Patients requiring prolonged periods of intubation and ventilation have an increased risk of ventilator-associated pneumonia. Prolonged immobilization also exposes the patient to thrombo-embolic disease. About 25% of patients die in the first 48hours. The duration of disease is typically 4-6 weeks in survivors. Recurrent episodes can occur if the patient does not receive active immunization. Localized tetanus symptoms may progress to the chronic form, which can persist for a long period. Psychological disturbances have been reported in some patients after their recovery.

Question 4 -Discuss the management of tetanus
Answer to Question 4

Tetanus should be managed in ICU. The goals of treatment include

– Stopping toxin production: by wound debridement; removal of necrotic tissues leads to the eradication of spores. Antibiotics prevent the proliferation of C.tetani. Metronidazole (500mg IV/6-8hrs) or penicillin (2-4MU/4-6hrs) can be used. – Neutralization of the unbound toxin: Because Tetanus toxin is irreversibly bound to neurons, much emphasis is placed on neutralizing the unbound toxin before it enters the nervous system. Human tetanus immunoglobulin should be administered as soon as possible. The dose varies from 500 to 6000UI. CDC recommends 500UI and this appears to be as effective as larger doses with less discomfort. Half of the dose should be infiltrated into and around the wound. – Vaccination: Tetanus does not confer immunity; vaccination is therefore recommended and should be administered at a site different from the site of inoculation of tetanus immunoglobulins. – Control of muscle spasms: Benzodiazepines (diazepam, midazolam) are generally effective in controlling rigidity and spasms. High doses may be needed as tetanus patients develop high tolerance for the sedating effect of benzodiazepines. Neuromuscular blocking drugs like pipecuronium, vecuronium can be used when sedation alone is unsuccessful. – Management of dysautonomia: IV magnesium sulphate reduces the risk of cardiovascular instability and the requirement for additional drugs to control spasms. Labetalol can also be used as it reduces the excessive amount of catecholamines. Morphine sulphate reduces anxiety and cardiovascular instability. –General supportive management: endotracheal intubation is recommended initially to prevent airway obstruction followed by early tracheostomy as the endotracheal tube can be a stimulus for spasms and there is a high probability of prolonged mechanical ventilation. Prophylaxis for thrombo-embolic events is important.

Question 5 -How can you prevent tetanus?
Answer to Question 5

Tetanus is a completely preventable disease. The expanded program on immunization recommends 3 doses of DTP vaccine (Diphteria-Tetanus-Pertussis) in infants. Booster doses are recommended in childhood and adolescence and/or early adulthood for long-term immunity. Diphteria-tetanus vaccine is used for adolescents and adults. In 2015 in South Africa, the coverage for DTP3 vaccination was 69%. Neonatal tetanus elimination programs favor immunization of women of childbearing age but there is no established program for men. In a study conducted in Ethiopia, 75.6% (n=45) of affected individuals were male and none of them reported prior immunization.


After generalized spasms with airways obstruction in casualty, our patient was intubated and a tracheostomy performed the following day. The wound was debrided a few hours after his admission. The patient received 500UI of IM human tetanus immunoglobulins at the casualty and IV metronidazole 500mg every 8hours for 7 days. He did not receive tetanus vaccination. Spasms were managed with diazepam, midazolam and cisacurium. Magnesium sulphate and clonidine were given for cardiovascular instability. Four days after admission, the patient developed fever, labile blood pressure with hypo- and hypertension, tachycardia and tachypnea. He also had acute kidney injury and liver impairment. Empiric antibiotic therapy was started, with no clear source of infection found. All cultures were negative. The patient died one week after his admission. The post mortem examination revealed a pulmonary embolism despite prophylaxis for thromboembolic disease.


Emphasis should be made on vaccination of adolescent and adult males.
Early management of tetanus in ICU is critical.
Complications are common and mortality remains high.

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  2. Thwaites CL, Loan HT. Eradication of tetanus. British Medical Bulletin. 2015, 116:69–77.
  3. Kyu H, Mumford JE, Stanaway JD et al. Mortality from tetanus between 1990 and2015: findings from the global burden of disease study 2015. BMC Public Health. 2017; 17:179
  4. Dalal S, Samuelson J, Reed J. Tetanus disease and deaths in men reveal need for vaccination. Bull World Health Organ. 2016; 94:613–621
  5. Sahilu A, Kedir I, Ayele Y. A Four Years Record Review of Tetanus Cases Admitted to Jimma University Specialized Hospital (JUSH), Southwest Ethiopia: A Slip of Tetanus Case Management? Int J Anesth Pain Med. 2015; 2 (1):1-7.
  6. Rodrigo C, Fernando D, Rajapakse S. Pharmacological management of tetanus: an evidence-based review. Critical Care 2014, 18:217.

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