Generalized tetanus: a pediatric case report and literature review

ABSTRACT

Pediatric tetanus is a rare and forgotten disease in countries with high childhood tetanus toxoid vaccination rates. Therefore, the clinical manifestations, treatment and management of this potentially life-threatening disease are not well known. With a literature review and discussion of tetanus management in pediatric patients, we describe a clinical course of a rare and fatal but vaccine-preventable disease, the generalized tetanus, in an adolescent who was successfully treated.

Tetanus; Children; Vaccine

INTRODUCTION

Tetanus is one of the diseases prevented by vaccines and is not transmitted from person to person¹. As a result of higher childhood tetanus toxoid vaccination rates, tetanus incidence has significantly decreased in recent years. There were 264 tetanus patients and 19 deaths reported in the US between 2009–2017, according to the Centers for Disease Control and Prevention². In the European Union, in 2018, 92 tetanus cases were documented and 48 were confirmed³. Nine cases of tetanus were reported in Turkey, in 2020⁴. But in countries where vaccination is insufficient, deaths from tetanus still occur. Tetanus-related deaths were estimated at 56,000 deaths worldwide each year⁵. The disease develops with the penetration of the anaerobe Clostridium tetani, common in the soil, into the traumatically injured tissue, producing a neurotoxin¹. The clinical forms of tetanus are generalized, localized, cephalic, and neonatal⁶. Generalized tetanus is the most frequent and fatal clinical form of tetanus¹. Herein, we describe an unimmunized patient, a 16-year-old boy, diagnosed with generalized tetanus who was successfully treated.

CASE REPORT

A previously healthy 16-year-old boy injured his right hand while carrying building construction materials made of iron. Ten days after the injury, he arrived at the emergency room with generalized spasms. Upon arrival, he developed a sore throat that progressed to trismus, rigidity of the jaw muscles, and sustained generalized muscle spasms. As the patient was unimmunized, tetanus infection was suspected based on clinical signs and symptoms. Tetanus toxoid vaccine was administered intramuscularly. Since tetanus immune globulin (TIG) was not available in the city, intramuscular equine antitoxin was administered after an intradermal test had been performed. Sufficient doses of equine antitoxin could not be obtained, so human TIG was procured from other hospitals. The patient was admitted to the pediatric intensive care unit (PICU) of our hospital, and informed consent was given by the patient’s parents.

Upon admission to our PICU, his vital signs were normal, and oxygen saturation was 98% on room air. He had tonic contraction and muscular spasms, dysphagia, trismus, muscular rigidity, and tachycardia. Laboratory studies showed the values for white blood cell count (12,070/μL), hemoglobin (11.5 g/dL), urea (31 mg/dL), creatinine (0.86 mg/dL), c-reactive protein (6.6 mg/L), sodium (138 mEq/L), potassium (4.3 mEq/L), creatine kinase (CK) (1,363 IU/L), calcium (9.7 mg/dL), phosphorus (4 mg/dL), magnesium (1.92 mg/dL), alanine aminotransferase (60.6 U/L) and aspartate aminotransferase (88.2 U/L).

He was given intravenous penicillin G (3 million units intravenously (IV) every six h), and metronidazole (500 mg IV every eight h) when he was admitted to our PICU. Human tetanus immune globulin (HTIG) was administered to the patient at the appropriate dose. He was monitored in a room in which reduced light and silence were provided in order to avoid triggering his symptoms. Because his muscle rigidity and spasms continued, diazepam (10 mg/dose in six doses), and baclofen (10 mg three times daily) were initiated. To suppress autonomic dysfunction and control spasms, a magnesium sulfate infusion was started. His clinical signs and laboratory results improved during follow-up. His muscle rigidity and spasms decreased and oral intake was increased. Serum levels of CK were normal. When his clinical signs improved, he was transferred from the PICU to the pediatric infectious disease ward.

After the patient’s contractions decreased and his tachycardia regressed in the follow-up, magnesium sulfate infusion and diazepam were gradually discontinued. The dose of baclofen was reduced based on the recommendations of a pediatric neurologist. Penicillin and metronidazole therapy was completed in 14 days. He was discharged with a recommendation to be admitted to hospital for a follow-up.

The patient came for a reexamination after discharge, he had no health problems during the follow-up, and the physical examination was normal. A program for tetanus toxoid vaccination was arranged for the completion of a total of three doses.

LITERATURE REVIEW

To find the most comprehensive and updated recommendations for the prevention and treatment of tetanus, a targeted literature study was carried out. We looked for English-language articles published in the last ten years using the keywords “Tetanus” and “Pediatrics” in the databases of PubMed and Medline. Original studies and case reports were included. 22 articles comprising 146 pediatric cases are listed in Table 1^-. The SPSS software (version 20, IBM, Armonk, New York, USA) was utilized for the statistical analysis of the studies included in the review. Descriptive statistics were used for the analysis of the data. According to the information provided, except for 12 patients diagnosed with otogenic tetanus, all 134 patients were unvaccinated or partially immunized. A total of 56 of the patients were diagnosed with neonatal tetanus. The neonate patients had history of unhealthy umbilical stump, lower abdominal septic skin infection, and post-circumcision infection. The other pediatric patients had history of trauma, lacerations, punctured injuries, and otogenic tetanus. All patients had typical symptoms of tetanus, such as lock-jaw, facial, abdominal muscle rigidity, painful neck stiffness, trismus, labile heart rate, tachypnea, hyperpyrexia, generalized spasms, risus sardonicus and opisthotonus. According to the data presented, among 146 pediatric patients with tetanus reported in the case series and studies in the literature, 41 (28%) of them died^-. Our research has limitations such as the small sample size because it only covers the articles published in PubMed.

Table 1
Neonatal and pediatric cases diagnosed with tetanus in the literature.

Articles	Number of patients	Age	Inoculation site	Presenting symptoms	Vaccination history	Treatment	Outcome
Bagcı6	1 patient	16 months	Mucosal erosion in right cheek	Rigidity of jaw, face and neck, salivation	Unvaccinated	HTIG, penicillin, metronidazole, midazolam, tetanus toxoid vaccine	Survived
Ahmed et al.7	5 patients	3 years	Foot laceration	Fever, abdominal distention, and back pain	Unvaccinated	Exploratory laparotomy, HTIG tetanus toxoid vaccine metronidazole.	Survived
		7 years	Hand laceration	Trismus, jaw pain, and neck, back, and leg stiffness	Unvaccinated	HTIG, tetanus toxoid vaccine, penicillin	Survived
		11 years	Knee laceration	Trismus, pain, and discharge from wound	Unvaccinated	HTIG, tetanus toxoid vaccine, metronidazole cefazolin	Survived
		9 years	Foot splinter	Trismus and dysphagia	Unvaccinated	HTIG tetanus toxoid vaccine. metronidazole	Survived
		7 years	Foot laceration	Trismus, sore throat, and body stiffness	Unvaccinated	Magnesium sulfate, HTIG tetanus toxoid vaccine, metronidazole	Survived
Bagcı8	1 patient	9 years	Trunk injury	Chest, abdomen, back muscle stiffness	Unvaccinated	HTIG, tetanus toxoid vaccine. metronidazole, baclofen, midazolam, penicillin G	Survived
Cejudo-García de Alba et al.9	1 patient	6 years	Right arm splinter	Abdominal muscle stiffness, trismus difficulty walking	Incomplete immunization	Metronidazole, penicillin, wound debrided, HTIG tetanus toxoid vaccine	Survived
Asín et al.10	1 patient	7-day-old newborn	Umbilical cord	Muscular spasms, Trismus rigidity	Unvaccinated	HTIG, metronidazole diazepam, ampicillin gentamicin	Survived
Sesama et al.11	1 patient	7 years	Left ear discharge	Reflex spasm of masseters, left eye ptosis	Unvaccinated	Diazepam, ceftriaxone, metronidazole, supportive management, HTIG, diazepam	Survived
Akane et al.12	1 patient	13 years	Fracture of right distal radius	Trismus, muscle rigidity, excessive diaphoresis, risus sardonicus	Partially immunized	HTIG, tetanus toxoid, metronidazole, diazepam, penicillin G	Survived
Douvoyiannis et al.13	1 patient	9 years	Nail	Painful neck stiffness, lockjaw	Unvaccinated	HTIG, tetanus toxoid, midazolam	Survived
Homola et al.14	1 patient	2 and a half years	Deep erosion in the nasal mucosa, nasal toy	Difficulty swallowing trismus	Unvaccinated	Clindamycin, metronidazole, HTIG, tetanus toxoid	Survived
Condé et al.15	39 patients	13 days (median age)	Post-circumcision: 2 Umbilical cord: 20 Wound: 12 Limb fracture: 1	Fever, generalized muscle spasm, trismus	Unvaccinated: 17 Received 1 dose: 19 Received 2 doses: 3	NR	Died (n=20) Survived (n=19)
Maharaj et al.16	1 patient	1 week	Lower abdominal skin infection	NR	Unvaccinated	Sedatives, muscle relaxants, antibiotics, intrathecal / intramuscular immunoglobulin, wound treatment	Survived
Nakubulwa et al.17	1 patient	9 days	None	Labile heart rate, tachypnea, hyperpyrexia, abdominal muscle rigidity, generalized spasms	Maternal partially immunized	Cefotaxime, gentamicin, metronidazole, diazepam, magnesium sulfate, equine tetanus antitoxin	Survived
Okidi et al.18	1 patient	5-day-old neonate	NR	Fever, refusal to breastfeed, excessive crying, difficulty in breathing	Unvaccinated	Diazepam, metronidazole, phenobarbital	Died
Tadele et al.19	24 patients	8 years (median age)	Trauma Tungiasis	Generalized tetanus symptoms	Maternal partially immunized	Diazepam, chlorpromazine, debridement, penicillin G, metronidazole, tetanus toxoid	Survived (n=17) Died (n=7)
Ogunkeyede et al.20	23 patients	3.4 years	Otogenic tetanus	Ear discharge, trismus and spasms	Complete tetanus immunization (12), unvaccinated (6), partial tetanus immunized (5)	Topical antibiotic ear dressing, tetanus toxoid, HTIG, antibiotic therapy, sedatives	Died (n=3) Survived (n=20)
Barlas et al.21	2 patients	12 years	Puncture on right foot	Lock-jaw, facial, abdominal muscle rigidity	Unvaccinated	HTIG, tetanus toxoid, metronidazole, diazepam, vancomycin, ceftazidime, rocuronium, baclofen, fentanyl	Survived
		6 years	Puncture on left foot	Back pain, difficulty in opening the mouth and swallowing	Unvaccinated	ampicillin-sulbactam, metronidazole, HTIG, tetanus toxoid, fentanyl, baclofen, midazolam	Survived
Aqeel et al.22	30 patients	Neonate	Unhealthy umbilical stump	Muscle spasm, refusal to eat, abnormal posture	Maternal unvaccinated: 27 Maternal partially immunized: 3	HTIG, penicillin G, gentamicin, muscle relaxant pavulon	Died (n=6) Survived (n=24)
Irie et al.23	1 patient	2 years	Severe thermal burn	Fever, refusal to eat, trismus, generalized contractures	Unvaccinated	HTIG, amoxicillin clavulanic acid, benzodiazepine	Died
Neal et al.24	1 patient	10 years	Foot puncture	Muscle spasms, trismus, fever, risus sardonicus, opisthotonus	Unvaccinated	Diazepam, metronidazole, HTIG, tetanus toxoid, surgical debridement	Survived
Şık et al.25	1 patient	12 years	Right foot laceration	Spasms of the right foot, back, tachycardia hypertension, rigidity	Unvaccinated	Diazepam, morphine, vecuronium, magnesium sulfate, crystalline penicillin, HTIG, tetanus toxoid, intrathecal baclofen	Survived
Felter et al.26	1 patient	14 years	Right foot laceration	Speaking with difficulty, bilateral ptosis, pain, swelling, sternal chest pain with palpitations	Unvaccinated	Diazepam, lorazepam, HTIG, tetanus toxoid, metronidazole ciprofloxacin	Survived
Gowda et al.27	8 patients	Range: 2–11 years	Right foot laceration, left finger	Lock jaw, difficulty in walking	Unvaccinated: 6 Vaccinated: 2	Tetanus toxoid, crystalline penicillin, wound management care, HTIG	Survived (n= 5) Died (n= 3)

• NR = not reported; HTIG = human tetanus immunoglobulin

DISCUSSION

Generalized tetanus has become one of the forgotten infectious diseases thanks to universal vaccination with the tetanus toxoid⁵. Our case report and literature review is a reminder of this neglected disease and underline the significance of early clinical suspicion for tetanus, which has a fatal clinical picture among unvaccinated children. This case report may raise awareness of this vaccine-preventable illness, and it should be noted that early diagnosis can be vitally important.

Symptoms of tetanus can appear days to weeks after a wound⁷. This disease is typically accompanied by symptoms such as dysphagia, muscular spasms, and trismus of the head and neck⁸. Generalized tetanus may evolve to broad muscle stiffness and opisthotonus²³. Muscle spasms can be very painful and are frequently triggered by stimulation²⁶. Tachycardia, bradycardia, blood pressure changes and arrhythmias can all be symptoms of autonomic instability¹⁷. The spasms last for three to four weeks. A full recovery can take months⁵,²⁶.

Generalized tetanus should be considered in patients with a history of injury, painful muscle spasms and tonic contractions, trismus, opisthotonus, dysphagia, apnea due to upper airway obstruction, stiff neck, and symptoms of autonomic hyperactivity, who live in areas with low vaccination rates¹,⁵. It’s important to rule out other causes of spasms, such as hypocalcemia and drug or toxin intake⁵. Tetanus is more likely to spread to those with diabetes, dirt-contaminated wounds, older people, and injectable drug users¹².

Similarly to our patient, people who have never had an immunization are obviously at a greater risk for infection, but as anti-tetanus toxin antibody concentration declines with age, older adults are also at a higher risk of infection¹². Tetanus in children is uncommon in developed countries. An anti-tetanus toxin antibody concentration of >0.01 IU/mL is typically regarded as the minimum protective threshold in modified enzyme-linked immunosorbent tests¹²,²⁸. The degree of protective anti-tetanus toxin antibodies remains debatable¹². Because tetanus immunity cannot be obtained spontaneously, it’s crucial to receive all recommended vaccinations in pediatrics and maintain antibody levels throughout the course of life by receiving booster shots every 10 years²⁸. Our patient’s wounds were contaminated with dirt and we were unable to detect his antitoxin antibody concentration.

Conversely, some other reports in the literature claim that people with minor or subtle wounds may potentially contract a tetanus infection¹². According to our literature review in Table 1, one pediatric patient who developed tetanus did not report an injury or wound¹⁷.

Tetanus is treated by neutralizing residual tetanus toxoid antibodies, eliminating pathogens in the injured area, supportive care for respiratory failure, and controlling muscular spasm symptoms²⁹. If left untreated, the case fatality rate is very high, almost 100%. Case mortality rates can decrease between 10% to 20% with appropriate therapy⁵. Pediatric intensive care is the cornerstone of management for generalized tetanus. To prevent triggering spasms, patients should be kept in quiet rooms with reduced light⁸.

Benzodiazepines are preferred as therapies because they help to control rigidity and spasms, and provide a sedative effect⁵. An additional antispasmodic medication that reduces autonomic hyperactivity, and is also effective on spasms, is intravenous magnesium sulfate²⁹. Other measures of tetanus management are active immunization and intramuscular injection of human TIG immediately after the diagnosis to prevent the worsening of the disease⁵. Human TIG neutralizes the unbound toxin⁵,¹². Intramuscular or intravenous equine antitoxin is a suitable alternative if HTIG is not provided¹⁷. If equine antitoxin is used, skin testing should be done before giving the full dose to exclude hypersensitivity effects²⁹. In a randomized controlled trial of 215 patients aged >16 years old, no advantage to using intramuscular human TIG (3,000 international units) in tetanus therapy versus intramuscular equine antitoxin (21,000 international units) was detected³⁰. Intravenous immune globulin can be given if HTIG or equine antitoxin are not available²⁸. To eliminate tetanus bacilli, antibiotics such as penicillin and metronidazole are recommended²⁹. While C. tetani is often susceptible to penicillin, it has a weak infiltration into abscesses and can be neutralized by other microbial pathogens. Metronidazole was demonstrated to have excellent results in a controlled trial²⁶. In several cases, surgical debridement is needed to eliminate spores and necrotic tissue that can provide a suitable environment for the further growth of spores⁹.

Long-term functional results of the recovered patients from tetanus may be compromised and functional disabilities have been reported in the literature³¹. Tetanus-infected neonates may have neurological impairment, cognitive disability and cerebral palsy in long period follow-up³².

It should be kept in mind that completing the full tetanus vaccination series during childhood, and maintaining immunity with tetanus booster shots during adulthood is essential and life-saving²⁸. As seen in our review, this fatal disease (neonatal tetanus) still exists in areas where vaccination is not sufficient²². It is essential to vaccinate previously unvaccinated mothers in the prenatal period to prevent neonatal tetanus³³. But even though the vaccine can be given at any stage during pregnancy, it is preferable for pregnant women to have the tetanus toxoid vaccination between 27 and 36 weeks of pregnancy²⁸. Pregnant women who are partially immunized or unimmunized should take 3 vaccines containing tetanus toxoid within the indicated period²⁸,³³. If a previously unvaccinated pregnant woman takes at least two doses of the tetanus toxoid-containing vaccines at the recommended intervals, the probability of neonatal tetanus is minimal²⁸.

CONCLUSION

In conclusion, we described tetanus disease as observed in an unvaccinated adolescent. To enable early diagnosis of generalized tetanus because of its high fatality, it is crucial to obtain a detailed patient medical history and a comprehensive physical examination. Treatment of punctured, crushed, and traumatic injuries should be enhanced carefully to prevent tetanus⁵. Based on the fact that tetanus bacteria are always in the soil, this fatal disease cannot be eradicated but it can be reduced with increased tetanus vaccination worldwide¹,⁵. Complete immunization is crucial because tetanus infection does not provide lifetime immunity to individuals who have had the disease⁵.

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• FUNDING: None

Publication Dates

• Publication in this collection
  26 June 2023
• Date of issue
  2023

History

• Received
  15 Mar 2023
• Accepted
  3 May 2023