Tetanus

Global epidemiology

Tetanus is a vaccine-preventable neurologic disease that remains an important public-health problem despite a substantial long-term decline in incidence. The continuing burden is concentrated disproportionately in resource-limited settings, where vaccination coverage, access to clean delivery and wound-care services, diagnostic capacity, and intensive-care support may be limited. A tertiary-hospital study from the Philippines described non-neonatal tetanus as decreasing globally but still endemic in resource-limited settings. ^[9]

Among children younger than 5 years, Global Burden of Disease Study 2021 estimates showed a marked reduction in worldwide incidence, from 308,931 cases in 1990 to 17,788 cases in 2021, accompanied by a significant decline in mortality over the same period. ^[16]D These improvements are consistent with the expanding use of tetanus-toxoid-containing vaccines and maternal and neonatal immunization strategies, although the persistence of cases indicates incomplete population protection. ^[16]D[22]D

Tetanus continues to occur in Asia, particularly among older children and adolescents in settings where primary-series completion and booster coverage are inconsistent. A systematic review of diphtheria, tetanus, pertussis, and poliovirus in Asian children aged 3–18 years identified outbreaks and rising incidence in some populations and examined the relationship with vaccination schedules, booster coverage, and booster immunogenicity. ^[3] In the United States, tetanus has become rare following introduction of tetanus-toxoid-containing vaccines, but childhood uptake is higher than adult uptake, leaving preventable immunity gaps in adults. ^[23]D

Population groups at increased risk

The principal population-level risk is inadequate or waning vaccine-derived immunity. In a United States National Health and Nutrition Examination Survey analysis, serologic immunity was assessed in persons aged ≥6 years, with vaccination history and demographic factors evaluated as potential determinants of protection; the study specifically highlighted suboptimal adult vaccine uptake despite high childhood coverage. ^[23]D In Austria, among 10,247 voluntarily tested residents, only 4% lacked seroprotection against tetanus, compared with 36% lacking diphtheria protection; however, these findings came from a tested population and should not be assumed to represent all residents. ^[107]

Pregnant women and their newborns remain a priority group in low- and middle-income countries because maternal tetanus-toxoid-containing vaccination is a central strategy for preventing maternal and neonatal tetanus. In a pooled analysis of 173,032 pregnant women from sub-Saharan African demographic and health surveys, investigators evaluated the prevalence and determinants of receiving two or more doses of tetanus-toxoid-containing vaccine. ^[22]D A Nigerian 2021 Multiple Indicator Cluster Survey likewise examined low and uneven tetanus-toxoid uptake among women of reproductive age, including differences by urban versus rural residence. ^[112] These findings support the importance of residence, service access, and other sociodemographic determinants when identifying populations at risk of inadequate protection. ^[22]D[112]

Clinical and host factors associated with fatal outcome

Risk factors for acquiring tetanus and risk factors for dying after disease should be distinguished. The strongest contemporary evidence on prognosis comes from hospitalized adults rather than the general population. A 2025 systematic review and meta-analysis of observational studies published from 2000 through February 2024 evaluated mortality and associated factors in hospitalized adult patients. ^[1] A separate systematic review and meta-analysis of 182 adult cases from 36 countries, reported between 1990 and 2024, identified autonomic dysfunction, opisthotonus, shorter incubation period, diabetes mellitus, cardiovascular disease, and ulcers or other dermatologic conditions as factors associated with fatality. ^[2]

Autonomic dysfunction and opisthotonus indicate severe disease and are particularly important prognostic markers. A short incubation period generally signals a more severe clinical course, while diabetes, cardiovascular disease, and ulcerative or dermatologic conditions may increase vulnerability or complicate management. ^[2] Hospital-based evidence from Bangladesh also specifically investigated factors associated with in-hospital mortality among adults with tetanus in two specialized infectious-disease hospitals, underscoring the importance of age, comorbidity, and disease severity in outcome assessment. ^[110] Findings from individual hospital studies should be generalized cautiously because referral patterns and access to critical care can strongly influence observed mortality. ^[9][110]

Prevention-related risk factors and immunity gaps

Incomplete immunization, failure to receive recommended boosters, and unequal access to maternal vaccination are preventable determinants of tetanus susceptibility. ^{[3][22]D[23]D[112]} Vaccination studies in infants, adolescents, and young children demonstrate that combined diphtheria-tetanus-containing vaccines are used across different schedules and age groups, including three-dose infant priming followed by booster vaccination and adolescent Td vaccination. ^[7][8][106] Real-world post-marketing surveillance has also evaluated the safety of DTaP-IPV/Hib vaccination in South Korean infants, supporting continued use of routine infant immunization to maintain protection. ^[111]

Environmental sanitation may influence the broader burden of vaccine-preventable diseases. An ecological analysis of 532 Indian districts evaluated whether increased household toilet availability and reduced open defecation following a nationwide sanitation campaign corresponded with changes in tetanus and other vaccine-preventable diseases among children younger than 5 years. ^[109] Because this was an ecological observational study, sanitation improvements should be considered a population-level correlate rather than a proven individual cause of tetanus reduction. ^[109]

Passive postexposure prophylaxis remains relevant when vaccination status is incomplete or unknown. A phase 3 trial compared recombinant monoclonal antibody siltartoxatug with plasma-derived human tetanus immunoglobulin in 675 participants and described human immunoglobulin as the recommended passive immunization therapy, while noting global supply limitations and continued use of equine antitoxin in some countries despite lack of WHO endorsement. ^[6]

The clinical presentation of tetanus is primarily defined by progressive muscle rigidity and paroxysmal spasms caused by the tetanospasmin toxin. While the classic presentation involves trismus and generalized hypertonicity, the disease can manifest in several distinct phenotypic variants depending on the portal of entry and the patient's age ^[9][36]D.

Presenting Symptoms

Patients typically present with a median duration of 4 days from the onset of symptoms to hospital admission ^[36]D. The incubation period—the time from inoculation to the first symptom—is variable but often ranges from 3 to 21 days; for instance, a classic case following a rusty nail puncture reported a 10-day incubation ^[33]C.

• Trismus (Lockjaw): This is the most common presenting symptom, occurring in approximately 85.7% of cases ^[36]D. It results from masseter muscle rigidity, making it difficult for the patient to open their mouth ^[9][27]C.
• Dysphagia and Neck Pain: Early symptoms often include difficulty swallowing or localized pain in the neck and jaw ^[32]C[33]C. In the elderly, dysphagia and tremors may be the only initial symptoms, leading to potential diagnostic delays ^[32]C[35]D.
• Portal of Entry: History should focus on potential inoculation sites. While traumatic wounds (e.g., rusty nails, scalp lacerations) are classic ^[29]C[33]C, atypical portals include breast cancer-related skin ulcers ^[27]C, ear discharge (otogenic tetanus) ^[31]C, and myelomeningocele repair sites in infants ^[30]C.

Neurological Examination Findings

The physical examination is the cornerstone of diagnosis, as laboratory confirmation is often difficult ^[31]C[39]D. The examination should be conducted in a quiet environment, as external stimuli can trigger painful spasms.

• Cranial Nerves: Trismus is the hallmark. Facial nerve involvement leads to risus sardonicus, a characteristic grimace caused by sustained contraction of the facial muscles ^[30]C. In cephalic tetanus, cranial nerve palsies (especially CN VII) may be present ^[29]C.
• Motor System: Generalized muscle rigidity is common. Opisthotonus, a state of severe hyperextension and spasticity in which the patient's head , neck, and spinal column enter a complete arching position, is a classic finding ^[27]C[30]C.
• Reflexes: Patients exhibit generalized hyperreflexia. Spasms are often paroxysmal and can be triggered by touch, light, or sound ^[35]D.
• Autonomic Nervous System: Autonomic nervous system dysfunction (ANSD) is a critical finding and a major cause of mortality ^[37]D. Signs include labile blood pressure, tachycardia, and intermittent hyperthermia ^[28]C[38]D.

Phenotypic Variants

Tetanus is classified into four clinical types based on the extent and location of symptoms.

Red Flags

Certain clinical signs indicate a high risk of rapid deterioration and require immediate intensive care intervention:

• Respiratory Compromise: Rigidity of the thoracic and abdominal muscles can lead to ventilatory failure. While specific FVC thresholds are used in some protocols, any sign of tachypnea or accessory muscle use in a tetanus patient is a critical warning ^[28]C[30]C.
• Autonomic Instability: Labile hemodynamics or profound diaphoresis suggest ANSD, which may require invasive monitoring and pharmacological management (e.g., magnesium sulfate) ^[38]D.
• Rapid Progression: A short interval between the first symptom and the first generalized spasm (the 'period of onset') is a poor prognostic indicator ^[39]D.

Atypical Presentations and Differentials

Clinicians must maintain a high index of suspicion in non-classic cases. Tetanus can occur even in individuals with a history of vaccination or "protective" antibody levels ^[33]C.

• Elderly Patients: May present with delirium or isolated tremors, often lacking the classic trismus initially ^[32]C[35]D.
• Crisponi Syndrome: This rare autosomal recessive disorder mimics neonatal tetanus, presenting with trismus, abundant salivation, and hyperthermia from day one of life ^[28]C. It is distinguished by characteristic facial dysmorphism and camptodactyly ^[28]C.
• Otogenic Tetanus: Presentation with ear discharge and localized rigidity, often in pediatric populations in resource-limited settings ^[31]C.

Diagnostic approach

Tetanus is identified clinically rather than by a single confirmatory laboratory test in the evidence supplied. The adult treatment trial enrolled patients on the basis of a clinical diagnosis of generalized tetanus, underscoring that recognition of the characteristic syndrome is central to diagnosis ^[41]. The diagnostic assessment should therefore document the pattern, progression, severity, probable portal of entry, vaccination status, and important mimics or complications before treatment is delayed ^[36]D[41].

The most useful initial clinical feature reported in contemporary inpatient data is trismus: it was present in 85.7% of hospitalized Korean patients with tetanus, all of whom had generalized disease ^[36]D. Assessment should also specifically record painful generalized muscle rigidity, stimulus-induced spasms, dysphagia, dysarthria, respiratory difficulty, autonomic instability, and progression from localized or cephalic manifestations to generalized disease; however, the supplied studies do not provide diagnostic sensitivities for these individual findings ^[36]D[41]. Absence of a documented wound or a clear vaccination history should not by itself exclude tetanus, because the cited cohorts included patients identified through clinical diagnosis and retrospective hospital records rather than a uniformly documented laboratory criterion ^[36]D[117]C.

History and examination

Obtain a detailed wound and exposure history, including recent laceration, puncture, burn, injection, surgery, crush injury, devitalized tissue, or contaminated wound, and determine whether wound care and vaccination were received. A laceration preceded generalized grade 4 tetanus in a reported adult case ^[46]C. Record the date of symptom onset and progression; in a Korean inpatient cohort, the median interval from symptom onset to admission was 4 days ^[36]D. Document prior tetanus-containing vaccine doses and the date of the last booster, while recognizing that serologic protection may be reduced or difficult to interpret in selected populations: durability of tetanus seroprotection was specifically studied in people living with HIV ^[120]C, and vaccine-response studies addressed children receiving abatacept ^[114] and children with inflammatory bowel disease ^[121].

Assess host factors that may alter pretest probability or the interpretation of vaccine history, including advanced age, HIV infection, immunosuppressive therapy, inflammatory bowel disease, substance-use disorder, and pregnancy. Older adults constitute an important contemporary patient group in Japan ^[42], while the Korean cohort had a mean age of 67.0 years ^[36]D. Hospitalization may provide an opportunity to identify incomplete tetanus vaccination among people with substance-use disorders ^[116]. For patients who are pregnant or of reproductive potential, document pregnancy status because trauma-related guidelines emphasize pregnancy testing or obstetric assessment in women of reproductive age when clinically indicated ^[40]; this is particularly relevant when a wound or traumatic event is the suspected portal of entry.

Severity classification and baseline workup

After clinical recognition, grade severity using a reproducible clinical system such as the Ablett classification. Contemporary studies explicitly classified patients as severe when they had Ablett grade III or IV disease ^[115], and another adult series divided patients into severe and non-severe groups using the same classification ^[117]C. Record airway and respiratory status, swallowing ability, frequency and triggers of spasms, consciousness, cardiovascular instability, and evidence of autonomic dysfunction. These findings determine the need for intensive monitoring; the randomized antitoxin trial enrolled adults with generalized tetanus admitted to an intensive care unit ^[41].

Baseline investigations should be directed toward immediate supportive decisions, identification of complications, and exclusion of alternative diagnoses rather than used to rule out tetanus. The supplied studies report collection of vital signs and laboratory findings in severe-tetanus cohorts ^[115][117]C, but do not establish a diagnostic laboratory threshold or a validated biomarker. Review medications and comorbidities, including anticoagulant or antiplatelet exposure, because severe spasms can cause traumatic complications even without anticoagulant therapy ^[124]C.

Targeted imaging and differential assessment

Imaging is indicated when the examination suggests injury or an alternative source of pain. Generalized spasms can produce fractures and other traumatic complications; computed tomography identified an iliopsoas hematoma in a 72-year-old patient with tetanus who had no anticoagulant or antiplatelet exposure ^[124]C. New focal lumbar, abdominal, hip, flank, or groin pain; falling hemoglobin; neurologic deficit; or unexplained hemodynamic change should therefore prompt targeted imaging, with CT considered when deep hemorrhage or structural injury is suspected ^[124]C.

The differential diagnosis should be guided by the clinical pattern and may include seizure disorders, drug-induced dystonia or rigidity, hypocalcemic tetany, meningitis or encephalitis, strychnine poisoning, and neuroleptic malignant syndrome; none of the supplied human studies validates a specific discriminator for these conditions. An animal tetanus case demonstrated that abnormal sleep-associated movements occurred without epileptiform EEG activity, but this observation is not validated for human diagnostic practice ^[47]C.

Diagnostic and therapeutic urgency

When the clinical syndrome is compatible with generalized tetanus, diagnostic evaluation must proceed in parallel with urgent treatment and intensive monitoring. The randomized trial specifically evaluated intramuscular human or equine antitoxin, with or without intrathecal human antitoxin, in clinically diagnosed adult generalized tetanus ^[41]; this supports avoiding delays while awaiting nonvalidated tests. Record baseline severity before antitoxin and subsequent interventions so that progression, complications, and functional outcome can be assessed consistently ^{[41][42][115]}.

Principles of care

Tetanus is a clinical emergency in which repetitive spasms, dysautonomia, and neuromuscular respiratory failure drive severe morbidity and mortality. ^[4] Management should therefore combine early toxin neutralisation, wound hygiene, antimicrobial treatment, sedation and analgesia, continuous monitoring, and airway support within an intensive-care framework. ^[129] Severe disease is particularly associated with autonomic dysfunction and opisthotonus; shorter incubation, diabetes mellitus, cardiovascular disease, and ulcers or other dermatological conditions have also been associated with fatal outcome in adult case-based evidence. ^[2] A systematic review and meta-analysis of hospitalised adults confirms that mortality remains substantial and that clinical severity and complications are important determinants of outcome. ^[1]

Antitoxin and wound management

Intramuscular antitoxin is used to neutralise circulating toxin, but peripherally administered antitoxin has limited penetration into the central nervous system, where tetanus toxin acts. ^[41] A factorial randomised trial in adults with generalised tetanus compared 3,000 IU human with 21,000 U equine intramuscular antitoxin and separately evaluated 500 IU intrathecal human antitoxin versus a sham procedure. ^[41] The trial was designed to determine whether preparation type and intrathecal administration improve outcomes; its design does not justify assuming benefit from intrathecal treatment in routine practice. ^[41]

Intrathecal human immunoglobulin remains an investigational or specialist intervention because evidence for clinical benefit is uncertain and lumbar puncture carries procedural concerns. ^[125]C In a pilot study of five adults, intrathecal administration was performed a median of 140 minutes after ICU admission; no serious procedure-related adverse effects occurred, although three participants had minor, probably related events that resolved spontaneously. ^[125]C These findings support feasibility and short-term procedural safety in an appropriately monitored setting, but they are insufficient to establish efficacy. ^[125]C

Wound care should include identification and appropriate hygiene of the inoculation site as part of a standardised tetanus protocol. ^[129] The available evidence does not establish that wound treatment alone modifies established neurological disease, so it should accompany—not replace—antitoxin, antimicrobial therapy, sedation, monitoring, and supportive care. ^[129]

Control of spasms and autonomic dysfunction

Benzodiazepines are used for muscle spasms but can cause respiratory depression and increase the need for mechanical ventilation, a major limitation where ventilatory support is inaccessible or unaffordable. ^[4] Intravenous magnesium sulfate is a potential adjunct because it can reduce neuromuscular excitability and influence autonomic dysfunction; it is inexpensive and widely available in low- and middle-income settings because of its use for eclampsia. ^[4]

Controlled clinical evidence indicates that magnesium improves muscle-spasm control and cardiovascular stability in severe tetanus. ^[55] In a randomised placebo-controlled study of 180 adults with severe tetanus, magnesium was associated with lower urinary adrenaline excretion and higher urinary noradrenaline excretion during the first 24 hours, supporting an effect on catecholamine handling and autonomic physiology. ^[55] A prospective adult study used an initial intravenous dose of 70 mg/kg, followed by infusion increments of 0.5 g/hour every 6 hours until spasms ceased or the patellar tendon reflex was abolished. ^[58] Such treatment requires close clinical monitoring because loss of reflexes and respiratory compromise may indicate excessive neuromuscular blockade. ^[58]

The evidence should be interpreted cautiously. A meta-analysis of three controlled studies involving 275 participants found no reduction in mortality with magnesium compared with placebo or diazepam; the relative risk was 0.80 (95% CI 0.41–1.58) versus placebo and 1.11 (95% CI 0.70–1.75) versus diazepam. ^[54] Effects on ICU duration, hospital duration, and ventilatory support were conflicting and could not be pooled. ^[54] The subsequent systematic review assessed magnesium’s safety and efficacy across studies but does not support presenting magnesium as a mortality-reducing therapy. ^[4] Magnesium should therefore be regarded as an adjunct for spasms and autonomic instability, not a substitute for airway preparedness or definitive critical care. ^[4][54][55]

Airway, respiratory, and cardiovascular support

Respiratory failure may result from neuromuscular dysfunction, severe spasms, sedative treatment, or associated pulmonary complications. ^[4] Patients require close observation for hypoxaemia and deteriorating ventilation, with prompt escalation to airway support and mechanical ventilation when clinically indicated. ^[129] In an Ethiopian adult cohort, complications occurred in 75% of patients; dysautonomia occurred in 58.8%, pneumonia in 44.1%, and hypoxaemia in 41.2%. ^[130] These findings support proactive respiratory surveillance, pulmonary hygiene, and early recognition of pneumonia and oxygenation failure. ^[130]

Autonomic dysfunction requires continuous cardiovascular and haemodynamic monitoring because it is both a frequent complication and a marker of poor prognosis. ^[2][55] Magnesium may improve cardiovascular control, but available controlled evidence demonstrates physiological and clinical control of autonomic manifestations rather than a proven survival benefit. ^[54][55]

Prognosis, rehabilitation, and systems of care

Tetanus commonly requires prolonged hospitalisation and critical-care resources; in a Korean series of 49 adults with generalised tetanus, the median hospital stay was 39 days and in-hospital mortality was 10.2%. ^[36]D Older adults may have persistent functional consequences, making assessment of activities of daily living and discharge rehabilitation important; a Japanese study specifically evaluated Barthel Index-based functional prognosis in older hospitalised adults. ^[42]

Recent observational studies have examined severe ICU tetanus, healthcare-associated infections, microbiology, treatment strategies, and outcomes in China and Brazil, as well as management and prognosis in Chinese tertiary hospitals. [115-117,126-128] These studies reinforce the need for protocolised ICU care, infection surveillance, and outcome assessment, although their retrospective designs do not establish superiority of any individual treatment. [115-117,126-129] A Tanzanian pre-post study evaluated implementation of a standardised tetanus-care protocol addressing monitoring, immune globulin, sedation, analgesia, wound hygiene, and airway support, supporting structured care pathways in resource-limited ICUs. ^[129] Neonatal and postneonatal disease require age-specific pathways; in a retrospective paediatric study, intrathecal immunoglobulin was evaluated as an addition to standard treatment in children, but the non-randomised design limits causal interpretation. ^[59]D[122]

Overall prognosis

Tetanus remains a life-threatening but potentially survivable neurologic infection. Prognosis depends substantially on disease severity, age, access to intensive care, complications, and the time from symptom onset to effective treatment. Contemporary evidence is heterogeneous because reported outcomes come mainly from retrospective hospital cohorts and differ in case mix, vaccination coverage, and available critical-care resources. A 2025 systematic review and meta-analysis specifically evaluated mortality and risk factors among hospitalised adults treated between 2000 and 2024, highlighting persistent uncertainty in the precise pooled mortality estimate and in the relative contribution of individual prognostic factors. ^[1]

Reported mortality varies widely. In a Chinese cohort of 75 adults with moderate or severe generalised tetanus, in-hospital mortality was 25.3%; approximately half the patients had severe disease, and severe tetanus was strongly associated with death (multivariable OR 30.364, 95% CI 1. ^[44] In two South Korean university hospitals, all 49 patients had generalised tetanus, five patients (10.2%) died, and the median hospital stay was 39 days, demonstrating that survivors commonly require prolonged inpatient care. ^[36]D A multicentre Bangladeshi study prospectively examined factors associated with adult in-hospital mortality using survival and multivariable Cox analyses, reflecting the continuing high fatality burden in settings where adult tetanus remains concentrated among older or inadequately immunised patients. ^[110] The African systematic review and meta-analysis likewise found substantial facility-based case fatality among adults, although outcomes varied between countries and hospitals. ^[53]

Factors associated with death or prolonged hospitalisation

Clinical severity is one of the most consistent prognostic determinants. Severe or advanced Ablett-class disease, autonomic instability, respiratory compromise, and the need for prolonged ventilatory or intensive-care support are clinically important markers of poor outcome; the association between severe tetanus and mortality was particularly pronounced in the Chinese prognostic cohort. ^[44] In neonatal tetanus, younger age was independently associated with mortality in a Vietnamese observational study of 107 infants: the odds ratio for mortality per age increment was 0.69 (95% CI 0.48–0.98), indicating poorer prognosis in younger neonates. ^[132] The same study evaluated a combined endpoint of death or prolonged hospital stay, underscoring that morbidity is not captured by mortality alone. ^[132]

Recent intensive-care cohorts continue to address outcomes in severe adult disease. A 2026 Chinese retrospective cohort studied adults with Ablett grade III or IV tetanus admitted to intensive care over a 10-year period and evaluated manifestations, treatment, complications, and outcomes. ^[115] A 2026 Brazilian 13-year series similarly assessed Ablett severity, healthcare-associated infections, microbiology, intensive-care course, and in-hospital mortality, providing contemporary data on complications that may prolong recovery even when the patient survives. ^[126] A 2024 Chinese tertiary-hospital study of 20 adults with generalised tetanus compared severe and non-severe disease and reported management and prognosis according to Ablett classification, but its small sample limits precision. ^[117]C

Functional recovery and persistent sequelae

Survival does not necessarily indicate immediate return to baseline function. A 2025 Japanese study specifically assessed activities of daily living using the Barthel Index before admission, at admission, and at discharge in older adults with tetanus, addressing functional prognosis in a high-income setting where most cases occur in older people. ^[42] Its single-centre retrospective design means that the findings should not be extrapolated directly to younger adults or resource-limited settings. ^[42] Long hospitalisation, intensive-care treatment, painful spasms, immobility, mechanical ventilation, and hospital-acquired infection can all delay rehabilitation; contemporary cohorts have therefore evaluated complications and length of stay in addition to death. ^{[36]D[115][126]}

Evidence for very long-term neurologic or psychological outcomes in human survivors remains limited in the supplied literature. Veterinary follow-up illustrates that post-tetanus sleep abnormalities may persist during recovery: in a cohort of 61 dogs, 11 (18%) died or were euthanised before discharge and at least 46% of surviving dogs developed clinically probable rapid-eye-movement sleep behaviour disorder. ^[131] These findings are not directly transferable to humans, but they support awareness that abnormal sleep or episodic motor behaviours during recovery may be mistaken for epilepsy and may affect quality of life. ^[131]

Prevention of recurrence and future risk

Recovery from tetanus does not reliably confer protective immunity; therefore, survivors require active immunisation according to vaccination guidance. Evidence on booster durability shows that a second reduced-antigen-content Tdap booster administered 10 years after an adolescent booster was evaluated in a phase III follow-up study of young adults, supporting continued maintenance of diphtheria and tetanus protection during adulthood. ^[70] Vaccine effectiveness is also relevant to population prognosis: a systematic review examined associations of BCG, DTP, and measles-containing vaccines with mortality in children younger than five years, including possible modification by age, sex, vaccine sequence, and vitamin A co-administration. ^[67] In pregnancy, tetanus-toxoid uptake remains an important determinant of maternal and neonatal protection; a Sierra Leone survey of 8,722 women assessed prevalence and predictors of vaccination during pregnancy. ^[133]

Protection may be less predictable in immunocompromised patients. In young children with polyarticular juvenile idiopathic arthritis receiving subcutaneous abatacept, a phase III substudy assessed maintenance of diphtheria and tetanus antibody responses after prior vaccination. ^[114] Children with inflammatory bowel disease have also been evaluated for tetanus seroprotection and routine vaccine coverage, with the available cohort reporting high overall age-appropriate coverage but not universal protection. ^[121] These findings support checking immunisation history and considering serologic or specialist assessment when immune dysfunction may reduce vaccine responsiveness. ^[114][121]

Treatment-related prognostic evidence

Because tetanus toxin acts within the central nervous system, intramuscular antitoxin may have limited penetration after toxin binding. A randomised factorial trial in Vietnamese adults with generalised tetanus compared human with equine intramuscular antitoxin and assessed adjunctive intrathecal human antitoxin, directly testing whether route and preparation influence clinical outcomes. ^[41] A preceding five-patient pilot study found intrathecal immunoglobulin feasible without serious procedure-related adverse effects, although three patients experienced minor, probably related adverse events that resolved spontaneously. ^[125]C These studies inform treatment strategy but do not eliminate the major prognostic effects of disease severity and intensive-care complications. ^[41][125]C

Adults and older adults

Adult immunity may be substantially lower than expected, particularly with increasing age. In a phase IV trial of individuals aged ≥16 years, prevaccination seroprotection (tetanus toxoid IgG ≥0.1 IU/mL) declined across the 16–18-, 19–49-, and ≥50-year groups from 44.00% to 18.47% and 5.38%, respectively; geometric mean concentrations declined from 0.079 to 0.052 and 0.033 IU/mL. A single adsorbed tetanus toxoid booster produced 100% seroprotection and at least 99.48% seroconversion across all age groups, with post-vaccination geometric mean concentrations of 6.831 IU/mL. ^[78]

A separate phase III randomized, double-blind trial in adults aged ≥18 years compared tetanus vaccine, adsorbed, with a control tetanus vaccine. Antibody concentrations were measured before vaccination, 30 days after vaccination, and, in the first 240 participants, 6 months after vaccination; at day 30, geometric mean concentrations were 3.205 in the experimental group and 2.387 in the control group, with a reported between-group P value of 0.0012. ^[134]

Older adults are disproportionately represented among tetanus patients in some high-income settings. A Japanese retrospective study specifically evaluated functional prognosis in hospitalized older adults using activities of daily living and Barthel Index assessments before admission, at admission, and at discharge. ^[42] Large retrospective studies from China similarly describe non-neonatal tetanus as predominantly affecting adults, including a 2,567-patient multicenter cohort with a median age of 53 years and 62.1% male participants. ^[128] Studies of adult generalized or severe tetanus in China and Brazil evaluated severity, intensive-care requirements, complications, treatment, and outcomes, emphasizing that severe disease remains clinically important despite vaccination availability. ^{[115][126][127]C[117]C}

Pregnancy and postpartum period

Tdap vaccination during pregnancy is studied primarily for neonatal protection through transplacental antibody transfer. A prospective Belgian study followed 96 pregnant women vaccinated between gestational weeks 16 and 32 and measured maternal total IgG, IgG subclasses, Fc-mediated effector features, and cord-blood antibodies to examine how gestational age at vaccination affects the balance between maternal antibody induction and placental transfer. ^[136] An observational study of 240 pregnant active-duty service members, matched 1:1 with non-pregnant service members, assessed anti-pertussis toxin IgG 9–15 months after Tdap vaccination, extending evaluation beyond the immediate post-vaccination period. ^[137]

A randomized phase II follow-up involving 400 pregnant women evaluated recombinant pertussis-containing vaccines with or without tetanus and diphtheria components. Maternal antibodies and transfer to neonates were assessed, and antibody persistence was followed to 2 months postpartum; the study reported effective maternal antibody transfer and safety data in mothers and neonates. ^[152] A systematic review examined vaccine-induced antibodies in human milk after vaccination during pregnancy or lactation, including the presence, duration, function, and potential infant-protective effects of antibodies; it also identified important gaps in evidence regarding how milk antibodies translate into clinical protection. ^[73]

Pregnant women and their infants remain vulnerable where maternal tetanus vaccination coverage is inadequate. A systematic review and meta-analysis assessed tetanus toxoid vaccination coverage among pregnant women in East Africa and investigated associated factors, reflecting persistent regional prevention gaps. ^[72] A separate systematic-review protocol was designed to evaluate acceptance and uptake of tetanus and other vaccines among pregnant and postpartum women in low- and middle-income countries, where coverage of recommended maternal vaccines is described as suboptimal. ^[79]

Available post-marketing and infant-outcome evidence is observational. A VAERS disproportionality analysis covering Tdap reports from 2015 through May 2025 used four signal-detection algorithms and specifically examined safety profiles in subpopulations, including pregnant individuals. ^[153] A retrospective cohort study using two US health systems assessed infant growth and healthcare utilization after maternal Tdap vaccination at ≥27 gestational weeks or after vaccination during lactation within 90 days postpartum; the study compared linked infants with unexposed groups. ^[154]

Immunocompromised individuals and transplant recipients

Kidney transplant recipients may have impaired responses to tetanus vaccination, particularly when receiving mycophenolate mofetil (MMF). In a randomized study of low immunological-risk recipients, participants were assigned 6 months after transplantation to tacrolimus/MMF or tacrolimus monotherapy; at 1 year after transplantation they received pneumococcal, tetanus, and influenza vaccines, with blood sampling before and 21 days after vaccination. MMF hampered antibody responses across a broad range of vaccines, including tetanus, compared with tacrolimus monotherapy. ^[74]

Trauma, substance use, and post-exposure prophylaxis

Trauma encounters provide an opportunity to identify inadequate tetanus protection. A Japanese claims-based cohort compared trauma patients born before 1968 with those born in 1968 or later, reflecting the introduction of routine tetanus immunization in 1968, and assessed whether patients received an initial tetanus toxoid dose after trauma. ^[80] Among hospitalized US adults with substance-use disorders, a large health-system study evaluated tetanus screening and vaccination during hospitalization and during the 90-day post-discharge surveillance period, highlighting hospitalization as an opportunity for preventive intervention. ^[116]

For tetanus post-exposure prophylaxis, a phase III randomized, double-blind active-controlled trial enrolled 675 participants in a 2:1 allocation to a single intramuscular dose of recombinant monoclonal antibody siltartoxatug 10 mg or plasma-derived human tetanus immunoglobulin 250 IU. The trial met its primary outcome and reported superiority of siltartoxatug for the prespecified comparison. ^[6]

Clinical implications

Special-population evidence supports particular attention to waning adult immunity, advanced age, pregnancy timing and antibody transfer, immunosuppressive therapy, trauma-related vaccination opportunities, and populations with substance-use disorders. ^{[78][134][136][137][152][72][74][80][116]} Evidence for maternal and infant outcomes is increasingly available but remains heterogeneous, with randomized immunogenicity studies, observational cohorts, surveillance databases, and systematic reviews addressing different endpoints. ^{[73][79][136][137][152][153][154]}

Core prevention strategy

Tetanus prevention depends primarily on completion and maintenance of tetanus-toxoid-containing vaccination, supplemented by appropriate wound management and targeted vaccination of populations with uncertain or declining immunity. Global elimination of maternal and neonatal tetanus has been achieved in many regions, but coverage gaps and sporadic cases persist, particularly in low-resource settings. ^[83] Adult tetanus remains clinically severe: a systematic review of 182 reported cases from 36 countries identified autonomic dysfunction, opisthotonus, short incubation, diabetes mellitus, cardiovascular disease, and ulcers or other dermatological conditions as important fatality-associated factors. ^[2]

Routine infant and childhood immunization

Primary immunization is generally delivered through combination vaccines containing diphtheria, tetanus, and pertussis antigens. In a phase III trial, 1,140 infants beginning vaccination at 3 months of age received three doses at 3, 4, and 5 months; the investigational three-component acellular pertussis vaccine was compared with licensed DTaP and DTaP-IPV-Hib controls. ^[135] In another phase III trial, 1,380 infants beginning at 2 months of age received schedules at 2/3/4 months or 2/4/6 months, with comparison against DTaP-IPV-Hib. ^[106] These studies evaluated safety and immunogenicity rather than population-level disease prevention, and their schedules should not be substituted for the immunization schedule recommended by the relevant national program. ^[135][106]

In the 3-, 4-, and 5-month trial, overall adverse reactions were lower with the investigational DTcP and co-purified DTaP vaccines than with DTaP-IPV-Hib (17.99% and 18.08% vs 21.96%), while the investigational vaccine was non-inferior and superior to co-purified DTaP for anti-pertussis toxin and anti-filamentous hemagglutinin responses. ^[135] South Korean post-marketing surveillance of DTaP-IPV/Hib in infants vaccinated from 2 months of age followed 646 infants for 30 days after each dose and provides real-world safety data, although it was non-comparative and primarily designed to assess adverse events. ^[111]

Adolescents and adults

Adult immunity may be substantially lower than childhood immunity. In a phase IV study of people aged ≥16 years, prevaccination seroprotection, defined as tetanus antibody ≥0.1 IU/mL, declined from 44.00% in participants aged 16–18 years to 18.47% in those aged 19–49 years and 5.38% in those aged ≥50 years; geometric mean concentrations similarly declined from 0.079 to 0.052 and 0.033 IU/mL. ^[78] A single adsorbed tetanus-toxoid booster produced 100% seroprotection, seroconversion of ≥99.48%, and a post-vaccination geometric mean concentration of 6.831 IU/mL across the studied age groups. ^[78]

A randomized phase III trial in adults aged ≥18 years compared an experimental adsorbed tetanus vaccine with a control tetanus vaccine. Antibody concentrations were assessed before vaccination, at 30 days, and, in the first 240 participants, at 6 months; the 30-day geometric mean concentration was higher in the experimental group than in the control group (3.205 vs 2.387; P = 0.0012). ^[134] These findings support the immunogenicity of adult tetanus vaccination but do not establish a universal booster interval. ^[134][78]

Pregnancy and prevention of infant disease

Maternal Tdap vaccination is intended to protect the pregnant individual and provide transplacental antibody to the fetus and newborn. A prospective study of 96 pregnant women vaccinated between 16 and 32 weeks' gestation evaluated maternal antibody responses, antibody subclasses, Fc-mediated functions, and cord-blood transfer; timing influenced the balance between maternal antibody induction and placental transfer efficiency. ^[136] Evidence concerning vaccine-induced antibodies in human milk indicates that antibodies may be present after vaccination during pregnancy or lactation, but the duration, functionality, and degree of infant clinical protection remain incompletely defined. ^[73]

A systematic-review protocol emphasizes that vaccine uptake among pregnant and postpartum women in low- and middle-income countries is often suboptimal and that maternal vaccination may provide passive IgG and secretory IgA protection during early infancy. ^[79] In East Africa, a systematic review and meta-analysis specifically examined pooled tetanus-toxoid vaccination coverage among pregnant women and associated determinants, highlighting persistent coverage gaps. ^[72] Observational studies found no evidence in the supplied summaries of adverse effects on infant growth or healthcare utilization after Tdap during pregnancy or lactation, although these data are retrospective and cannot fully exclude confounding. ^[154] Pregnancy may also modify longer-term antibody responses: an observational comparison assessed anti-pertussis toxin IgG 9–15 months after vaccination in pregnant and non-pregnant service members. ^[137]

Screening and missed-opportunity prevention

Routine population serologic screening is not established by the supplied evidence. Serology may be useful when vaccination records are unavailable or immunity is uncertain. Among migrant adolescents aged 13–18 years arriving in Geneva, a dTPa-IPV booster was administered at the first visit and immunity was assessed approximately one month later, illustrating a catch-up approach for individuals lacking documentation. ^[92]D

Hospitalization and trauma encounters are opportunities to assess tetanus vaccination status and vaccinate when indicated. In a large US health-system study of adults with substance-use disorders, investigators measured tetanus screening and vaccination during hospitalization and within 90 days after discharge, reflecting the high-risk status of this population and the potential value of inpatient preventive care. ^[116] A Japanese claims-data study evaluated tetanus-toxoid administration after trauma and compared people born before 1968 with those born in 1968 or later, because routine tetanus immunization began in Japan in 1968; the study assessed adherence to trauma prophylaxis protocols. ^[80]

Special populations may require individualized assessment. A small quasi-experimental study of 16 hematopoietic stem-cell transplant recipients used three Tdap doses at intervals of at least 30 days, beginning 6 months after transplantation, and measured component-specific immune responses. ^[93]D Undernutrition may influence vaccine antibody levels: a South African birth-cohort analysis of 621 fully vaccinated children examined stunting and other growth measures in relation to tetanus, measles, and Hib antibodies. ^[85]

Safety surveillance and evidence limits

US VAERS disproportionality surveillance from 2015 through May 2025 evaluated reported adverse events after Tdap, including signals in specific subpopulations; spontaneous-reporting analyses detect reporting patterns but cannot establish incidence or causality. ^[153] Evidence in donkeys showed immune responses after a tetanus-containing equine vaccine, but veterinary findings are not directly transferable to human prevention. ^[138]

Scope and evidence update

Tetanus prevention continues to rely on active immunisation with tetanus toxoid (TT)-containing vaccines and passive protection with tetanus immunoglobulin (TIG); coverage gaps and sporadic disease remain important, particularly in low-resource settings.^[83] Hospitalised adult tetanus remains associated with substantial mortality, and a 2025 systematic review and meta-analysis evaluated mortality and prognostic factors across observational studies published from 2000 to February 2024.^[1] These findings support maintaining high vaccination coverage, rapid assessment of immunisation history after wound exposure, and timely access to passive immunisation when clinically indicated; the supplied references do not provide a replacement wound-management algorithm.^[1][83]

Active immunisation and schedule optimisation

The WHO-aligned infant DTwP-containing schedule is being evaluated against alternative schedules. The OptImms trials in Uganda and Nepal randomised healthy infants aged 42–50 days to five DTwP-Hib-HepB schedules, including the WHO schedule at 6, 10, and 14 weeks and reduced two-dose or delayed three-dose schedules.^[141] The stated objective was to determine whether alternatives could preserve early pertussis antibody levels before boosting while creating capacity for integration of additional vaccines; the supplied abstract does not provide the comparative outcome data, so alternative schedules should not be substituted for national or WHO schedules solely on the basis of this citation.^[141]

Maternal pertussis vaccination is relevant to protection during early infancy. In the Gambian GaPs trial, maternal Tdap-IPV vaccination was compared with tetanus-toxoid vaccination, while infants subsequently received either acellular- or whole-cell pertussis-containing primary vaccination.^[97] A linked immunological substudy assessed pertussis-specific mucosal responses, including antibodies and mucosal-resident memory T-cell activation, after maternal vaccination and infant primary vaccination.^[96] A further analysis examined whether maternal vaccination altered infant anti-pertussis-toxin antibody epitopes and avidity, rather than antibody quantity alone.^[143] These studies address pertussis protection and immune response; they do not establish a different tetanus-containing schedule for routine care.^{[96][97][143]}

A birth dose of a three-component acellular pertussis vaccine was studied in infants who then received Infanrix hexa at 2, 4, and 6 months. The trial assessed later antibody responses after high- or low-dose pertussis-containing boosters at 18 months and 4 years and specifically evaluated whether the birth dose impaired booster responses.^[98] The available abstract reports that the birth-dose strategy did not impair antibody responses to later childhood doses.^[98]

Dose-sparing and coadministration research may affect future programme design but should not be interpreted as tetanus-specific guidance. A phase 2/3 Indian trial compared an adjuvanted IPV dose containing approximately one-quarter of the antigen content of full-dose IPV with standard IPV in infants aged 6–8 weeks who had received birth bivalent OPV.^[142] In England, children whose mothers had received an IPV-containing pertussis vaccine during pregnancy were assessed after the preschool dTaP-IPV booster because maternal vaccination had previously been associated with lower poliovirus titres after primary immunisation.^[103]

Maternal, adolescent, and adult vaccination resources

Maternal pertussis immunisation is supported by safety and effectiveness research. A Japanese retrospective cohort assessed maternal and infant outcomes after DTaP vaccination during pregnancy, including pregnancy complications, delivery mode, preterm birth, low birth weight, and congenital anomalies.^[145] Another Japanese study evaluated transplacental pertussis-antibody transfer after maternal DTaP vaccination.^[146] In a US military cohort, anti-pertussis-toxin IgG responses 9–15 months after Tdap were compared between pregnant and non-pregnant service members.^[137] An Italian population-based cohort examined associations between influenza and Tdap vaccination during pregnancy and infant pertussis- or influenza-related hospitalisation and emergency visits before 6 months of age.^[149]

Adolescent and adult programmes remain important because immunity and vaccine uptake may decline. US surveillance assessed whether adolescents aged 13–17 years were up to date for Tdap, MenACWY, and HPV vaccination and also measured influenza and COVID-19 vaccination status.^[150] A Chinese cross-sectional study of 1,522 adults examined factors associated with intention to receive tetanus booster vaccination, including knowledge, medical history, service preferences, and behavioural responses.^[140] A US claims analysis evaluated coadministration of recombinant zoster vaccine with influenza, pneumococcal, and tetanus-diphtheria or Tdap vaccines among adults aged ≥50 years, supporting coadministration as an uptake strategy where permitted by local recommendations.^[148]

Implementation and programme quality

Low DPT3 coverage in rural, peri-urban, and urban Uganda was investigated through a cross-sectional study designed to identify context-specific barriers and propose unified recommendations for improving immunisation uptake.^[147] These implementation findings should be considered when adapting delivery services, outreach, and follow-up systems to local populations.^[147]

Tetanus toxoid is also used as a carrier platform in conjugate vaccines. A Nepali phase III trial evaluated the immunogenicity and safety of Vi-DT typhoid conjugate vaccine in children older than 6 months and younger than 18 years, using Vi-TT as comparator and defining seroconversion as at least a fourfold rise in Vi antibody titre.^[144] This evidence concerns typhoid vaccination and does not replace routine tetanus immunisation.^[144]

Passive immunisation and emerging products

Plasma-derived human tetanus immunoglobulin (HTIG) remains the reference passive-immunisation product described in the supplied evidence, although global supply shortages and theoretical infectious-transmission concerns are noted.^[6] Equine tetanus antitoxin remains used in some countries but is described as not endorsed by WHO because of safety concerns.^[6] A phase 3 randomised, double-blind trial enrolled 675 participants and compared a single intramuscular 10 mg dose of recombinant monoclonal antibody siltartoxatug with 250 IU HTIG for tetanus post-exposure prophylaxis; the trial met its primary outcome and reported superiority of siltartoxatug to HTIG.^[6] Siltartoxatug should therefore be regarded as an emerging product pending incorporation into national and international guidance, regulatory decisions, and availability assessments.^[6]

Practical interpretation

Use national or WHO schedules for routine TT-containing vaccination unless an authorised programme specifies otherwise.^[83][141] Maternal pertussis vaccination, birth-dose strategies, IPV dose-sparing, and conjugate-vaccine studies provide programme and immunological evidence but are not, by themselves, indications to alter tetanus prophylaxis.^{[96][97][98][103][142][143][144]} Maintain attention to adult boosters, adolescent coverage, access barriers, and product supply, while recognising that the supplied studies do not provide a complete wound-risk classification or TIG dosing protocol.^{[1][6][83][140][147][150]}