Controlled release vaccine implants for delivery of booster immunisations.

Most current animal vaccine regimes involve a primary vaccination followed sometime later by a booster vaccination. This presents challenges when vaccinating difficult to access animals such as livestock. Mustering livestock to deliver a vaccine boost is costly and stressful for animals. Thus, we have produced a platform system that can be administered at the same time as the priming immunisation and delivers payload after an appropriate delay time to boost the immune response, without need for further handling of animals. A 30 × 2 mm osmotically triggered polymer implant device with burst-release characteristics delivered the booster dose of a tetanus vaccine. Blood samples were collected from an experimental group that received the priming vaccine and implant on day 0 and control group that received the initial vaccine (tetanus toxoid) and then a bolus dose 28 days later via subcutaneous injection. The two groups showed identical weight gain curves. T cell proliferation following in vitro stimulation with antigen was identical between the two groups at all time points. However, serum IgG antibody responses to the tetanus toxoid antigen were significantly higher in the control group at weeks 8 and 12. The implant capsules stayed at the site of implantation and at week 12 there was evidence of tissue integration. No local reactions at the implant site were observed, other than mild thickening of the skin in half of the experimental group animals and no other adverse health events were recorded in either group.

Progress Toward Achieving and Sustaining Maternal and Neonatal Tetanus Elimination - Worldwide, 2000-2020.

Maternal and neonatal tetanus (MNT)* remains a major cause of neonatal mortality with an 80%-100% case-fatality rate among insufficiently vaccinated mothers after unhygienic deliveries, especially in low-income countries (1). In 1989, the World Health Assembly endorsed elimination† of neonatal tetanus; the activity was relaunched in 1999 as the MNT elimination (MNTE)§ initiative, targeting 59¶ priority countries. MNTE strategies include 1) achieving ≥80% coverage with ≥2 doses of tetanus toxoid-containing vaccine (TTCV2+)** among women of reproductive age through routine and supplementary immunization activities (SIAs)†† in high-risk districts,§§ 2) achieving ≥70% of deliveries by a skilled birth attendant,¶¶ and 3) implementing neonatal tetanus case-based surveillance (2). This report summarizes progress toward achieving and sustaining MNTE during 2000-2020 and updates a previous report (3). By December 2020, 52 (88%) of 59 priority countries had conducted TTCV SIAs. Globally, infants protected at birth*** against tetanus increased from 74% (2000) to 86% (2020), and deliveries assisted by a skilled birth attendant increased from 64% (2000-2006) to 83% (2014-2020). Reported neonatal tetanus cases worldwide decreased by 88%, from 17,935 (2000) to 2,229 (2020), and estimated deaths decreased by 92%, from 170,829 (2000) to 14,230 (2019).††† By December 2020, 47 (80%) of 59 priority countries were validated to have achieved MNTE, five of which conducted postvalidation assessments.§§§ To achieve elimination in the 12 remaining countries and sustain elimination, innovation is needed, including integrating SIAs to cover multiple vaccine preventable diseases and implementing TTCV life course vaccination.

Mucosal and systemic immune responses following mucosal immunisation of tetanus toxoid entrapped in lipid nanoparticles prepared by microwave reactor.

In this study, the use of a microwave reactor, which allowed high input of energy into a pressurised system in a short period of time, was investigated for preparation of lipid nanoparticles (LNPs). The aim was to optimise the formulation process by reducing manufacturing time. Two types of LNPs were prepared; non-ionic surfactant vesicles (NISV) and bilosomes (modified NISV incorporating bile salts), with a model antigen (tetanus toxoid, TT) and the immune response induced after mucosal (nasal and oral, respectively) administration was assessed. The TT loaded LNPs were characterised in terms of particle size, size distribution, morphology, and entrapment efficiency. Immunisation was evaluated by lethal challenge with tetanus toxin in an animal model. The efficiency of vaccination was evaluated by measuring the anti-TT IgG antibody levels in the vaccinated animals. Bilosomes formed by this method showed an immunogen entrapment efficiency of ∼30% which was significantly (p < 0.05) higher than entrapment efficiency in the NISV. The percentage of animals that survived when challenged with tetanus toxin correlated with the level of IgG determined in the serum of mice immunised with LNPs by the mucosal route. Moreover, there were significant (p < 0.05) differences between orally and nasally immunised groups. Animal groups immunised bilosomes via the oral route showed the highest level of IgG (1.2 ± 0.13) compared to the positive control, LN + Xn, and no immunised group. Similarly, groups immunised via the nasal route showed significantly (p < 0.0001) higher titres compared with the control group. Mucosal TT was capable of inducing systemic specific IgG anti-TT responses that were higher than the parenteral vaccine.

Nonspecific Regulation of the Number of Immunocompetent Cells Under the Influence of DT Toxoid in Children With Glomerulonephritis.

Background: Studies aimed at identifying the mechanisms of the immunoregulatory effect of vaccination with diphtheria and tetanus toxoid on the parameters of adaptive immunity in children with kidney pathology are limited. The study aimed to study the effect of revaccination against diphtheria and tetanus on the proliferation and differentiation of immunocompetent cells, the formation of specific antibodies, and the course of the disease in children with glomerulonephritis (GN). Methods: The study included 45 children with glomerulonephritis (GN) aged 5 to 15 years, in remission from 6 months up to 4 years. Of these, 25 children were revaccinated with DT toxoid (Diphtheria-Tetanus toxoid with reduced antigenic content) and 20 were in the control group (not vaccinated). The frequency of development of local and systemic reactions and the course of GN were assessed. The subpopulation structure of lymphocytes was studied in dynamics after 1-6-12 months by flow cytometry and IgG levels to diphtheria and tetanus were studied by ELISA. Results: In 92% of children with GN, the post-vaccination period was uneventful. 8% showed a rise in temperature up to 37.3°C, without the development of local reactions. During the year, none of the patients had an exacerbation of GN or a concomitant disease. After revaccination with DT toxoid, a significant increase in IgG antibodies against diphtheria and tetanus was revealed, which persisted after 12 months - 7.5 [5.1-10.8] IU/mL (p <0.001) and 7.2 [4.8-10.7] IU/mL (p <0.001), respectively. In the post-vaccination period, a multidirectional change in the concentration of T-lymphocytes was noted: with an initially increased level, their percentage after revaccination with DT toxoid decreases from 83 (81-86) % to 78 (76-80)% after a month (p = 0.04) and up to 75 (69-79)% after 12 months (p<0.001). In the control group, such a decrease was not observed. A similar picture was observed for T-helpers, cytotoxic T-lymphocytes, and in patients with an initially low percentage of cytotoxic T-lymphocytes, on the contrary, its increase was noted (p<0.001), which is comparable with the value of this parameter in the group of children with initially normal value (H = 0.54, p = 0.76). The same patterns were observed in the change in the content of B-cells: one month after revaccination, the relative level of B-cells in patients with an initially lowered value increased (p = 0.02) and remained for 12 months (p<0.001). Conclusion: Revaccination with DT toxoid in children with GN not only does not cause undesirable changes in the system of immunocompetent cells but also has an immunomodulatory effect, which contributes to the favorable maintenance of the remission period of the disease.

Progress and barriers towards maternal and neonatal tetanus elimination in the remaining 12 countries: a systematic review.

This systematic review assessed the progress and barriers towards maternal and neonatal tetanus elimination in the 12 countries that are yet to achieve elimination, globally. Coverage of at least 80% (the coverage level required for elimination) was assessed among women of reproductive age for five factors: (1) at least two doses of tetanus toxoid-containing vaccine, (2) protection at birth, (3) skilled birth attendance, (4) antenatal care visits, and (5) health facility delivery. A scoping review of the literature and data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys provided insights into the barriers to attaining maternal and neonatal tetanus elimination. Findings showed that none of the 12 countries attained at least 80% coverage for women of reproductive age receiving at least two doses of tetanus toxoid-containing vaccine or protection at birth according to the data from Demographic and Health Surveys or Multiple Indicator Cluster Surveys. Barriers to maternal and neonatal tetanus elimination were mostly related to health systems and socioeconomic factors. Modification to existing maternal and neonatal tetanus elimination strategies, including innovations, will be required to accelerate maternal and neonatal tetanus elimination in these countries.

Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic lymphocytic leukemia.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) experience hypogammaglobinemia and non-neutropenic infections. In this exploratory proof of concept study, our objective was to determine the prevalence of humoral immunodeficiency in patients with CLL and serum IgG ≥ 400 mg/dL, and to evaluate the efficacy of subcutaneous immunoglobulin (SCIG) in this population. PATIENTS AND METHODS: Patients with CLL with serum IgG ≥ 400 mg/dL were evaluated for serum IgG, IgM, IgA, along with pre/post vaccine IgG titers to diphtheria, tetanus, and Streptococcus pneumoniae. Patients with evidence of humoral dysfunction were treated with SCIG with Hizentra every 7±2 days for 24 weeks. RESULTS: Fifteen patients enrolled with median IgG = 782 mg/dL [IQR: 570 to 827], and 6/15 (40%) responded to vaccination with Td, while 5/15 (33%) responded to vaccination with PPV23. 14/15 (93.3%) demonstrated humoral immunodeficiency as evidenced by suboptimal vaccine responses, and were treated with SCIG. In patients treated with SCIG, serum IgG increased from 670 mg/dL [IQR: 565 to 819] to 1054 mg/dL [IQR: 1040 to 1166] after 24 weeks (95% CI: 271-540). For streptococcus pneumoniae, the median protective serotypes at baseline was 8 [IQR: 4 to 9] and increased to 17 [IQR: 17 to 19] after 24 weeks (95% CI: 6.93-13.72). Non-neutropenic infections (NNI) decreased from 14 to 5 during treatment with SCIG. CONCLUSIONS: Patients with CLL demonstrate humoral immunodeficiency despite IgG > 400 mg/dL. For these patients, SCIG is well tolerated and efficacious in improving serum IgG, specific IgG to streptococcus pneumoniae, and may decrease reliance on antibiotics for the treatment of NNIs. CLINICAL TRIALS REGISTRATION: NCT03730129.

Case Report: Anaphylactoid Shock Associated with Snakebite Envenoming in Portugal.

Although rare in Portugal, snakebite envenoming entails severe morbidity and mortality. We present the case of a 65-year-old woman bitten on her leg in a northern coastal region in Portugal, on a walk during the COVID-19 pandemic lockdown. Despite first looking for help at the nearest pharmacy, she developed anaphylactoid shock and was promptly driven to a tertiary hospital, where antivenom was administered in a timely manner under close monitoring. Prophylactic antibiotics were started and maintained based on elevated inflammatory markers and signs of wound inflammation. She evolved favorably, with rapid weaning of vasopressors and resolution of end-organ dysfunction. This case highlights the importance of prompt recognition and describes crucial steps in envenomation management in a country where snakebite is infrequent, but potentially fatal.

Don't Be a Stiff: A Review Article on the Management of Tetanus.

Vaccine-preventable diseases, such as tetanus, are oftentimes a thought of the past in countries that only see a handful of cases per year. In recent years, though, there has been more controversy around vaccinations and fewer individuals getting vaccinated. This movement has resulted in vaccine-preventable diseases resurfacing (e.g., measles). Tetanus is one of the diseases that health care providers should continue to be familiar with in regard to its clinical presentation and the treatments that are available to manage the corresponding signs and symptoms. Because tetanus is an acute, toxin-mediated illness that can be fatal, prevention and treatment are critical. This article briefly summarizes tetanus and the therapies considered to be first line in its management.

Clinical Decision Support Reduces Unnecessary Tetanus Vaccinations in the Emergency Department.

STUDY OBJECTIVE: Tetanus is the most common vaccination given in the emergency department; yet, administrations of tetanus vaccine boosters in the ED may not comply with the US Centers for Disease Control and Prevention's recommended vaccination schedule. We implemented a clinical decision support alert in the electronic health record that warned providers when ordering a tetanus vaccine if a prior one had been given within 10 years and studied its efficacy to reduce potentially unnecessary vaccines in the ED. METHODS: This was a retrospective, quasi-experimental, 1-group, pretest-posttest study in 3 hospital EDs in Boston, MA. We studied adult patients for whom tetanus vaccines were ordered despite a history of vaccination within the prior 10 years. We compared the number of potentially unnecessary tetanus vaccine administrations in a baseline phase (when the clinical decision support alert was not visible) versus an intervention phase. RESULTS: Of eligible patients, 22.1% (95% confidence interval [CI] 21.8% to 22.4%) had prior tetanus vaccines within 5 years, 12.8% (95% CI 12.5% to 13.0%) within 5 to 10 years, 3.8% (95% CI 3.6% to 3.9%) more than 10 years ago, and 61.3% (95% CI 60.9% to 61.7%) had no prior tetanus vaccination documentation. Of 60,983 encounters, 337 met the inclusion criteria. A tetanus vaccination was administered in 91% (95% CI 87% to 96%) of encounters in the baseline phase, compared to 55% (95% CI 47% to 62%) during the intervention. The absolute risk reduction was 36.7% (95% CI 28.0% to 45.4%), and the number of encounters needed to alert to avoid 1 potentially unnecessary tetanus vaccine (number needed to treat) was 2.7 (95% CI 2.2% to 3.6%). For patients with tetanus vaccines within the prior 5 years, the absolute risk reduction was 47.9% (95% CI 35.5 % to 60.3%) and the number needed to treat was 2.1 (95% CI 1.7% to 2.8%). CONCLUSION: A clinical decision support alert that warns ED clinicians that a patient may have an up-to-date tetanus vaccination status reduces potentially unnecessary vaccinations.

Plasma cell immunoglobulin heavy chain repertoire dynamics before and after tetanus booster vaccination.

Antibody sequence repertoire analysis of plasma cells (PC) isolated before and 1 week after a vaccine provides time-specific snapshots of the antibody response. Comparison of the immunoglobulin (Ig) sequences pre- and post-vaccination allows analysis of maturation over time and identification of antigen specific Ig. Here we compare the Ig heavy chain (Ig-H) repertoire of circulating PCs isolated from 109 peripheral blood mononuclear cells (PBMC) collected by apheresis 1 week after a tetanus toxoid vaccine booster with the Ig-H repertoire of PCs collected 2 and 11 weeks prior to the booster. A total of 21,060 unique Ig nucleotide sequences encoding 14,307 unique heavy chain complementarity determining region 3 (CDR-H3) amino acid sequences, also called clonotypes, were identified. Only 466 clonotypes (3.3%) were present at all 3 time points. In contrast, 90% of the 30 highest frequency CDR-H3 regions at +1w were also identified at another time point and 50% were present at all time points, suggesting the rapid expansion of a memory B cell population. The tetanus toxoid specificity of the CDR-H3 region with the 7th highest frequency at +1w was confirmed using immunoprecipitation and mass spectroscopy, and two public tetanus toxoid-specific CDR-H3 regions were also overrepresented at +1w. In summary, we have used the tetanus vaccine model system to demonstrate that bulk PC Ig repertoire analysis can identify PC populations that expand and mature following antigen exposure. The application of this approach before and after clinical infections should advance our understanding of clinical protection and facilitate vaccine design.

Evaluation of Immune and Vaccine Competence in Steroid-Sensitive Nephrotic Syndrome Pediatric Patients.

Idiopathic nephrotic syndrome is a childhood renal disease characterized by a damage of the glomerular filtration barrier leading to an intense leakage of proteins into the urine. This severe proteinuria causes a transient but strong reduction of serum IgG. Therefore, evaluation of vaccine competence by measuring serum levels of protective antibodies can be misleading in nephrotic syndrome, especially during the active phase of disease. To overcome this issue, in parallel to measuring serum antigen-specific IgG, we quantified by ELISPOT the number of antigen-specific memory B cells induced by previous immunization with tetanus and hepatitis B virus (HBV) in 11 steroid-sensitive nephrotic syndrome (SSNS) pediatric patients at onset before any immunosuppressive treatment (mean age 5.1±0.9 years). Five age-matched children with non-immunomediated nephro-urologic disorders were also enrolled as controls (mean age 6.9±2.3 years). Low total serum IgG levels (<520 mg/dl) were found in all the analyzed SSNS patients. In parallel, median levels of anti-tetanus and anti-HBV IgG were significantly reduced compared to controls [0.05 (0.03-0.16) vs. 0.45 (0.29-3.10) IU/ml and 0.0 (0.0-0.5) vs. 30.3 (5.5-400.8) mIU/ml, respectively; p = 0.02 for both], with serum IgG titers below protective threshold in 7/11 SSNS patients for tetanus and in 9/11 SSNS patients for HBV. In contrast, all SSNS patients had a competent B-cell response, showing an amount of total IgG-secreting B cells >1,000 counts/106 stimulated cells. The amount of anti-tetanus and anti-HBV IgG-secreting B cells was also comparable to that of controls (p = 0.24, p = 0.32, respectively), with a frequency of memory anti-tetanus and anti-HBV IgG secreting B cells >0.1% of total IgG secreting B cells. In conclusion, SSNS children at disease onset pre-immunosuppressive therapy showed a competent immune and vaccine response against tetanus and HBV, which can be correctly evaluated by quantification of antigen-specific memory B cells rather than by measuring serum IgG levels. This approach allows early identification of the impairment of immune and vaccine competence, which may derive from protracted use of different immunosuppressive drugs during disease course.

Rabies post-exposure prophylaxis in Germany - What are the challenges?

Rabies post-exposure prophylaxis (R-PEP) including wound treatment, vaccination and application of rabies immunoglobulin (RIG) is essential in preventing rabies mortality. Today, Germany is officially declared free from terrestrial rabies and rabies is only found in bats. However, physicians in A&E Departments are frequently consulted on the need for R-PEP. We retrospectively analysed patients who received R-PEP at the A&E Department of the University Hospital Bonn between 01.01.2013 and 30.06.2019. Demographic data, travel history, clinical and laboratory findings, previous rabies vaccinations and R-PEP vaccination regimen were recorded. During the study period, 90 patients received R-PEP at the University Hospital Bonn, in 10 cases without indication for R-PEP. Altogether, we found deviations from R-PEP guidelines in 51% (n = 41/80). Infiltration of RIG was missed in 12 patients and incorrectly administrated in 24 patients. Furthermore, vaccination scheme was incorrect in 11 patients. Correct wound washing and documentation of tetanus status was missing in 14% and 63% of patients, respectively. Despite rabies elimination in Germany patients frequently seek advice for R-PEP, the majority returning from foreign travel. Our data show that there is a high need for education on indication for R-PEP before and after travel and for implementation of precise R-PEP guidelines in daily clinical practice.

Tetanus and tetanus neurotoxin: From peripheral uptake to central nervous tissue targets.

Tetanus is a deadly but preventable disease caused by a protein neurotoxin produced by Clostridium tetani. Spores of C. tetani may contaminate a necrotic wound and germinate into a vegetative bacterium that releases a toxin, termed tetanus neurotoxin (TeNT). TeNT enters the general circulation, binds to peripheral motor neurons and sensory neurons, and is transported retroaxonally to the spinal cord. It then enters inhibitory interneurons and blocks the release of glycine or GABA causing a spastic paralysis. This review attempts to correlate the metalloprotease activity of TeNT and its trafficking and localization into the vertebrate body to the nature and sequence of appearance of the symptoms of tetanus.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) vs. a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine in meningococcal vaccine-naïve and meningococcal C conjugate vaccine-primed toddlers: a phase III randomised study.

Vaccination remains the best strategy to reduce invasive meningococcal disease. This study evaluated an investigational tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT) vs. a licensed tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MCV4-TT) (NCT02955797). Healthy toddlers aged 12-23 months were included if they were either meningococcal vaccine-naïve or MenC conjugate (MCC) vaccine-primed (≥1 dose of MCC prior to 12 months of age). Vaccine-naïve participants were randomised 1:1 to either MenACYW-TT (n = 306) or MCV4-TT (n = 306). MCC-primed participants were randomised 2:1 to MenACYW-TT (n = 203) or MCV4-TT (n = 103). Antibody titres against each of the four meningococcal serogroups were measured by serum bactericidal antibody assay using the human complement. The co-primary objectives of this study were to demonstrate the non-inferiority of MenACYW-TT to MCV4-TT in terms of seroprotection (titres ≥1:8) at Day 30 in both vaccine-naïve and all participants (vaccine-naïve and MCC-primed groups pooled). The immune response for all four serogroups to MenACYW-TT was non-inferior to MCV4-TT in vaccine-naïve participants (seroprotection: range 83.6-99.3% and 81.4-91.6%, respectively) and all participants (seroprotection: range 83.6-99.3% and 81.4-98.0%, respectively). The safety profiles of both vaccines were comparable. MenACYW-TT was well-tolerated and demonstrated non-inferior immunogenicity when administered to MCC vaccine-primed and vaccine-naïve toddlers.

Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen.

B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendritic cells and infecting follicular helper (TFH) and regulatory (TFR) T-cells in germinal centers (GCs). Thus, follicular and GC B-cells are persistently exposed to viral antigens. Despite recent development of potent HIV immunogens, numerous questions are still open regarding GC reaction during early HIV/SIV infection. Here, we dissect the dynamics of B- and T-cells in GCs of macaques acutely infected by SIV (Group SIV+) or vaccinated with Tetanus Toxoid (Group TT), a T-dependent model antigen. Systemic inflammation and mobilization of antigen-presenting cells in inguinal lymph nodes and spleen are lower in Group TT than in Group SIV+. Despite spleen GC reaction of higher magnitude in Group SIV+, the development of protective immunity could be limited by abnormal helper functions of TFH massively polarized into TFH1-like cells, by inflammation-induced recruitment of fCD8 (either regulatory or cytotoxic) and by low numbers of TFR limiting TFH/TFR competition for high affinity B-cells. Increased GC B-cells apoptosis and accumulation of CD21lo memory B-cells, unable to further participate to GC reaction, likely contribute to eliminate SIV-specific B-cells and decrease antibody affinity maturation. Surprisingly, functional GCs and potent TT-specific antibodies develop despite low levels of CXCL13.

A case of recurrent sterile abscesses following tetanus-diphtheria vaccination treated with corticosteroids.

BACKGROUND: Vaccinations have been widely used worldwide since their invention to prevent various diseases, but they can also have some adverse effects ranging from mild local reactions to serious side effects. These adverse effects are generally self-limited and resolve within a short time without any treatment. While a sterile abscess following vaccination is a rare condition in adults, many cases have been reported regarding children in the literature. Here, we report a case of recurrent sterile abscesses, which occurred after a Td vaccination, treated with corticosteroids. CASE PRESENTATION: A 22-year old woman was admitted to our department with a complaint of swelling at the site of the vaccination. On physical examination, this mass was about 6 × 6 cm in size and fluctuating, but there were no pain complaints and no redness present. She had received her Td vaccination 3 weeks ago and the swelling had started at the site of the injection 4 days following this immunization. Oral amoxicillin/clavulanic acid and local antibiotic cream were administered for 10 days. The laboratory values were unremarkable. Despite the administration of antibiotics, the swelling did not regress, and on the contrary, continued to increase in size. On ultrasound, two interconnected abscesses were observed in the subcutaneous area, and did not involve the muscle tissue. Later, the abscesses were completely drained, and the samples were cultured. The current antibiotics were continued. The gram staining of the samples revealed abundant leukocytes but no microorganisms. The solid and liquid cultures of the materials remained negative. Despite the administration of multiple drainages and antibiotics, the mass recurred. Finally, the patient was considered to have a sterile abscess due to Td immunization. The antimicrobials were stopped. Local and oral corticosteroids were initiated. The swelling regressed significantly, and the treatments continued for 7 days. The patient has been doing well and has had no recurrence for over a year. CONCLUSIONS: Corticosteroids appeared to improve the patient and therefore we suggest that the efficacy and route of administration of steroids in this situation should be explored further.

Generalized, non-neonatial tetanus is a highly fatal disease in Afghanistan: A case series study.

OBJECTIVES: To describe the clinical features and outcomes of a case series of adult tetanus and illustrate inadequacies in confronting this preventable disease. DESIGN AND METHODS: This study retrospectively evaluated 24 relatively severe, confirmed cases of tetanus, diagnosed between March 2017 and December 2018, in Kabul Antani Hospital, Afghanistan. RESULTS: Regarding the source of the infection: 18 patients (75%) had a history of injuries, 1 had a history of a dog bite and 1 was an intravenous drug user; 4 patients had no external injuries or wounds. Dysphagia was the main clinical manifestation for which patients sought medical treatment (50%). Of the 12 patients who died, 7 presented with confusion and seizure, 1 with acute kidney injury, and 2 with pneumonia. CONCLUSIONS: Mortality due to tetanus is high in Afghanistan (Case Fatality Rate (CFR) 50%)), suggesting an urgent need for vaccination policy and programs, post-exposure protocols, and facilities equipped for the treatment of adult tetanus. The Ministry of Public Health of Afghanistan should seek to improve the accessibility, distribution and recording of tetanus immunization through vaccination.