Tetanus management in a high-resource emergency department: A case report.

Any patient presenting with trismus should have tetanus considered as a differential diagnosis. Early recognition, timely treatment and supportive care can improve patient outcomes. Treatment with tetanus immunoglobulin to neutralize the toxin, antimicrobials to treat the infection and sedation in the intensive care unit are key therapeutic options.

Neonatal Tetanus Still Exists: A Case Report and Review of Literature.

Neonatal tetanus (NT) remains the leading cause of death in underdeveloped countries, although it is relatively rare in developed countries. Umbilical stump sepsis in newborns born to unvaccinated mothers is a major risk factor for NT. The World Health Organization describes NT as an infection that affects infants who lose the ability to suck between 3 and 28 days of age, becoming rigid and having spasms. Limited resources in underdeveloped countries have made the management of NT difficult. In this report, we describe a fatal case of NT in a newborn born to a mother who had not received any tetanus toxoid-containing vaccine. This study aims to make neonatal health professionals aware of the symptoms of NT so that they can diagnose it early and provide the appropriate care to save lives, and stress the importance of tetanus vaccination and maintaining hygienic conditions throughout pregnancy and childbirth to prevent this disease.

The tyrosine phosphatases LAR and PTPRδ act as receptors of the nidogen-tetanus toxin complex.

Tetanus neurotoxin (TeNT) causes spastic paralysis by inhibiting neurotransmission in spinal inhibitory interneurons. TeNT binds to the neuromuscular junction, leading to its internalisation into motor neurons and subsequent transcytosis into interneurons. While the extracellular matrix proteins nidogens are essential for TeNT binding, the molecular composition of its receptor complex remains unclear. Here, we show that the receptor-type protein tyrosine phosphatases LAR and PTPRδ interact with the nidogen-TeNT complex, enabling its neuronal uptake. Binding of LAR and PTPRδ to the toxin complex is mediated by their immunoglobulin and fibronectin III domains, which we harnessed to inhibit TeNT entry into motor neurons and protect mice from TeNT-induced paralysis. This function of LAR is independent of its role in regulating TrkB receptor activity, which augments axonal transport of TeNT. These findings reveal a multi-subunit receptor complex for TeNT and demonstrate a novel trafficking route for extracellular matrix proteins. Our study offers potential new avenues for developing therapeutics to prevent tetanus and dissecting the mechanisms controlling the targeting of physiological ligands to long-distance axonal transport in the nervous system.

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges.

Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates.

Characterization of neutralizing chimeric heavy-chain antibodies against tetanus toxin.

Tetanus toxin (TeNT) is one of the most toxic proteins. Neutralizing antibodies against TeNT are effective in prevention and treatment. In this study, 14 anti-tetanus nanobodies were obtained from a phage display nanobody library by immunizing a camel with the C-terminal receptor-binding domain of TeNT (TeNT-Hc) as the antigen. After fusion with the human Fc fragment, 11 chimeric heavy-chain antibodies demonstrated nanomolar binding toward TeNT-Hc. The results of toxin neutralization experiments showed that T83-7, T83-8, and T83-13 completely protected mice against 20 × the median lethal dose (LD50) at a low concentration. The neutralizing potency of T83-7, T83-8, and T83-13 against TeNT is 0.4 IU/mg, 0.4 IU/mg and 0.2 IU/mg, respectively. In the prophylactic setting, we found that 5 mg/kg of T83-13 provided the mice with full protection from tetanus, even when they were injected 14 days before exposure to 20 × LD50 TeNT. T83-7 and T83-8 were less effective, being fully protective only when challenged 7 or 10 days before exposure, respectively. In the therapeutic setting, 12 h after exposure to TeNT, 1 ~ 5 mg/kg of T83-7, and T83-8 could provide complete protection for mice against 5 × LD50 TeNT, while 1 mg/kg T83-13 could provide complete protection 24 h after exposure to 5 × LD50 TeNT. Our results suggested that these antibodies represent prophylactic and therapeutic activities against TeNT in a mouse model. The T83-7, T83-8, and T83-13 could form the basis for the subsequent development of drugs to treat TeNT toxicity.

Antibody levels following vaccination of beef calves with a tetanus toxoid.

Tetanus is a preventable, yet often fatal, disease affecting many species, including beef cattle. Vaccination for tetanus is recommended for calves at high risk of disease, but typical beef cattle management practices often make adherence to vaccine manufacturers' guidance for a second (booster) dose of vaccine difficult. This study examined the antibody response following a single dose of tetanus toxoid, as well as following booster vaccination at various intervals. Anti-tetanus IgG antibodies were detectable 25 days (D25) after a single dose, and rose following booster at either D25 D109 after initial vaccination. Antibody levels then declined numerically from D109 to D179 for calves boostered at D25 but rose on D179 for those receiving a second dose on D109. The relatively rapid response in IgG production, even in the absence of a booster vaccine, may suggest value in vaccinating calves for tetanus at time of greatest risk, even if a booster cannot be administered. The study also provides support for priming of the immune response lasting at least until D109 after primary immunization.

Comparison of the penile microbiome in infant male circumcision: Mogen clamp versus Shangring.

BACKGROUND: This study aimed to characterise the infant penile (coronal sulcus) microbiome and the effects of early infant male circumcision (EIMC), following a standard surgical method (Mogen Clamp) and a non-surgical alternative (ShangRing). METHODS: We collected coronal sulcus swabs at baseline and on days 7 and 14 post-circumcision from infants assigned to receive EIMC by Mogen Clamp (n = 15) or ShangRing (n = 15), in a randomised trial in Rakai and Kakuuto, Uganda. We used 16S rRNA gene-based sequencing and broad-coverage qPCR to characterise the infant penile microbiome and assess the effects of EIMC in both study arms. FINDINGS: Prior to EIMC, the infant penile microbiome had a mixture of facultative and strict anaerobes. In both study arms, EIMC caused penile microbiome proportional abundance changes characterised by decreases in penile anaerobes [ShangRing Prevotella: -15.0%, (SD = 19.1); Mogen clamp Prevotella: -3.6% (11.2); ShangRing Veillonella: -11.3% (17.2); Mogen clamp Veillonella: -2.6% (11.8)] and increases in skin-associated facultative anaerobes [ShangRing Corynebacterium: 24.9%, (22.4); Mogen clamp Corynebacterium: 4.7% (21.3); ShangRing Staphylococcus: 21.1% (20.5); Mogen clamp Staphylococcus: 18.1% (20.1)]. Clostridium tetani was not detected during the study. INTERPRETATION: Mogen Clamp and ShangRing EIMC both changed the composition of the infant penile microbiome by reducing the proportional abundances of anaerobes and uropathogens, which is consistent with medical male circumcision findings in adults. C. tetani was not increased by either EIMC method. FUNDING: Bill and Melinda Gates Foundation.

A Dual Strategy-In Vitro and In Silico-To Evaluate Human Antitetanus mAbs Addressing Their Potential Protective Action on TeNT Endocytosis in Primary Rat Neuronal Cells.

Tetanus disease, caused by C. tetani, starts with wounds or mucous layer contact. Prevented by vaccination, the lack of booster shots throughout life requires prophylactic treatment in case of accidents. The incidence of tetanus is high in underdeveloped countries, requiring the administration of antitetanus antibodies, usually derived from immunized horses or humans. Heterologous sera represent risks such as serum sickness. Human sera can carry unknown viruses. In the search for human monoclonal antibodies (mAbs) against TeNT (Tetanus Neurotoxin), we previously identified a panel of mAbs derived from B-cell sorting, selecting two nonrelated ones that binded to the C-terminal domain of TeNT (HCR/T), inhibiting its interaction with the cellular receptor ganglioside GT1b. Here, we present the results of cellular assays and molecular docking tools. TeNT internalization in neurons is prevented by more than 50% in neonatal rat spinal cord cells, determined by quantitative analysis of immunofluorescence punctate staining of Alexa Fluor 647 conjugated to TeNT. We also confirmed the mediator role of the Synaptic Vesicle Glycoprotein II (SV2) in TeNT endocytosis. The molecular docking assays to predict potential TeNT epitopes showed the binding of both antibodies to the HCR/T domain. A higher incidence was found between N1153 and W1297 when evaluating candidate residues for conformational epitope.

Tetanus- a case report highlighting the challenges in diagnosis and treatment.

Tetanus has become an increasingly rare infectious disease due to the development of successful vaccination programs in the mid-20th century. In resource-rich countries, mainly unvaccinated or partly vaccinated risk groups are affected, whereas tetanus still remains prevalent in resource-limited countries. The decreasing incidence in developed countries has hindered clinical trials evaluating the best treatment modalities for tetanus infections. Current guidelines are based on a small number of studies and case reports. So far, these studies have shown potential benefits of treating tetanus infections with benzodiazepines, magnesium sulfate and baclofen. Additionally, several treatments have been shown to be useful in stabilizing and supporting patients with tetanus. However, each treatment modality has limitations, from negative side effects to logistical challenges, especially in developing countries. Therefore, further knowledge is required to evaluate the best use of each treatment and to further optimize patient care. This knowledge can contribute to the reduction of the burden of disease in countries where tetanus remains prevalent and where resources are limited, though vaccination is the most effective method to achieve this. This case report describes the treatment of a Dutch patient with tetanus infection and illustrates the role of benzodiazepines as well as other key aspects of treating patients with tetanus.

Single immunization of non-adjuvanted recombinant TTFC-mi3 nanoparticle vaccine elicited a rapid and potent protective immunity against tetanus.

The conventional inactivated tetanus toxin plays an instrumental role in preventing tetanus. Nevertheless, the challenges associated with its production process, the potential for adverse reactions, and reduced effectiveness in vulnerable populations such as neonates and the elderly rise the need for a novel tetanus toxin vaccine. Recombinant subunit vaccine offer a viable solution, and the tetanus toxin fragment C (TTFC) is emerging as a promising candidate. In this study, through spontaneous isopeptide bond formation we conjugated the recombinant TTFC to self-assembled mi3 nanoparticle, which derived from an optimized KDPG aldolase, and generated the TTFC-mi3 protein nanoparticle vaccine. We found that TTFC-mi3 is stable, uniform spherical nanoparticles. Comparing with the free TTFC alone, TTFC-mi3 enhances the uptake and subsequent activation of dendric cells (DCs). In addition, a single dose of adjuvant-free TTFC-mi3 elicited a more rapid and potent protective immunity in mice. Moreover, TTFC-mi3 is of favorable safety in vitro and in vivo. Our findings indicate that TTFC-mi3 is a rapid-response, non-aluminum-adjuvanted vaccine against tetanus.

Spike-induced cytoarchitectonic changes in epileptic human cortex are reduced via MAP2K inhibition.

Interictal spikes are electroencephalographic discharges that occur at or near brain regions that produce epileptic seizures. While their role in generating seizures is not well understood, spikes have profound effects on cognition and behaviour, depending on where and when they occur. We previously demonstrated that spiking areas of human neocortex show sustained MAPK activation in superficial cortical Layers I-III and are associated with microlesions in deeper cortical areas characterized by reduced neuronal nuclear protein staining and increased microglial infiltration. Based on these findings, we chose to investigate additional neuronal populations within microlesions, specifically inhibitory interneurons. Additionally, we hypothesized that spiking would be sufficient to induce similar cytoarchitectonic changes within the rat cortex and that inhibition of MAPK signalling, using a MAP2K inhibitor, would not only inhibit spike formation but also reduce these cytoarchitectonic changes and improve behavioural outcomes. To test these hypotheses, we analysed tissue samples from 16 patients with intractable epilepsy who required cortical resections. We also utilized a tetanus toxin-induced animal model of interictal spiking, designed to produce spikes without seizures in male Sprague-Dawley rats. Rats were fitted with epidural electrodes, to permit EEG recording for the duration of the study, and automated algorithms were implemented to quantify spikes. After 6 months, animals were sacrificed to assess the effects of chronic spiking on cortical cytoarchitecture. Here, we show that microlesions may promote excitability due to a significant reduction of inhibitory neurons that could be responsible for promoting interictal spikes in superficial layers. Similarly, we found that the induction of epileptic spikes in the rat model produced analogous changes, including reduced neuronal nuclear protein, calbindin and parvalbumin-positive neurons and increased microglia, suggesting that spikes are sufficient for inducing these cytoarchitectonic changes in humans. Finally, we implicated MAPK signalling as a driving force producing these pathological changes. Using CI-1040 to inhibit MAP2K, both acutely and after spikes developed, resulting in fewer interictal spikes, reduced microglial activation and less inhibitory neuron loss. Treated animals had significantly fewer high-amplitude, short-duration spikes, which correlated with improved spatial memory performance on the Barnes maze. Together, our results provide evidence for a cytoarchitectonic pathogenesis underlying epileptic cortex, which can be ameliorated through both early and delayed MAP2K inhibition. These findings highlight the potential role for CI-1040 as a pharmacological treatment that could prevent the development of epileptic activity and reduce cognitive impairment in both patients with epilepsy and those with non-epileptic spike-associated neurobehavioural disorders.

Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines.

Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.

Seroprotection against tetanus in the Italian general population.

BACKGROUND: Tetanus is a non-communicable disease, preventable with vaccination. Despite the implemented vaccination strategy, a certain number of tetanus cases per year continue to occur. The aim of the study was to evaluate the seroprevalence of anti-tetanus antibodies in the Italian population by age, sex and geographical area. METHODS: To determine the level of tetanus-specific antibodies, an immunoenzymatic assay was used. RESULTS: A total of 3,821 serum samples were collected in the years 2019-20 from healthy subjects aged 6-90 years residing in 13 Italian regions. Overall, 85 % of the tested subjects resulted positive. The rate of subjects protected against tetanus showed a gradual decrease from the younger age groups to the older ones (6-12 years: 93.6 %, 13-24 years: 91.8 %, 25-39 years: 91.0 %, 40-64 years: 78.2 %, ≥ 65 years: 45.3 %); this is particularly evident in the Southern regions and Islands. Moreover, the prevalence of subjects with low protection (<0.1 IU/ml) was significantly higher in the ≥ 65 age group (10.3 %). Males and females' prevalence showed a significant difference only in the oldest age group (M: 60.8 %, F: 30.4 %). In general, a higher prevalence was observed for Northern (90.8 %) and Central regions (87.3 %) than Southern regions and Islands (80.0 %). CONCLUSION: These data, compared with epidemiological ones which showed a high number of cases in the elderly, confirmed that the population with lower protection has a greater risk of contracting the disease, demonstrating the need for adequate immunization through both primary vaccination and boosters for all ages and both sexes, in order to provide lifelong protection.

Management Strategies for Common Animal Bites in Pediatrics: A Narrative Review on the Latest Progress.

Animal bites are a common reason for children to visit primary care and emergency departments. Dog bites are the most prevalent, followed by cat bites at 20-30%. Other animals such as bats, monkeys, snakes, and rats collectively contribute less than 1% of cases. Hospitalization is necessary in only 4% of animal bite incidents. The main aim of this narrative review is to summarize the main protocols currently followed in pediatrics in cases involving the most common bites from different animal species. Analysis of the literature showed that the management of common animal bites in children presents a multifaceted challenge requiring a comprehensive understanding of the epidemiology, clinical presentation, and treatment modalities associated with each specific species. Effective wound management is paramount in reducing the risk of infection and promoting optimal healing outcomes. Additionally, tetanus vaccination status should be assessed and updated as necessary, and prophylactic antibiotics may be indicated in certain cases to prevent secondary infections. Furthermore, the role of rabies prophylaxis cannot be overstated, particularly in regions where rabies is endemic or following bites from high-risk animals. In addition to medical management, psychosocial support for both the child and their caregivers is integral to the overall care continuum. Future studies exploring the efficacy of novel treatment modalities, such as topical antimicrobial agents or advanced wound dressings, may offer new insights into optimizing wound healing and reducing the risk of complications.

Childhood vaccination trends during 2019 to 2022 in Tanzania and the impact of the COVID-19 pandemic.

The COVID-19 pandemic has significantly disrupted healthcare systems at all levels globally, notably affecting routine healthcare services, such as childhood vaccination. This study examined the impact of these disruptions on routine childhood vaccination programmes in Tanzania. We conducted a longitudinal study over four years in five Tanzanian regions: Mwanza, Dar es Salaam, Mtwara, Arusha, and Dodoma. This study analyzed the trends in the use of six essential vaccines: Bacille Calmette-Guérin (BCG), bivalent Oral Polio Vaccine (bOPV), Diphtheria Tetanus Pertussis, Hepatitis-B and Hib (DTP-HepB-Hib), measles-rubella (MR), Pneumococcal Conjugate Vaccine (PCV), and Rota vaccines. We evaluated annual and monthly vaccination trends using time-series and regression analyses. Predictive modeling was performed using an autoregressive integrated moving average (ARIMA) model. A total of 32,602,734 vaccination events were recorded across the regions from 2019 to 2022. Despite declining vaccination rates in 2020, there was a notable rebound in 2021, indicating the resilience of Tanzania's immunization program. The analysis also highlighted regional differences in vaccination rates when standardized per 1000 people. Seasonal fluctuations were observed in monthly vaccination rates, with BCG showing the most stable trend. Predictive modeling of BCG indicated stable and increasing vaccination coverage by 2023. These findings underscore the robustness of Tanzania's childhood immunization infrastructure in overcoming the challenges posed by the COVID-19 pandemic, as indicated by the strong recovery of vaccination rates post-2020. We provide valuable insights into the dynamics of vaccination during a global health crisis and highlight the importance of sustained immunization efforts to maintain public health.

Management of severe tetanus in Afghanistan: lessons from the field.

INTRODUCTION: Tetanus is a rather rare disease in the Western countries thanks to widespread vaccination programs and the availability of prophylactics for patients with tetanus-prone injuries. The few cases that do occur are promptly managed in intensive care units (ICUs). However, tetanus is not so rare in developing countries, where access to a suitable level of care is limited. An unstable political situation can be a significant factor influencing patient outcomes. CASE REPORT: A ten-year-old boy presented at the EMERGENCY hospital in Lashkar-Gah (southern Afghanistan) with generalized tetanus after falling off his bicycle. In response to his rapidly deteriorating general conditions - respiratory failure and hemodynamic instability - the patient was urgently transferred by ambulance to the ICU at the EMERGENCY hospital in Kabul (northern Afghanistan). The patient was placed on mechanical ventilation while receiving intravenous sedation and pharmacologic paralysis for almost four weeks. A prolonged infusion of a high dose of magnesium sulphate and labetalol was also given to counteract autonomic dysfunction. Multiple complications related to the long stay in the ICU were observed and promptly addressed. During this period, several mass casualties took place in Kabul, which stretched the hospital's surge capacity. The patient was discharged and accompanied back to Lashkar-Gah three months after his admission to the hospital. CONCLUSION: This case report shows some of the many difficulties that arise when managing a patient with severe tetanus in a war zone where resources are limited.

The Impact of the Coronavirus Pandemic on Vaccination Coverage in Latin America and the Caribbean.

BACKGROUND: Routine vaccination coverage in Latin America and the Caribbean declined prior to and during the coronavirus pandemic. We assessed the pandemic's impact on national coverage levels and analyzed whether financial and inequality indicators, immunization policies, and pandemic policies were associated with changes in national and regional coverage levels. METHODOLOGY: We compared first- and third-dose coverage of diphtheria-pertussis-tetanus-containing vaccine (DTPcv) with predicted coverages using time series forecast modeling for 39 LAC countries and territories. Data were from the PAHO/WHO/UNICEF Joint Reporting Form. A secondary analysis of factors hypothesized to affect coverages during the pandemic was also performed. RESULTS: In total, 31 of 39 countries and territories (79%) had greater-than-predicted declines in DTPcv1 and DTPcv3 coverage during the pandemic, with 9 and 12 of these, respectively, falling outside the 95% confidence interval. Within-country income inequality (i.e., Gini coefficient) was associated with significant declines in DTPcv1 coverage, and cross-country income inequality was associated with declines in DTPcv1 and DTPcv3 coverages. Observed absolute and relative inequality gaps in DTPcv1 and DTPcv3 coverage between extreme country quintiles of income inequality (i.e., Q1 vs. Q5) were accentuated in 2021, as compared with the 2019 observed and 2021 predicted values. We also observed a trend between school closures and greater-than-predicted declines in DTPcv3 coverage that approached statistical significance (p = 0.06). CONCLUSION: The pandemic exposed vaccination inequities in LAC and significantly impacted coverage levels in many countries. New strategies are needed to reattain high coverage levels.

Safety assessments of recombinant DTaP vaccines developed in South Korea.

Purpose: Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines. Materials and Methods: The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. Results: HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. Conclusion: There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.

Number of tetanus toxoid injections before birth and associated factors among pregnant women in low and middle income countries: Negative binomial poisson regression.

BACKGROUND: In low- and middle-income countries where vaccination rates are low, tetanus is still an important threat to public health. Although maternal and neonatal tetanus remains a major global health concern, its magnitude and determinates are not well studied. Therefore, this study aimed to assess the number of tetanus toxoid injections and associated factors among pregnant women in low- and middle-income countries. METHODS: Data from the most recent Demographic and Health Surveys, which covered 60 low- and middle-income countries from 2010 to 2022, was used for secondary data analysis. The study included a total of 118,704 pregnant women. A statistical software package, STATA 14, was used to analyze the data. A negative binomial regression of a cross-sectional study was carried out. Factors associated with the number of tetanus vaccinations were declared significant at a p-value of < 0.05. The incidence rate ratio and confidence interval were used to interpret the results. A model with the smallest Akaike Information Criterion and Bayesian Information Criterion values and the highest log likelihood was considered the best-fit model for this study. RESULTS: In low- and middle-income countries, 26.0% of pregnant women took at least two doses of the tetanus toxoid vaccine. Factors such as maternal education, primary (IRR = 1.22, 95% CI: 1.17, 1.26), secondary (IRR = 1.19, 95% CI: 1.15, 1.23), higher (IRR = 1.16, 95% CI: 1.12, 1.20), employment (IRR = 1.11, 95% CI: 1.09, 1.13), 1-3 ANC visits (IRR = 2.49, 95% CI: 2.41, 2.57), ≥4 visits (IRR = 2.94, 95% CI: 2.84, 3.03), wealth index (IRR = 1.06; 95% CI: 11.04, 1.08), ≥birth order (IRR = 1.04, 95% CI: 1.02, 1.27), distance to health facility (IRR = 1.02, 95% CI: 1.00, 1.03), and health insurance coverage (IRR = 1.08; 95% CI: 1.06, 1.10) had a significant association with the number of tetanus vaccinations among pregnant women. CONCLUSIONS AND RECOMMENDATIONS: This study concludes that the number of tetanus toxoid vaccinations among pregnant women in low- and middle-income countries is low. In the negative binomial model, the frequency of tetanus vaccinations has a significant association with maternal employment, educational status, wealth index, antenatal care visits, birth order, distance from a health facility, and health insurance. Therefore, the ministries of health in low and middle-income countries should give attention to those women who had no antenatal care visits and women from poor wealth quantiles while designing policies and strategies.

Evidence for Immunity against Tetanus, Diphtheria, and Pertussis through Natural Infection or Vaccination in Adult Solid Organ Transplant Recipients: A Systematic Review.

(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT) recipients, either through natural infection or vaccination. (2) Methods: This systematic review was conducted per PRISMA guidelines. We assessed the risk of bias using the Cochrane RoB 2 and ROBINS-I and summarized the findings narratively due to the heterogeneity of the studies. (3) Results: Of the 315 screened articles, 11 were included. Tetanus immunity varied between 55% and 86%, diphtheria immunity from 23% to 75%, and pertussis immunity was between 46% and 82%. Post-vaccination immunity showed variation across the studies, with some indicating reductions and others no change, with antibody responses influenced by transplanted organs, gender, age, and immunosuppressive regimens. The single randomized study exhibited a low risk of bias, while of the ten non-randomized studies, six showed moderate and four serious risks of bias, necessitating cautious interpretation of results. (4) Conclusions: SOT recipients exhibit considerable immunity against tetanus and diphtheria at transplantation, but this immunity decreases over time. Although vaccination can enhance this immunity, the response may be suboptimal, and the increased antibody levels may not persist, underscoring the need for tailored vaccination strategies in this vulnerable population.