Tetanus Toxoid Research Articles

IJCM_47A: A hospital based study to assess the utilization of ANC services among married women of reproductive age group in the sub District Hospital, West Delhi, India

Background: Antenatal Services provided by government and its timely utilization are vital for the health outcomes of the mother as well as of child. Objective: To study the current pattern of utilization of antenatal services. To assess the factors influencing utilization of antenatal services. Methodology: A facility based cross-sectional descriptive study was conducted at immunization clinic of sub district hospital from Aug 2022 to Oct 2022 among 230 randomly selected mothers whose child was less than one year. A pre-test self-administrative questionnaire was applied to collect the data and complied. Appropriate statistics was be applied to achieve desired results. Results: Mean age of the participants were 27.88 ±4.6 years. More than half of the participants were identified as Hindu by religion. Most of them were classified under a lower socio-economic status. All participants were literate. Out of the total, 63 (27.4%) were primigravida, and rest were multigravida. While three-fourths of the women registered their pregnancies early, 74.3% attended at least four antenatal care (ANC) visits. Moreover, 87.4% received two doses or one booster dose of Td vaccination, and 83.9% took a minimum of 100 Iron Folic Acid tablets. However, only 66.5% of the participants reported having fully utilized Anti natal care services. Conclusion: Females of young age with primary education and those belonging to the Muslim religion were found to have inadequate utilization of complete antenatal care (ANC), despite the presence of government-funded primary care services.

Safety and immunogenicity of a single dose of Tdap compared to Td in pregnant women in Mali and 3 its effect on infant immune responses: a single-centre, randomised, double-blind, active-controlled phase 2 study

While maternal pertussis vaccination is a strategy to reduce infant morbidity, safety and immunogenicity data are limited in sub-Saharan Africa. We aimed to evaluate the safety of a single dose of tetanus, diphtheria and acellular pertussis vaccine (Tdap) vaccine compared to tetanus and diphtheria vaccine (Td) vaccine in pregnant women in Bamako, Mali and to assess the pertussis toxin (PT) antibody response at birth. In this phase 2, single-centre, randomised, double-blind, active-controlled study, from 23 January 2019 to 10 July 2019, healthy 18-39 year old women in the second trimester of a singleton pregnancy were randomised 2:1 to receive Tdap or Td. Blood was tested for serum immunoglobulin G (IgG) against PT and other vaccine antigens using a qualified Meso Scale Discovery multiplex immunoassay. The co-primary objectives evaluated safety and birth anti-PT levels. Infant immune responses to whole-cell pertussis vaccine (DTwP) were assessed. Statistical analysis was descriptive. This trial is registered with clinicaltrials.gov, NCT03589768. 133 women received Tdap and 67 received Td, with 126 and 66 livebirths, respectively. In the Tdap group, 22 serious adverse events (SAEs) including one maternal death occurred in 20 participants (15·0%), with 10 SAEs in 10 participants (14·9%) in the Td group. Among infants, 18 events occurred among 13 participants (10.3%) and 8 SAEs in 6 participants (9.1%), including three and two infant deaths, occurred in Tdap and Td groups, respectively. None were related to study vaccines. Anti-PT geometric mean concentration (GMC) at birth in the Tdap group was higher than in the Td group (55.4 [46.2-66.6] IU/ml vs 7.9 [5.4-11.5] IU/ml). One month after the third dose of DTwP, the GMC in infants born to mothers in the Tdap group were lower compared to the Td group (20.2 [13.7-29.9] IU/ml vs 77.2 [32.2-184.8] IU/ml). By 6 months of age, the anti- PT GMCs were 17.3 [12.8-23.4] IU/ml and 67.1 [35.5-126.7] IU/ml in Tdap and Td groups, respectively. At birth, anti-tetanus toxin (TT) GMCs were higher in infants in the Td vs Tdap group (5.9 [5.0-7.0] IU/ml vs 4.1 [3.5-4.8] IU/ml). Anti-diphtheria toxin GMCs were similar in both groups. Tdap administered to pregnant women in Mali is safe and well-tolerated. Infants of mothers who received Tdap were born with high PT and protective anti-TT antibody levels. By six months of age, after primary vaccination, the PT levels were lower in the Tdap group compared to the Td group. The blunted immune responses to primary DTwP vaccination in the Tdap infant group warrant further study. This project was funded by National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under contract numbers 75N93021C00012 (The Emmes Company), and HHSN27220130000221 (University of Maryland, Baltimore). Dr. Susana Portillo was supported by NIH award no. T32AI007524. NIAID, NIH provided Tdap vaccine (BOOSTRIX).

Surveillance for adverse events following immunization with DTaP-containing combination vaccines in Linping, China, 2019-2022.

The DTaP-Hib and DTaP-IPV/Hib combination vaccine can be used as a substitute for the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). We aimed to evaluate the safety of multi-component vaccines containing DTaP by analyzing the reporting rates and characteristics of adverse events following immunization (AEFIs) in Linping District during the years 2019 to 2022. We obtained data of AEFI and vaccination from the National AEFI Surveillance System of China and Zhejiang Municipal Immunization Information Management System, respectively, during 2019-2022 for a descriptive, epidemiological analysis. The total number of AEFI reported following vaccinations with DTaP-containing combination vaccines was 802 in Linping District from 2019 to 2022. The overall reporting rates of AEFIs following DTaP, DTaP-Hib, and DTaP-IPV/Hib vaccinations were 445.72 (537 cases), 536.29 (45 cases), and 306.13 (220 cases) per 100,000 doses in Linping District from 2019 to 2022, respectively. Only one case of a serious AEFI following DTaP vaccination, with a reporting rate of 0.83 per 100,000 doses. The composition ratio of vaccine product-related reactions for DTaP, DTaP-Hib, and DTaP-IPV/Hib were 99.81, 97.78, and 100.00%, respectively. The composition ratio of coincidental events for DTaP and DTaP-Hib were 0.19 and 2.22%, respectively. The reporting rates of total AEFIs for DTaP-IPV/Hib were lower than for DTaP. The reporting rate of local induration for DTaP-Hib was lower than for DTaP, and the reporting rates of local redness & swelling and local induration for DTaP-IPV/Hib were both lower than for DTaP. DTaP-IPV/Hib had a higher proportion of AEFIs in first quarter compared to DTaP. The reporting rate after the second dose of DTaP-Hib was higher than that of DTaP, and the reporting rates of AEFIs after the first dose and third dose of DTaP-IPV/Hib were lower than DTaP. The reported AEFIs to multi-component vaccines containing DTaP components during 2019-2022 in Linping District were mainly mild vaccine reactions. DTaP-containing combination vaccines demonstrated a good safety profile.

Abstract 6637: The Haemophilus influenzae vaccine mitigates pancreatic tumor progression and lowers immunoregulatory cell levels in the tumor microenvironment

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease projected to become the second leading cause of cancer deaths by 2030. First-line chemotherapies gemcitabine and FOLFIRINOX provide little therapeutic benefit and are accompanied by severe adverse toxicities, precluding long-term treatment. In addition, PDAC is notoriously refractory to checkpoint inhibitor immunotherapies, due to poor immunogenicity and a tumor microenvironment dominated by suppressive cell types. Thus, there is an unmet need for innovative, immune-based strategies to combat PDAC. A previous study utilized engineered bacteria to effectively kill PDAC tumor cells by directly delivering immunogenic tetanus toxoid to the tumor. Given the potential toxicity in using live bacteria, our group utilized a less toxic alternative, an FDA-approved Haemophilus influenzae type b vaccine (HibVx) also containing a tetanus toxoid component. To determine the antitumor potential of HibVx, our group used a physiologically relevant murine model, low T cell clone murine PDAC tumor model 641c95 and clinically relevant KPC mice model for PDAC. After tumors were established, animals received three consecutive daily treatments of HibVx via intraperitoneal injection. HibVx-treated animals experienced a dramatic reduction in tumor growth compared to PBS-treated controls (p<0.001). Given that tetanus toxoid is highly immunogenic in nature, changes in intratumoral immune cell populations following HibVx treatments were of great interest. Using flow cytometry analysis, HibVx-treated tumors had a significant increase in natural killer cells compared to control tumors (p<0.05). In addition, HibVx affected myeloid-derived suppressor cell populations (MDSCs), which are heavily implicated in the suppressive nature of PDAC tumors. HibVx also significantly decreased MDSCs within the tumor (p<0.05). In all, these findings position HibVx as an effective immunostimulatory agent that can be used as an alternative to live bacteria-based therapy for the treatment of PDAC. Citation Format: Eileena F. Giurini, Sam G. Pappas, Kajal H. Gupta. The Haemophilus influenzae vaccine mitigates pancreatic tumor progression and lowers immunoregulatory cell levels in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6637.

Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial

The critical roles of CD4+ T cells have been understudied for cancer vaccines. Here we report long-term clinical outcomes of a randomized multicenter phase II clinical trial (NCT00118274), where patients with high-risk melanoma received a multipeptide vaccine targeting CD8+ T cells (12MP) and were randomized to receive either of two vaccines for CD4+ (helper) T cells: 6MHP (6 melanoma-specific helper peptides), or tet (a nonspecific helper peptide from tetanus toxoid). Cyclophosphamide (Cy) pre-treatment was also assessed. Primary outcomes for T cell responses to 12MP, 6MHP, and tet were previously reported, suggesting immunogenicity of both vaccines but that CD8 T cell responses to 12MP were lower when tet was replaced with 6MHP. Here, in post-hoc analyses, we report durable prolongation of overall survival by adding 6MHP instead of tet. That benefit was experienced only by male patients. A favorable interaction of 6MHP and Cy is also suggested. Multivariable Cox regression analysis of the intent-to-treat population identify vaccine arm (12MP + 6MHP+Cy) and patient sex (male) as the two significant predictors of enhanced survival. These findings support the value of adding cognate T cell help to cancer vaccines and also suggest a need to assess the impact of patient sex on immune therapy outcomes.

Evaluation of IgG antibody response to diphtheria toxin one month after tetanusdiphtheria vaccination among 7-years-old children in a mountainous district in the Northern region of Viet Nam in 2020

Under the outbreak of diphtheria disease mostly among preschool and primary school children, following the recommendations of WHO, Vietnam has implemented a second booster dose of diphtheria vaccine since 2019 for children at 7 years old in some at-risk provinces. This study evaluated the IgG antibody response to diphtheria toxid in a group of 7-year-old children living in Tran Yen district, Yen Bai province, after receiving one dose of Tetanus-diphtheria (Td) vaccine with reduced diphtheria toxoid in 2020. The study involved community intervention, monitoring 98 7 yearold children who received the Td vaccine to compare the proportion of children with a full protective antibody level (antibody concentration ≥ 0.1IU/mL) before and one month after vaccination. The results showed that the proportion of children with a protective antibody level against diphtheria toxin increased from 35% to 95% one month after vaccination. The intervention coefficient was 171%. 80% of children achieved long-term protective antibody levels (≥ 1.0IU/mL). The Td vaccine helped children achieve full and long-term protective antibody levels, even in those without the complete primary vaccination series and those with only baseline or no protection levels. Vaccinating 7-year-old children in areas with limited vaccination coverage and no actual circulating diphtheria cases is effective and necessary to prevent disease outbreaks. The study’s results suggest the Ministry of Health should consider including the Td vaccine in the Expanded Immunization Program for regular vaccination for 7-year-old children instead of approving current annual plans.

Humoral and cellular immune responses induced by serogroup W135 meningococcal conjugate and polysaccharide vaccines

Investigating the mechanisms by which W135 meningococcal conjugate (PSW135-TT) activates adaptive immune responses in mice can provide a comprehensive understanding of the immune mechanisms of bacterial polysaccharide conjugate vaccines. We compared B-cell and T-cell immune responses immunized with W135 meningococcal capsular polysaccharides (PSW135), tetanus toxoid (TT) and PSW135-TT in mice. The results showed that PSW135-TT could induce higher PSW135-specific and TT-specific IgG antibodies with a significant enhancement after two doses. All serum antibodies immunized with PSW135- TT had strong bactericidal activity, whereas none of the serum antibodies immunized with PSW135 had bactericidal activity. Besides, IgM and IgG antibodies immunized with PSW135-TT after two doses were positively correlated with the titer of bactericidal antibodies. We also found Th cells favored Th2 humoral immune responses in PSW135-TT, PSW135, and TT-immunized mice, especially peripheral blood lymphocytes. Furthermore, PSW135-TT and TT could effectively activate bone marrow derived dendritic cells (BMDCs) and promote BMDCs to highly express major histocompatibility complex Ⅱ (MHCⅡ), CD86 and CD40 molecules in mice, whereas PSW135 couldn’t. These data verified the typical characteristics of PSW135-TT and TT as T cell dependent antigen (TD-Ag) and PSW135 as T cell independent antigen (TI-Ag), which will be very helpful for further exploration of the immune mechanism of polysaccharide-protein conjugate vaccines and improvement of the quality of bacterial polysaccharide conjugate vaccines in future.

Typhoid Conjugate Vaccine: A Boon for Endemic Regions.

Typhoid fever has the highest disease burden in countries in low- and middle-income countries, primarily located in Asia and Sub-Saharan Africa. Previous typhoid vaccines such as the live attenuated typhoid (Ty21a) vaccine and Vi (virulence) capsular polysaccharide vaccine had the limitation that they could not be administered with other standard childhood immunizations and were ineffective in children under two years of age. To address these shortcomings of the previous vaccines, typhoid conjugate vaccines (TCVs) were developed and prequalified by the World Health Organization. Cross-reacting material and tetanus toxoid are widely used as carrier proteins in TCVs. According to various studies, TCV has higher efficacy, has a more extended protection period, and is safe and immunogenic in infants as young as six months. This review article aims to comprehensively appraise the data available on TCVs' efficacy, duration of protection, safety, and immunogenicity in endemic regions.

Knowledge and practices of biosecurity measures in the students of the last year of the Nursing Career of an Ecuadorian university

Introduction: Biosafety is currently the pillar where risk prevention converges, adopted not only by health teams, but also by the general population. Objective: To determine the level of knowledge and practice of biosafety measures among students in the last year of the nursing career at a public university in Quito, Ecuador. Methodology: A cross-sectional descriptive study was carried out, with a population of 140 students of the rotating internship of the Nursing career. Data were obtained relating the variables: knowledge of biosafety standards of rotating interns and the places where they performed their pre-professional internships, with a confidence level of 95%, considering p < 0.05 as significant, a previously validated and structured questionnaire was applied with 16 questions validated with a Cronbach's Alpha of 0.85, which covered the principles of biosafety. Results: it was evidenced that 100% of the students knew the hand washing procedure; 86% knew about the knowledge, norms, and principles of biosafety; with respect to waste management, only 76% were clear about the procedure; 54% knew how to proceed with the treatment of contaminated material. Regarding the use of personal protective equipment (PPE), 91% of the students used the surgical mask as protection in the places of practice and only 39% used the N95 respirator. The vaccination used before performing their practices it was evidenced that 100% of the participants had the COVID- 19 vaccine, followed by the Hepatitis B vaccine with 94%, the Diphtheria and Tetanus vaccine was used in 91% and 70% the influenza vaccine. Conclusions: It could be determined that biosafety knowledge was high in the evaluated students, on the other hand, biosafety practices, the use of personal protective equipment (PPE), depend on the complexity and level of care where the practices were performed, more emphasis should be made regarding waste management and treatment of contaminated material. In health careers, the evaluation of adherence to biosafety practices is of vital importance.

Pilot Study on Evaluating the Impact of Tetanus, Diphtheria, and Pertussis (Tdap), Influenza, and COVID-19 Vaccinations on Antibody Responses in Pregnant Women.

This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.

Adherence to Advisory Committee on Immunization Practices in diabetes mellitus patients in Saudi Arabia: A multicenter retrospective study.

Patients with diabetes mellitus (DM) are predisposed to an increased risk of infection signifying the importance of vaccination to protect against its potentially severe complications. The Centers for Disease Control and Prevention/Advisory Committee on Immunization Practices (CDC/ACIP) issued immunization re-commendations to protect this patient population. To assess the adherence of patients with DM to the CDC/ACIP immunization recommendations in Saudi Arabia and to identify the factors associated with the vaccine adherence rate. An observational retrospective study conducted in 2023 was used to collect data on the vaccination records from 13 diabetes care centers in Saudi Arabia with 1000 eligible patients in phase I with data collected through chart review and 709 patients in phase II through online survey. Among participants, 10.01% (n = 71) had never received any vaccine, while 85.89% (n = 609) received at least one dose of the coronavirus disease 2019 (COVID-19) vaccine, and 34.83% (n = 247) had received the annual influenza vaccine. Only 2.96% (n = 21), 2.11% (n = 15), and 1.12% (n = 8) received herpes zoster, tetanus, diphtheria, and pertussis (Tdap), and human papillomavirus (HPV) vaccines, respectively. For patients with DM in Saudi Arabia, the rate of vaccination for annual influenza and COVID-19 vaccines was higher compared to other vaccinations such as herpes zoster, Tdap, pneumococcal, and HPV. Factors such as vaccine recommendations provided by family physicians or specialists, site of care, income level, DM-related hospitalization history, residency site, hemoglobin A1c (HbA1c) level, and health sector type can significantly influence the vaccination rate in patients with DM. Among non-vaccinated patients with DM, the most reported barriers were lack of knowledge and fear of side effects. This signifies the need for large-scale research in this area to identify additional factors that might facilitate adherence to CDC/ACIP vaccine recommendations in patients with DM. In Saudi Arabia, patients with DM showed higher vaccination rates for annual influenza and COVID-19 vaccines compared to other vaccinations such as herpes zoster, Tdap, pneumococcal, and HPV. Factors such as vaccine recommendations provided by family physicians or specialists, the site of care, income level, DM-related hospitalization history, residency site, HbA1c level, and health sector type can significantly influence the vaccination rate in patients with DM.

Signatures of neurological adverse events after vaccination

There have been reports associated with the development of neurological adverse events (AEs) post-vaccination. Here, we retrospectively examine the Vaccine Adverse Events Reporting System (VAERS) database for neurological AEs reported following vaccination. Since VAERS is a passive reporting system, to minimize reporting bias and to reduce background events, this retrospective study examines both age-stratified AE reports made with onset within 24 h of immunization, and age-stratified AE reports regardless of timeframe from immunization. Immediate temporal onset data patterns for febrile convulsion, seizure, and syncope AEs were observed for multiple vaccines. For age-stratified AEs in infants up to 3 years of age, the following patterns of high association were observed: (i) Aphasia, autism spectrum disorder, and speech disorder were found to be highly associated with the measles, mumps, and rubella and hepatitis B (HepB) vaccines; (ii) febrile convulsion and syncope were found to be highly associated with the meningococcal group B vaccine; and (iii) seizures were found to be highly associated with diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccines.

Protective doses of tetanus toxoid immunization and its associated factors among mothers in southern Ethiopia

ABSTRACT The World Health Organization recommends tetanus toxoid immunization before or during pregnancy for all women of childbearing age. The goal is to reduce maternal and neonatal mortality due to tetanus. According to the 2016 Ethiopia Demographic and Health Survey (EDHS) report, more than half (51%) of women did not receive protective doses of tetanus immunization. To the best of our knowledge, this study uniquely tried to assess the level of protective doses of tetanus toxoid immunization in southern Ethiopia. A community-based cross-sectional study was conducted among 580 randomly selected participants. Variable with p-value of less than .25 in the bivariate analysis were included in the multivariable logistic regression analysis. Finally, statistical significance was declared at a p-value of less than .05. The proportion of protective doses of tetanus toxoid immunization uptake in the area was found to be 41.9% (95% CI: 38–46%). Being enrolled in formal education [AOR = 6.55, 95% CI: 3.23–9.01], having at least two postnatal care visits [AOR = 3.82; 95% CI: 1.78–6.40], having at least four antenatal care visits [AOR = 2.56; 95% CI: 1.41–4.34], and being visited by Health Extension Workers [AOR = 2.66; 95% CI: 1.42–4.01] were found to be factors enhancing the uptake of protective doses of tetanus toxoid immunization. Generally, the uptake or prevalence of the protective doses of tetanus toxoid immunization in the area was lower than the World Health Organization’s target. Therefore, all responsible bodies, including healthcare providers, need to strengthen counseling mothers to enhance the uptake of tetanus toxoid immunization.

Atopic dermatitis phenotype affects expression of atopic diseases despite similar mononuclear cell cytokine response

BackgroundThe atopic march refers to the co-expression and progression of atopic diseases in childhood, often beginning with atopic dermatitis, although children may not “progress” through each atopic disease. ObjectiveWe hypothesized that future atopic disease expression is modified by atopic dermatitis phenotype, and that these differences result from underlying dysregulation of cytokine signaling. MethodsChildren (n=285) were enrolled into the Childhood Origins of ASThma birth cohort and followed prospectively. Rates of atopic dermatitis, food allergy, allergic rhinitis, and asthma were assessed longitudinally from birth to 18 years of age. Associations between atopic dermatitis phenotype and food allergy, allergic rhinitis, asthma, allergic sensitization, exhaled nitric oxide, and lung function were determined. Peripheral blood mononuclear cell responses (IL-5, IL-10, IL-13, IFN-γ) to dust mite, phytohemagglutinin, Staphylococcus aureus Cowan I, and tetanus toxoid were compared among atopic dermatitis phenotypes. ResultsAtopic dermatitis at year 1 was associated with an increased risk of food allergy (p=0.004). Both persistent and late-onset atopic dermatitis were associated with an increased risk of asthma (p=<0.001), rhinitis (p<0.001), elevated total IgE (p=<0.001), percentage of aeroallergens with detectable IgE (p<0.001), and elevated exhaled nitric oxide (p=0.002). Longitudinal analyses did not reveal consistent differences in PBMC responses among dermatitis phenotypes. ConclusionAtopic dermatitis phenotype is associated with differential expression of other atopic diseases. Our findings suggest peripheral blood cytokine dysregulation is not a mechanism underlying this process, and immune dysregulation may be mediated at mucosal surfaces or in secondary lymphoid organs.

Urgent Management of Penetrating Ocular Injury: A Case Report and Review of the Literature.

Ocular globe injury is a severe ophthalmic emergency that requires immediate attention in the emergency department. In this case report, we present a 35-year-old male who suffered a penetrating ocular injury and globe rupture caused by a nail puncture. The patient presented with severe pain and visual loss and was treated with tetanus vaccination, empirical antibiotics, and pain control, followed by an urgent orbital computed tomography (CT) scan and consultation with an ophthalmologist. The CT scan revealed a retained nail in the ocular space, and an urgent operation was performed to repair the eyeball rupture, remove the intraocular foreign body, and perform an anterior vitrectomy. The patient was discharged 6 days after the operation with a visual acuity of 20/400 and an ocular trauma score of 34. This case highlights the importance of initial emergency physician decision-making and the need for a thorough history-taking and examination when encountering penetrating ocular injuries.

Mycophenolate mofetil hampers antibody responses to a broad range of vaccinations in kidney transplant recipients: Results from a randomized controlled study

To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients. In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort. Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n=37, TACmono: n=34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p=0.016), tetanus (TAC/MMF 35%, TACmono 82%, p<0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p=0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p=0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p=0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p=0.040). MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.

Pharmacists’ role in maternal immunization

Maternal immunization is an important strategy to safeguard infants against vaccine-preventable diseases such as pertussis, which poses a significant economic burden on the health care system. Although the Tetanus, Diphtheria, and Pertussis vaccine has been recommended for pregnant individuals since 2018, uptake varies widely across Canadian provinces. As 4.5 million Canadians do not have access to a regular physician, there is a need to find alternate ways of informing pregnant individuals about maternal immunization schedules. Given the wide accessibility of pharmacists across Canada, they should have a leading role in informing pregnant individuals about maternal vaccines. Training guidelines for pharmacists would ensure informative and effective conversations about vaccinations and promote vaccine safety and benefits, facilitating administration. Increased participation from pharmacists can significantly contribute to improving maternal and child health outcomes, with the goal of reducing the burden of vaccine-preventable diseases in Canada.

Geospatial and multilevel clustering of zero-dose children in Kikwit, Democratic Republic of the Congo in 2022.

Zero-dose children remain highly vulnerable to vaccine-preventable diseases and can sustain transmission even in highly vaccinated populations. The WHO Immunization Agenda 2030 has prioritised reaching out to these children. We assessed the spatial distribution of zero-dose children together with the associated risk factors in a provincial capital in the Democratic Republic of Congo. A cross sectional survey was conducted in the city of Kikwit between September 28 and October 14, 2022. Data were collected both at household and health area level. QGIS and SATscan were used to describe and identify hotspots among zero-dose children, and a mixed effect logistic regression model was used to identify risk factors. Overall, 1,863 children aged 12-23 months were enrolled. Kikwit city had a 16.3% zero-dose prevalence, with significant variation between and within health zones. Two hotspots were identified through geospatial analysis, each spanning multiple health areas. Multilevel analysis revealed significant clustering at health area level and found six associated risk factors. These include the absence of home visits by community health workers (aOR = 1.90), living more than a kilometre from a health centre (aOR = 1.95), the mother's lack of tetanus vaccination (aOR = 3.16), and inability to name a vaccine-preventable disease (aOR = 3.20). However, secondary (aOR = 0.56) or tertiary (aOR = 0.21) education of mothers/guardians and belonging to Bunda (aOR = 0.36) or Mbala (aOR = 0.52) ethnicity reduced the risk of zero-dose. We observed a high prevalence of zero-dose children with a heterogeneous spatial distribution of epidemiological importance. Due to sub-zonal diversity, a health zone approach to reduce zero-dose immunization appears very limited. Zero-dose prevalence was related to the community health workers' home visit, to the distance of residence to a health centre and to household-level factors. Geospatial results could help in targeting priority health areas and communities for vaccination.

Cost-effectiveness analysis of pertussis booster vaccination for adolescents in Japan

IntroductionIn Japan, the introduction of a fifth diphtheria–tetanus–acellular pertussis (DTaP) vaccination has been considered, and adolescents aged 11–12 years old who are currently receiving the diphtheria–tetanus (DT) vaccine are one candidate group. We analyze the cost-effectiveness of replacing the DT vaccine with the DTaP vaccine for 11-year-old adolescents and investigate the indirect effect of vaccinated adolescents on unvaccinated infant siblings. We undertake two analyses using high- and low-morbidity pertussis cases, and based on the results, present suggestions for pertussis prevention in the post-COVID-19 pandemic era. MethodWe used the number of pertussis cases in 2019 as the high-morbidity case and the average number of cases in 2020–2021 as the low-morbidity case, and evaluated the incremental cost-effectiveness ratio (ICER) of the DTaP strategy to the DT strategy based on quality-adjusted life years (QALYs). The economic model contained adolescent and infant sub-models. The indirect effect for infants was considered as the probability of unvaccinated infants avoiding pertussis infection from their vaccinated siblings. ResultsThe ICER from the payers’ perspective was Japanese yen (JPY) 4,254,515 per QALY gained in the high-morbidity case and JPY 62,546,776 per QALY gained in the low-morbidity case. The sensitivity analysis showed that the utility of pertussis had the greatest impact on the ICER, with a 60.58% and 0% probability that the ICER was less than JPY 5 million per QALY gained in the high-morbidity case and low-morbidity case, respectively. ConclusionThe cost-effectiveness of replacing the DT vaccine with the DTaP vaccine is affected by the level of pertussis morbidity, with the ICER becoming more favorable in the high-morbidity case. The indirect effect has little impact on the ICER. Thus, policy-makers should continue to monitor the pertussis epidemic in the post-COVID-19 era, and determine the need to introduce a booster based on perceived trends.

Potential Protectivity of a Conjugated COVID-19 Vaccine against Tetanus.

PastoCovac is a subunit protein vaccine against COVID-19 which contains the tetanus toxoid as a carrier conjugated to SARS-CoV-2 RBD. The primary goal of the tetanus application was to elicit a stronger specific response in the individuals. However, conjugate vaccines have the potency to generate anticarrier antibodies in addition to the target antigen. Therefore, the present study aimed to evaluate the PastoCovac vaccine in the humoral immune induction against tetanus. Six groups of individuals, including those who received one, two, or three doses of the PastoCovac vaccine, Td vaccine, and also the controls who received other COVID-19 vaccines (except PastoCovac), were investigated. The anti-tetanus IgG was assessed by an ELISA assay in all vaccinated groups. The antibody persistency against tetanus in the group who received one dose of the PastoCovac vaccine was also assessed on day 60, 90, and 180 after the last injection. The anti-tetanus antibody titer in the three groups of PastoCovac recipients was positive, though additional doses of the vaccine led to a significant antibody rise (p = 0.003). Notably, the comparison of the mean antibody titer between the Td recipients and those who received one/two doses of PastoCovac showed that the mean rise in the antibody titer before and after the injection was not significant. Although the antibody titer on day 180 decreased to a lower level than on day 21, it was still estimated to be highly positive against tetanus. Eventually, none of the PastoCovac recipients presented vaccine side-effects during the follow-up. The current data indicate that the tetanus conjugate vaccine against COVID-19, PastoCovac, could induce immune responses against tetanus, which can persist for at least 6 months. Combination vaccine formulae containing TT and DT as carriers for conjugate vaccines could be considered instead of TT and/or DT boosters in adults if they are indicated.