Uptake of protective tetanus toxoid vaccine doses and maternal associated factors during pregnancy in armed conflict zone, hospital-based cross-sectional study.

Background: Vaccinating pregnant women with tetanus toxoid (TT) is crucial to prevent neonatal tetanus, reducing related deaths by 94%. In conflict zones with restricted access to deliveries, neonates face a fatality rate of 80%-100%. This study explores the uptake of protective TT vaccine doses and maternal associated factors during pregnancy in an armed conflict zone. Methods: A hospital-based, descriptive, cross-sectional study was conducted of 357 pregnant women at delivery using simple random sampling. Data were collected through interviews with a structured questionnaire, and entered using Epi-data version 3.1, and exported using SPSS version 22 for further analysis. Binary and multivariable logistic regression analyses were used to identify significant variables for receiving protective TT doses during pregnancy at P < 0.05. Result: In this study, 355 pregnant women were included, with response rate of 99.4%. The mean age of the participants was 27.65 ± 6.23 years. During the study period, 67.3% of pregnant women received a protective TT vaccine dose while 33.3% were missed due to escalated armed conflict. The dropout rates were significant from TT5 to TT2 (17.6%), TT5 to TT3 (11.9%), and TT5 to TT4 (6.1%). However, maternal associated factors for the uptake of the TT protective vaccine dose were identified, including being aged 36-49 years [adjusted odds ratio (AOR) = 3.7; 95% confidence interval (CI) 1.54-7.8; P = 0.001], completing high school (AOR = 3.05; 95% CI 1.5-8.9; P = 0.02), having an antenatal care follow-up (AOR = 9.4; 95% CI 2.9-24.3; P = 0.001), previous media exposure (AOR = 15.5; 95% CI 7.5-25.3; P = 0.001), and good maternal knowledge (AOR = 2.7; 95% CI 1.8-4.9; P = 0.02). Conclusion: The uptake of the protective TT vaccine dose among pregnant women in a continued armed conflict area was low compared with previous study findings. Efforts should be made to increase vaccine uptake and reduce dropout rates by addressing both community and individual-level factors.

Predictors of Tetanus Vaccine Uptake among Pregnant Women in Khartoum State, Sudan: A Hospital-Based Cross-Sectional Study.

Tetanus toxoid (TT) vaccination during pregnancy has been proven as an effective preventative measure to reduce the incidence of maternal and neonatal morbidity and mortality worldwide. This study aimed to assess the determinants of TT vaccine uptake among pregnant women at two public maternity specialized hospitals in Sudan. A hospital-based cross-sectional study was conducted at two public hospitals, Omdurman Maternity Hospital and Al Saudi Hospital in Omdurman, Khartoum State, in Sudan from February to April 2020. Logistic regression analysis was carried out to identify factors associated with receiving three or more doses of the TT vaccine among pregnant women, presented as odds ratios, with p-values < 0.05 considered significant (at a 95% confidence interval). The study recruited 350 pregnant women, with 313 participants included in the analysis. This study found that only 40% of the pregnant women had received three doses or more of the TT vaccine. Pregnant women who attended Al Saudi Hospital were less likely to be vaccinated with the recommended dose of the TT vaccine in districts at high risk (received ≥3 doses) compared to those who attended Omdurman Hospital [OR = 0.49 (95% C.I. 0.29-0.82), p-value < 0.05]. Furthermore, the number of children at home was a significant predictor of the mothers' immunization status as those with five children or more were ten times more likely to be vaccinated with three doses or more [OR = 10.54 (95% C.I. 4.30-25.86), p-value < 0.05]. We conclude that this low rate of TT vaccine uptake found in this study among pregnant women increases the number of newborn babies susceptible to contracting neonatal tetanus. The findings of this study should be considered in the development of communication strategies targeting and prioritizing at-risk groups to increase TT vaccine uptake among pregnant women in Sudan.

Annual two-dose tetanus toxoid vaccination induces protective humoral immunity to all age groups of rhesus macaques.

A tetanus outbreak occurred during 2014-2015 in the rhesus macaques reared in an open enclosure in our facility. As the soil of the facility was suspected to be contaminated with Clostridium tetani spores, there was a risk of further tetanus occurring among the macaques. To protect them from tetanus, a tetanus toxoid vaccination was recommended; however, the vaccinated elderly animals might not be effectively protected due to insufficient humoral immune responses. Hence, we evaluated the dynamics of antibody responses among rhesus macaques of all age groups vaccinated with two-dose tetanus toxoid at a 1-year interval during a 3-year follow-up study. The vaccination developed anti-tetanus toxin-specific antibodies in animals of all age groups, the antibody levels peaked 1 year after the second vaccination, and the peak levels decreased with age. However, the levels among elderly individuals (aged ≥13 years) were still higher than the threshold level, which was supposed to protect them from tetanus development. Although the rhesus macaques in our facility had a risk of occasional exposure to the spores due to the outbreak, no incidence of tetanus has ever occurred to date. These results indicate that the vaccination protocol is effective in protecting not only younger but also older animals from tetanus.

Assessment of tetanus revaccination regimens in horses not vaccinated in the previous year.

A two-dose revaccination against tetanus is recommended for horses over 2 years old in Japan with no history of vaccination in the previous year. Here, the need for two-dose revaccination was evaluated in terms of antibody titers for each vaccine type, namely monovalent or multivalent. There was no difference in antibody titers between one- and two-dose regimens for up to 1 year, except at 8 weeks with the multivalent vaccine, and all horses had sufficient antibody titers for 1 year of tetanus prophylaxis. These results suggest that one-dose revaccination, regardless of the vaccine type, is as effective as two-dose in preventing tetanus for at least 1 year in horses not vaccinated in the previous year.

Engineering of tetanus toxoid-loaded polymeric microneedle patches.

This study is aimed to fabricate tetanus toxoid laden microneedle patches by using a polymeric blend comprising of polyvinyl pyrrolidone and sodium carboxymethyl cellulose as base materials and sorbitol as a plasticizer. The tetanus toxoid was mixed with polymeric blend and patches were prepared by using vacuum micromolding technique. Microneedle patches were evaluated for physical attributes such as uniformity of thickness, folding endurance, and swelling profile. Morphological features were assessed by optical and scanning electron microscopy. In vitro performance of fabricated patches was studied by using bicinchoninic acid assay (BCA). Insertion ability of microstructures was studied in vitro on model skin parafilm and in vivo in albino rat. In vivo immunogenic activity of the formulation was assessed by recording immunoglobulin G (IgG) levels, interferon gamma (IFN-γ) levels, and T-cell (CD4+ and CD8+) count following the application of dosage forms. Prepared patches, displaying sharp-tipped and smooth-surfaced microstructures, remained intact after 350 ± 36 foldings. Optimized microneedle patch formulation showed ~ 74% swelling and ~ 85.6% vaccine release within an hour. The microneedles successfully pierced parafilm. Histological examination of microneedle-treated rat skin confirmed disruption of epidermis without damaging the underneath vasculature. A significant increase in IgG levels (~ 21%), IFN-γ levels (~ 30%), CD4+ (~ 41.5%), and CD8+ (~ 48.5%) cell count was observed in tetanus vaccine-loaded microneedle patches treated albino rats with respect to control (untreated) group at 42nd day of immunization. In conclusion, tetanus toxoid-loaded microneedle patches can be considered as an efficient choice for transdermal delivery of vaccine without inducing pain commonly experienced with hypodermic needles.

Safety and Immunogenicity of a Recombinant Tetanus Vaccine in Healthy Adults in China: A Randomized, Double-Blind, Dose Escalation, Placebo- and Positive-Controlled, Phase 1/2 Trial.

Tetanus is a fatal but vaccine-preventable disease. The currently available tetanus vaccines are tetanus toxoid (TT)-based. Although these vaccines are generally effective, challenges in vaccine development and access remain. A randomized, double-blind, dose escalation, placebo- and positive-controlled, phase 1/2 trial (ChiCTR1800015865) is performed to evaluate the safety and immunogenicity of an alternative recombinant tetanus vaccine based on the Hc domain of tetanus neurotoxin (TeNT-Hc) in healthy adult volunteers. The primary outcome is the safety profile of the recombinant tetanus vaccine, and immunogenicity is the secondary outcome. 150 eligible participants were enrolled and randomly assigned to receive one of the three doses of recombinant tetanus vaccine (TeNT-Hc 10/20/30 µg), TT vaccine, or placebo. The recombinant tetanus vaccine shows a good safety profile. The frequency of any solicited and unsolicited adverse events after each vaccination does not differ across the vaccine and placebo recipients. No serious treatment-related adverse events occur. The recombinant tetanus vaccine shows strong immune responses (seroconversion rates, geometric mean titer, and antigen-specific CD4+/CD8+ T-cell responses), which are roughly comparable to those of the TT vaccine. In conclusion, the findings from this study support that recombinant tetanus vaccine is safe and immunogenic; thereby, it represents a novel vaccine candidate against tetanus.

Erythema multiforme induced by tetanus toxoid vaccine.

Erythema multiforme (EM) is an immunomediated mucocutaneous disorder of usually unknown etiology which has been known to occur following an infection like herpes virus or exposure to drugs. It primarily affects adolescents, young adults, but can occur at any age. Vaccines are also documented as precipitating factors for EM. In the year 2017, the case of a 25-year-old male patient with lesions of EM which appeared after 30 min of administration of tetanus toxoid vaccine is reported here.

Knowledge and health beliefs of reproductive-age women in Alexandria about tetanus toxoid immunization.

BACKGROUND: Maternal neonatal tetanus is a substantial public health problem in many developing countries. In 2017, nearly, 30,848 newborns died of neonatal tetanus; thus, high immunization coverage remains a necessity. This study aims to assess knowledge and health beliefs of reproductive-age women in Alexandria about tetanus toxoid immunization. METHODS: A cross-section survey of 700 females attending health offices in Alexandria was done using an interview questionnaire to collect data regarding women's knowledge and beliefs about tetanus toxoid vaccine (TTV) and maternal and neonatal tetanus (MNT). Nine health offices were selected using multi-stage random sampling. RESULTS: Most of studied women (83.6%) had poor knowledge of MNT and TTV. The highest percentage of women had low perception of susceptibility to MNT (48.0%), moderate perception of severity of MNT (57.4%) and barriers to TTV (58.9%), high perception of benefits of TTV (86.6%), and high self-efficacy in taking the vaccine (76.2%). Less than one-third of the sampled women (27.7%) were immune by (TT2+). Logistic regression models showed that the place of antenatal care, level of knowledge, perceived barriers, and socio-economic level were significant predictors of immunity status (p = 0.008, p = 0.032, p = 0.011, and p = 0.001, respectively). CONCLUSION: Women lacked information about MNT/TTV and may even have been discouraged by their private obstetricians from taking the vaccine. Perceived barriers to receiving tetanus toxoid vaccination were shown to be an important predictor of immunization behavior.

Effect of cash incentives on tetanus toxoid vaccination among rural Nigerian women: a randomized controlled trial.

Tetanus toxoid vaccination is freely available for most women in developing countries, yet maternal and neonatal tetanus are still prevalent in 13 countries, 9 of which are in sub-Saharan Africa. We evaluated whether providing cash incentives increases the uptake of tetanus toxoid vaccination among women of childbearing age in rural northern Nigeria. We randomized amounts of cash incentives to women in three groups: 5 Nigerian naira (C5), 300 naira (C300), and 800 naira (C800) (150 naira = 1 U.S. dollar). Overall, of 2,482 women from 80 villages, 1,803 (72.6%) women successfully received the vaccination (419 of 765 [54.8%] women in C5, 643 of 850 [75.7%] women in C300, and 741 of 867 [85.5%] women in C800). Women in C300 and C800 were significantly more likely to receive the vaccine than women in C5. We further found that transportation costs are one of the significant barriers that prevent women from receiving vaccination at clinics, and that cash incentives compensate for transportation costs unless such costs are large.

Diverse effects on vaccine-specific serum IgG titres and memory B cells upon methotrexate and anti-TNF-α therapy in children with rheumatic diseases: A cross-sectional study.

OBJECTIVES: We aimed at a comprehensive evaluation of how anti-TNF-α therapy and methotrexate treatment interferes with B cell memory in children with Paediatric Rheumatic Disease (PRD), by evaluating existing B cell phenotypes, and preserved vaccine-specific memory B cells and IgG titres generated prior to disease and treatment. METHODS: In a cross-sectional study on children with PRD on various treatments, we measured titre levels and avidity strength of serum IgG specific against measles, rubella and tetanus. We also quantified transitional B cells and resting, atypical, and activated memory B cells with flow cytometry, and enumerated antigen-specific memory B cells with ELISpot. RESULTS: For children who had received a tetanus booster, patients treated with any disease-modifying anti-rheumatic drug (DMARD) had lower tetanus serum IgG compared to healthy controls and NSAID-treated patients. Patients without a measles booster had lower levels of measles-specific memory B cells, but all vaccine-specific memory B cells were preserved in patients with booster. We furthermore found that the mature B cell compartment was phenotypically similar between patients and healthy controls. CONCLUSIONS: We concluded that the general and vaccine-specific memory B cell compartment is well preserved in children with PRD and DMARD treatment, but that they might have lower serum tetanus IgG. We emphasize the importance for these children to follow the full vaccination schedule, and suggest to re-measure tetanus titres as they reach adulthood.

Introduction. Maternal immunization - Promises and concerns.

In this issue of Vaccine, the maternal immunization platform as an approach to protect mothers and infants against diverse pathogens is presented. Potential vaccine targets and the safety, science, trial designs, ethical considerations, and international perspectives focusing on low and middle income countries (LMIC) are discussed. This information provides a timely update because maternal immunization is increasingly being considered as an intervention to prevent maternal and/or neonatal disease. Prioritization of vaccine targets for maternal immunization by researchers, public health officials and health care workers needs to begin now.