[Expert consensus on the use of tetanus vaccines for the high-risk group of post-traumatic tetanus].

Tetanus remains a potentially fatal disease with highly severe consequences worldwide. China has eliminated neonatal tetanus since 2012, but post-traumatic tetanus still represents a substantial public health burden. It is of great significance to implement active pre-exposure immunization among the high-risk group of post-traumatic tetanus in China, which can help reduce the burden of post-traumatic tetanus. Based on the World Health Organization's position paper on tetanus vaccines and relevant regulations and standards issued by China. This consensus introduces the pre-exposure immunization prevention strategies for tetanus both domestically and internationally, as well as the definition of a high-risk group of post-traumatic tetanus in China. It also provides recommendations on using active immunological preparation for tetanus, which can be used as a reference for relevant personnel engaged in disease prevention, control, and vaccination.

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.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

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.

Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response.

For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMVBp) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMVBp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMVBp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMVBp and the immunogens at varying levels. These assays demonstrated that OMVBp exhibits adjuvant properties even at the low concentration employed (1.5 µg of protein per dose). As this effect was notably enhanced at medium (3 µg) and high concentrations (6 µg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMVBp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMVBp, specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001). When assessing the adjuvant properties of OMVBp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMVE.coli) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species. Nonetheless, it's crucial to highlight that OMVBp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMVBp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.

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.

Efficacy of typhoid vaccines against culture-confirmed Salmonella Typhi in typhoid endemic countries: a systematic review and meta-analysis.

BACKGROUND: Typhoid is a serious public health threat in many low-income and middle-income countries. Several vaccines for typhoid have been recommended by WHO for typhoid prevention in endemic countries. This study aimed to review the efficacy of typhoid vaccines against culture-confirmed Salmonella enterica serovar Typhi. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for studies published in English between Jan 1, 1986 and Nov 2, 2023. We included randomised controlled trials (RCTs) comparing typhoid vaccines with a placebo or another vaccine. This meta-analysis evaluated the efficacy and safety of several typhoid vaccines, including live attenuated oral Ty21a vaccine, Vi capsular polysaccharide (Vi-PS), Vi polysaccharide conjugated to recombinant Pseudomonas aeruginosa exotoxin A vaccine (Vi-rEPA), and Vi-tetanus toxoid conjugate vaccine (TCV). The certainty of evidence for key outcomes was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. The outcome of interest was typhoid fever confirmed by the isolation of Salmonella enterica serovar Typhi in blood and adverse events following immunisation. This study is registered with PROSPERO (CRD42021241043). FINDINGS: We included 14 RCTs assessing four different vaccines (Ty21a: four trials; Vi-PS: five trials; Vi-rEPA: one trial; TCV: four trials) involving 585 253 participants. All trials were conducted in typhoid endemic countries and the age of participants ranged from 6 months to 50 years. The pooled efficacy against typhoid fever was 45% (95% CI 33-55%; four trials; 247 649 participants; I2 59%; moderate certainty) for Ty21a and 58% (44-69%; five trials; 214 456 participants; I2 34%; moderate certainty) for polysaccharide Vi-PS. The cumulative efficacy of two doses of Vi-rEPA vaccine at 2 years was 91% (88-96%; one trial; 12 008 participants; moderate certainty). The pooled efficacy of a single shot of TCV at 2 years post-immunisation was 83% (77-87%; four trials; 111 130 participants; I2 0%; moderate certainty). All vaccines were safe, with no serious adverse effects reported in the trials. INTERPRETATION: The existing data from included trials provide promising results regarding the efficacy and safety of the four recommended typhoid vaccines. TCV and Vi-rEPA were found to have the highest efficacy at 2 years post-immunisation. However, follow-up data for Vi-rEPA are scarce and only TCV is pre-qualified by WHO. Therefore, roll-out of TCV into routine immunisation programmes in typhoid endemic settings is highly recommended. FUNDING: There was no funding source for this study.

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

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.

Detection of tetanus toxoid with iron magnetic nanobioprobe.

Diagnosis of diseases with low facilities, speed, accuracy and sensitivity is an important matter in treatment. Bioprobes based on iron oxide nanoparticles are a good candidate for early detection of deadly and infectious diseases such as tetanus due to their high reactivity, biocompatibility, low production cost and sample separation under a magnetic field. In this study, silane groups were coated on surface of iron oxide nanoparticles using tetraethoxysilane (TEOS) hydrolysis. Also, NH2groups were generated on the surface of silanized nanoparticles using 3-aminopropyl triethoxy silane (APTES). Antibody was immobilized on the surface of silanized nanoparticles using TCT trichlorothriazine as activator. Silanization and stabilized antibody were investigated by using of FT-IR, EDX, VSM, SRB technique. UV/vis spectroscopy, fluorescence, agglutination test and ELISA were used for biosensor performance and specificity. The results of FT-IR spectroscopy showed that Si-O-Si and Si-O-Fe bonds and TCT chlorine and amine groups of tetanus anti-toxoid antibodies were formed on the surface of iron oxide nanoparticles. The presence of Si, N and C elements in EDX analysis confirms the silanization of iron oxide nanoparticles. VSM results showed that the amount of magnetic nanoparticles after conjugation is sufficient for biological applications. Antibody stabilization on nanoparticles increased the adsorption intensity in the uv/vis spectrometer. The fluorescence intensity of nano bioprobe increased in the presence of 10 ng ml-1. Nanobio probes were observed as agglomerates in the presence of tetanus toxoid antigen. The presence of tetanus antigen caused the formation of antigen-nanobioprobe antigen complex. Identification of this complex by HRP-bound antibody confirmed the specificity of nanobioprobe. Tetanus magnetic nanobioprobe with a diagnostic limit of 10 ng ml-1of tetanus antigen in a short time can be a good tool in LOC devices and microfluidic chips.

Intensification of integrated immunization services to recover routine vaccination coverage and bring COVID-19 vaccine to the population of Iraq in 2022.

INTRODUCTION: COVID-19 seriously impacted routine immunization (RI) in Iraq. Coverage declined to a 6-year low in 2021, and COVID-19 vaccination uptake was slow. In response, government implemented intensification of integrated immunization services (3IS), a nationwide approach comprising regular outreach sessions of COVID-19 vaccination and RI for children who had either missed doses or never commenced scheduled vaccination (zero-dose children). We describe the 3IS and its impact on vaccination coverage in Iraq. METHODS: 3IS comprised new outreach sessions for urban and rural communities where administrative data suggested there were gaps in coverage. Groups of six personnel from each of 1,321 primary healthcare centres implemented six outreach sessions per month during February-November 2022. Community engagement was an integral component. We compared RI administrative data (2019-2022) and data reported during 3IS activities to assess its impact. RESULTS: In total 4,189,859 vaccine doses were administered during 72,495 3IS outreach sessions, over one-fifth of 19,106,849 vaccine doses administered in Iraq over these 10 months. Among them, 957,874 (22.9 %) were COVID-19 vaccines, adding slightly to national coverage, and 3,231,985 (77.1 %) were RI vaccines, dramatically reducing zero-dose children, adding 18 %, 25 %, 21 %, and 31 % to 2022 penta1, penta3, measles first-dose and MMR1 vaccine coverage, and contributing to national coverage of 102.2 %, 94.5 %, 91.8 % and 96.3 % for these vaccines during February-November, respectively. Moreover, 3IS sessions delivered 133,528 doses of tetanus toxoid, 16,353 doses of adult HepB vaccine, and 315,032 vitamin A doses to eligible individuals. CONCLUSION: In the context of global encouragement to integrate vaccination services, Iraq's 3IS approach enabled dramatic improvements in RI coverage, virtual elimination of zero-dose status among children born during the pandemic, and small improvements in COVID-19 and adult vaccination. Our findings provide lessons for future integrated primary care towards universal health coverage in Iraq, and for other countries yet to undertake integration.

Re-N-acetylation of group B Streptococcus type Ia capsular polysaccharide improves the immunogenicity of glycoconjugate vaccines.

The capsular polysaccharides (CPS) of Group B Streptococcus play a crucial role as virulence determinants and are potential candidates for antigenic components in vaccine formulations. Alkaline treatments are commonly used to extract polysaccharides owing to their efficiency and cost-effectiveness; however, they may induce the removal of N-acetyl groups from CPS. This study involved re-N-acetylation of CPS Ia to improve its biological functionality. The structural modifications and enhanced antigenicity of CPS Ia were observed after re-N-acetylation. The tetanus toxoid (TT) was conjugated with either partially de-N-acetylated or fully re-N-acetylated CPS. As a result, the conjugate containing re-N-acetylated CPS (IaReN-TT) enhanced the induction of IgG antibody levels and functional antibodies in mice. Both passive and active protection assays substantiated the superior protective efficacy of IaReN-TT, suggesting that the re-N-acetylation of CPS Ia could be a critical step in refining the immunogenic profile of glycoconjugate vaccines.

Awareness of Tetanus Toxoid Vaccination among Women of Reproductive Age Attending Outpatient Department in a Tertiary Level Hospital.

Maternal and neonatal tetanus is still a major but preventable cause of mortality in many developing countries like Bangladesh. Women of reproductive age are very prone to tetanus infection. This descriptive cross-sectional study was carried out at outpatient department (OPD) of Sir Salimullah Medical College and Mitford Hospital, Bangladesh from October 2019 to April 2020 to determine the level of awareness about Tetanus Toxoid (TT) vaccination in women of reproductive age 15-49 years. Data were collected from 342 women by face to face interview with a semi-structured questionnaire. A large number of the respondents (43.27%) were belonged to 15-24 years age group, majority (92.98%) were Muslim and most of them (41.28%) were SSC passed. A very large number of them (78.36%) were married and (64.55%) had 1-2 children. More than three quarter (78.36%) of women heard about tetanus and 83.96% women thought that tetanus is preventable by TT vaccination. Among the respondents who had heard about tetanus, majority (68.67%) of them had taken TT vaccine, 92.58% of them had taken the first dose before 25 years of age and 71.05% had completed the full course. Regarding awareness of the respondents, 65.79% were aware of risk of neonatal tetanus of an unimmunized mother & 61.19% distinguished that agent of tetanus can be transmitted through wounds. It is considered that the findings of the study will provide a useful basis for further research and planning.

COT-TT vaccine attenuates cocaine-seeking and cocaine-conditioned place preference in rats.

Vaccination active, promising alternative immunological strategy to treat of CUD. Various models of cocaine vaccines have been evaluated in animals and humans with relative success. In this sense, it is necessary to improve or optimize the cocaine vaccines already evaluated. Our laboratory previously reported the efficacy of the tetanus toxoid-conjugated morphine vaccine (M6-TT). The M6-TT vaccine can generate high titers of antibodies and reduce heroin-induced behavioral effects in rodents. So, it would be plausible to assume that if we modify the M6-TT vaccine by changing the hapten and maintaining the rest of the structural elements of the vaccine, we will maintain the properties of the M6-TT vaccine (high antibody titers). The objective of this study was to determine whether the antibodies generated by a tetanus toxoid-conjugated cocaine vaccine (COC-TT) can recognize and capture cocaine and decrease the cocaine-induced reinforcing effects. Male Wistar rats were immunized with the COC-TT. A solid-phase antibody-capture ELISA was used to monitor antibody titer responses after each booster dose in vaccinated animals. The study used cocaine self-administration and place-preference testing to evaluate the cocaine-reinforcing effects. The COC-TT vaccine could generate high levels of anti-cocaine antibodies. The antibodies reduced the cocaine self-administration and cocaine place preference. In addition, they decreased the cocaine-induced Fos protein expression. These findings suggest that the COC-TT vaccine generates a robust immunogenic response capable of reducing the reinforcing effects of cocaine, which supports its possible future use in clinical trials in patients with CUD.

Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses.

Infants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on infant gut microbiota and its association with tetanus toxoid vaccine responses. We evaluated the gut microbiota of 82 South African (61 iHEU and 21 iHUU) and 196 Nigerian (141 iHEU and 55 iHUU) infants at <1 and 15 weeks of life by 16S rRNA gene sequencing. Anti-tetanus antibodies were measured by enzyme-linked immunosorbent assay at matched time points. Gut microbiota in the 278 included infants and its succession were more strongly influenced by geographical location and age than by HIV exposure. Microbiota of Nigerian infants, who were exclusively breastfed, drastically changed over 15 weeks, becoming dominated by Bifidobacterium longum subspecies infantis. This change was not observed among South African infants, even when limiting the analysis to exclusively breastfed infants. The Least Absolute Shrinkage and Selection Operator regression suggested that HIV exposure and gut microbiota were independently associated with tetanus titers at week 15, and that high passively transferred antibody levels, as seen in the Nigerian cohort, may mitigate these effects. In conclusion, in two African cohorts, HIV exposure minimally altered the infant gut microbiota compared to age and setting, but both specific gut microbes and HIV exposure independently predicted humoral tetanus vaccine responses.IMPORTANCEGut microbiota plays an essential role in immune system development. Since infants HIV-exposed and uninfected (iHEU) are more vulnerable to infectious diseases than unexposed infants, we explored the impact of HIV exposure on gut microbiota and its association with vaccine responses. This study was conducted in two African countries with rapidly increasing numbers of iHEU. Infant HIV exposure did not substantially affect gut microbial succession, but geographic location had a strong effect. However, both the relative abundance of specific gut microbes and HIV exposure were independently associated with tetanus titers, which were also influenced by baseline tetanus titers (maternal transfer). Our findings provide insight into the effect of HIV exposure, passive maternal antibody, and gut microbiota on infant humoral vaccine responses.

Development of a monoclonal antibody sandwich ELISA for the determination of antigen content and quality in diphtheria vaccines.

At present, quality control of diphtheria vaccines by both manufacturers and national control laboratories relies heavily on in vivo assays to confirm potency. As part of the VAC2VAC project we have developed a monoclonal antibody (mAb) enzyme-linked immunosorbent assay (ELISA) to measure the relative amount and quality of diphtheria toxoid (DTxd) in diphtheria-tetanus based vaccines and believe this test has the potential to play a key role in a control strategy no longer including an in vivo potency test. The mAb ELISA is highly specific, has good dilutional linearity, and is suitable for detecting DTxd in a range of different human vaccine products. We demonstrate the ability of the assay to discriminate between batches of different content and quality using vaccine batches that were prepared to contain differing amounts of DTxd or were altered by exposure to heat or oxidative stress. We also demonstrate successful transfer of the method to other laboratories and show that different diphtheria antigen materials may be able to serve as a reference antigen for local standardization of the method. The assay is ideally suited for incorporation into a consistency approach for routine diphtheria vaccine quality control testing and may be suitable to serve as the stability indicating test in replacement of the current in vivo potency test.

Diphtheria vaccines help to protect against diphtheria infection. Currently, animal tests are used to ensure the potency of such vaccines. Since these tests were first introduced, there have been improvements in non-animal technologies that can be used to ensure consistent production of potent vaccine batches. To demonstrate that a new batch of diphtheria vaccine is consistent with a previous batch of known potency, the quality and amount of the component that stimulates the immune response upon vaccination must be assessed in comparison. We have developed an assay that can measure the quality of a range of different diphtheria vaccine product types. The assay is very specific and reliable, and different laboratories obtained comparable results, showing that the assay is suited for routine use. Once validated by manufacturers and recognized by regulators, this assay will greatly reduce the number of animals needed for batch release of diphtheria vaccines.

Autopsy of tetanus with foot gangrene as portal of entry.

Non-traumatic chronic skin lesions are the second most common cause of tetanus. Herein, we describe an 85-year-old woman who presented with a chronically infected skin lesion. She developed tetanus while in hospital and died of respiratory failure, after refusing mechanical ventilation. Routine immunization against tetanus began in Japan during 1968; hence many people born before 1968 are unvaccinated. Mortality due to tetanus is high and the proportion with protective antibodies is low in older adults. Therefore, we recommend tetanus vaccination for older persons in Japan who have chronic skin lesions and have never been vaccinated.

Serologic Immunity to Tetanus in the United States, National Health and Nutrition Examination Survey, 2015-2016.

BACKGROUND: Tetanus, a life-threatening infection, has become rare in the United States since introduction of tetanus toxoid-containing vaccines (TTCVs), recommended as a childhood series followed by decennial boosters beginning at age 11-12 years; vaccination uptake is high in children but suboptimal in adults. The objective of this study was to estimate the prevalence of sero-immunity to tetanus among persons aged ≥6 years in the United States and to identify factors associated with tetanus sero-immunity. Understanding population protection against tetanus informs current and future vaccine recommendations. METHODS: Anti-tetanus toxoid antibody concentrations were measured for participants of the 2015-2016 National Health and Nutrition Examination Survey (NHANES) aged ≥6 years for whom surplus serum samples were available using a microsphere-based multiplex antibody capture assay. Prevalence of sero-immunity, defined as ≥0.10 IU/mL, was estimated overall and by demographic characteristics. Factors associated with tetanus sero-immunity were examined using multivariable regression. RESULTS: Overall, 93.8% of the US population aged ≥6 years had sero-protection against tetanus. Prevalence of sero-immunity was above 90% across racial/ethnic categories, sex, and poverty levels. By age, ≥ 90% had protective sero-immunity through age 69 years, but prevalence of sero-immunity declined thereafter, with 75.8% of those aged ≥80 years having protective sero-immunity. Older age (adjusted prevalence ratio [aPR]: 0.89, 95% confidence interval [CI]: .85-.92) and being born outside the United States (aPR: 0.96, 95% CI: .93-.98) were significantly associated with lower prevalence of sero-immunity. CONCLUSIONS: The majority of the US population has vaccine-induced sero-immunity to tetanus, demonstrating the success of the vaccination program.