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Background: Vaccination during pregnancy with tetanus, diphtheria, acellular pertussis (aP) (Tdap) anti-gens is important for early protection of newborn infants against pertussis, particularly for preterm infants. This study evaluated the effect of Tdap vaccination during pregnancy on the immunogenicity of a diphtheria (D), tetanus (T), aP, inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influen-zae type b (PRP ti T) vaccine in term and preterm populations.Methods: A prospective, observational study (NCT02511327) recruited women and their infants based on delivery (term or preterm) and vaccination status (vaccinated with a Tdap vaccine [BoostrixTM, GlaxoSmithKline] during pregnancy or not vaccinated in the last 5 years). All infants received licensed DTaP-IPV-HB-PRP ti T (HexyonTM, Sanofi) (8, 12, 16 week primary series and booster at 13 months of age [preterm infants] or 15 months of age [term infants]). Immunogenicity was evaluated using validated assays. Data were pooled into term (N = 127) and preterm infants (N = 105), and infants of women who received a Tdap vaccine during pregnancy (N = 199) or not (N = 33).Results: Before primary vaccination, antibody levels were higher for term than preterm infants for anti-D, anti-polio 1, 2, 3, anti-PT, anti-FHA, and anti-PRP, and similar for anti-HBs and anti-T. At this time, infants of Tdap-vaccinated women had higher anti-D, anti-T, anti-PT, anti-FHA, and anti-PRP antibody levels than infants of Tdap-unvaccinated women; anti-HBs and anti-polio antibody levels were similar in both groups. Post-primary, pre-booster, and post-booster, there were only small differences in seroprotection rates (anti-D, anti-T, anti-polio 1, 2, 3, anti-HBs, anti-PRP) and seroconversion rates (anti-PT, anti-FHA), except for anti-HBs >= 10 mIU/mL and anti-PRP >= 0.15 lg/mL post-primary vaccination (higher for term [98.31 % and 90.91 %, respectively] versus preterm infants [89.80 % and 79.41 %, respectively]).Conclusions: These data support the use of DTaP-IPV-HB-PRP ti T vaccine for primary and booster vacci-nation in term and preterm born infants and in infants born to Tdap-vaccinated or Tdap-unvaccinated women.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Parents and healthcare providers usually defer or avoid immunization for children with neurological conditions. This study was conducted to investigate the common issues of immunization among these special children and the impact of specialists' recommendation on improving immunization practice.We included 2,221 children with underlying neurological conditions seeking vaccination consultation at the first Immunization Advisory Clinic in China during 2017-2019. The primary neurological conditions and immunization status were analyzed. All parents were informed to self-report the adverse events following catch-up immunization. For specially concerned children with hereditary disorders, immune-related encephalopathy and epilepsy, we conducted the active follow-up to monitor the compliance with recommendation and the adverse events.All counselling children were assessed as not having any contraindication of immunization. A total of 2,019 (90.9%) children with underlying neurological conditions had delayed immunization and 99 (4.5%) had non-immunization. The coverage rate of age-appropriate vaccines was 56.1%. The most concerned vaccines were diphtheria, tetanus and acellular pertussis combined vaccine, diphtheria and tetanus combined vaccine, meningococcal polysaccharide vaccine and Japanese encephalitis vaccine. Resuming immunization was recommended for the 2,048 (92.2%) children. Most of counselling children complied with the specialists' recommendation. Neither progress nor flaring of the neurological medical conditions was reported from parents.Vaccine hesitancy was a common issue for Chinese children with all kinds of neurological conditions. Specialized consultation on immunization is helpful to build vaccine confidence for the special children. Immunization for children with underlying neurological conditions is generally safe.

This study examined healthcare resource use (HCRU) for selected vaccine-preventable diseases (VPD) in secondary care in England.The hospital episode statistics (HES) dataset covering all secondary care interactions within the English National Health Service (NHS) from 2015 to 2021 was used to identify and track HCRU for patients with a primary or secondary diagnosis for pertussis and Haemophilus influenzae type b (Hib), or a primary diagnosis only for hepatitis B, diphtheria, poliomyelitis, or tetanus. The first documented diagnosis during the study period (01/04/2015-31/03/2021) was the index event.7,274 patients with a total of 5,554,343 patient-days (mean follow up 1,491 days) were included. The total number of hospital admissions was 27,092 and total inpatient cost was £4,987,770, with hepatitis B making up ∼80 % of this. Mean outpatient hospital appointments per patient were highest for tetanus (4.00), but total outpatient AE cost burden was highest for Hib (£643,343 [mean per attendance £144.57]). For patients 0-9 years of age (n = 1,917), pertussis (n = 1,547) and Hib (n = 313) were by far the most commonly coded diseases. Hepatitis B was the most common disease in adults of working age and Hib was most prevalent in adults of retirement age. Surprisingly, poliomyelitis was observed in the database potentially due to historic diagnoses and/or coding inaccuracy. Other discrepancies with surveillance data were noted.VPDs impose a large burden on the NHS, but there is potential to reduce this and improve public health by optimising vaccination schedules, improving access and ensuring high coverage rates.

Safety and potency assessment for batch release testing of established vaccines still relies partly on animal tests. An important avenue to move to batch release without animal testing is the consistency approach. This approach is based on thorough characterization of the vaccine to identify critical quality attributes that inform the use of a comprehensive set of non-animal tests to release the vaccine, together with the principle that the quality of subsequent batches follows from their consistent production. Many vaccine antigens are by themselves not able to induce a protective immune response. The antigens are therefore administered together with adjuvant, most often by adsorption to aluminium salts. Adjuvant function is an important component of vaccine potency, and an important quality attribute of the final product. Aluminium adjuvants are capable of inducing NLRP3 inflammasome activation. The aim of this study was to develop and evaluate an in vitro assay for NLRP3 inflammasome activation by aluminium-adjuvanted vaccines. We evaluated the effects of Diphtheria-Tetanus-acellular Pertussis combination vaccines from two manufacturers and their respective adjuvants, aluminium phosphate (AP) and aluminium hydroxide (AH), in an in vitro assay for NLRP3 inflammasome activation. All vaccines and adjuvants tested showed a dose-dependent increase in IL-1β production and a concomitant decrease in cell viability, suggesting NLRP3 inflammasome activation. The results were analysed by benchmark dose modelling, showing a similar 50% effective dose (ED50) for the two vaccine batches and corresponding adjuvant of manufacturer A (AP), and a similar ED50 for the two vaccine batches and corresponding adjuvant of manufacturer B (AH). This suggests that NLRP3 inflammasome activation is determined by the adjuvant only. Repeated freeze-thaw cycles reduced the adjuvant biological activity of AH, but not AP. Inflammasome activation may be used to measure adjuvant biological activity as an important quality attribute for control or characterization of the adjuvant.

Since the establishment of the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions in 2015, there has been an urgent need for field validation of pharmacovigilance feasibility in low- and middle-income countries. In this study, we assess the availability and quality of archival medical records at ten randomly selected high-traffic maternity wards in Kinshasa province, Democratic Republic of Congo (DRC).A retrospective cohort of mother-child pairs was established from all recorded births taking place at study sites between July 1, 2019 to February 28, 2020 through digitization of medical records. Adverse birth outcomes and maternal vaccination status, where available and linkable, were defined according to GAIA. Basic demographic information on mothers and newborns was also tabulated; birth outcomes were assessed for both intra-site prevalence and a pooled prevalence.A total of 7,697 mother-newborn pair records were extracted, with 37% of infants screening positive as cases of adverse outcomes. Maternal vaccination information was linkable to 67% of those cases. In total, 51% of stillbirths, 98% of preterm births, 100% of low birthweight infants, 90% of small for gestational age infants, 100% of microcephalic infants, and 0% of neonatal bloodstream infections were classifiable according to GAIA standards following initial screening. Forty percent of case mothers had some indication of tetanus vaccination prior to delivery in their medical records, but only 26% of case mothers met some level of GAIA definition for maternal vaccination during the pregnancy of interest.Archival birth records from delivery centers can be feasibly utilized to screen for stillbirth and maternal tetanus vaccination, and to accurately classify preterm birth, low birthweight, small for gestational age, and congenital microcephaly. Assessment of other neonatal outcomes were limited by inconsistent postpartum infant follow-up and records keeping.

Background Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might improve clinical outcomes compared with intramuscular injection. Methods In a 2 × 2 factorial trial, all patients aged 16 years or older with a clinical diagnosis of generalised tetanus admitted to the intensive care unit of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were eligible for study entry. Participants were randomly assigned first to 3000 IU human or 21 000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff masked to treatment allocations. The primary outcome was requirement for mechanical ventilation. The analysis was done in the intention-to-treat population. The study is registered at ClinicalTrials.gov, NCT02999815; recruitment is completed. Findings 272 adults were randomly assigned to interventions between Jan 8, 2017, and Sept 29, 2019, and followed up until May, 2020. In the intrathecal allocation, 136 individuals were randomly assigned to sham procedure and 136 to antitoxin; in the intramuscular allocation, 109 individuals were randomly assigned to equine antitoxin and 109 to human antitoxin. 54 patients received antitoxin at a previous hospital, excluding them from the intramuscular antitoxin groups. Mechanical ventilation was given to 56 (43%) of 130 patients allocated to intrathecal antitoxin and 65 (50%) of 131 allocated to sham procedure (relative risk [RR] 0·87, 95% CI 0·66–1·13; p=0·29). For the intramuscular allocation, 48 (45%) of 107 patients allocated to human antitoxin received mechanical ventilation compared with 48 (44%) of 108 patients allocated to equine antitoxin (RR 1·01, 95% CI 0·75–1·36, p=0·95). No clinically relevant difference in adverse events was reported. 22 (16%) of 136 individuals allocated to the intrathecal group and 22 (11%) of 136 allocated to the sham procedure experienced adverse events related or possibly related to the intervention. 16 (15%) of 108 individuals allocated to equine intramuscular antitoxin and 17 (16%) of 109 allocated to human antitoxin experienced adverse events related or possibly related to the intervention. There were no intervention-related deaths. Interpretation We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe, but did not provide overall benefit in addition to intramuscular antitoxin administration.

Vaccinations are reported at the state level, but services are delivered at the county level through health departments (HD). This research contributes statistical models to predict county level HPV vaccination.Using a cross sectional study design, secondary data were analyzed for the years 2016-2018 for all counties of GA. Study population was male and female adolescents aged 13-17 who received the tetanus, diphtheria and pertussis (Tdap) vaccine. The number of administered HPV vaccine doses and HPV vaccination coverage rate were modeled using indicators of HD clinic access, age, sex, race/ethnicity, socioeconomic status, education, median household income, health insurance, and urban/rural residence.By county the number of administered HPV vaccine doses showed a statistically significant positive association with indicators of HD clinic access: public transit and the number of HD private clinics. HPV vaccination coverage showed a statistically significant negative association with White race and rural residency.Examining Tdap vaccinated adolescents conservatively predicted HPV vaccination and controlled for multiple confounders such as vaccination ineligibility, vaccine exemption, and vaccine opposition. Within this population, public health professionals and clinicians could use these statistical models to target HPV vaccination efforts among non-Hispanic whites and rural communities at the county level.

Infections can have a significant impact on morbidity and mortality in multiple sclerosis (MS) patients. Therefore, vaccinations are of immense importance. If vaccination willingness is to be increased, possible influencing factors should be identified. The aim of the present study was to investigate the status of active immunisation in MS patients in association with sociodemographic, clinical-neurological, psychopathological and personality variables using the NEO-Five Factor Inventory, the Temperament and Character Inventory-Revised and the Hospital Anxiety and Depression Scale.Four hundred and four MS patients from two German neurological hospitals were examined for their vaccination attitudes, in detail, the general willingness to vaccinate and the current vaccination status of mumps, measles and rubella (MMR) as well as tetanus and influenza. We also looked at the current level of disability in relation to the current vaccination status, as well as possible associated personality and psychopathological variables.Patients with a complete MMR vaccination status were significantly younger and those with a complete influenza vaccination status were significantly older than those with related incomplete vaccination status. Tetanus vaccination status completeness did not differ depending on age and did not show substantial association with personality scores. However, influenza vaccination completeness was associated with differences in personality and psychopathological variables; extraversion, openness, novelty seeking, harm avoidance and anxiety. A reported general vaccination willingness was significantly correlated with the current completeness of tetanus and influenza vaccinations. Novelty seeking, persistence, extraversion, agreeableness, conscientiousness and neuroticism were found associated with an increased vaccination willingness. Anxiety and depression were not related to general vaccination willingness.No specific personality trait could be defined on its own in relation to general vaccination willingness or complete vaccination status. Younger patients should be made more aware of influenza vaccination. Reasons for rather low vaccination rates need to be further investigated.

Background A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PTgen) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women. Methods A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 μg PTgen and 1 μg FHA (ap1gen), tetanus, reduced-dose diphtheria (Td) combined to ap1gen (Tdap1gen) or combined to recombinant pertussis containing 2 μg PTgen and 5 μg FHA (Tdap2gen), or one dose of licensed recombinant TdaP vaccine containing 5 μg PTgen and 5 μg FHA (Boostagen®, TdaP5gen) or licensed Tdap vaccine containing 8 μg of chemically inactivated pertussis toxoid (PTchem), 8 μg FHA, and 2.5 μg pertactin (PRN) (BoostrixTM, Tdap8chem). Serum Immunoglobulin G (IgG) antibodies against vaccine antigens were measured before and 28 days after vaccination by ELISA. To advance to a trial in pregnant women, formulations had to induce a PT-IgG seroresponse rate with a 95% confidence interval (95% CI) lower limit of ≥ 50%. Results Between 5 and 22 July 2018, a total of 250 women with median age of 31 years were enrolled. Post-vaccination PT-IgG seroresponse rates were 92% (95% CI 81–98) for ap1gen, 88% (95% CI 76–95) for Tdap1gen, 80% (95% CI 66–90) for Tdap2gen, 94% (95% CI 83–99) for TdaP5gen, and 78% (95% CI 64–88) for Tdap8chem. Frequencies of injection site and systemic reactions were comparable between the groups. No serious adverse events were reported during the 28-day post-vaccination period. Conclusions All recombinant acellular pertussis vaccines were safe and immunogenic in women of childbearing age, and all met pre-defined immunogenicity criteria to advance to a trial in pregnant women. Clinical Trial Registration: Thai Clinical Trial Registry, TCTR20180321004.

The drastic decline of Ukraine's immunization coverage since 2009 led to concerns about potential resurgence diphtheria and tetanus, along with other vaccine-preventable diseases.To assess population immunity against diphtheria and tetanus, we tested specimens from the serosurvey conducted in 2017 among children born in 2006-2015, the birth cohorts targeted by the nationwide outbreak response immunization following a circulating vaccine-derived poliovirus type 1 outbreak in Zakarpattya province in 2015. We surveyed four regions of Ukraine, using cluster sampling in Zakarpattya, Sumy, and Odessa provinces and simple random sampling in Kyiv City. We tested serum specimens for IgG antibodies against diphtheria and tetanus, using microbead assays (MBA). We estimated seroprevalence and calculated 95% confidence intervals. We also obtained information on the immunization status of surveyed children.Seroprevalence of ≥0.1 IU/mL diphtheria antibodies was80% in all survey sites (50.0%-79.2%). Seroprevalence of ≥0.1 IU/mL tetanus antibodies was ≥80% in Sumy, Kyiv City, and Odessa (80.2%-89.1%) and 61.6% in Zakarpattya. Across the sites, the proportion of children vaccinated age-appropriately with diphtheria-tetanus-containing vaccines (DTCV) was 28.5%-57.4% among children born in 2006-2010 and 34.1%-54.3% among children born in 2011-2015. The proportion of recipients of 3 DTCV doses increased from 7.1%-16.7% among children born in 2006-2010 to 19.8%-38.6% among children born in 2011-2015, as did the proportion of recipients of zero DTCV doses (2.6%-8.8% versus 8.0%-14.0%, respectively).Protection against diphtheria among children born in 2006-2015 was suboptimal (80%), particularly in Zakarpattya. Protection against tetanus was adequate (≥80%) except in Zakarpattya. Diphtheria-tetanus immunization status was suboptimal across all sites. Catch-up vaccination of unvaccinated/under-vaccinated children and other efforts to increase immunization coverage would close these immunity gaps and prevent the resurgence of diphtheria and tetanus in Ukraine, particularly in Zakarpattya.

Background There are worrying indications that diphtheria-tetanus-pertussis (DTP) vaccine has negative non-specific effects for females. We previously found, in a trial of early-Bacillus Calmette-Guerin (BCG) to low weight (LW) neonates, that receiving early-DTP (before 2 months of age), was associated with increased female mortality compared with no-DTP/delayed-DTP. Within a subsequent LW trial, we aimed to retest this observation. Methods Between 2010 and 2014, in Guinea-Bissau, 2,398 infants were randomised 1:1 to early-BCG (intervention) or delayed-BCG (standard practice for LW neonates) and visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. DTP is recommended at 6 weeks of age. We examined the effect of having “early-DTP” versus “no-DTP” at the time of the 2-month visit on all-cause mortality between the 2- and 6-month visits in Cox models stratified by sex and adjusted for BCG-group and 2-month-weight-for-age (z-scores) providing adjusted mortality rate ratios (aMRRs). We analysed to which extent conditions varied between the present and the previous LW trials and how that might have affected the overall result of comparing the early-DTP and the no-DTP groups. Results At the time of the 2-month visit, 75% (1,795/2,398) had received DTP. Those vaccinated had better anthropometric indices than no-DTP infants at birth and by 2 months of age. Between the 2- and 6-month visits, 29 deaths occurred. The early-DTP/no-DTP aMRR was 1.09 (95% CI: 0.44–2.69); 1.19 (0.45–3.15) for females and 0.77 (0.14–4.19) for males. Compared to the previous study, the present study cohort had 56% (30–72%) lower overall mortality, fewer no-DTP infants, higher BCG vaccination coverage and several more oral polio vaccine campaigns. Conclusion We did not find that early-DTP was associated with increased female mortality as found in a previous study; differences in results may partly be due to a decline in overall mortality and changes in vaccination practices.

GSK initiated a Pregnancy Registry in the United States (US) for the reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap; Boostrix, GSK) vaccine with the aim to detect and describe pregnancy outcomes in women vaccinated with Boostrix 28 days before estimated conception or during pregnancy.Voluntary reports of pregnancy exposure to Boostrix received from spontaneous and post-marketing surveillance sources in the US were assessed. Reports were classified as prospective or retrospective based on the knowledge of pregnancy outcomes at the time of reporting. For completeness, reports of exposure to Boostrix or to the Tdap-inactivated poliovirus vaccine (Boostrix-IPV, GSK) reported to the global safety database from countries outside the US were also evaluated.From May 2005 to August 2019, 1517 (1455 prospective and 62 retrospective) pregnancy reports were received in the Boostrix US Pregnancy Registry. Of the prospective reports, 250 had known outcomes: 244 live infants with no apparent birth defects (BDs), three live infants with BDs, and three spontaneous abortions with no apparent BDs. Of the retrospective reports, 55 had known outcomes: 33 live infants with no apparent BDs, 16 live infants with BDs, one spontaneous abortion with no apparent BDs, four stillbirths with no apparent BDs, and one stillbirth with BDs. Cumulatively, 1321 pregnancy reports (1006 for Boostrix; 315 for Boostrix-IPV) were received from countries outside the US. Of these, 163 prospective reports and 551 retrospective reports had known outcomes. Results were in line with those from the Boostrix US Pregnancy Registry.Data currently available from the Boostrix US Pregnancy Registry and from countries outside the US suggested that exposure to Boostrix or Boostrix-IPV during pregnancy does not raise safety concerns related to adverse pregnancy outcomes or BDs.

Background Routine adolescent vaccination recommendations in the United States include tetanus, diphtheria, and acellular pertussis, quadrivalent meningococcal conjugate vaccine, and human papillomavirus vaccines. Although coverage for these individual vaccines is known, limited data are available on composite completion for all three vaccines. Methods This cross-sectional analysis of pooled 2015–2018 National Immunization Survey–Teen data used logistic regression to estimate model-adjusted composite vaccination completion nationally and by state among United States adolescents aged 17 years. National Immunization Survey–Teen data were combined with state-level data to estimate a multilevel model identifying factors associated with composite vaccination completion. Results The pooled model-adjusted composite vaccination completion was 30.6% (95% confidence interval [CI], 30.13%–31.04%) nationally, varying from 11.3% in Idaho (6.91%–17.95%) to 56.4% (49.81%–62.82%) in Rhode Island. Individual-level factors with the greatest impact on composite completion were having a provider's recommendation for human papillomavirus vaccination (odds ratio, 3.24; 95% CI, 2.76–3.80) and a check-up visit at age 16–17 years (odds ratio, 2.35; 95% CI, 1.80–3.07), with other individual-level factors associated with completion including being Medicaid insured, female, Hispanic, or non-Hispanic black. State-level quadrivalent meningococcal conjugate vaccination mandates were also associated with an increased likelihood of composite vaccination completion (odds ratio, 1.64; 95% CI, 1.16–2.33). Conclusions Fewer than one-third of 17-year-old individuals have completed all three recommended vaccines, with rates varying by state. Although this study identified implementable strategies to improve composite completion, additional research is needed to further understand factors associated with adolescent vaccination completion.

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

Background Serum IgG anti-Vi titers attained by 327 children 6–23 months of age immunized with Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar TCV®), of whom 193/327 received a booster dose 2 years post-primary vaccination, were previously reported. Methods Anti-Vi IgG in boosted and unboosted children 3, 5, and 7 years post-primary immunization were monitored using three different enzyme-linked immunosorbent assays (ELISAs): Vacczyme™ kit ELISA (all specimens); “Szu” ELISA (all specimens), and National Institute of Biological Standards NIBSC ELISA (subset). Endpoints analyzed included: persisting seroconversion (titer remaining ≥ 4-fold above baseline), geometric mean titer (GMT), geometric mean-fold rise post-vaccination, and percent exhibiting putative protective anti-Vi level (≥2 µgSzu/ml) using Szu method and National Institutes of Health IgG reference standard. In assessing the persistence of elevated anti-Vi titers stimulated by Typbar-TCV®, four subgroups were compared based on whether or not the initially enrolled children were boosted on day 720 and whether they provided serum on all key timepoints, or if they missed one or more timepoints: i) Among boosted participants, an “All Specimens Cohort” (ASC) comprised 86 children who provided sera on days 42, 720 (booster), 762 (42 days post-booster), 1095, 1825 and 2555, to define kinetics of the Vi antibody response in a fully compliant cohort of boosted children monitored over seven years; ii) Among non-boosted subjects, a compliant All Specimens Cohort of 25 children provided sera on days 0, 42, 720, 1095, 1825, and 2555; iii) Among boosted children, an “Any Available Specimen” (AAS) subgroup consisted of boosted children who provided sera on days 0, 42, and 720 days and also on one or more of days 762, 1095, 1825, or 2555 but not on all those time points; iv) Among the non-boosted subjects, there was also an Any Available Specimen subgroup of 47 children who provided sera on days 0 and 42, of whom 41 subsequently contributed sera on one or more of days 1095, 1825 and 2555. Results Vacczyme™ GMTs among boosted ASC children (N = 86) increased significantly on day 762, and remained 32-fold, 14-fold, and 10-fold over baseline at 3, 5 and 7 years; among unboosted ASC children (N = 25), GMTs remained 21-fold, 8-fold and 5-fold over baseline, respectively. Post-primary vaccination, 72% and 44% of unboosted ASC subjects (N = 25) exhibited persisting seroconversion by Vacczyme™ at 5 and 7 years, respectively; the corresponding numbers for ASC boosted subjects were 84% and 71%. Amongst the four sub-groups, boosted subjects showed higher prevalence of persisting seroconversion at most time points with the gap widening by 7th year, though not statistically significant (except 3rd year). Tested by Szu and also NIBSC ELISAs, 92–100% of unboosted ASC children showed persisting seroconversion at 7 years with 100% also exceeding the Szu protective threshold. Conclusion To extend protection, administering a booster of Typbar TCV® to children ∼5 years after their primary dose, i.e., coinciding with school entry, may be advisable. Typbar TCV® is presently the only WHO pre-qualified Vi conjugate vaccine with reported efficacy, effectiveness, and long-term immunogenicity findings.

Vaccination in pregnancy (VIP) is dually beneficial - it protects the mother and the baby from tetanus, influenza, and pertussis. VIP uptake is low in many countries. Vaccine hesitancy, defined by the World Health Organization (WHO) as a "delay in acceptance or refusal of vaccination despite the availability of vaccination services" is one of WHO's ten threats to global health per 2019. According to extensive research, mostly from high-income countries (HIC) and limited to tetanus, influenza and pertussis vaccines, lack of provider recommendations, safety concerns, and limitations in access are the main barriers to VIP. Health care provider recommendation is the leading facilitator for VIP across various socioeconomic status groups. Data on strategies to overcome patient, provider, and system barriers to VIP are inconsistent, contradictory, or lacking. Patient-focused research on evidence-based strategies to overcome provider and system barriers is needed. Furthermore, VIP programs require embedded continuous quality improvement to ensure sustainability.

Introduction Adults from racial and ethnic minorities and low-income groups are disproportionately affected by vaccine-preventable diseases. The objective of this study is to examine the trends in adult vaccination coverage in the U.S. by race/ethnicity and SES from 2010 to 2019. Methods Temporal trends in influenza; pneumococcal; herpes zoster; and tetanus, diphtheria, and acellular pertussis vaccination coverage were examined by race/ethnicity and SES in 2020 using the National Health Interview Surveys from 2010 to 2019. Results Influenza vaccination coverage differed by race/ethnicity among adults aged ≥65 years (61.4% for Black, 63.9% for Hispanic, 71.9% for Asian, and 72.4% for White adults). Race/ethnicity, household income, education level, and health insurance type were significantly associated with receipt of influenza; pneumococcal; tetanus, diphtheria, and acellular pertussis; and zoster vaccinations among adults aged ≥65 years in a multivariable-adjusted regression model. Socioeconomic differences in influenza vaccine uptake narrowed among adults aged 18–64 years from 2010 to 2019. By contrast, racial/ethnic and socioeconomic differences in vaccine uptake persisted from 2010 to 2019 among adults aged ≥65 years. Conclusions Racial and ethnic disparities in vaccine uptake persisted over the last decade. Socioeconomic disparities in influenza vaccine coverage narrowed among adults aged 18–64 years; however, disparities persisted among adults aged ≥65 years. Efforts are urgently needed to achieve equity in immunization rates.

Expanded programs on immunization (EPIs) are country-specific vaccine programs designed and implemented to prevent childhood diseases globally, including in Thailand. Hill tribe children in Thailand live in remote areas with underdeveloped education systems and low economic status. This study aimed to assess serocoverage under the EPI and access to vaccination clinics.A cross-sectional study was performed to assess serocoverage after childhood vaccination among hill tribe children who lived in 34 selected villages in Chiang Rai Province, Thailand. A validated questionnaire was administered, and 3-mL blood specimens were collected. Antibodies against hepatitis B surface antigen (anti-HBs), hepatitis B core antigen (anti-HBc), measles, Japanese encephalitis virus (JEV), and tetanus were detected. Chi-square tests were performed to detect the different proportion of patients with antibodies with different characteristics.Half of the hill tribe children aged 1-18 years did not have medical evidence (logbook) of immunization. More than 98.0% of the children who had medical evidence received the recommended immunizations. Only half of the children had anti-HBs (51.1%), and 22.3% had antibodies against JEV. The majority were found to be positive for antibodies against measles (83.3%) and tetanus (91.4%). Sex (p-value = 0.028), tribe (p-value 0.001), age (p-value 0.001), and parents' monthly income (p-value = 0.008) were associated with a lack of medical evidence.Existing immunization programs for hill tribe children in Thailand should be urgently evaluated and monitored for effectiveness.

Background Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. Methods We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. Findings 41 344 children were vaccinated in April–May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, pInterpretation Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. Funding The study was funded by the Bill & Melinda Gates Foundation.

Current international guidelines recommend routinely vaccinating haematopoetic stem cell transplant (HSCT) recipients. Despite significant infection-related mortality following autologous HSCT, routine vaccination programmes (RVP) completion is poor. For recovered HSCT recipients, it is uncertain whether catch-up vaccination remains worthwhile years later. To determine potential susceptibility to vaccine preventable infections, we measured antibody titres in 56 patients, a median of 7 years (range 0–29) following autologous HSCT, who had not completed RVP. We found that almost all participants had inadequate titres against diphtheria (98.2%) and pneumococcal infection (100%), and a significant proportion had inadequate titres against measles (34.5%). Of those subsequently vaccinated according to available guidelines, many mounted adequate serological responses. These data suggest a pragmatic catch-up approach for autologous HSCT recipients who have not completed RVP is advisable, with universal vaccination against some pathogens (e.g. Streptococcus pneumoniae and diphtheria) and serologically-guided approaches for others (e.g. measles and varicella zoster virus).

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6-70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients' characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.

Background Maternal immunization has the potential to reduce both maternal and infant morbidity and mortality by protecting women from complications during pregnancy as well as conferring protection for babies who are too young to be vaccinated. Limited evidence is available about the drivers of maternal immunization in middle-income countries such as Peru. Vaccines against tetanus, diphtheria and influenza are recommended beginning in the second trimester in Peru; however, vaccination coverage has remained low in Peru compared to other countries in the region. As additional vaccines are recommended for administration in pregnancy, a better understanding of the perceptions and attitudes of pregnant women that influence vaccination are needed to design communication materials. Methods We conducted an exploratory qualitative study to understand the individual level factors influencing pregnant women’s vaccine uptake. We interviewed pregnant women about their knowledge, perceptions and experiences with vaccination during pregnancy. Community health workers recruited women in a peri urban area of Peru in April 2018. Results Twelve women were interviewed, the majority of which had received vaccination during the current pregnancy. The most common reasons for vaccination were to protect the baby and because vaccines are effective. Concerns included vaccine safety during pregnancy and adverse effects on the unborn baby. Some women mentioned that because vaccines are given later in pregnancy, the unborn baby is stronger, so vaccines will not harm them. Women highlighted that the main reason for not being vaccinated was lack of information. They also noted that they were the decision-maker in whether or not they were vaccinated. Most women said that they trusted healthcare providers and that trust was linked to providing information through open communication. Conclusions Overall, participants were supportive of maternal vaccination. They believed that vaccines were effective in protecting both their unborn baby and themselves. The main reason given for non-vaccination was lack of knowledge about vaccination in pregnancy. The strong desire expressed by study participants to get more information presents an opportunity for immunization programs to develop interventions that facilitate better information dissemination to pregnant women to increase vaccination uptake.

Objectives To evaluate the concordance between maternal report of antepartum tetanus, diphtheria, pertussis (Tdap) vaccination and vaccination status documented in the electronic medical record (EMR), as well as factors associated with discordance. Study design A survey was completed by a convenience sample of postpartum patients in a New York metropolitan hospital. The survey collected patients’ demographic information, health beliefs, and whether they received Tdap vaccine during this pregnancy. The patient's Tdap vaccination status was abstracted from the EMR, a combination of data gathered from the obstetrician and patient's hospital record. Kappa statistics measured the agreement between maternal report and EMR on antepartum Tdap vaccination. Univariate and multivariable logistic regression analyses were performed to identify maternal characteristics associated with discordance. Results Of the 1571 patients with Tdap status available in the EMR, 1549 patients (92%) reported on receipt status for Tdap vaccination during pregnancy; 1328 maternal reports (86%) agreed with the EMR for Tdap status (kappa = 0.72, 95% CI 0.68-0.75). Several factors were statistically significant in multivariable analyses: lower income was associated with greater discordance (ie, overreporting; P = .02), as well as certain health beliefs including “Pregnant women should be concerned about the possibility of pertussis in their babies” (aOR 2.86, 95% CI 1.02-8.04) and “My friends would probably think getting a Tdap vaccine is a good idea” (aOR 2.36, 95% CI 1.11-4.99). Conclusions Maternal recall of Tdap vaccination during pregnancy is consistent with the EMR. This supports the value of maternal report in determining Tdap vaccination status, which is especially important when vaccination records are not available.

Objectives Country of origin might affect vaccine uptake in children born to immigrants. We aimed to evaluate differences in childhood vaccination coverage (VC) and timeliness by macro-area of origin of foreign mothers residing in Italy. Study design Multicentre retrospective birth cohorts. Methods We analysed data of 23,287 children born in 2009–2014 to foreign women in the cities of Rome, Turin and Treviso. We retrieved data through record-linkage of the population, vaccination and birth registries. We estimated VCs at different ages for vaccines against tetanus, measles and meningococcal group-C, using the Kaplan–Meier method. Factors associated with vaccine uptake were evaluated using multilevel Poisson models. Results Estimates of VC at any age and for all antigens were significantly lower in children born to women from Asia and higher in children born to women from Africa, as compared to other macro-areas. Similar differences by area of origin were observed for timeliness; independently of mother's sociodemographic characteristics and neonatal outcomes, the probability of delay vaccination after 2 years of age for each antigen was highest in children born to women from Asia. The risk of missed vaccination for all antigens was significantly higher in children born to younger and unemployed women. Conclusions Factors related to area of origin (e.g., cultural habits, language skills) are likely to affect parents’ decision to vaccinate their children. These factors, as well as sociodemographic characteristics, should be adequately investigated and addressed to increase vaccine uptake in foreign children, especially those born to Asian women.

Aim Pertussis is a respiratory tract infection, the vaccine for which was introduced in the Expanded Programme on Immunization (EPI) in Guizhou Province of China (hereafter referred as Guizhou) in the 1980s. This vaccine rapidly decreased incidence rates of pertussis in the province, however, despite the wide high coverage of the diphtheria, tetanus and acellular pertussis (DTaP) combined vaccine, there has been a resurgence of pertussis since 2014. Even with this recent increase in disease transmission, risk factors for pertussis infection have not been evaluated in Guizhou. We aimed to provide information on pertussis risk factors and insight on designing targeted pertussis control policies and measures through this study. Methods A 1∶2 matched retrospective case-control study was conducted between 2016 and 2017, involving infants and children younger than 6 years old and parents of the participants. The enrolled cases included clinical and laboratory confirmed pertussis cases according to the WHO-recommended pertussis definition. Controls were selected from children in the same neighborhood who were not diagnosed with pertussis prior to our investigation and did not exhibit any clinical manifestations of pertussis. Results The household size [Matched odds ratio (ORm) = 1.4, 95% confidence interval (CI): 1.1–1.7] and household members with antecedent cough (ORm = 3.6, 95% CI: 1.8–7.2) were significantly associated with their child’s pertussis onset. The parents’ occupations were significantly associated with their child’s pertussis onset (ORm = 9.4, 95% CI: 1.6–54.8, for mother side; ORm = 4.5, 95% CI: 1.2–16.5, for father side), when they worked in the business and/or service industry. Having family members with a history of cough was an independent risk factor for pertussis [Adjusted odds ratio (AOR) = 43.6, 95% CI: 2.7–694.0]. Besides, the parents' demographic characteristics and DTaP doses were not found to be independent factors. Conclusion Household exposure is an important risk factor for pertussis infection in infants and young children and should therefore be considered as a major factor during formulation of pertussis control policies and measures.

Stingray envenomation is common in coastal regions around the world and may result in intense pain that can be challenging to manage. Described therapies involve hot water immersion and potentially other options such as opioid and nonopioid analgesics, removal of the foreign body, wound debridement, antibiotics for secondary infection, and tetanus toxoid. However, for some patients, this may not be enough. Peripheral nerve blockade is a frequently used perioperative analgesic technique, but it has rarely been described in the management of stingray envenomation. Here, we report a case of stingray envenomation in an otherwise healthy 36-y-old male with pain refractory to traditional therapies. After admission for pain control, the patient received an ultrasound-guided sciatic popliteal nerve block. Upon completion of the peripheral nerve block, the patient reported rapid and complete resolution of the intense pain, which did not return thereafter.

Background: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. Methods: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7–366/7 weeks’ gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11–18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. Results: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4–1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). Conclusions: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. Clinical Trial Registration. ClinicalTrials.gov: NCT02853929. publishedVersion

Adult pertussis vaccination is increasingly recommended to control pertussis in the community. However, there is little data on the duration and kinetics of immunity to pertussis boosters in adults. We compared IgG responses to vaccination with a tetanus, low-dose diphtheria, low-dose acellular pertussis (Tdap) booster at 1 week, 1 month and 1 year post-vaccination in whole-cell (wP)-primed Australian paediatric healthcare workers who had received an adult Tdap booster 5-12 years previously, to those who received their first Tdap booster. Tdap vaccination was well tolerated in both groups. Previously boosted adults had significantly higher pre-vaccination IgG concentrations for all vaccine-antigens, and more were seropositive for pertussis toxin (PT)-specific IgG (≥ 5 IU/mL) (69.5%; 95% confidence interval (CI) 59.5-79.5) than adults in the naïve group (45.2%; 95% CI 32.8-57.5). Tdap vaccination significantly increased IgG responses 1 month post-vaccination in both groups. This increase was more rapid in previously boosted than in naïve adults, with geometric mean fold-increases in PT-IgG at 1 week post vaccination of 3.6 (95% CI 2.9-4.3) and 2.6 (95% CI 2.2-3.2), respectively. Antibody waning between 1 month and 1 year post-vaccination was similar between groups for IgG specific to PT and filamentous haemagglutinin (FHA), but was faster for IgG against pertactin (PRN) in the naïve group (GMC ratio 0.36; 95% CI 0.31-0.42) than the previously boosted group (GMC ratio 0.45; 95% CI 0.39-0.50). At baseline, all but one adult had protective IgG titres against tetanus toxin (TT) (≥ 0.1 IU/mL), and 75.6% in the previously boosted and 61.3% in the naïve group had protective IgG titres against diphtheria toxoid (DT) of ≥ 0.1 IU/mL. This study shows that pertussis immune memory is maintained up to 12 years after Tdap vaccination in wP-primed Australian adults. There was no evidence that pertussis immune responses waned faster after a booster dose. These findings support current recommendations of repeating Tdap booster vaccination in paediatric healthcare workers at least every 10 years. Clinical trials registry: ACTRN12615001262594.

Objective: to investigate pertussis vaccination rates during pregnancy and the routine recommendation rates by maternity healthcare professionals (HCPs), including influencing factors, in Korea. Materials and methods: Two different questionnaires were developed and conducted anonymously for pregnant or postpartum women and maternity HCPs in 30 multi-centers. Maternal pertussis vaccination rates and maternity HCPs’ recommendation rates were analyzed. Independent influencing factors were analyzed using multivariate logistic regression analysis, respectively. Results: The rate of pertussis vaccination during pregnancy among 466 women was 67%. Among 164 multiparous women, 35.5% received pertussis vaccinations during every pregnancy. However, 27.9% among all pregnant women did not receive information about pertussis and vaccination. The independent influencing factors for maternal pertussis vaccination, given as the tetanus, diphtheria and acellular pertussis (Tdap), were “getting informed” (OR 18.597, 95% CI 11.206–30.861), “informed by OBGYN doctors” (OR 4.426, 95% CI 2.144–9.267), and “metropolitan residence” (OR 3.048, 95% CI 1.419–6.548). Among a total of 373 maternity HCPs, 210 (56.3%) routinely recommended pertussis vaccination, but 21.7% of the total maternity HCP participants did not know the maternal Tdap guideline. The independent factors affecting routine recommendation were the awareness of guideline (OR 9.771, 95% CI 5.227–18.265, p

Animal and human bite injuries are a public health burden. Dog bites outnumber cat bites, but cat bites pose the greatest risk for infection. Skin and soft tissue infections are the most frequent infectious manifestations resulting from bite injury, although invasive infection may occur through direct inoculation or dissemination through the bloodstream. Although contemporary, well-designed trials are needed to inform clinical practice, preemptive antibiotic therapy after a bite injury is warranted for injuries posing high risk for infection and for patients at risk of developing severe infection; antibiotics should target aerobic and anaerobic microbes that comprise the oral and skin flora.

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

Background Maintaining a high vaccination coverage rate (VCR) throughout the lifetime and complying with the National Immunization Program are essential to optimize the protection of the population. The study objectives were to evaluate the evolution of the VCRs and the compliance with the vaccination visits for the diphtheria, tetanus, poliomyelitis and pertussis boosters in France since the changes implemented in the 2013 National Immunization Program. Methods Cumulative booster VCRs were estimated at all vaccination visits, from 2013 to 2017, among persons eligible for a booster vaccination from a 1/97th random sample of French claims data. Broader age groups around the recommended ages by the vaccination schedule (6, 11–13, 25, 45, 65, 75, 85, 95y) were used: all persons aged 5 to 8, 10 to 15, 21 to 29, 41 to 49, 61 to 69, 71 to 79, 81 to 89 and 91 to 99. Results Over the study period, the diphtheria-tetanus-poliomyelitis booster VCRs increased, reaching in 2017: 73.3% at 8 years old, 75.6% at 15 years old, 46.6% at 29 years old, 38.4% at 49 years old, 36.3% at 69 years old, 30.8% at 79 years old, 22.1% at 89 years old and 11.0% at 99 years old. The pertussis VCRs were also increasing at all vaccination visits, in particular at the vaccination visits at 6 and 11–13 years old (from 16.4% to 63.8% and from 50.3% to 61.2%, respectively). Delayed vaccinations were observed at all vaccination visits. Conclusion VCRs for Diphtheria, Tetanus, Poliomyelitis and Pertussis booster vaccination increased from 2013 to 2017 while remaining suboptimal across all ages and lower in the adult populations. The analysis also shows that the introduction in 2013 of a pertussis vaccination at 6 years of age was relatively well-established in 2017 while other changes in recommendations were slowly or partially implemented.

Highlights • MAL-ED Bangladesh birth cohort data used in the analysis. • Relationship between vaccine titers and micronutrient data explored. • Positive association found between serum zinc level and tetanus vaccine titer. • The finding implicates the importance of improving zinc nutrition status of the children., Background Vaccine-preventable infectious diseases are often responsible for childhood morbidity and high rates of mortality. Immune response to the vaccine is associated with multiple factors in early childhood and measured by antibody titers. Among them, micronutrient deficiencies such as vitamin D and zinc deficiencies are the most important in resource-limited settings like Bangladesh. Objective We aimed to evaluate the association of vaccine response to low serum zinc and vitamin D levels in children. Methods We evaluated vaccine response for measles and poliovirus, tetanus and pertussis toxoid, and Ig A antibody levels to rotavirus by ELISA and serum vitamin D and zinc at 7 and 15 months in the MAL-ED birth cohort of the Bangladesh site. By using population-specific generalized estimating equations (GEE), the association between each explanatory variable and the binary outcome variable was examined longitudinally where the dependent variable was vaccine titers and the independent variables were low serum vitamin D and zinc levels. Results The GEE multivariable model identified a positive association between serum zinc level and tetanus vaccine titer (OR: 1.84; 95% CI: 1.07–3.17 and p value = 0.028) after adjusting for age, gender, birth weight, WAMI score, diarrhea, ALRI, exclusive breastfeeding, serum ferritin, serum retinol and undernutrition (stunting, wasting, underweight). No association was found between the rest of the vaccine titers with serum vitamin D and zinc level (p > 0.05). Conclusion In the MAL-ED birth cohort, where children were followed for five years, serum zinc level had a positive impact on tetanus vaccine titers.

Highlights • Immunization inequities persist in India despite substantial gains. • Sociodemographic characteristics contribute to non-immunization or under-immunization. • Tailored interventions can improve immunization coverage for those at high risk., Objectives While India has made substantial progress in introducing new vaccines and scaling up immunization coverage, inequities persist sub-nationally. This study was performed to investigate the risk of under-immunization based on class membership and to identify heterogeneous classes based on sociodemographic characteristics in pediatric and maternal populations in India through latent class analysis. Methods Data from the most recent National Family Health Survey conducted in 2015–2016 were used. Latent class analysis was used to model immunization coverage in children aged 12–23 months and mothers, and to identify subgroups to characterize those at risk of not being immunized. Results Patterns of sociodemographic characteristics were found to contribute to non-immunization or under-immunization among pediatric and maternal populations in India. Individuals who fit into one of three categories were identified in both populations: those at high, medium, and lower risk of not being immunized. Lower socioeconomic status, lack of antenatal care, and lower maternal education put individuals at higher risk of not being immunized with routine childhood vaccines and maternal tetanus toxoid. Conclusions Predisposing risk factors can persistently impact immunization status despite improvements in immunization access in India. Tailored programmatic interventions should be developed to improve immunization coverage among those children and mothers who are at highest risk of being under-immunized or not immunized.

INTRODUCTION. Maternal vaccination is critical for improving maternal and child health. Quality Improvement (QI) models(), such as the Centers for Disease Control and Prevention’s (CDC) Assessment, Feedback, Incentives, eXchange (AFIX)() model, have not yet been adapted to maternal vaccinations. This study assesses the impact of AFIX-OB, an adapted version of AFIX for obstetric settings, on maternal vaccination rates. METHODS. Between December 2016 and May 2018, state health departments and obstetric practices in Colorado and Georgia implemented the adapted AFIX-OB model. The model addressed unique patterns in patient encounters, practice flow, health records systems and competing clinical priorities in the obstetric setting through a menu of clearly-defined QI strategies, bi-weekly technical assistance meetings with designated immunization champions, incentives for champions/staff, and adapted tools to aid each practice during implementation. Vaccination rates were assessed by random chart reviews pre- and post-intervention. RESULTS. The AFIX-OB model was evaluated in eleven obstetric practices in two states as part of a multi-level intervention to increase maternal vaccination. Post AFIX-OB implementation, documented influenza vaccination rates increased from 56% at baseline to 65% (p

The existing vaccine paradigm assumes that vaccines only protect against the target infection, that effective vaccines reduce mortality corresponding to the target infection's share of total mortality, and that the effects of vaccines are similar for males and females. However, epidemiological vaccine research has generated observations that contradict these assumptions and suggest that vaccines have important non-specific effects on overall health in populations. These include the observations that several live vaccines reduce the incidence of all-cause mortality in vaccinated compared with unvaccinated populations far more than can be explained by protection against the target infections, and that several non-live vaccines are associated with increased all-cause mortality in females. In this Personal View we describe current observations and contradictions and define six emerging principles that might explain them. First, that live vaccines enhance resistance towards unrelated infections. Second, non-live vaccines enhance the susceptibility of girls to unrelated infections. Third, the most recently administered vaccination has the strongest non-specific effects. Fourth, combinations of live and non-live vaccines given together have variable non-specific health effects. Fifth, vaccinating children with live vaccines in the presence of maternal immunity enhances beneficial non-specific effects and reduces mortality. Finally, vaccines might interact with other co-administered health interventions, for example vitamin A supplementation. The potential implications for child health are substantial. For example, if BCG vaccination was given to children at birth, if higher measles vaccination coverage could be obtained, if diphtheria, tetanus, and pertussis-containing vaccines were not given with or after measles vaccine, or if the BCG strain with the best non-specific effects could be used consistently, then child mortality could be considerably lower. Pursuing these emerging principles could improve our understanding and use of vaccines globally.

Background The DTaP-IPV/Hib combination vaccine can replace the acellular tetanus vaccine, polio vaccine, and the Haemophilus influenzae type B vaccine. Data on the safety of DTaP-IPV/Hib vaccines are required. We aimed to evaluate the safety of the vaccination program. Methods Using the National Adverse Events Following Immunization (AEFI) surveillance system (CNAEFIS) in Guangzhou, China, a retrospective study was performed from May 11, 2011, to December 31, 2017. There were 376 cases of adverse events after vaccination with the DTaP IPV/Hib vaccine. The primary analysis indicators were the number of vaccines used, the number of AEFI reports received, and the reporting rate (per 100,000). Results From May 1, 2011, to December 31, 2017, 516,000 doses of vaccine were inoculated, and 376 cases of adverse reactions were reported; the reporting rate was 72.8 per 100,000 vaccines. There were eight cases of serious AEFIs (1.5 per 100,000), with four cases of thrombocytopenic purpura (0.8 per 100,000); three cases of cyanosis of the lips, stiffness, and flexion of limbs, and convulsions (0.6 per 100,000); and one case of a high fever (0.2 per 100,000). The highest incidence of AEFIs occurred after the fourth dose (n = 207, 55.0%, 40.1 per 100,000), followed by the first dose (n = 81, 21.5%, 15.7 per 100,000), second dose (n = 48, 12.8%, 9.3 per 100,000) and third dose (n = 40, 10.6%, 7.7 per 100,000). The AEFI incidence was higher after injection of the vaccine into the deltoid muscle of the upper arm (n = 276, 73.4%, 53.5 per 100,000) than after injection of the vaccine into the thigh (n = 100, 26.6%, 19.4 per 100,000). There was a significant difference between AEFIs after injection into the deltoid of the upper arm deltoid and the thigh (x2 = 164.8, P Conclusions Most of the reported AEFIs after DTaP-IPV/Hib vaccination are not serious. There were four cases of TP in this study; vaccination may be a rare cause of thrombocytopenic purpura.

Introduction In a pediatric clinic in California (US), 3823 patients were vaccinated with potentially-compromised vaccines following lapses in cold storage chain management between February 2014 and April 2015. A revaccination program was initiated in May 2015. Families were contacted by mail and encouraged to discuss follow-up options with their care team, namely: revaccination, serological testing and/or revaccination, or no further action. This study aimed: to understand which families were more likely to respond to the outreach, and to engage in any testing and/or revaccination; to determine whether or not vaccination with these potentially-compromised vaccines elicited sufficient immune response in pediatric patients; and to estimate the program cost. Methods Patients who had received potentially-compromised vaccines were identified, and relevant data were extracted from their electronic health records. Logistic regression analyses were performed to identify factors associated with response to outreach, serological testing and/or revaccination. Results 3823 patients between 0 and 21 years received an average of 3.1 potentially-compromised vaccines. 2547 revaccinations were performed (1515 patients) and 544 patients had serological testing results. Non-immune titer levels were only reported for 3–4% and 8% of the tested patients who had received potentially-compromised tetanus and hepatitis B vaccines, respectively, and only for children two years old and younger. Three years after the revaccination program started, 77% of all cases were considered resolved and 62.5% of patients (1970/3152) who were administered potentially-compromised vaccines were either revaccinated or had seroprotective titers. Response to outreach and decision to choose serological testing and/or revaccinate were affected by patient age, race/ethnicity and zip code median income (p Conclusion We observed race/ethnicity, patient age and income differences in response to the outreach and decision-making. For patients vaccinated with potentially-compromised vaccines, serological testing should be considered prior to revaccination. Revaccination may not be the most appropriate course of action for all patients.

Open pediatric forearm fractures are common injuries that present to emergency departments across the United States. A total of 32% to 80% of all open pediatric fractures involve the forearm. Standard treatment for these injuries includes prompt intravenous antibiotic administration, tetanus prophylaxis, and usually bedside irrigation as a temporizing measure. Gustilo and Anderson type 2 and 3 open pediatric forearm fractures are generally managed with formal irrigation and debridement and fracture stabilization in the operating room. Management of Gustilo and Anderson type 1 open pediatric forearm fractures is not standardized, and level I evidence is currently lacking. Based on the existing data available, early antibiotic administration, bedside irrigation, and fracture stabilization in the emergency department may be a safe and effective initial treatment for these injuries, conferring a low risk for subsequent infection.

Highlights • Manufacturing of the smallpox vaccine at the end of the 19th century was the beginning of the vaccine industry in the United States. • There is not information regarding the stocks or seed viruses used to manufacture those early vaccines. • Historical information, will allow a better understanding of the origin and evolution of the vaccine used to eradicate smallpox., For the first 80–90 years after Jenner’s discovery of vaccination in 1796, the main strategy used to disseminate and maintain the smallpox vaccine was arm-to-arm vaccination, also known as Jennerian or humanized vaccination. A major advance occurred after 1860 with the development of what was known as “animal vaccine”, which referred to growing vaccine material from serial propagation in calves before use in humans. The use of “animal vaccine” had several advantages over arm-to-arm vaccination: it would not transmit syphilis or other human diseases, it ensured a supply of vaccine even in the absence of the spontaneous occurrence of cases of cowpox or horsepox, and it allowed the production of large amounts of vaccine. The “animal vaccine” concept was introduced in the United States in 1870 by Henry Austin Martin. Very rapidly a number of “vaccine farms” were established in the U.S. and produced large quantities of “animal vaccine”. These “vaccine farms” were mostly established by medical doctors who saw an opportunity to respond to an increasing demand of smallpox vaccine from individuals and from health authorities, and to make a profit. The “vaccine farms” evolved from producing only smallpox “animal vaccine” to manufacturing several other biologics, including diphtheria- and other antitoxins. Two major incidents of tetanus contamination happened in 1901, which led to the promulgation of the Biologics Control Act of 1902. The US Secretary of the Treasury issued licenses to produce and sell biologicals, mainly vaccines and antitoxins. Through several mergers and acquisitions, the initial biologics licensees eventually evolved into some of the current major American industrial vaccine companies. An important aspect that was never clarified was the source of the vaccine stocks used to manufacture the smallpox “animal vaccines”. Most likely, different smallpox vaccine stocks were repeatedly introduced from Europe, resulting in polyclonal vaccines that are now recognized as “variants” more appropriately than “strains”. Further, clonal analysis of modern “animal vaccines” indicate that they are probably derived from complex recombinational events between different strains of vaccinia and horsepox. Modern sequencing technologies are now been used by us to study old smallpox vaccine specimens in an effort to better understand the origin and evolution of the vaccines that were used to eradicate the smallpox.

Background Invasive meningococcal disease has a high mortality rate in individuals aged ≥56 years, but no vaccine is currently licensed in the USA for this age group. This study assessed the safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) compared with a meningococcal quadrivalent polysaccharide vaccine (MPSV4) in this age group. Methods This was a Phase III, modified double-blind, randomized, non-inferiority study (NCT02842866) across 35 clinical sites in the USA and Puerto Rico in individuals aged ≥56 years. A single dose of the MenACYW-TT (n = 451) or MPSV4 vaccine (n = 455) was administered on Day 0. A serum bactericidal assay with human (hSBA) and baby rabbit (rSBA) complement was used to measure antibodies against serogroups A, C, W, and Y test strains at baseline and Day 30. Safety data were collected up to six months post-vaccination. Results The seroresponse to MenACYW-TT was non-inferior to MPSV4 for each of the serogroups (A: 58.2% vs. 42.5%; C: 77.1% vs. 49.7%; W: 62.6% vs. 44.8%, Y: 74.4% vs. 43.4%, respectively). At Day 30, participants achieving hSBA titers ≥1:8 were higher for all serogroups after MenACYW-TT vs. MPSV4 (77.4–91.7 vs. 63.1–84.2%, respectively). No safety concerns were identified for either vaccine. Conclusion MenACYW-TT was well-tolerated and immunogenic in ≥56-year-olds, offering the potential to replace MPSV4 in this age group.

Highlights • Low-dose tetanus-diphtheria (Td) vaccine is currently not licensed for children age 4–7 years. • Evidence suggests using Td as a second booster in ages 4–7 years yields durable immunity. • Evidence supports the recommendation to use Td booster dose in ages 4–7 years., For lifetime protection against diphtheria and tetanus, the World Health Organization (WHO) recommends six doses of diphtheria and tetanus containing vaccines. Td (reduced diphtheria toxoid, ≥2–5 IU) vaccines are currently licensed for ages 7 years and older, but use of Td vaccine for ages 4 years and older would have advantages for immunization programs in many low- and middle-income countries. For this reason, WHO convened an expert consultation to review the currently available evidence for the use of Td vaccine from 4 to 7 years of age which concluded: (1) no relevant biological difference in immune response in the relevant age group compared with children over 7 years of age; (2) adequate seroprotection in several studies with Td vaccine in the 4–7 age group and many studies using combination vaccines; (3) durable and protective response of at least 9–11 years duration in several longitudinal and modelling studies, (4) less reactogenicity compared with use of full-dose diphtheria vaccine, potentially improving the vaccination experience; and (5) adequate control of diphtheria in several countries using Td-containing combination vaccines in 4–7 year old children. On this basis, the experts concluded that from a programmatic perspective, Td vaccine given in ages 4–7 years, as a second booster dose in a six-dose series, would provide adequate protection against diphtheria and tetanus and recommended steps to include this change in age extension listed in the package insert.

Background To provide continuing protection, available meningococcal vaccines must provide long-term persistence of circulating functional antibodies against prevalent serogroups causing invasive meningococcal disease (IMD). This study assessed antibody persistence and safety of the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) and the meningococcal serogroup C vaccine conjugated to Corynebacterium diphtheriae CRM197 protein (MenC-CRM) for up to 6 years after booster dosing in children. Methods In the primary vaccination study, children were vaccinated at age 12 to 23 months. In the first extension study, children who completed the primary study received a booster dose 4 years later with the same primary vaccine. The current study assessed antibody persistence at 2 to 6 years postbooster against each of the 4 meningococcal serogroups using serum bactericidal assays using rabbit (rSBA) or human (hSBA) complement with antibody titer thresholds of ≥1:8 or ≥1:4, respectively, and geometric mean titers (GMTs). Safety evaluations during this period included serious adverse events (SAEs) related to vaccination and any event related to lack of vaccine efficacy. Results A total of 184 subjects were enrolled (MenACWY-TT = 159; MenC-CRM = 25). For MenACWY-TT, the percentages of subjects with rSBA titers ≥1:8 ranged from 96.7% to 100% across serogroups at 2 years postbooster and 71.6% to 94.0% at 6 years postbooster; rSBA GMTs decreased from Year 2 to 4 and generally remained stable thereafter. The percentages of subjects in the MenACWY-TT group with hSBA titers ≥1:4 were 70.0% to 100% across serogroups at 2 years postbooster and 58.5% to 98.5% at 6 years postbooster. No lack of efficacy, SAEs, or vaccine-related adverse events were reported. Conclusions The persistence of rSBA and hSBA antibodies was shown up to 6 years postbooster (10 years postprimary vaccination) with either MenACWY-TT or MenC-CRM, suggesting that this schedule may provide long-term protection against IMD. Clinicaltrials.gov: NCT01900899.

MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for use in individuals ≥6 weeks of age. We evaluated the safety and immunogenicity of MenACYW-TT when compared to a licensed quadrivalent conjugate meningococcal vaccine (Menveo®; MCV4-CRM; GlaxoSmithKline, Italy), and when co-administered with tetanus, diphtheria, acellular pertussis (Tdap) and human papilloma virus (HPV4) vaccines in healthy meningococcal vaccine-naïve adolescents (10-17 years old) in the United States of America.In this pivotal Phase II, open-label, multicenter study, 1715 participants were randomized to receive MenACYW-TT, MCV4-CRM, MenACYW-TT co-administered with Tdap and HPV4, or Tdap and HPV4 vaccines alone (NCT02199691). The primary objective was to evaluate whether antibody responses to MenACYW-TT antigens were non-inferior to antibody responses after MCV4-CRM administration. Meningococcal antibody titers were determined using human complement serum bactericidal assay (hSBA) with titers measured at baseline, and 30 days post vaccination (D30). A vaccine seroresponse was defined as baseline titers 1:8 with post-vaccination titers ≥1:8 or baseline titers ≥1:8 with a ≥4-fold increase at post-vaccination. Safety data were collected up to six months post-vaccination.Non-inferiority was demonstrated for MenACYW-TT vs MCV4-CRM (primary endpoint), and for MenACYW-TT co-administered with Tdap and HPV4 vs MenACYW-TT alone (secondary endpoint). The vaccine seroresponse rate was higher with MenACYW-TT than with MCV4-CRM, for each serogroup: A: 75.6% vs 66.4%; C: 97.2% vs 72.6%; W: 86.2% vs 66.6%; Y: 97.0% vs 80.8%. The safety profiles of MenACYW-TT, MCV4-CRM, and Tdap and HPV4 vaccines, administered with or without MenACYW-TT, were comparable. There were no vaccine-related serious adverse events.The MenACYW-TT vaccine was well tolerated and generated an immune response that was non-inferior to the licensed MCV4-CRM vaccine. Immunogenicity and safety profiles were comparable when MenACYW-TT was administered with or without Tdap and HPV4 vaccines in meningococcal vaccine-naïve adolescents.

Schools are increasingly being used to deliver vaccines. In 2015/16 three school-based vaccination programmes were delivered to adolescents in England: human papillomavirus (HPV), meningococcal groups A, C, W and Y disease (MenACWY) and tetanus, diphtheria and polio (Td/IPV). We assessed how school delivery models impact vaccine coverage and how a delivery model for one programme may impact another. Routinely collected national data were analysed to ascertain the school grade achieving highest coverage within each one-dose programme and to compare two-dose delivery models (within year vs across years) for the HPV vaccine. We also assessed whether the HPV delivery model was associated with coverage in other programmes. MenACWY and Td/IPV coverage was highest in younger school grades. Overall similar HPV coverage was achieved with both models (86.7% two doses within one year, 85.8% two doses across two years, p = 0.20). High two-dose HPV coverage in 2015/16 was reported in areas that achieved high HPV coverage in 2013/14 when three doses were required. Areas with high three-dose coverage in 2013/14 achieved higher coverage with a within-one-year approach (92.0% vs 85.2%, p 0.001), whilst areas reporting low coverage in 2013/14 achieved lower but similar coverage in 2015/16 with both models (79.2% vs 80.9% p = 0.29). MenACWY and Td/IPV coverage were higher in areas with high HPV coverage in 2013/14. Among high HPV coverage areas, MenACWY coverage was higher when HPV doses were delivered within year. School-based programmes should be offered as early as feasible and acceptable to optimise coverage. The choice of delivery model for HPV should take into account local performance and provider experience. Single providers may delivery multiple vaccines and the delivery for one programme may affect the performance of other programmes. Providers should consider local circumstances including past and current vaccine coverage and factors influencing coverage when deciding what delivery model to adopt.

Objectives: The Ministry of Health (MOH), Singapore, conducted the National Paediatric Seroprevalence Survey 2018 (NPSS 2018) to estimate the latest immunity levels against measles, rubella, varicella, diphtheria, tetanus and hepatitis B, and the seroprevalence of chronic hepatitis B virus (HBV) carriage in children and adolescents in Singapore. Methods: The survey involved prospective collection of residual sera from 1,200 children and adolescents aged 1–17 years in two public acute hospitals. Enzyme-linked immunosorbent assays (EIA) or plague reduction neutralisation tests (PRNT) were used to determine the seroprevalence of the vaccine-preventable diseases. Results: Overall prevalence of measles and rubella antibodies among Singaporean children and adolescents aged 1–17 years were 98.2% (95% CI: 91.2–98.8%) and 94.8% (95% CI: 93.4–95.9%) respectively. 97.1% (95% CI: 96.0–97.9%) of subjects had at least basic protection against diphtheria, while 89.3% (95% CI: 87.5–91.0%) were protected against tetanus. The prevalence of chronic HBV carriage was 0.4% (95% CI: 0.2–1.0%), while 45.7% (95% CI: 42.9–48.5%) were immune against HBV. The seroprevalence for varicella antibodies was 52.9% (95% CI: 50.1–55.7%). Concordance between vaccination status and seroprevalence was observed for measles, rubella, diphtheria and tetanus. Conclusion: Singapore’s children and adolescents are well-protected against measles, rubella, diphtheria and tetanus. Continual efforts in ensuring high vaccination coverage should be sustained. Keywords: Seroprevalence, Survey, Vaccine, Immunity, Children, Adolescents, Singapore, Epidemiology, Public health

Poisoning by venomous creatures is common. Most is benign, causing only minor irritation or pain, but rarely significant morbidity and mortality can occur. Medically important venomous creatures include snakes, spiders, scorpions and marine creatures. For suspected cases of severe envenoming, seek early expert advice from a clinical toxicologist or poisons information centre. First aid measures include pressure bandaging of the affected limb with immobilization in suspected snakebite and funnel web spider bite, and administration of vinegar after removing tentacles in box jellyfish stings. Management of severe envenoming requires resuscitation with early provision of antivenom where available. Ensure the patient has adequate tetanus prophylaxis. Pain is often prominent and adequate analgesia should be provided. Primary prevention of bites and stings is crucial to reduce the impact of envenoming.

Objectives To describe health care providers' experiences recommending human papillomavirus (HPV) vaccination before age 11 years as part of a multisession intervention to improve HPV vaccination coverage. Study design Between 2016 and 2018, we conducted 30-minute qualitative interviews with intervention participants approximately 1 month after intervention completion. Interviews explored participants' experiences with new strategies, including changing the age of routine recommendation. Thematic analysis of interview transcripts involved both deductive and inductive approaches. Results Twenty-six participants at 5 clinical sites were interviewed. Most were female (88%) primary care providers (46%), and worked 1.5-3.0 clinical days weekly. Many providers described initial skepticism about recommending vaccination before age 11 years, fearing that removing the HPV vaccine from the adolescent bundle with tetanus and meningitis vaccines would decrease parental acceptance. However, providers uniformly reported high parental acceptance owing to reduced stigma relating to sexual activity and the opportunity to administer fewer shots at each visit. Providers also noted that initiating vaccination earlier increased opportunities to complete the series and decreased the need for resource-intensive vaccine recall programs. Conclusions Providers had positive experiences recommending HPV vaccination before age 11 years. Routine recommendation before age 11 years may offer advantages related to fewer shots per visit, fewer missed opportunities, and reduction of parental concerns related to sexual activity.

Summary Background Low vaccination coverage as well as incomplete and delayed vaccinations pose a risk for the individual and population protection from vaccine-preventable diseases. Aim To describe vaccination patterns for nationally recommended basic and supplementary vaccinations in Swiss preschool children. Methods We performed a descriptive study based on administrative claims data from a large Swiss health insurer (Helsana), in cohorts of children born between January 2010 and December 2016. We assessed coverage rates of nationally recommended basic vaccinations (i.e., diphtheria, tetanus, acellular pertussis [DTaP], Haemophilus influenzae type b [Hib], poliomyelitis [IPV], measles, mumps, and rubella [MMR]) and supplementary vaccinations (i.e., pneumococcal conjugate vaccine [PCV] and meningococcal group C conjugate vaccine [MCV]) for each birth cohort at the age of 13, 25, and 37 months. Additionally, we analysed timeliness of vaccinations using inverse Kaplan-Meier curves. Results were extrapolated to the Swiss population. Results The study population comprised 563,216 children. We observed continuously increasing coverage rates for all vaccinations until the 2015 birth cohort. Overall, up-to-date status for the first dose of studied vaccinations at 37 months was as follows: DTaP: 95.4%; Hib: 94.9%; IPV: 95.5%; MMR: 86.8%; PCV: 83.2%; and MCV: 66.7%. On average, however, only seven out of ten children had an up-to-date status for completed basic vaccinations; even less (six out of ten) were up-to-date for recommended supplementary vaccinations at 37 months of age. Moreover, 4% of all analysed children received none of the recommended vaccinations and there were substantial regional differences. Delays in vaccine administration were common. The most frequently postponed basic vaccination was MMR; 22.6% of children vaccinated with the first dose experienced delays relative to age-appropriate standards. Conclusion To avoid future outbreaks and transmission of vaccine-preventable diseases, vaccination coverage in Switzerland must be further improved. In addition, more emphasis should be placed on timely vaccination.

Globally, 13 countries have yet to eliminate maternal and neonatal tetanus. While efforts have improved access to tetanus toxoid containing vaccines (TTCVs) and increased clean delivery practices, reaching elimination targets (1 case of neonatal tetanus per 1000 live births per district per year) may require significant resources to reach the remaining high risk and hard-to-reach districts.We estimated the cost to achieve maternal and neonatal tetanus elimination (MNTE) in three years in the remaining 13 countries: Afghanistan, Angola, Central African Republic, Democratic Republic of the Congo, Guinea, Mali, Nigeria, Pakistan, Papua New Guinea, Somalia, South Sudan, Sudan, and Yemen. Costs were estimated for: (1) vaccination campaigns using standard TTCVs and TT-Uniject™ targeting women of reproductive age in high risk areas, (2) additional vaccinations delivered to pregnant women at antenatal care (ANC) clinics, (3) clean delivery and umbilical cord care promotion, (4) neonatal tetanus surveillance strengthening, and (5) validation activities. We forecasted the averted mortality to assess the cost-effectiveness of achieving MNTE.It will cost an estimated US$197.7 million to realize MNTE over three years. These costs include $161.4 million for vaccination campaigns, $6.1 million for routine vaccination during ANC, $23.3 million for promotion of clean delivery practices, $4 million for surveillance, and $3 million for validation of MNTE. Achieving MNTE will avert approximately 70,000 neonatal deaths over ten years of vaccine protection, resulting in approximately 4.4 million life years gained. It will cost $2,900 per death averted and $45 per life year gained.Maternal and neonatal tetanus can be eliminated with significant financial investment, high prioritization, and strong political will. While substantial costs must be incurred to reach hard-to-reach populations, MNTE should be accomplished as a matter of health equity, and will significantly contribute to reaching the United Nations' Sustainable Development Goals.