Disparate kinetics in immune response of two different Haemophilus influenzae type b conjugate vaccines: Immunogenicity and safety observations from a randomized controlled phase IV study in healthy infants and toddlers using a 2+1 schedule.

Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.

Vaccination against Haemophilus influenzae type b (Hib) is included in the majority of national immunization programs worldwide and has shown to be effective in preventing Hib disease. In Europe, different vaccines containing Hib components are marketed. We compared the immune response and safety of 2 of these (DTPa-HBV-IPV/Hib, Ih group) and DTaP5-HB-IPV-Hib, Va group) in infants and toddlers, when used in a 2 + 1 schedule, i.e. two primary vaccination doses (at 2 and 4 months of age of the infant), followed by one booster dose at the age of one year. One month after the booster vaccination, the antibody concentration ratio between both groups (Ih group/Va group) was 0.917 (95% CI: 0.710­1.185) showing the DTPa-HBV-IPV/Hib vaccine was non-inferior to the DTaP5-HB-IPV-Hib vaccine; the difference in percentage of participants (Ih group ­ Va group) with antibody concentrations above 5 µg/mL was -6.3% (95% CI: −14.1% to 1.5%), which did not meet the pre-defined criterion for non-inferiority. In the Ih group, the quality of antibodies produced was somewhat higher versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. The kinetics of the immune response are different between the 2 vaccines. Since both vaccines contain different additional components (conjugated proteins), a possible effect of concomitant (simultaneously administered) vaccines was studied. Further investigations to confirm our findings are needed.

Immunogenicity and Safety of a Hexavalent DTwP-IPV-HB-PRP~T Vaccine Versus Separate DTwP-HB-PRP~T, bOPV, and IPV Vaccines Administered at 2, 4, 6 Months of Age Concomitantly With Rotavirus and Pneumococcal Conjugate Vaccines in Healthy Infants in Thailand.

BACKGROUND: This study investigated the immunogenicity and safety of a fully liquid, hexavalent, diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)- Haemophilus influenzae b (PRP-T) vaccine compared to licensed DTwP-HB-PRP~T, IPV, and bivalent oral poliovirus (bOPV) vaccines following co-administration with other pediatric vaccines [pneumococcal conjugate vaccine (PCV13) and rotavirus vaccine]. METHODS: Phase III, randomized, open-label study in Thailand. Healthy infants received DTwP-IPV-HB-PRP~T at 2, 4 and 6 months of age (N = 228), or DTwP-HB-PRP~T and bOPV (2, 4 and 6 months of age) and IPV (4 months of age) (N = 231). All participants received PCV13 (2, 4 and 6 months of age) and rotavirus vaccine (2 and 4 months of age). Immunogenicity for all antigens was assessed using validated assays, and noninferiority post-third dose was evaluated for anti-D, anti-T, anti-pertussis [anti-pertussis toxin (anti-PT) and anti-fimbriae 2/3 (anti-FIM)], anti-polio 1, 2, 3, anti-HB, and anti-PRP~T. Safety was assessed using parental reports. RESULTS: Noninferiority was demonstrated for each antigen, and overall noninferiority of DTwP-IPV-HB-PRP~T versus DTwP-HB-PRP~T+bOPV+IPV was concluded. Similarity in each group was observed for the GMC ratio for antirotavirus antibodies (20.9 and 17.3, respectively) and anti-PCV13 antibodies (range: 8.46-32.6 and 7.53-33.1, respectively). Two serious adverse events were related to DTwP-IPV-HB-PRP~T (febrile convulsion and acute febrile illness) and 1 was related to DTwP-HB-PRP~T+bOPV+IPV (febrile seizure), but overall there were no safety concerns with similar rates of participants experiencing solicited (99.1% and 98.3%) and unsolicited (19.3% and 19.5%) adverse events in each group. CONCLUSIONS: This study confirmed the suitability of DTwP-IPV-HB-PRP~T primary series vaccination in combination with rotavirus and PCV13 vaccines.

Routine Vaccination Coverage - Worldwide, 2020.

Endorsed by the World Health Assembly in 2020, the Immunization Agenda 2030 (IA2030) strives to reduce morbidity and mortality from vaccine-preventable diseases across the life course (1). This report, which updates a previous report (2), presents global, regional,* and national vaccination coverage estimates and trends as of 2020. Changes are described in vaccination coverage and the numbers of unvaccinated and undervaccinated children as measured by receipt of the first and third doses of diphtheria, tetanus, and pertussis-containing vaccine (DTP) in 2020, when the COVID-19 pandemic began, compared with 2019. Global estimates of coverage with the third dose of DTP (DTP3) and a polio vaccine (Pol3) decreased from 86% in 2019 to 83% in 2020. Similarly, coverage with the first dose of measles-containing vaccine (MCV1) dropped from 86% in 2019 to 84% in 2020. The last year that coverage estimates were at 2020 levels was 2009 for DTP3 and 2014 for both MCV1 and Pol3. Worldwide, 22.7 million children (17% of the target population) were not vaccinated with DTP3 in 2020 compared with 19.0 million (14%) in 2019. Children who did not receive the first DTP dose (DTP1) by age 12 months (zero-dose children) accounted for 95% of the increased number. Among those who did not receive DTP3 in 2020, approximately 17.1 million (75%) were zero-dose children. Global coverage decreased in 2020 compared with 2019 estimates for the completed series of Haemophilus influenzae type b (Hib), hepatitis B vaccine (HepB), human papillomavirus vaccine (HPV), and rubella-containing vaccine (RCV). Full recovery from COVID-19-associated disruptions will require targeted, context-specific strategies to identify and catch up zero-dose and undervaccinated children, introduce interventions to minimize missed vaccinations, monitor coverage, and respond to program setbacks (3).

Subnational inequalities in diphtheria-tetanus-pertussis immunization in 24 countries in the African Region.

OBJECTIVE: To analyse subnational inequality in diphtheria-tetanus-pertussis (DTP) immunization dropout in 24 African countries using administrative data on receipt of the first and third vaccine doses (DTP1 and DTP3, respectively) collected by the Joint Reporting Process of the World Health Organization and the United Nations Children's Fund. METHODS: Districts in each country were grouped into quintiles according to the proportion of children who dropped out between DTP1 and DTP3 (i.e. the dropout rate). We used six summary measures to quantify inequalities in dropout rates between districts and compared rates with national dropout rates and DTP1 and DTP3 immunization coverage. FINDINGS: The median dropout rate across countries was 2.4% in quintiles with the lowest rate and 14.6% in quintiles with the highest rate. In eight countries, the difference between the highest and lowest quintiles was 14.9 percentage points or more. In most countries, underperforming districts in the quintile with the highest rate tended to lag disproportionately behind the others. This divergence was not evident from looking only at national dropout rates. Countries with the largest inequalities in absolute subnational dropout rate tended to have lower estimated national DTP1 and DTP3 immunization coverage. CONCLUSION: There were marked inequalities in DTP immunization dropout rates between districts in most countries studied. Monitoring dropout at the subnational level could help guide immunization interventions that address inequalities in underserved areas, thereby improving overall DTP3 coverage. The quality of administrative data should be improved to ensure accurate and timely assessment of geographical inequalities in immunization.

Response to Vaccination in Infants Exposed to Antitumor Necrosis Factor Alpha In Utero.

In this retrospective cohort study, the response to routinely administered Haemophilus influenzae type B vaccine, pneumococcal and pertussis vaccinations in 27 children exposed to antitumor necrosis factor alpha (anti-TNFα) during pregnancy was measured. The overall vaccination response seems comparable for children exposed to anti-TNFα and healthy infants. After primary vaccination series, inadequate response was present in some patients and might be related to exposure to anti-TNFα.

The Challenge of Achieving Immunity Through Multiple-Dose Vaccines in Madagascar.

Administration of many childhood vaccines requires that multiple doses be delivered within a narrow time window to provide adequate protection and reduce disease transmission. Accurately quantifying vaccination coverage is complicated by limited individual-level data and multiple vaccination mechanisms (routine and supplementary vaccination programs). We analyzed 12,541 vaccination cards from 6 districts across Madagascar for children born in 2015 and 2016. For 3 vaccines-pentavalent diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine (DTP-HB-Hib; 3 doses), 10-valent pneumococcal conjugate vaccine (PCV10; 3 doses), and rotavirus vaccine (2 doses)-we used dates of vaccination and birth to estimate coverage at 1 year of age and timeliness of delivery. Vaccination coverage at age 1 year for the first dose was consistently high, with decreases for subsequent doses (DTP-HB-Hib: 91%, 81%, and 72%; PCV10: 82%, 74%, and 64%; rotavirus: 73% and 63%). Coverage levels between urban districts and their rural counterparts did not differ consistently. For each dose of DTP-HB-Hib, the overall percentage of individuals receiving late doses was 29%, 7%, and 6%, respectively; estimates were similar for other vaccines. Supplementary vaccination weeks, held to help children who had missed routine care to catch up, did not appear to increase the likelihood of being vaccinated. Maintaining population-level immunity with multiple-dose vaccines requires a robust stand-alone routine immunization program.

Circulation of pertussis and poor protection against diphtheria among middle-aged adults in 18 European countries.

Reported incidence of pertussis in the European Union (EU) and the European Economic Area (EEA) varies and may not reflect the real situation, while vaccine-induced protection against diphtheria and tetanus seems sufficient. We aimed to determine the seroprevalence of DTP antibodies in EU/EEA countries within the age groups of 40-49 and 50-59 years. Eighteen countries collected around 500 samples between 2015 and 2018 (N = 10,302) which were analysed for IgG-DTP specific antibodies. The proportion of sera with pertussis toxin antibody levels ≥100 IU/mL, indicative of recent exposure to pertussis was comparable for 13/18 countries, ranging between 2.7-5.8%. For diphtheria the proportion of sera lacking the protective level (<0.1 IU/mL) varied between 22.8-82.0%. For tetanus the protection was sufficient. Here, we report that the seroprevalence of pertussis in these age groups indicates circulation of B. pertussis across EU/EEA while the lack of vaccine-induced seroprotection against diphtheria is of concern and deserves further attention.

Effect of Haemophilus influenzae Type b Vaccination on Nasopharyngeal Carriage Rate in Children, Tehran, 2019.

BACKGROUND: Haemophilus influenzae (H. influenzae) strains, which commonly reside as commensals within the human pharynx and can remain as an asymptomatic carrier, but become invasive leading to pneumonia, septic arthritis, or meningitis. The Pentavac (pentavalent vaccine, manufactured by India, SII (DTwP-HepB-Hib)) was introduced to the Iranian National Immunization Plan in November 2014. The aim of this study is to investigate H. influenzae type b (Hib) carrier rate among children under 6 years old in Tehran. METHODS: This cross-sectional study was performed on 902 children including vaccinated/unvaccinated in the age of 6 months to 6 years, in Tehran. Sampling was performed from July 2019 to September 2019. Nasopharyngeal samples were taken from children by sterile swab. The PCR method was used to extract DNA. Then, all H. influenzae isolates were initially confirmed by molecular tests. BexA was used to distinguish typeable H. influenzae strains from nontypeable Haemophilus influenzae (NTHi). RESULTS: A total of 902 children were enrolled in the study: 452 were female (51%). H. influenzae carriage rate was 267 (29%), of that 150 samples (16.6%) were typeable. The nasopharyngeal Hib carrier rate in the children was 2.6% (24/902). 262 cases did not receive Hib vaccine. Analysis in nonnursery's children aged 4 to 6 (unvaccinated) years showed that the lower educational level of father, mother, and family number correlated with increased odds of colonization of children with Hib. CONCLUSION: Our findings showed a significant decrease (60%) in the overall Hib nasopharyngeal carriage in healthy children under six years after 5 years after the start of Hib vaccination.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study.

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Safety of Diphtheria and Tetanus Toxoids and Acellular Pertussis (DTaP) Vaccine in Adults in Japan.

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is generally used for booster vaccination of infants in Europe and the United States to avoid increased reactogenicity after diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccination. However, Japan has extended the use of additional DTaP vaccination without reducing the antigen dose for diphtheria and pertussis in adolescents and adults, despite limited reports on its safety in adults. This prospective, observational, questionnaire-based study investigated the occurrence of adverse events (AEs) following DTaP vaccination between June 2018 and June 2019 in participants aged 10 years or older. Of the 250 eligible participants, 235 (94%) responded regarding AEs. Among them, 133 (56.6%) reported AEs, of which 39 reported systemic AEs (16.6%) and 120 reported local AEs (51.1%) attributed to DTaP vaccination. The incidence of local AEs was markedly higher with DTaP vaccination than with non-DTaP vaccination (51.1% vs. 10.5%), and AEs appeared later (P < 0.01) and lasted longer (P < 0.01) with DTaP vaccination. However, more than 75% of these AEs resolved within 7 days. DTaP vaccination was not associated with any serious AEs. These results indicate that the DTaP vaccine can be widely used as a booster in adults as an alternative to the Tdap vaccine.

Worldwide inverse correlation between Bacille Calmette-Guérin (BCG) immunization and COVID-19 mortality.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has spread to all countries in the world, and different countries have been impacted differently. The study aims to understand what factors contribute to different COVID-19 impacts at the country level. METHODS: Multivariate statistical analyses were used to evaluate COVID-19 deaths and cases relative to nine other demographic and socioeconomic factors in all countries and regions of the world using data as of August 1, 2020. The factors analyzed in the study include a country's total COVID-19 deaths and cases per million population, per capita gross domestic product (GDP), population density, virus tests per million population, median age, government response stringency index, hospital beds availability per thousand population, extreme poverty rate, Bacille Calmette-Guérin (BCG) vaccination rate, and diphtheria-tetanus-pertussis (DTP3) immunization rate. RESULTS: The study reveals that COVID-19 deaths per million population in a country most significantly correlates, inversely, with the country's BCG vaccination rate (r = - 0.50, p = 5.3e-5), and also significantly correlates a country's per capita GDP (r = 0.39, p = 7.4e-3) and median age (r = 0.30, p = 0.042), while COVID-19 cases per million population significantly correlate with per capita GDP and tests per thousand population. To control for possible confounding effects of age, the correlation was assessed in countries propensity score matched for age. The inverse correlation between BCG vaccination rates and COVID-19 case (r = - 0.30, p = 0.02) and death (r = - 0.42, p = 0.0007) remained significant among the top 61 countries with the highest median age. CONCLUSION: This study contributes to a growing body of evidence supporting the notion that BCG vaccination may be protective against COVID-19 mortality.

Vaccination Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten - United States, 2019-20 School Year.

State and local school vaccination requirements serve to protect students against vaccine-preventable diseases (1). This report summarizes data collected by state and local immunization programs* on vaccination coverage among children in kindergarten (kindergartners) in 48 states, exemptions for kindergartners in 49 states, and provisional enrollment and grace period status for kindergartners in 28 states for the 2019-20 school year, which was more than halfway completed when most schools moved to virtual learning in the spring because of the coronavirus 2019 (COVID-19) pandemic. Nationally, vaccination coverage† was 94.9% for the state-required number of doses of diphtheria and tetanus toxoids, and acellular pertussis vaccine (DTaP); 95.2% for 2 doses of measles, mumps, and rubella vaccine (MMR); and 94.8% for the state-required number of varicella vaccine doses. Although 2.5% of kindergartners had an exemption from at least one vaccine,§ another 2.3% were not up to date for MMR and did not have a vaccine exemption. Schools and immunization programs can work together to ensure that undervaccinated students are caught up on vaccinations in preparation for returning to in-person learning. This follow-up is especially important in the current school year, in which undervaccination is likely higher because of disruptions in vaccination during the ongoing COVID-19 pandemic (2-4).

Childhood vaccinations: Hidden impact of COVID-19 on children in Singapore.

Although the direct health impact of Coronavirus disease (COVID-19) pandemic on child health is low, there are indirect impacts across many aspects. We compare childhood vaccine uptake in three types of healthcare facilities in Singapore - public primary care clinics, a hospital paediatric unit, and private paediatrician clinics - from January to April 2020, to baseline, and calculate the impact on herd immunity for measles. We find a 25.6% to 73.6% drop in Measles-Mumps-Rubella (MMR) uptake rates, 0.4 - 10.3% drop for Diphtheria-Tetanus-Pertussis-inactivated Polio-Haemophilus influenza (5-in-1), and 8.0-67.8% drop for Pneumococcal conjugate vaccine (PCV) across all 3 sites. Consequent herd immunity reduces to 74-84% among 12-month- to 2-year-olds, well below the 95% coverage that is protective for measles. This puts the whole community at risk for a measles epidemic. Public health efforts are urgently needed to maintain efficacious coverage for routine childhood vaccines during the COVID-19 pandemic.

Reduced Mortality After Oral Polio Vaccination and Increased Mortality After Diphtheria-tetanus-pertussis Vaccination in Children in a Low-income Setting.

PURPOSE: The diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) were introduced in children 3 of 5 months of age in 1981-1983 in Bandim, in the capital of Guinea-Bissau. Because DTP has been linked to deleterious nonspecific effects (NSEs) and OPV to beneficial NSEs, we followed up this cohort to 3 years of age and examined the effects of DTP with OPV on all-cause mortality and the interactions of DTP and OPV with the measles vaccine (MV). METHODS: DTP and OPV were offered at 3 monthly community weighing sessions. Vaccination groups were defined by the last vaccine received. We compared overall mortality for different groups in Cox proportional hazards regression models, reporting hazards ratios (HRs) with 95% CIs. FINDINGS: The study cohort included 1491 children born in Bandim from December 1980 to December 1983. From 3 to 35 months of age, with censoring for MV, children vaccinated with DTP and/or OPV had higher mortality than both unvaccinated children (HR = l.66; 95% CI, 1.03-2.69) and OPV-only vaccinated children (HR = 2.81; 95% CI, 1.02-7.69); DTP-only vaccinated children had higher mortality than OPV-only vaccinated children (HR = 3.38; 95% CI, 1.15--9.93). In the age group of 3-8 months, before MV is administered, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 3.38; 95% CI, 1.59-7.20). Between 9 and 35 months of age, when MV is given, DTP-vaccinated and MV-unvaccinated children had higher mortality (HR = 2.76; 95% CI, 1.36-5.59) than children who had received MV after DTP, and among children who received DTP with MV or after MV, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 6.25; 95% CI, 2.55-15.37). IMPLICATIONS: Because the 2 vaccines had differential effects and the healthiest children were vaccinated first, selection biases are unlikely to explain the estimated impact on child survival. OPV had beneficial NSEs, and administration of OPV with DTP may have reduced the negative effects of DTP.

Persistence of Hepatitis B Immune Memory Until 6 Years of Age Following Hexavalent DTaP-IPV-HB-PRP~T Vaccination in a 3-, 5- and 11- to 12-month Schedule and Response to a Subsequent Hepatitis B Challenge Vaccination.

Anti-hepatitis B (HBs) antibody persistence and hepatitis B challenge were evaluated at 6 years of age following vaccination of fully liquid DTaP-IPV-HB-PRP~T or reconstituted DTaP-IPV-HB//PRP~T at 3, 5, 11-12 months of age. At 6 years, 53.8% and 73.5% had seroprotective anti-HBs antibodies (≥10 mIU/mL), increasing to 96.7% and 95.9% postchallenge, confirming a strong anamnestic response in primed vaccinees.

Timeliness of immunisation with the pentavalent vaccine at different levels of the health care system in the Lao People's Democratic Republic: A cross-sectional study.

BACKGROUND: The timely administration of vaccines is considered to be important for both individual and herd immunity. In this study, we investigated the timeliness of the diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (pentavalent) vaccine, scheduled at 6, 10 and 14 weeks of age in the Lao People's Democratic Republic. We also investigated factors associated with delayed immunization. METHODS: 1162 children aged 8-28 months who had received the full course of the pentavalent vaccine at different levels of the health care system were enrolled. Vaccination dates documented in hospital records and/or immunisation cards were recorded. Age at vaccination and time intervals between doses were calculated. Predictors for timely completion with the pentavalent vaccine at 24 weeks were assessed by bivariate and multivariable analyses. RESULTS: Several discrepancies in dates between vaccination documents were observed. In general, vaccination with the pentavalent vaccine was found to be delayed, especially in health care settings below the provincial hospital level. Compared to the central hospital level, less participants who were vaccinated at the district/health center level received the third dose by 16 (48% at the central hospital level vs. 7.1% at the district and 12.4% at the health center level) and 24 weeks of age (94.4% at the central hospital level vs 64.6% at the district-outreach and 57.4% at the health center level) respectively. In logistic regression analyses, lower education level of the mother as well as vaccination by outreach service, were independently associated with delayed completion of vaccination. CONCLUSION: We observed a general delay of vaccination, especially at lower ranked facilities, which correlated with indicators of poor access to health services. This highlights the need for further improving health equity in rural areas. Age-appropriate vaccination should become a quality indicator for the national immunization programme. In addition, we recommend further training of the health care staff regarding the importance of reliable documentation of dates.

Impacto en niños menores de un año del programa de vacunación con dTpa en embarazadas en Castelló / Impact in children under the age of one of Tdap vaccination programme on pregnant women in Castelló

INTRODUCCIÓN: Se analiza el cambio en las tasas de incidencia de tosferina en menores de un año en Castelló, antes y después de la introducción de la vacunación a embarazadas en enero de 2015. MÉTODOS: Se han comparado las tasas de incidencia del periodo postvacunal (2015-2018) con el prevacunal (2011-2014) en todas las edades, niños de 3 a 11 meses y menores de 3 meses. Se han calculado los riesgos relativos y sus intervalos de confianza al 95%. RESULTADOS: La tasa global fue superior en el periodo postvacunal que en el prevacunal (0,23 vs. 0,15 por 1.000 personas-año), pero disminuyó en los menores de 3 meses. Los riesgos relativos fueron: 1,56 (IC 95% 1,34-1,82) para todas las edades; 1,73 (IC 95% 0,87-3,57) para 3 a 11 meses, y 0,35 (IC 95% 0,16-0,69) para menores de 3 meses. Un patrón similar se observó para niños hospitalizados. CONCLUSIONES: La tasa de incidencia en menores de 3 meses se redujo en un 65%, y el riesgo de hospitalización en un 71%, lo que evidencia que la medida ha sido efectiva. Esta reducción de la incidencia ocurrió de forma específica en este grupo de edad y no en otros

INTRODUCTION: The objective was to compare incidence rates of pertussis in children under the age of one in Castelló, before and after the introduction of vaccination of pregnant women in January 2015. METHODS: The incidence of the post-vaccine period (2015-2018) was compared with the pre-vaccine period (2011-2014) in all ages, in children from 3 to 11 months and under 3 months. The relative risks and their 95% confidence intervals (95% CI) were calculated. RESULTS: The overall rate of pertussis in all ages was higher in the post-vaccine period than in the pre-vaccine period (0.23 vs. 0.15 per 1.000 person-years), but decreased in those under 3 months. The relative risks were: 1.56 (95% CI 1.34-1.82) in all ages; 1.73 (95% CI 0.87-3.57) for children aged 3 to 11 months, and 0.35 (95% CI 0.16-0.69) for children under 3 months. A similar pattern was observed for hospitalised children. CONCLUSIONS: The incidence rate in children under 3 months was reduced by 65% in the period after the intervention, and the hospitalisation risk rate by 71%, suggesting that the measure has been effective and specific for this age group

Association between season of vaccination and antibody levels against infectious diseases.

Vaccination has reduced the disease burden of vaccine-preventable diseases. However, the extent to which seasonal cycles of immunity could influence vaccine-induced immunity is not well understood. A national cross-sectional serosurveillance study performed in the Netherlands (Pienter-2) yielded data to investigate whether season of vaccination was associated with antibody responses induced by DT-IPV (diphtheria, tetanus and poliomyelitis), MMR (measles, mumps and rubella) and meningococcus C (MenC) vaccines in children. In total, 434 children met the inclusion criteria to study DT-IPV immunity, 811 for MMR and 311 for MenC. Differences in log(antibody levels) by season of vaccination were investigated with linear multivariable regression analyses. Seroconversion rates varied according to season of vaccination for rubella (90% of autumn-vaccinated children vs. 99% of winter-vaccinated had concentrations above cut-off levels). Summer-vaccinated boys showed a slower decline of tetanus antibodies (6% per month), in comparison with winter-vaccinated boys. In conclusion, season of vaccination showed little association with immunological protection. However, a number of associations were seen with a P-value of about 0.03; and adding data from a just-completed nationwide serological study might add more power to the current study. Further immunological and longitudinal investigations could help understand the mechanisms of seasonal influence in vaccine-induced responses.

Tetanus Vaccination 2020 and Collateral Protections against Pertussis and Diphtheria.

Tetanus is a life-threatening but vaccine-preventable disease caused by the toxin of the bacterium Clostridium tetani and is characterized by muscle spasms and autonomic nervous system dysfunction. It is prevented through vaccination with tetanus toxoid, but because the causative agent is widespread in the environment, eradication is impossible. Therefore, efforts to reduce incidence are aimed at reaching elimination, rather than eradication. This article reviews the pathogenesis, clinical manifestation and treatment of tetanus, and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus in the United States.