Adverse events following immunization of co- and separate administration of DTaP-IPV/Hib vaccines: A real-world comparative study.

To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.

Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.

BACKGROUND: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. METHODS AND FINDINGS: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). CONCLUSIONS: Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. TRIAL REGISTRATION: Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).

Exploring the "Urban Advantage" in Access to Immunization Services: A Comparison of Zero-Dose Prevalence Between Rural, and Poor and Non-poor Urban Households Across 97 Low- and Middle-Income Countries.

Urban children are more likely to be vaccinated than rural children, but that advantage is not evenly distributed. Children living in poor urban areas face unique challenges, living far from health facilities and with lower-quality health services, which can impact their access to life-saving vaccines. Our goal was to compare the prevalence of zero-dose children in poor and non-poor urban and rural areas of low- and middle-income countries (LMICs). Zero-dose children were those who failed to receive any dose of a diphtheria-pertussis-tetanus (DPT) containing vaccine. We used data from nationally representative household surveys of 97 LMICs to investigate 201,283 children aged 12-23 months. The pooled prevalence of zero-dose children was 6.5% among the urban non-poor, 12.6% for the urban poor, and 14.7% for the rural areas. There were significant differences between these areas in 43 countries. In most of these countries, the non-poor urban children were at an advantage compared to the urban poor, who were still better off or similar to rural children. Our results emphasize the inequalities between urban and rural areas, but also within urban areas, highlighting the challenges faced by poor urban and rural children. Outreach programs and community interventions that can reach poor urban and rural communities-along with strengthening of current vaccination programs and services-are important steps to reduce inequalities and ensure that no child is left unvaccinated.

Persistence and heterogeneity of the effects of educating mothers to improve child immunisation uptake: Experimental evidence from Uttar Pradesh in India.

Childhood vaccinations are among the most cost-effective health interventions. Yet, in India, where immunisation services are widely available free of charge, a substantial proportion of children remain unvaccinated. We revisit households 30 months after a randomised experiment of a health information intervention designed to educate mothers on the benefits of child vaccination in Uttar Pradesh, India. We find that the large short-term effects on the uptake of diphtheria-pertussis-tetanus and measles vaccination were sustained at 30 months, suggesting the intervention did not simply bring forward vaccinations. We apply causal forests and find that the intervention increased vaccination uptake, but that there was substantial variation in the magnitude of the estimated effects. We conclude that characterising those who benefited most and conversely those who benefited least provides policy-makers with insights on how the intervention worked, and how the targeting of households could be improved.

Determinants of incomplete penta vaccination among children aged 12 to 23 months in South-West Ethiopia.

Globally dropout rate for the three dose of penta (DPT) vaccine was highest in the African region. This mainly occurred in the African Region including Ethiopia. Despite high national incomplete vaccination status, there is lack of study on the determinants of incomplete vaccination in south west region, Ethiopia. Therefore, this study was conducted to identify determinants of incomplete Penta vaccination among children aged 12 to 23 months in Mettu district South-West Ethiopia. A Community based case-control study was conducted from April 24, May 23, 2022 in South-west Ethiopia. Data was collected from 297 participants (99 cases and 198controls) by using simple random sampling techniques. Cases were children age from 9 to 23 months who missed at least one dose from the routine vaccine and controls were completed the entire routine vaccine schedule. Data was entered to Epi-data version 3.1 and exported to SPSS version 23 for statistical analyses. Binary and multivariable logistic regression with a 95% CI and a p-value of < 0.05 was done to declare statistical significance. A total of 95 cases and 197 controls participated in the study. Rural residence [AOR: 3.9; 95% CI; (1.6, 9.4)], wealth indexes [AOR: 3.6; 95% CI; (1.8,7.0)], mothers unimmunized tetanus toxoid [AOR: 4.3; 95% CI; (2.1, 8.6)], postponed schedule [AOR: 4.6; 95% CI; (2.4, 8.8)], un satisfied to service [AOR: 3.7; 95% CI; (1.7,7.6)] and poor perception on benefit of vaccine [AOR:2.7; 95% CI; (1.2, 6.1)] were determinants of incomplete vaccination. Rural Residence, Family wealth index of poor; Mother not received tetanus vaccination; postponed vaccination schedule client satisfaction and caretaker perception on benefit of vaccination were identified determinants of incomplete vaccination.Health information should be given for the community and child caretaker on the benefit of complete vaccination. Community should be encouraged to not post pond vaccine schedule. Pregnant women should be strengthening to receive tetanus toxoid vaccine during pregnancy.

Vaccine Coverage at 36 Months and 7 Years by Parental Birth Country, Washington State.

BACKGROUND AND OBJECTIVES: Ensuring equitable vaccination access for immigrant communities is critical for guiding efforts to redress health disparities, but vaccine coverage data are limited. We evaluated childhood vaccination coverage by parental birth country (PBC) through the linkage of Washington State Immunization Information System data and birth records. METHODS: We conducted a retrospective cohort evaluation of children born in Washington from January 1, 2006 to November 12, 2019. We assessed up-to-date vaccination coverage status for measles, mumps, and rubella (MMR), diphtheria, tetanus, and pertussis (DTaP), and poliovirus vaccines at ages 36 months and 7 years. Children with ≥1 parent(s) born in selected non-US countries were compared with children with 2 US-born parents, using Poisson regression models to provide prevalence ratios. RESULTS: We identified 902 909 eligible children, of which 24% had ≥1 non-US-born parent(s). Vaccination coverage at 36 months by PBC ranged from 41.0% to 93.2% for ≥1 MMR doses and ≥3 poliovirus doses and 32.6% to 86.4% for ≥4 DTaP doses. Compared with children of US-born parents, the proportion of children up to date for all 3 vaccines was 3% to 16% higher among children of Filipino-, Indian-, and Mexican-born parents and 33% to 56% lower among children of Moldovan-, Russian-, and Ukrainian-born parents. Within-PBC coverage patterns were similar for all vaccines with some exceptions. Similar PBC-level differences were observed at 7 years of age. CONCLUSIONS: The linkage of public health data improved the characterization of community-level childhood immunization outcomes. The findings provide actionable information to understand community-level vaccination determinants and support interventions to enhance vaccine coverage.

Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines.

Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.

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).