Immunogenicity and safety of adsorbed diphtheria-purified pertussis-tetanus-inactivated polio (Sabin strain)-Haemophilus type b conjugate combined vaccine (DPT-IPV-Hib) in healthy Japanese Infants ≥ 2 and < 43 months of Age: A phase III, multicenter, active controlled, assessor-blinded, randomized, parallel-group study.

OBJECTIVE: This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV-Haemophilus influenzae type b [Hib]) in healthy Japanese infants aged ≥ 2 and < 43 months using a concomitant vaccination with ActHIB® (Hib) and Tetrabik (DPT-IPV) as a comparator. METHODS: This study was conducted as a phase 3, multicenter, active controlled, assessor-blinded, randomized, parallel-group study. Participants received a total of 4 subcutaneous doses (3 primary immunization doses and a booster dose) of either the experimental drug (DPT-IPV-Hib) or the active comparator (Hib + DPT-IPV). The primary endpoints were the anti-PRP antibody prevalence rate with ≥ 1 µg/mL, and the antibody prevalence rates against pertussis, diphtheria toxin, tetanus toxin, and attenuated poliovirus after the primary immunization. RESULTS: In 267 randomized participants (133 in the DPT-IPV-Hib group and 134 in the Hib + DPT-IPV group), the antibody prevalence rates after the primary immunization in both groups were 100.0 % and 88.7 % for anti-PRP antibody with ≥ 1 µg/mL, 99.2 % and 98.5 % against diphtheria toxin, and 100.0 % and 99.2 % against tetanus toxin, respectively. The antibody prevalence rates against pertussis and attenuated poliovirus were 100.0 % in both groups. The non-inferiority of the DPT-IPV-Hib group to the Hib + DPT-IPV group was verified for all measured antibodies. In both groups, all the GMTs of antibodies after the primary immunization were higher than those before the first dose, and those after the booster dose were higher than those after the primary immunization. No safety issues were identified. CONCLUSION: A single-agent Gobik, the first DPT-IPV-Hib pentavalent vaccine approved in Japan, was confirmed to simultaneously provide primary and booster immunizations against Hib infection, pertussis, diphtheria, tetanus, and poliomyelitis and to have a preventive effect and safety comparable to concomitant vaccination with Hib (ActHIB®) and DPT-IPV quadrivalent vaccine (Tetrabik).

Global vaccine coverage and childhood survival estimates: 1990-2019.

Objective: To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019. Methods: We used child mortality and vaccine coverage data from the Global Burden of Disease Study. We used a modified child survival framework and applied a mixed-effects regression model to estimate the reduction in deaths in children younger than 5 years associated with eight vaccines. Findings: Between 1990 and 2019, the diphtheria-tetanus-pertussis (DTP), measles, rotavirus and Haemophilus influenzae type b vaccines were significantly associated with an estimated 86.9 (95% confidence interval, CI: 57.2 to 132.4) million fewer deaths in children younger than 5 years worldwide. This decrease represented a 24.2% (95% CI: 19.8 to 28.9) reduction in deaths relative to a scenario without vaccines. The DTP and measles vaccines averted 46.7 (95% CI: 30.0 to 72.7) million and 37.9 (95% CI: 25.4 to 56.8) million deaths, respectively. Of the total reduction in child mortality associated with vaccines, 84.2% (95% CI: 83.0 to 85.1) occurred in 73 countries supported by Gavi, the Vaccine Alliance, with an estimated 45.4 (95% CI: 29.8 to 69.2) million fewer deaths from 2000 to 2019. The largest reductions in deaths associated with these four vaccines were in India, China, Ethiopia, Pakistan and Bangladesh (in order of the size of reduction). Conclusion: Vaccines continue to reduce childhood mortality significantly, especially in Gavi-supported countries, emphasizing the need for increased investment in routine immunization programmes.

Acceptance and willingness to pay for DTaP-HBV-IPV-Hib hexavalent vaccine among parents: A cross-sectional survey in China.

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age (p < .001), parents' education level (p = .024), and perceived price barriers (p < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.

Exploring trends and determinants of basic childhood vaccination coverage: Empirical evidence over 41 years.

Vaccination is widely considered to be one of the most important prevention measures as a health strategy. This paper examines trends in basic childhood vaccination coverage and which country and time-dependent determinants may have influenced childhood immunization rates (1-dose BCG, 1- and 3-dose DTP (diphtheria, tetanus, pertussis), 1-dose measles, and 3-dose polio) between 1980 and 2020 across 94 countries. We identify economic, inequality, demographic, health, education, labor market, environmental, and political stability factors of immunization. To do this, we use data from the annual WHO and United Nations International Children's Emergency Fund (UNICEF) coverage estimates. The empirical analysis consists of generalized estimating equation models to assess relationships between immunization rates and socioeconomic factors. Additionally, we follow the Barro and Sala-i-Martín approach to identify conditional convergence. Our findings show the strongest positive statistically significant association between immunization rates and GDP per capita, as well as births attended by skilled health staff. Moreover, our research demonstrates conditional convergence, indicating that countries converge towards different steady states. The present study brings new insights to investigating the determinants of childhood vaccination coverage and provides significant implications for health policies.

A phase 4, open-label study to evaluate the safety and immunogenicity of DTaP5-HBV-IPV-Hib in children previously vaccinated with DTaP2-HBV-IPV-Hib or DTaP5-HBV-IPV-Hib (V419-016).

DTaP5-HBV-IPV-Hib (Vaxelis®) is a hexavalent combination vaccine (HV) indicated in infants and toddlers for the prevention of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive disease due to Haemophilus influenzae type b. Switching between HVs during the childhood vaccination series is sometimes necessary due to, for example, vaccine availability, health-care provider preference, and/or tender awards. The purpose of this study was to describe the safety, tolerability, and immunogenicity of a booster dose of Vaxelis® in participants who previously received a primary infant series of either DTaP2-HBV-IPV-Hib (Hexyon®) or Vaxelis®. Healthy participants approximately 11-13 months of age who previously received a two-dose primary series of Hexyon® (HHV group) or Vaxelis® (VVV group) all received a Vaxelis® booster dose. Immunogenicity was evaluated by measuring antibody levels to individual vaccine antigens approximately 30 days following booster vaccination. Safety was evaluated as the proportion of participants with adverse events (AEs). The proportions of participants with antibody-specific responses for antigens contained in both Vaxelis® and Hexyon® at 30 days post-toddler-booster vaccination with Vaxelis® were comparable between groups, and higher in the VVV group for Vaxelis® antigens PRN and FIM2/3. The overall proportions of participants with AEs were generally comparable between groups. Following a booster dose of Vaxelis®, immune responses were comparable between groups for all shared antigens, and higher in the VVV group for antigens found only in Vaxelis®. The booster was well tolerated in both groups. These data support the use of Vaxelis® as a booster in mixed HV regimens.

BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models.

The protection afforded by acellular pertussis vaccines wanes over time, and there is a need to develop improved vaccine formulations. Options to improve the vaccines involve the utilization of different adjuvants and administration via different routes. While intramuscular (IM) vaccination provides a robust systemic immune response, intranasal (IN) vaccination theoretically induces a localized immune response within the nasal cavity. In the case of a Bordetella pertussis infection, IN vaccination results in an immune response that is similar to natural infection, which provides the longest duration of protection. Current acellular formulations utilize an alum adjuvant, and antibody levels wane over time. To overcome the current limitations with the acellular vaccine, we incorporated a novel TLR4 agonist, BECC438b, into both IM and IN acellular formulations to determine its ability to protect against infection in a murine airway challenge model. Following immunization and challenge, we observed that DTaP + BECC438b reduced bacterial burden within the lung and trachea for both administration routes when compared with mock-vaccinated and challenged (MVC) mice. Interestingly, IN administration of DTaP + BECC438b induced a Th1-polarized immune response, while IM vaccination polarized toward a Th2 immune response. RNA sequencing analysis of the lung demonstrated that DTaP + BECC438b activates biological pathways similar to natural infection. Additionally, IN administration of DTaP + BECC438b activated the expression of genes involved in a multitude of pathways associated with the immune system. Overall, these data suggest that BECC438b adjuvant and the IN vaccination route can impact efficacy and responses of pertussis vaccines in pre-clinical mouse models.

Cost-effectiveness analysis of pertussis booster vaccination for adolescents in Japan.

INTRODUCTION: In Japan, the introduction of a fifth diphtheria-tetanus-acellular pertussis (DTaP) vaccination has been considered, and adolescents aged 11-12 years old who are currently receiving the diphtheria-tetanus (DT) vaccine are one candidate group. We analyze the cost-effectiveness of replacing the DT vaccine with the DTaP vaccine for 11-year-old adolescents and investigate the indirect effect of vaccinated adolescents on unvaccinated infant siblings. We undertake two analyses using high- and low-morbidity pertussis cases, and based on the results, present suggestions for pertussis prevention in the post-COVID-19 pandemic era. METHOD: We used the number of pertussis cases in 2019 as the high-morbidity case and the average number of cases in 2020-2021 as the low-morbidity case, and evaluated the incremental cost-effectiveness ratio (ICER) of the DTaP strategy to the DT strategy based on quality-adjusted life years (QALYs). The economic model contained adolescent and infant sub-models. The indirect effect for infants was considered as the probability of unvaccinated infants avoiding pertussis infection from their vaccinated siblings. RESULTS: The ICER from the payers' perspective was Japanese yen (JPY) 4,254,515 per QALY gained in the high-morbidity case and JPY 62,546,776 per QALY gained in the low-morbidity case. The sensitivity analysis showed that the utility of pertussis had the greatest impact on the ICER, with a 60.58% and 0% probability that the ICER was less than JPY 5 million per QALY gained in the high-morbidity case and low-morbidity case, respectively. CONCLUSION: The cost-effectiveness of replacing the DT vaccine with the DTaP vaccine is affected by the level of pertussis morbidity, with the ICER becoming more favorable in the high-morbidity case. The indirect effect has little impact on the ICER. Thus, policy-makers should continue to monitor the pertussis epidemic in the post-COVID-19 era, and determine the need to introduce a booster based on perceived trends.

Prevalence and underreporting of immunization errors in childhood vaccination: results of a household survey.

OBJECTIVE: To investigate underreporting of immunization errors based on vaccination records from children under five years of age. METHOD: An epidemiological, cross-sectional analytical study, carried out through a household survey with 453 children aged 6 months to 4 years in three municipalities in Minas Gerais in 2021. A descriptive analysis was carried out, and the prevalence of the error was calculated per 100 thousand doses applied between 2016 and 2021. The magnitude was estimated of the association between variables by prevalence and 95% Confidence Intervals (95%CI). To analyze underreporting, State reporting records were used. RESULTS: A prevalence of immunization errors was found to be 41.9/100,000 doses applied (95%CI:32.2 - 51.6). The highest prevalence occurred between 2020 (50.0/100,000 doses applied) and 2021 (78.6/100,000 doses applied). The most frequent error was an inadequate interval between vaccines (47.2%) associated with adsorbed diphtheria, tetanus and pertussis (DTP) vaccine (13.7/100,000) administration. Vaccination delay was related to immunization errors (7.55 95% CI:2.30 - 24.80), and the errors found were underreported. CONCLUSION: The high prevalence of underreported errors points to a worrying scenario, highlighting the importance of preventive measures.

Is health expenditure on immunisation associated with immunisation coverage in sub-Saharan Africa? A multicountry analysis, 2013-2017.

OBJECTIVES: The designing of contextually tailored sustainable plans to finance the procurement of vaccines and the running of appropriate immunisation programmes are necessary to address the high burden of vaccine-preventable diseases and low immunisation coverage in sub-Saharan Africa (SSA). We sought to estimate the minimum fraction of a country's health budget that should be invested in national immunisation programmes to achieve national immunisation coverage of 80% or greater depending on the context, with and without donors' support. DESIGN: Multicountry analysis of secondary data using retrieved publicly available data from the WHO, Global Alliance for Vaccines and Immunization (GAVI) and World Bank databases. SETTING: Data on 24 SSA countries, between 2013 and 2017. METHODS: We model the variations in immunisation coverage across the different SSA countries using a fractional logit model. Three different generalised linear models were fitted to explore how various explanatory variables accounted for the variability in each of the three different vaccines-measles-containing vaccine (MCV)1, diphtheria, pertussis, tetanus (DPT3) and BCG. RESULTS: We observed an association between current health expenditure (as a percentage of gross domestic product) and immunisation coverage for BCG (OR=1.01, 95% CI: 1.01 to 1.04, p=0.008) and DPT3 (OR=1.01, 95% CI: 1.0 to 1.02, p=0.020) vaccines. However, there was no evidence to indicate that health expenditure on immunisation (as a proportion of current health expenditure) could be a strong predictor of immunisation coverage (DPT, OR 0.96 (95% CI 0.78 to 1.19; p=0.702); BCG, OR 0.91 (0.69 to 1.19; p=0.492); MCV, OR 0.91 (0.69 to 1.19; p=0.482)). We demonstrate in selected countries that to achieve the GAVI target of 80% in the countries with low DPT3 coverage, health expenditure would need to be increased by more than 45%. CONCLUSIONS: There is a need to facilitate the development of strategies that support African countries to increase domestic financing for national immunisation programmes towards achieving 2030 targets for immunisation coverage.

Equity in vaccine coverage in Uganda from 2000 to 2016: revealing the multifaceted nature of inequity.

BACKGROUND: This study analyses vaccine coverage and equity among children under five years of age in Uganda based on the 2016 Uganda Demographic and Health Survey (UDHS) dataset. Understanding equity in vaccine access and the determinants is crucial for the redress of emerging as well as persistent inequities. METHODS: Applied to the UDHS for 2000, 2006, 2011, and 2016, the Vaccine Economics Research for Sustainability and Equity (VERSE) Equity Toolkit provides a multivariate assessment of immunization coverage and equity by (1) ranking the sample population with a composite direct unfairness index, (2) generating quantitative measure of efficiency (coverage) and equity, and (3) decomposing inequity into its contributing factors. The direct unfairness ranking variable is the predicted vaccination coverage from a logistic model based upon fair and unfair sources of variation in vaccination coverage. Our fair source of variation is defined as the child's age - children too young to receive routine immunization are not expected to be vaccinated. Unfair sources of variation are the child's region of residence, and whether they live in an urban or rural area, the mother's education level, the household's socioeconomic status, the child's sex, and their insurance coverage status. For each unfair source of variation, we identify a "more privileged" situation. RESULTS: The coverage and equity of the Diphtheria-Pertussis-Tetanus vaccine, 3rd dose (DPT3) and the Measles-Containing Vaccine, 1st dose (MCV1) - two vaccines indicative of the health system's performance - improved significantly since 2000, from 49.7% to 76.8% and 67.8% to 82.7%, respectively, and there are fewer zero-dose children: from 8.4% to 2.2%. Improvements in retaining children in the program so that they complete the immunization schedule are more modest (from 38.1% to 40.8%). Progress in coverage was pro-poor, with concentration indices (wealth only) moving from 0.127 (DPT3) and 0.123 (MCV1) in 2000 to -0.042 and -0.029 in 2016. Gains in overall equity (composite) were more modest, albeit significant for most vaccines except for MCV1: concentration indices of 0.150 (DPT3) and 0.087 (MCV1) in 2000 and 0.054 and 0.055 in 2016. The influence of the region and settings (urban/rural) of residence significantly decreased since 2000. CONCLUSION: The past two decades have seen significant improvements in vaccine coverage and equity, thanks to the efforts to strengthen routine immunization and ongoing supplemental immunization activities such as the Family Health Days. While maintaining the regular provision of vaccines to all regions, efforts should be made to alleviate the impact of low maternal education and literacy on vaccination uptake.

Trends in childhood vaccination in Pakistan and associated factors; 2006-2018.

INTRODUCTION: Pakistan still has ongoing transmission of wild type polio virus. This study aims to determine changes in full vaccination with recommended Expanded Program on Immunization vaccines, including polio, by several socio-economic and demographic factors. METHODS: We used three waves of Pakistan's Demographic and Health Survey, a population-based cross-sectional study from 2006-07 (N = 1471), 2012-13 (N = 1706), and 2017-18 (N = 1549), analyzed by residence, wealth, and sociodemographic factors. Analysis was limited to children aged 12-23 months in Punjab, Sindh, Northwest Frontier Province/Khyber Pakhtunkhwa and Balochistan. Full vaccination was measured as receipt of one Bacillus Calmette-Guérin dose, one measles dose, 3 polio doses, and 3 Diphtheria-Tetanus-Pertussis doses. Odds ratios (ORs) and 95 % confidence intervals (CIs) from logistic regression were used to determine associations between undervaccination and demographic variables. RESULTS: Full vaccination coverage was 50.6 % in 2006-07, 54.7 % in 2012-13, and 68.3 % in 2017-18. In 2006-07, the odds of undervaccination were significantly higher in Sindh (OR: 1.74, 95 % CI: 1.30, 2.31) than Punjab, and disparities across province changed over time (P < 0.0001); notably, undervaccination was significantly higher in Sindh, KPK, and Balochistan than Punjab in 2017. Compared to the middle wealth quintile, the poorest had significantly higher odds of undervaccination in 2006-07 (OR: 2.58, 95 % CI: 1.76, 3.78), and this did not significantly change over time (P = 0.2168). The proportion of those with a polio birth dose increased across waves from 56.3 % in 2006-07 to 83.7 % in 2017-18; receiving three or more polio vaccine doses remained unchanged. CONCLUSION: This study showed that the proportion of fully vaccinated children in Pakistan increased across three waves. Full vaccination and administration of polio vaccine birth doses have increased recently in Pakistan. The association between undervaccination with province differed significantly across the waves, with vaccination disparities between provinces increasing. Those in the poorest wealth quintile had the greatest odds of undervaccination.

Missed opportunities: Reducing zero dose children amongthe urban poor after COVID, Mumbai India, 2022.

Reaching urban poor populations poses challenges for equitable immunization coverage. Furthermore, COVID disrupted routine immunization services. In Mumbai, India, first dose diphtheria tetanus pertussis containing vaccine (DTPCV1)coverage dropped from 88% (2019) to 76% (2021). We identified and characterized 125 zero-dose (those withoutDTPCV1)migrant children in urban Mumbai in October 2022. Almost half were born elsewhere than Mumbai; 53% resided at their present location for less than a year. More than half were 12-59 months of age, well-beyond the age for first routine childhood immunizations.Three of four zero dose children had received birth dose vaccination in the hospital; but failed to receive DTPCV1. Vaccine hesitancy, awareness gaps and operational issues were common reasons for non-vaccination. Despite frequent visits to health facilities for illness,only a third of facility staff asked or advised parents about vaccination.Missed opportunities were much more common in private than government facilities.For the vast majority (88%), residential sites were included in local routine immunization micro-plans and distances to immunization sites were short (less than 1 km for 94 % of families).However, planned session frequency was inadequate half of the time. Expanded efforts to reach migrant urban poor children are needed to ensure vaccine equity.

Do Pentavalent (DTwP-Hib-HBV) vaccines have sex-differential nonspecific effects? An observational study.

Vaccines may alter the ability to combat infections unrelated to the target disease, i.e. have "nonspecific effects." The non-live Diphtheria-Tetanus-Pertussis vaccine (DTP) has been associated with increased child mortality, especially for females. In 2008, the DTP-containing Pentavalent vaccine replaced DTP vaccine in Guinea-Bissau. We investigate female relative to male mortality after Penta vaccination. In Guinea-Bissau, Bandim Health Project (BHP) registered children's vaccination and vital status at biannual village visits and provided vaccines. Among children Penta-vaccinated by BHP, we compared mortality of males and females in Cox proportional hazards models. Children aged 6 weeks to 8 months entered the analysis at the date of vaccination and were followed for up to 6 months. Between September 2008 and December 2017, 33,989 children aged 6 weeks to 8 months were under surveillance. Of these 12,753 (females: 6,363; males: 6,390) received Penta by the BHP and entered the study contributing with 19,667 observations. The mortality rate following Penta vaccination was 25.2 per 1,000 person years for females and 26.6 for males, resulting in an adjusted Female/Male mortality rate ratio of (F/M aMRR) 1.01 (0.82-1.25). The association between sex and mortality differed by timeliness of vaccination, F/M aMRR: 0.62 (0.41-0.93) for children vaccinated below median age, and F/M aMRR: 1.38 (0.90-2.13) for children vaccinated above median age. We did not find higher overall mortality in females than males after Penta vaccination. Our findings suggest that mortality differences between males and females following Penta vaccination may depend on timeliness of Penta vaccination.

FACTORS INFLUENCING ANTI-POLYRIBOSYLRIBITOL PHOSPHATE TITRES IN YOUNG NIGERIAN CHILDREN PRIMED WITH DTWP-HEPB-HIB VACCINE.

Introduction: Recent research suggests that variation in vaccine-induced immune responses is influenced by genetic, nutritional, environmental, and vaccine-related factors, with significant vaccine design and programmatic policy implications. Haemophilus influenzae type b (Hib) Conjugate Vaccine (HCV) stimulates the production of antiPolyribosylribitol phosphate (anti-PRP) antibodies, which confer long-term protection against invasive Hib disease and nasopharyngeal colonization by Hib at titre levels ≥1µg/mL and ≥5µg/mL respectively. This study investigated the influence of these factors on the protective anti-PRP levels in children aged 6-23 months in Obi L.G.A. of Nasarawa State, Nigeria. Methods: The study was a cross-sectional, two-stage household-level cluster survey involving 267 children who had completed the E.P.I. schedule of HCV-containing DTwP-HepB-Hib. Validated questionnaires were used for enrolment and relevant clinical and laboratory evaluations including anti-PRP, ABO/Rhesus antigens, and Haemoglobin genotype assays were conducted. Regression analyses were performed using Stata to explore the correlation between sociodemographic/vaccine-related factors, nutritional status, genotype, ABO/Rhesus antigens, and protective anti-PRP titres. Results: Bivariate analysis showed that age, breastfeeding practice, household size/under-five number, nutritional, socioeconomic, Measles/Yellow fever vaccination, and Rhesus statuses were significantly associated with anti-PRP titre. However, multivariate analysis revealed that age between 6-11 months (AOR=3.12,95%CI=1.15-8.50), households with less than three under-fives (AOR=2.33,95%CI=1.14-4.78), middle socioeconomic class (AOR=3.15,95%CI=1.42-6.98), wasting (AOR=2.27,95%CI=1.23-4.22) and Measles/Yellow fever vaccination (AOR=2.90,95%CI=1.38-6.07) were significantly correlated with protective anti-PRP titres. Conclusion: Results indicate that the family and socioeconomic milieu influence anti-PRP titre, and Measles/Yellow fever vaccines may have a beneficial non-specific effect on HCV-induced seroprotection in Nigerian children.

Development of a composite scoring system to rank communities at high risk of zero-dose children in Cameroon: A geospatial analysis.

Background: Despite growing efforts to improve access to vaccination, millions of children, especially in developing countries, have not received a single dose of diphtheria, tetanus, and pertussis (DTP) vaccine. Consequently, they are often called zero-dose children (ZDC). With limited health resources, prioritising communities for rapid and mass zero-dose catch-up vaccination in missed communities to avert epidemic outbreaks is complicated by unreliable denominators used to compute vaccination coverages. Incorporating other indicators of access and utilisation of vaccination services can help with identifying and ranking missed communities based on the likelihood of finding ZDC. We described the process of generating a scoring method to rank health areas in Cameroon based on their likelihood of containing ZDC. Methods: We used geospatial analysis to compute and aggregate health area characteristics, including hard-to-reach (HTR) areas (defined as areas of settlement above a one- (for urban areas) or 15-kilometre radius (for rural areas) beyond a vaccinating health facility), amount of area covered by slums and new area settlement, and percentage of children unvaccinated for DTP-1. We attributed a weight based on the ability to limit accessibility or utilisation of vaccination services to each characteristic and computed the score as a weighted average of health area characteristics. The health area score ranged from 0 to 1, with higher scores representing a higher likelihood of containing ZDC. We stratified the analysis by rural and urban health areas. Results: We observed substantial district and regional variations in health area scores, with hotspots health areas (administrative level 4) observed in the Far North (0.83), North (0.81), Adamawa (0.80), East (0.75), and South West (0.67) regions. The Adamawa region had the highest percentage of health areas with the highest score (78%), followed by the East (50%), West (48%), and North (46%) regions. For most regions (Far North, South, South West, Littoral, West, and North West), DTP-1 contributed the most to the score. However, HTR settlement areas within a health area contributed substantially to the overall score in the East, North, and Adamawa regions. Conclusions: We found substantial variations in health area scores with hotspots in the Far North, North, Adamawa, East, and South West regions. Although DTP-1 could be used as an indicator to identify health areas with ZDC for most communities, HTR settlement area was a valuable indicator in ranking priority health areas in the East, North, and Adamawa regions, further emphasising the need to consider other indicators before prioritisation.

Vaccination coverage of children with rheumatic diseases compared with healthy controls: a retrospective case-control study.

OBJECTIVE: To reveal the vaccination status of patients with pediatric rheumatic disease (PedRD) and to compare this with healthy controls. METHODS: The electronic health records of the Ministry of Health regarding the vaccination status of children with PedRD followed in a tertiary hospital were analyzed cross-sectionally and compared with their healthy controls. The missing vaccines were reported according to individual, age-appropriate schedule and causes of skipped vaccines in both groups were investigated with an online survey. RESULTS: The vaccination rate of patients in the last examination was 71.4% (90/126) and 95.7% (110/115) in healthy controls (p < 0.001). Measles-mumps-rubella vaccine, diphtheria, the administration rates of the second dose of tetanus-acellular pertussis-inactivated polio and Haemophilus influenzae type B, chickenpox, and hepatitis A vaccines were significantly lower in patients than in controls (p values 0.004, 0.02, 0.01, 0.013, respectively). The pre-diagnosis incomplete vaccination proportion was significantly higher in the patient group (16.6%) than in healthy controls (4.3%) (p = 0.002). In the patient group, the proportion of incomplete live-attenuated vaccines after diagnosis (25%) was more than pre-diagnosis (61.1%) (p = 0.04), while the proportion of incomplete non-live vaccines before and after diagnosis was similar (47.2% and 50%, respectively) (p = 0.73). The major reasons for missed vaccines were physicians' recommendations (15.6%), the presence of PedRD diagnosis (12.5%), and the drugs used (12.5%). CONCLUSION: Vaccination coverage of PedRD patients has been shown to lag behind the routine vaccination schedule (71.4%). In addition to new recommendations, electronic health system records for vaccination may be appropriate for the follow-up of these patients, and the addition of reminder alerts may be useful to reduce the rate of missed vaccinations.

Coverage with Selected Vaccines and Exemption from School Vaccine Requirements Among Children in Kindergarten - United States, 2022-23 School Year.

U.S. states and local jurisdictions set vaccination requirements for school attendance and conditions and procedures for exemptions from these requirements. States annually report data to CDC on the number of children in kindergarten who meet, are exempt from, or are in the process of meeting requirements. National- and state-level estimates for complete vaccination with measles, mumps, and rubella vaccine (MMR); diphtheria, tetanus, and acellular pertussis vaccine (DTaP); poliovirus vaccine (polio); and varicella vaccine (VAR); exemptions from vaccination; and legally allowed kindergarten attendance while meeting requirements were based on data reported by 49 states and the District of Columbia (DC) for the 2022-23 school year. This kindergarten class became age-eligible to complete most state-required vaccinations during the COVID-19 pandemic. National coverage remained near 93% for all vaccines; exemptions were low but increased to 3%, compared with those during the 2021-22 school year (2.6%). At the state level, coverage with MMR, DTaP, polio, and VAR decreased in 29, 31, 28, and 25 states, respectively, compared with coverage during the 2021-22 school year. Exemptions increased in 40 states and DC, with 10 states reporting an exemption from at least one vaccine for >5% of kindergartners. Schools and providers should work to ensure that students are vaccinated before school entry, such as during the enrollment process, which is often several months before school starts. State and local provisional enrollment periods that allow students to attend school while on a catch-up schedule also provide the opportunity to fully vaccinate students and to prevent nonmedical exemptions resulting from lingering undervaccination due to COVID-19 pandemic-related barriers to vaccination, such as reduced access to vaccination appointments.

Recurrent diphtheria outbreaks in Nigeria: A review of the underlying factors and remedies.

INTRODUCTION: The introduction of the diphtheria-tetanus-pertussis (DTP) vaccine into childhood immunization programs resulted in its widespread elimination in high-income countries. However, Nigeria is currently experiencing an outbreak. The primary cause of diphtheria outbreaks and its high mortality rates in Nigeria was waning herd immunity due to low DTP coverage and a lack of diphtheria antitoxin (DAT), respectively. However, the underlying causes of Nigeria's low DTP coverage and DAT supply remain unknown. METHOD: Relevant studies and reports included in our review were obtained by a search through Google Scholar, PubMed, and organization websites using the terms "Diphtheria-Pertussis-Tetanus vaccine OR Diphtheria antitoxin and Nigeria OR Diphtheria Outbreak." All articles considering diphtheria outbreaks, DTP vaccine, and DAT supply in Nigeria were considered without time restriction due to the paucity of data. We used the narrative synthesis approach to critically appraise, analyze, and draw inferences from the selected articles. RESULTS: The main causes of low DTP coverage are insufficient supply, an inefficient cold chain system, and low uptake due to poor health literacy and negative sociocultural and religious beliefs, whereas the key barriers to DAT availability are insufficient production by pharmaceutical industries because of low demand and priority. CONCLUSION: The underlying causes of Nigeria's low DTP coverage and DAT supply are multifactorial. Both short-term and long-term measures are needed to control this outbreak and prevent future occurrences.

DTaP-IPV-HB-Hib vaccine (Hexaxim): an update 10 years after first licensure.

INTRODUCTION: Hexaxim® is fully liquid, hexavalent, combination vaccine that provides immunization against diphtheria, tetanus, pertussis (whooping cough), polio, hepatitis B, and invasive diseases caused by Haemophilus influenzae type b. Combination vaccines such as Hexaxim reduce the number of injections needed, improving both vaccination compliance and operational efficiency. AREAS COVERED: Safety and immunogenicity data were reviewed from >25 clinical trials involving approximately 7200 infants/toddlers, identified using PubMed searches to April 2023. These trials have evaluated a diverse range of primary series and booster schedules, including antibody persistence, co-administration of Hexaxim with other routine pediatric vaccines, and specific populations (born to Tdap-vaccinated women, preterm, and immunocompromised infants). Lastly, post-marketing surveillance and real-world effectiveness data were assessed. EXPERT OPINION: An extensive program of clinical development prior to licensure demonstrated favorable vaccine safety and good immunogenicity of each antigen, and Hexaxim was first approved for use in 2012. In the 10 years since licensure, Hexaxim has been adopted widely, with more than 180 million doses distributed worldwide. The widespread use of this hexavalent vaccine is a crucial tool in the ongoing and future control of six pediatric infectious diseases globally.