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.

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.

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.

Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow.

Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect different activation environments or maturation of their precursors. Here we define human BMPC heterogeneity and track the recruitment of antibody-secreting cells (ASC) from SARS-CoV-2 vaccine immune reactions to the bone marrow (BM). Trajectories based on single-cell transcriptomes and repertoires of peripheral and BM ASC reveal sequential colonisation of BMPC compartments. In activated B cells, IL-21 suppresses CD19 expression, indicating that CD19low-BMPC are derived from follicular, while CD19high-BMPC originate from extrafollicular immune reactions. In primary immune reactions, both CD19low- and CD19high-BMPC compartments are populated. In secondary immune reactions, most BMPC are recruited to CD19high-BMPC compartments, reflecting their origin from extrafollicular reactivations of memory B cells. A pattern also observable in vaccinated-convalescent individuals and upon diphtheria/tetanus/pertussis recall-vaccination. Thus, BMPC diversity reflects the evolution of a given humoral immune response.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.