-
Nature Communications Mar 2024Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a...
Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.
Topics: Adolescent; Humans; Bordetella pertussis; Immunity, Humoral; Tetanus; Whooping Cough; Diphtheria; Vaccines, Combined; Antibodies, Bacterial; Diphtheria-Tetanus-acellular Pertussis Vaccines; Poliovirus Vaccine, Inactivated; Vaccination; Immunization, Secondary; Corynebacterium; Poliovirus; Interferons; Antiviral Agents
PubMed: 38459022
DOI: 10.1038/s41467-024-46560-w -
Journal of Infection and Public Health Apr 2024Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different...
Prevalence of infectious diseases, immunity to vaccine-preventable diseases and chronic medical conditions among Ukrainian refugees in Germany - A cross sectional study from the German Network University Medicine (NUM).
BACKGROUND
Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022.
METHODS
Using different media, we recruited Ukrainian refugees at 13 sites between 9-12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration.
RESULTS
Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children. Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B.
CONCLUSIONS
We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Communicable Diseases; Cross-Sectional Studies; Eastern European People; Germany; Prevalence; Refugees; Tuberculosis; Universities; Vaccine-Preventable Diseases
PubMed: 38458134
DOI: 10.1016/j.jiph.2024.02.003 -
The Pediatric Infectious Disease Journal Jun 2024Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains.
METHODS
This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events.
RESULTS
Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13.
CONCLUSIONS
PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.
Topics: Humans; Pneumococcal Vaccines; Infant; Double-Blind Method; Male; Female; Antibodies, Bacterial; Vaccines, Conjugate; Immunogenicity, Vaccine; Measles-Mumps-Rubella Vaccine; Pneumococcal Infections; Immunoglobulin G; Chickenpox Vaccine; Immunization Schedule; Streptococcus pneumoniae; Child, Preschool; Diphtheria-Tetanus-acellular Pertussis Vaccines; Vaccines, Combined
PubMed: 38456705
DOI: 10.1097/INF.0000000000004300 -
PloS One 2024Nigeria has a high proportion of the world's underimmunised children. We estimated the inequities in childhood immunisation coverage associated with socioeconomic,...
Systematic review of social determinants of childhood immunisation in low- and middle-income countries and equity impact analysis of childhood vaccination coverage in Nigeria.
BACKGROUND
Nigeria has a high proportion of the world's underimmunised children. We estimated the inequities in childhood immunisation coverage associated with socioeconomic, geographic, maternal, child, and healthcare characteristics among children aged 12-23 months in Nigeria using a social determinants of health perspective.
METHODS
We conducted a systematic review to identify the social determinants of childhood immunisation associated with inequities in vaccination coverage among low- and middle-income countries. Using the 2018 Nigeria Demographic and Health Survey (DHS), we conducted multiple logistic regression to estimate the association between basic childhood vaccination coverage (1-dose BCG, 3-dose DTP-HepB-Hib (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B), 3-dose polio, and 1-dose measles) and socioeconomic, geographic, maternal, child, and healthcare characteristics in Nigeria.
RESULTS
From the systematic review, we identified the key determinants of immunisation to be household wealth, religion, and ethnicity for socioeconomic characteristics; region and place of residence for geographic characteristics; maternal age at birth, maternal education, and household head status for maternal characteristics; sex of child and birth order for child characteristics; and antenatal care and birth setting for healthcare characteristics. Based of the 2018 Nigeria DHS analysis of 6,059 children aged 12-23 months, we estimated that basic vaccination coverage was 31% (95% CI: 29-33) among children aged 12-23 months, whilst 19% (95% CI:18-21) of them were zero-dose children who had received none of the basic vaccines. After controlling for background characteristics, there was a significant increase in the odds of basic vaccination by household wealth (AOR: 3.21 (2.06, 5.00), p < 0.001) for the wealthiest quintile compared to the poorest quintile, antenatal care of four or more antenatal care visits compared to no antenatal care (AOR: 2.87 (2.21, 3.72), p < 0.001), delivery in a health facility compared to home births (AOR 1.32 (1.08, 1.61), p = 0.006), relatively older maternal age of 35-49 years compared to 15-19 years (AOR: 2.25 (1.46, 3.49), p < 0.001), and maternal education of secondary or higher education compared to no formal education (AOR: 1.79 (1.39, 2.31), p < 0.001). Children of Fulani ethnicity in comparison to children of Igbo ethnicity had lower odds of receiving basic vaccinations (AOR: 0.51 (0.26, 0.97), p = 0.039).
CONCLUSIONS
Basic vaccination coverage is below target levels for all groups. Children from the poorest households, of Fulani ethnicity, who were born in home settings, and with young mothers with no formal education nor antenatal care, were associated with lower odds of basic vaccination in Nigeria. We recommend a proportionate universalism approach for addressing the immunisation barriers in the National Programme on Immunization of Nigeria.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Developing Countries; Immunization; Nigeria; Social Determinants of Health; Vaccination Coverage; Infant
PubMed: 38446836
DOI: 10.1371/journal.pone.0297326 -
Southern African Journal of Infectious... 2024Classical toxin-mediated respiratory diphtheria has become less common because of widespread effective vaccination globally but invasive disease as a result of...
BACKGROUND
Classical toxin-mediated respiratory diphtheria has become less common because of widespread effective vaccination globally but invasive disease as a result of non-toxigenic strains of is not prevented by vaccination and may result in severe disease, including infective endocarditis (IE).
OBJECTIVES
To describe the outbreak and subsequent investigation of a cluster of five cases of non-toxigenic endocarditis.
METHOD
A retrospective observational case series of five cases of non-toxigenic endocarditis identified in the rural West Coast district of the Western Cape province of South Africa between May 2021 and June 2021.
RESULTS
Non-toxigenic IE had an aggressive clinical course with high mortality in this cohort. Only one of five patients survived to hospital discharge. The surviving patient received a prompt diagnosis with early surgical intervention but still had a complicated clinical course. Notably, only one case had a pre-existing risk factor for IE, namely a prosthetic valve. Whole genome sequencing of clinical isolates confirmed that all isolates were of the same novel sequence type of non-toxigenic but despite a thorough investigation no epidemiological link was ever found between the cases.
CONCLUSION
Non-toxigenic strains of are less well known but may be highly virulent and cause severe invasive disease.
CONTRIBUTION
This is the largest cluster of non-toxigenic IE ever described in South Africa and expands the body of literature on this unusual but possibly emerging infection.
PubMed: 38444885
DOI: 10.4102/sajid.v39i1.539 -
Vaccine Mar 2024The adjuvanted recombinant zoster vaccine (RZV; Shingrix®, GSK) is a subunit vaccine that has been approved for the prevention of herpes zoster in adults.... (Review)
Review
BACKGROUND
The adjuvanted recombinant zoster vaccine (RZV; Shingrix®, GSK) is a subunit vaccine that has been approved for the prevention of herpes zoster in adults. Co-administration of two vaccines in a single visit is a strategy to improve overall vaccine coverage.
OBJECTIVES
This review aims to consolidate available clinical data on RZV co-administration, providing an overview of safety, reactogenicity and immunogenicity.
METHODS
RZV co-administration data were obtained from five randomised, open-label, phase III clinical trials with similar study designs. The co-administered vaccines included: quadrivalent seasonal inactivated influenza vaccine (IIV4; NCT01954251), 23-valent pneumococcal polysaccharide vaccine (PPSV23; NCT02045836), reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (Tdap; NCT02052596), 13-valent pneumococcal conjugate vaccine (PCV13; NCT03439657) and COVID-19 mRNA-1273 booster (NCT05047770). Eligible participants were healthy adults aged ≥50 years.
RESULTS
A total of 3,974 participants were vaccinated (co-administration: 1,973; sequential: 2,001) across the five trials. Vaccine response rates to RZV were similar for co-administration (range: 95.8-99.1 %) and sequential groups (range: 95.1-99.1 %). Immune responses to RZV and the other vaccines (with the exception of pertactin) were non-inferior when the vaccines were co-administered compared with sequentially administered. Overall incidences of solicited local and general adverse events (AEs), unsolicited AEs, serious AEs or potential immune-mediated diseases were similar after co-administration or sequential administration. Myalgia was the most common solicited systemic AE (co-administration: 38-64 %; sequential: 30-59 %). Shivering and fever were more common after co-administration (16 % and 21 %, respectively) than after sequential administration (both 7 %) of RZV and PPSV23.
CONCLUSIONS
Co-administration of RZV with routine vaccines does not significantly alter the reactogenicity, immunogenicity or safety of RZV or the co-administered vaccine. Healthcare practitioners should consider routine co-administration of RZV with other adult vaccines to improve vaccination coverage.
Topics: Adult; Humans; Herpes Zoster Vaccine; Herpes Zoster; Diphtheria-Tetanus-acellular Pertussis Vaccines; Vaccines, Synthetic; Adjuvants, Immunologic; Vaccines, Combined; Immunogenicity, Vaccine
PubMed: 38423814
DOI: 10.1016/j.vaccine.2024.02.035 -
BMC Pediatrics Feb 2024In Germany, various preventive services are offered to children and adolescents. These include regular standardized examinations (so called U/J examinations) and several...
The role of sociodemographic, psychosocial, and behavioral factors in the use of preventive healthcare services in children and adolescents: results of the KiGGS Wave 2 study.
BACKGROUND
In Germany, various preventive services are offered to children and adolescents. These include regular standardized examinations (so called U/J examinations) and several vaccinations. Although strongly recommended, most of them are not mandatory. Our aim is to identify factors associated with the use of U/J examinations and vaccination against diphtheria, hepatitis B, Hib, pertussis, polio, and tetanus. While previous research has focused on sociodemographic factors, we also include socioeconomic, behavioral, and psychosocial factors.
METHODS
We analyzed cross-sectional data from 15,023 participants (aged 0-17 years) of the nationwide representative KiGGS Wave 2 Survey. Participation in U/J examinations was assessed using a questionnaire, filled out by participants and/or their parents. Information on vaccination status was drawn from the participants' vaccination booklets. To identify relevant determinants for the use of preventive examinations and vaccinations, unadjusted and adjusted logistic regression models were employed with up to 16 different independent variables.
RESULTS
Various independent variables showed an association with the use of preventive services. Higher socioeconomic status, absence of migration background, and lower household size were associated with significantly higher utilization of U examinations. Parents' marital status, area of residence, behavioral and psychosocial factors yielded insignificant results for most U/J examinations. Higher vaccination rates were found for children with no migration background, with residence in eastern Germany, lower household size, and with married parents.
CONCLUSION
This study attempted to depict the influence of sociodemographic, psychosocial, and behavioral factors on the use of several preventive services. Our results indicate that predominantly sociodemographic variables influence the use of preventive services. Further efforts should be made to investigate the interplay of different determinants of healthcare use in children and adolescents.
Topics: Child; Humans; Adolescent; Cross-Sectional Studies; Preventive Health Services; Vaccination; Surveys and Questionnaires; Delivery of Health Care
PubMed: 38419000
DOI: 10.1186/s12887-024-04650-0 -
BMC Pediatrics Feb 2024Health policymakers aiming to reduce under-5 mortality (U5M) often lack data regarding how successful interventions in other countries were implemented. The Exemplars in...
BACKGROUND
Health policymakers aiming to reduce under-5 mortality (U5M) often lack data regarding how successful interventions in other countries were implemented. The Exemplars in U5M Study identified countries that achieved significant reductions in amenable U5M. This case study in Peru used implementation research to explore the contextual factors and strategies that contributed to the successful implementation of key evidence-based interventions (EBIs).
METHODS
This research utilized a hybrid implementation research framework and a mixed-methods approach to understand the factors associated with EBI implementation and the successful reduction of U5M between 2000-2015. A desk review of existing literature on EBIs and U5M in Peru was completed, and in-depth interviews were performed with key Peruvian informants to understand the implementation strategies employed and the contextual factors that facilitated or were barriers to success. For the purposes of this analysis, three EBIs were selected and evaluated: antenatal care visits (ANC), facility-based deliveries, and infant vaccination.
RESULTS
Between 2000-2015, the percent of mothers attending at least four antenatal care visits rose from 69% to 96.9%, and the percent of facility-based deliveries increased from 56 to 91%. Three doses of the tetanus/diphtheria/pertussis vaccine, widely acknowledged as a key global health indicator, reached 90% by 2015. Key informants noted that economic growth, financial reforms, strong national commitment to reduce poverty in Peru, and national prioritization of maternal and child health, were important contextual factors that contributed to the successful reduction of U5M. They noted key strategies that helped achieve success during the implementation of EBIs, including utilization of data for decision-making, adaptation driven by cultural sensitivity to address gaps in coverage, and a focus on equity and anti-poverty initiatives with the participation of government, civil society, and political parties to assure continuity of policies.
CONCLUSION
Several EBIs contributed to the successful reduction of U5M in Peru between 2000-2015. Strategies such as the focus on equity throughout the study period contributed to an increase in coverage of EBIs like ANC visits, facility-based deliveries and infant vaccination which worked to reduce U5M. Understanding how Peru successfully implemented programs that reduced preventable infant and child deaths could be useful to replicating this substantial public health success in other low- and middle-income countries.
Topics: Infant; Child; Humans; Pregnancy; Female; Peru; Prenatal Care; Poverty; Child Health; Mothers
PubMed: 38413926
DOI: 10.1186/s12887-023-03890-w -
Frontiers in Molecular Biosciences 2024Apical periodontitis (AP) is a painful disease that develops quickly following dental infections and is primarily characterized by robust inflammation surrounding the...
Apical periodontitis (AP) is a painful disease that develops quickly following dental infections and is primarily characterized by robust inflammation surrounding the tissues of the affected tooth, resulting in disruption of bone homeostasis and periradicular bone loss. Moreover, there are distinct clinical presentations, symptoms, and responses to AP treatment between male and female subjects, creating a desperate need to further understand the sex-specific mechanisms of AP. With the growing evidence that nociceptors modulate AP development, we utilized RNA sequencing in nociceptor-ablated (Nav1.8 , diphtheria toxin A) transgenic mice to study the nociceptor regulation of the periapical lesion transcriptome using a rodent model of AP in female mice over 14 days. Overall, we found that female mice exhibit unique patterns of differentially expressed genes throughout AP infection compared to male mice and that the expression of these genes is regulated by nociceptors. Additionally, nociceptor ablation results in a more significant enrichment of biological processes related to immune responses earlier compared to cre-control (Nav1.8 ) females and greater expression of genes involved in inflammatory processes and osteolytic activity. Therefore, while nociceptor ablation augments inflammatory and bone resorption responses in both males and females in a mouse model of AP, transcriptomic analyses demonstrate that the mechanisms through which nociceptors modulate AP are distinct between sexes. These studies will provide the foundation needed to study further mechanisms of sex differences in AP, an area with a desperate need for investigation to treat current AP patients. Understanding these mechanisms can ultimately inform treatment options to alleviate suffering for millions of patients suffering from AP.
PubMed: 38404963
DOI: 10.3389/fmolb.2024.1338511