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Biomolecules May 2024Diabetic retinopathy (DR) affects over 140 million people globally. The mechanisms that lead to blindness are still enigmatic but there is evidence that sustained...
Diabetic retinopathy (DR) affects over 140 million people globally. The mechanisms that lead to blindness are still enigmatic but there is evidence that sustained inflammation and hypoxia contribute to vascular damage. Despite efforts to understand the role of inflammation and microglia in DR's pathology, the contribution of astrocytes to hypoxic responses is less clear. To investigate the role of astrocytes in hypoxia-induced retinopathy, we utilized a 7-day systemic hypoxia model using the GFAP-Cre:Rosa26 transgenic mouse line. This allows for the induction of inflammatory reactive astrogliosis following tamoxifen and diphtheria toxin administration. We hypothesize that DTx-induced astrogliosis is neuroprotective during hypoxia-induced retinopathy. Glial, neuronal, and vascular responses were quantified using immunostaining, with antibodies against GFAP, vimentin, IBA-1, NeuN, fibrinogen, and CD31. Cytokine responses were measured in both the brain and serum. We report that while both DTx and hypoxia induced a phenotype of reduced microglia morphological activation, DTx, but not hypoxia, induced an increase in the Müller glia marker vimentin. We did not observe that the combination of DTx and hypoxic treatments exacerbated the signs of reactive glial cells, nor did we observe a significant change in the expression immunomodulatory mediators IL-1β, IL2, IL-4, IL-5, IL-6, IL-10, IL-18, CCL17, TGF-β1, GM-CSF, TNF-α, and IFN-γ. Overall, our results suggest that, in this hypoxia model, reactive astrogliosis does not alter the inflammatory responses or cause vascular damage in the retina.
Topics: Animals; Gliosis; Mice; Microglia; Ependymoglial Cells; Disease Models, Animal; Mice, Transgenic; Retina; Hypoxia; Astrocytes; Glial Fibrillary Acidic Protein; Diabetic Retinopathy; Cytokines; Vimentin; Diphtheria Toxin
PubMed: 38785974
DOI: 10.3390/biom14050567 -
Frontiers in Public Health 2024Routine immunization programs have focused on increasing vaccination coverage, which is equally important for decreasing vaccine-preventable diseases (VPDs),...
INTRODUCTION
Routine immunization programs have focused on increasing vaccination coverage, which is equally important for decreasing vaccine-preventable diseases (VPDs), particularly in low- and lower-middle-income countries (LMICs). We estimated the trends and projections of age-appropriate vaccination coverage at the regional and national levels, as well as place of residence and wealth index in LMICs.
METHODS
In total, 174 nationally representative household surveys from 2000 to 2020 from 41 LMICs were included in this study. Bayesian hierarchical regression models were used to estimate trends and projections of age-appropriate vaccination.
RESULTS
The trend in coverage of age-appropriate Bacillus Calmette-Guérin (BCG), third dose of diphtheria, tetanus, and pertussis (DTP3), third dose of polio (polio3), and measles-containing vaccine (MCV) increased rapidly from 2000 to 2020 in LMICs. Findings indicate substantial increases at the regional and national levels, and by area of residence and socioeconomic status between 2000 and 2030. The largest rise was observed in East Africa, followed by South and Southeast Asia. However, out of the 41 countries, only 10 countries are estimated to achieve 90% coverage of the BCG vaccine by 2030, five of DTP3, three of polio3, and none of MCV. Additionally, by 2030, wider pro-urban and -rich inequalities are expected in several African countries.
CONCLUSION
Significant progress in age-appropriate vaccination coverage has been made in LMICs from 2000 to 2020. Despite this, projections show many countries will not meet the 2030 coverage goals, with persistent urban-rural and socioeconomic disparities. Therefore, LMICs must prioritize underperforming areas and reduce inequalities through stronger health systems and increased community engagement to ensure high coverage and equitable vaccine access.
Topics: Humans; Vaccination Coverage; Developing Countries; Asia; Africa South of the Sahara; Immunization Programs; Infant; Child, Preschool; Bayes Theorem; Vaccination
PubMed: 38784590
DOI: 10.3389/fpubh.2024.1371258 -
Human Vaccines & Immunotherapeutics Dec 2024The COVID-19 pandemic has significantly disrupted healthcare systems at all levels globally, notably affecting routine healthcare services, such as childhood...
The COVID-19 pandemic has significantly disrupted healthcare systems at all levels globally, notably affecting routine healthcare services, such as childhood vaccination. This study examined the impact of these disruptions on routine childhood vaccination programmes in Tanzania. We conducted a longitudinal study over four years in five Tanzanian regions: Mwanza, Dar es Salaam, Mtwara, Arusha, and Dodoma. This study analyzed the trends in the use of six essential vaccines: Bacille Calmette-Guérin (BCG), bivalent Oral Polio Vaccine (bOPV), Diphtheria Tetanus Pertussis, Hepatitis-B and Hib (DTP-HepB-Hib), measles-rubella (MR), Pneumococcal Conjugate Vaccine (PCV), and Rota vaccines. We evaluated annual and monthly vaccination trends using time-series and regression analyses. Predictive modeling was performed using an autoregressive integrated moving average (ARIMA) model. A total of 32,602,734 vaccination events were recorded across the regions from 2019 to 2022. Despite declining vaccination rates in 2020, there was a notable rebound in 2021, indicating the resilience of Tanzania's immunization program. The analysis also highlighted regional differences in vaccination rates when standardized per 1000 people. Seasonal fluctuations were observed in monthly vaccination rates, with BCG showing the most stable trend. Predictive modeling of BCG indicated stable and increasing vaccination coverage by 2023. These findings underscore the robustness of Tanzania's childhood immunization infrastructure in overcoming the challenges posed by the COVID-19 pandemic, as indicated by the strong recovery of vaccination rates post-2020. We provide valuable insights into the dynamics of vaccination during a global health crisis and highlight the importance of sustained immunization efforts to maintain public health.
Topics: Humans; Tanzania; COVID-19; Vaccination; Longitudinal Studies; Infant; Child, Preschool; Immunization Programs; Child; BCG Vaccine; SARS-CoV-2; Pandemics
PubMed: 38780570
DOI: 10.1080/21645515.2024.2356342 -
Journal of Urban Health : Bulletin of... Jun 2024Urban children are more likely to be vaccinated than rural children, but that advantage is not evenly distributed. Children living in poor urban areas face unique... (Comparative Study)
Comparative Study
Exploring the "Urban Advantage" in Access to Immunization Services: A Comparison of Zero-Dose Prevalence Between Rural, and Poor and Non-poor Urban Households Across 97 Low- and Middle-Income Countries.
Urban children are more likely to be vaccinated than rural children, but that advantage is not evenly distributed. Children living in poor urban areas face unique challenges, living far from health facilities and with lower-quality health services, which can impact their access to life-saving vaccines. Our goal was to compare the prevalence of zero-dose children in poor and non-poor urban and rural areas of low- and middle-income countries (LMICs). Zero-dose children were those who failed to receive any dose of a diphtheria-pertussis-tetanus (DPT) containing vaccine. We used data from nationally representative household surveys of 97 LMICs to investigate 201,283 children aged 12-23 months. The pooled prevalence of zero-dose children was 6.5% among the urban non-poor, 12.6% for the urban poor, and 14.7% for the rural areas. There were significant differences between these areas in 43 countries. In most of these countries, the non-poor urban children were at an advantage compared to the urban poor, who were still better off or similar to rural children. Our results emphasize the inequalities between urban and rural areas, but also within urban areas, highlighting the challenges faced by poor urban and rural children. Outreach programs and community interventions that can reach poor urban and rural communities-along with strengthening of current vaccination programs and services-are important steps to reduce inequalities and ensure that no child is left unvaccinated.
Topics: Humans; Infant; Developing Countries; Rural Population; Urban Population; Health Services Accessibility; Female; Male; Diphtheria-Tetanus-Pertussis Vaccine; Poverty; Vaccination Coverage; Immunization Programs; Prevalence
PubMed: 38767765
DOI: 10.1007/s11524-024-00859-7 -
BioRxiv : the Preprint Server For... May 2024Antibody-secreting cells (ASCs) are generated following B cell activation and constitutively secrete antibodies. As such, ASCs are key mediators of humoral immunity...
Antibody-secreting cells (ASCs) are generated following B cell activation and constitutively secrete antibodies. As such, ASCs are key mediators of humoral immunity whether it be in the context of pathogen exposure, vaccination or even homeostatic clearance of cellular debris. Therefore, understanding basic tenants of ASC biology such as their differentiation kinetics following B cell stimulation is of importance. Towards that aim, we developed a mouse model which expresses simian (a.k.a., diphtheria toxin receptor ()) under the control of the endogenous locus (or J-DTR). ASCs from these mice expressed high levels of cell surface DTR and were acutely depleted following diphtheria toxin treatment. Furthermore, proof-of-principle experiments demonstrated the ability to use these mice to track ASC reconstitution following depletion in 3 distinct organs. Overall, J-DTR mice provide a new and highly effective genetic tool allowing for the study of ASC biology in a wide range of potential applications.
PubMed: 38766257
DOI: 10.1101/2024.05.06.592703 -
Frontiers in Pediatrics 2024Pretransplant vaccination is generally recommended to solid organ transplant recipients. In infants with congenital nephrotic syndrome (CNS), the immune response is...
BACKGROUND
Pretransplant vaccination is generally recommended to solid organ transplant recipients. In infants with congenital nephrotic syndrome (CNS), the immune response is hypothetically inferior to other patients due to young age and urinary loss of immunoglobulins, but data on the immunization response in severely nephrotic children remain scarce. If effective, however, early immunization of infants with CNS would clinically be advantageous.
METHODS
We investigated serological vaccine responses in seven children with CNS who were immunized during nephrosis. Antibody responses to measles-mumps-rubella -vaccine (MMR), a pentavalent DTaP-IPV-Hib -vaccine (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, type b), varicella vaccine, combined hepatitis A and B vaccine, and pneumococcal conjugate vaccine (PCV) were measured after nephrectomy either before or after kidney transplantation.
RESULTS
Immunizations were started at a median age of 7 months [interquartile range (IQR) 7-8], with a concurrent median proteinuria of 36,500 mg/L (IQR 30,900-64,250). Bilateral nephrectomy was performed at a median age of 20 months (IQR 14-25), and kidney transplantation 10-88 days after the nephrectomy. Antibody levels were measured at median 18 months (IQR 6-23) after immunization. Protective antibody levels were detected in all examined children for hepatitis B (5/5), (7/7), rubella virus (2/2), and mumps virus (1/1); in 5/6 children for varicella; in 4/6 for poliovirus and vaccine-type pneumococcal serotypes; in 4/7 for type B and ; in 1/2 for measles virus; and in 2/5 for hepatitis A. None of the seven children had protective IgG levels against .
CONCLUSION
Immunization during severe congenital proteinuria resulted in variable serological responses, with both vaccine- and patient-related differences. Nephrosis appears not to be a barrier to successful immunization.
PubMed: 38756974
DOI: 10.3389/fped.2024.1392873 -
Nature Communications May 2024Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect...
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 CD19-BMPC are derived from follicular, while CD19-BMPC originate from extrafollicular immune reactions. In primary immune reactions, both CD19- and CD19-BMPC compartments are populated. In secondary immune reactions, most BMPC are recruited to CD19-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.
Topics: Humans; Plasma Cells; Interleukins; Bone Marrow; Antigens, CD19; Immunity, Humoral; COVID-19; SARS-CoV-2; Bone Marrow Cells; Single-Cell Analysis; Adult; B-Lymphocytes; Antibody-Producing Cells; Female; Male; Vaccination; Middle Aged; Diphtheria-Tetanus-Pertussis Vaccine
PubMed: 38755157
DOI: 10.1038/s41467-024-48570-0 -
Clinical and Experimental Vaccine... Apr 2024Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore,...
PURPOSE
Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines.
MATERIALS AND METHODS
The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments.
RESULTS
HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups.
CONCLUSION
There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.
PubMed: 38752005
DOI: 10.7774/cevr.2024.13.2.155 -
Nature Medicine May 2024How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African...
How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.
Topics: Humans; HLA-DRB1 Chains; Infant; Black People; Hepatitis B Vaccines; Quantitative Trait Loci; Male; Female; Uganda; Antibody Formation; Pertussis Vaccine; Vaccination; Whooping Cough
PubMed: 38740997
DOI: 10.1038/s41591-024-02944-5 -
Microbial Genomics May 2024Cutaneous ulcers are common in yaws-endemic areas. Although often attributed to ' subsp. and , quantitative PCR has highlighted a significant proportion of these ulcers...
Using 16s rRNA sequencing to characterize the microbiome of tropical cutaneous ulcer disease: insights into the microbial landscape and implications for diagnosis and treatment.
Cutaneous ulcers are common in yaws-endemic areas. Although often attributed to ' subsp. and , quantitative PCR has highlighted a significant proportion of these ulcers are negative for both pathogens and are considered idiopathic. This is a retrospective analysis utilising existing 16S rRNA sequencing data from two independent yaws studies that took place in Ghana and the Solomon Islands. We characterized bacterial diversity in 38 samples to identify potential causative agents for idiopathic cutaneous ulcers. We identified a diverse bacterial profile, including , , , spp and , consistent with findings from previous cutaneous ulcer microbiome studies. No single bacterial species was universally present across all samples. The most prevalent bacterium, , appeared in 42% of samples, suggesting a multifactorial aetiology for cutaneous ulcers in yaws-endemic areas. This study emphasizes the need for a nuanced understanding of potential causative agents. The findings prompt further exploration into the intricate microbial interactions contributing to idiopathic yaw-like ulcers, guiding future research toward comprehensive diagnostic and therapeutic strategies.
Topics: Humans; RNA, Ribosomal, 16S; Microbiota; Skin Ulcer; Ghana; Male; Yaws; Retrospective Studies; Female; Adult; Bacteria; Melanesia; Middle Aged; Staphylococcus; Streptococcus pyogenes; Arcanobacterium; Campylobacter
PubMed: 38739120
DOI: 10.1099/mgen.0.001234