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The Journal of Infection May 2024
Topics: Humans; COVID-19; Pakistan; Diphtheria; Immunization, Secondary; SARS-CoV-2; Male; Pandemics; COVID-19 Vaccines; Female
PubMed: 38513739
DOI: 10.1016/j.jinf.2024.106141 -
PloS One 2024Vaccination is widely considered to be one of the most important prevention measures as a health strategy. This paper examines trends in basic childhood vaccination...
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.
Topics: Child; Humans; Infant; Vaccination Coverage; Immunization Programs; Vaccination; Immunization; Socioeconomic Factors; Diphtheria-Tetanus-Pertussis Vaccine
PubMed: 38512892
DOI: 10.1371/journal.pone.0300404 -
Nature Communications Mar 2024Neurointestinal diseases cause significant morbidity and effective treatments are lacking. This study aimes to test the feasibility of transplanting autologous enteric...
Neurointestinal diseases cause significant morbidity and effective treatments are lacking. This study aimes to test the feasibility of transplanting autologous enteric neural stem cells (ENSCs) to rescue the enteric nervous system (ENS) in a model of colonic aganglionosis. ENSCs are isolated from a segment of small intestine from Wnt1::Cre;R26iDTR mice in which focal colonic aganglionosis is simultaneously created by diphtheria toxin injection. Autologous ENSCs are isolated, expanded, labeled with lentiviral-GFP, and transplanted into the aganglionic segment in vivo. ENSCs differentiate into neurons and glia, cluster to form neo-ganglia, and restore colonic contractile activity as shown by electrical field stimulation and optogenetics. Using a non-lethal model of colonic aganglionosis, our results demonstrate the potential of autologous ENSC therapy to improve functional outcomes in neurointestinal disease, laying the groundwork for clinical application of this regenerative cell-based approach.
Topics: Mice; Animals; Hirschsprung Disease; Stem Cell Transplantation; Neural Stem Cells; Neurons; Enteric Nervous System; Colorectal Neoplasms
PubMed: 38509106
DOI: 10.1038/s41467-024-46793-9 -
Vaccine Apr 2024Previous studies have shown that vaccination against measles, mumps, and rubella (MMR) may have beneficial non-specific effects, reducing the risk of infections not...
Is vaccination against measles, mumps, and rubella associated with reduced rates of antibiotic treatments among children below the age of 2 years? Nationwide register-based study from Denmark, Finland, Norway, and Sweden.
OBJECTIVES
Previous studies have shown that vaccination against measles, mumps, and rubella (MMR) may have beneficial non-specific effects, reducing the risk of infections not targeted by the vaccine. We investigated if MMR vaccine given after the third dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP3), was associated with reduced rates of antibiotic treatments.
METHODS
Register-based cohort study following children from the age of recommended MMR vaccination until age 2 years. We included 831,287 children born in Denmark, Finland, Norway, and Sweden who had received DTaP3 but not yet MMR vaccine. Cox proportional hazards regression with age as the underlying timescale and vaccination status as a time-varying exposure was used to estimate covariate-adjusted Hazard Ratios (aHRs) and inverse probability of treatment weighted (IPTW) HRs of antibiotic treatments. Summary estimates were calculated using random-effects meta-analysis.
RESULTS
Compared with only having received DTaP3, receipt of MMR vaccine after DTaP3 was associated with reduced rates of antibiotic treatments in all countries: the aHR was 0.92 (0.91-0.93) in Denmark, 0.92 (0.90-0.94) in Finland, 0.84 (0.82-0.85) in Norway, and 0.87 (0.85-0.90) in Sweden, yielding a summary estimate of 0.89 (0.85-0.93). A stronger beneficial association was seen in a negative control exposure analysis comparing children vaccinated with DTaP3 vs two doses of DTaP.
CONCLUSIONS
Across the Nordic countries, receipt of MMR vaccine after DTaP3 was associated with an 11% lower rate of antibiotic treatments. The negative control analysis suggests that the findings are affected by residual confounding. Findings suggest that potential non-specific effects of MMR vaccine are of limited clinical and public health importance for the milder infections treated out-of-hospital in the Nordic setting.
Topics: Child; Child, Preschool; Humans; Infant; Cohort Studies; Denmark; Finland; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Norway; Rubella; Sweden; Vaccination
PubMed: 38508926
DOI: 10.1016/j.vaccine.2024.03.026 -
The Journal of Antimicrobial... May 2024Corynebacterium (C.) sp. 22KM0430 related to C. oculi and isolated from a dog exhibited resistance to tetracycline, and its WGS analysis revealed a putative resistance...
BACKGROUND
Corynebacterium (C.) sp. 22KM0430 related to C. oculi and isolated from a dog exhibited resistance to tetracycline, and its WGS analysis revealed a putative resistance gene on a 35 562-bp plasmid also harbouring the MLSB resistance gene erm(X).
OBJECTIVES
To characterize the novel tetracycline resistance gene tet(65) and demonstrate its functionality by expression in C. glutamicum and Escherichia coli and plasmid curing of the host strain.
METHODS
tet(65) was cloned with and without its repressor tetR(65) and expressed in C. glutamicum DSM20300 and E. coli DH5α. Plasmid was cured by non-selective passages. Minimal inhibitory concentrations (MICs) of tetracyclines were determined according to CLSI guidelines. Association of tet(65) with efflux was shown by the addition of reserpine to MIC assays. Phylogenetic position and transmembrane structure of Tet(65) were analysed using MEGA11 and DeepTMHMM.
RESULTS
Tet(65) shows 73% amino acid identity with the closest related Tet(Z), contains 12 transmembrane domains and is structurally related to the Major Facilitator Superfamily. The tetracycline MICs decreased in the plasmid-cured strain and increased when tet(65) was expressed in C. glutamicum and in E. coli. The MICs of tetracycline decreased in the presence of reserpine indicating that tet(65) functions as an efflux pump. A GenBank search also identified tet(65) in C. diphtheriae and Brevibacterium (B.) casei and B. luteolum.
CONCLUSIONS
A novel tetracycline efflux gene tet(65) was identified in a C. oculi related species and was also present in the human pathogen C. diphtheriae and in Brevibacterium species indicating broader potential for dissemination.
Topics: Plasmids; Tetracycline Resistance; Microbial Sensitivity Tests; Anti-Bacterial Agents; Escherichia coli; Corynebacterium; Animals; Drug Resistance, Multiple, Bacterial; Phylogeny; Dogs; Tetracycline; Cloning, Molecular; Corynebacterium Infections; Dog Diseases
PubMed: 38497972
DOI: 10.1093/jac/dkae066 -
MSphere Apr 2024Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination...
UNLABELLED
Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies.
IMPORTANCE
Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.
Topics: Humans; Female; Antibodies, Bacterial; Milk, Human; Whooping Cough; Immunoglobulin G; Diphtheria-Tetanus-acellular Pertussis Vaccines; Pregnancy; Adult; Diphtheria; Tetanus; Young Adult; Vaccination; Immunity, Maternally-Acquired
PubMed: 38497618
DOI: 10.1128/msphere.00527-23 -
Frontiers in Immunology 2024
Topics: Humans; Inflammasomes; Reactive Oxygen Species; NLR Family, Pyrin Domain-Containing 3 Protein; Cell Death; Communicable Diseases
PubMed: 38476228
DOI: 10.3389/fimmu.2024.1378506 -
Nature Communications Mar 2024Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We...
Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We combine mouse models allowing diphtheria toxin-mediated damage of specific epithelial cell types and parallel GFP-labeling of functionally dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncover cell types, including Krt13 basal and Krt15 club cells, detect an intermediate cell state between basal and goblet cells, reveal goblet cells as actively dividing progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also show that diphtheria toxin-expressing cells can persist in the lung, express specific inflammatory factors, and transcriptionally resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to concise epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.
Topics: Mice; Animals; Humans; Diphtheria Toxin; Lung; Cell Differentiation; Gene Expression Profiling; Cell Division
PubMed: 38472236
DOI: 10.1038/s41467-024-46469-4 -
Frontiers in Immunology 2024Tetanus, diphtheria, acellular pertussis (Tdap) vaccination is recommended to be administered in every pregnancy. Although the safety of this strategy has been...
BACKGROUND
Tetanus, diphtheria, acellular pertussis (Tdap) vaccination is recommended to be administered in every pregnancy. Although the safety of this strategy has been confirmed, the immunogenicity of Tdap vaccination in two successive pregnancies has not yet been described. This study investigated Tdap-specific immunity levels and transplacental transfer in two successive pregnancies after repeated Tdap-vaccination.
METHODS
Women enrolled in prior studies on Tdap vaccination during pregnancy were invited to participate in a follow-up study if they became pregnant again. Women who received a Tdap vaccine in both pregnancies were considered for this analysis. Tdap-specific total IgG and IgG subclasses were measured with a multiplex immunoassay.
RESULTS
In total, 27 participants with a mean interval between deliveries of 2.4 years were included in the analysis. In maternal serum, Tdap-specific total IgG levels were comparable at both deliveries whereas in cord serum, all Tdap-specific total IgG antibody levels were reduced at the second compared to the first delivery. This was largely reflected in the IgG1 levels in maternal and cord serum. Transplacental transfer ratios of total IgG and IgG1 were also mostly reduced in the second compared to the first pregnancy.
CONCLUSION
This study reports for the first time Tdap-specific total IgG and IgG subclass levels and transfer ratios after repeated Tdap vaccination in successive pregnancies. We found reduced transfer of most Tdap-specific IgG and IgG1 antibodies in the successive pregnancy. As pertussis-specific antibodies wane quickly, Tdap vaccination in each pregnancy remains beneficial. However, more research is needed to understand the impact of closely spaced booster doses during pregnancy on early infant protection against pertussis.
Topics: Pregnancy; Humans; Female; Diphtheria-Tetanus-acellular Pertussis Vaccines; Whooping Cough; Diphtheria; Tetanus; Follow-Up Studies; Antibodies, Bacterial; Immunoglobulin G; Vaccination
PubMed: 38464513
DOI: 10.3389/fimmu.2024.1360201 -
Infectious Diseases and Therapy Apr 2024Bacterial infections have a significant impact on human health; they can cause severe morbidity and mortality, particularly in susceptible populations. Epidemiological...
INTRODUCTION
Bacterial infections have a significant impact on human health; they can cause severe morbidity and mortality, particularly in susceptible populations. Epidemiological surveillance is a critical tool for monitoring the population's health and facilitate the prevention and control of infectious disease outbreaks. Knowing the burden of bacterial communicable diseases is an initial core step toward public health goals.
METHODS
Saudi epidemiology surveillance data were utilized to depict the changing epidemiology of bacterial infectious diseases in Saudi Arabia from 2018 to 2021. The cumulative numbers of cases, demographics, and incidence rates were analyzed and visualized. Parametric tests were used to compare the difference in the mean values between categorical variables. Regression analysis was employed to estimate trends in disease rates over time. Statistical significance was set at p value ≤ 0.05.
RESULTS
The results revealed that brucellosis, tuberculosis, and salmonellosis were the most frequently reported bacterial infectious diseases in Saudi Arabia. Males were more significantly affected by brucellosis and tuberculosis infections than females. Salmonellosis infections were more significant among Saudi citizens, while pulmonary tuberculosis was more significant in non-Saudis. Interestingly, there was a decline in the incidence rates of numerous bacterial infectious diseases during the Coronavirus Disease 2019 (COVID-19) pandemic and COVID-19 restrictions. Some bacterial infectious diseases were rarely reported in Saudi Arabia, including syphilis and diphtheria.
CONCLUSIONS
The future perspective of this research is to enhance disease surveillance reporting by including different variables, such as the source of infection, travel history, hospitalization, and mortality rates. The aim is to improve the sensitivity and specificity of surveillance data and focus on the mortality associated with bacterial pathogens to identify the most significant threats and set a public health priority.
PubMed: 38461481
DOI: 10.1007/s40121-024-00942-1