Search Results (317)

School vaccination programs are crucial for achieving high immunisation coverage among adolescents, but substantial disparities exist across schools and regions. This ecological study aimed to determine associations between school characteristics and vaccination coverage for diphtheria–tetanus–acellular pertussis (dTpa) and human papillomavirus (HPV) vaccines among year 7 students in southeastern Sydney. An analysis of data from 70 mainstream schools participating in the 2019 South Eastern Sydney Local Health District School Vaccination Program utilised quasi-Poisson regression models to assess associations between vaccination coverage and school attendance, socio-educational status, Aboriginal enrolments, language background other than English (LBOTE), school sector (government, Catholic, or independent), and coeducation status. Median school coverage was 88% for dTpa, 88% for HPV—girls, and 86% for HPV—boys, with interquartile ranges of 82–93%, 84–92%, and 78–91%, respectively. Higher school attendance was associated with increased dTpa vaccination coverage (PR 1.14, 95% CI 1.02–1.27). Single-sex schools showed higher HPV vaccination coverage compared to coeducational schools for both girls (PR 2.24, 95% CI 2.04–2.46) and boys (PR 1.89, 95% CI 1.72–2.08). No significant associations were found for ICSEA, Aboriginal enrolments, LBOTE, or school sector. School attendance and coeducational status significantly influenced vaccination coverage, with differential impacts on dTpa and HPV vaccines. These findings highlight the need for targeted strategies to address disparities in school-based vaccination programs. Research using qualitative methods could be useful to understand the beliefs and attitudes contributing to these disparities in vaccine uptake so that programs can be tailored to maximise participation. Full article

This study aimed to investigate the knowledge, attitudes, and behaviors of family physicians (FPs), pediatricians (PPs), and obstetricians and gynecologists (OGs) regarding vaccine administration during pregnancy in Turkey as factors that contribute to decision-making. The survey was distributed among FPs, OGs, and PPs, and participants were asked to rate their knowledge on specific topics using a five-point scale ranging from “Not Effective” to “Effective”. The tetanus and diphtheria (Td) vaccine was highly recommended by 94.9% of physicians and considered very effective. Among the physicians surveyed, 80% of PPs and 66.0% of OGs were aware of the disease burden of pertussis. We also found that 74.5% of FPs and 77.2% of PPs believed they needed more information about vaccination during pregnancy. All physicians surveyed agreed or strongly agreed that explaining the disease risks and benefits of vaccination increases the vaccine acceptance rate. The results of this survey study indicate that the knowledge and awareness of physicians need to be improved to increase vaccination rates during pregnancy in Turkey, and it is essential to incorporate influenza and tetanus, diphtheria, and pertussis (TdaP) vaccines into the standard maternal immunization schedule for newborns. Full article

This study aims to evaluate and compare cellular therapy with human Wharton’s jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund’s complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 10⁵. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases. Full article

(1) Background: “Zero-dose” (ZD) refers to a child who has not received any doses of the pentavalent (diphtheria–tetanus–pertussis–Haemophilus influenzae type b (Hib)–hepatitis B) vaccine. ZD children are vulnerable to vaccine-preventable diseases (VPDs). Luambo health district (HD) is one of 26 HDs in Kasai Central Province in Democratic Republic of the Congo and had the largest number of ZD children in 2021. This study was conducted to identify factors associated with ZD status among children in Luambo HD. (2) Methods: We conducted a mixed-methods study of children aged 12–23 months in Luambo HD. (3) Results: A total of 445 children aged 12–23 months were included in the study, including 89 cases and 356 controls. Children who were born in Angola (AOR = 3.2; 95% CI = 1.1 to 9.8; p = 0.046), born at home (AOR = 5.2; 95% CI = 2.1 to 12.5; p < 0.001), whose mothers did not receive antenatal care (AOR = 4.4; 95% CI = 1.2 to 16.3; p = 0.023), or did not know any vaccine preventable disease (AOR = 13.3; 95% CI = 4.6 to 38.4; p < 0.001) were more likely to be ZD than their counterparts. In addition, perceptions of children’s parents influenced child immunization. (4) Conclusions: Factors associated with being a ZD child suggest inequalities in vaccination that need to be addressed through appropriate interventions. Maternal and child health services need to be strengthened while also targeting children’s fathers. This will make it possible to considerably reduce the proportion of ZD and undervaccinated children and effectively fight against VPDs. Full article

LPA₃ receptors were expressed in TREx HEK 293 cells, and their signaling and phosphorylation were studied. The agonist, lysophosphatidic acid (LPA), increased intracellular calcium and ERK phosphorylation through pertussis toxin-insensitive processes. Phorbol myristate acetate, but not LPA, desensitizes LPA₃-mediated calcium signaling, the agonists, and the phorbol ester-induced LPA₃ internalization. Pitstop 2 (clathrin heavy chain inhibitor) markedly reduced LPA-induced receptor internalization; in contrast, phorbol ester-induced internalization was only delayed. LPA induced rapid β-arrestin–LPA₃ receptor association. The agonist and the phorbol ester-induced marked LPA₃ receptor phosphorylation, and phosphorylation sites were detected using mass spectrometry. Phosphorylated residues were detected in the intracellular loop 3 (S221, T224, S225, and S229) and in the carboxyl terminus (S321, S325, S331, T333, S335, Y337, and S343). Interestingly, phosphorylation sites are within sequences predicted to constitute β-arrestin binding sites. These data provide insight into LPA₃ receptor signaling and regulation. Full article

Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel^® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos^®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates. Full article

Experimental autoimmune encephalomyelitis (EAE) is a powerful model to study multiple sclerosis (MS). One of the approaches for EAE is to actively immunize with myelin-derived peptides with immune adjuvants. One of the commonly used immune adjuvants is pertussis toxin (PTx), without which EAE disease is mild with relatively longer onset. However, pertussis toxin can also inhibit G protein-coupled receptor (GPCR) signaling so it can confound investigations into the role of GPCRs in EAE or therapies designed to target GPCRs. Since EAE via active immunization without PTx results in a relatively mild disease state, we wanted to confirm that appropriate signaling molecules for the disease were being induced in one target tissue (i.e., brain). RNA-Seq analysis of whole brain tissue demonstrated that the MS signaling pathway was strongly activated in symptomatic mice. In addition, there was activation of Th1 (IFN signaling), Th2 (IL-4 signaling), and Th17 (IL-17 signaling). In comparing canonical pathways from our mouse mild EAE brains with a human MS atlas, EAE shared the most pathways with active and inactive lesions. An advantage of this approach is that disease induction is slower to develop and results in modest clinical signs, which likely more closely mimic human disease onset. Full article

Pregnancy after organ transplantation is considered high-risk and requires supervision in specialized centers. The impact of immunosuppression on the developing fetus is still the subject of research. It has been shown that it affects lymphocyte populations in the first year of life. For this reason, researchers suggest postponing mandatory infant vaccinations. The aim of the study was to analyze the influence of intrauterine exposure of the fetus to immunosuppression on the immunogenicity of protective vaccinations against selected bacterial pathogens. The ELISA method was used to determine the concentration of post-vaccination IgG antibodies against diphtheria, tetanus, pertussis, tuberculosis, H. influenzae type B, and S. pneumoniae in 18 children of mothers who underwent organ transplantation. The results were compared with the control group (n = 21). A comparison of the incidence of adverse post-vaccination reactions between the analyzed groups was also performed. There were no statistically significant differences in the immunogenicity of the analyzed vaccines between children of mothers who underwent organ transplantation and the age-matched general pediatric population. There were no differences in the incidence of adverse post-vaccination reactions between the analyzed groups. The obtained results do not indicate the need to modify the current protective vaccination schemes against bacterial pathogens in children of mothers who underwent organ transplantation. Full article

Microbicides, which are classified as topical antiseptic agents, are a revolutionary advancement in HIV prevention aimed to prevent the entry of infectious agents into the human body, thus stopping the sexual transmission of HIV and other sexually transmitted diseases. Microbicides represent the promise of a new age in preventive measures against one of the world’s most pressing health challenges. In addition to their direct antiviral effects during HIV transmission, microbicides also influence vaginal mucosal immunity. This article reviews microbicides by presenting different drug classifications and highlighting significant representatives from each group. It also explains their mechanisms of action and presents information about vaginal mucosal immune responses, emphasizing the critical role they play in responding to HIV during sexual transmission. The article discusses the following groups of microbicides: surfactants or membrane disruptors, vaginal milieu protectors, anionic polymers, dendrimers, carbohydrate-binding proteins, HIV replication inhibitors (reverse transcriptase inhibitors), and multi-purpose prevention technologies, which combine protection against HIV, other sexually transmitted diseases, and contraception. For each chemical compound, the article provides a brief overview of relevant preclinical and clinical research, emphasizing their potential as microbicides. The article offers insights into the multifaceted impact of microbicides, which signify a pivotal step forward in the pursuit of effective and accessible pre-exposure prophylaxis (PrEP). Full article

Respiratory tract infections (RTIs) can lead to both recurrent seasonal epidemic outbreaks and devastating pandemics. The aim of this study was to evaluate the epidemiologic characteristics and pathogen spectrum of RTIs using a multiplex RT-PCR panel. A total of 9354 cases with suspected RTIs between February 2021 and July 2023 were included in this study. A total of 11,048 nasopharyngeal and oropharyngeal samples from these patients were analyzed for 23 respiratory tract pathogens using multiplex RT-PCR. H. influenzae and S. pneumoniae were considered as colonizing bacteria. At least one pathogen was detected in 70.66% of the samples; viral pathogens were detected in 48.41% of the samples, bacterial pathogens were detected in 16.06% of the samples, and viral + bacterial pathogens were detected in 35.53% of the samples. The most frequently detected viral pathogen was rhinovirus/enterovirus (RV/EV) (19.99%). Interestingly, in 2021, respiratory syncytial virus A/B showed atypical activity and replaced RV/EV as the most prevalent pathogen. Human bocavirus, H. influenzae, and S. pneumoniae were detected at higher rates in males (p: 0.038, p: 0.042, and p: 0.035, respectively), while SARS-CoV-2 and B. pertussis were detected at higher rates in females (p < 0.001 and p: 0.033). RTIs were found at higher rates in children (p < 0.001). SARS-CoV-2 and human coronaviruses 229E were detected at higher rates in adults (p < 0.001 and p: 0.001). This comprehensive study with a large sample size investigating RTI pathogens was the first in Türkiye. Understanding the current viral circulation using multiplex RT-PCR panels enables clinicians to predict the most likely pathogens affecting patients and contributes to patient management, in addition to anticipating potential threats. Full article

Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B. pertussis prevalence in pediatric patients admitted to the Reference Italian Pediatric Hospital, located in Rome, from January 2015 to July 2023. A total of 5464 tests for B. pertussis were performed during the study period, and 6.9% were positive. At the time of the COVID-19 pandemic, there was a sharp decrease in the presence of B. pertussis, which reappeared only in August 2023, recording five new cases. All five children presented with paroxysmal cough 5 to 10 days before admission. Four patients had other mild respiratory symptoms and moderate B. pertussis DNA levels (Ct mean: 26). Only one child, with very high B. pertussis DNA levels (Ct: 9), presented with severe respiratory failure. The patients with mild/moderate infection achieved clinical recovery while the patient with the severe manifestation died of cardiac arrest. These observations highlight the reemergence of pertussis even in vaccinated countries and its association with morbidity and mortality especially in young children. This emphasizes the importance of rapid diagnosis to immediately implement appropriate treatment and monitoring of immune status. Full article

Yeast two-hybrid approaches, which are based on fusion proteins that must co-localise to the nucleus to reconstitute the transcriptional activity of GAL4, have greatly contributed to our understanding of the nitrogen interaction network of cyanobacteria, the main hubs of which are the trimeric PII and the monomeric PipX regulators. The bacterial two-hybrid system, based on the reconstitution in the E. coli cytoplasm of the adenylate cyclase of Bordetella pertussis, should provide a relatively faster and presumably more physiological assay for cyanobacterial proteins than the yeast system. Here, we used the bacterial two-hybrid system to gain additional insights into the cyanobacterial PipX interaction network while simultaneously assessing the advantages and limitations of the two most popular two-hybrid systems. A comprehensive mutational analysis of PipX and bacterial two-hybrid assays were performed to compare the outcomes between yeast and bacterial systems. We detected interactions that were previously recorded in the yeast two-hybrid system as negative, as well as a “false positive”, the self-interaction of PipX, which is rather an indirect interaction that is dependent on PII homologues from the E. coli host, a result confirmed by Western blot analysis with relevant PipX variants. This is, to our knowledge, the first report of the molecular basis of a false positive in the bacterial two-hybrid system. Full article

Pertussis continues to be a significant public health concern. We aimed to examine the epidemiological characteristics of pertussis in Vojvodina, which accounts for almost a third of Serbia’s population. Our aim was to determine the overall and age-specific incidence and mortality rates of pertussis in Vojvodina from 1948 to 2023, as well as the coverage of immunization against pertussis from 1960 to 2023. In the period 1948–2023, 42,259 cases of pertussis were reported. Following the introduction of the DTwP vaccine (1960) in Serbia, the reported incidence of pertussis began to decline. In 2001, for the first time since introduction of pertussis surveillance in Vojvodina, no pertussis cases were reported. Since 2012, the reported incidence of pertussis has once again increased, and peaked (41.1/100,000) in 2023, approaching the incidence rates recorded shortly after the introduction of DTwP vaccine. A shift in the age profile of pertussis from children aged 0–6 years to school-aged children (7–14 years) occurred between 2012 and 2023, when 48.3% of pertussis cases occurred in this age group. Although the incidence rates of pertussis among individuals aged 20 years and older were significantly lower than among younger age groups, there is evidence of an increasing trend in pertussis cases, particularly among those aged 40–49 years, since 2012. Based on the findings of this study, it is imperative to introduce additional booster doses of the aP vaccine for individuals aged 14 years, along with implementing maternal immunization strategies targeting women of childbearing age. Full article

The COVID-19 pandemic has globally disrupted immunisation practices, impacting vulnerable populations such as pregnant women (PW), who harbour concerns about future children’s immunisations. This study aimed to assess the pandemic’s impact on PW’s attitudes towards childhood vaccinations. During three consecutive flu seasons from October 2019 to January 2022, a cross-sectional study was conducted in a large Italian teaching hospital using a questionnaire. The chi-square test was performed to compare each season. Across the 2019–2020 to 2021–2022 seasons, course attendance by PW surged from 105 to 340. Significant shifts in vaccination intentions were noted, including a 7.5% decrease in measles vaccination intent (p = 0.02) and a 10% decrease in that of pertussis (p = 0.004) from 2019–2020 to 2020–2021. While perceived contagion risk decreased, disease severity perceptions increased, with few significant differences. A statistically significant reduction was noted in the proportion of participants suspecting economic motives behind NHS workers’ promotion of childhood vaccinations. Furthermore, the pandemic period saw an increase in the perceived utility of non-institutional websites and the advice of physicians outside the NHS. These findings will help develop evidence-based, tailored interventions and communication strategies to address vaccine hesitancy and ensure optimal vaccination coverage among children born during and after the pandemic. Full article

Background: Routine vaccination coverage in Latin America and the Caribbean declined prior to and during the coronavirus pandemic. We assessed the pandemic’s impact on national coverage levels and analyzed whether financial and inequality indicators, immunization policies, and pandemic policies were associated with changes in national and regional coverage levels. Methodology: We compared first- and third-dose coverage of diphtheria–pertussis–tetanus-containing vaccine (DTPcv) with predicted coverages using time series forecast modeling for 39 LAC countries and territories. Data were from the PAHO/WHO/UNICEF Joint Reporting Form. A secondary analysis of factors hypothesized to affect coverages during the pandemic was also performed. Results: In total, 31 of 39 countries and territories (79%) had greater-than-predicted declines in DTPcv1 and DTPcv3 coverage during the pandemic, with 9 and 12 of these, respectively, falling outside the 95% confidence interval. Within-country income inequality (i.e., Gini coefficient) was associated with significant declines in DTPcv1 coverage, and cross-country income inequality was associated with declines in DTPcv1 and DTPcv3 coverages. Observed absolute and relative inequality gaps in DTPcv1 and DTPcv3 coverage between extreme country quintiles of income inequality (i.e., Q1 vs. Q5) were accentuated in 2021, as compared with the 2019 observed and 2021 predicted values. We also observed a trend between school closures and greater-than-predicted declines in DTPcv3 coverage that approached statistical significance (p = 0.06). Conclusion: The pandemic exposed vaccination inequities in LAC and significantly impacted coverage levels in many countries. New strategies are needed to reattain high coverage levels. Full article