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Vaccines Apr 2024A seroepidemiological study was conducted in 2018 to assess diphtheria and tetanus antibodies in Guangzhou, China. Diphtheria and tetanus antibody concentrations were...
A seroepidemiological study was conducted in 2018 to assess diphtheria and tetanus antibodies in Guangzhou, China. Diphtheria and tetanus antibody concentrations were measured with an enzyme-linked immunosorbent assay. A total of 715 subjects were enrolled in the study. The overall diphtheria and tetanus toxoid IgG-specific antibody levels were 0.126 IU/mL (95% CI: 0.115, 0.137) and 0.210 IU/mL (95% CI: 0.185, 0.240), respectively; the overall positivity rate was 61.82% (95% CI: 58.14, 65.39) and 71.61% (95% CI: 68.3, 74.92), respectively. The diphtheria and tetanus antibody concentration was decreased by age and increased by doses. The geometric mean concentrations and positivity rate of diphtheria and tetanus antibodies were lowest and below the essential protection level in people over 14 years of age. Compared to children and adolescents, middle-aged people and the aged are at much higher risk of infection with Corynebacterium diphtheriae and Clostridium tetani. The current diphtheria and tetanus immunization schedule does not provide persistent protection after childhood. There is an urgent need to adjust the current immunization schedule.
PubMed: 38675763
DOI: 10.3390/vaccines12040381 -
Vaccines Apr 2024Diphtheria and tetanus could lead to serious morbidity. We aimed to evaluate immunity levels by measuring specific IgG antibodies for diphtheria and tetanus in serum...
Diphtheria and tetanus could lead to serious morbidity. We aimed to evaluate immunity levels by measuring specific IgG antibodies for diphtheria and tetanus in serum samples from a nationally expanded sample of the Greek population. A geographically stratified sampling approach based on regional units (NUTS level 2) was applied by considering variables such as age group (30-80+) and sex. In total, 1201 persons (47.7% males and 52.3% females) participated in the survey. Bivariate analysis revealed a negative relationship between diphtheria and tetanus median antibody titers and age. The overall seropositivity rate for diphtheria IgG antibodies (≥0.10 IU/mL) was estimated at 31.5%. Regarding tetanus, the total seropositivity rate was estimated at 59.5% (tetanus IgG antibodies ≥0.10 IU/mL). Logistic regression analysis indicated that age groups <40 years and 40-59 years were independently associated with tetanus seropositivity. Logistic regression also revealed that male sex and being aged 60-69 years were independent risk factors for diphtheria-related seropositivity. Lastly, being resident of some regions was an independent risk factor for both diphtheria- and tetanus-related seropositivity. The present study shows that Greek adults are still not completely immune to diphtheria and tetanus. It is likely possible to achieve optimal immunization coverage by implementing serviceable public health initiatives after comprehending real community needs.
PubMed: 38675760
DOI: 10.3390/vaccines12040378 -
Journal of Medical Case Reports Apr 2024Optic neuritis (ON) is an inflammatory demyelinating condition of the optic nerve, with various causes. Its incidence is higher in children and young adults than in...
BACKGROUND
Optic neuritis (ON) is an inflammatory demyelinating condition of the optic nerve, with various causes. Its incidence is higher in children and young adults than in older adults of both genders, but is more common in women than in men. ON is rarely associated with mydriasis, and it is seldom triggered by vaccines against tetanus and diphtheria.
CASE REPORT
A 36-year-old Caucasian woman presented with bilateral ON that had started 18 days after administration of a booster dose of the double adult vaccine (dT) against diphtheria and tetanus. Bilateral mydriasis persisted after treatment and clinical resolution of the ON. She experienced severe headache, blurred vision, decreased visual acuity in the right eye and bilateral mydriasis, a diagnosis confirmed by imaging tests. Treatment with oral corticosteroids resulted in rapid resolution of the neuritis; however, mydriasis persisted for several months.
CONCLUSION
This study describes a very unusual case of bilateral ON associated with prolonged mydriasis after vaccination against tetanus and diphtheria that regressed after treatment with oral corticosteroids. Prolonged mydriasis was the manifestation that differed from the other cases previously described.
Topics: Humans; Optic Neuritis; Female; Adult; Mydriasis; Vaccination; Treatment Outcome; Diphtheria-Tetanus Vaccine
PubMed: 38659067
DOI: 10.1186/s13256-024-04526-y -
Vaccine: X Jun 2024Diphtheria-tetanus-acellular pertussis, polio, and Haemophilus influenza type B (DTaP-IPV/Hib) combination vaccine was introduced as a part of the Korea National...
BACKGROUND
Diphtheria-tetanus-acellular pertussis, polio, and Haemophilus influenza type B (DTaP-IPV/Hib) combination vaccine was introduced as a part of the Korea National Immunization Program (NIP) on June 19, 2017. Combination vaccines can improve vaccination rates by simplifying the vaccination schedule.
OBJECTIVE
To explain how the introduction of DTaP-IPV/Hib in the NIP has changed vaccination practices for infants.
METHODS
Using a nationwide vaccine registry, the proportion of infants who completed the full recommended doses of the primary series of DTaP, IPV, and Hib (D-I-H) within 12 months of age was estimated among those born between 2013 and 2019. Among those, the proportions of those who received the same DTaP components for all 3 doses during the primary series were calculated for the 2013-2016 and the 2017-2019 birth cohorts. Those who received the same component of DTaP throughout the entire primary vaccination schedule were categorized into 3 groups by DTaP components to compare the average frequency of medical visits for vaccination.
RESULTS
A total of 2,703,822 infants were born between 2013 and 2019, of which 96.7% completed full doses of the primary D-I-H series within 12 months of age. For the 2013-2016 birth cohorts, most received DTaP-IPV-only (75.4%), while most of the 2017-2019 birth cohorts received DTaP-IPV/Hib-only (81.0%) to complete the 3 doses for primary D-I-H series. The average frequency of medical visits for vaccination showed a significant difference across the 3 groups classified by DTaP components in every birth cohort (p < 0.001).
CONCLUSIONS
After the introduction of DTaP-IPV/Hib, most infants completed the primary D-I-H series with the combination vaccine and there was a significant reduction in the average number of medical visits for vaccination. Our findings provide important insights for countries considering the introduction of combination vaccines into their NIP.
PubMed: 38655547
DOI: 10.1016/j.jvacx.2024.100484 -
Frontiers in Immunology 2024For several years, we have been committed to exploring the potential of -derived outer membrane vesicles (OMV) as a promising third-generation vaccine against the...
For several years, we have been committed to exploring the potential of -derived outer membrane vesicles (OMV) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMV as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMV combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMV and the immunogens at varying levels. These assays demonstrated that OMV exhibits adjuvant properties even at the low concentration employed (1.5 μg of protein per dose). As this effect was notably enhanced at medium (3 μg) and high concentrations (6 μg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMV exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMV, specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001). When assessing the adjuvant properties of OMV compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from (OMV) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species. Nonetheless, it's crucial to highlight that OMV notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMV as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.
Topics: Bordetella pertussis; Animals; Adjuvants, Immunologic; Mice; Th1 Cells; Whooping Cough; Female; Immunoglobulin G; Pertussis Vaccine; Antibodies, Bacterial; Spike Glycoprotein, Coronavirus; Mice, Inbred BALB C; SARS-CoV-2; Bacterial Outer Membrane Proteins; Humans; COVID-19; Tetanus Toxoid
PubMed: 38650936
DOI: 10.3389/fimmu.2024.1387534 -
Cureus Mar 2024infection, causing diphtheria, is a public health concern, particularly in developing nations like Pakistan. Despite immunization efforts, recent outbreaks since 2022...
BACKGROUND
infection, causing diphtheria, is a public health concern, particularly in developing nations like Pakistan. Despite immunization efforts, recent outbreaks since 2022 have emphasized the continuing threat. This study focuses on describing the clinical characteristics of children with diphtheria-induced myocarditis and exploring the association between early cardiac abnormalities, future fatality rates, and contributing factors.
METHODS
A one-year cross-sectional study was undertaken at Lady Reading Hospital MTI Peshawar, encompassing 73 pediatric patients diagnosed with diphtheria-associated myocarditis. Data, including demographic characteristics, cardiac enzymes, and serial ECG and echocardiography data, were gathered from the health management information system (HMIS). Institutional Ethical Committee approval was obtained, and informed consent was waived due to its retrospective nature.
RESULTS
Gender distribution within the study was balanced, with 35 males (47.9%) and 38 females (52.1%). ECG data revealed various prevalence rates: 27.4% for rhythm abnormalities, 20% for conduction abnormalities, 6.8% for ischemia alterations, and 20.5% for normal findings. Treatment measures included anti-diphtheria serum (ADS) in 87.7% and temporary pacemaker placement (TPM) in 13.7% of patients. Echo findings indicated a variety of cardiac dysfunctions: 53.4% with no dysfunction, 9.6% mild malfunction, 6.8% with moderate dysfunction, and 30.1% with severe dysfunction. The categorization of creatine kinase (CK), lactate dehydrogenase (LDH), and troponin I (Trop I) gave insights into the biochemical aspects.
CONCLUSION
This study gives a full insight into the clinical symptoms of diphtheria-induced myocarditis in children. The findings can help establish a foundation for ongoing study into potential gender-related trends in clinical outcomes, contributing to improved care and preventative methods.
PubMed: 38650814
DOI: 10.7759/cureus.56744 -
Frontiers in Microbiology 2024The Vi-diphtheria toxoid typhoid conjugate vaccine (Vi-DT) has shown promising results in preventing typhoid fever in children under 2 years of age. However, a thorough...
BACKGROUND
The Vi-diphtheria toxoid typhoid conjugate vaccine (Vi-DT) has shown promising results in preventing typhoid fever in children under 2 years of age. However, a thorough assessment of its safety and immunogenicity is required to inform vaccination strategies. This systematic review and meta-analysis aimed to determine the safety and immunogenicity of Vi-DT in children below 2 years.
METHODS
We systematically searched multiple databases, including PubMed, Web of Science, and Scopus, for relevant studies published up to September 2023. We included studies reporting on the safety and immunogenicity outcomes of Vi-DT compared to the control or Vi-tetanus toxoid conjugated vaccine (Vi-TT) in children below 2 years. We applied a random-effects model for meta-analysis using RevMan 5.4. We expressed the results as risk ratio (RR) with a 95% confidence interval (95%CI).
RESULTS
In this analysis, five studies were selected, encompassing 1,292 children under 2 years who received the Vi-DT vaccine. No significant difference in immediate reactions was observed within 30 min post-vaccination between Vi-DT and control groups (RR: 0.99 [95% CI: 0.19, 5.26]), nor between Vi-DT and Vi-TT groups. For solicited adverse events within 4 weeks, the VI-DT group showed no significant increase in adverse events compared to control (RR: 0.93 [95% CI: 0.78, 1.12]) or Vi-TT (RR: 0.86 [95% CI: 0.69, 1.07]). Similarly, within 7 days post-vaccination, risk ratios indicated no significant differences in adverse events between the groups. The 4-week seroconversion rate was significantly higher in the Vi-DT group compared to the control (RR: 1.99 [95% CI: 1.07, 3.69]), but no difference was found between Vi-DT and Vi-TT. Adverse events associated with typhoid conjugate vaccines were predominantly non-serious, including fever and injection site reactions. Serious adverse events were rare but included conditions like pneumonia and gastroenteritis.
CONCLUSION
This meta-analysis highlights Vi-DT safety and immunogenicity in six to 24-month-old children. The findings support the use of this Vi-DT to expand typhoid vaccination in endemic regions, in line with WHO's strategy.
PubMed: 38646637
DOI: 10.3389/fmicb.2024.1385834 -
Frontiers in Pediatrics 2024Ethiopia is the fourth leading contributor to the global total of zero-dose children (those who lack the first dose of diphtheria-tetanus-pertussis containing vaccine)...
BACKGROUND
Ethiopia is the fourth leading contributor to the global total of zero-dose children (those who lack the first dose of diphtheria-tetanus-pertussis containing vaccine) and has substantial regional variations in zero-dose children. This study explored the spatial pattern of zero-dose children aged 12-35 months in Ethiopia.
METHODS
A survey was conducted in pastoralist regions, developing regions, newly-established regions, conflict-affected areas, underserved urban populations, hard-to-reach areas, internally displaced populations, and refugees. Spatial autocorrelation was measured using the Global Moran'sstatistic. Getis-Ord Gi* statistics was applied to calculate the spatial variability of the high and low prevalence rates of zero-dose children. The spatial interpolation technique was also applied to estimate unknown values that fall between known values. Inverse distance weighting interpolation method was used to predict the risk of zero-dose children. ArcGIS version 10.8 was used for the spatial analysis.
RESULTS
A total of 3,646 children aged 12-35 months were included in the study. The spatial distribution of zero-dose children in Ethiopia was non-random (Global Moran's = 0.178971, < 0.001). According to the hotspot analysis, western, eastern and northern parts of Somali and western and central parts of Afar regions had the highest load of zero-dose children (hotspot areas) followed by the Northeastern part of Amhara and southeastern part of Oromia regions. On the other hand, Southern Nations, Nationalities, and Peoples, Sidama, and the Eastern part of the Southwest Ethiopia peoples regions were identified as cold spot areas. The spatial interpolation analysis corresponded with the hotspot analysis results where western and central parts of Afar and western, eastern and northern parts of Somali regions were identified as high-risk areas for zero-dose children. However, Addis Ababa, Dire Dawa, Harari, Southern Nations, Nationalities, and Peoples, Sidama, Southwest Ethiopia Peoples, and parts of Oromia were found to be low-risk areas for zero-dose children.
CONCLUSION
The spatial analysis identified that zero-dose children had a significant spatial variation across the study areas. High clusters of zero-dose children were detected in Afar and Somali regions. Implementing routine and mop-up vaccination campaigns in the identified hotspot areas will help Ethiopia to improve coverage and reduce immunization inequalities.
PubMed: 38638589
DOI: 10.3389/fped.2024.1337922 -
Journal of the American Chemical Society May 2024Protein lipidation dynamically controls protein localization and function within cellular membranes. A unique form of protein -fatty acylation in , termed protein...
Protein lipidation dynamically controls protein localization and function within cellular membranes. A unique form of protein -fatty acylation in , termed protein -mycoloylation, involves the attachment of mycolic acids─unusually large and hydrophobic fatty acids─to serine residues of proteins in these organisms' outer mycomembrane. However, as with other forms of protein lipidation, the scope and functional consequences of protein -mycoloylation are challenging to investigate due to the inherent difficulties of enriching and analyzing lipidated peptides. To facilitate the analysis of protein lipidation and enable the comprehensive profiling and site mapping of protein -mycoloylation, we developed a chemical proteomics strategy integrating metabolic labeling, click chemistry, cleavable linkers, and a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employing LC separation and complementary fragmentation methods tailored to the analysis of lipophilic, MS-labile -acylated peptides. Using these tools in the model organism , we identified approximately 30 candidate -mycoloylated proteins, including porins, mycoloyltransferases, secreted hydrolases, and other proteins with cell envelope-related functions─consistent with a role for -mycoloylation in targeting proteins to the mycomembrane. Site mapping revealed that many of the proteins contained multiple spatially proximal modification sites, which occurred predominantly at serine residues surrounded by conformationally flexible peptide motifs. Overall, this study (i) discloses the putative protein -mycoloylome for the first time, (ii) yields new insights into the undercharacterized proteome of the mycomembrane, which is a hallmark of important pathogens (e.g., , ), and (iii) provides generally applicable chemical strategies for the proteomic analysis of protein lipidation.
Topics: Proteomics; Bacterial Proteins; Corynebacterium glutamicum; Mycolic Acids; Tandem Mass Spectrometry; Chromatography, Liquid; Acylation; Click Chemistry
PubMed: 38635392
DOI: 10.1021/jacs.4c02278 -
Investigative Ophthalmology & Visual... Apr 2024This study aims to elucidate the calcitonin gene-related peptide (CGRP) mediation and primary mechanism of corneal sensory nerves on tear production of the lacrimal...
PURPOSE
This study aims to elucidate the calcitonin gene-related peptide (CGRP) mediation and primary mechanism of corneal sensory nerves on tear production of the lacrimal gland.
METHODS
Mouse corneal denervation models were constructed through surgical axotomy, pharmacologic treatment with capsaicin or resiniferatoxin, and Trpv1-Cre/DTR mice with diphtheria toxin injection. The capsaicin-treated mice received subconjunctival injection of CGRP or substance P, while the normal C57BL/6J mice were administered with CGRP receptor antagonist BIBN-4096. Furthermore, double immunostaining of c-FOS+ and choline acetyltransferase was used to evaluate the activation of the superior salivatory nucleus (SSN). Mouse lacrimal glands were collected for transcriptomic sequencing and subsequent RNA and protein expression analysis.
RESULTS
The corneal denervated mice exhibited a significant reduction in corneal sensitivity and tear secretion. In capsaicin-treated mice, tear secretion decreased to 2.5 ± 0.5 mm compared to 6.3 ± 0.9 mm in control mice (P < 0.0001). However, exogenous administration of CGRP in capsaicin-treated mice increased tear secretion from 2.6 ± 0.5 mm to 4.5 ± 0.5 mm (P = 0.0009), while BIBN-4096 treatment reduced tear secretion to 3.4 ± 0.5 mm when compared to 7.3 ± 0.7 mm in control mice (P = 0.0022). Furthermore, c-FOS+ cell number in the SSN increased by twofold (P = 0.0168) after CGRP administration compared with capsaicin-treated mice. In addition, the expressions of CCNA2, Ki67, PCNA, and CDK1 in acinar cells of the lacrimal gland were impaired by corneal denervation and alleviated by CGRP administration.
CONCLUSIONS
CGRP released by corneal sensory nerves mediates tear secretion of the lacrimal gland, providing a new strategy for improving tear secretion in patients with neurotrophic keratitis.
Topics: Animals; Mice; Calcitonin Gene-Related Peptide; Capsaicin; Genes, fos; Lacrimal Apparatus; Mice, Inbred C57BL; Proto-Oncogene Proteins c-fos
PubMed: 38635244
DOI: 10.1167/iovs.65.4.30