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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 -
Human Vaccines & Immunotherapeutics Dec 2024DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and...
DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age ( < .001), parents' education level ( = .024), and perceived price barriers ( < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.
Topics: Child; Humans; Vaccines, Combined; Cross-Sectional Studies; Haemophilus influenzae type b; China; Diphtheria-Tetanus-Pertussis Vaccine; Hepatitis B Vaccines; Haemophilus Vaccines
PubMed: 38619056
DOI: 10.1080/21645515.2024.2333098 -
Cureus Mar 2024Even though immunization can prevent illness, diphtheria, which is caused by toxic strains of Corynebacterium diphtheriae, remains a serious public health risk. Although...
Even though immunization can prevent illness, diphtheria, which is caused by toxic strains of Corynebacterium diphtheriae, remains a serious public health risk. Although the worldwide incidence has declined, it still poses a serious hazard in developing countries, such as Pakistan, where new data suggest an increase in cases. A significant proportion of patients with respiratory diphtheria experience cardiac complications, specifically myocarditis, which carries a high death risk of 50% to 75%. The diphtheria toxin's affinity for cardiac tissues is the cause of these consequences, which include arrhythmias and myocardial dysfunction. Recent studies from Lady Reading Hospital in Peshawar show the seriousness of the situation, with 73 patients presenting with cardiac complications in just one year, resulting in a devastating fatality rate despite early management. This highlights the pressing need for increased awareness and all-encompassing immunization campaigns, particularly for children who have received insufficient vaccinations. Timely vaccination and booster doses are critical for reducing myocarditis-related mortality, mandating prioritizing immunization efforts to defend susceptible populations globally.
PubMed: 38618353
DOI: 10.7759/cureus.56093 -
International Journal of Infectious... Jul 2024This study investigates placental antibody transfer following recombinant pertussis vaccination in pregnancy in a real-world setting. (Observational Study)
Observational Study
AIM/OBJECTIVE
This study investigates placental antibody transfer following recombinant pertussis vaccination in pregnancy in a real-world setting.
METHODS
This postmarketing observational study recruited pregnant women vaccinated with monovalent recombinant acellular pertussis (aP) vaccine (aP; n = 199) or combined to tetanus-diphtheria (TdaP; n = 200), or Td-vaccine only (n = 54). Pregnancy, delivery, and neonatal outcomes were assessed. Cord blood was collected postdelivery and pertussis toxin (PT)-IgG, filamentous hemagglutinin (FHA)-IgG, and PT-neutralizing antibodies (PT-Nab) were assessed.
RESULTS
No adverse pregnancy, delivery, or neonatal outcomes attributed to aP TdaP, or Td vaccination were reported. High anti-PT antibody levels were detected in cord samples from women vaccinated with aP (geometric mean concentration [GMC] PT-IgG 206.1 IU/ml, 95% confidence intervals [CI]: 164.3-258.6; geometric mean titer [GMT] PT-Nab 105.3 IU/ml, 95% CI: 81.7-135.8) or TdaP (GMC PT-IgG 153.1 IU/ml, 95% CI: 129.1-181.5; GMT PT-Nab 81.5 IU/ml, 95% CI: 66.4-100.0). In the Td-only group, anti-PT antibodies were low (GMC PT-IgG 6.5 IU/ml, 95% CI: 4.9-8.8; GMT PT-Nab 3.8 IU/ml, 95% CI: 2.8-5.1). The same was found for FHA-IgG. Recombinant pertussis vaccination at <27 or 27-36 weeks gestation induced similar cord pertussis antibody levels.
CONCLUSION
This first real-world study confirms that recombinant pertussis vaccination in the second or third trimester of pregnancy results in high levels of passive immunity in infants. Thai Clinical Trial Registry: TCTR20200528006.
Topics: Humans; Female; Pregnancy; Adult; Antibodies, Bacterial; Immunity, Maternally-Acquired; Whooping Cough; Immunoglobulin G; Fetal Blood; Vaccines, Synthetic; Pertussis Vaccine; Young Adult; Maternal-Fetal Exchange; Diphtheria-Tetanus-acellular Pertussis Vaccines; Infant, Newborn; Pertussis Toxin; Antibodies, Neutralizing; Bordetella pertussis; Vaccination
PubMed: 38609035
DOI: 10.1016/j.ijid.2024.107047 -
Experimental Neurology Jun 2024Animals on Earth need to hold postures and execute a series of movements under gravity and atmospheric pressure. VAChT-Cre is a transgenic Cre driver mouse line that...
Type selective ablation of postnatal slow and fast fatigue-resistant motor neurons in mice induces late onset kinetic and postural tremor following fiber-type transition and myopathy.
Animals on Earth need to hold postures and execute a series of movements under gravity and atmospheric pressure. VAChT-Cre is a transgenic Cre driver mouse line that expresses Cre recombinase selectively in motor neurons of S-type (slow-twitch fatigue-resistant) and FR-type (fast-twitch fatigue-resistant). Sequential motor unit recruitment is a fundamental principle for fine and smooth locomotion; smaller-diameter motor neurons (S-type, FR-type) first contract low-intensity oxidative type I and type IIa muscle fibers, and thereafter larger-diameter motor neurons (FInt-type, FF-type) are recruited to contract high-intensity glycolytic type IIx and type IIb muscle fibers. To selectively eliminate S- and FR-type motor neurons, VAChT-Cre mice were crossbred with NSE-DTA mice in which the cytotoxic diphtheria toxin A fragment (DTA) was expressed in Cre-expressing neurons. The VAChT-Cre;NSE-DTA mice were born normally but progressively manifested various characteristics, including body weight loss, kyphosis, kinetic and postural tremor, and muscular atrophy. The progressive kinetic and postural tremor was remarkable from around 20 weeks of age and aggravated. Muscular atrophy was apparent in slow muscles, but not in fast muscles. The increase in motor unit number estimation was detected by electromyography, reflecting compensatory re-innervation by remaining FInt- and FF-type motor neurons to the orphaned slow muscle fibers. The muscle fibers gradually manifested fast/slow hybrid phenotypes, and the remaining FInt-and FF-type motor neurons gradually disappeared. These results suggest selective ablation of S- and FR-type motor neurons induces progressive muscle fiber-type transition, exhaustion of remaining FInt- and FF-type motor neurons, and late-onset kinetic and postural tremor in mice.
Topics: Animals; Motor Neurons; Mice; Mice, Transgenic; Tremor; Muscle Fibers, Slow-Twitch; Muscle Fibers, Fast-Twitch; Muscular Diseases; Muscle Fatigue; Posture; Animals, Newborn; Disease Models, Animal
PubMed: 38599366
DOI: 10.1016/j.expneurol.2024.114772 -
Frontiers in Public Health 2024The DTaP-Hib and DTaP-IPV/Hib combination vaccine can be used as a substitute for the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). We aimed to...
BACKGROUND
The DTaP-Hib and DTaP-IPV/Hib combination vaccine can be used as a substitute for the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). We aimed to evaluate the safety of multi-component vaccines containing DTaP by analyzing the reporting rates and characteristics of adverse events following immunization (AEFIs) in Linping District during the years 2019 to 2022.
METHODS
We obtained data of AEFI and vaccination from the National AEFI Surveillance System of China and Zhejiang Municipal Immunization Information Management System, respectively, during 2019-2022 for a descriptive, epidemiological analysis.
RESULTS
The total number of AEFI reported following vaccinations with DTaP-containing combination vaccines was 802 in Linping District from 2019 to 2022. The overall reporting rates of AEFIs following DTaP, DTaP-Hib, and DTaP-IPV/Hib vaccinations were 445.72 (537 cases), 536.29 (45 cases), and 306.13 (220 cases) per 100,000 doses in Linping District from 2019 to 2022, respectively. Only one case of a serious AEFI following DTaP vaccination, with a reporting rate of 0.83 per 100,000 doses. The composition ratio of vaccine product-related reactions for DTaP, DTaP-Hib, and DTaP-IPV/Hib were 99.81, 97.78, and 100.00%, respectively. The composition ratio of coincidental events for DTaP and DTaP-Hib were 0.19 and 2.22%, respectively. The reporting rates of total AEFIs for DTaP-IPV/Hib were lower than for DTaP. The reporting rate of local induration for DTaP-Hib was lower than for DTaP, and the reporting rates of local redness & swelling and local induration for DTaP-IPV/Hib were both lower than for DTaP. DTaP-IPV/Hib had a higher proportion of AEFIs in first quarter compared to DTaP. The reporting rate after the second dose of DTaP-Hib was higher than that of DTaP, and the reporting rates of AEFIs after the first dose and third dose of DTaP-IPV/Hib were lower than DTaP.
CONCLUSION
The reported AEFIs to multi-component vaccines containing DTaP components during 2019-2022 in Linping District were mainly mild vaccine reactions. DTaP-containing combination vaccines demonstrated a good safety profile.
Topics: China; Diphtheria-Tetanus-acellular Pertussis Vaccines; Immunization; Vaccination; Vaccines, Combined; Humans
PubMed: 38596516
DOI: 10.3389/fpubh.2024.1278513 -
Vaccine Nov 2023Many western countries are challenged by delayed and insufficient vaccination coverage rates in children, and thus missing WHO coverage targets. This study aimed to... (Observational Study)
Observational Study
AIMS
Many western countries are challenged by delayed and insufficient vaccination coverage rates in children, and thus missing WHO coverage targets. This study aimed to estimate vaccination coverage and timeliness in Swiss children over a decade. Furthermore, we evaluated the impact of COVID-19, regional variations, and the adherence to the amended vaccination schedule in 2019.
METHODS
Retrospective observational study with Swiss health insurance claims data including birth cohorts 2012-2021 of children continuously observed until ages 13, 25, and 48 months respectively. We used population-weighted proportions and time-to-event analyses to describe coverage and timeliness of diphtheria/tetanus/pertussis/poliomyelitis/haemophilus influenzae type b (DTaP-IPV-Hib), measles/mumps/rubella (MMR), hepatitis B (HBV), pneumococcal (PCV), and meningococcal (MCV) vaccinations according to the national schedule. The potential impact of COVID-19 and vaccination schedule adherence were evaluated descriptively. Logistic regression was used to investigate regional factors potentially associated with non-vaccination.
RESULTS
120,073 children, representing between 12 and 17 % of all Swiss children born in corresponding years, were included. Coverage remained stable or improved over the years. The 2019 amendment of the national immunization schedule was associated with an increase of ~10 % points in full coverage in Swiss children for DTaP-IPV-Hib, MMR and HBV despite the concurrent COVID-19 pandemic. Nonetheless, full vaccination coverage remained below 90 % with many vaccination series being delayed or not completed. The comparison across the different vaccines revealed large differences in coverage. Moreover, we observed large regional differences in non-vaccination with children living in rural and German-speaking areas more likely to be entirely unvaccinated.
CONCLUSION
Full vaccination coverage in Swiss children is still below 90 % with many vaccinations administered delayed. Given regional differences, missed or delayed booster vaccinations, and differences in vaccine-specific acceptability, more effort may be needed to achieve national vaccination targets.
Topics: Child; Humans; Infant; Vaccination Coverage; Birth Cohort; Pandemics; Switzerland; Diphtheria-Tetanus-Pertussis Vaccine; Vaccination; Rubella Vaccine; Immunization Schedule; Haemophilus Vaccines; COVID-19
PubMed: 38593195
DOI: 10.1016/j.vaccine.2023.10.043