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BMC Primary Care Jun 2024Preconceptual care aiming to improve health is influenced by various factors including health literacy. Considering the importance and necessity of high quality...
BACKGROUND AND AIM
Preconceptual care aiming to improve health is influenced by various factors including health literacy. Considering the importance and necessity of high quality preconceptual care, this study aimed to determine the relationship between health literacy and receiving components of preconceptual care prior to pregnancy.
METHODS
This cross-sectional study included 693 participants with pregnancies of less than 14 weeks gestation referred to health centers and gynecologists in Shiraz city, Iran. Multi-stage sampling was done from May 2021 to February 2022 in 18 comprehensive urban health centers and 20 gynecology offices via proportional allocation method. The data collection tool comprised a questionnaire consisting of 3 parts: (1) individual and fertility characteristics, (2) information related to the components of preconceptual care and (3) health literacy for Iranian adults. This was completed by individual participants via the self-reporting method.
RESULTS
The majority of participants were between 30 and 34 years old. They also identified as women with a university education and were predominantly unemployed. The mean health literacy of participants was 76.81%. Health literacy obtained the highest mean score in the dimension of 'understanding' and the lowest mean score in the dimension of 'access'. The frequency of preconceptual counseling, folic acid supplement consumption, exercise, blood testing, dental visits, genetic counseling, Pap smear testing and rubella, diphtheria, and hepatitis vaccinations prior to pregnancy was 66.8%, 53.8%, 45.6%, 71.86%, 44.44%, 12%, 53.4%, 10.83%, respectively. Many (> 64%) received preconceptual care at specialist gynecology offices. Results demonstrated that health literacy had a statistically significant relationship with preconceptual care, folic acid consumption, exercise and dental care, (p < 0.001), along with blood testing and Pap smear testing (p < 0.05).
CONCLUSION
Overall, our results demonstrate that despite health literacy being optimal, uptakes of some components of preconceptual care are low. As such, it will be important to further raise awareness of the importance of preconceptual care for people prior to pregnancy as a priority in health promotion and education.
Topics: Humans; Female; Cross-Sectional Studies; Health Literacy; Pregnancy; Adult; Preconception Care; Iran; Young Adult; Surveys and Questionnaires; Health Knowledge, Attitudes, Practice
PubMed: 38862877
DOI: 10.1186/s12875-024-02467-5 -
Revista Panamericana de Salud Publica =... 2024To assess changes in reproductive, maternal, newborn, child, and adolescent health (RMNCAH) in Haiti from August 2018 to September 2021, before and during the COVID-19...
OBJECTIVE
To assess changes in reproductive, maternal, newborn, child, and adolescent health (RMNCAH) in Haiti from August 2018 to September 2021, before and during the COVID-19 pandemic.
METHODS
A retrospective study using surveillance data from the Haitian Unique Health Information System, examining two periods: pre- and peri-COVID-19 pandemic. Health indicators at the national level in the two periods were compared using two-sample -tests for proportions, and average absolute monthly changes were calculated using variance-weighted regression.
RESULTS
There was a statistically significant decline in the proportion of most of the indicators assessed from the pre- to the peri-COVID-19 pandemic period. However, the most affected indicators were the proportions of pregnant women with four antenatal care visits, with five antenatal care visits or more, and those who received a second dose of tetanus vaccine, which decreased by over 4 percentage points during the two periods. Likewise, the proportions of children who received diphtheria, tetanus, and pertussis (DTaP), BCG, polio, pentavalent, and rotavirus vaccines also all declined by over 8 percentage points. In contrast, pneumococcal conjugate vaccine increased by over 4 percentage points. A statistically significant decrease was also observed in the average absolute monthly changes of several reproductive and child health indicators assessed.
CONCLUSIONS
The COVID-19 pandemic may have contributed to the decline observed in several RMNCAH indicators in Haiti. However, the role played by the sociopolitical crisis and control exercised by armed groups over the population in the last three years cannot be ruled out.
PubMed: 38859812
DOI: 10.26633/RPSP.2024.57 -
NPJ Vaccines Jun 2024Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes...
Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines.
PubMed: 38858423
DOI: 10.1038/s41541-024-00890-4 -
PLoS Medicine Jun 2024In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.
BACKGROUND
In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule.
METHODS AND FINDINGS
OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again).
CONCLUSIONS
Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups.
TRIAL REGISTRATION
Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).
Topics: Humans; Infant; Double-Blind Method; Immunoglobulin E; Female; Male; Diphtheria-Tetanus-Pertussis Vaccine; Immunization Schedule; Australia; Vaccines, Combined; Pertussis Vaccine; Food Hypersensitivity; Poliovirus Vaccine, Inactivated; Haemophilus Vaccines; Whooping Cough; Immunogenicity, Vaccine; Antibodies, Bacterial
PubMed: 38857311
DOI: 10.1371/journal.pmed.1004414 -
China CDC Weekly May 2024In China, there is limited data available on the use and coverage of the non-program, combined diphtheria, tetanus toxoid, acellular pertussis adsorbed, inactivated...
WHAT IS ALREADY KNOWN ON THIS TOPIC?
In China, there is limited data available on the use and coverage of the non-program, combined diphtheria, tetanus toxoid, acellular pertussis adsorbed, inactivated poliovirus and haemophilus influenzae type b (DTaP-IPV/Hib) pentavalent vaccine, and its role as a substitute for the separately administered standalone program vaccines.
WHAT IS ADDED BY THIS REPORT?
We evaluated the use and coverage of the pentavalent vaccine in nine provincial-level administrative divisions (PLADs) spanning eastern, central, and western China from 2019 to 2021. Initial use and coverage were low, but demonstrated annual growth albeit with regional and urban-rural discrepancies. The pentavalent vaccine was increasingly substituted for standalone vaccines over the course of this period.
WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?
Parents in China are increasingly opting to replace the standard program vaccines with voluntarily purchased combination vaccines, particularly the pentavalent vaccine. The development of combination vaccines should thus be promoted in China, as it could enhance utilization and coverage rates, and decrease the economic burden.
PubMed: 38854752
DOI: 10.46234/ccdcw2024.083 -
EBioMedicine Jun 2024Maternal pertussis vaccination with Tdap vaccine is recommended to protect newborns from severe postnatal infection. HIV-exposed uninfected (HEU) infants have a higher... (Observational Study)
Observational Study
BACKGROUND
Maternal pertussis vaccination with Tdap vaccine is recommended to protect newborns from severe postnatal infection. HIV-exposed uninfected (HEU) infants have a higher incidence of pertussis infection and may particularly benefit from maternal immunization. The impact of HIV infection on the quality of IgG and memory B cell (MBC) responses to Tdap vaccination in pregnant women (PW) living with HIV (PWH) is unknown.
METHODS
In this observational study, humoral immune responses to Tdap vaccination, including IgG levels, Fc-dependent effector functions, and MBC frequencies, were measured before and after vaccination in 40 PWH and 42 HIV-uninfected PW. Placental transfer of IgG and avidity were assessed in cord blood (CB). Soluble and cellular immune activation markers were quantified at baseline.
FINDINGS
One month after vaccination, PWH had lower frequencies of MBC compared with HIV-uninfected PW. At delivery, PWH had attenuated pertussis-specific IgG levels and Fc-dependent effector functions. Reduced levels of maternal vaccine polyfunctional IgG and IgG avidity were transferred to HEU as compared to HIV-unexposed newborns. After adjustment with ethnicity, maternal antibody levels and gestational age at vaccination, HIV infection was independently associated with decreased levels of PT specific-IgG in CB. Both maternal and neonatal pertussis-specific IgG responses as well as PT-specific IgG avidity were inversely correlated with maternal sCD14 levels before vaccination among PWH.
INTERPRETATION
Maternal HIV infection is associated with attenuated humoral immune responses to Tdap vaccination that correlate with sCD14. Suboptimal transfer of maternal immunity may further increase the risk of severe pertussis infection in HEU infants.
FUNDING
This work was supported by IRIS Fund managed by the Foundation Roi Baudouin [2017J1820690206902], Association Vésale pour la Recherche Médicale and the Medical Council of CHU Saint-Pierre and has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services, under Award No. U19AI145825. N.D. is a clinical researcher and A.M. is Research Director at the Fonds de la Recherche Scientifique (F.R.S.-FNRS), Belgium. M.E.A. was partially supported by NIHNIAID1U19AI14825. This article is published with the support of the Fondation Universitaire of Belgium.
Topics: Humans; Female; Pregnancy; HIV Infections; Immunoglobulin G; Adult; Memory B Cells; Diphtheria-Tetanus-acellular Pertussis Vaccines; Antibodies, Bacterial; Infant, Newborn; Vaccination; Whooping Cough; Antibody Affinity
PubMed: 38848615
DOI: 10.1016/j.ebiom.2024.105179 -
Journal of Dermatological Science May 2024Atopic dermatitis (AD), a chronic inflammatory skin disease with T cell activation as a key feature, in which Th2 cell-mediated responses play a pivotal role. Regulatory...
BACKGROUND
Atopic dermatitis (AD), a chronic inflammatory skin disease with T cell activation as a key feature, in which Th2 cell-mediated responses play a pivotal role. Regulatory T cells (Treg) are central immune cells that restrict autoimmunity and inflammation in the body. Patients with immune dysregulation, polyendocrinopathy, or enteropathy X-linked syndrome, an immune disease characterized by a deficiency in Treg, develop skin inflammation and allergic disorders, indicating that Treg play a crucial role in the development of allergic skin inflammation.
OBJECTIVE
we investigated the underlying mechanisms by which Treg control cutaneous allergic inflammation.
METHODS
An allergic skin inflammation mouse model was constructed using MC903, and Treg-depleted mouse model was constructed using diphtheria toxin. Neutralization of IFN-γ was constructed using anti-mouse-IFN-γ mouse antibody. Neutrophil infiltration was analyzed by flow cytometry and immunohistochemistry. Neutrophil extracellular traps (NETs), a process called NETosis, were detected using immunofluorescence. In vitro neutrophil stimulation and immunocytochemistry was conducted to demonstrate the effect of IFN-γ on NETosis.
RESULTS
The depletion of Foxp3 Treg led to significantly exacerbated AD-like skin inflammation, including increased recruitment of neutrophils and expression of Th1 cytokine IFN-γ. Neutrophil infiltrating in skin of Treg-depleted mice released more NETs than wild type. Neutralization of IFN-γ abolished neutrophil infiltration and NETosis in Treg-depleted mice. Neutrophils stimulated with IFN-γ were more prone to release NETs in vitro. Finally, Foxp3 Treg control cutaneous allergic inflammation by regulating IFN-γ-driven neutrophilic infiltration and NETosis.
CONCLUSION
Our results highlight the previously underestimated Treg-IFN-γ-neutrophil inflammatory axis.
PubMed: 38845244
DOI: 10.1016/j.jdermsci.2024.05.002 -
Arthritis Research & Therapy Jun 2024The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF‑06835375, a potent selective afucosyl immunoglobulin... (Randomized Controlled Trial)
Randomized Controlled Trial
A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis.
BACKGROUND
The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF‑06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
METHODS
This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18-70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.03-6 mg) or placebo in six sequential single ascending dose (SAD) cohorts. In Part B, patients received repeat doses of subcutaneous PF-06835375 (dose range: 0.3-10 mg) or placebo on Days 1 and 29 in five multiple ascending dose (MAD) cohorts. Tetanus/Diphtheria (Td) and Meningococcal B (MenB/Trumenba™) vaccines were administered at Day 4 (Td and MenB) and Week 8 (MenB only) to assess PF-06835375 functional effects. Endpoints included treatment-emergent adverse events (TEAEs), pharmacokinetic parameters, pharmacodynamic effects on B and cTfh cells, and biomarker counts, vaccine response, and exploratory differential gene expression analysis. Safety, pharmacokinetic, and pharmacodynamic endpoints are summarized descriptively. The change from baseline of B and Tfh cell-specific genes over time was calculated using a prespecified mixed-effects model, with a false discovery rate < 0.05 considered statistically significant.
RESULTS
In total, 73 patients were treated (SAD cohorts: SLE, n = 17; RA, n = 14; MAD cohorts: SLE, n = 22; RA, n = 20). Mean age was 53.3 years. Sixty-two (84.9%) patients experienced TEAEs (placebo n = 17; PF-06835375 n = 45); most were mild or moderate. Three (9.7%) patients experienced serious adverse events. Mean t ranged from 3.4-121.4 h (SAD cohorts) and 162.0-234.0 h (MAD cohorts, Day 29). B and cTfh cell counts generally showed dose-dependent reductions across cohorts (range of mean maximum depletion: 67.3-99.3%/62.4-98.7% [SAD] and 91.1-99.6%/89.5-98.1% [MAD], respectively). B cell-related genes and pathways were significantly downregulated in patients treated with PF-06835375.
CONCLUSIONS
These data support further development of PF-06835375 to assess the clinical potential for B and Tfh cell depletion as a treatment for autoimmune diseases.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03334851.
Topics: Humans; Middle Aged; Adult; Double-Blind Method; Female; Male; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Aged; Receptors, CXCR5; Young Adult; Dose-Response Relationship, Drug; Adolescent; Antibodies, Monoclonal, Humanized; Antirheumatic Agents
PubMed: 38845046
DOI: 10.1186/s13075-024-03337-2 -
Nature Communications Jun 2024Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity...
Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9CD55 APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9CD55 APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male.
Topics: Humans; Animals; Single-Cell Analysis; Diabetes Mellitus, Type 2; Homeostasis; Male; Mice; Stem Cells; Glucose; Obesity; Adipocytes; Intra-Abdominal Fat; Adipose Tissue; Mice, Inbred C57BL; Lipolysis; Female; Middle Aged
PubMed: 38844451
DOI: 10.1038/s41467-024-48914-w