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Current Medical Research and Opinion Jun 2024In 2019, the United States Advisory Committee on Immunization Practices (ACIP) updated their meningococcal serogroup B (MenB) vaccination recommendation for...
OBJECTIVE
In 2019, the United States Advisory Committee on Immunization Practices (ACIP) updated their meningococcal serogroup B (MenB) vaccination recommendation for 16-23-year-olds from individual to shared clinical decision-making (SCDM). SCDM recommendations are individually based and informed by a decision process between patients and healthcare providers (HCPs). MenB vaccination among 16-23-year-olds remains low. We examined recorded conversations in which MenB vaccine-related discussions between HCPs and patients/caregivers took place, and how these interactions changed following the updated SCDM recommendation.
METHODS
An analysis of recordings where MenB vaccination was discussed between HCPs and patients (16-23 years old)/caregivers was conducted using retrospective anonymized dialogue data (January 2015-October 2022). Shared decision-making strength was measured using a modified OPTION5 framework.
RESULTS
Of 97 included recorded conversations, the average duration was 11.3 min. Within these conversations, MenB disease was discussed for 0.25 min (38.9% of words in total vaccine-preventable diseases discussion) and MenB vaccination was discussed for 1.36 min (60.9% of words in total vaccine discussion), on average. HCPs spoke 78.8% of MenB vaccine-related words and most (99.0%) initiated the MenB vaccination discussion. In 40.2% of recordings, HCPs acknowledged the MenB vaccine without providing a clear recommendation. HCP recommendations often favored MenB vaccination (87.0%) and recommendations were 21.4% stronger post-recommendation change to SCDM. As measured by the modified OPTION5 framework, most recordings did not reflect a high degree of shared decision-making between HCPs and patients/caregivers.
CONCLUSIONS
MenB vaccination discussions were brief, and the degree of shared decision-making was low. Targeted education of HCPs and patients/caregivers may improve MenB vaccination awareness, SCDM implementation, and vaccine uptake.
PubMed: 38860982
DOI: 10.1080/03007995.2024.2362924 -
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 -
MMWR. Morbidity and Mortality Weekly... Jun 2024Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and...
Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).
Topics: Humans; Meningococcal Infections; United States; France; Saudi Arabia; Young Adult; Adult; Adolescent; Male; Female; Neisseria meningitidis; Child; Child, Preschool; United Kingdom; Middle Aged; Infant; Aged; Travel-Related Illness; Disease Outbreaks; Travel
PubMed: 38843099
DOI: 10.15585/mmwr.mm7322e1 -
Revista Paulista de Pediatria : Orgao... 2024To analyze the vaccination coverage and abandonment rates among children under two years old in Brazil, from 2015 to 2021.
OBJECTIVE
To analyze the vaccination coverage and abandonment rates among children under two years old in Brazil, from 2015 to 2021.
METHODS
A time-series ecological study. The dependent variables of the research were "vaccination coverage" and "abandonment rate", both assessed by Brazilian region. The data were extracted in July 2022 from the Information System of the National Immunization Program. The Prais-Winsten technique was used for the trend analysis, with the aid of the STATA 16.0 software.
RESULTS
The mean vaccination coverage in Brazil was 76.96%, with a decreasing trend during the period (Annual Percent Change=-5.12; confidence interval - CI95% -7.81; -2.34); in 2015, the rate was 88.85% and it dropped to 62.35% in 2021. In turn, the overall abandonment rate was 24.00% in 2015 and 9.01% in 2021, with a mean of 10.48% and a stationary trend (Annual Percentage Change=-9.54; CI95% -22.92; 6.12). In 2021, all the vaccines presented coverage values below 74.00% in the country.
CONCLUSIONS
The vaccination coverage rate trend among children under two years old was stationary or decreasing for all the immunobiologicals in all Brazilian regions, with the exception of yellow fever in the South and Southeast regions. There was an increase in the abandonment rate trend for the Meningococcal C vaccine in the country and, specifically in relation to the regions, for BCG in the North, Northeast, and Midwest and for Meningococcal C in the North and Northeast.
Topics: Humans; Brazil; Vaccination Coverage; Infant; Immunization Programs; Vaccination; Time Factors
PubMed: 38836806
DOI: 10.1590/1984-0462/2024/42/2023116 -
Lancet (London, England) Jun 2024
Topics: Humans; Nigeria; Meningococcal Vaccines; Meningitis, Meningococcal
PubMed: 38823982
DOI: 10.1016/S0140-6736(24)00880-8 -
Frontiers in Cellular and Infection... 2024The genus , which colonizes mucosal surfaces, includes both commensal and pathogenic species that are exclusive to humans. The two pathogenic species are closely... (Review)
Review
The genus , which colonizes mucosal surfaces, includes both commensal and pathogenic species that are exclusive to humans. The two pathogenic species are closely related but cause quite different diseases, meningococcal sepsis and meningitis () and sexually transmitted gonorrhea ). Although obvious differences in bacterial niches and mechanisms for transmission exists, pathogenic have high levels of conservation at the levels of nucleotide sequences, gene content and synteny. Species of express broad-spectrum -linked protein glycosylation where the glycoproteins are largely transmembrane proteins or lipoproteins localized on the cell surface or in the periplasm. There are diverse functions among the identified glycoproteins, for example type IV biogenesis proteins, proteins involved in antimicrobial resistance, as well as surface proteins that have been suggested as vaccine candidates. The most abundant glycoprotein, PilE, is the major subunit of pili which are an important colonization factor. The glycans attached can vary extensively due to phase variation of protein glycosylation ( genes and polymorphic gene content. The exact roles of glycosylation in remains to be determined, but increasing evidence suggests that glycan variability can be a strategy to evade the human immune system. In addition, pathogenic and commensal appear to have significant glycosylation differences. Here, the current knowledge and implications of protein glycosylation genes, glycan diversity, glycoproteins and immunogenicity in pathogenic are summarized and discussed.
Topics: Humans; Bacterial Proteins; Glycoproteins; Glycosylation; Neisseria gonorrhoeae; Neisseria meningitidis; Polysaccharides; Meningitis, Meningococcal; Gonorrhea
PubMed: 38808060
DOI: 10.3389/fcimb.2024.1407863 -
Vaccine May 2024Pneumococcal meningitis outbreaks occur sporadically in the African meningitis belt. Outbreak control guidelines and interventions are well established for meningococcal...
INTRODUCTION
Pneumococcal meningitis outbreaks occur sporadically in the African meningitis belt. Outbreak control guidelines and interventions are well established for meningococcal but not pneumococcal meningitis. Mathematical modelling is a useful tool for assessing the potential impact of different pneumococcal control strategies. This work aimed to estimate the impact of reactive vaccination with pneumococcal conjugate vaccine (PCV) had it been implemented in past African meningitis belt outbreaks and assess their efficiency relative to existing routine infant immunisation with PCV.
METHODS & RESULTS
Using recent pneumococcal meningitis outbreaks in Burkina Faso, Chad, and Ghana as case studies, we investigated the potential impact of reactive vaccination. We calculated the number needed to vaccinate to avert one case (NNV) in each outbreak setting and over all outbreaks and compared this to the NNV for existing routine infant vaccination. We extended previous analyses of reactive vaccination by considering longer-term protection in vaccinees over five years, incorporating a proxy for indirect effects. We found that implementing reactive vaccination in previous pneumococcal meningitis outbreaks could have averted up to 10-20 % of outbreak cases, with the biggest potential impact in Brong Ahafo, Ghana (2015-2016) and Goundi, Chad (2009). The NNV, and hence the value of reactive vaccination, varied greatly. 'Large' (80 + cumulative modelled cases per 100,000 population) and/or 'prolonged' (exceeding a response threshold of 10 suspected cases per 100,000 per week for four weeks or more) outbreaks had NNV estimates under 10,000. For routine infant vaccination with PCV, the estimated NNV ranged from 3,100-5,600 in Burkina Faso and 1,500-2,600 in Ghana.
IMPLICATIONS
This analysis provides evidence to inform the design of pneumococcal meningitis outbreak response guidelines. Countries should consider reactive vaccination in each outbreak event, together with maintaining routine infant vaccination as the primary intervention to reduce pneumococcal disease burden and outbreak risk.
PubMed: 38797628
DOI: 10.1016/j.vaccine.2024.05.031 -
The Lancet. Infectious Diseases May 2024Increased rates of sexually transmitted infections (STIs) are reported among men who have sex with men (MSM) and new interventions are needed. We aimed to assess whether...
Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 × 2 factorial design.
BACKGROUND
Increased rates of sexually transmitted infections (STIs) are reported among men who have sex with men (MSM) and new interventions are needed. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of chlamydia or syphilis (or both) and whether the meningococcal group B vaccine (4CMenB) could reduce the incidence of gonorrhoea in this population.
METHODS
ANRS 174 DOXYVAC is a multicentre, open-label, randomised trial with a 2 × 2 factorial design conducted at ten hospital sites in Paris, France. Eligible participants were MSM aged 18 years or older, HIV negative, had a history of bacterial STIs within the 12 months before enrolment, and who were already included in the ANRS PREVENIR study (a cohort of MSM using pre-exposure prophylaxis with tenofovir and emtricitabine for HIV prevention). Participants were randomly assigned (2:1) to doxycycline PEP (two pills of 100 mg each orally within 72 h after condomless sex, with no more than three doses of 200 mg per week) or no PEP groups and were also randomly assigned (1:1) to the 4CMenB vaccine (GlaxoSmithKline, Paris, France; two intramuscular injections at enrolment and at 2 months) or no vaccine groups, using a computer-generated randomisation list with a permuted fixed block size of four. Follow-up occurred for at least 12 months (with visits every 3 months) up to 24 months. The coprimary outcomes were the risk of a first episode of chlamydia or syphilis (or both) after the enrolment visit at baseline for the doxycycline intervention and the risk of a first episode of gonorrhoea starting at month 3 (ie, 1 month after the second vaccine dose) for the vaccine intervention, analysed in the modified intention-to-treat population (defined as all randomly assigned participants who had at least one follow-up visit). This trial is registered with ClinicalTrials.gov, NCT04597424 (ongoing).
FINDINGS
Between Jan 19, 2021, and Sept 19, 2022, 556 participants were randomly assigned. 545 (98%) participants were included in the modified intention-to-treat analysis for the doxycycline PEP and no PEP groups and 544 (98%) were included for the 4CMenB vaccine and no vaccine groups. The median follow-up was 14 months (IQR 9-18). The median age was 40 years (34-48) and all 545 participants were male. There was no interaction between the two interventions (p≥0·1) for the primary outcome. The incidence of a first episode of chlamydia or syphilis (or both) was 8·8 per 100 person-years (35 events in 362 participants) in the doxycycline PEP group and 53·2 per 100 person-years (80 events in 183 participants) in the no PEP group (adjusted hazard ratio [aHR] 0·17 [95% CI 0·12-0·26]; p<0·0001). The incidence of a first episode of gonorrhoea, starting from month 3 was 58·3 per 100 person-years (103 events in 274 participants) in the 4CmenB vaccine group and 77·1 per 100 person-years (122 events in 270 participants) in the no vaccine group (aHR 0·78 [95% CI 0·60-1·01]; p=0·061). There were no deaths during the study. One drug-related serious adverse event (fixed-drug eruption) occurred in the doxycycline PEP group. Six (2%) participants in the doxycycline group discontinued doxycycline PEP because of gastrointestinal adverse events.
INTERPRETATION
Doxycycline PEP strongly reduced the incidence of chlamydia and syphilis in MSM, but we did not show efficacy of the 4CmenB vaccine for gonorrhoea. Doxycycline PEP should be assessed in other populations, such as heterosexual men and women, and its effect on antimicrobial resistance carefully monitored.
FUNDING
ANRS Maladies Infectieuses Emergentes.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
PubMed: 38797183
DOI: 10.1016/S1473-3099(24)00236-6 -
Vaccines Apr 2024The Banalia health zone in the Democratic Republic of Congo reported a meningitis epidemic in 2021 that evolved outside the epidemic season. We assessed the effects of...
BACKGROUND
The Banalia health zone in the Democratic Republic of Congo reported a meningitis epidemic in 2021 that evolved outside the epidemic season. We assessed the effects of the meningitis epidemic response.
METHODS
The standard case definition was used to identify cases. Care was provided to 2651 in-patients, with 8% of them laboratory tested, and reactive vaccination was conducted. To assess the effects of reactive vaccination and treatment with ceftriaxone, a statistical analysis was performed.
RESULTS
Overall, 2662 suspected cases of meningitis with 205 deaths were reported. The highest number of cases occurred in the 30-39 years age group (927; 38.5%). Ceftriaxone contributed to preventing deaths with a case fatality rate that decreased from 70.4% before to 7.7% after ceftriaxone was introduced ( = 0.001). W was isolated, accounting for 47/57 (82%), of which 92% of the strains belonged to the clonal complex 11. Reactive vaccination of individuals in Banalia aged 1-19 years with a meningococcal multivalent conjugate (ACWY) vaccine (Menactra) coverage of 104.6% resulted in an 82% decline in suspected meningitis cases (incidence rate ratio, 0.18; 95% confidence interval, 0.02-0.80; = 0.041).
CONCLUSION
Despite late detection (two months) and reactive vaccination four months after crossing the epidemic threshold, interventions implemented in Banalia contributed to the control of the epidemic.
PubMed: 38793712
DOI: 10.3390/vaccines12050461 -
Journal of Medical Virology Jun 2024The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to...
The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine-associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine-associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine-associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine-associated facial paralysis from 49 537 reports of all-cause facial paralysis. Vaccine-associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID-19) pandemic, which is attributable to the COVID-19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID-19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60-29.03]; IC, 3.37 [IC, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella-zoster, meningococcal, Ad-5 vectored COVID-19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole-virus COVID-19 vaccines. Concerning age- and sex-specific risks, vaccine-associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine-associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine-induced facial paralysis, primarily owing to COVID-19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine-associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.
Topics: Humans; Facial Paralysis; Pharmacovigilance; Male; World Health Organization; Female; Adult; Middle Aged; Adolescent; Young Adult; Databases, Factual; Child; Child, Preschool; Aged; Incidence; Vaccines; Global Health; COVID-19; Infant; Vaccination; SARS-CoV-2
PubMed: 38783823
DOI: 10.1002/jmv.29682