-
Human Vaccines & Immunotherapeutics Dec 2023Human papillomavirus (HPV) vaccination uptake in the United States remains suboptimal, and continues to trail that of tetanus, diphtheria, and acellular pertussis (Tdap)...
Human papillomavirus (HPV) vaccination uptake in the United States remains suboptimal, and continues to trail that of tetanus, diphtheria, and acellular pertussis (Tdap) vaccination and quadrivalent meningococcal conjugate vaccination (MCV4). This is despite these three vaccines all being recommended for routine adolescent use within the 2005-2006 time period. One strategy to improve HPV vaccination is starting the vaccine series at the first opportunity - currently as young as 9 years of age. Little is known about the epidemiology of age at HPV vaccination, and the frequency of vaccination occurring at 9-10 years of age. Using 2020 National Immunization Survey-Teen (NIS-Teen) data, we analyzed age at HPV vaccine initiation and proportion of initiators completing the HPV vaccine series relative to age at initiation. Overall, 4.0% of US adolescents initiated HPV vaccination at 9-10 years of age, with higher initiation among younger birth cohorts (4.8% for 13-year-olds and 5.1% for 14-year-olds) than older cohorts (3.1% for both 16 and 17 year-olds). Age cohorts maximized HPV vaccine completion after 3-4 years. Among those initiating at ages 9-10, 93% of 13-year-olds completed the series. Among those initiating at 11-12, completion rates rose from 66% among 13-year-olds to 90.2% among 16-year-olds. Among those initiating at age 13-14, completion rose from 61% among 15-year-olds to 84.9% among 17-year-olds. This manuscript serves as a starting point of comparison for future epidemiologic evaluations of HPV vaccination at the first opportunity.
Topics: Adolescent; Humans; United States; Child; Child, Preschool; Papillomavirus Infections; Diphtheria-Tetanus-acellular Pertussis Vaccines; Immunization Schedule; Meningococcal Vaccines; Vaccination; Immunization; Papillomavirus Vaccines
PubMed: 37138466
DOI: 10.1080/21645515.2023.2204784 -
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 -
Signal Transduction and Targeted Therapy Feb 2024Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines...
Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines and medical devices). It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted 'reduction, replacement and refinement' principle, which has been highly considered by regulatory agencies from different countries. We used NF-κB, a central signalling molecule mediating inflammatory responses, as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal. Here, we show that this test can quantitatively and sensitively detect endotoxin (lipopolysaccharide from different strains) and nonendotoxin (lipoteichoic acid, zymosan, peptidoglycan, lectin and glucan), has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals (group A & C meningococcal polysaccharide vaccine; basiliximab; rabies vaccine (Vero cells) for human use, freeze-dried; Japanese encephalitis vaccine (Vero cells), inactivated; insulin aspart injection; human albumin; recombinant human erythropoietin injection (CHO Cell)). The within-laboratory reproducibility of the test in three independent laboratories was 85%, 80% and 80% and the interlaboratory reproducibility among laboratories was 83.3%, 95.6% and 86.7%. The sensitivity (true positive rate) and specificity (true negative rate) of the test were 89.9% and 90.9%, respectively. In summary, the test provides a novel alternative for pyrogen detection.
Topics: Animals; Chlorocebus aethiops; Rabbits; Humans; Pyrogens; NF-kappa B; Vero Cells; Reproducibility of Results; Cell Line
PubMed: 38369543
DOI: 10.1038/s41392-024-01744-0 -
HIV Medicine Sep 2023People living with HIV have been shown to have an increased risk of invasive meningococcal disease. In some countries, meningococcal vaccines are now routinely...
The propositive study: Immunogenicity and safety of a four-component recombinant protein-based vaccine against MenB and a quadrivalent conjugate MenACWY vaccine in people living with HIV.
BACKGROUND
People living with HIV have been shown to have an increased risk of invasive meningococcal disease. In some countries, meningococcal vaccines are now routinely recommended to all people living with HIV, but no study has yet assessed the immunogenicity and safety of a meningococcal serogroup B vaccine or the co-administration of a MenB and MenACWY vaccine in people living with HIV.
METHODS
This phase IV open-label clinical trial investigated the immunogenicity and safety of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in a population of people living with HIV. Immunogenicity analysis was performed before vaccination and 1 month after the second doses of 4CMenB and MenACWY. Primary outcome measures were serum bactericidal assay geometric mean titres against three MenB reference strains at baseline and 1 month post vaccination, the proportion of participants achieving a putative protective titre of ≥4, and the proportion of participants with a ≥4-fold rise in titre from baseline. Secondary outcome measures were serum bactericidal assay geometric mean titres against MenA, C, W, and Y reference strains at baseline and 1 month post vaccination, the proportion achieving a putative protective titre of ≥8, and the proportion with a ≥4-fold rise in titre from baseline. Safety outcomes were solicited and unsolicited adverse events in the 7 days following vaccination. The trial was registered with clinicaltrials.gov (NCT03682939).
FINDINGS
In total, 55 participants aged 20-45 years were enrolled. All participants (100%; 95% confidence interval [CI] 93-100) achieved putative protective titres for two of the three MenB strains and for MenA, W, and Y. A total of 98% (95% CI 89-100) achieved a protective titre for the third MenB strain and 94% (95% CI 83-99) for MenC. No serious adverse events were reported.
INTERPRETATION
4CMenB and MenACWY were immunogenic and well-tolerated in a population of people living with HIV 1 month after two doses.
Topics: Humans; Meningococcal Vaccines; Meningococcal Infections; Vaccines, Combined; HIV Infections; Recombinant Proteins
PubMed: 37088964
DOI: 10.1111/hiv.13495 -
JAMA Network Open Jan 2024Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort.
IMPORTANCE
Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort.
OBJECTIVE
To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023.
EXPOSURE
A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021.
MAIN OUTCOMES AND MEASURES
Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood.
RESULTS
The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.
Topics: Child; Humans; Male; Female; Infant; Child, Preschool; Sweden; Cohort Studies; Retrospective Studies; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Bacterial; Meningitis, Pneumococcal; Hearing Loss; Deafness; Seizures
PubMed: 38241045
DOI: 10.1001/jamanetworkopen.2023.52402 -
European Geriatric Medicine May 2024Invasive meningococcal disease (IMD) is a devastating condition. While most attention is directed towards disease in children and adolescents, IMD poses an important... (Review)
Review
PURPOSE
Invasive meningococcal disease (IMD) is a devastating condition. While most attention is directed towards disease in children and adolescents, IMD poses an important cause of morbidity and mortality in adults ≥60 years. While immunization is a critical component of healthy ageing strategies, meningococcal immunization is not routinely offered to older adults. The aim of this review was to summarize clinical and epidemiological aspects of IMD and available immunization strategies, with a particular focus on disease in older individuals, to emphasize the importance of this rather neglected area.
METHODS
An expert working group was established to evaluate clinical and epidemiological data to raise awareness of IMD in older individuals, and develop suggestions to improve the existing burden.
RESULTS
Routine child and adolescent meningococcal immunization has substantially reduced IMD in these targeted populations. Consequently, prevalence and proportion of IMD among those ≥60 years, mostly unvaccinated, is increasing in developed countries (accounting for up to 25% of cases). IMD-related mortality is highest in this age-group, with substantial sequelae in survivors. IMD due to serogroups W and Y is more prevalent among older adults, often with atypical clinical features (pneumonia, gastrointestinal presentations) which may delay timely treatment.
CONCLUSIONS
IMD in older adults remains overlooked and greater awareness is required at clinical and societal levels. We encourage clinicians and immunization policy makers to reconsider IMD, with a call for action to remedy existing inequity in older adult access to protective meningococcal immunization.
PubMed: 38709380
DOI: 10.1007/s41999-024-00969-0 -
BMC Microbiology Nov 2023Neisseria meningitidis can be carried asymptomatically in the human oropharynx without causing symptoms. Meningococcal carriage is relevant to the epidemiology of...
BACKGROUND
Neisseria meningitidis can be carried asymptomatically in the human oropharynx without causing symptoms. Meningococcal carriage is relevant to the epidemiology of invasive meningococcal disease (IMD). No carriage studies have been performed among the general population in Lithuania, whereas the incidence of IMD in Lithuania was among the highest in European countries from 2009 to 2019.
RESULTS
We analyzed a total of 401 oropharyngeal samples collected from university students from December 2021 to February 2023 for N. meningitidis carriage using direct swab PCR assays and culture. The overall carriage prevalence based on both or either swab PCR or culture was 4.99%. PCR-based assays were used to characterize 15 carriage isolates, including detection of genogroup, multilocus sequence typing profile, and typing of antigens PorA and FetA. The most common carriage isolates were capsule null locus (cnl), accounting for 46.7%, followed by genogroups B (26.7%) and Y (13.3%). We also performed a molecular characterization of invasive N. meningitidis isolates collected during the COVID-19 pandemic and post-pandemic period to understand better the meningococcal carriage in the context of prevailing invasive strains. Despite the substantial decrease in the incidence of IMD during the 2020-2022 period, clonal complex 32 (CC32) of serogroup B continued to be the most prevalent IMD-causing CC in Lithuania. However, CC32 was not detected among carriage isolates. The most common CCs were CC269, CC198, and CC1136. The antigen peptide variants found in most carried isolates were classified as 'insufficient data' according to the MenDeVAR Index to evaluate the potential coverage by the 4CMenB vaccine. Nearly half of the isolates were potentially covered by the Men-Fhbp vaccine. Resistance to ciprofloxacin was detected only for one cnl isolate. All isolates were susceptible to penicillin and ceftriaxone. Our analysis identified frequent partying (≥ 4 times/month) as a risk factor for meningococcal carriage, whereas smoking, living in a dormitory, and previous COVID-19 illness were not associated with the carriage.
CONCLUSIONS
Our study revealed a low prevalence of meningococcal carriage among university students in Lithuania. The carriage isolates showed genetic diversity, although almost half of them were identified as having a null capsule locus.
Topics: Male; Humans; Female; Neisseria meningitidis; Meningococcal Infections; Lithuania; Pandemics; Universities; Meningococcal Vaccines; Serogroup; Bacterial Vaccines; Students; Antigens, Bacterial
PubMed: 37978423
DOI: 10.1186/s12866-023-03111-5 -
Vaccine May 2024The rates of nasopharyngeal meningococcal carriage in healthcare workers are unknown. Meningococcal vaccine is recommended for risk groups but healthcare workers are not...
The rates of nasopharyngeal meningococcal carriage in healthcare workers are unknown. Meningococcal vaccine is recommended for risk groups but healthcare workers are not included in risk groups for many countries. Herein, we aimed to investigate the nasopharyngeal meningococcal carriage rates, basal and after one dose of Men-ACWY-DT vaccine response on the 30th day by evaluating meningococcus IgG antibody levels and decolonization at month six after vaccination among the detected carriers. Nasopharyngeal swab samples were taken before vaccination to evaluate meningococcal carriage in healthcare workers. All participants received a single dose of Men-ACWY-DT vaccine. Serum samples were collected immediately before vaccination and again on day 30 post-vaccination. Antibodies in the stored sera were analyzed using the ELISA method. Participants who were determined to carry meningococci at the initial visit underwent another round of nasopharyngeal swab tests six months post-vaccination to check for decolonization. Between November 2020 and May 2021, we evaluated samples from 100 physicians [52 % females, 28.28 ± 4.45 (min: 24, max: 49)]. The majority of the physicians worked in the emergency department (45 %), followed by the infectious diseases clinic (14 %). Fifty-eight physicians had a history of at least one contact with a meningococcus-infected patient, and 53 (91.4 %) had used prophylactic antibiotics at least once due to this exposure. None of the study group nasopharyngeal swab cultures were positive for Neisseria meningitidis. Before the Men-ACWY-DT vaccine, anti-meningococcus IgG positivity was detected in the serum samples of only 3 (3 %) participants. By day 30 after vaccination, 48 % of participants showed positive for antibodies. As we didn't detect nasopharyngeal carriage in any participants, we didn't evaluate decolonization among carriers six months post-vaccination. Notably, detection of antibodies was evident in about half of the participants on day 30 after receiving a single dose of the Men-ACWY-DT vaccine.
PubMed: 38719693
DOI: 10.1016/j.vaccine.2024.05.004 -
Vaccines Aug 2023This cross-sectional survey was conducted to investigate the willingness and uptake of recommended vaccinations against influenza, meningococcal B and ACWY,...
This cross-sectional survey was conducted to investigate the willingness and uptake of recommended vaccinations against influenza, meningococcal B and ACWY, pneumococcal, rotavirus and the influencing factors among 565 parents of children aged 6 months to 5 years with chronic medical conditions in Italy. Only 34.9% of the sample received all vaccinations. Parents whose selected child was vaccinated against the five diseases were those who had received recommendations from physicians, who did not believe that children should get fewer vaccinations at the same time, those whose child was aged 2-3 and 4-5 years compared to 6 months-1 year, and those who acquired information from physicians. Only 17.9% were willing to vaccinate their child. Parents with a university degree, those who acquired information from physicians, and those whose child had a more recent diagnosis were more likely to be willing to vaccinate their child. Parents who believed that children should get fewer vaccines at the same time, those without a university degree, and those who did not acquire information from physicians were more likely to not have vaccinated their child because they were concerned about vaccines' side effects. Public health policymakers should provide efforts to promote the uptake for an adequate protection of this high-risk group.
PubMed: 37766100
DOI: 10.3390/vaccines11091423 -
International Immunology Mar 2024Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date,...
Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N.meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal assays (SBA) based protective coverage of OMV vaccine to X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the W+B OMV vaccine, either adjuvanted with Alum, CpG ODN or their combinations and compared with a MenACYW conjugate vaccine (NimenrixTM, Pfizer) and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through ELISA and SBA. Antibody responses and SBA titers were significantly higher in the W+B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the W+B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the W+B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines.
PubMed: 38536954
DOI: 10.1093/intimm/dxae016