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Vaccine Aug 2022The risk of developing pneumococcal infections increases with certain chronic conditions and in immunocompromised patients. We aimed to monitor pneumococcal vaccination... (Observational Study)
Observational Study
INTRODUCTION
The risk of developing pneumococcal infections increases with certain chronic conditions and in immunocompromised patients. We aimed to monitor pneumococcal vaccination coverage in at-risk patients and to examine factors associated with pneumococcal vaccination in France.
MATERIAL AND METHODS
In this annual cross-sectional study, at-risk patients were extracted between 2014 and 2018 from the National Health Insurance's (NHI) General scheme's claims database with their vaccine reimbursements. Descriptive analyses and a logistic model were performed to assess the influence of healthcare use and medical and demographic factors on pneumococcal vaccination.
RESULTS AND DISCUSSION
In 2018, 4.5% of 4,045,021 at-risk adults were up to date with their pneumococcal vaccination. During the study period, the number of patients with chronic medical conditions (86% of 4,045,021) increased by 10.1%, but vaccination coverage decreased from 12.9% to 2.9%. The population with immunocompromised status (14% of 4,045,021) increased by 16.2% and vaccination coverage from 10.3% to 18.8%. Influenza vaccination coverage was much higher and stable (around 45.0%). Factors associated with pneumococcal vaccination were: immunocompromised status vs. having a chronic medical condition (odds ratio [OR] 4.72), influenza vaccination (OR 2.36-3.42), hepatitis B vaccination (OR 2.82), DTPolio vaccination (OR 1.52), ≥5 specialist physicians' visits (OR 1.17), and age above 74 (OR 1.12). Pneumococcal vaccine dispensing was extremely low (median of 9per GP,1per specialist over 9 years) despite frequent healthcare visits.
CONCLUSION
Pneumococcal and influenza vaccination coverage of adults at risk of pneumococcal disease fell well below public health expectations. Invitations for pneumococcal vaccination should be sent by the NHI to high-risk patients. Patient management protocols should include pneumococcal vaccination. Patients with multiple comorbidities are a high-priority population given the large potential health gains offered by pneumococcal vaccination. Commitment of both scientific societies and health authorities is urgently needed to increase vaccination coverage in at-risk populations.
Topics: Adult; Cross-Sectional Studies; Humans; Influenza Vaccines; Influenza, Human; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccination; Vaccination Coverage
PubMed: 35811205
DOI: 10.1016/j.vaccine.2022.06.071 -
Vaccine Aug 2015Streptococcus pneumoniae (pneumococcus) remains one of the most commonly identified causes of bacterial infection in the general population, and the risk is 30-100 fold... (Review)
Review
Streptococcus pneumoniae (pneumococcus) remains one of the most commonly identified causes of bacterial infection in the general population, and the risk is 30-100 fold higher in HIV-infected individuals. Both innate and adaptive host immune responses to pneumococcal infection are important against pathogen invasion. Pneumococcal-specific IgA antibody (Ab) is key to control infection at the mucosal sites. Ab responses against pneumococcal infection by B cells can be generated through T cell-dependent or T cell-independent pathways. Depletion of CD4+ T cells is a hallmark of immunodeficiency in HIV infection and this defect also contributes to B cell dysfunction, which predisposes to infections such as the pneumococcus. Two pneumococcal vaccines have been demonstrated to have potential benefits for HIV-infected patients. One is a T cell dependent 13-valent pneumococcal conjugate vaccine (PCV13); the other is a T cell independent 23-valent pneumococcal polysaccharide vaccine (PPV23). However, many questions remain unknown regarding these two vaccines in the clinical setting in HIV disease. Here we review the latest research regarding B cell immune responses against pneumococcal antigens, whether derived from potentially invading pathogens or vaccinations, in the setting of HIV-1 infection.
Topics: B-Lymphocytes; HIV Infections; HIV-1; Humans; Immunity, Humoral; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 26141012
DOI: 10.1016/j.vaccine.2015.06.077 -
Microbiology Spectrum Jun 2023Pneumococcal pneumonia remains a WHO high-priority disease despite multivalent conjugate vaccines administered in clinical practice worldwide. A protein-based,...
Pneumococcal pneumonia remains a WHO high-priority disease despite multivalent conjugate vaccines administered in clinical practice worldwide. A protein-based, serotype-independent vaccine has long-promised comprehensive coverage of most clinical isolates of the pneumococcus. Along with numerous pneumococcal surface protein immunogens, the pneumococcal serine-rich repeat protein (PsrP) has been investigated as a potential vaccine target due to its surface exposure and functions toward bacterial virulence and lung infection. Three critical criteria for its vaccine potential - the clinical prevalence, serotype distribution, and sequence homology of PsrP - have yet to be well characterized. Here, we used genomes of 13,454 clinically isolated pneumococci from the Global Pneumococcal Sequencing project to investigate PsrP presence among isolates, distribution among serotypes, and interrogate its homology as a protein across species. These isolates represent all age groups, countries worldwide, and types of pneumococcal infection. We found PsrP present in at least 50% of all isolates across all determined serotypes and nontypeable (NT) clinical isolates. Using a combination of peptide matching and HMM profiles built on full-length and individual PsrP domains, we identified novel variants that expand PsrP diversity and prevalence. We also observed sequence variability in its basic region (BR) between isolates and serotypes. PsrP has a strong vaccine potential due to its breadth of coverage, especially in nonvaccine serotypes (NVTs) when exploiting its regions of conservation in vaccine design. An updated outlook on PsrP prevalence and serotype distribution sheds new light on the comprehensiveness of a PsrP-based protein vaccine. The protein is present in all vaccine serotypes and highly present in the next wave of potentially disease-causing serotypes not included in the current multivalent conjugate vaccines. Furthermore, PsrP is strongly correlated with clinical isolates harboring pneumococcal disease as opposed to pneumococcal carriage. PsrP is also highly present in strains and serotypes from Africa, where the need for a protein-based vaccine is the greatest, giving new reasoning to pursue PsrP as a protein vaccine.
Topics: Humans; Streptococcus pneumoniae; Vaccines, Conjugate; Prevalence; Pneumococcal Infections; Pneumococcal Vaccines
PubMed: 36995217
DOI: 10.1128/spectrum.03252-22 -
Frontiers in Immunology 2022During the past decades, with the implementation of pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugate vaccines (PCVs), a dramatic reduction in vaccine...
During the past decades, with the implementation of pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugate vaccines (PCVs), a dramatic reduction in vaccine type diseases and transmissions has occurred. However, it is necessary to develop a less expensive, serotype-independent pneumococcal vaccine due to the emergence of nonvaccine-type pneumococcal diseases and the limited effect of vaccines on colonization. As next-generation vaccines, conserved proteins, such as neuraminidase A (NanA), elongation factor Tu (Tuf), and pneumolysin (Ply), are promising targets against pneumococcal infections. Here, we designed and constructed a novel fusion protein, NanAT1-TufT1-PlyD4, using the structural and functional domains of full-length NanA, Tuf and Ply proteins with suitable linkers based on bioinformatics analysis and molecular cloning technology. Then, we tested whether the protein protected against focal and lethal pneumococcal infections and examined its potential protective mechanisms. The fusion protein NanAT1-TufT1-PlyD4 consists of 627 amino acids, which exhibits a relatively high level of thermostability, high stability, solubility and a high antigenic index without allergenicity. The purified fusion protein was used to subcutaneously immunize C57BL/6 mice, and NanAT1-TufT1-PlyD4 induced a strong and significant humoral immune response. The anti-NanAT1-TufT1-PlyD4 specific IgG antibody assays increased after the first immunization and reached the highest value at the 35th day. The results from experiments showed that anti-NanAT1-TufT1-PlyD4 antisera could inhibit the adhesion of to A549 cells. In addition, immunization with NanAT1-TufT1-PlyD4 significantly reduced colonization in the lung and decreased the damage to the lung tissues induced by infection. After challenge with a lethal dose of serotype 3 (NC_WCSUH32403), a better protection effect was observed with NanAT1-TufT1-PlyD4-immunized mice than with the separate full-length proteins and the adjuvant control; the survival rate was 50%, which met the standard of the marketed vaccine. Moreover, we showed that the humoral immune response and the Th1, Th2 and Th17-cellular immune pathways are involved in the immune protection of NanAT1-TufT1-PlyD4 to the host. Collectively, our results support that the novel fusion protein NanAT1-TufT1-PlyD4 exhibits extensive immune stimulation and is effective against pneumococcal challenges, and these properties are partially attributed to humoral and cellular-mediated immune responses.
Topics: Mice; Animals; Streptococcus pneumoniae; Antibodies, Bacterial; Mice, Inbred C57BL; Pneumococcal Vaccines; Pneumococcal Infections
PubMed: 36389808
DOI: 10.3389/fimmu.2022.1043293 -
Pediatric Nephrology (Berlin, Germany) Jan 2023Pneumococcal infections are common in children with nephrotic syndrome. Knowledge of the commonly available serotypes and antibiotic susceptibility will help in...
BACKGROUND
Pneumococcal infections are common in children with nephrotic syndrome. Knowledge of the commonly available serotypes and antibiotic susceptibility will help in prevention and appropriate management of pneumococcal sepsis, especially in resource-limited countries.
METHODS
Demographic, clinical, and laboratory data on children with nephrotic syndrome and pneumococcal infections were extracted from the electronic medical records.
RESULTS
Sixty-three isolates of pneumococci obtained from 60 children with nephrotic syndrome, over a period of 14 years, were included in the study. This represented 18% of all pneumococcal infections occurring in children during the same period. Commonly available vaccines covered up to 58% of all the serotypes causing infection. Severe disease, with shock, intensive care admission and/or meningitis, was observed in 38% children and mortality was observed in 10%. Resistance to commonly used antibiotics was not observed, except for erythromycin.
CONCLUSIONS
Pneumococcal sepsis was observed to be common in children with nephrotic syndrome and results in significant morbidity and mortality. Commonly used antibiotics were observed to be effective in management of the infections.
Topics: Child; Humans; Infant; Nephrotic Syndrome; Developing Countries; Pneumococcal Infections; Streptococcus pneumoniae; Bacteremia; Anti-Bacterial Agents; Pneumococcal Vaccines
PubMed: 35425998
DOI: 10.1007/s00467-022-05550-0 -
Factors associated with pneumococcal carriage and density in infants and young children in Laos PDR.PloS One 2019Nasopharyngeal carriage of Streptococcus pneumoniae (the pneumococcus) is a precursor to pneumococcal disease. Several host and environmental factors have been...
Nasopharyngeal carriage of Streptococcus pneumoniae (the pneumococcus) is a precursor to pneumococcal disease. Several host and environmental factors have been associated with pneumococcal carriage, however few studies have examined the relationship between host factors and pneumococcal carriage density. We sought to identify risk factors for pneumococcal carriage and density using data from cross-sectional pneumococcal carriage surveys conducted in the Lao People's Democratic Republic before and after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Nasopharyngeal swabs were collected infants from aged 5-8 weeks old (n = 999) and children aged 12-23 months (n = 1,010), pneumococci detected by quantitative PCR, and a risk factor questionnaire completed. Logistic and linear regression models were used to evaluate associations between participant characteristics and pneumococcal carriage and density. In infants aged 5-8 weeks, living in a household with two or more children under the age of five years (aOR 1.97; 95% CI 1.39-2.79) and low family income (aOR 1.64; 95% CI 0.99-2.72) were positively associated with pneumococcal carriage. For children aged 12-23 months, upper respiratory tract infection (URTI) symptoms (aOR 2.64; 95% CI 1.97-3.53), two or more children under five in the household (aOR 2.40; 95% CI 1.80-3.20), and rural residence (aOR 1.84, 95% CI 1.35-2.50) were positively associated with pneumococcal carriage. PCV13 vaccination was negatively associated with carriage of PCV13 serotypes (aOR 0.60; 95% CI 0.44-0.83). URTI symptoms (p < 0.001), current breastfeeding (p = 0.005), rural residence (p = 0.012), and delivery by Caesarean section (p = 0.035) were associated with higher mean pneumococcal density in pneumococcal carriers (both age groups combined). This study provides new data on pneumococcal carriage and density in a high disease burden setting in southeast Asia.
Topics: Carrier State; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Infant, Newborn; Laos; Male; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Risk Factors; Serogroup; Serotyping; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 31661527
DOI: 10.1371/journal.pone.0224392 -
Archivos de Bronconeumologia Mar 2023Fifteen and 20-valent pneumococcal conjugate vaccines (PCV15; PCV20) were recently licensed to prevent pneumococcal disease in adults. In the absence of efficacy or... (Review)
Review
INTRODUCTION
Fifteen and 20-valent pneumococcal conjugate vaccines (PCV15; PCV20) were recently licensed to prevent pneumococcal disease in adults. In the absence of efficacy or effectiveness data for these new vaccines, studies comparing 23-valent pneumococcal polysaccharide vaccine (PPV23) and PCV13 might help inform decision-making on how to best implement expanded-valency PCVs. Comparing PPV23 and PCV13 is problematic, as no head-to-head clinical trials evaluated efficacy. Comparing effectiveness results across observational studies that vary by population, design, and outcomes is difficult. To address these limitations, we undertook a narrative review of studies that assessed PPV23 and PCV13 vaccine effectiveness (VE) in the same adult populations.
METHODS
We conducted a literature search in PubMed and Google Scholar and screened 525 studies using a standardized evaluation framework.
RESULTS
Nine studies met inclusion criteria, all from high-income countries. None evaluated invasive pneumococcal disease (IPD) alone. VE against vaccine-type pneumococcal pneumonia ranged from 2 to 6% for PPV23 and 41 to 71% for PCV13. VE against pneumococcal pneumonia or severe pneumococcal disease (IPD or pneumococcal pneumonia) ranged from -10 to 11% for PPV23, 40 to 79% for PCV13, and 39 to 83% for sequential PCV13/PPV23. VE against all-cause pneumonia or lower respiratory tract infection ranged from -8 to 3% for PPV23 and 9 to 12% for PCV13.
CONCLUSIONS
Overall, PCV13 demonstrated better protection than PPV23 against pneumococcal disease and all-cause respiratory outcomes in the included studies. Where evaluated, sequential PCV13/PPV23 vaccination showed little benefit over PCV13 alone. Results support the use of PCVs to protect against pneumococcal disease and respiratory infections in adults.
Topics: Humans; Adult; Pneumonia, Pneumococcal; Pneumococcal Infections; Streptococcus pneumoniae; Pneumococcal Vaccines; Vaccination; Vaccines, Conjugate
PubMed: 36681604
DOI: 10.1016/j.arbres.2022.12.015 -
Pediatrics Mar 2020Most countries use 3-dose pneumococcal conjugate vaccine (PCV) schedules; a 4-dose (3 primary and 1 booster) schedule is licensed for US infants. We evaluated the...
BACKGROUND
Most countries use 3-dose pneumococcal conjugate vaccine (PCV) schedules; a 4-dose (3 primary and 1 booster) schedule is licensed for US infants. We evaluated the invasive pneumococcal disease (IPD) breakthrough infection incidence in children receiving 2 vs 3 primary PCV doses with and without booster doses (2 + 1 vs 3 + 1; 2 + 0 vs 3 + 0).
METHODS
We used 2001-2016 Active Bacterial Core surveillance data to identify breakthrough infections (vaccine-type IPD in children receiving ≥1 7-valent pneumococcal conjugate vaccine [PCV7] or 13-valent pneumococcal conjugate vaccine [PCV13] dose) among children aged <5 years. We estimated schedule-specific IPD incidence rates (IRs) per 100 000 person-years and compared incidence by schedule (2 + 1 vs 3 + 1; 2 + 0 vs 3 + 0) using rate differences (RDs) and incidence rate ratios.
RESULTS
We identified 71 PCV7 and 49 PCV13 breakthrough infections among children receiving a schedule of interest. PCV13 breakthrough infection rates were higher in children aged <1 year receiving the 2 + 0 (IR: 7.8) vs 3 + 0 (IR: 0.6) schedule (incidence rate ratio: 12.9; 95% confidence interval: 4.1-40.4); PCV7 results were similar. Differences in PCV13 breakthrough infection rates by schedule in children aged <1 year were larger in 2010-2011 (2 + 0 IR: 18.6; 3 + 0 IR: 1.4; RD: 16.6) vs 2012-2016 (2 + 0 IR: 3.6; 3 + 0 IR: 0.2; RD: 3.4). No differences between schedules were detected in children aged ≥1 year for PCV13 breakthrough infections.
CONCLUSIONS
Fewer PCV breakthrough infections occurred in the first year of life with 3 primary doses. Differences in breakthrough infection rates by schedule decreased as vaccine serotypes decreased in circulation.
Topics: Child, Preschool; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Incidence; Infant; Male; Pneumococcal Infections; Pneumococcal Vaccines; Treatment Failure; United States
PubMed: 32054822
DOI: 10.1542/peds.2019-0836 -
Frontiers in Cellular and Infection... 2022(), or the pneumococcus, is a Gram-positive bacterium that colonizes the upper airway. is an opportunistic pathogen capable of life-threatening disease should it... (Review)
Review
(), or the pneumococcus, is a Gram-positive bacterium that colonizes the upper airway. is an opportunistic pathogen capable of life-threatening disease should it become established in the lungs, gain access to the bloodstream, or disseminate to vital organs including the central nervous system. is encapsulated, allowing it to avoid phagocytosis, and current preventative measures against infection include polyvalent vaccines composed of capsular polysaccharide corresponding to its most prevalent serotypes. The pneumococcus also has a plethora of surface components that allow the bacteria to adhere to host cells, facilitate the evasion of the immune system, and obtain vital nutrients; one family of these are the choline-binding proteins (CBPs). Pneumococcal surface protein A (PspA) is one of the most abundant CBPs and confers protection against the host by inhibiting recognition by C-reactive protein and neutralizing the antimicrobial peptide lactoferricin. Recently our group has identified two new roles for PspA: binding to dying host cells via host-cell bound glyceraldehyde 3-phosphate dehydrogenase and co-opting of host lactate dehydrogenase to enhance lactate availability. These properties have been shown to influence localization and enhance virulence in the lower airway, respectively. Herein, we review the impact of CBPs, and in particular PspA, on pneumococcal pathogenesis. We discuss the potential and limitations of using PspA as a conserved vaccine antigen in a conjugate vaccine formulation. PspA is a vital component of the pneumococcal virulence arsenal - therefore, understanding the molecular aspects of this protein is essential in understanding pneumococcal pathogenesis and utilizing PspA as a target for treating or preventing pneumococcal pneumonia.
Topics: Animals; Antibodies, Bacterial; Bacterial Proteins; Humans; Mice; Mice, Inbred BALB C; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 35186799
DOI: 10.3389/fcimb.2022.826264 -
Vaccine May 2023In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a... (Randomized Controlled Trial)
Randomized Controlled Trial
In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a randomized immunogenicity trial comparing the two schedules. Carriage prevalence measured at the time of booster and 6 months later in 191 of the 213 study infants was 57 % (109/191) and 60 % (114/190) respectively. There were eight episodes of vaccine-type (VT) or vaccine-related 6C carriage in the 2 + 1 and six in the 1 + 1 group; ≥4-fold rises in serotype-specific IgG in 71 children with paired post-booster and follow up blood samples at 21-33 months of age were found in 20 % (7/35) of the 2 + 1 and 15 % (6/41) of the 1 + 1 group. VTs identified in carriage and inferred from serology were similar comprising 3, 19A and 19F. Dropping a priming dose from the 2 + 1 PCV 13 schedule did not increase VT carriage in the study cohort. Ongoing population level carriage studies will be important to confirm this.
Topics: Child; Humans; Infant; Antibodies, Bacterial; Immunization Schedule; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; United Kingdom; Vaccines, Conjugate
PubMed: 37045683
DOI: 10.1016/j.vaccine.2023.04.017