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Arthritis Research & Therapy May 2015The aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent... (Randomized Controlled Trial)
Randomized Controlled Trial
The association between antibody levels before and after 7-valent pneumococcal conjugate vaccine immunization and subsequent pneumococcal infection in chronic arthritis patients.
INTRODUCTION
The aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients.
METHODS
A cohort of 497 patients (RA=248 and SpA=249) received a single dose of PCV7. At vaccination, patients were treated with methotrexate (MTX; n=85), anti-tumour necrosis factor (anti-TNF) + MTX (n=169), anti-TNF monotherapy (n=158) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics (n=85). Antibody levels of serotypes 6B and 23B were analyzed before and 4 to 6 weeks after vaccination using standard enzyme-linked immunosorbent assay (ELISA). Serious pneumococcal infections (pneumonia/lower respiratory tract infection, meningitis, sepsis, septic arthritis) occurring within 4.5 years after vaccination were identified in the Skåne Healthcare Register using the International Classification of Diseases, tenth revision (ICD-10) codes. The association between post-vaccination antibody levels and protection against infections and determination of protective cutoff levels was explored using receiver operating characteristic (ROC) curves. Predictors of infection were studied using regression analyses.
RESULTS
Eighteen infections were registered in 15 patients before vaccination and 27 infections in 23 patients after vaccination. Patients with serious infections after vaccination had significantly lower post-vaccination antibody titres for both 6B (P=0.04) and 23 F (P=0.04). Post-vaccination antibody levels of at least 1.29 mg/L and 1.01 mg/L for 6B and 23, respectively, were associated with better protection from serious infections. Higher age, concomitant prednisolone but not MTX or anti-TNF were associated with such infections.
CONCLUSIONS
Patients with more robust antibody responses after vaccination with pneumococcal conjugate vaccine were less likely to suffer from serious infections. High age and prednisolone at vaccination were associated with putative serious pneumococcal infections in this cohort.
TRIAL REGISTRATION NUMBER
EudraCT EU 2007-006539-29 and NCT00828997 . Registered 23 January 2009.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Arthritis, Rheumatoid; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Immunization; Immunologic Factors; Male; Middle Aged; Pneumococcal Infections; Young Adult
PubMed: 25986458
DOI: 10.1186/s13075-015-0636-z -
Anales de Pediatria Jun 2022Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its...
BACKGROUND
Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13).
METHODS
Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period).
RESULTS
We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 casos per 100 000 habitantes ( -62%; P < .001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 casos/100 000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P = .00). The incidence of serotype 3 decreased from 10.4 to 6.9 casos per 100 000 population, although it was the serotype involved most frequently in patients with severe disease.
CONCLUSIONS
After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD.
Topics: Child; Child, Preschool; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Prospective Studies; Serogroup; Vaccines, Conjugate
PubMed: 34238710
DOI: 10.1016/j.anpede.2021.06.005 -
Journal of Visualized Experiments : JoVE Feb 2013Experimental human pneumococcal carriage (EHPC) is scientifically important because nasopharyngeal carriage of Streptococcus pneumoniae is both the major source of...
UNLABELLED
Experimental human pneumococcal carriage (EHPC) is scientifically important because nasopharyngeal carriage of Streptococcus pneumoniae is both the major source of transmission and the prerequisite of invasive disease. A model of carriage will allow accurate determination of the immunological correlates of protection, the immunizing effect of carriage and the effect of host pressure on the pathogen in the nasopharyngeal niche. Further, methods of carriage detection useful in epidemiologic studies, including vaccine studies, can be compared.
AIM
We aim to develop an EHPC platform that is a safe and useful reproducible method that could be used to down-select candidate novel pneumococcal vaccines with prevention of carriage as a surrogate of vaccine induced immunity. It will work towards testing of candidate vaccines and descriptions of the mechanisms underlying EHPC and vaccine protection from carriage. Current conjugate vaccines against pneumococcus protect children from invasive disease although new vaccines are urgently needed as the current vaccine does not confer optimal protection against non-bacteraemic pneumonia and there has been evidence of serotype replacement with non-vaccine serotypes.
METHOD
We inoculate with S. pneumoniae suspended in 100 μl of saline. Safety is a major factor in the development of the EHPC model and is achieved through intensive volunteer screening and monitoring. A safety committee consisting of clinicians and scientists that are independent from the study provides objective feedback on a weekly basis. The bacterial inoculum is standardized and requires that no animal products are inoculated into volunteers (vegetable-based media and saline). The doses required for colonization (10(4)-10(5)) are much lower than those used in animal models (10(7)). Detecting pneumococcal carriage is enhanced by a high volume (ideally > 10 ml) nasal wash that is relatively mucus free. This protocol will deal with the most important parts of the protocol in turn. These are (a) volunteer selection, (b) pneumococcal inoculum preparation, (c) inoculation, (d) follow-up and (e) carriage detection.
RESULTS
Our current protocol has been safe in over 100 volunteers at a range of doses using two different bacterial serotypes. A dose ranging study using S. pneumoniae 6B and 23F is currently being conducted to determine the optimal inoculation dose for 50% carriage. A predicted 50% rate of carriage will allow the EHPC model to have high sensitivity for vaccine efficacy with small study numbers.
Topics: Adolescent; Adult; Carrier State; Humans; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Young Adult
PubMed: 23439027
DOI: 10.3791/50115 -
Vaccine Mar 2024Pneumococcus remains a major cause of adult lower respiratory tract infections (LRTI). Few data exist on the relative contribution of serotypes included in pneumococcal...
INTRODUCTION
Pneumococcus remains a major cause of adult lower respiratory tract infections (LRTI). Few data exist on the relative contribution of serotypes included in pneumococcal vaccines to community-acquired pneumonia (CAP) and non-pneumonic (NP) LRTI. We measured the burden of all and vaccine-serotype pneumococcal respiratory infection following SARS-CoV-2 emergence to inform evidence-based vaccination policy.
METHODS
A prospective cohort study at two Bristol hospitals (UK) including all adults age ≥ 18-years hospitalised with acute lower respiratory tract disease (aLRTD) from Nov2021-Nov2022. LRTI patients were classified as: a) radiographically-confirmed CAP (CAP+/RAD+), b) clinically-diagnosed CAP without radiological confirmation (CAP+/RAD-), or c) NP-LRTI. Pneumococcus was identified by blood culture, BinaxNOW™and serotype-specific urine antigen detection assays (UAD).
RESULTS
Of 12,083 aLRTD admissions, 10,026 had LRTI and 2,445 provided urine: 1,097 CAP + RAD+; 207 CAP + RAD-; and 1,141 NP-LRTI. Median age was 71.1y (IQR57.9-80.2) and Charlson comorbidity index = 4 (IQR2-5); 2.7 % of patients required intensive care, and 4.4 % died within 30-days of hospitalisation. Pneumococcus was detected in 280/2445 (11.5 %) participants. Among adults aged ≥ 65y and 18-64y, 12.9 % (198/1534) and 9.0 % (82/911), respectively, tested pneumococcus positive. We identified pneumococcus in 165/1097 (15.0 %) CAP + RAD+, 23/207 (11.1 %) CAP + RAD-, and 92/1141 (8.1 %) NP-LRTI cases. Of the 280 pneumococcal cases, 102 (36.4 %) were due to serotypes included in PCV13 + 6C, 115 (41.7 %) in PCV15 + 6C, 210 (75.0 %) in PCV20 + 6C/15C and 228 (81.4 %) in PPV23 + 15C. The most frequently identified serotypes were 8 (n = 78; 27.9 % of all pneumococcus), 7F (n = 25; 8.9 %), and 3 (n = 24; 8.6 %).
DISCUSSION
Among adults hospitalised with respiratory infection, pneumococcus is an important pathogen across all subgroups, including CAP+/RAD- and NP-LRTI. Despite 20-years of PPV23 use in adults ≥ 65-years and herd protection due to 17-years of PCV use in infants, vaccine-serotype pneumococcal disease still causes a significant proportion of LRTI adult hospitalizations. Direct adult vaccination with high-valency PCVs may reduce pneumococcal disease burden.
Topics: Adult; Humans; Aged; Serogroup; Pneumonia, Pneumococcal; Prospective Studies; Streptococcus pneumoniae; Pneumococcal Infections; Respiratory Tract Infections; Pneumococcal Vaccines; Community-Acquired Infections; United Kingdom; Vaccines, Conjugate
PubMed: 38336560
DOI: 10.1016/j.vaccine.2024.02.007 -
Microbiology (Reading, England) Feb 2006The innate immune system provides a non-specific first line of defence against microbes and is crucial both in the development and effector stages of subsequent adaptive... (Review)
Review
The innate immune system provides a non-specific first line of defence against microbes and is crucial both in the development and effector stages of subsequent adaptive immune responses. Consistent with its importance, study of the innate immune system is a broad and fast-moving field. Here we provide an overview of the recent key advances made in this area with relation to the important pathogen Streptococcus pneumoniae (the pneumococcus).
Topics: Humans; Immunity, Innate; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Toll-Like Receptors
PubMed: 16436416
DOI: 10.1099/mic.0.28551-0 -
Human Vaccines & Immunotherapeutics Dec 2021The universal administration of pneumococcal conjugate vaccines (PCVs) had been demonstrated as an effective way to prevent infection. However, the immunity induced by... (Review)
Review
The universal administration of pneumococcal conjugate vaccines (PCVs) had been demonstrated as an effective way to prevent infection. However, the immunity induced by PCVs protected against the infections caused by vaccine serotypes, which were usually more frequent than non-vaccine serotypes (NVTs). The prevalence and pathogenicity of NVTs after universal vaccination have caused widespread concern. We reviewed the epidemiology of non-PCV13 e before and after PCV13 introduction, and explored the potential reasons for the spread of NVTs. Emerging and spreading NVTs can be regarded as the focus for future serotype epidemiological survey and vaccine optimization.IPD: invasive pneumococcal disease PCV: pneumococcal conjugate vaccines VT: vaccine serotypeNVT: non-vaccine serotype.
Topics: Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 34726580
DOI: 10.1080/21645515.2021.1985353 -
Identifying UK travellers at increased risk of developing pneumococcal infection: a novel algorithm.Journal of Travel Medicine Aug 2021In 2016, the travel subcommittee of the UK Joint Committee on Vaccination and Immunisation (JCVI) recommended that 13-valent PCV (PCV13) could be offered to travellers...
BACKGROUND
In 2016, the travel subcommittee of the UK Joint Committee on Vaccination and Immunisation (JCVI) recommended that 13-valent PCV (PCV13) could be offered to travellers aged over 65 years, visiting countries without infant PCV immunization programmes. This study aimed to identify, collate and review the available evidence to identify specific countries where UK travellers might be at an increased risk of developing pneumococcal infection. The data were then used to develop an algorithm, which could be used to facilitate implementation of the JCVI recommendation.
METHODS
We conducted a systematic search of the published data available for pneumococcal disease, PCV vaccine implementation, coverage data and programme duration by country. The primary data sources used were World Health Organization databases and the International Vaccine Access Centre Vaccine Information and Epidemiology Window-hub database. Based on the algorithm, the countries were classified into 'high overall risk', 'intermediate overall risk' and 'low overall risk' from an adult traveller perspective. This could determine whether PCV13 should be recommended for UK adult travellers.
RESULTS
A data search for a total of 228 countries was performed, with risk scores calculated for 188 countries. Overall, 45 countries were classified as 'high overall risk', 86 countries as 'intermediate overall risk', 57 countries as 'low overall risk' and 40 countries as 'unknown'.
CONCLUSION
To our knowledge this is the first attempt to categorize the risk to UK adult travellers of contracting pneumococcal infection in each country, globally. These findings could be used by national travel advisory bodies and providers of travel vaccines to identify travellers at increased risk of pneumococcal infection, who could be offered PCV immunization.
Topics: Adult; Aged; Algorithms; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; United Kingdom; Vaccination; Vaccines, Conjugate
PubMed: 33978186
DOI: 10.1093/jtm/taab063 -
BMJ Global Health Jun 2021Empiric data on indirect (herd) effects of pneumococcal conjugate vaccines (PCVs) in settings with low or heterogeneous PCV coverage are limited. The indirect effects of... (Observational Study)
Observational Study
Indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with acute respiratory infection despite heterogeneous vaccine coverage: an observational study in Lao People's Democratic Republic.
INTRODUCTION
Empiric data on indirect (herd) effects of pneumococcal conjugate vaccines (PCVs) in settings with low or heterogeneous PCV coverage are limited. The indirect effects of PCV, which benefits both vaccinated and non-vaccinated individuals, are mediated by reductions in vaccine-type (VT) carriage (a prerequisite for disease). The aim of this study among hospitalised children in Lao People's Democratic Republic (Lao PDR) is to determine the effectiveness of a 13-valent PCV (PCV13) against VT pneumococcal nasopharyngeal carriage (direct effects) and the association between village-level PCV13 coverage and VT carriage (indirect effects).
METHODS
Pneumococcal nasopharyngeal carriage surveillance commenced in December 2013, shortly after PCV13 introduction (October 2013). We recruited and swabbed children aged 2-59 months admitted to hospital with acute respiratory infection. Pneumococci were detected using quantitative real-time PCR and serotyped using microarray. PCV13 status and village-level PCV13 coverage were determined using written immunisation records. Associations between both PCV13 status and village-level PCV13 coverage and VT carriage were calculated using generalised estimating equations, controlling for potential confounders.
RESULTS
We enrolled 1423 participants and determined PCV13 coverage for 368 villages (269 863 children aged under 5 years). By 2017, median village-level vaccine coverage reached 37.5%, however, the IQR indicated wide variation among villages (24.1-56.4). Both receipt of PCV13 and the level of PCV13 coverage were independently associated with a reduced odds of VT carriage: adjusted PCV13 effectiveness was 38.1% (95% CI 4.1% to 60.0%; p=0.032); and for each per cent increase in PCV13 coverage, the estimated odds of VT carriage decreased by 1.1% (95% CI 0.0% to 2.2%; p=0.056). After adjustment, VT carriage decreased from 20.0% to 12.8% as PCV13 coverage increased from zero to 60% among under 5.
CONCLUSIONS
Despite marked heterogeneity in PCV13 coverage, we found evidence of indirect effects in Lao PDR. Individual vaccination with PCV13 was effective against VT carriage.
Topics: Child; Humans; Laos; Pneumococcal Infections; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 34108146
DOI: 10.1136/bmjgh-2021-005187 -
Frontiers in Immunology 2022Circadian rhythms affect the progression and severity of bacterial infections including those caused by , but the mechanisms responsible for this phenomenon remain...
Circadian rhythms affect the progression and severity of bacterial infections including those caused by , but the mechanisms responsible for this phenomenon remain largely elusive. Following advances in our understanding of the role of replication of within splenic macrophages, we sought to investigate whether events within the spleen correlate with differential outcomes of invasive pneumococcal infection. Utilising murine invasive pneumococcal disease (IPD) models, here we report that infection during the murine active phase (zeitgeber time 15; 15h after start of light cycle, 3h after start of dark cycle) resulted in significantly faster onset of septicaemia compared to rest phase (zeitgeber time 3; 3h after start of light cycle) infection. This correlated with significantly higher pneumococcal burden within the spleen of active phase-infected mice at early time points compared to rest phase-infected mice. Whole-section confocal microscopy analysis of these spleens revealed that the number of pneumococci is significantly higher exclusively within marginal zone metallophilic macrophages (MMMs) known to allow intracellular pneumococcal replication as a prerequisite step to the onset of septicaemia. Pneumococcal clusters within MMMs were more abundant and increased in size over time in active phase-infected mice compared to those in rest phase-infected mice which decreased in size and were present in a lower percentage of MMMs. This phenomenon preceded significantly higher levels of bacteraemia alongside serum IL-6 and TNF-α concentrations in active phase-infected mice following re-seeding of pneumococci into the blood. These data greatly advance our fundamental knowledge of pneumococcal infection by linking susceptibility to invasive pneumococcal infection to variation in the propensity of MMMs to allow persistence and replication of phagocytosed bacteria. These findings also outline a somewhat rare scenario whereby the active phase of an organism's circadian cycle plays a seemingly counterproductive role in the control of invasive infection.
Topics: Animals; Macrophages; Mice; Phagocytosis; Pneumococcal Infections; Sepsis; Streptococcus pneumoniae
PubMed: 35720383
DOI: 10.3389/fimmu.2022.907461 -
Clinical Infectious Diseases : An... Apr 2020Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the...
BACKGROUND
Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years.
METHODS
There were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012-December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE).
RESULTS
Comparing 2014 with 2016-2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6-21.8) for all pneumococci and 39.2% (95% CI 26.7-46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7-33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4-35.8) by 2018, with a decrease of 36.3% (95% CI 23.8-46.9) for VT IPD and an increase of 101.4% (95% CI 62.0-145.4) for non-VT IPD.
CONCLUSIONS
Following PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates.
Topics: Asian People; Cambodia; Child; Child, Preschool; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Vaccines, Conjugate
PubMed: 31175819
DOI: 10.1093/cid/ciz481