Valent Conjugate Vaccine Research Articles

Pneumococcal vaccination

Pneumokokken sind der häufigste bakterielle Erreger der ambulant erworbenen Pneumonie und gehören weltweit zu den häufigsten impfpräventablen Todesursachen. Es gibt einen Polysaccharidimpfstoff, der die Kapselpolysaccharide von 23 der über 90 bekannten Serotypen enthält, einen guten Schutz vor invasiven Pneumokokkeninfektionen vermittelt, aber T‑Zellen nicht stimuliert und damit kein immunologisches Gedächtnis hinterlässt. Bei Immunsupprimierten hat er eine eingeschränkte Wirksamkeit. Zunächst für Kleinkinder und später auch für Erwachsene wurde ein 13-valenter Konjugatimpfstoff zugelassen, der weniger Serotypen erfasst, aber ein immunologisches Gedächtnis hinterlässt und eine mukosale Immunität, d. h. die Eradikation gesunder Pneumokokkenträger und damit Herdenprotektionseffekte, vermittelt. Die STIKO empfiehlt derzeit bei verschiedenen Komorbiditäten sowie als Standardimpfung ab 60 Jahre die Indikationsimpfung mit PPV23, ggf. mit Wiederholungsimpfung nach frühestens 6 Jahren. Patienten mit Immunsuppression, chronischem Nierenversagen oder chronischer Leberinsuffizienz sollten wegen der eingeschränkten Wirksamkeit von PPV23 sowie einem hohen Risiko für Infektionen eine sequenzielle Impfung (zuerst PCV13, gefolgt von PPV23 nach 6 bis 12 Monaten) erhalten.

A Population-Based Descriptive Atlas of Invasive Pneumococcal Strains Recovered Within the U.S. During 2015-2016.

Invasive pneumococcal disease (IPD) has greatly decreased since implementation in the U.S. of the 7 valent conjugate vaccine (PCV7) in 2000 and 13 valent conjugate vaccine (PCV13) in 2010. We used whole genome sequencing (WGS) to predict phenotypic traits (serotypes, antimicrobial phenotypes, and pilus determinants) and determine multilocus genotypes from 5334 isolates (~90% of cases) recovered during 2015–2016 through Active Bacterial Core surveillance. We identified 44 serotypes; 26 accounted for 98% of the isolates. PCV13 serotypes (inclusive of serotype 6C) accounted for 1503 (28.2%) isolates, with serotype 3 most common (657/5334, 12.3%), while serotypes 1 and 5 were undetected. Of 305 isolates from children <5 yrs, 60 (19.7%) were of PCV13 serotypes 19A, 19F, 3, 6B, and 23F (58/60 were 19A, 19F, or 3). We quantitated MLST-based lineages first detected during the post-PCV era (since 2002) that potentially arose through serotype-switching. The 7 predominant emergent post-PCV strain complexes included 23B/CC338, 15BC/CC3280, 19A/CC244, 4/CC439, 15A/CC156, 35B/CC156, and 15BC/CC156. These strains accounted for 332 isolates (6.2% of total) and were more frequently observed in children <5 yrs (17.7%; 54/305). Fifty-seven categories of recently emerged (in the post PCV7 period) putative serotype-switch variants were identified, accounting for 402 isolates. Many of these putative switch variants represented newly emerged resistant strains. Penicillin-nonsusceptibility (MICs > 0.12 μg/ml) was found among 22.4% (1193/5334) isolates, with higher penicillin MICs (2–8 μg/ml) found in 8.0% (425/5334) of isolates that were primarily (372/425, 87.5%) serotypes 35B and 19A. Most (792/1193, 66.4%) penicillin-nonsusceptible isolates were macrolide-resistant, 410 (34.4%) of which were erm gene positive and clindamycin-resistant. The proportion of macrolide-resistant isolates increased with increasing penicillin MICs; even isolates with reduced penicillin susceptibility (MIC = 0.06 μg/ml) were much more likely to be macrolide-resistant than basally penicillin-susceptible isolates (MIC < 0.03 μg/ml). The contribution of recombination to strain diversification was assessed through quantitating 35B/CC558-specific bioinformatic pipeline features among non-CC558 CCs and determining the sizes of gene replacements. Although IPD has decreased greatly and stabilized in the post-PCV13 era, the species continually generates recombinants that adapt to selective pressures exerted by vaccines and antimicrobials. These data serve as a baseline for monitoring future changes within each invasive serotype.

The increasing incidence of empyema

The aim of this review is to highlight recent changes concerning the incidence of empyema. In this article we have focused on community-acquired empyema The incidence of empyema seems to have been increasing both in children and adults worldwide in the past decades, mainly in healthy young adults and in older patients. The bacteriology of pleural infection is changing as well. In children, the most common microorganism that causes empyema continues to be Streptococcus pneumoniae. Interestingly, the widespread use of the seven valent conjugate vaccine has produced a replacement phenomenon with the emergence of some pneumococcal serotypes such as serotypes 1, 3 and 19A, which have a higher propensity to cause empyema. Moreover increases in the incidence of empyema due to Staphylococcus aureus have also been observed. In adults, increases in the rate of empyema due to Streptococcus milleri group and S. aureus have been reported. Continued surveillance in the epidemiology of empyema is needed. Progress in new strategies of prevention, such as a new generation of conjugate pneumococcal vaccines and protein-based vaccines, could become an important step in the control of this important complication.

Pneumococcal infections and adult with risk factors

Streptococcus pneumoniae is an important bacterium in humans, and is a cause of upper and lower respiratory tract infections, meningitis, bacteremia, and/or invasive infections. An analysis of literature allows identifying the main risk factors; spleen dysfunctions, sickle cell anemia, alcohol abuse, chronic liver disease, cirrhosis, ischemic cardiac diseases, congestive cardiac failure, diabetes mellitus, obesity, chronic lung disease, immunodeficient patients including HIV infection, and old age. S. pneumoniae infections are more frequent and more severe in these patients. The pathophysiological mechanisms involved may be associated. These populations at risk should receive anti-pneumococcal vaccination. The availability of a 13 valent conjugate vaccine for adult opens new perspectives, but its clinical effectiveness needs to be proved for these patients at risk.

The UK-ESPE study: paediatric empyema in the UK

<h3>Aims</h3> The incidence of paediatric empyema has been rising in the UK. The UK-ESPE study aims to monitor the changing epidemiology of paediatric empyema and to compare empyema management across the UK. <h3>Methods</h3> Demographic, clinical and microbiological data on children with empyema undergoing pleural drainage were obtained from 19 paediatric respiratory centres from September 2006 until March 2011. Culture negative samples of pleural fluid were investigated using pneumococcal PCR. Pneumococcal PCR positive samples then underwent non-culture serotyping using an assay capable of detecting 14 serotypes/groups. Robust multivariate survival models were used to analyse length of stay (LOS). Chi-squared, Kruskal-Wallis and Fisher9s test were used for other analyses. <h3>Results</h3> Data on 635 children were obtained (56% male, median age 4.3 years). Where a microbiological cause was identified (n=287), Streptococcus pneumoniae accounted for 68%, Streptococcus pyogenes 14% and Staphylococcus aureus 4%. A pneumococcal serotype was detected in 125 patients; of these serotype 1 accounted for 46% and other prominent serotypes were 3 (22%), 7 (12%) and 19A (9%). Serotypes covered by the 7 valent conjugate vaccine (PCV-7) accounted for 48% of serotypes detected in 2006/07 but had disappeared by 2010/11. Non-PCV-7 serotypes increased over the same period. When comparing severity between serotypes, 19A was associated with severe disease and the only reported death. Median tertiary LOS was 8 days (range 3-33) and median total hospital stay (THS) 11 days (range 5-43). Surgical methods (open thoracotomy or video-assisted thoracoscopy) were associated with a decrease in tertiary LOS of 41% (95% Confidence intervals 7-88%, p=0.015) and THS of 43% (95% CI 7-92%, p=0.015) when compared to non-surgical methods (thoracocentesis +/- fibrinolysis). This effect did not achieve significance when each treatment group was analysed separately. Antibiotic choice in the tertiary centre did not significantly change either LOS measure. <h3>Conclusions</h3> Pneumococcus was the most commonly identified cause of paediatric empyema in the UK. The incidence of causative serotypes has evolved over time. Continuing surveillance is required to monitor changes following the introduction of the 13 valent vaccine in 2010. Primary surgical strategies were associated with reduced hospital stay in this cohort but this needs further investigation.

Immunisation of immunocompromised children against pneumococcus: which vaccine should now be used?: Abstract G164 Table 1

Although efficacy has never been demonstrated in children, 23-valent pneumococcal vaccine (PPV23) consisting of multiple unconjugated capsular polysaccharides has long been recommended for many children in high risk groups. Even since licensure of lower valency conjugated vaccines for which efficacy data are strong, PPV23 has continued to be recommended as part of a combined schedule and for children aged &gt;5 years. Children with chronic renal diseases are representative of broader high risk groups having susceptibility both related to primary disease and immunosuppressive treatment. The authors immunised PCV7-naïve children with seven valent conjugate vaccine (PCV7) and 6 m later with a test dose (0.1 ml) of 23valent polysaccharide vaccine (challenge). Serum was collected immediately before (V1 and V3) and 28–42 days after (V2 and V4) each vaccine dose and assayed (Luminex bead) for IgG antibody to PCV7 serotypes (ST). 75 children (51 male) aged 2.6–18.7 years (mean 11.5) were enrolled in three UK centres. 42 were post-renal transplant and 19 had chronic renal failure, of whom eight were on renal replacement therapy and two were awaiting transplant. Two had glomerulonephritis with low C3 and/or C4 and 14 had nephrotic syndrome that was steroid resistant and/or frequently relapsing. Geometric mean concentrations (n=55, μg/ml) at the four study visits (V) are shown in the table. Serum antibody responses to PCV7 showed mean 14.1-fold rises (range 5.8–19.1 for the seven serotypes). 75% (ST4) to 88% (STs 18C and 23F) achieved serum concentrations ≥0.35 μg/ml. After falling to mean 0.5 of post immunisation, a mean twofold titre rise (range 1.5–2.4) occurred after challenge, suggesting immunological memory. Children (n=10) who had received PPV23 prior to the study had much lower responses to PCV7 (p=0.01) suggesting hyporesponsiveness but had similar fold-rises (p=0.52) on PPV23 challenge. PCV7 was highly immunogenic in these immunocompromised children. These results confirm that, after inducing short-lived antibody responses, PPV23 induces hyporesponsiveness to pneumococcal antigens. With the availability of 10- and 13-valent conjugate vaccines, in the absence of evidence of benefit and in the presence of evidence of potential harm, consideration should now be given to cessation of use of PPV23 in childhood.

Serotypes and antimicrobial susceptibilities of invasive Streptococcus pneumoniae pre- and post-seven valent pneumococcal conjugate vaccine introduction in Alberta, Canada, 2000–2006

Alberta, Canada introduced the Streptococcus pneumoniae seven valent conjugate vaccine (PCV7) program for children less than 2 years of age in September 2002. We determined the rates of invasive pneumococcal disease in Alberta, Canada 2 years pre- and 4 years post-PCV7 introduction (2000–2006) as well as the rates of antibiotic resistance and serotype distribution in this same time period. Overall, PCV7 serotypes decreased 61% from 2000 to 2006. The greatest decrease in incidence of invasive pneumococcal disease occurred in children less than 2 years of age declining from a high of 96.7/100,000 (2000) to 25.8/100,000 (2006) ( P < 0.0001). Non-susceptibility of S. pneumoniae isolates to penicillin dropped significantly from 14% in 2000 to 4.6% in 2006 ( P < 0.0001). Non-susceptible erythromycin isolates also decreased from 8.8% (2000) to 5.8% (2006) ( P = 0.13). The introduction of PCV7 in Alberta, Canada has decreased the incidence of invasive pneumococcal disease in Alberta as well as resulting in a decrease in antibiotic resistance over this same time frame, principally for penicillin resistance.

Changes in treatment strategies for acute otitis media after full implementation of the pneumococcal seven valent conjugate vaccine

Administration of the pneumococcal seven valent conjugate vaccine (PCV-7) results in significant reductions in the incidence of invasive pneumococcal disease and nasopharyngeal colonization rates; however, the reduction in the overall incidence of acute otitis media (AOM) is minimal. Despite an ongoing shortage of PCV-7 in the United States, during which children are receiving fewer doses at longer intervals than the recommended dosing schedule, the incidence of invasive pneumococcal disease in young children has continued to decrease. The purpose of this article is to review why the reported effect of PCV-7 on AOM infection rates does not match the reduction in invasive pneumococcal disease or the reduction in nasopharyngeal carriage of Streptococcus pneumoniae. The potential effect of a fully implemented PCV-7 schedule on AOM infections is calculated based on serotype-specific AOM reduction rates observed in clinical studies. Clinical success rates of various antimicrobials used in the treatment of AOM in children fully immunized with PCV-7 also are calculated based on projected PCV-7-induced changes in pathogen profiles and documented antimicrobial resistance rates. Questions regarding potential serotype substitution in children with AOM but not invasive pneumococcal disease, the increased incidence of infection with Haemophilus influenzae in children immunized with PCV-7 and the possibility of herd immunity also will be addressed. Although the majority of penicillin-nonsusceptible S. pneumoniae are included in PCV-7, AOM caused by these strains will not completely disappear, especially in children 24 months of age and younger. Consequently, clinicians must continue to consider penicillin-nonsusceptible pneumococci when prescribing antimicrobials for AOM.