Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them.
Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating.
Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017.
The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.

Background: Streptococcus pneumoniae infection among adults, especially in adults over 60 years old in China results in a large number of hospitalizations and a substantial financial burden. This study assessed the vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases among the elderly aged 60 years or older in Shanghai, China. Methods: We conducted a test-negative case-control study among the elderly aged 60 years or older who sought care at hospitals in 13 districts of Shanghai from September 14, 2013 to August 31, 2019. A case was defined as pneumococcal disease and testing positive for Streptococcus pneumoniae. Controls had symptoms congruent with pneumococcal disease but were negative for Streptococcus pneumoniae. We conducted 1:2 matching by gender, age, hospital and admission date. Vaccination status was verified from the immunization system database. VE was calculated with conditional logistic regression according to the formula (1-OR) ×100%. Results: Overall, 603 adults aged 60 years or older with pneumococcal disease and positive for Streptococcus pneumoniae were included as cases, and 19.6% (118 persons) had a recorded PPV23 vaccination. The controls included 1,206 adults, whose vaccination rate was 23.8% (287 persons). The VE against pneumococcal diseases among the whole population was 24% (95% CI: 2%, 40%) and among women 44% (95% CI: 6%, 67%). After adjusting for multiple variables, the effectiveness of PPV23 against pneumococcal diseases was still statistically significant with VE for all of 25% (95% CI: 3%, 42%) and VE for women of 49% (95% CI: 11%, 71%). Conclusion: PPV23 was effective against pneumococcal diseases in adults aged 60 years or older in Shanghai, China. Its relatively high effectiveness among women warrants this group to be particularly targeted for vaccination, with further research on why vaccination effectiveness is less among men.

BACKGROUND: Invasive pneumococcal disease (IPD) in people ≥60 years old is on the rise in Germany. There has been a recommendation for pneumococcal vaccination in this age group since 1998.
METHODS: We determined the vaccination status of people ≥60 years old with IPD in Germany. We assessed vaccine effectiveness (VE) of the recommended 23-valent polysaccharide vaccine (PPV23) against IPD using the indirect cohort method.
RESULTS: The rate of pneumococcal vaccination in older adults with IPD is low, 26%, with only 16% of people receiving a pneumococcal vaccine within five years of the IPD episode. Age- and gender- adjusted vaccine effectiveness (VE) for PPV23 was 37% (95% confidence interval 12% - 55%). For people vaccinated with PPV23 less than two years prior to IPD, VE was -20% (-131% - 34%), between two and four years prior to IPD, VE was 56% (20% - 76%), and 47% (17% - 63%) for those vaccinated ≥5 five years ago. Excluding serotype 3, overall VE for the remaining serotypes in PPV23 was 63% (49% - 74%). For people receiving PPV23 within the past two years, VE against all serotypes except 3 was 49% (12% - 71%); for people vaccinated between two and four years prior to IPD 66% (37% - 82%); for those vaccinated ≥five years ago, 69% (50% - 81%). VE of PPV23 against serotype 3 IPD only was -110% (-198% - -47%).
CONCLUSIONS: To reduce IPD in older adults in Germany, we must increase the rate of pneumococcal vaccine uptake. For 22/23 serotypes, PPV23 was effective. Serotype 3 remains a major problem.
BACKGROUND: This work was supported by an investigator-initiated research grant from Pfizer.

This study examines the relationship of pneumococcal vaccination rates, influenza, measles-mumps-rubella (MMR) diphtheria-tetanus-pertussis vaccinations (DTP), polio, Haemophilus influenzae type B (Hib), and Bacillus Calmette-Guerin (tuberculosis) vaccination rates to COVID-19 case and death rates for 51 nations that have high rates of COVID-19 testing and for which nearly complete childhood, at-risk adult and elderly pneumococcal vaccination data were available. The study is unique in a large number of nations examined, the range of vaccine controls, in testing effects of combinations of vaccinations, and in examining the relationship of COVID-19 and vaccination rates to invasive pneumococcal disease (IPD). Analysis of Italian regions and the states of the United States were also performed. Significant positive correlations were found between IPD (but not lower respiratory infections) and COVID-19 rates, while significant negative correlations were found between pneumococcal vaccination and COVID-19 rates. Influenza and MMR vaccination rates were negatively correlated with lower respiratory infection (LRI) rates and may synergize with pneumococcal vaccination rates to protect against COVID-19. Pneumococcal and influenza vaccination rates were independent of other vaccination rates. These results suggest that endemic rates of bacterial pneumonias, for which pneumococci are a sentinel, may set regional and national susceptibility to severe COVID-19 disease and death.

Infections with the pathogen, Streptococcus pneumoniae, are a common cause of morbidity and mortality worldwide. It particularly affects those at the extremes of age and immunocompromised individuals. Preventing pneumococcal disease is paramount in at risk individuals, and pneumococcal vaccination should be offered. Here, we discuss the role of pneumococcal vaccination in specific groups of immunocompromised hosts.

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol.

BACKGROUND: Introduction of pneumococcal conjugate vaccines (PCVs) has reduced the disease caused by vaccine serotypes in children, providing herd protection to adults. However, the emergence of nonvaccine serotypes is of great concern worldwide.
METHODS: This study includes national laboratory data from invasive pneumococcal disease (IPD) cases that affected pediatric and adult populations during 2009-2019. The impact of implementing different vaccine strategies for immunocompetent adults by comparing Spanish regions that used the 13-valent PCV (PCV13) vs regions that used the 23-valent pneumococcal polysaccharide vaccine (PPV23) was also analyzed for 2017-2019.
RESULTS: The overall reductions in IPD cases by PCV13 serotypes in children and adults were 88% and 59%, respectively, during 2009-2019, with a constant increase in serotype 8 in adults since 2015. IPD cases by additional serotypes covered by PPV23 increased from 20% in 2009 to 52% in 2019. In children, serotype 24F was the most frequent in 2019, whereas serotypes 3 and 8 accounted for 36% of IPD cases in adults. Introduction of PCV13 or PPV23 in the adult calendar of certain Spanish regions reduced the IPD cases by PCV13 serotypes by up to 25% and 11%, respectively, showing a decrease of serotype 3 when PCV13 was used.
CONCLUSIONS: Use of PCV13 in children has affected the epidemiology, reducing the burden of IPD in children but also in adults by herd protection; however, the increase in serotype 8 in adults is worrisome. Vaccination with PCV13 in adults seems to control IPD cases by PCV13 serotypes including serotype 3.

BACKGROUND: Epidemiological studies suggest that there is a link between pneumococcal infection and adverse cardiovascular outcomes such as myocardial infarction. Multiple studies have evaluated the protective effect of the 23-valent polysaccharide pneumococcal vaccination (PPV23), but results have varied. Therefore, a meta-analysis was conducted to summarize available evidence on the impact of PPV23 on cardiovascular disease.
METHODS: A literature search from January 1946 to September 2019 was conducted across Embase, Medline and Cochrane. All studies were included that evaluated PPV23 compared with a control (placebo, no vaccine or another vaccine) for any cardiovascular events, including: myocardial infarction (MI), heart failure and cerebrovascular events. Risk ratios (RRs) were pooled using random effects models.
RESULTS: Eighteen studies were included, with a total of 716,108 participants. Vaccination with PPV23 was associated with decreased risk of any cardiovascular event (RR: 0.91; 95% CI: 0.84-0.99), and MI (RR: 0.88; 95% CI: 0.79-0.98) in all age groups, with a significant effect in those aged ≥65 years, but not in the younger age group. Similarly, PPV23 vaccine was associated with significant risk reduction in all-cause mortality in all ages (RR: 0.78; 95% CI: 0.68-0.88), specifically in those aged ≥65 years (RR: 0.71; 95% CI: 0.60-0.84). A significant risk reduction in cerebrovascular disease was not observed following pneumococcal vaccination.
CONCLUSIONS: Polysaccharide pneumococcal vaccination decreased the risk for some adverse cardiovascular events, specifically acute MI in the vaccinated population, particularly for those individuals aged ≥65 years. It would be highly beneficial to vaccinate the population who is at greater risk of cardiovascular diseases.

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BACKGROUND: Long-term comparative immunologic response to 13-valent pneumococcal conjugate vaccine (PCV13) versus 23-valent polysaccharide vaccine (PPV23) among HIV-infected adults has not yet been investigated.
METHODS: In this prospective pilot study, we quantified in HIV-positive adults serotype-specific IgG concentrations of the 12 pneumococcal serotypes shared by both vaccines 5 years after vaccination with two doses of PCV13 8 weeks apart (group 1) or one dose of PPV23 (group 2) and compared them with those assessed prior to vaccination (BL) and after 1 year (T1). Comparison of immunogenicity was based on geometric mean concentration (GMC), proportion of individuals with ≥ twofold increase from BL in specific antibody concentration against ≥ 2 serotypes and percentage of individuals with serotype-specific IgG ≥ 0.35 μg/ml, ≥ 1 μg/ml and ≥ individual serotype-specific correlates of protection.
RESULTS: We included 91 subjects (median CD4+ 650 cells/µl, > 90% with HIV-RNA < 50 copies/ml); patients in groups 1 (n = 42) and 2 (n = 49) were homogeneous for the main characteristics. GMCs were significantly higher in the PCV13 group than in the PPV23 group for serotype 19F (p = 0.003). Both vaccines revealed higher significant GMCs to most serotypes compared with BL, i.e., eight in group 1 vs. seven in group 2. With respect to T1, GMCs decreased significantly in the PCV13 group for eight vs. ten serotypes in the PPV23 group. More participants in the PCV13 group had ≥ 2 increase from BL in antibody levels to ≥ 2 serotypes compared with the PPV23 group (78.6% vs. 59.2%, p = 0.042). Overall, the percentage of subjects with serotype-specific IgG ≥ 0.35 μg/ml, ≥ 1 μg/ml and ≥ individual serotype-specific correlates of protection was similar between groups.
CONCLUSIONS: In this study with HIV-positive adults with a favorable viro-immunologic profile, both vaccines were shown to achieve a long-term durable serologic response. We found minor differences in immunogenicity between the two vaccines, which favored PCV13 over PPV23 5 years after immunization.
BACKGROUND: ClinicalTrials.gov identifier, NCT02123433.