A longitudinal analysis of pneumococcal vaccine serotypes in pneumonia patients in Germany

Recently, a 15-valent (PCV15) and a 20-valent pneumococcal conjugate vaccine (PCV20) have been licensed by the US Food and Drug Administration and are under evaluation by the European Medicines Agency.PCV15 contains all serotypes of the 13-valent conjugate vaccine (PCV13) plus serotype 22F and 33F and PCV20 includes PCV13 serotypes plus serotype 8, 10A, 11A, 12F, 15B, 22F and 33F. We investigated pneumococcal serotype distribution, secular trends and proportion of pneumonia caused by serotypes included in PCV13, PCV15, PCV20, and the 23-valent pneumococcal polysaccharide vaccine (PPV23) among adult patients with all-cause community-acquired pneumonia (CAP) between 2013 and 2019. We applied logistic mixed regression modelling to assess annual trends. Urine samples from adult patients with CAP treated in the community or hospital in Germany and included in the CAPNETZ study, a prospective multi-centre cohort study, were analysed by two serotype-specific multiplex urinary antigen detection assays (UAD1/UAD2) at Pfizer's Vaccines Research and Development Laboratory. UAD1 detects serotypes in PCV13, UAD2 detects additional serotypes in PCV20 plus serotypes 2, 9N, 17F and 20. Out of 1,831 patients screened, urine samples with a valid UAD test result were available for 1,343 patients (73.3%). Among those patients, 829 patients (61.7%) were male, 792 patients (59,0%) were aged 60 years and above, 1038 patients (77.3%) had at least one comorbidity and 1,204 patients (89.7%) were treated in the hospital. The overall proportion of vaccine-type pneumonia among all-cause CAP for PCV13, PCV15, PCV20 and PPV23 was 7.7% (n=103), 9.1% (n=122), 12.3% (n=165) and 13.3% (n=178). Over the entire observation period, we did not observe evidence for significant annual trends in pneumococcal vaccine serotype coverage against pneumonia in adults (PCV13: OR 0.94, 95% CI 0.83-1.05; PCV15: OR 0.93, 95% CI 0.84-1.03; PCV20: OR 0.95, 95% CI 0.86-1.04; PPV23: OR 0.99, 95% CI 0.90-1.08). In conclusion, our data show that i) the infant vaccination program of PCV13, which started in Germany 2010 did not result in a relevant and sustained decrease of PCV13 serotypes in pneumonia in adults and ii) that the gap in the coverage between PCV20 and PPV23 was small and did not increase over the entire observation time.

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Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands

European Respiratory Journal ◽

10.1183/13993003.00325-2015 ◽

2015 ◽

Vol 46 (5) ◽

pp. 1407-1416 ◽

Cited By ~ 56

Author(s):

Marie-Josée J. Mangen ◽

Mark H. Rozenbaum ◽

Susanne M. Huijts ◽

Cornelis H. van Werkhoven ◽

Douwe F. Postma ◽

...

Keyword(s):

Cost Effectiveness ◽

High Risk ◽

The Netherlands ◽

Conjugate Vaccine ◽

Pneumococcal Conjugate Vaccine ◽

Pneumococcal Disease ◽

Community Acquired Pneumonia ◽

Base Case ◽

Vaccination Strategies ◽

Vaccine Type

The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands.Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65–74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted.The ICER for base-case was €8650 per QALY (95% CI 5750–17 100). Vaccination of high-risk individuals aged 65–74 years was cost-saving and extension to medium-risk individuals aged 65–74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100.PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries.

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Post hoc analysis of the efficacy of the 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia in at-risk older adults

Vaccine ◽

10.1016/j.vaccine.2018.01.049 ◽

2018 ◽

Vol 36 (11) ◽

pp. 1477-1483 ◽

Cited By ~ 16

Author(s):

José A. Suaya ◽

Qin Jiang ◽

Daniel A. Scott ◽

William C. Gruber ◽

Chris Webber ◽

...

Keyword(s):

Older Adults ◽

At Risk ◽

Conjugate Vaccine ◽

Pneumococcal Conjugate Vaccine ◽

Community Acquired Pneumonia ◽

Post Hoc Analysis ◽

Vaccine Type ◽

Post Hoc

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244. Development, Qualification, and Clinical Validation of an Immunodiagnostic assay for the Detection of 11 Additional S. pneumoniae Serotype-Specific Polysaccharides in Human Urine

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.319 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S138-S138

Author(s):

Warren Vincent. Kalina ◽

Victor Souza ◽

Kangjian Wu ◽

Peter Giardina ◽

Andrew McKeen ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Pneumococcal Disease ◽

Invasive Disease ◽

Community Acquired Pneumonia ◽

Urine Samples ◽

Clinical Validation ◽

Assay Sensitivity ◽

Clinical Sensitivity ◽

Luminex Technology ◽

Urinary Antigen Detection

Abstract Background Identifying Streptococcus pneumoniae (Sp) serotypes by urinary antigen detection assay (UAD) is the most sensitive and specific way to evaluate the changing epidemiology of non-bacteremic community-acquired pneumonia (CAP) and efficacy of pneumococcal vaccines. We first described an UAD to detect the Sp serotypes 1,-3,-4,-5,-6A,-6B,-7F,-9V,-14,-18C,-19A,-19F,-23F covered by the 13-valent Sp conjugate vaccine PCV13. To assess the pneumococcal disease burden of additional serotypes, a UAD-2 assay was developed to diagnose 11 additional Sp serotypes (-2,-8,-9N,-10A,-11A,-12F,-15B,-17F,-20,-22F,-33F). Methods UAD-2 specificity was achieved by capturing highly purified pneumococcal polysaccharides with serotype-specific monoclonal antibodies using Luminex technology. Assay qualification assessed accuracy, precision, and sample linearity. Serotype positivity was based on cutoffs determined by non-parametric statistical evaluation of urine samples from individuals without pneumococcal disease. Clinical sensitivity and specificity of the positivity cutoffs were assessed in a clinical validation. Results The UAD-2 was shown to be specific and reproducible. Clinical validation using urine samples from invasive disease patients demonstrated assay sensitivity and specificity of 92.2% and 95.9%, respectively compared with a gold standard of isolating and typing (by Quellung) Sp bacteria from patient samples. Analysis of 11,087 CAP patients showed a UAD-2 and UAD-1 serotype prevalence of 4.33% and 4.60%, respectively (bacteremic and non-bacteremic CAP combined). Conclusion The qualified/clinically validated UAD-2 method has applicability in understanding the epidemiology of nonbacteremic Sp CAP as well as assessing vaccine efficacy of future pneumococcal conjugate vaccines. Disclosures All authors: No reported disclosures.

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Effectiveness of the 13-valent pneumococcal conjugate vaccine against adult pneumonia in Italy: a case–control study in a 2-year prospective cohort

BMJ Open ◽

10.1136/bmjopen-2017-019034 ◽

2018 ◽

Vol 8 (3) ◽

pp. e019034 ◽

Cited By ~ 9

Author(s):

Rosa Prato ◽

Francesca Fortunato ◽

Maria Giovanna Cappelli ◽

Maria Chironna ◽

Domenico Martinelli

Keyword(s):

Conjugate Vaccine ◽

Pneumococcal Conjugate Vaccine ◽

Prospective Cohort ◽

Case Control ◽

Community Acquired Pneumonia ◽

Vaccine Uptake ◽

Pneumococcal Strain ◽

Vaccine Type ◽

Matched Case ◽

Control Study

ObjectivesCurrent strategies to prevent adult pneumococcal disease have been recently reviewed in Italy. We did a postlicensure study to estimate the direct vaccine effectiveness (VE) of the 13-valent pneumococcal conjugate vaccine (PCV13) against adult pneumococcal community-acquired pneumonia (pCAP).Study designBetween 2013 and 2015, a 2-year prospective cohort study of adults with CAP was conducted in the Apulia region of Italy where the average vaccine uptake of PCV13 was 32% among adults ≥65 years. The test-negative design was used to estimate VE against all episodes of confirmed pCAP and vaccine-type (VT)-CAP. VE in a subgroup of patients managed in the community was also estimated using a matched case–control design. VE was calculated as one minus the OR times 100%.ResultsThe overall VE of PCV13 was 33.2% (95% CI −106.6% to 82%) against pCAP irrespective of serotype and 38.1% (95% CI −131.9% to 89%) against VT-CAP in the cohort of adults ≥65 years. The VE was 42.3% (95% CI −244.1% to 94.7%) against VT-CAP in the age group at higher vaccine uptake. For the subgroup of cases managed in the community, the overall VE against disease due to any pneumococcal strain was 88.1% (95% CI 4.2% to 98.5%) and 91.7% (95% CI 13.1% to 99.2%) when we controlled for underlying conditions.ConclusionsAlthough our results are non-significant, PCV13 promises to be effective against all confirmed pCAP already with modest levels of uptake in the population of adults ≥65 years of age. Larger studies are needed to confirm the direct vaccine benefits.

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Qualification and Clinical Validation of an Immunodiagnostic Assay for Detecting 11 Additional Streptococcus pneumoniae Serotype–specific Polysaccharides in Human Urine

Clinical Infectious Diseases ◽

10.1093/cid/ciaa158 ◽

2020 ◽

Author(s):

Warren V Kalina ◽

Victor Souza ◽

Kangjian Wu ◽

Peter Giardina ◽

Andrew McKeen ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Sensitivity And Specificity ◽

Pneumococcal Disease ◽

Community Acquired Pneumonia ◽

Urine Samples ◽

Clinical Validation ◽

Assay Sensitivity ◽

Luminex Technology ◽

Urinary Antigen Detection ◽

Nonparametric Statistical

Abstract Background Identifying Streptococcus pneumoniae serotypes by urinary antigen detection (UAD) assay is the most sensitive way to evaluate the epidemiology of nonbacteremic community-acquired pneumonia (CAP). We first described a UAD assay to detect the S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, covered by the licensed 13-valent S. pneumoniae conjugate vaccine. To assess the substantial remaining pneumococcal disease burden after introduction of several pneumococcal vaccines, a UAD-2 assay was developed to detect 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F) in individuals with radiographically confirmed CAP. Methods The specificity of the UAD-2 assay was achieved by capturing pneumococcal polysaccharides with serotype-specific monoclonal antibodies, using Luminex technology. Assay qualification was used to assess accuracy, precision, and sample linearity. Serotype positivity was based on cutoffs determined by nonparametric statistical evaluation of urine samples from individuals without pneumococcal disease. The sensitivity and specificity of the positivity cutoffs were assessed in a clinical validation, using urine samples obtained from a large study that measured the proportion of radiographically confirmed CAP caused by S. pneumoniae serotypes in hospitalized US adults. Results The UAD-2 assay was shown to be specific and reproducible. Clinical validation demonstrated assay sensitivity and specificity of 92.2% and 95.9% against a reference standard of bacteremic pneumonia. In addition, the UAD-2 assay identified a S. pneumoniae serotype in 3.72% of nonbacteremic CAP cases obtained from hospitalized US adults. When combined with bacteremic CAP cases, the proportion of pneumonias with a UAD-2 serotype was 4.33%. Conclusions The qualified/clinically validated UAD-2 method has applicability in understanding the epidemiology of nonbacteremic S. pneumoniae CAP and for assessing the efficacy of future pneumococcal conjugate vaccines that are under development.

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