Non-invasive Pneumococcal Pneumonia Research Articles

Incidence of Invasive and Noninvasive Pneumococcal Pneumonia Hospitalizations in People Aged ≥50 Years: Assessing Variability Across Denmark and Spain.

Determining pneumococcal pneumonia (PP) burden in the elderly population is challenging due to limited data on invasive PP (IPP) and, in particular, noninvasive PP (NIPP) incidence. Using retrospective cohorts of adults aged ≥50 years in Denmark (2 782 303) and the Valencia region, Spain (2 283 344), we found higher IPP hospitalization rates in Denmark than Valencia (18.3 vs 9/100 000 person-years [PY], respectively). Conversely, NIPP hospitalization rates were higher in Valencia (48.2 vs 7.2/100 000 PY). IPP and NIPP rates increased with age and comorbidities in both regions, with variations by sex and case characteristics (eg, complications, mortality). The burden of PP in adults is substantial, yet its true magnitude remains elusive. Discrepancies in clinical practices impede international comparisons; for instance, Valencia employed a higher frequency of urinary antigen tests compared to Denmark. Additionally, coding practices and prehospital antibiotic utilization may further influence these variations. These findings could guide policymakers and enhance the understanding of international disparities in disease burden assessments.

Adult non-invasive pneumococcal pneumonia in Portugal is dominated by serotype 3 and non-PCV13 serotypes 3-years after near universal PCV13 use in children.

Non-invasive pneumococcal pneumonia (NIPP) is possibly the most frequent infection by Streptococcus pneumoniae in adults. However, the herd effect of vaccinating children in adult NIPP (aNIPP) remains poorly characterized. We determined the serotype distribution and antimicrobial susceptibility of isolates causing aNIPP (>18 years) in 2016-2018 in Portugal; 3 years with near universal vaccination of children with the 13-valent conjugate vaccine (PCV13), following over a decade of significant PCV use in children in the private market. Among the 1,149 aNIPP isolates, the most frequent serotypes detected were: 3 (n = 168, 14.6%), 11A (n = 102, 8.9%), 19F (n = 70, 6.1%), 23A and 23B (n = 62, 5.4% each), 9N (n = 60, 5.2%), 8 and 29/35B (n = 43, 3.7% each); together accounting for 53% of all isolates. The serotype distribution causing aNIPP was stable in 2016-2018, with the serotypes included in PCV7 still being important causes of disease and serotype 3, a PCV13 serotype, remaining the leading cause of aNIPP. There was an increase in penicillin non-susceptibility from 17% in 2016 to 24% in 2018 (p = 0.018). Some PCV13 serotypes, such as 14, 19A and 19F were associated to resistance, which may have contributed to their persistence. The fact that close to 20% of aNIPP is caused by four non-vaccine serotypes (23A, 23B, 9N, and 29/35B) and that there were significant differences in serotype distribution relative to invasive disease, stress the importance of maintaining the surveillance of these infections. The lack of a continued herd effect from vaccinating children and the significant fraction of aNIPP potentially preventable by PCV13 (30%), PCV15 (34%), PCV20 (53%) and the 23-valent polysaccharide vaccine (61%) underscore the importance of considering the broader use of pneumococcal vaccines in adults.

Non-invasive pneumococcal pneumonia due to vaccine serotypes: A systematic review and meta-analysis.

SummaryBackgroundNon-invasive pneumococcal pneumonia causes significant morbidity and mortality in older adults. Understanding pneumococcal sero-epidemiology in adults ≥50 years is necessary to inform vaccination policies and the updating of pneumococcal vaccines.MethodsWe conducted a systematic review and random-effects meta-analysis to determine the proportion of community-acquired pneumonia (CAP) in people ≥50 years due to pneumococcus and the proportion caused by pneumococcal vaccine serotypes. We searched MEDLINE, EMBASE and PubMed from 1 January 1990 to 30 March 2021. Heterogeneity was explored by subgroup analysis according to a) patient group (stratified versus age) and depth of testing, b) detection/serotyping method, and c) continent. The protocol is registered with PROSPERO (CRD42020192002).FindingsTwenty-eight studies were included (34,216 patients). In the period 1–5 years after introduction of childhood PCV10/13 immunisation, 18% of CAP cases (95% CI 13–24%) were attributable to pneumococcus, with 49% (43–54%) of pneumococcal CAP due to PCV13 serotypes. The estimated proportion of pneumococcal CAP was highest in one study that used 24-valent serotype-specific urinary-antigen detection (ss-UAD)(30% [28–31%]), followed by studies based on diagnostic serology (28% [24–33%]), PCR (26% [15–37%]), ss-UAD14 (17% [13–22%]), and culture alone (14% [10–19%]). A higher estimate was observed in Europe (26% [21–30%] than North America (11% [9–12%](p<0·001). PCV13-serotype estimates were also influenced by serotyping methods.InterpretationNon-invasive pneumococcal CAP and vaccine-type pneumococcal CAP remains a burden in older adults despite widespread introduction of pneumococcal infant immunisation. Studies heavily reliant on ss-UADs restricted to vaccine-type serotypes may overestimate the proportion of potentially vaccine-preventable pneumococcal pneumonia. Sero-epidemiological data from low-income countries are lacking.

Estimation of the incidence of hospitalization for non-invasive pneumococcal pneumonia in the Norwegian population aged 50 years and older.

Abstract The purpose of this study was to estimate simple measures of the burden of non-invasive pneumococcal pneumonia (PnPn) hospitalisations in those aged 50 years and older (50+) in Norway. We conducted a retrospective register-based study and used discharge codes from the Norwegian Patient Register (NPR). We identified episodes of non-invasive PnPn in 2015 to 2016 and predicted its incidence from 2015 to 2019 based on the trend found in notified invasive pneumococcal disease cases. Overall, we identified 45–46 hospital episodes per 100 000 population of non-invasive PnPn in 2015 and 2016, each episode taking 6–8 days, and with increasing incidence with higher age. Among all identified PnPn episodes, 3 out of 4 were classified as non-invasive. We predicted that the monthly number of non-invasive PnPn episodes ranges from 39 [95% confidence interval (CI) 24–55] in August to 97 (95% CI 74–134) in December. No annual trend was identified. This study indicates that the burden of non-invasive PnPn hospitalisation has a substantial impact on the health and health care use of the 50+ population in Norway, despite the childhood immunisation programme. Many hospitalisations may be prevented through vaccination.

Non-Invasive Pneumococcal Pneumonia Due to Vaccine Serotypes: A Systematic Review and Meta-Analysis

Background: Non-invasive pneumococcal pneumonia causes significant morbidity and mortality in older adults globally. Understanding pneumococcal sero-epidemiology in adults ≥50 years is necessary to inform pneumococcal vaccination policies and direct the updating of pneumococcal vaccines. Methods: We conducted a systematic review and random-effects meta-analysis to determine the proportion of community-acquired pneumonia (CAP) in people ≥50 years due to pneumococcus and the proportion caused by current pneumococcal vaccine serotypes. Heterogeneity was explored by subgroup analysis according to a) patient group (stratified versus age) and depth of testing, b) detection/serotyping method, and c) continent. The protocol is registered with PROSPERO (CRN42020192002).Findings There were 28 included studies (34,216 patients). The estimated proportion of pneumococcal CAP was highest in studies that mainly used 24-valent serotype-specific urinary antigen detection (ss-UAD)(30% [95%CI 28-31%]), followed by serology (29% [26-32%]), PCR (21% [20-23%]), ss-UAD13 (17% [13-22%]), and culture alone (14% [10-19%]). Inter-continental heterogeneity was observed, with a higher pooled estimate in Europe (26% [21-30%, I2 =92%] than North America (11% [9-12%, I2 =87·2%](p<0·001). PCV13-serotype estimates were also influenced by serotyping methods. Interpretation: Non-invasive pneumococcal CAP, including disease due to current pneumococcal vaccine serotypes, remains a burden in adults aged ≥50 years, despite the introduction of pneumococcal infant immunisation in most countries. Studies heavily reliant on ss-UADs restricted to vaccine-type serotypes may overestimate the proportion of potentially vaccine-preventable pneumococcal pneumonia. Sero-epidemiological data from low-income countries are lacking. Funding LL is funded by the National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, UK. Declaration of Interest: Professor Lim reports grants from National Institute for Health Research (NIHR), grants from Pfizer, outside the submitted work. All other authors declare no competing interests.

1480. Incidence of Non-Invasive Pneumococcal Pneumonia in Children in the United States before and after Introduction Pneumococcal Conjugate Vaccines (PCV7 and PCV13) during 1998-2018

BackgroundPneumonia causes significant pediatric morbidity, mortality, and healthcare resource utilization. S. pneumoniae is a leading cause of bacterial pneumonia in children. Merck is developing V114, an investigational 15-valent PCV that contains PCV13 serotypes as well as 22F and 33F. To demonstrate the potential value of V114, it is important to estimate the remaining burden associated with pneumococcal pneumonia (PP). This study was to estimate incidence rates (IRs) of non-invasive PP before and after PCV7 and PCV13 introduction in children in the US.MethodsPP-related claims in children < 18 years were identified in the IBM MarketScan® Commercial database (1998-2018) using pneumococcal specific ICD9/10 codes. Claims with any invasive pneumococcal disease ICD9/10 codes were excluded. An episode could comprise one or more claims. Episodes with any inpatient stays were categorized as inpatient, and as outpatient otherwise. Age-stratified (< 2, 2-4, and 5-17 years) IRs were episodes per 100,000 patient-years (PYs) during the pre-PCV7 (1998-1999), early and late PCV7 (2001-2005, 2006-2009), and early and late PCV13 (2011-2013, 2014-2018) periods.ResultsInpatient and outpatient PP IRs decreased steadily in children < 2 years (146.8, 117.9, 102.0, 67.8, and 32.2 per 100,000 PYs for pre-PCV7, early and late PCV7, and early and late PCV13 periods, respectively; Figure 1). In children 2-4 years, IRs increased slightly from 88.6 to 90.0 per 100,000 PYs from the pre-PCV7 to early PCV7 period, then declined to 83.9 and 30.8 per 100,000 PYs in the late PCV7 and late PCV13 periods, respectively (Figure 2). In children 5-17 years, IRs declined from 35.3 to 34.2 per 100,000 PYs from the pre-PCV7 to early PCV7 period, stabilized at 34.1 per 100,000 PYs in the late PCV7 period, followed by a steeper decline to 12.5 per 100,000 PYs in the late PCV13 period (Figure 3). The majority of episodes were outpatient in all three age groups.Figure 1. Non-invasive pneumococcal pneumonia incidence in children <2 years, episodes per 100,000 patient-years (1998 - 2018) Figure 2. Non-invasive pneumococcal pneumonia incidence in children 2 - 4 years, episodes per 100,000 patient-years (1998 - 2018) Figure 3. Non-invasive pneumococcal pneumonia incidence in children 5 - 17 years, episodes per 100,000 patient-years (1998 - 2018) ConclusionIn children < 2 years, IRs of non-invasive PP decreased after introduction of PCV7 and PCV13. Following introduction of PCV 7 and PCV13, there remains a residual burden of non-invasive PP in children in the US. The impact of future PCVs on PP will depend on the proportion of PP caused by S. pneumoniae and vaccine-type serotypes.DisclosuresTianyan Hu, PhD, Merck (Employee, Shareholder) Yan Song, PhD, Merck (Consultant) Nicolae Done, PhD, Merck & Co., Inc. (Consultant) Qing liu, PhD, Merck (Consultant) James Signorovitch, PhD, Merck & Co., Inc. (Consultant) Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder)

Cost-effectiveness of continuing pneumococcal conjugate vaccination at age 65 in the context of indirect effects from the childhood immunization program

The findings and conclusions in this report are those of the authors and do not necessarily represent the official positon of the Centers for Disease Control and Prevention. BackgroundContinued indirect effects provided by the childhood pneumococcal conjugate vaccine (13-valent pneumococcal conjugate vaccine [PCV13]) program in the United States have decreased disease in the adult population, reducing the potential direct effects of vaccinating older adults. ObjectiveWe examined the incremental cost-effectiveness of continuing to recommend PCV13 in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) at age 65 compared to a strategy that only included a recommendation for PPSV23 at age 65. MethodsWe used a probabilistic model following a cohort of 65 year olds in 2019. We used vaccination coverage and disease incidence estimates for healthy adults and adults with chronic medical conditions. We incorporated continued indirect effects from the childhood PCV13 program on adult disease incidence. ResultsIn the base case scenario, continuing to recommend PCV13 at age 65 cost $561,682 per quality-adjusted life year (QALY) gained. In a scenario where PPSV23 provided modest protection against non-invasive pneumococcal pneumonia, costs increased to $2.3 million per QALY. These estimates are larger than our prior estimates for cost-effectiveness of this recommendation in the context of predicted indirect effects due to new data indicating PCV13 provided limited impact on serotype 3, the major cause of the remaining PCV13-type disease. Under our prior assumptions about PCV13 effectiveness against serotype 3 disease, the cost of continuing the recommendation is $207,607 per QALY. ConclusionIndirect effects from the childhood PCV13 program have dramatically increased the cost per QALY of continuing to recommend PCV13 at age 65 after only a few years.

A positive pneumococcal urinary antigen test promotes narrow spectrum antibiotic use in patients with non-invasive pneumococcal pneumonia

BackgroundWe compared changes in antibiotics in patients diagnosed with noninvasive pneumococcal pneumonia (NPP) by pneumoccocal urinary antigen tests or respiratory cultures. MethodsWe compared patients diagnosed by pneumococcal urinary antigen tests or respiratory cultures that grew Streptococcus pneumoniae. We assessed the time from sample receipt to final result and antibiotic regimens, including an Antibiotic Spectrum Index (ASI). ResultsSeventy-two cases of NPP were diagnosed by pneumococcal urinary antigen and 87 by respiratory cultures, with a median time from sample receipt to final result of 0.21 days (interquartile range (IQR) 0.17–1.17) and 3.21 days (IQR 3.17–4.21 days), respectively. Among 123 cases without antibiotic allergies, between days 0 and 2, the ASI decreased in 36% (18/50) of cases diagnosed by urinary antigen compared to 10% (7/73) of cases diagnosed by respiratory culture (P < 0.01). ConclusionsPositive pneumococcal urinary antigen tests lead to early deescalation of antibiotics more frequently than respiratory cultures.

Long-term Impact of Pneumococcal Conjugate Vaccines on Invasive Disease and Pneumonia Hospitalizations in Indigenous and Non-Indigenous Australians.

Universal pneumococcal conjugate vaccine (PCV) programs began in Indigenous Australian children in 2001 and all children in 2005, changing to 13-valent PCV (PCV13) in 2011. We used laboratory data for invasive pneumococcal disease (IPD) and coded hospitalizations for noninvasive pneumococcal community-acquired pneumonia (PnCAP) to evaluate long-term impact. Annual incidence (per 100 000 population) was calculated for age-specific total IPD, PCV13 non-7-valent PCV (PCV7) serotypes, and PnCAP by Indigenous status. Incidence in the pre-universal PCV7 (2002-2004), early PCV7 (2005-2007), pre-PCV13 (2008 to mid-2011), and post-PCV13 (mid-2011 to 2016) periods was used to calculate incidence rate ratios (IRRs). In the total population, all-age incidence of IPD declined from 11.8 pre-PCV7 to 7.1 post-PCV13 (IRR, 0.61 [95% confidence interval {CI}, .59-.63]) but for PnCAP declined among ages <1 year (IRR, 0.34 [95% CI, .25-.45]) and 1-4 years (IRR, 0.50 [95% CI, .43-.57]) but increased significantly among age ≥5 years (IRRs, 1.08-1.14). In Indigenous people, baseline PCV13 non-PCV7 IPD incidence was 3-fold higher, amplified by a serotype 1 epidemic in 2011. By 2015-2016, although incidence of IPD and PnCAP in children aged <5 years decreased by 38%, neither decreased in people aged ≥5 years. Fifteen years post-PCV and 5 years post-PCV13, direct and indirect impact on IPD and PnCAP differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.Fifteen years after pneumococcal conjugate vaccine (PCV) introduction and 5years post-PCV13, direct and indirect impact on invasive pneumococcal disease and pneumococcal community-acquired pneumonia differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.

1461. Non-Invasive Pneumococcal Pneumonia in the United States, 2013–2014

BackgroundSurveillance for pneumococcal pneumonia (PP) is challenging due to limitations of available diagnostic tests. Previous studies estimated PP from all-cause pneumonia or invasive pneumonia (i.e., positive S. pneumoniae sterile site culture). In 2014, pneumococcal conjugate vaccine (PCV13) was recommended for adults ≥65 years old. We established population-based surveillance for non-invasive pneumococcal pneumonia (NPP) to estimate disease burden and establish a baseline for PCV13 impact evaluation.MethodsWe defined a case as clinically or radiographically confirmed pneumonia, positive pneumococcal urine antigen test (UAT), and no evidence of invasive pneumococcal disease in a hospitalized adult ≥18 years old residing in our surveillance areas, which overlap with active bacterial core surveillance areas representing 17,000,000 adults across the United States. We estimated NPP incidence (cases/100,000 population) using US Census data and applying two adjustment factors: (1) the proportion of pneumonia tested by UAT in sampled facilities to account for the fact not all possible cases are tested and (2) the proportion of pneumonia seen at facilities offering UAT in the catchment area.ResultsIn 2013–2014, 1,854 patients met our case definition; median age was 65 years (range 18–102). On average, patients were diagnosed on hospital Day 1 (range −3 to 30 days) and hospitalized for 5 days (range <1–152). Adjusting the crude incidence of 6/100,000 (reported UAT cases) by factors 1 and 2, we estimated NPP incidence to be 99/100,000 population.Clinical Description of Patients with UAT Confirmed NPP (N 1,854) n (%)Age ≥65 years953(51)Radiographically confirmed pneumonia1,604(87)Intensive care unit admission653(35)Died119(6)Underlying medical condition1,752(95)Immunocompromising condition764(41)Smoke tobacco677(37)ConclusionOur population-based surveillance system allows us to estimate the incidence of laboratory confirmed NPP. Given imperfect UAT sensitivity, this is an underestimate. A more sensitive and serotype-specific UAT could provide improved detection and understanding of NPP. Nonetheless, NPP surveillance allows us to better understand populations at risk for NPP and establish a baseline to evaluate impact of PCV13 on NPP incidence among adults.Disclosures L. H. Harrison, Merck: sponsored symposium on pneumococcal vaccines, Speaker honorarium. W. Schaffner, Merck: Member, Data Safety Monitoring Board, Consulting fee; Pfizer: Member, Data Safety Monitoring Board, Consulting fee; Dynavax: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee; SutroVax: Consultant, Consulting fee; Shionogi: Consultant, Consulting fee.

1452. Non-invasive Pneumococcal Pneumonia in Adults in Portugal: Continued Decline of PCV13 Serotypes (2015–2017)

BackgroundIn 2015, PCV13 was introduced in the National Immunization Plan in Portugal for children, although it was not significantly used in adults. However, changes in the pneumococcal population causing non-invasive pneumococcal pneumonia (NIPP) in adults (≥18 years) can occur due to herd effects. To evaluate this, we monitored the serotypes and antimicrobial resistance of adult NIPP isolates in 2015–2017. Methods. A total of 1,142 isolates were recovered, serotyped by Quellung and tested for susceptibility to antimicrobials by disk diffusion or Etest.ResultsAmong the 1,142 isolates, 52 different serotypes were found and 59 isolates were nontypeable (5%). The most common were serotypes 3 (13%), 11A (8%), 19F, 9N and 23A (5% each), 23B, 16F and 6C (4% each). There were strong variations in the proportion of some serotypes, suggesting that factors other than vaccine pressure could also impact on serotype prevalence. Although a considerable number of isolates still expressed the additional serotypes included in PCV13 (addPCV13 = 200), the overall proportion of addPCV13 serotypes remained relatively stable in this time period. However, when comparing with the previous period (2012–2014), there was a significant decrease in the proportion of addPCV13 serotypes, from 22 to 17.7% (P = 0.007). Serotypes included in PCV7 (11%, n = 122) and the serotypes exclusively found in the 23-valent polysaccharide vaccine (30%, n = 339) did not change significantly in 2015–2017. Non-vaccine types were expressed by 42% of the isolates (n = 481) and their proportion was also stable throughout the study. Overall, resistance did not change relative to 2012–2014, with 22% erythromycin resistance and 18% penicillin nonsusceptibility.ConclusionAfter the introduction of PCV13 in the National Immunization Plan for children, a significant decrease in the proportion of PCV13 serotypes was noted in the adult population, although a considerable fraction of disease is still caused by vaccine serotypes. Moreover, nonvaccine serotypes are becoming important causes of NIPP, emphasizing the importance of continued surveillance studies.Disclosures M. Ramirez, Pfizer: Speaker’s Bureau, Speaker honorarium; GlaxoSmithKline: Consultant, Consulting fee; Merck Sharp and Dohme: Consultant, Consulting fee. J. Melo-Cristino, Pfizer: Grant Investigator and Speaker’s Bureau, Research grant and Speaker honorarium; Merck Sharp and Dohme.: Speaker’s Bureau, Speaker honorarium.

Conjugate vaccine serotypes persist as major causes of non-invasive pneumococcal pneumonia in Portugal despite declines in serotypes 3 and 19A (2012-2015).

Non-invasive pneumococcal pneumonia (NIPP) is a frequent cause of morbidity and mortality worldwide. The 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program of children living in Portugal in 2015. Until then, PCV7 (since late 2001) and PCV13 (since early 2010) were given through the private market. We determined the serotype distribution and antimicrobial susceptibility of isolates causing adult NIPP in 2012–2015 and compared the results with previously published data (2007–2011). There were 50 serotypes among the 1435 isolates. The most common were serotypes: 3 (14%), 11A (8%), 19F (6%), 23A (5%), 6C (5%), 19A (4%), 23B (4%), 9N (4%) and non-typable isolates (4%). When considering data since the availability of PCV13 for children in the private market, the proportion of PCV13 serotypes declined from 44.0% in 2010 to 29.7% in 2015 (p < 0.001), mainly due to early decreases in the proportions of serotypes 3 and 19A. In contrast, during the same period, PCV7 serotypes (11.9% in 2012–2015) and the serotypes exclusive of the 23-valent polysaccharide vaccine (26.0% in 2012–2015), remained relatively stable, while non-vaccine types increased from 27.0% in 2010 to 41.9% in 2015 (p<0.001). According to the Clinical and Laboratory Standards Institute (CLSI) breakpoints, penicillin non-susceptible and erythromycin resistant isolates accounted for 1% and 21.7%, respectively, of the isolates recovered in 2012–2015, with no significant changes seen since 2007. Comparison of NIPP serotypes with contemporary invasive disease serotypes identified associations of 19 serotypes with either disease presentation. The introduction of PCV13 in the national immunization program for children from 2015 onwards may lead to reductions in the proportion of NIPP due to vaccine serotypes but continued NIPP surveillance is essential due to a different serotype distribution from invasive disease.

Retrospective cost-effectiveness of the 23-valent pneumococcal polysaccharide vaccination program in Australia

BackgroundThe Australian infant pneumococcal vaccination program was funded in 2005 using the 7-valent pneumococcal conjugate vaccine (PCV7) and the 13-valent conjugate vaccine (PCV13) in 2011. The PCV7 and PCV13 programs resulted in herd immunity effects across all age-groups, including older adults. Coincident with the introduction of the PCV7 program in 2005, 23-valent pneumococcal polysaccharide vaccine (PPV23) was funded for all Australian adults aged over 65 years. MethodsA multi-cohort Markov model with a cycle length of one year was developed to retrospectively evaluate the cost-effectiveness of the PPV23 immunisation program from 2005 to 2015. The analysis was performed from the healthcare system perspective with costs and quality-adjusted life years discounted at 5% annually. The incremental cost-effectiveness ratio (ICER) for PPV23 doses provided from 2005 to 2015 was calculated separately for each year when compared to no vaccination. Parameter uncertainty was explored using deterministic and probabilistic sensitivity analysis. ResultsIt was estimated that PPV23 doses given out over the 11-year period from 2005 to 2015 prevented 771 hospitalisations and 99 deaths from invasive pneumococcal disease (IPD). However, the estimated IPD cases and deaths prevented by PPV23 declined by more than 50% over this period (e.g. from 12.9 deaths for doses given out in 2005 to 6.1 in 2015), likely driven by herd effects from infant PCV programs. The estimated ICER over the period 2005 to 2015 was approximately A$224,000/QALY gained compared to no vaccination. When examined per year, the ICER for each individual year worsened from $140,000/QALY in 2005 to $238,000/QALY in 2011 to $286,000/QALY in 2015. ConclusionThe cost-effectiveness of the PPV23 program in older Australians was estimated to have worsened over time. It is unlikely to have been cost-effective, unless PPV23 provided protection against non-invasive pneumococcal pneumonia and/or a low vaccine price was negotiated. A key policy priority should be to review of the future use of PPV23 in Australia, which is likely to be more cost-effective in certain high-risk groups.

Impact of 13-valent pneumococcal conjugate vaccination introduction in children on pneumonia hospitalizations among adults aged 65 or more in Portugal

Background The incidence of pneumonia and pneumonia related hospitalizations still increasing in different European and American Countries. However, in western countries this increase is driven by secondary diagnoses, recurrent pneumonia episodes in elderly and among those with comorbidities. Given the high frequency of Streptococcus pneumoniae among all pneumonia, it is reasonable to expect that a wide use of pneumococcal vaccines would reduce the burden of pneumonia in the elderly due to a direct and indirect effect. In Portugal, pneumococcal vaccines are available since 1996: pneumococcal polysaccharide vaccine (PPSV23) in 1996; heptavalent conjugated pneumococcal vaccines (PCV7) in 2001; PCV10 in April 2009 and PCV13 in January 2010. PPSV23 and PCV13 are widely recommended for risk groups and elderly. PCV7 serotypes reduced from 31% in 1999–2003 to 11% in 2009–2011 in non-invasive pneumococcal pneumonia (PP), but no decreasing trend was observed for PCV13 and PPSV23 serotypes until 2011. Trends in pneumococcal pneumonia after PCV13 introduction are not known in Portugal. Thus, this study aims to assess population level impact of infant PCV13 introduction on burden of pneumonia among adults aged 65 or more in Portugal through comparison of trends in PP hospitalization rates before and after PCV13 introduction. Methods We performed an ecological study using hospital discharge registry data. Pneumococcal Pneumonia was defined as having a principal diagnosis coded as 481 (International Classification for Diseases - 9th version). To assess trends in hospitalization rates before (July 2003–June 2009) and after (July 2010–June 2016) PCV13 introduction interrupted time series analysis was used. Annual average change of pneumonia hospitalization rates was estimated by Poisson regression models adjusted for seasonality and allowing for over-depression. PP hospitalization rates estimated after immunization program introduction were compared with those projected based on pre-vaccination period trend. Bacterial pneumonia caused by pathogens other than S. pneumoniae was used for sensitivity analysis. Results At baseline, the overall PP hospitalization rate was 10.2/104. The rates varied markedly by age group, the highest baseline rates were observed among those aged 85 years or more, 38.6/104 in males and 23.4/104 in females. Statistically significant decline in overall PP hospitalization rate was verified during pre-PCV13 period, the rate decreased on average by 4.6% per year (IRR = 0.954; 95% CI: 0.943 to 0.964). The decreasing trend continued after PCV13 introduction, with more pronounced decline of 12.8% (IRR = 0.872; 95% CI: 0.858 to 0.886) per year. The decrease in PP hospitalizations was significant in all subgroups, the largest decline in both pre-PCV13 (5.8% per year) and PCV13 (14.3% per year) periods was verified for males aged 75–84. Smaller decrease was observed for Bacterial pneumonia after 2010 (IRR = 0.915; 95% CI: 0.913 to 0.937). Conclusions Using population-based nationwide registry data, we found considerable decrease in hospitalizations’ rates for PP in adults aged 65 or more years following infant PCV13 introduction in Portugal. Given the ecological design, we cannot exclude the effect of factors other than vaccination, namely changes in diagnosis and coding practices or the reduction of other pneumonia risk factors as tobacco, since decreasing trend was also observed for bacterial pneumonia after 2010.

Economic evaluation of pneumococcal vaccines for adults aged over 50 years in Belgium

ABSTRACTStreptococcus pneumoniae causes a high disease burden including pneumonia, meningitis and septicemia. Both a polysaccharide vaccine targeting 23 serotypes (PPV23) and a 13-valent conjugate vaccine (PCV13) are indicated for persons aged over 50 years. We developed and parameterized a static multi-cohort model to estimate the incremental cost-effectiveness and budget-impact of these vaccines at different uptake levels. Using three different vaccine efficacy scenarios regarding non-invasive pneumococcal pneumonia and extensive uni- and multivariate sensitivity analyses, we found a strong preference for PPV23 over PCV13 in all age groups at willingness to pay levels below €300 000 per quality adjusted life year (QALY). PPV23 vaccination would cost on average about €83 000, €60 000 and €52 000 per QALY gained in 50–64, 65–74 and 75–84 year olds, whereas for PCV13 this is about €171 000, €201 000 and €338 000, respectively. Strategies combining PPV23 and PCV13 vaccines were most effective but generally less cost-effective. When assuming a combination of increased duration of PCV13 protection, increased disease burden preventable by PCV13 and a 75% reduction of the PCV13 price, PCV13 could become more attractive in <75 year olds, but would remain less attractive than PPV23 from age 75 years onwards. These observations are independent of the assumption that PPV23 has 0% efficacy against non-invasive pneumococcal pneumonia. Pneumococcal vaccination would be most cost-effective in Belgium, when achieving high uptake with PPV23 in 75–84 year olds, as well as by negotiating a lower market-conform PPV23 price to improve uptake and cost-effectiveness.

Noninvasive Pneumococcal Pneumonia in Adults in Portugal (2012–2015): Resilience of Vaccine Serotypes and Emergence of Non-vaccine Serotypes

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) is available in Portugal through the private sector for children since 2010. In 2015 it was included in the national immunization program for children. With the aim of evaluating a possible herd effect, we monitored the serotypes and antimicrobial resistance of isolates (2012–2015) causing noninvasive pneumococcal pneumonia (NIPP) in adults (≥18 yrs).Methods1435 adult NIPP isolates were recovered, serotyped by the Quellung reaction and tested for susceptibility to antimicrobials by disk diffusion or Etest.ResultsThere were 50 different serotypes among the 1435 isolates. The most common were serotypes 3 (14%), 11A (8%), 19F (6%), 23A (5%), 6C (5%), 19A (4%), 23B (4%) and 9N (4%). Non-typable isolates accounted for 4% of the collection. The overall proportion of PCV13 serotypes declined from 44% in 2010 to 30% in 2015 (P < 0.001) although it remained relatively stable in 2012–2015. Several serotypes exhibited strong fluctuations in 2007–2015, suggesting that adult NIPP was under the influence of both vaccine-related and non-vaccine-related pressures. PCV7 serotypes (12% in 2012–2015) and the serotypes exclusively found in the 23-valent polysaccharide vaccine (26% in 2012–2015) did not change significantly in 2007–2015, while non-vaccine types increased in proportion (from 27% in 2010 to 42% in 2015, P < 0.001). Penicillin non-susceptibility and erythromycin resistance was found in 18% and 22% of the isolates recovered in 2012–2015, with no significant changes seen since 2007.ConclusionWhile a significant fraction of NIPP is still caused by vaccine serotypes, the availability of PCV13 in the national immunization program for children from 2015 onwards may further reduce their importance in NIPP, questioning the need for adult vaccination.Disclosures M. Ramirez, Pfizer: Speaker’s Bureau, Speaker honorarium; GSK: Consultant, Consulting fee; J. Melo-Cristino, Pfizer: Grant Investigator, Independent Contractor and Speaker’s Bureau, Grant recipient, Research grant and Speaker honorarium; GSK: Grant Investigator and Speaker’s Bureau, Grant recipient and Speaker honorarium; Bial: Speaker’s Bureau, Speaker honorarium; Novartis: Speaker’s Bureau, Speaker honorarium

Invasive Disease vs Urinary Antigen-Confirmed Pneumococcal Community-Acquired Pneumonia

The burden of pneumococcal disease is measured only through patients with invasive pneumococcal disease. The urinary antigen test (UAT) for pneumococcus has exhibited high sensitivity and specificity. We aimed to compare the pneumococcal pneumonias diagnosed as invasive disease with pneumococcal pneumonias defined by UAT results. A prospective observational study of consecutive nonimmunosuppressed patients with community-acquired pneumonia was performed from January 2000 to December 2014. Patients were stratified into two groups: invasive pneumococcal pneumonia (IPP) defined as a positive blood culture or pleural fluid culture result and noninvasive pneumococcal pneumonia (NIPP) defined as a positive UAT result with negative blood or pleural fluid culture result. We analyzed 779 patients (15%) of 5,132, where 361 (46%) had IPP and 418 (54%) had NIPP. Compared with the patients with IPP, those with NIPP presented more frequent chronic pulmonary disease and received previous antibiotics more frequently. Patients with IPP presented more severe community-acquired pneumonia, higher levels of inflammatory markers, and worse oxygenation at admission; more pulmonary complications; greater extrapulmonary complications; longer time to clinical stability; and longer length of hospital stay compared with the NIPP group. Age, chronic liver disease, mechanical ventilation, and acute renal failure were independent risk factors for 30-day crude mortality. Neither IPP nor NIPP was an independent risk factor for 30-day mortality. A high percentage of confirmed pneumococcal pneumonia is diagnosed by UAT. Despite differences in clinical characteristics and outcomes, IPP is not an independent risk factor for 30-day mortality compared with NIPP, reinforcing the importance of NIPP for pneumococcal pneumonia.

Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly

BackgroundHerd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older in the period 2008–2013. MethodsThis is a post hoc analysis of two prospective studies from the Netherlands. Serotype specific urinary antigen detection and routine microbiological testing were used to categorize episodes as IPD or non-IPD PCAP caused by 7-valent pneumococcal conjugate vaccine (PCV7), PCV10-7 (three additional PCV10 serotypes), PCV13-10 (three additional PCV13 serotypes), and non-PCV13 serotypes. Proportions per vaccine-serotype group were assessed per year from June 1st to May 31st. Time trends were compared to national IPD data. ResultsOf 270 non-IPD PCAP episodes with known serotype, PCV7 serotypes decreased from 28% in 2008/2009 to 7% in 2012/2013 (p-value for trend <0.001). No change in PCV10-7 (19% overall) and PCV13-10 (29% overall) serotypes was observed. Non-PCV13 serotypes increased from 30% in 2008/2009 to 37% in 2012/2013 (p-value for trend 0.048). Trends corresponded with national IPD data. ConclusionPCV7 serotypes declined in non-IPD PCAP among elderly between 2008 and 2013, comparable to IPD data. No reduction in the additional PCV10 serotypes could be demonstrated within the first two years after PCV10 introduction.

Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

BackgroundPneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown.MethodsIn a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease.ResultsIn the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, −5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group.ConclusionsAmong older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.)

Non-invasive pneumococcal pneumonia in Portugal--serotype distribution and antimicrobial resistance.

There is limited information on the serotypes causing non-invasive pneumococcal pneumonia (NIPP). Our aim was to characterize pneumococci causing NIPP in adults to determine recent changes in serotype prevalence, the potential coverage of pneumococcal vaccines and changes in antimicrobial resistance. Serotypes and antimicrobial susceptibility profiles of a sample of 1300 isolates recovered from adult patients (≥18 yrs) between 1999 and 2011 (13 years) were determined. Serotype 3 was the most frequent cause of NIPP accounting for 18% of the isolates. The other most common serotypes were 11A (7%), 19F (7%), 19A (5%), 14 (4%), 22F (4%), 23F (4%) and 9N (4%). Between 1999 and 2011, there were significant changes in the proportion of isolates expressing vaccine serotypes, with a steady decline of the serotypes included in the 7-valent conjugate vaccine from 31% (1999–2003) to 11% (2011) (P<0.001). Taking together the most recent study years (2009–2011), the potential coverage of the 13-valent conjugate vaccine was 44% and of the 23-valent polysaccharide vaccine was 66%. While erythromycin resistance increased from 8% in 1999–2003 to 18% in 2011 (P<0.001), no significant trend was identified for penicillin non-susceptibility, which had an average value of 18.5%. The serotype distribution found in this study for NIPP was very different from the one previously described for IPD, with only two serotypes in common to the ones responsible for half of each presentation in 2009–2011 – serotypes 3 and 19A. In spite of these differences, the overall prevalence of resistant isolates was similar in NIPP and in IPD.