2714. Streptococcus pneumoniae Nasopharyngeal Carriage in Canadian Adults Hospitalized with Community-Acquired Pneumonia from 2010 to 2017

Abstract Background Streptococcus pneumoniae can colonizes the human nasopharynx, and can cause life-threatening infections like community-acquired pneumonia (CAP) and invasive pneumococcal diseases (IPD). In Canada, the 13-valent conjugate vaccine (PCV13) was introduced in childhood immunization since 2010, with hopes that it would not only protect the vaccinated, but also confer indirect protection to adults through herd immunity. Given data on S. pneumoniae nasopharyngeal (NP) carriage in adults is scarce, this study reports on S. pneumoniae-positivity and serotype distribution in adult carriage from years 2010 to 2017. Methods Active surveillance was performed in adults hospitalized with for CAP or IPD from December 2010 to 2017. For assessment of S. pneumoniae carriage, NP swabs were tested using lytA and cpsA real-time PCR. S. pneumoniae-positive NPs were subjected to serotyping using conventional and real-time multiplex PCRs. Results Overall, 6472 NP swabs were tested, and Spn was identified in 366 (5.7%). Of the 366 S. pneumoniae-positive NP swabs, a serotype was assigned in 355 (97.0%). From years 2010 to 2017, the proportion of S. pneumoniae-positive NP swabs declined from 8.9% to 4.3%. This was also reflected in the proportion of serotypeable results attributed to PCV13 serotypes, which also declined from 76.9% to 42.2%. The decline was primarily attributed to PCV13 serotypes 7F and 19A. PCV13 serotype 3 remained predominant throughout the study, as did non-PCV13 serotypes like 22F, 33F, and 11A. On the other hand, a proportional rise over time was noted for non-vaccine serotypes (from 15.4% to 31.1%). This was primarily attributed to serotypes 23A, 15A, and 35B. Conclusion Monitoring serotype trends is important to assess the impact of pneumococcal vaccines. While herd immunity from PCV13 childhood immunization was anticipated, few studies have assessed its impact on adult carriage. This study described Spn serotype distribution in adults over years 2010 to 2017, demonstrating not only a reduction of PCV13 serotypes over time, but a proportional rise in non-vaccine serotypes. These emerging serotypes may represent the emergence of serotype replacement. Ongoing serotype surveillance will be needed to compare S. pneumoniae carriage to serotypes associated with pneumococcal CAP and IPD. Disclosures All authors: No reported disclosures.

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Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency

Scientific Reports ◽

10.1038/s41598-020-75691-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Alessandra Løchen ◽

Nicholas J. Croucher ◽

Roy M. Anderson

Keyword(s):

Pneumococcal Disease ◽

Vaccine Uptake ◽

Partial Replacement ◽

Age Group ◽

Serotype Distribution ◽

Post Vaccination ◽

Vaccine Serotypes ◽

European North ◽

Serotype Replacement ◽

The Impact

Abstract Streptococcus pneumoniae is a significant cause of otitis media, pneumonia, and meningitis. Only seven of the approximately 100 serotypes were initially included in the pneumococcal polysaccharide conjugate vaccine (PCV) in 2000 before it was expanded in subsequent years. Although the invasive pneumococcal disease (IPD) incidence due to vaccine serotypes (VT) has declined, partial replacement by non-vaccine serotypes (NVT) was observed following widespread vaccine uptake. We conducted a trend analysis assembling the available evidence for PCV impact on European, North American and Australian national IPD. Significant effectiveness against VT IPD in infants was observed, although the impact on national IPD incidence varied internationally due to serotype replacement. Currently, NVT serotypes 8, 9N, 15A and 23B are increasing in the countries assessed, although a variety of other NVTs are affecting each country and age group. Despite these common emerging serotypes, there has not been a dominant IPD serotype post-vaccination as there was pre-vaccination (serotype 14) or post-PCV7 (serotype 19A), suggesting that future vaccines with additional serotypes will be less effective at targeting and reducing IPD in global populations than previous PCVs. The rise of diverse NVTs in all settings’ top-ranked IPD-causing serotypes emphasizes the urgent need for surveillance data on serotype distribution and serotype-specific invasiveness post-vaccination to facilitate decision making concerning both expanding current vaccination programmes and increasing vaccine valency.

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Insights Into the Effects of Mucosal Epithelial and Innate Immune Dysfunction in Older People on Host Interactions With Streptococcus pneumoniae

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.651474 ◽

2021 ◽

Vol 11 ◽

Author(s):

Caroline M. Weight ◽

Simon P. Jochems ◽

Hugh Adler ◽

Daniela M. Ferreira ◽

Jeremy S. Brown ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Older People ◽

Immune Cell ◽

Herd Immunity ◽

Pneumococcal Infection ◽

Innate Immune ◽

Older Individuals ◽

Serotype Replacement ◽

Pneumococcal Colonization ◽

The Impact

In humans, nasopharyngeal carriage of Streptococcus pneumoniae is common and although primarily asymptomatic, is a pre-requisite for pneumonia and invasive pneumococcal disease (IPD). Together, these kill over 500,000 people over the age of 70 years worldwide every year. Pneumococcal conjugate vaccines have been largely successful in reducing IPD in young children and have had considerable indirect impact in protection of older people in industrialized country settings (herd immunity). However, serotype replacement continues to threaten vulnerable populations, particularly older people in whom direct vaccine efficacy is reduced. The early control of pneumococcal colonization at the mucosal surface is mediated through a complex array of epithelial and innate immune cell interactions. Older people often display a state of chronic inflammation, which is associated with an increased mortality risk and has been termed ‘Inflammageing’. In this review, we discuss the contribution of an altered microbiome, the impact of inflammageing on human epithelial and innate immunity to S. pneumoniae, and how the resulting dysregulation may affect the outcome of pneumococcal infection in older individuals. We describe the impact of the pneumococcal vaccine and highlight potential research approaches which may improve our understanding of respiratory mucosal immunity during pneumococcal colonization in older individuals.

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High-throughput nanofluidic real-time PCR to discriminate Pneumococcal Conjugate Vaccine (PCV)-associated serogroups 6, 18, and 22 to serotypes using modified oligonucleotides.

10.21203/rs.3.rs-798778/v1 ◽

2021 ◽

Author(s):

Sarah Leah Downs ◽

Shabir Ahmed Madhi ◽

Lara van Der Merwe ◽

Marta Coelho Nunes ◽

Courtney Paige Olwagen

Keyword(s):

Real Time ◽

High Throughput ◽

Real Time Pcr ◽

Limit Of Detection ◽

Locked Nucleic Acid ◽

Clinical Samples ◽

Taqman Assay ◽

Vaccine Serotypes ◽

Serotype Replacement ◽

The Impact

Abstract Current real-time Polymerase Chain Reaction (qPCR) methods are unable to distinguish serotypes 6A from 6B, 18C from 18A/B and 22F from 22A. We established a nanofluidic real-time PCR (Fluidigm) for serotyping that included Dual-Priming-Oligonucleotides (DPO), a Locked-Nucleic-Acid (LNA) probe and TaqMan assay-sets for high-throughput serotyping. The designed assay-sets target capsular gene wciP in serogroup 6, wciX and wxcM in serogroup 18, and wcwA in serogroup 22. An algorithm combining results from published assay-sets (6A/B/C/D; 6C/D; 18A/B/C; 22A/F) and designed assay-sets for 6A/C; 18B/C/F; 18C/F, 18F and 22F was validated through blind analysis of 1973 archived clinical samples collected from South African children ≤ 5-years-old (2009-11), previously serotyped with the culture-based Quellung method. All assay-sets were efficient (92–101%), had low variation between replicates (R2 > 0.98), and were able to detect targets at a limit of detection (LOD) of < 100 Colony-Forming-Units (CFU)/ml of sample. There was high concordance (Kappa = 0.73–0.92); sensitivity (85–100%) and specificity (96–100%) for Fluidigm compared with Quellung for serotyping 6A; 6B; 6C; 18C and 22F. Fluidigm distinguishes vaccine-serotypes 6A, 6B, 18C, next-generation PCV-serotype 22F and non-vaccine-serotypes 6C, 6D, 18A, 18B, 18F and 22A. Discriminating single serotypes is important for assessing serotype replacement and the impact of PCVs on vaccine- and non-vaccine serotypes.

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High-throughput nanofluidic real-time PCR to discriminate Pneumococcal Conjugate Vaccine (PCV)-associated serogroups 6, 18, and 22 to serotypes using modified oligonucleotides

Scientific Reports ◽

10.1038/s41598-021-03127-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

S. L. Downs ◽

S. A. Madhi ◽

L. Van der Merwe ◽

M. C. Nunes ◽

C. P. Olwagen

Keyword(s):

Real Time ◽

High Throughput ◽

Real Time Pcr ◽

Limit Of Detection ◽

Locked Nucleic Acid ◽

Clinical Samples ◽

Taqman Assay ◽

Vaccine Serotypes ◽

Serotype Replacement ◽

The Impact

AbstractCurrent real-time high-throughput Polymerase Chain Reaction (qPCR) methods do not distinguish serotypes 6A from 6B, 18C from 18A/B and 22F from 22A. We established a nanofluidic real-time PCR (Fluidigm) for serotyping that included Dual-Priming-Oligonucleotides (DPO), a Locked-Nucleic-Acid (LNA) probe and TaqMan assay-sets for high-throughput serotyping. The designed assay-sets target capsular gene wciP in serogroup 6, wciX and wxcM in serogroup 18, and wcwA in serogroup 22. An algorithm combining results from published assay-sets (6A/B/C/D; 6C/D; 18A/B/C; 22A/F) and designed assay-sets for 6A/C; 18B/C/F; 18C/F, 18F and 22F was validated through blind analysis of 1973 archived clinical samples collected from South African children ≤ 5-years-old (2009–2011), previously serotyped with the culture-based Quellung method. All assay-sets were efficient (92–101%), had low variation between replicates (R2 > 0.98), and were able to detect targets at a limit of detection (LOD) of < 100 Colony-Forming-Units (CFU)/mL of sample. There was high concordance (Kappa = 0.73–0.92); sensitivity (85–100%) and specificity (96–100%) for Fluidigm compared with Quellung for serotyping 6A; 6B; 6C; 18C and 22F. Fluidigm distinguishes vaccine-serotypes 6A, 6B, 18C, next-generation PCV-serotype 22F and non-vaccine-serotypes 6C, 6D, 18A, 18B, 18F and 22A. Discriminating single serotypes is important for assessing serotype replacement and the impact of PCVs on vaccine- and non-vaccine serotypes.

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Prevalence of antibodies against measles, mumps and rubella in the childhood population in Singapore, 2008–2010

Epidemiology and Infection ◽

10.1017/s0950268812002130 ◽

2012 ◽

Vol 141 (8) ◽

pp. 1721-1730 ◽

Cited By ~ 10

Author(s):

L. W. ANG ◽

F. Y. LAI ◽

S. H. TEY ◽

J. CUTTER ◽

L. JAMES ◽

...

Keyword(s):

Confidence Interval ◽

Herd Immunity ◽

Age Groups ◽

Childhood Immunization ◽

Mmr Vaccine ◽

Immunization Programme ◽

Childhood Population ◽

The Impact ◽

Over Time

SUMMARYWe undertook a national paediatric seroprevalence survey of measles, mumps and rubella (MMR) in Singapore to assess the impact of the national childhood immunization programme against these three diseases after introduction of the trivalent MMR vaccine in 1990. The survey involved 1200 residual sera of Singapore residents aged 1–17 years collected from two hospitals between 2008 and 2010. The overall prevalence of antibodies against measles, mumps and rubella was 83·1% [95% confidence interval (CI) 80·9–85·1], 71·8% (95% CI 69·1–74·2) and 88·5% (95% CI 86·6–90·2), respectively. For all three diseases, the lowest prevalence was in children aged 1 year (47·8–62·3%). The seroprevalence of the vaccinated children declined over time. The national MMR immunization programme is effective in raising the herd immunity of the childhood population, although certain age groups are more susceptible to infection, in particular, those who are not eligible for vaccination at age <15 months.

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Levofloxacin-Resistant Invasive Streptococcus pneumoniae in the United States: Evidence for Clonal Spread and the Impact of Conjugate Pneumococcal Vaccine

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.9.3491-3497.2004 ◽

2004 ◽

Vol 48 (9) ◽

pp. 3491-3497 ◽

Cited By ~ 84

Author(s):

Mathias W. R. Pletz ◽

Lesley McGee ◽

James Jorgensen ◽

Bernard Beall ◽

Richard R. Facklam ◽

...

Keyword(s):

United States ◽

Streptococcus Pneumoniae ◽

The United States ◽

Fluoroquinolone Resistance ◽

Active Efflux ◽

Vaccine Serotypes ◽

Drug Classes ◽

Control And Prevention ◽

Clonal Spread ◽

The Impact

ABSTRACT The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, ≥8 mg/liter) S. pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain23F-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.

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Evaluating post-vaccine expansion patterns of pneumococcal serotypes

10.1101/2020.05.31.20116228 ◽

2020 ◽

Author(s):

Maile T. Phillips ◽

Joshua L. Warren ◽

Noga Givon-Lavi ◽

Adrienn Tothpal ◽

Gili Regev-Yochay ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Invasive Pneumococcal Disease ◽

Jewish Population ◽

Pneumococcal Disease ◽

Pneumococcal Serotypes ◽

Conjugate Vaccines ◽

Pneumococcal Conjugate Vaccines ◽

Vaccine Serotypes ◽

Serotype Replacement ◽

Disease Understanding

ABSTRACTStreptococcus pneumoniae remains a leading cause of morbidity and mortality. Pneumococcal conjugate vaccines (PCVs) are effective but target only a fraction of the more than 90 pneumococcal serotypes. As a result, the introduction of PCVs has been followed by the emergence of non-vaccine serotypes. With higher-valency PCVs currently under development, there is a need to understand and predict patterns of serotype replacement to anticipate future changes. In this study, we evaluated patterns of change in serotype prevalence post-PCV introduction in Israel. We found that the assumption that non-vaccine serotypes increase by the same proportion overestimates changes in serotype prevalence in Jewish and Bedouin children. Furthermore, pre-vaccine prevalence was positively associated with increases in prevalence over the study period. From our analyses, serotypes 12F, 8, 16F, 33F, 9N, 7B, 10A, 22F, 24F, and 17F were estimated to have gained the most cases of invasive pneumococcal disease through serotype replacement in the Jewish population. However, this model also failed to quantify some additional cases gained, suggesting that changes in carriage in children alone may be insufficient to explain serotype replacement in disease. Understanding of serotype replacement is important as higher-valency vaccines are introduced.

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Serotype Distribution of Streptococcus pneumoniae causing Invasive Pneumococcal Disease at Bambino Gesù Children's Hospital in Rome: Is It Time for a New Vaccine?

Journal of Pediatric Infectious Diseases ◽

10.1055/s-0037-1615784 ◽

2018 ◽

Vol 14 (01) ◽

pp. 013-015

Author(s):

Elena Bozzola ◽

Andrzej Krzysztofiak ◽

Annausa Pantosti ◽

Laura Lancella ◽

Paola Bernaschi ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Invasive Pneumococcal Disease ◽

Pneumococcal Disease ◽

Pediatric Age ◽

Immunization Programs ◽

Serotype Distribution ◽

Conjugate Vaccines ◽

Pneumococcal Conjugate Vaccines ◽

Children's Hospital ◽

The Impact

AbstractDiseases caused by Streptococcus pneumoniae are mostly preventable infections by current immunization programs. The objective of this study was to evaluate the impact of the introduction of the heptavalent and the 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) on the burden of pneumococcal disease and on the serotype distribution of S. pneumoniae causing invasive pneumococcal diseases (IPDs) in the pediatric age over a 5-year study (from January 2008 till December 2012). We observed a decrease in IPD rate in children after PCV13 introduction despite increases in nonvaccine serotype (NVS) rates in 2011. Nevertheless, from 2012, an increase in IPD rates due to non-PCV13 serotypes was observed.

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2715. Pneumococcal Community-Acquired Pneumonia Attributed to PCV13 Serotypes in Hospitalized Adults: Comparison of the 50–64 and 65+ Age Groups

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2392 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S955-S955

Author(s):

Jason J LeBlanc ◽

May ElSherif ◽

Lingyun Ye ◽

Donna MacKinnon-Cameron ◽

Ardith Ambrose ◽

...

Keyword(s):

Herd Immunity ◽

Age Groups ◽

Outcome Data ◽

Community Acquired Pneumonia ◽

Childhood Immunization ◽

Age Cohorts ◽

Vaccine Type ◽

Age Cohort ◽

Canadian Provinces ◽

Quellung Reaction

Abstract Background In healthy adults aged ≥65 years, direct immunization with the 13-valent pneumococcal conjugate vaccine (PCV13) was shown effective at preventing vaccine-type pneumococcal community-acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD). Although PCV13 was licensed for use in Canadian adults aged >50 years, it was recommended for immunocompromised individuals who are at highest risk of IPD. In 2016, a recommendation was issued for use of PCV13 in immunocompetent adults aged ≥65 years, for the prevention of pCAP and IPD. This study aimed to compare pCAP cases attributed to PCV13 serotypes in adults aged 50–64 and ≥65 years. Methods Active surveillance for CAP and IPD was performed from 2010 to 2015 in adult hospitals across five Canadian provinces. To identify pCAP, blood culture, sputum culture, or a PCV13 serotype-specific urine antigen detection (ssUAD) were used. Serotype was assigned using Quellung reaction, PCR, or ssUAD. All pCAP cases were categorized by serotype and age groups. Patient demographics and outcome data were collected. Results Over years 2010–2015, 6687 CAP cases were tested. 835 pCAP cases were identified, of which 418 (50%) caused by a PCV13 serotype. The majority (74%) of PCV13-associated pCAP occurred in the adults aged ≥50 years, whereas only 41.4% (173/418) were in adults ≥65 years. PCV13 pCAP cases declined over the years, likely through herd immunity from childhood immunization. The yearly proportion of pCAP attributed to PCV13 serotypes for ages ≥50 remained high (67.5 to 80.6%), compared those occurring in the ≥65 age groups (35.1 to 49.4%). Compared with test-negative controls, pCAP cases in both age groups were more likely to be admitted to ICU, require mechanical ventilation, and had higher mortality. Of pCAP deaths, 61.4% and 82.3% were in the ≥65 and ≥50 age cohorts, respectively. Conclusion From year 2010 to 2015, adults hospitalized with PCV13 pCAP in the ≥65 age cohort accounted for less than half of the cases, whereas including the 50–64 age cohort increased the proportion to 74%. Similarly, the proportion of PCV13 pCAP deaths that occurred in adults aged ≥50 years was 82%, compared with 61% in the ≥65 age cohort. Expansion of PCV13 recommendations to include adults 50–64 years of age should be considered. Disclosures All authors: No reported disclosures.

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Invasive pneumococcal disease in Latvia seven years after PCV10 introduction

European Journal of Public Health ◽

10.1093/eurpub/ckz187.078 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

L Savrasova ◽

I Zeltina ◽

A Villerusha ◽

S Balasegaram

Keyword(s):

Invasive Pneumococcal Disease ◽

Pneumococcal Disease ◽

Case Fatality ◽

Annual Incidence ◽

Surveillance Data ◽

Serotype Distribution ◽

Vaccine Serotypes ◽

Serotype Replacement ◽

Increasing Trend ◽

And Control

Abstract Background In 2009 in Latvia, invasive pneumococcal disease (IPD) became notifiable for physicians and in 2010 vaccination of infants with PCV7 commenced. In 2012 PCV10 vaccination was introduced. The objectives of our study were to evaluate trend of incidence and trend serotype distribution of IPD in Latvia and to investigate factors associated with death from IPD. Methods Laboratory confirmed IPD cases are passively notified to the Centre for Disease Prevention and Control of Latvia by laboratories and clinicians. We calculated incidence by age, sex, case fatality and trend in serotypes. Results From 2012 to 2018, 466 cases of IPD were reported, mean annual incidence 3.4/100,000. The notified incidence remained stable from 2012-2014 (2.7), peaked in 2015 (4.4) and fell to 3.9 in 2018. The highest mean annual IPD incidence was in infants (4.8) and in elderly (6). The highest mean annual incidence was reported in males (4.5) in comparison to females (2.4) (IR-1.8 95%CI 1.6-2.4). Case fatality was 19% (87/466) and 23% (37/162) in cases aged > =65 years. 90% (421/466) of isolates were serotyped. The proportion of PCV10 vaccine serotypes fell from 50% (20/40) in 2012 to 19% (14/74) in 2018 (chi2 test for trend =0.000). Since year 2017, PPV23nonPCV13 and Non-vaccine serotypes become more common. We detected PCV13 serotype (RR 2.04 95%CI 1.37-3.02), S.pneumoniae serotype 3 (RR 1. 91 95% CI 1.25-2.93) significantly associated with IPD death. Conclusions Surveillance data indicate evidence of serotype replacement. Surveillance evaluation should asses the representativeness of notification. Furthermore S. pneumoniae carriage study may be useful to characterise serotype circulation. Serotype 3 and age demonstrate independent and significant association with fatal IPD outcome. Key messages IPD surveillance data analysis indicated evidence of serotype replacement with PPV23nonPCV13, NonVaccine serotypes. Serotype 19A becomes more common with significant increasing trend. Serotype 3 and age independently and significantly associated with fatal IPD outcome. S.pneumoniae carriage study would be very useful providing more evidence of characterizing serotypes circulation.

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