Tamara Pilishvili, United States of America

Centers for Disease Control and Prevention Division of Bacterial Diseases

Presenter of 1 Presentation

 Conference Calendar

Long-term Impact of Pneumococcal Conjugate Vaccine (PCV) on Antibiotic Resistant Invasive Pneumococcal Disease (IPD) in the United States (ID 892)

Session Name
Vaccines - Impact of Vaccine programs and Serotype Replacement
Presenter
Authors

Abstract

Background

PCVs have been recommended for U.S. children since 2000 and for adults aged ≥65 years since 2014. We evaluated impact of PCVs on antibiotic non-susceptible (NS) IPD.

Methods

IPD cases were identified through CDC’s Active Bacterial Core surveillance during 1998-2018. Isolates were serotyped and classified as PCV13 or non-vaccine type (NVT). We applied 2019 Clinical and Laboratory Standards Institute breakpoints to minimum inhibitory concentrations (using broth microdilution or whole genome sequencing) to classify isolates as NS to >1 antibiotic (NS-IPD) or to >3 drug classes (multi-drug-NS). Incidence rates (per 100,000) were calculated using U.S. Census Bureau population denominators.

Results

From 1998-1999 to 2017-2018, penicillin-NS IPD incidence decreased from 12 to 0.4 among children <5 years-old and from 5 to 0.8 among adults ≥65 years-old. Incidence of PCV13-type NS-IPD decreased among all ages, while incidence of NVT NS-IPD increased for all ages (Figure). In 2018, serotypes 19A (37%), 23A (13%) and 23B (13%) and serotypes 35B (42%), 19A (19%), and 15A (12%) accounted for most penicillin NS and multi-drug-NS IPD, respectively.

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Conclusions

NS-IPD incidence decreased following 18 years of PCV use among children, driven by reductions in PCV serotypes. Increases in NVTs have started to erode PCV benefits on NS-IPD, especially among adults.

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Author Of 5 Presentations

 Conference Calendar

BACTERIAL MUTATIONS ASSOCIATED WITH MENINGITIS AMONG INVASIVE PNEUMOCOCCAL DISEASE (IPD) PATIENTS (ID 826)

Session Name
Basic Sciences - Genomics and Transmission
Presenter
Authors

Abstract

Background

Our understanding on bacterial genetic determinants of pneumococcal disease manifestation is still limited. We aim to confirm the previous findings and identify additional bacterial variants associated with meningitis.

Methods

We sequenced IPD isolates identified through the Active Bacterial Core surveillance (ABCs) in the United States from 2016 to 2017. We evaluated the association between meningitis and a previously reported pneumococcal pbp1b641C allele by using a mixed-effects logistic regression model accounting for population structure (represented by multi-locus sequence type) and potential confounders (pneumococcal serotype, antibiotic resistance, and patient age). We also performed a k-mer based bacterial genome-wide association study (GWAS).

Results

Among all 5560 sequenced IPD isolates, 371 (6.7%) were from meningitis cases. Among the 576 isolates carrying the pbp1b641C allele, 86 (14.9%) were meningitis. After adjusting for covariates, the pbp1b641C allele was significantly associated with meningitis (OR=1.76, 95% CI,1.10-2.81). Pneumococcal genome contents explained 8.2% (95% CI,1.6%-13.2%) of variation in meningitis in the GWAS. Additional pneumococcal mutations that showed significant association were identified in loci including SP_1448 (conserved hypothetical protein, p=1.7×10-8), SP_2167 (L-fuculokinase, p=3.6×10-8), and SP_0647 (phosphotransferase, p=1.0×10-7).

Conclusions

IPD manifestation varied significantly according to pneumococcal genomes. More knowledge on such mutations could help better understand bacterial pathogenesis and clinical outcome.

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GENOMIC CLUSTERS OF INVASIVE PNEUMOCOCCAL DISEASE (IPD) ISOLATES, USA, 2015-2017 (ID 833)

Session Name
Population Sciences - Epidemics, Outbreaks and Special Settings
Presenter
Authors

Abstract

Background

Outbreaks of pneumococcal infections have been reported in closed settings and are often caused by clusters of genomically highly related isolates (genomic clusters), suggesting close transmission connections.

Methods

We used whole-genome sequencing (WGS) to characterize all IPD isolates identified through the Active Bacterial Core surveillance (ABCs) from 2015 to 2017. We identified genomic clusters by performing hierarchical cluster analysis of pair-wise genomic distances and applying a cut-off value of 3-base difference per 1.8Mb shared genome.

Results

WGS characterized 8029 isolates representing 87% of all IPD cases. The cluster analysis identified 379 genomic clusters accounting for 847 (11%) of the isolates. Higher proportions of clustered isolates (isolates belonging to any clusters) were found in serotypes 12F (36%), 4 (26%), and 7F (25%), while lower proportions were found in serotypes 35F, 7C, 15A, 23B (each <1.5%), and penicillin non-susceptible isolates (4%). Clustered isolates were significantly associated with patients who were homeless (OR=3.3), who were injecting drugs (OR=2.1), and who were 25 to 50 years of age (OR=1.5; all p-values < 0.001).

Conclusions

IPD genomic clusters were associated with specific patient and strain features in the ABCs population. Understanding the dynamics and demographics of vaccine-serotype clusters could help identify new target groups to inform vaccine policy.

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EPIDEMIOLOGY OF INVASIVE PNEUMOCOCCAL DISEASE (IPD) FOLLOWING 18 YEARS OF PNEUMOCOCCAL CONJUGATE VACCINE (PCV) USE IN THE UNITED STATES (ID 849)

Session Name
Vaccines - Impact of Vaccine programs and Serotype Replacement
Presenter
Authors

Abstract

Background

PCVs have been recommended for U.S. children since 2000 and for adults aged ≥65 years since August 2014. We evaluated PCV impact on IPD.

Methods

IPD cases (isolation of pneumococcus from sterile sites) were identified through CDC’s Active Bacterial Core surveillance during 1998-2018. Isolates were serotyped by Quellung or whole genome sequencing and classified as PCV13-type and non-vaccine-type (NVT). Incidence rates (cases/100,000) were calculated using U.S. Census Bureau population denominators.

Results

During 1998-2018, overall and PCV13-type IPD rates declined significantly among children and adults aged ≥65 years (Figures); serotypes 3, 19A, and 19F caused most of the remaining PCV13-type IPD. NVT IPD rates did not change. The most common NVTs in 2018 were 22F (10% of all IPD), 9N (7%) and 15A (5%). Among children, the proportion of cases with meningitis increased from 5% to 14%(p<0.01), and the proportion with pneumonia/empyema increased from 17% to 31%(p<0.01). Among adults, the proportion of cases with meningitis did not change (3%), while the proportion with pneumonia/empyema increased from 72% to 76%(p=0.01).

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Conclusions

Overall IPD incidence among children and adults decreased following PCV introduction for children, driven primarily by reductions in PCV-type IPD. Increases in NVT IPD were minimal compared with PCV benefits.

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Long-term Impact of Pneumococcal Conjugate Vaccine (PCV) on Antibiotic Resistant Invasive Pneumococcal Disease (IPD) in the United States (ID 892)

Session Name
Vaccines - Impact of Vaccine programs and Serotype Replacement
Presenter
Authors

Abstract

Background

PCVs have been recommended for U.S. children since 2000 and for adults aged ≥65 years since 2014. We evaluated impact of PCVs on antibiotic non-susceptible (NS) IPD.

Methods

IPD cases were identified through CDC’s Active Bacterial Core surveillance during 1998-2018. Isolates were serotyped and classified as PCV13 or non-vaccine type (NVT). We applied 2019 Clinical and Laboratory Standards Institute breakpoints to minimum inhibitory concentrations (using broth microdilution or whole genome sequencing) to classify isolates as NS to >1 antibiotic (NS-IPD) or to >3 drug classes (multi-drug-NS). Incidence rates (per 100,000) were calculated using U.S. Census Bureau population denominators.

Results

From 1998-1999 to 2017-2018, penicillin-NS IPD incidence decreased from 12 to 0.4 among children <5 years-old and from 5 to 0.8 among adults ≥65 years-old. Incidence of PCV13-type NS-IPD decreased among all ages, while incidence of NVT NS-IPD increased for all ages (Figure). In 2018, serotypes 19A (37%), 23A (13%) and 23B (13%) and serotypes 35B (42%), 19A (19%), and 15A (12%) accounted for most penicillin NS and multi-drug-NS IPD, respectively.

resistancetrends.png

Conclusions

NS-IPD incidence decreased following 18 years of PCV use among children, driven by reductions in PCV serotypes. Increases in NVTs have started to erode PCV benefits on NS-IPD, especially among adults.

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IMPACT OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE (PCV13) ON NON-BACTEREMIC PNEUMOCOCCAL PNEUMONIA (NBPP) IN THE UNITED STATES 2013-2017 (ID 222)

Session Name
Vaccines - Impact of Vaccine programs and Serotype Replacement
Presenter
Authors

Abstract

Background

PCV13 was recommended for U.S. children in 2010 and for adults ≥65 years in 2014. Vaccine coverage among adults ≥65 years was 43% in 2017. We evaluated PCV13 impact on NBPP among adults.

Methods

NBPP cases (clinically or radiographically-confirmed pneumonia and a positive pneumococcal urine antigen test in a hospitalized adult aged ≥18 years) were identified at select hospitals in 10 sites within CDC’s Active Bacterial Core surveillance during 2013-2017. NBPP rates (cases per 100,000) were estimated using U.S. Census Bureau population denominators and adjusted for the proportion of pneumonia patients tested by UAT and the number of pneumonia admissions in the catchment area.

Results

Between 2013 and 2017, 4,430 NBPP cases were identified. From 2013 to 2014, rates of NBPP declined from 153 to 90 (41% reduction, 95%CI 30%, 51%) in ≥65 year-olds; 60 to 40 (34% reduction, 95%CI 22%, 45%) in 50-64 year-olds; and 15 to 10 (36% reduction, 95%CI 25%, 47%) in 18-49 year-olds. From 2014 to 2017, rates of NBPP increased in all ages but remained below 2013 rates (Figure).

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Conclusions

Reductions in NBPP among adults were primarily due to indirect effects of PCV13 use in children, with no additional declines following PCV13 introduction for adults aged ≥65 years.

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