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Displaying One Session

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Session Description
Please note: Each presentation is followed by about 3 minutes of Q&A. The audience is encouraged to send questions to the speakers from the beginning of their presentations. Q&A time is included in each speaker’s presentation duration, accounting for at least 25% active learning for the maximum registrants anticipated.

Introduction (ID 828)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Lecture Time
15:05 - 15:10

O071 - RAPID WANING OF PCV13 VACCINE-INDUCED ANTIBODY AND PERSISTENT VACCINE SEROTYPE PNEUMOCOCCAL CARRIAGE AMONG CHILDREN UNDER-5-YEARS IN BLANTYRE, MALAWI, USING A 3+0 SCHEDULE: AN OBSEVATIONAL STUDY (ID 265)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Lecture Time
15:10 - 15:20

Abstract

Background

Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine serotype (VT) invasive pneumococcal disease (IPD), carriage and transmission. Following Malawi’s 2011 PCV13 introduction (3+0 schedule) we demonstrated substantial residual VT carriage among PCV-vaccinated children. To assess the hypothesis that vaccine-induced IgG wanes below levels associated with preventing carriage and disease, we investigated serotype-specific IgG dynamics through a pragmatic method of cross-sectional population-based immunogenicity profiling among PCV-vaccinated children aged <5 years.

Methods

Using 638 plasma samples, serotype-specific IgG to PCV13 VTs were measured using a standardised EIA and direct binding electrochemiluminescence-based methods in a WHO Reference laboratory. We developed a modelling framework using linear splines and censored regression to estimate population-averaged serological profiles. Leveraging carriage data, we estimated serotype-specific correlates of protection (CoP) against pneumococcal carriage.

Results

There was no consistent anti-serotype-3 vaccine response. Though diverse in profile, remaining VTs showed a vaccine-induced increase in IgG followed by rapid waning and then a subsequent increase, presumably due to natural exposure. The population-based age range at IgG nadir was 11.24 (19F & 23F) to 27.33 months (7F). IgG titres of 7 VTs waned temporarily (longest duration: 33.5 months, serotype-4) below the putative CoP for disease and 5 VTs did not attain CoP for carriage post-vaccination. Estimated CoP’s against VT carriage (0.50μg/mL - 2.5μg/mL) were higher than putative CoPs for IPD.

Conclusions

This pragmatic population-based method of serological profiling offers insights into serotype-specific immunity with important biological consequences for protection. When evaluating pneumococcal vaccine strategies, limiting early waning of VT immunity should be a priority.

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O072 - THE METABOLIC, VIRULENCE AND ANTIMICROBIAL RESISTANCE PROFILES OF COLONIZING STREPTOCOCCUS PNEUMONIAE SHIFT AFTER PCV13 INTRODUCTION IN URBAN MALAWI (ID 571)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Lecture Time
15:20 - 15:30

Abstract

Background

Streptococcus pneumoniae naturally undergoes genotypic fluctuations. We previously showed a high residual prevalence of vaccine serotype (VT) pneumococci (18% in under 5’s) 7 years after PCV13 introduction in Malawi. Here, we address the hypothesis that following vaccine introduction in high disease and carriage settings, adapted pneumococcal genotypes emerge with the potential to facilitate vaccine escape.

Methods

2804 S. pneumoniae isolates were collected and sequenced during rolling cross-sectional carriage surveys in Blantyre, 4-8 years after PCV13 introduction. We identified the serotype and the antimicrobial resistance characteristics genomically. Further, we developed a pipeline to cluster the bacterial population based on its metabolic core genes (Metabolic Genotypes, MTs). Relative fitness was assessed by in vitro growth and epithelial adhesion/invasion using Detroit 562 nasopharyngeal cells.

Results

We show marked changes in S. pneumoniae carriage population genetics. High residual pneumococcal carriage is characterised by persistent MTs in VT (e.g. 3 and 23F) and emerging new MTs in non-VT (NVT; 38 and 23B). These metabolic genotypes show distinct virulence and antimicrobial resistance (AMR) profiles, including genes responsible for metabolism and carbohydrate transport, and toxin-antitoxin systems located in an integrative-conjugative region suggestive of horizontal gene transfer. We identified convergent evolution between MTs isolated in different countries, result of genetic bottleneck. These emergent genotypes were found to have differential growth, haemolytic, or epithelial adhesion/invasion traits that may confer advantage in the nasopharyngeal niche.

Conclusions

This vaccine-induced shift in metabolic genotypes, antimicrobial resistance and colonization adaptations extends beyond simple serotype replacement, could further undermine vaccine control and promote the spread of AMR.

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O073 - PHYLOGENETIC PATTERNS OF PEDIATRIC INVASIVE PNEUMOCOCCAL SEROTYPE DECLINE, PERSISTENCE, AND EMERGENCE IN UTAH FOLLOWING PNEUMOCOCCAL VACCINE INTRODUCTION (ID 598)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Lecture Time
15:30 - 15:40

Abstract

Background

Streptococcus pneumoniae is a common cause of pediatric invasive bacterial infections. Incidence of invasive pneumococcal disease (IPD) has decreased following pneumococcal conjugate vaccine (PCV) introduction. However, limited efficacy against some serotypes and emergence of new serotypes threatens vaccine durability.

Methods

We performed Illumina sequencing, de novo genome assembly/annotation, serotyping, pan-genome assembly and global pneumococcal sequence cluster (GPSC) assignment of clinical sterile site pneumococcal isolates from pediatric patients at Primary Children’s Hospital (Salt Lake City, UT) isolated between 1996-2018. Antimicrobial resistance was determined phenotypically and genomically. Core genome SNP alignment was used for maximum likelihood phylogeny.

Results

366 pneumococcal isolates from 39 serotypes (ST) were analyzed. Some GPSC with predominantly vaccine serotypes declined during the study period, including GPSC31 (ST1), GPSC1 (ST19A/F), and GPSC15 (ST7F); GPSC12 (ST3) and GPSC119 (ST19F) increased, comprising 24% of post-PCV13 strains. Two GPSC appeared to undergo serotype switching following PCV introduction: GPSC4 and 6, from ST19A and ST9V to ST15B/C and ST35B, respectively. Notably, many GPSC6 isolates retained multiple drug resistance despite the switch. Predominantly non-vaccine serotype GPSC emerged representing 33% of post-PCV13 isolates, including GPSC3 (ST11A and 33F), GPSC5 (ST23A/B1), GPSC7 (ST23A/B/B1), GPSC19 (ST22F), GPSC98 (ST8), and GPSC140 (ST15A).

Conclusions

While some PCV serotypes are now infrequently isolated from IPD patients, others including ST3 and ST19F have remained common and phylogenetically similar despite vaccine pressure. Additionally, phylogenetic diversification promotes continual emergence of new pneumococcal serotypes, and novel vaccine approaches are needed.

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O074 - ASSESSING THE EARLY IMPACT OF PCV13 SCHEDULE CHANGE AND THE ROLE OF VIRAL COINFECTION IN PNEUMOCOCCAL EMPYEMA IN AUSTRALIAN CHILDREN (ID 779)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Lecture Time
15:40 - 15:50

Abstract

Background

Streptococcus pneumoniae (pneumococcus) is the predominant cause of pleural empyema in children. Australia recently transitioned from a 3+0 to 2+1 schedule of 13-valent pneumococcal conjugate vaccine (PCV13). The impact on empyema-associated serotypes is unknown. Viral coinfection increases pneumococcal density, however the impact on frequency, pathogenesis and serotype aetiology is unclear. This study will evaluate the early impact of the PCV13 schedule change on empyema-associated pneumococcal serotypes and the role of viral co-infection.

Methods

We are recruiting 150 children and adolescents (<18yrs) with empyema, collecting pleural fluids, nasopharyngeal, and oropharyngeal swabs. Pneumococcal-positive samples will be identified using our recently developed multiplex-qPCR. Serotyping will be performed by pneumococcal TaqMan Array Cards, comparing serotypes before and after the PCV13 schedule change. Pleural fluids and swabs will be assessed by respiratory tract microbiota TaqMan Array Cards to determine frequency and aetiology of viral coinfection.

Results

Thus far, 36/50 (72%) pleural fluids were pneumococcus positive. Most (26/36, 72%) pneumococcal empyemas were caused by serotype 3. The percentage caused by serotype 3 increased from 20/29 (69%) in the 3+0 schedule era to 6/7 (86%) in the 2+1 schedule era (p = 0.1868, Fisher’s exact test). For patients with swabs available for testing, 10/22 (45%) had a viral coinfection, with Parainfluenza and Respiratory Syncytial Virus most prevalent.

Conclusions

Our project will investigate the epidemiology of empyema in a PCV13-vaccinated setting, and reveal the contribution of viruses to the pathogenesis of pneumococcal empyema. Our findings will be particularly relevant for countries considering transitioning from a 3+0 schedule to a 2+1 schedule.

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O075 - GENOMIC EPIDEMIOLOGY OF PNEUMOCOCCI IN THE UK FROM PRE-PCV7 TO POST-PCV13: MODELLING OF CARRIAGE DYNAMICS AND DISEASE BURDEN FORECASTING (ID 328)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Lecture Time
15:50 - 16:00

Abstract

Background

Pneumococcal carriage population dynamics in England have been monitored by five nasopharyngeal surveys undertaken by the UK Health Security Agency (previously Public Health England): pre-PCV7 (2001-2002); post-PCV7 (2008-2009); and post-PCV13 in 2012-2013, 2015-2016 and 2017-2018. A previous study sequenced 877 of these isolates. Contemporaneous isolates from child and adult invasive disease across England (N=1546) were also sequenced to compare the dynamics of disease and carriage.

Methods

Isolates were serotyped using PneumoCAT and categorised into strains using PopPUNK. The distribution of genes across isolates was analysed with Panaroo. Simulations used an updated version of the multi-locus negative frequency-dependent selection (NFDS) model (https://github.com/nickjcroucher/multilocusNFDS). Parameters were estimated through approximate Bayesian computation using the ELFI package.

Results

Estimates of NFDS strength were similar to those from fits to independent datasets that only spanned the introduction of PCV7, confirming NFDS models more accurately replicated the population dynamics than equivalent neutral models. Simulations reproduced the elimination of vaccine-type strains, expansion of some non-vaccine-type strains, and serotype switching within strains. Forward simulations were used to predict carriage dynamics post-PCV15 and post-PCV20. When combined with estimates of genotype invasiveness in infants and adults, these enabled the forecasting of invasive disease burdens after the next generation of conjugate vaccines.

Conclusions

Genomic data and models can improve our understanding of the PCV-associated changes in the carried pneumococcal populations. Forecasts of carriage dynamics combined with invasiveness estimates can be used to predict PCV effectiveness, and highlight the serotypes most likely to cause a substantial burden of disease in children and adults post-PCV.

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O076 - EFFECTIVENESS AND IMPACT OF 13-VALENT PNEUMOCOCCAL VACCINES AGAINST INVASIVE DISEASE CAUSED BY SEROTYPE 3 PNEUMOCOCCUS: RESULTS OF SPIDNET, A EUROPEAN MULTICENTRE STUDY (2012-2019) (ID 561)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Lecture Time
16:00 - 16:10

Abstract

Background

Serotype 3 is the second most frequent serotype causing invasive pneumococcal disease (IPD) in the European countries participating in the S. pneumoniae Invasive Disease network (SpIDnet). We measured the 13-valent conjugate vaccine (PCV13) effectiveness (VE) and impact (VI) of vaccination programmes using this vaccine on serotype 3 IPD.

Methods

We used the indirect cohort method to measure VE among 12-59-month-old children using data collected between 2012 and 2019 in nine SpIDnet sites. We calculated VE=(1-vaccination odds ratio)*100, adjusted for age, underlying conditions, notification year and site. Using surveillance data from five sites with PCV13 uptake >90%, we calculated site-specific incidence rate ratios (IRR) comparing serotype 3 IPD incidence in 2019 with the mean incidence during the PCV7 period by age group (<5, 5-64, 65+ years). We calculated VI=(1-pooled IRR)*100 using random effects meta-analysis.

Results

PCV13 VE against serotype 3 IPD was 67% (95%CI: 38; 82) (cases/vaccinated=104/67; controls/vaccinated=875/813). In 2019, serotype 3 IPD incidence increased by 13% (-96 to 35) in children aged < 5 years, by 5% (-27 to 13) in 5-64 year-olds and by 8% (-7 to 25) in 65+ year-olds.

Conclusions

Our results suggest a moderate PCV13 effectiveness in children and no vaccine impact in the three age groups included after nine years of the vaccine use. This suggests no effect on the carriage of this serotype. Effectiveness against serotype 3 IPD and serotype 3 carriage needs to be improved in future vaccine formulations.

Acknowledgments: SpIDnet was funded by participating sites and European Centre for Disease Prevention and Control.

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O077 - EFFECT OF PNEUMOCOCCAL CONJUGATE VACCINE AVAILABILITY ON STREPTOCOCCUS PNEUMONIAE INFECTIONS AND GENETIC RECOMBINATION IN CHINA FROM 2009 TO 2019 (ID 623)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Presenter
Lecture Time
16:10 - 16:20

Abstract

Background

How a pause in pneumococcal conjugate vaccine (PCV) vaccination affects pneumococcal disease (PD) or Streptococcus pneumoniae epidemiology is unknown. Based on the unique PCV introduction timeline (PCV gap: April 2015 - April 2017) in China, we aimed to evaluate the effect of the PCV gap on PD and pneumococcal genome variation over the last decade.

Methods

S. pneumoniae isolates (n=386) were collected retrospectively from eight sites in China from 2009 to 2019. Pathogenic pneumococci (n=184) were designated as those collected from blood, cerebrospinal fluid, bronchoalveolar lavage fluid, and infection sites. An interrupted time series analysis was conducted to estimate changes in PD according to PCV availability. The recombination frequency of whole genome-sequenced strains was estimated via SNP calling to reveal pneumococcal genetic variation.

Results

Children were the most infected cohort (n=128), with the major diagnosis being lower respiratory tract infection (LRTI). The ratio of vaccine-type LRTI (VT-LRTI) decreased in the later PCV7 period (2013-March 2015) and increased again in children once PCV7 went off the market in April 2015 (p=0.0007). Increased pneumococcal genetic recombination activity was observed, and the most prevalent clone CC271 strains showed slowed (p=0.0293) recombination activities upon PCV removal.

Conclusions

A PCV gap would restore vaccine-type PD, while bacterial genetic variation also responded accordingly. It is essential to promote a continuous PCV vaccination and strengthen S. pneumoniae molecular epidemiology surveillance for PD prevention. Our findings will benefit PCV vaccination strategies for China and any region that may encounter an unanticipated PCV vaccination pause.

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O078 - PREVALENCE OF PNEUMOCOCCAL SEROTYPES CAUSING COMMUNITY-ACQUIRED PNEUMONIA IN THE ELDERLY IN ITALY USING URINARY ANTIGEN DETECTION TEST: THE PUMA STUDY, 2017-2020 (ID 433)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:35
Room
Birchwood Ballroom
Lecture Time
16:20 - 16:30

Abstract

Background

In Italy, pneumococcal conjugate vaccines (PCVs) have been included in the National Immunization Program for infant since 2005 (PCV13 since 2010) and for adults aged ≥50 years since 2011. Our study assessed pneumococcal serotype distribution of community-acquired pneumonia (CAP) among older adults hospitalized from September 2017 to February 2020.

Methods

PUMA was a 3-year cohort study that enrolled adults aged ≥65 years old, hospitalized with clinical and radiographically confirmed CAP in 8 hospital centres from 4 Italian regions (Veneto, Liguria, Apulia and Sicily). Pneumococcus was identified using serotype-specific urinary antigen detection assays (UAD 1/2) and BinaxNow®. UAD1 detects serotypes in PCV13, UAD2 detects additional serotypes in 23-valent pneumococcal polysaccharide vaccine (PPV23).

Results

Among 1155 hospitalized CAP patients, 59.2% were male and 51.5% were ≥80 years old. Overall, 92.2% of patients had ≥1 pre-existing risk factor for CAP: most frequently chronic obstructive pulmonary disease (33.3%), chronic cardiac disease (32.6%), and diabetes mellitus (30.0%). 21.7% of CAP patients had been ever vaccinated with PCV13 only (8.1%), PPV23 only (6.8%) or both (6.8%). Pneumococcus was identified in 144 patients (12.5%). 73.6% of pCAP was caused by a non-PCV13 serotype (Table 1).

figure 1.jpg

Conclusions

In the context of high pediatric and limited adult PCV13 immunization, older adult vaccine-serotype CAP has declined, although serotype 3 remains the most frequent serotype identified. Non-vaccine serotypes now cause most hospitalized pCAP in older adults, often from serotypes in newer expanded valency PCVs (PCV15 and PCV20) recently licensed in the United States.

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