Carmen L. Sheppard, United Kingdom

Sustaining herd protection via reduced dose schedules may ameliorate pneumococcal conjugate vaccine costs. However, there is limited understanding of pneumococcal transmission pathways and their role in herd immunity. We aimed to develop and validate phylogenetic methods for detecting the occurrence and direction of pneumococcal transmission.

Methods

Based on the timing of serotype-specific carriage within a household, 10 likely transmission pairs and the corresponding transmission direction were identified from a longitudinal study of nasopharyngeal carriage in the UK and sequenced by whole genome sequencing. Any metadata were blinded, and linkage and the transmission direction inferred from the genomic data alone using Phyloscanner.

Results

Unblinding revealed that transmission pair linkage via genomics was identical to that based on epidemiological criteria. One instance of co-colonization was detected and only the dominant serotype was transmitted. All transmission pairs had moderate to strong phylogenetic signals suggesting transmission direction, however, only 6/10 directions were concordant with the epidemiological metadata.

Conclusions

Phylogenetics did successfully predict transmission pairs in this small sample. To improve the inference of transmission direction we will consider factors including sequencing coverage, degrees of intra-host diversity, and phylogenetic uncertainty, although concordance with epidemiolocal metadata may be limited by imperfect sensitivity of culture-based tests for pneumococcal detection.

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DISCOVERY OF A NOVEL PNEUMOCOCCAL CAPSULE TYPE WITHIN SEROGROUP 24 (ID 818)

Session Name

Basic Sciences - Conventional and Molecular Microbiology

Presenter

Karsten Maruhn, Germany

Authors

Abstract

Abstract

Background

Pneumococcal capsules are important in pathogenesis and vaccine development. Serotype 24F capsule consists of a hexasaccharide repeating unit with arabinitol (WO 2019/050815 AI). Here, we describe the discovery of a novel serotype (“24X”) within serogroup 24.

Methods

Serological properties of pneumococcal isolates were studied using Quellung. Serotypes 24F, 24A, 24B and 24X were subjected to whole genome sequencing (WGS). The capsular polysaccharide (CPS) structures were elucidated by NMR and GC-MS.

Results

Multiple pneumococcal isolates from several countries reacted with both factor sera 24d and 24e. Since this reaction pattern has not been reported and is unique, the isolates were provisionally labelled to be serotype “24X.” Genetic studies of cps loci could not distinguish 24X from 24F or 24B. Chemical structure studies of serogroup 24 members showed that 24B CPS is like 24F except for having ribitol instead of arabinitol, 24X CPS contains both repeat units of 24F and 24B. These findings could explain their reactivity with factor sera 24d and 24e.

Conclusions

The 24X capsule has a distinct serology and repeating unit structure, which qualify it as a new serotype. According to the Danish naming system, 24X was named serotype 24C. Correlation of cps loci with the capsule structure is under investigation.

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PNEUMOCOCCAL CARRIAGE AND ANTIBODY PERSISTENCE FOLLOWING PCV13 DELIVERED AS ONE PRIMARY AND ONE BOOSTER (1+1) VERSUS TWO PRIMARY DOSES AND A BOOSTER IN UK INFANTS (ID 900)

Session Name

Vaccines - Pneumococcal Vaccines Development

Presenter

David Goldblatt, United Kingdom

Authors

CASE FATALITY RATES ASSOCIATED WITH INVASIVE PNEUMOCOCCAL DISEASE DECLINED AFTER PCV13 IMPLEMENTATION IN ENGLAND (ID 1018)

Session Name

Clinical Sciences - Disease Burden in Infants, Children/Youth, and Adults

Presenter

Godwin Oligbu, United Kingdom

Authors

Abstract

Abstract

Background

The serotypes causing invasive pneumococcal disease (IPD) have changed significantly since the introduction of the 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines (PCV) in England. Since case fatality rate (CFR) varies across different pneumococcal serotypes, we analysed trends in deaths and CFR before and after implementation of the two PCV programmes in England

Methods

Public Health England conducts enhanced IPD surveillance in England. Cases and deaths occurring within 7 days of IPD diagnosis were used to calculate CFR during 2002/03-2018/19.

Results

The number of IPD deaths increased from 744 in 2005/16 just before PCV7 was implemented and peaked at 756 in 2009/10 just before PCV13 replaced PCV7 and then declined to 450 cases in 2013/14, when IPD cases were also at their lowest. Since then, IPD cases and deaths increased and peaked in 2018/19 before declining in 2018/19. CFR trends followed IPD deaths until 2008/09 peaking at 14.4% and then gradually declined to 9.9% in 2018/19. This was because the replacing serotypes after PCV13 implementation, especially serotypes 8 and 12F, were associated with lower age-adjusted CFR compared to PCV13 serotypes.

Conclusions

CFR declined only after PCV13 replaced PCV7 in 2010. The current replacing serotypes are associated with lower CFR than PCV13 serotypes.

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