Population genomics of post-vaccine changes in pneumococcal epidemiology.
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ABSTRACT:
SUBMITTER: Croucher NJ
PROVIDER: S-EPMC3725542 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Streptococcus pneumoniae is a major cause of invasive disease of young children in low- and middle-income countries. In southern India, pneumococcal conjugate vaccines (PCVs) that can prevent invasive pneumococcal disease began to be used more frequently after 2015. To characterize pneumococcal evolution during the early time period of PCV uptake in southern India, genomes were sequenced and selected characteristics were determined for 402 invasive isolates collected from children <5 years of age during routine surveillance from 1991 to 2020. Overall, the prevalence and diversity of vaccine type (VT) and non-vaccine type (NVT) isolates did not significantly change post-uptake of PCV. Individually, serotype 1 and global pneumococcal sequence cluster (GPSC or strain lineage) 2 significantly decreased, whereas serotypes 6B, 9V and 19A and GPSCs 1, 6, 10 and 23 significantly increased in proportion post-uptake of PCV. Resistance determinants to penicillin, erythromycin, co-trimoxazole, fluoroquinolones and tetracycline, and multidrug resistance significantly increased in proportion post-uptake of PCV and especially among VT isolates. Co-trimoxazole resistance determinants were common pre- and post-uptake of PCV (85 and 93 %, respectively) and experienced the highest rates of recombination in the genome. Accessory gene frequencies were seen to be changing by small amounts across the frequency spectrum specifically among VT isolates, with the largest changes linked to antimicrobial resistance determinants. In summary, these results indicate that as of 2020 this pneumococcal population was not yet approaching a PCV-induced equilibrium and they highlight changes related to antimicrobial resistance. Augmenting PCV coverage and prudent use of antimicrobials are needed to counter invasive pneumococcal disease in this region.
| S-EPMC10926699 | biostudies-literature
Project description:The implementation of pneumococcal conjugate vaccines (PCVs) has led to a decline in vaccine-type disease. However, there is evidence that the epidemiology of non-typeable Haemophilus influenzae (NTHi) carriage and disease can be altered as a consequence of PCV introduction. We explored the epidemiological shifts in NTHi carriage using whole genome sequencing over a 5-year period that included PCV13 replacement of PCV7 in the UK's National Immunization Programme in 2010. Between 2008/09 and 2012/13 (October to March), nasopharyngeal swabs were taken from children <5 years of age. Significantly increased carriage post-PCV13 was observed and lineage-specific associations with Streptococcus pneumoniae were seen before but not after PCV13 introduction. NTHi were characterized into 11 discrete, temporally stable lineages, congruent with current knowledge regarding the clonality of NTHi. The increased carriage could not be linked to the expansion of a particular clone and different co-carriage dynamics were seen before PCV13 implementation when NTHi co-carried with vaccine serotype pneumococci. In summary, PCV13 introduction has been shown to have an indirect effect on NTHi epidemiology and there exists both negative and positive, distinct associations between pneumococci and NTHi. This should be considered when evaluating the impacts of pneumococcal vaccine design and policy.
| S-EPMC6202451 | biostudies-literature
Project description:Streptococcus pneumoniae is common nasopharyngeal commensal bacterium and important human pathogen. Vaccines against a subset of pneumococcal antigenic diversity have reduced rates of disease, without changing the frequency of asymptomatic carriage, through altering the bacterial population structure. These changes can be studied in detail through using genome sequencing to characterise systematically-sampled collections of carried S. pneumoniae. This dataset consists of 616 annotated draft genomes of isolates collected from children during routine visits to primary care physicians in Massachusetts between 2001, shortly after the seven valent polysaccharide conjugate vaccine was introduced, and 2007. Also made available are a core genome alignment and phylogeny describing the overall population structure, clusters of orthologous protein sequences, software for inferring serotype from Illumina reads, and whole genome alignments for the analysis of closely-related sets of pneumococci. These data can be used to study both bacterial evolution and the epidemiology of a pathogen population under selection from vaccine-induced immunity.
| S-EPMC4622223 | biostudies-literature
Project description:Streptococcus pneumoniae (the pneumococcus) is a common nasopharyngeal commensal that can cause invasive pneumococcal disease (IPD). Each component of current protein-polysaccharide conjugate vaccines (PCVs) generally induces immunity specific to one of the approximately 100 pneumococcal serotypes, and typically eliminates it from carriage and IPD through herd immunity. Overall carriage rates remain stable owing to replacement by non-PCV serotypes. Consequently, the net change in IPD incidence is determined by the relative invasiveness of the pre- and post-PCV-carried pneumococcal populations. In the present study, we identified PCVs expected to minimize the post-vaccine IPD burden by applying Bayesian optimization to an ecological model of serotype replacement that integrated epidemiological and genomic data. We compared optimal formulations for reducing infant-only or population-wide IPD, and identified potential benefits to including non-conserved pneumococcal carrier proteins. Vaccines were also devised to minimize IPD resistant to antibiotic treatment, despite the ecological model assuming that resistance levels in the carried population would be preserved. We found that expanding infant-administered PCV valency is likely to result in diminishing returns, and that complementary pairs of infant- and adult-administered vaccines could be a superior strategy. PCV performance was highly dependent on the circulating pneumococcal population, further highlighting the advantages of a diversity of anti-pneumococcal vaccination strategies.
| S-EPMC7614922 | biostudies-literature
Project description:BackgroundStreptococcus 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.MethodsIn this study, we fit a hierarchical Bayesian regression model to evaluate patterns of change in serotype prevalence post-PCV introduction in Israel from 2009 to 2016.ResultsWe 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.ConclusionsUnderstanding of serotype replacement is important as higher-valency vaccines are introduced.
| S-EPMC7664987 | biostudies-literature
Project description:Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.
| S-EPMC8730465 | biostudies-literature
Project description:BackgroundIntroduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria.MethodsThis was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST).ResultsThe prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (?90%) in infants aged <9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage.ConclusionsPneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our findings provide sound baseline data for impact assessment following vaccine introduction in Nigeria.
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Project description:Population Architecture using Genomics and Epidemiology (PAGE)
| PRJNA158499 | ENA
Project description:Many bacterial species are composed of multiple lineages distinguished by extensive variation in gene content. These often cocirculate in the same habitat, but the evolutionary and ecological processes that shape these complex populations are poorly understood. Addressing these questions is particularly important for Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen, because the changes in population structure associated with the recent introduction of partial-coverage vaccines have substantially reduced pneumococcal disease. Here we show that pneumococcal lineages from multiple populations each have a distinct combination of intermediate-frequency genes. Functional analysis suggested that these loci may be subject to negative frequency-dependent selection (NFDS) through interactions with other bacteria, hosts or mobile elements. Correspondingly, these genes had similar frequencies in four populations with dissimilar lineage compositions. These frequencies were maintained following substantial alterations in lineage prevalences once vaccination programmes began. Fitting a multilocus NFDS model of post-vaccine population dynamics to three genomic datasets using Approximate Bayesian Computation generated reproducible estimates of the influence of NFDS on pneumococcal evolution, the strength of which varied between loci. Simulations replicated the stable frequency of lineages unperturbed by vaccination, patterns of serotype switching and clonal replacement. This framework highlights how bacterial ecology affects the impact of clinical interventions.
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Project description:Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
| S-EPMC10781627 | biostudies-literature