Increase in serotype 6C pneumococcal carriage, United Kingdom.
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ABSTRACT:
SUBMITTER: Tocheva AS
PROVIDER: S-EPMC2874357 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We have recently reported a new pneumococcal serotype (6C), which is closely related to serotype 6A (I. H. Park et al., J. Clin. Microbiol. 45:1225-1233, 2007). To investigate the genetic basis for serotype 6C, we studied the capsule gene loci of 14 6C isolates from three different continents, including one isolated in Alabama 27 years ago. The wciN region of all 6C isolates has a 1,029-bp-long sequence that replaces the 1,222-bp-long sequence of the 6A wciN region. This recombination event has created a new 1,125-bp-long open reading frame which encodes a product that is also homologous to glycosyl transferases. Flanking this introduced gene is 300 bp upstream and 100 bp downstream with only about 90% homology with 6A and which is identical in all 6C isolates. Transfer of the wciN region converts 6A to 6C. Determination of the DNA sequence of the entire capsule gene locus of one 6C isolate showed that the 6C capsule gene locus is almost identical (>98% homologous) to that of 6A except for the wciN region. These findings indicate that the 6C capsule type originated more than 27 years ago by a single recombination event in a 6A locus in which 6A wciN was replaced by a gene of unknown origin.
| S-EPMC1951153 | biostudies-literature
Project description:Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7) is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n?=?15) and disease (n?=?4) states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST) clonal complex 395 (CC395). A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design.
| S-EPMC3665553 | biostudies-literature
Project description:The seven-valent pneumococcal conjugate vaccine (PCV7) was added to the UK national immunisation programme in September 2006. PCV13 replaced PCV7 in April 2010. As carriage precedes disease cases this study collected carried pneumococci from children each winter from 2006/7 to 2010/11 over PCV introduction. Conventional microbiology and whole genome sequencing were utilised to characterise pneumococcal strains. Overall prevalence of pneumococcal carriage remained stable. Vaccine serotypes (VT) decreased (p<0.0001) with concomitant increases in non-vaccine serotypes (NVT). In winter 2010/11 only one isolate of PCV7 VT was observed (6B). PCV13 unique VTs decreased between winters immediately preceding and following PCV13 introduction (p=0.04). Significant decreases for VTs 6B, 19F, 23F (PCV7) and 6A (PCV13) and increases for NVT 21, 23B, 33F and 35F were detected. The serotype replacement was accompanied by parallel changes in genotype prevalence for associated sequence types with clonal expansion contributing to replacement. By winter 2010/11, serotype coverage of PCV7 and PCV13 was 1% and 11% respectively. VT replacement was observed for PCV7 and PCV13 serotypes. Conjugate vaccine design and use requires continuous monitoring and revision.
| S-EPMC4392391 | biostudies-literature
Project description:After switching from 13-valent to 10-valent pneumococcal conjugate vaccine (PCV10) (2015-2016) for children in Belgium, we observed rapid reemergence of serotype 19A invasive pneumococcal disease (IPD). Whole-genome sequencing of 166 serotype 19A IPD isolates from children (n = 54) and older adults (n = 56) and carriage isolates from healthy children (n = 56) collected after the vaccine switch (2017-2018) showed 24 sequence types (STs). ST416 (global pneumococcal sequence cluster [GPSC] 4) and ST994 (GPSC146) accounted for 75.9% of IPD strains from children and 65.7% of IPD (children and older adults) and carriage isolates in the PCV10 period (2017-2018). These STs differed from predominant 19A IPD STs after introduction of PCV7 (2011) in Belgium (ST193 [GPSC11] and ST276 [GPSC10]), which indicates that prediction of emerging strains cannot be based solely on historical emerging strains. Despite their susceptible antimicrobial drug profiles, these clones spread in carriage and IPD during PCV10 use.
| S-EPMC9328928 | biostudies-literature
Project description:MenACWY conjugate vaccination was recently introduced in the United Kingdom for adolescents and young adults to reduce disease from infection by Neisseria meningitidis group W. We conducted a cross-sectional meningococcal carriage study in first-year UK university students. Despite 71% MenACWY vaccine coverage, carriage of group W increased substantially.
| S-EPMC5443439 | biostudies-literature
Project description:BackgroundThe importance of specific serotypes causing invasive pneumococcal disease (IPD) differs by age. Data on pneumococcal carriage in different age groups, along with data on serotype-specific invasiveness, could help explain these age-related patterns and their implications for vaccination.MethodsUsing pneumococcal carriage and disease data from Israel, we evaluated the association between serotype-specific IPD in adults and serotype-specific carriage prevalence among children in different age categories, while adjusting for serotype-specific invasiveness. We estimated carriage prevalence using different age groupings that were selected a priori. The Deviance Information Criterion was used to determine which age groupings of carriage data best fit the adult IPD data. Serotype-specific disease patterns were further evaluated by stratifying IPD data by comorbidity status.ResultsThe relative frequency of serotypes causing IPD differed between adults and children, and also differed between older and younger adults and between adults with and without comorbidities. Serotypes overrepresented as causes of IPD in adults were more commonly carried in older children compared with younger children. In line with this, the serotype-specific frequency of carriage in older children, rather than infants, best correlated with serotype-specific IPD in adults.ConclusionsThese analyses demonstrate that the serotype patterns in carriage in older children, rather than infants, are best correlated with disease patterns in adults. This might suggest these older children are more influential for disease patterns in adults. These insights could help in optimizing vaccination strategies to reduce disease burden across all ages.
| S-EPMC8315131 | biostudies-literature
Project description:BackgroundPneumococcal colonization is a precursor to pneumonia, and pneumococcal conjugate vaccines (PCV) can decrease vaccine-type (VT) colonization. Pneumococcal colonization studies are traditionally done among healthy children in the community; however, VT colonization prevalence may differ between these children and those with pneumonia. We assessed overall and VT pneumococcal colonization and factors associated with colonization among children with and without pneumonia after Mozambique introduced 10-valent PCV (PCV10) in 2013.MethodsWe used data from ongoing pneumonia surveillance in children aged <5 years and from cross-sectional nasopharyngeal colonization surveys conducted in October 2014 -April 2015 and October 2015 -May 2016. Pneumonia was defined using WHO standard criteria for radiologically confirmed pneumonia. Children with pneumonia enrolled from January 2014 -April 2016 were compared to children without pneumonia enrolled from the cross-sectional surveys. Clinical data and nasopharyngeal (NP) swabs were collected from each child. NP specimens were cultured for pneumococci, and culture-negative specimens from children with pneumonia underwent polymerase chain reaction (PCR).ResultsOf 778 and 927 children with and without pneumonia, 97.4% and 27.0% were exposed to antibiotics before swab collection, respectively. Based on culture, pneumococcal colonization was 45.1% for children with and 84.5% for children without pneumonia (P<0.001); VT pneumococcal colonization was 18.6% for children with and 23.4% for children without pneumonia (P = 0.02). The addition of PCR in children with pneumonia increased overall and VT-pneumococcal colonization to 79.2% and 31.1%, respectively. In multivariable analysis including PCR results, pneumonia was associated with VT pneumococcal colonization (adjusted OR: 1.4, 95%CI: 1.10-1.78).ConclusionVaccine-type pneumococcal colonization remains common among children with and without pneumonia post-PCV10 introduction in Mozambique. In a population of children with high antibiotic exposure, the use of PCR for culture-negative NP swabs can improve assessment of pneumococcal colonization and circulating serotypes.
| S-EPMC6019677 | biostudies-literature
Project description:There are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess PCV carriage using rolling, prospective nasopharyngeal carriage surveys between 2015 and 2018, 3.6-7.1 years after Malawi's 2011 PCV13 introduction. Carriage decay rate is analysed using non-linear regression. Despite evidence of reduction in VT carriage over the study period, there is high persistent residual carriage. This includes among PCV-vaccinated children 3-5-year-old (16.1% relative reduction from 19.9% to 16.7%); PCV-unvaccinated children 6-8-year-old (40.5% reduction from 26.4% to 15.7%); HIV-infected adults 18-40-years-old on antiretroviral therapy (41.4% reduction from 15.2% to 8.9%). VT carriage prevalence half-life is similar among PCV-vaccinated and PCV-unvaccinated children (3.26 and 3.34 years, respectively). Compared with high-income settings, there is high residual VT carriage 3.6-7.1 years after PCV introduction. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns, is required.
| S-EPMC7203201 | biostudies-literature
Project description:Streptococcus pneumoniae is an opportunistic pathogen that, while usually carried asymptomatically, can cause severe invasive diseases like meningitis and bacteremic pneumonia. A central goal in S. pneumoniae public health management is to identify which serotypes (immunologically distinct strains) pose the most risk of invasive disease. The most common invasiveness metrics use cross-sectional data (i.e., invasive odds ratios (IOR)), or longitudinal data (i.e., attack rates (AR)). To assess the reliability of these metrics we developed an epidemiological model of carriage and invasive disease. Our mathematical analyses illustrate qualitative failures with the IOR metric (e.g., IOR can decline with increasing invasiveness parameters). Fitting the model to both longitudinal and cross-sectional data, our analysis supports previous work indicating that invasion risk is maximal at or near time of colonization. This pattern of early invasive disease risk leads to substantial (up to 5-fold) biases when estimating underlying differences in invasiveness from IOR metrics, due to the impact of carriage duration on IOR. Together, these results raise serious concerns with the IOR metric as a basis for public health decision-making and lend support for multiple alternate metrics including AR.
| S-EPMC10786323 | biostudies-literature
Project description:BackgroundIn 2007, Park et al. identified a novel serotype among Streptococcus pneumoniae serogroup 6 which they named serotype 6C. The aim of this study was to evaluate with the Neufeld test a novel S. pneumoniae serotype 6C type specific polyclonal antiserum. In addition, serotype 6C isolates found in Denmark in 2007 and 2008 as well as eight old original serotype 6A isolates were characterised.MethodsIn this study, 181 clinical Streptococcus pneumoniae isolates from Denmark 2007 and 2008 were examined; 96 isolates had previously been typed as serotype 6A and 85 as serotype 6B. In addition, eight older isolates from 1952 to 1987, earlier serotyped as 6A, were examined. Serotype 6C isolates were identified by PCR and serotyping with the Neufeld test using the novel type specific polyclonal antiserum, factor antiserum 6 d, in addition to factor antisera 6b, 6b* (absorbed free for cross-reactions to serotype 6C) and 6c. All antisera are commercially available and antiserum 6b obtained from the supplier after 1 January 2009 is antiserum 6b*. All serotype 6C isolates were further characterised using multi-locus sequence typing.ResultsWhen retesting all 96 original serotype 6A isolates by PCR and the Neufeld test, 29.6% (24 of 81) of the invasive isolates in Denmark from 2007 and 2008 were recognised as serotype 6C. In addition, three of eight old isolates originally serotyped as 6A were identified to be serotype 6C. The oldest serotype 6C isolate was from 1962. The serotype 6C isolates belonged to eleven different sequence types (ST) and nine clonal complexes (CC), ST1692 (CC395), ST386 (CC386) and ST481 (CC460) were the predominant types.ConclusionsWe tested a novel polyclonal antiserum 6 d, as well as modified antiserum 6b*, provided a scheme for the serotyping of S. pneumoniae serogroup 6 using the Neufeld test and compared the serotyping method with PCR based methods. The two types of methods provided the same results. In future, it will, therefore, be possible to test also serotype 6C in accordance to the standard method for serotyping of S. pneumoniae recommended by WHO.Among all invasive isolates from Denmark 2007 and 2008, serotype 6C constituted 29.6% of the original serotype 6A isolates. The serotype 6C isolates were found to be diverse belonging to a number of different STs and CCs of which most have been observed in other countries previously. Serotype 6C is regarded as an "old" serotype being present among S. pneumoniae isolates in Denmark for at least 48 years. The genetic diversity of serotype 6C isolates and their genetic relationship to other serotypes suggested that serotype 6C strains may have arisen from several different independent recombination events involving different parental strains such as serotypes 6A, 6B, 23F and 4.
| S-EPMC2949764 | biostudies-literature