Multiple Colonization with S. pneumoniae before and after Introduction of the Seven-Valent Conjugated Pneumococcal Polysaccharide Vaccine

Brugger, Silvio D.; Frey, Pascal M.; Aebi, Suzanne; Hinds, Jason; Mühlemann, Kathrin

doi:10.1371/journal.pone.0011638

Cited by 89 publications

(80 citation statements)

References 34 publications

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“…Immunoblotting methods have been developed and have improved sensitivity and specificity but are not used routinely in most laboratories (9,12). New methods include PCR with multiple primer sets targeting serotype-specific regions of cps (8, 11, 34, 35, 39, 50-52, 54), but serotype coverage is limited, which may not allow detection of replacement serotypes after conjugate vaccination (15,56). Microarray methods for serotyping can provide coverage of all known serotypes (19,60,62,65), but its high cost would limit its introduction in resourcepoor regions with high burdens of disease.…”

Section: Discussionmentioning

confidence: 99%

Sequetyping: Serotyping Streptococcus pneumoniae by a Single PCR Sequencing Strategy

et al. 2012

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dThe introduction of pneumococcal conjugate vaccines necessitates continued monitoring of circulating strains to assess vaccine efficacy and replacement serotypes. Conventional serological methods are costly, labor-intensive, and prone to misidentification, while current DNA-based methods have limited serotype coverage requiring multiple PCR primers. In this study, a computer algorithm was developed to interrogate the capsulation locus (cps) of vaccine serotypes to locate primer pairs in conserved regions that border variable regions and could differentiate between serotypes. In silico analysis of cps from 92 serotypes indicated that a primer pair spanning the regulatory gene cpsB could putatively amplify 84 serotypes and differentiate 46. This primer set was specific to Streptococcus pneumoniae, with no amplification observed for other species, including S. mitis, S. oralis, and S. pseudopneumoniae. One hundred thirty-eight pneumococcal strains covering 48 serotypes were tested. Of 23 vaccine serotypes included in the study, most (19/22, 86%) were identified correctly at least to the serogroup level, including all of the 13-valent conjugate vaccine and other replacement serotypes. Reproducibility was demonstrated by the correct sequetyping of different strains of a serotype. This novel sequence-based method employing a single PCR primer pair is cost-effective and simple. Furthermore, it has the potential to identify new serotypes that may evolve in the future.

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Section: Discussionmentioning

confidence: 99%

Sequetyping: Serotyping Streptococcus pneumoniae by a Single PCR Sequencing Strategy

et al. 2012

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“…Multiple serotypes co-circulate within host populations [1]; epidemiological modelling suggests that serotypes vary in their ability to displace, and to prevent displacement by, competing serotypes [3,7,10,13,14]. Instances of co-colonization by multiple S. pneumoniae strains have been observed during carriage in humans [15]. In addition, serotype replacement has been observed in experiments in a mouse model [14], and in humans following vaccination programmes [16].…”

Section: Introductionmentioning

confidence: 99%

Variation in Streptococcus pneumoniae susceptibility to human antimicrobial peptides may mediate intraspecific competition

2012

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Streptococcus pneumoniae is a facultative pathogen inhabiting the nasopharynx of humans where it is exposed to a range of antimicrobial peptides (AMPs) of the innate immune response. It is possible therefore that the susceptibility of strains to AMPs plays a role in determining their ability to colonize, and furthermore, that AMPs could mediate competitive interactions between co-colonizing genotypes. However, little is known about patterns of natural variation in AMP susceptibility of S. pneumoniae, and it is unclear whether the susceptibilities of an isolate to multiple human AMPs are correlated. We tested this by characterizing the susceptibility of 31 S. pneumoniae natural isolates to human neutrophil peptide (HNP-1) (a-defensin) and LL-37 (cathelicidin). We observed significant variation in susceptibility between isolates to both AMPs, and in the majority of isolates, susceptibilities to HNP-1 and LL-37 were uncorrelated. Clinical isolates were more susceptible to AMPs than were carriage isolates. The polysaccharide capsule of S. pneumoniae is thought to protect cells against AMPs. However, serotype alone could not explain the observed variation in susceptibility suggesting that genetic background plays an equally important role. We tested directly whether AMPs could mediate competition between isolates using competition experiments in the presence and absence of AMPs. These experiments demonstrated that AMPs could indeed reverse the outcome of competition between selected isolates. AMP-mediated competition could therefore contribute to the maintenance of intraspecific genetic diversity in S. pneumoniae.

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“…However, pneumococcal vaccination has minimal impact on the overall rate of pneumococcal carriage due to replacement by nonvaccine serotypes (3,8,11). Reports demonstrating an inverse relationship between nasopharyngeal carriage of vaccine type S. pneumoniae and Staphylococcus aureus (2,21,22) and increases in the proportion of otitis media caused by nontypeable H. influenzae following PCV7 vaccination (1,4,41) generated concern that removal of vaccine type pneumococci from the nasopharynx could facilitate colonization by other respiratory pathogens.…”

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confidence: 99%

Effect of Pneumococcal Vaccination on Nasopharyngeal Carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian Children

et al. 2012

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The 7-valent pneumococcal conjugate vaccine (PCV7) reduces carriage of vaccine type Streptococcus pneumoniae but leads to replacement by nonvaccine serotypes and may affect carriage of other respiratory pathogens. We investigated nasopharyngeal carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian infants participating in a pneumococcal vaccine trial using quantitative PCR. Vaccination did not affect pathogen carriage rates or densities, whereas significant differences between the two major ethnic groups were observed. N asopharyngeal (NP) carriage of pathogenic bacteria is the primary reservoir for maintaining bacterial species within a population (7) and is considered a prerequisite for development of major childhood diseases, including bacterial pneumonia, meningitis, and otitis media. Streptococcus pneumoniae is the most common bacterial cause of childhood pneumonia and is responsible for at least 800,000 child deaths annually, primarily in developing countries (18,33). While rarely fatal, otitis media is the most frequently reported childhood bacterial infection: approximately 80% of children experience otitis media by age three (17). S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the predominant causes of otitis media (36).PCV7 (Prevnar; Pfizer Inc.) effectively reduces carriage and subsequent disease caused by the serotypes of S. pneumoniae included in the vaccine. However, pneumococcal vaccination has minimal impact on the overall rate of pneumococcal carriage due to replacement by nonvaccine serotypes (3,8,11). Reports demonstrating an inverse relationship between nasopharyngeal carriage of vaccine type S. pneumoniae and Staphylococcus aureus (2,21,22) and increases in the proportion of otitis media caused by nontypeable H. influenzae following PCV7 vaccination (1, 4, 41) generated concern that removal of vaccine type pneumococci from the nasopharynx could facilitate colonization by other respiratory pathogens. This study aimed to evaluate the effects of pneumococcal immunization on carriage of respiratory pathogens in a high-risk population.A quantitative real-time PCR (qPCR) method was developed to measure S. pneumoniae, H. influenzae, M. catarrhalis, and S. aureus and applied to nasopharyngeal swabs collected from 17-month-old participants in a phase II pneumococcal vaccine trial in Suva, Fiji. The trial investigated appropriate infant dosing strategy of PCV7 and effects of a 23-valent polysaccharide (23vPPS; Pneumovax; Merck & Co., Inc.) booster given at 12 months. Enrollment, ethical approval, and swab collection and storage have been detailed previously (25,27,29). Swabs (collected in 2006 and in STGG media (19) were transported to Melbourne, Australia, on dry ice and stored at Ϫ80°C until use. The following sample groups were examined: group A (n ϭ 54), who received three doses of PCV7 at 6, 10, and 14 weeks of age; group B (n ϭ 48), who received three PCV7 doses plus a booster of 23vPPS at 12 months of age; and group H...

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Multiple Colonization with S. pneumoniae before and after Introduction of the Seven-Valent Conjugated Pneumococcal Polysaccharide Vaccine

Cited by 89 publications

References 34 publications

Sequetyping: Serotyping Streptococcus pneumoniae by a Single PCR Sequencing Strategy

Sequetyping: Serotyping Streptococcus pneumoniae by a Single PCR Sequencing Strategy

Variation in Streptococcus pneumoniae susceptibility to human antimicrobial peptides may mediate intraspecific competition

Effect of Pneumococcal Vaccination on Nasopharyngeal Carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian Children

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