Seven-Valent Pneumococcal Conjugate Vaccine and Nasopharyngeal Microbiota in Healthy Children

Emerging Infectious Diseases (Impact Factor: 6.75). 02/2014; 20(2):201-10. DOI: 10.3201/eid2002.131220
Source: PubMed


Seven-valent pneumococcal conjugate vaccine (PCV-7) is effective against vaccine serotype disease and carriage. Nevertheless, shifts in colonization and disease toward nonvaccine serotypes and other potential pathogens have been described. To understand the extent of these shifts, we analyzed nasopharyngeal microbial profiles of 97 PCV-7-vaccinated infants and 103 control infants participating in a randomized controlled trial in the Netherlands. PCV-7 immunization resulted in a temporary shift in microbial community composition and increased bacterial diversity. Immunization also resulted in decreased presence of the pneumococcal vaccine serotype and an increase in the relative abundance and presence of nonpneumococcal streptococci and anaerobic bacteria. Furthermore, the abundance of Haemophilus and Staphylococcus bacteria in vaccinees was increased over that in controls. This study illustrates the much broader effect of vaccination with PCV-7 on the microbial community than currently assumed, and highlights the need for careful monitoring when implementing vaccines directed against common colonizers.

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Available from: Krzysztof Trzciński, Feb 11, 2014
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    • "Understanding the relationships between microbes of the upper respiratory tract (URT) during perturbations is anticipated to provide insights into the pathogenesis of URT infections. Studies of the nasopharyngeal microbiota in children have observed changes due to season (winter/fall versus spring) [4] and treatment with antimicrobials or the heptavalent conjugated pneumococcal polysaccharide vaccine [6,7]. Specific commensal taxa have been negatively associated with colonization of known pathogenic bacteria and with acute otitis media in children, and these relationships changed depending on antibiotic usage [8]. "
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    ABSTRACT: Background The bacterial communities of the nasopharynx play an important role in upper respiratory tract infections (URTIs). Our study represents the first survey of the nasopharynx during a known, controlled viral challenge. We aimed to gain a better understanding of the composition and dynamics of the nasopharyngeal microbiome during viral infection. Methods Rhinovirus illnesses were induced by self-inoculation using the finger to nose or eye natural transmission route in ten otherwise healthy young adults. Nasal lavage fluid samples (NLF) samples were collected at specific time points before, during, and following experimental rhinovirus inoculation. Bacterial DNA from each sample (N = 97 from 10 subjects) was subjected to 16S rRNA sequencing by amplifying the V1-V2 hypervariable region followed by sequencing using the 454-FLX platform. Results This survey of the nasopharyngeal microbiota revealed a highly complex microbial ecosystem. Taxonomic composition varied widely between subjects and between time points of the same subject. We also observed significantly higher diversity in not infected individuals compared to infected individuals. Two genera – Neisseria and Propionibacterium – differed significantly between infected and not infected individuals. Certain phyla, including Firmicutes, Actinobacteria, and Proteobacteria, were detected in all samples. Conclusions Our results reveal the complex and diverse nature of the nasopharyngeal microbiota in both healthy and viral-challenged adults. Although some phyla were common to all samples, differences in levels of diversity and selected phyla were detected between infected and uninfected participants. Deeper, species-level metagenomic sequencing in a larger sample is warranted.
    06/2014; 2(1):22. DOI:10.1186/2049-2618-2-22
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    ABSTRACT: The widespread use of the 7-valent pneumococcal conjugate vaccine has been associated with epidemiological changes of mucosal and invasive pneumococcal disease. No study describes the impact of 13-valent pneumococcal conjugate vaccine (PCV13) on chronic sinusitis in children. We describe changes in epidemiology of S. pneumoniae chronic sinusitis after the introduction of PCV13 at Texas Children's Hospital (TCH). We identified patients <18 years with positive sinus culture for S. pneumoniae who underwent endoscopic sinus surgery due to chronic sinusitis from August 2008 to December 2013 at TCH. Isolates were serotyped by the capsular swelling method. Demographic and clinical information was collected retrospectively. The χ2 test and Fisher's exact test were used to analyze dichotomous variables. We identified 91 cases of chronic sinusitis with positive sinus culture for S. pneumoniae. Sixty-one (67%) isolates were non-PCV13 serotypes. PCV13 cases decreased 31% in the post-PCV13 period (p=0.003). Serotype 19A decreased 27% in the post-PCV13 period (p=0.007), but accounted for all the isolates with penicillin MIC ≥ 4µg/ml and ceftriaxone MIC ≥2 µg/ml. Serotypes 19A (38%) and 15C (17%) were the most common in the pre- and post-PCV13 periods, respectively. The most common organism co-isolated was Haemophilus influenzae (52%). Isolation of Prevotella spp. increased in the post-PCV13 period (p=0.02). S. pneumoniae continues to represent an important pathogen in chronic sinusitis in children < 5 years. After the introduction of PCV13, S. pneumoniae isolation declined in children with chronic sinusitis at TCH. We also observed a substantial reduction of PCV13 serotypes, predominantly serotype 19A.
    The Pediatric Infectious Disease Journal 04/2014; 33(10). DOI:10.1097/INF.0000000000000387 · 2.72 Impact Factor
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    ABSTRACT: While nasopharyngeal sampling is the gold standard for the detection of Streptococcus pneumoniae carriage, historically seen, saliva sampling also seems highly sensitive for pneumococcal detection. We investigated S. pneumoniae carriage in saliva from fifty schoolchildren by conventional and molecular methods. Saliva was first culture-enriched for pneumococci, after which, DNA was extracted from all bacterial growth and tested by quantitative-PCR (qPCR) for pneumococcus-specific genes lytA and piaA. Next, serotype composition of the samples was determined by serotype-specific qPCRs, conventional-PCRs (cPCR) and sequencing of cPCR amplicons. Although only 2 (4%) of 50 samples were positive by conventional diagnostic culture, 44 (88%) were positive for pneumococci by qPCR. In total, we detected the presence of at least 81 pneumococcal strains representing 20 serotypes in samples from 44 carriers with 23 carriers (52%) positive for multiple (up to 6) serotypes. The number of serotypes detected per sample correlated with pneumococcal abundance. This study shows that saliva could be used as a tool for future pneumococcal surveillance studies. Furthermore, high rates of pneumococcal carriage and co-carriage of multiple pneumococcal strains together with a large number of serotypes in circulation suggests a ubiquitous presence of S. pneumoniae in saliva of school-aged children. Our results also suggest that factors promoting pneumococcal carriage within individual hosts may weaken competitive interactions between S. pneumoniae strains.
    PLoS ONE 07/2014; 9(7):e102045. DOI:10.1371/journal.pone.0102045 · 3.23 Impact Factor
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