Nasopharyngeal Carriage of<i>Streptococcus pneumoniae</i>Shortly before Vaccination with a Pneumococcal Conjugate Vaccine Causes Serotype‐Specific Hyporesponsiveness in Early Infancy

Dagan, Ron; Givon-Lavi, Noga; Greenberg, David; Fritzell, Bernard; Siegrist, Claire Anne

doi:10.1086/652006

Cited by 93 publications

(59 citation statements)

References 39 publications

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“…Second, no sufficient opsonization activity was found, probably because of the lower avidity of serotype-specific IgG against pneumococcal infection (17,30). Third, pneumococcal carriage in the nasopharynx was detected, which may also be caused by immune paralysis (32,33). In this study, the level of anti-6B IgG was higher than 0.35 g/ml (2.1 g/ml), whereas the OI was Ͻ8.…”

Section: Discussioncontrasting

confidence: 53%

Capsule Switching and Antimicrobial Resistance Acquired during Repeated Streptococcus pneumoniae Pneumonia Episodes

et al. 2015

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e Streptococcus pneumoniae colonizes the nasopharyngeal mucus in healthy people and causes otitis media, pneumonia, bacteremia, and meningitis. In this study, we analyzed an S. pneumoniae strain that caused 7 repeated pneumonia episodes in an 80-month-old patient with cerebral palsy during a period of 25 months. A total of 10 S. pneumoniae strains were obtained from sputum samples, and serotype 6B was isolated from samples from the first 5 episodes, whereas serotype 6A was isolated from samples from the last 2. Whole-genome sequencing showed clonality of the 10 isolates with 10 single nucleotide polymorphisms (SNPs) in the genomes. Among these SNPs, one single point mutation in the wciP gene was presumed to relate to the serotype switching from 6B to 6A, and the other mutations in parC and gyrA were related to fluoroquinolone resistance. These results suggested that an S. pneumoniae strain, which asymptomatically colonized the patient's nasopharynx or was horizontally transmitted from an asymptomatic carrier, caused the repeated pneumonia events. Phenotypic variations in the capsule type and antimicrobial susceptibility occurred during the carrier state. Hyporesponsiveness to serotypes 6B and 6A of S. pneumoniae was found even after vaccination with the 7-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine. After an additional vaccination with the 13-valent pneumococcal conjugate vaccine, opsonic activities for both serotypes 6A and 6B significantly increased and are expected to prevent relapse by the same strain. Streptococcus pneumoniae is the etiologic agent of several bacterial diseases, such as otitis media, pneumonia, bacteremia, and meningitis (1-3), and it can asymptomatically colonize a child's nasopharynx for months (4). Colonization by S. pneumoniae is a prerequisite for various types of pneumococcal diseases and the source of transmission of the bacterium between people (5, 6). In Japan, approximately 80% of 3-year-old children were colonized by this bacterium, which may cause pneumococcal diseases, at least once (7).Since 2000, the widespread use of 7-and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) has reduced the incidence of pneumococcal infections (8-11) and the colonization rate of the vaccine serotypes but has not affected the overall colonization (12-15). In Japan, PCV7 was introduced in 2010 and was replaced by PCV13 in November 2013. After 2011, invasive pneumococcal disease (IPD) caused by S. pneumoniae isolates belonging to serotypes included in the PCV7 decreased (16). However, some unusual vaccine failures and/or breakthrough infection cases were reported together with the hyporesponsiveness to one or several serotypes (17).Since 2011, we have observed repeated pneumococcal pneumonia episodes in a child who has an underlying disease. Although vaccinations with PCV7 were performed, an additional 6 pneumococcal pneumonia infections occurred during the following 24 months. In this longitudinal study, we analyzed 10 S. pneu...

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Section: Discussioncontrasting

confidence: 53%

Capsule Switching and Antimicrobial Resistance Acquired during Repeated Streptococcus pneumoniae Pneumonia Episodes

et al. 2015

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“…Third, it may not prevent nasopharyngeal (NP) colonization (165)(166)(167) or mucosal infections (nonbacteremic pneumonia and otitis media) (168,169). Finally, antibody concentrations after subsequent doses of PPV23 appear to be lower than those after primary vaccination (170,171); this hyporesponsiveness is related to the large amount of PS in PPV23, which is thought to exhaust the memory B-cell pool without replenishment (172).…”

Section: Polysaccharide Vaccinesmentioning

confidence: 99%

Pneumococcal Capsules and Their Types: Past, Present, and Future

et al. 2015

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SUMMARY Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules.

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“…Dagan et al reported that in subjects carrying VT pneumococci before the first dose of PCV7, the serum IgG response to the carried serotype after 2 or 3 doses was significantly lower than that in noncarriers (9). Furthermore, the prevalence of pneumococal phenotypes is associated with the structure of the capsular polysaccharide (10,11).…”

Section: Discussionmentioning

confidence: 99%

Changes in Streptococcus pneumoniae Serotypes in the Nasopharynx of Japanese Children after Inoculation with a Heptavalent Pneumococcal Conjugate Vaccine

et al. 2014

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SUMMARY:In this study, we prospectively investigated changes in Streptococcus pneumoniae serotypes among Japanese children after heptavalent pneumococcal conjugate vaccine (PCV7) inoculation. We acquired nasopharyngeal swabs from the children at each routine PCV7 inoculation and again at least 2 months after the last PCV7 inoculation. We defined 2 periods with regard to each culture: the inoculation period as``the period of pre-or incomplete vaccination'' and post-inoculation as``the period of post-or completed vaccination.'' The prevalence of vaccine-type (VT) pneumococci was significantly reduced from 9.5z in the inoculation-period cultures to 2.9z in the post-inoculation cultures ( P º 0.01). There was no statistical difference in the prevalence of non-vaccine-type pneumococci between the inoculation-period and post-inoculation cultures (24.1z versus 23.4z). The protection of PCV7 against nasopharyngeal colonization was inferred from the decrease in VT carriage post-inoculation. The decrease in VT carriage may be conducive to reducing VT transmission within the study area.

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Nasopharyngeal Carriage ofStreptococcus pneumoniaeShortly before Vaccination with a Pneumococcal Conjugate Vaccine Causes Serotype‐Specific Hyporesponsiveness in Early Infancy

Abstract: isrctn.org identifier: ISRCTN28445844.

Cited by 93 publications

References 39 publications

Capsule Switching and Antimicrobial Resistance Acquired during Repeated Streptococcus pneumoniae Pneumonia Episodes

Capsule Switching and Antimicrobial Resistance Acquired during Repeated Streptococcus pneumoniae Pneumonia Episodes

Pneumococcal Capsules and Their Types: Past, Present, and Future

Changes in Streptococcus pneumoniae Serotypes in the Nasopharynx of Japanese Children after Inoculation with a Heptavalent Pneumococcal Conjugate Vaccine

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