Influenza-like Illness Incidence Is Not Reduced by Influenza Vaccination in a Cohort of Older Adults, Despite Effectively Reducing Laboratory-Confirmed Influenza Virus Infections.

Background: Data on the relative contribution of influenza virus and other respiratory pathogens to respiratory infections in community-dwelling older adults (≥60 years) are needed.

Methods: A prospective observational cohort study was performed in the Netherlands during 2 winters. Nasopharyngeal and oropharyngeal swabs were collected during influenza-like illness (ILI) episodes and from controls.

Immunogenicity, Safety and Reactogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable H. influenzae Protein D Conjugate Vaccine Coadministered With DTPa-IPV-Hib in Dutch Children: A Randomized Controlled Trial.

Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and DTPa-IPV-Hib (Pediacel Sanofi Pasteur MSD) when coadministered.

Methods: We performed booster assessment in a randomized controlled trial in the Netherlands.

Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients.

Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187).

Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children.

Rationale: Many bacterial pathogens causing respiratory infections in children are common residents of the respiratory tract. Insight into bacterial colonization patterns and microbiota stability at a young age might elucidate healthy or susceptible conditions for development of respiratory disease.

Objectives: To study bacterial succession of the respiratory microbiota in the first 2 years of life and its relation to respiratory health characteristics.

The impact of breastfeeding on nasopharyngeal microbial communities in infants.

Rationale: Breastfeeding elicits significant protection against respiratory tract infections in infancy. Modulation of respiratory microbiota might be part of the natural mechanisms of protection against respiratory diseases induced by breastfeeding.

Objectives: To study the association between breastfeeding and nasopharyngeal microbial communities, including all cultivable and noncultivable bacteria.

Seven-valent pneumococcal conjugate vaccine and nasopharyngeal microbiota in healthy children.

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.

Immunogenicity of 13-valent pneumococcal conjugate vaccine administered according to 4 different primary immunization schedules in infants: a randomized clinical trial.

Importance: Immunization schedules with pneumococcal conjugate vaccine (PCV) differ among countries regarding the number of doses, age at vaccinations, and interval between doses.

Objective: To assess the optimal primary vaccination schedule by comparing immunogenicity of 13-valent PCV (PCV13) in 4 different immunization schedules.

Design, Setting, And Participants: An open-label, parallel-group, randomized clinical trial of healthy term infants in a general community in The Netherlands conducted between June 30, 2010, and January 25, 2011, with 99% follow-up until age 12 months.

Perceived discomfort levels in healthy children participating in vaccine research.

When assessing the risks of a research protocol, review boards need to consider not only the possible harms but also the expected discomfort levels caused by the various study procedures. However, data on how children experience various study procedures are scarce. This study assessed perceived discomfort levels in 671 healthy children aged 0-2 years under-going vaccinations, venipunctures, and nasopharyngeal swab taking.

Superiority of trans-oral over trans-nasal sampling in detecting Streptococcus pneumoniae colonization in adults.

The human nasopharynx is the main reservoir for Streptococcus pneumoniae. We applied conventional and molecular methods to determine the prevalence of S. pneumoniae nasopharyngeal colonization in adults.

Effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine on nasopharyngeal bacterial colonization in young children: a randomized controlled trial.

Background: This study evaluated the effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) on nasopharyngeal bacterial colonization compared with the 7-valent pneumococcal conjugate vaccine (7vCRM) in young children.

Methods: A randomized controlled trial in the Netherlands, initiated 2 years after 7vCRM introduction, was conducted between 1 April 2008 and 1 December 2010. Infants (N = 780) received either PHiD-CV or 7vCRM (2:1) at 2, 3, 4, and 11-13 months of age.

Associations between pathogens in the upper respiratory tract of young children: interplay between viruses and bacteria.

Background: High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease.

Methodology/principal Findings: We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial.

Salivary immune responses to the 7-valent pneumococcal conjugate vaccine in the first 2 years of life.

Background: The CRM197-conjugated 7-valent pneumococcal vaccine (PCV7) is protective against vaccine serotype disease and nasopharyngeal carriage. Data on PCV7-induced mucosal antibodies in relation to systemic or natural anticapsular antibodies are scarce.

Methods: In a randomized controlled setting, children received PCV7 at age 2 and 4 months (2-dose group), at age 2, 4 and 11 months (2+1-dose group) or no PCV7 (control group).

Alternative sampling methods for detecting bacterial pathogens in children with upper respiratory tract infections.

Nasopharyngeal sampling is used for detecting bacteria commonly involved in upper respiratory tract infections, but it requires training and may not always be well tolerated. We sampled children (n = 66) of ages 0 to 4 years, with rhinorrhea, by using a nasopharyngeal swab, a nasal swab, and nose blowing/wiping into a paper tissue. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus were cultured at similar rates across methods with high concordance (80 to 97%), indicating that they are reliably detected by alternative means.

Long-term effects of pneumococcal conjugate vaccine on nasopharyngeal carriage of S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis.

Background: Shifts in pneumococcal serotypes following introduction of 7-valent pneumococcal conjugate vaccine (PCV-7) may alter the presence of other bacterial pathogens co-inhabiting the same nasopharyngeal niche.

Methodology/principal Findings: Nasopharyngeal prevalence rates of S. pneumoniae, S.

Nasopharyngeal colonization elicits antibody responses to staphylococcal and pneumococcal proteins that are not associated with a reduced risk of subsequent carriage.

Knowledge of the immunological correlates of Staphylococcus aureus and Streptococcus pneumoniae colonization is required for the search for future protein vaccines. We evaluated natural antibody levels against pneumococcal and staphylococcal proteins in relation to previous bacterial colonization with both pathogens. In a randomized controlled trial, nasopharyngeal samples were obtained from children at 1.

Effect of 7-valent pneumococcal conjugate vaccine on nasopharyngeal carriage with Haemophilus influenzae and Moraxella catarrhalis in a randomized controlled trial.

Seven-valent CRM197-conjugated pneumococcal conjugate vaccine (PCV7(CRM197)) reduces both vaccine serotype nasopharyngeal colonization and vaccine serotype acute otitis media by 50-60%. However, overall pneumococcal carriage and impact on otitis media are partly offset by concomitant increase of nonvaccine serotypes. We investigated in a randomized controlled trial the impact of 2-doses and 2+1-doses of PCV7(CRM197) on carriage of Streptococcus pneumoniae and of other nasopharyngeal commensals and well-known otitis media pathogens, Haemophilus influenzae and Moraxella catarrhalis, in children.

Lower immunoglobulin G antibody responses to pneumococcal conjugate vaccination at the age of 2 years after previous nasopharyngeal carriage of Streptococcus pneumoniae.

Objective: To determine whether nasopharyngeal pneumococcal carriage with serotypes 6B, 19F, or 23F interferes with immunoglobulin G (IgG) antibody responses to vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) at the age 24 months.

Study Design: Blood samples were collected before and after a PCV7 challenge vaccination at age 24 months from subsets of children participating in a randomized controlled trial. Children previously had received two doses of PCV7 at 2 and 4 months, two plus one doses of PCV7 at 2, 4, and 11 months, or no dosage until 24 months.

Effect of seven-valent pneumococcal conjugate vaccine on Staphylococcus aureus colonisation in a randomised controlled trial.

Background: Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the effect of PCV7 on nasopharyngeal colonisation with S. aureus in children and parents.

Impact of infant and preschool pertussis vaccinations on memory B-cell responses in children at 4 years of age.

Whooping cough, caused by Bordetella pertussis, is reemerging in the vaccinated population. Antibody levels to pertussis antigens wane rapidly after both whole-cell (wP) and acellular pertussis (aP) vaccination and protection may largely depend on long-term B- and T-cell immunity. We studied the effect of wP and aP infant priming at 2, 3, 4 and 11 months according to the Dutch immunization program on pertussis-specific memory B-cell responses before and after a booster vaccination with either a high- or low-pertussis dose vaccine at 4 years of age.

Nontypeable Haemophilus influenzae invasive disease in The Netherlands: a retrospective surveillance study 2001-2008.

Background: Nontypeable (unencapsulated) strains of Haemophilus influenzae (ntHi) are usually involved in respiratory tract infections and otitis media but may also cause invasive disease. The epidemiology, the course of disease, and the outcome of ntHi invasive disease are not well established. For prevention, risk groups that might benefit from vaccination have to be defined.

Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine and DTPa-IPV-Hib when coadministered as a 3-dose primary vaccination schedule in The Netherlands: a randomized controlled trial.

Background: Recent reviews have highlighted the unpredictability of immunologic interference when multivalent conjugated vaccines are coadministered with other pediatric vaccines.

Objective: To evaluate immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix, GlaxoSmithKline Biologicals) and DTPa-IPV-Hib (Pediacel, Sanofi Pasteur MSD) when coadministered as a 3-dose primary vaccination course.

Material And Methods: In a single-blind, single-center, randomized controlled trial in the Netherlands, healthy infants (n = 780) were randomly assigned (1:1:1) to receive either (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix Hexa, GlaxoSmithKline Biologicals), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (Prevenar/Prevnar, Pfizer Inc.

Carriage of Streptococcus pneumoniae 3 years after start of vaccination program, the Netherlands.

To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) program, we conducted a cross-sectional observational study on nasopharyngeal carriage of Streptococcus pneumoniae 3 years after implementation of the program in the Netherlands. We compared pneumococcal serotypes in 329 prebooster 11-month-old children, 330 fully vaccinated 24-month-old children, and 324 parents with age-matched pre-PCV7 (unvaccinated) controls (ages 12 and 24 months, n = 319 and n = 321, respectively) and 296 of their parents. PCV7 serotype prevalences before and after PCV7 implementation, respectively, were 38% and 8% among 11-month-old children, 36% and 4% among 24-month-old children, and 8% and 1% among parents.

Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins.

Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the 1950s in developed countries pertussis vaccinations are included in the national immunization program. However, antibody levels rapidly wane after both whole cell and acellular pertussis vaccination.

Pneumococcal conjugate vaccination and nasopharyngeal acquisition of pneumococcal serotype 19A strains.

Context: The rapid increase in multiresistant serotype 19A as a cause of invasive and respiratory pneumococcal disease has been associated in time with the widespread implementation of 7-valent pneumococcal conjugate vaccination (PCV-7) in several countries. Because spontaneous fluctuations in time and antibiotic selective pressure may have induced this serotype 19A increase, controlled studies are needed to assess the role of PCV-7.

Objective: To examine the association of PCV-7 vaccination and nasopharyngeal acquisition of serotype 19A pneumococci, their clonal distribution, and antibiotic susceptibility.

Comparability of antibody response to a booster dose of 7-valent pneumococcal conjugate vaccine in infants primed with either 2 or 3 doses.

In this cohort study we compared IgG antibody levels between infants immunized with 7-valent CRM197-conjugated pneumococcal vaccine (PCV-7) at 2, 4 and 11 months and at 2, 3, 4 and 11 months of age, as measured by double adsorption ELISA. Pre- and post-booster levels following the 2+1- and 3+1-dose schedule were comparable for 5 out of 7 serotypes except for serotypes 6B and 19F. The proportion of children reaching post-booster antibody thresholds were comparable except for 6B (>or=1.