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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. Nasopharyngeal prevalence rates of S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis were investigated before, 3 and 4.5 years after introduction of PCV-7 in the national immunisation program in children at 11 and 24 months of age, and parents of 24-month-old children (n≈330/group) using conventional culture methods. Despite a virtual disappearance of PCV-7 serotypes over time, similar overall pneumococcal rates were observed in all age groups, except for a significant reduction in the 11-month-old group (adjusted Odds Ratio after 4.5 years 0.48, 95% Confidence Interval 0.34-0.67). Before, 3 and 4.5 years after PCV-7 implementation, prevalence rates of S. aureus were 5%, 9% and 14% at 11 months of age (3.59, 1.90-6.79) and 20%, 32% and 34% in parents (1.96, 1.36-2.83), but remained similar at 24 months of age, respectively. Prevalence rates of H. influenzae were 46%, 65% and 65% at 11 months (2.22, 1.58-3.13), 52%, 73% and 76% at 24 months of age (2.68, 1.88-3.82) and 23%, 30% and 40% in parents (2.26, 1.58-3.33), respectively. No consistent changes in M. catarrhalis carriage rates were observed over time. In addition to large shifts in pneumococcal serotypes, persistently higher nasopharyngeal prevalence rates of S. aureus and H. influenzae were observed among young children and their parents after PCV-7 implementation. These findings may have implications for disease incidence and antibiotic treatment in the post-PCV era.

Background Recurrent respiratory tract infections (rRTIs) frequently affect young children and are associated with antibody deficiencies. We investigated the prevalence of and epidemiological risk factors associated with antibody deficiencies in young children with rRTIs and their progression over time, and linked these to prospectively measured RTI symptoms. Methods We included children <7 years with rRTIs in a prospective cohort study. Patient characteristics associated with antibody deficiencies were identified using multivariable logistic regression analysis. Results We included 146 children with a median age of 3.1 years. Daily RTI symptoms were monitored in winter in n  = 73 children and repeated immunoglobulin level measurements were performed in n  = 45 children. Antibody deficiency was diagnosed in 56% and associated with prematurity (OR 3.17 [1.15–10.29]) and a family history of rRTIs (OR 2.37 [1.11–5.15]). Respiratory symptoms did not differ between children with and without antibody deficiencies. During follow-up, antibody deficiency diagnosis remained unchanged in 67%, while 18% of children progressed to a more severe phenotype. Conclusion Immune maturation and genetic predisposition may lie at the basis of antibody deficiencies commonly observed in early life. Because disease severity did not differ between children with and without antibody deficiency, we suggest symptom management can be similar for all children with rRTIs. Impact An antibody deficiency was present in 56% of children <7 years with recurrent respiratory tract infections (rRTIs) in a Dutch tertiary hospital setting. Prematurity and a family history of rRTIs were associated with antibody deficiencies, suggesting that immune maturation and genetic predisposition may lie at the basis of antibody deficiencies in early life. RTI symptoms did not differ between children with and without antibody deficiency, suggesting that symptom management can be similar for all children with rRTIs, irrespective of humoral immunological deficiencies. During follow-up, 18% of children progressed to a more severe phenotype, emphasizing that early diagnosis is warranted to prevent long-term morbidity and increase quality of life.

Cystic fibrosis (CF) is characterized by early structural lung disease caused by pulmonary infections. The nasopharynx of infants is a major ecological reservoir of potential respiratory pathogens. To investigate the development of nasopharyngeal microbiota profiles in infants with CF compared with those of healthy control subjects during the first 6 months of life. We conducted a prospective cohort study, from the time of diagnosis onward, in which we collected questionnaires and 324 nasopharynx samples from 20 infants with CF and 45 age-matched healthy control subjects. Microbiota profiles were characterized by 16S ribosomal RNA-based sequencing. We observed significant differences in microbial community composition (P < 0.0002 by permutational multivariate analysis of variance) and development between groups. In infants with CF, early Staphylococcus aureus and, to a lesser extent, Corynebacterium spp. and Moraxella spp. dominance were followed by a switch to Streptococcus mitis predominance after 3 months of age. In control subjects, Moraxella spp. enrichment occurred throughout the first 6 months of life. In a multivariate analysis, S. aureus, S. mitis, Corynebacterium accolens, and bacilli were significantly more abundant in infants with CF, whereas Moraxella spp., Corynebacterium pseudodiphtericum and Corynebacterium propinquum and Haemophilus influenzae were significantly more abundant in control subjects, after correction for age, antibiotic use, and respiratory symptoms. Antibiotic use was independently associated with increased colonization of gram-negative bacteria such as Burkholderia spp. and members of the Enterobacteriaceae bacteria family and reduced colonization of potential beneficial commensals. From diagnosis onward, we observed distinct patterns of nasopharyngeal microbiota development in infants with CF under 6 months of age compared with control subjects and a marked effect of antibiotic therapy leading toward a gram-negative microbial composition.

(2012) Correction: Long-Term Effects of Pneumococcal Conjugate Vaccine on Nasopharyngeal Carriage of S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis. No competing interests declared.

Background Many studies support the protective effect of breastfeeding on respiratory tract infections. Although infant formulas have been developed to provide adequate nutritional solutions, many components in human milk contributing to the protection of newborns and aiding immune development still need to be identified. In this paper we present the methodology of the “Protecting against Respiratory tract lnfections through human Milk Analysis” (PRIMA) cohort, which is an observational, prospective and multi-centre birth cohort aiming to identify novel functions of components in human milk that are protective against respiratory tract infections and allergic diseases early in life. Methods For the PRIMA human milk cohort we aim to recruit 1000 mother–child pairs in the first month postpartum. At one week, one, three, and six months after birth, fresh human milk samples will be collected and processed. In order to identify protective components, the level of pathogen specific antibodies, T cell composition, Human milk oligosaccharides, as well as extracellular vesicles (EVs) will be analysed, in the milk samples in relation to clinical data which are collected using two-weekly parental questionnaires. The primary outcome of this study is the number of parent-reported medically attended respiratory infections. Secondary outcomes that will be measured are physician diagnosed (respiratory) infections and allergies during the first year of life. Discussion The PRIMA human milk cohort will be a large prospective healthy birth cohort in which we will use an integrated, multidisciplinary approach to identify the longitudinal effect human milk components that play a role in preventing (respiratory) infections and allergies during the first year of life. Ultimately, we believe that this study will provide novel insights into immunomodulatory components in human milk. This may allow for optimizing formula feeding for all non-breastfed infants.