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

Abstract

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. Nasopharyngeal samples taken at 5, 11, 14, 18, and 24 months of age were cultured to detect Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. Polymerase chain reaction assays quantified H. influenzae and S. pneumoniae and confirmed H. influenzae as nontypeable (NTHi). Primary outcome measure was vaccine efficacy (VE) against NTHi colonization.

Results: In both groups, NTHi colonization increased with age from 33% in 5-month-olds to 65% in 24-month-olds. Three months postbooster, VE against colonization was 0.5% (95% confidence interval [CI], -21.8% to 18.4%) and VE against acquisition 10.9% (95% CI, -31.3% to 38.9%). At each sampling moment, no differences between groups in either NTHi prevalence or H. influenzae density were detected. Streptococcus pneumoniae (range, 39%-57%), M. catarrhalis (range, 63%--69%), and S. aureus (range, 9%-30%) colonization patterns were similar between groups.

Conclusions: PHiD-CV had no differential effect on nasopharyngeal NTHi colonization or H. influenzae density in healthy Dutch children up to 2 years of age, implying that herd effects for NTHi are not to be expected. Other bacterial colonization patterns were also similar.

Trial registration: ClinicalTrials.gov NCT00652951.

Figure 1.

Trial profile. *Parents of children interested in participating in the study were “redundant” when they were still in the information process after target enrollment had already been achieved. Consequently, the informed consent procedure was cancelled. ^aCoadministered with diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus and Hib vaccine (DTPa-HBV-IPV/Hib [GlaxoSmithKline Vaccines]). ^bCoadministered with DTPa-IPV-Hib. Abbreviations: 7vCRM, 7-valent pneumococcal conjugate vaccine; NP, nasopharyngeal; PHiD-CV, pneumococcal nontypeable Haemophilus influenzae protein D–conjugate vaccine.

Figure 2.

Density of Haemophilus influenzae in nasopharyngeal samples of children (total vaccinated cohort). Density of H. influenzae was measured in original swab media by quantitative polymerase chain reaction targeting the glycosyltransferase gene with values of ≥200 genomic equivalents (GEs) per milliliter defined as positive for the presence of H. influenzae. Point estimates of the geometric means of GEs per milliliter are shown with their 95% confidence intervals (error bars). Abbreviations: 7vCRM, 7-valent pneumococcal conjugate vaccine; lgtC, glycosyltransferase gene; PHiD-CV, pneumococcal nontypeable Haemophilus influenzae protein D–conjugate vaccine.

Figure 3.

Density of Streptococcus pneumoniae in nasopharyngeal samples of children (total vaccinated cohort). Density of S. pneumoniae was measured in original swab media by quantitative polymerase chain reaction targeting the autolysin gene with values of ≥900 genomic equivalents (GEs) per milliliter defined as positive for the presence of S. pneumoniae. Point estimates of the geometric means of GEs per milliliter are shown with their 95% confidence intervals (error bars). Abbreviations: 7vCRM, 7-valent pneumococcal conjugate vaccine; lytA, autolysin gene; PHiD-CV, pneumococcal nontypeable Haemophilus influenzae protein D–conjugate vaccine.