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

Elske J M van Gils, Eelko Hak, Reinier H Veenhoven, Gerwin D Rodenburg, Debby Bogaert, Jacob P Bruin, Loek van Alphen, Elisabeth A M Sanders, Elske J M van Gils, Eelko Hak, Reinier H Veenhoven, Gerwin D Rodenburg, Debby Bogaert, Jacob P Bruin, Loek van Alphen, Elisabeth A M Sanders

Abstract

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.

Methodology/principal findings: This study was part of a randomised controlled trial on the effect of PCV7 on pneumococcal carriage, enrolling healthy newborns who were randomly assigned (1:1:1) to receive PCV7 (1) at 2 and 4 months of age (2) at 2, 4 and 11 months or (3) no PCV7 (controls). Nasopharyngeal colonisation of S. aureus was a planned secondary outcome. Nasopharyngeal swabs were obtained from all children over a 2-year period with 6-months interval and from one parent at the child's age of 12 and 24 months and cultured for Streptococcus pneumoniae and S. aureus. Between July 2005 and February 2006, 1005 children were enrolled and received either 2-doses of PCV7 (n = 336), 2+1-doses (336) or no dose (n = 333) before PCV7 implementation in the Dutch national immunization program. S. aureus colonisation had doubled in children in the 2+1-dose group at 12 months of age compared with unvaccinated controls (10.1% versus 5.0%; p = 0.019). A negative association for co-colonisation of S. pneumoniae and S. aureus was observed for both vaccine serotype (adjusted odds ratio (aOR) 0.53, 95% confidence interval (CI) 0.38-0.74) and nonvaccine serotype pneumococci (aOR 0.67, 95% CI 0.52-0.88).

Conclusions/significance: PCV7 induces a temporary increase in S. aureus colonisation in children around 12 months of age after a 2+1-dose PCV7 schedule. The potential clinical consequences are unknown and monitoring is warranted.

Trial registration: ClinicalTrials.gov NCT00189020.

Conflict of interest statement

Competing Interests: R.V. has received research support from GlaxoSmithKline and Wyeth/Pfizer for vaccine studies and consulting fees for GlaxoSmithKline. E.S. has received research support from Wyeth/Pfizer and Baxter, consulting fees for Wyeth/Pfizer and GlaxoSmithKline, lecturing fees from Wyeth/Pfizer, and grant support from Wyeth/Pfizer and GlaxoSmithKline for vaccine studies. These grants were not received for the research described in this paper. This does not alter our adherence to all the PLoS ONE policies on sharing data and materials. The other authors have declared that no competing interests exist.

Figures

Figure 1. S. pneumoniae and S aureus…
Figure 1. S. pneumoniae and S aureus colonisation in PCV7-unvaccinated control children in The Netherlands.
PCV7 indicates 7-valent pneumococcal conjugate vaccine; wks – weeks; m – months.
Figure 2. Effect of PCV7 on nasopharyngeal…
Figure 2. Effect of PCV7 on nasopharyngeal S aureus colonisation in children.
PCV7 indicates 7-valent pneumococcal conjugate vaccine; wks – weeks; m – months * P

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