Systematic review of the effect of pneumococcal conjugate vaccine dosing schedules on vaccine-type nasopharyngeal carriage

Abstract

Background: Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine type (VT) pneumococci, an important driver of vaccine programs' overall benefits. The dosing schedule that best reduces carriage is unclear.

Methods: We performed a systematic review of English language publications from 1994 to 2010 (supplemented post hoc with studies from 2011) reporting PCV effects on VT carriage to assess variability in effect by dosing schedule.

Results: We identified 32 relevant studies (36 citations) from 12,980 citations reviewed. Twenty-one (66%) evaluated PCV7; none used PCV10 or PCV13. Five studies evaluated 2 primary doses and 13 three primary doses. After the first year of life, 14 evaluated 3-dose primary series with PCV booster (3+1), seven 3 doses plus 23-valent polysaccharide booster "3+1PPV23," five "3+0," four "2+1," three "2+1PPV23" and two "2+0." Four studies directly compared schedules. From these, 3 primary doses reduced VT carriage more than 2 doses at 1-7 months following the series (1 study significant; 2 borderline). In a study, the 2+1 schedule reduced VT carriage more than 2+0 at 18, but not at 24 months of age. One study of a 23-valent pneumococcal polysaccharide vaccine booster showed no effect. All 16 clinical trials with unvaccinated controls and 11 observational studies with before-after designs showed reduction in VT carriage.

Conclusions: The available literature demonstrates VT-carriage reduction for 2+0, 2+1, 3+0 and 3+1 PCV schedules, but not for 23-valent pneumococcal polysaccharide vaccine booster. Comparisons between schedules show that 3 primary doses and a 2+1 schedule may reduce carriage more than 2 primary doses and a 2+0 schedule, respectively.

FIGURE 1.

Literature search results for carriage citations identified from search strategy, as strategy as detailed in the Methods Appendix. Study families include 1 or more citation generated from a single protocol or data collection system, and the primary citation identifies the citation within each study family that contains the most detailed information regarding vaccine-type carriage. Supplemental citations contain additional data not contained in the citation for the primary study.

FIGURE 2.

Difference in VT carriage prevalence between vaccinated and unvaccinated or placebo groups for clinical trials by primary dosing series (2 or 3 doses) for carriage assessed in the first year of life.^,,,,,,,,, Two and 3 primary doses were given between 6 weeks and 6 months for all regimens. Studies denoted on y-axis with primary dosing series (2 or 3 doses), first author’s last name (with reference number in brackets) and mean or median age in months (m) of children at time of NP specimen collection. Products are listed as PCV-valency and manufacturer name. Confidence intervals are displayed by error bars. Data points are labeled with sample size, an asterisk (*) if statistically significant when compared with controls and/or NR if statistical significance was not reported. All others were not statistically significant. GSK, GlaxoSmithKline.

FIGURE 3.

Difference in VT-carriage prevalence between vaccinated and unvaccinated or placebo groups for clinical trials by dosing series for carriage assessed after the first year of life.^{,,,,,,,,,,,,,} All primary doses were given between 6 weeks and 6 months of age (6 weeks to 4 months for 2 doses, 6 weeks to 6 months for 3 doses), and booster doses given at 11–18 months of age. Studies denoted on y-axis with schedule, first author’s last name (with reference number in brackets)and mean or median age in months (m) of children at time of NP specimen collection. Products are listed as PCV-valency and manufacturer name. Confidence intervals are displayed by error bars. Data points are labeled with sample size, an asterisk (*) if statistically significant when compared with controls, and NR if statistical significance compared with controls was not reported. All others were not statistically significant. GSK, GlaxoSmithKline.

FIGURE 4.

Percent of vaccine-type carriage among children in pre-post trend studies over time by schedule. Year of PCV introduction is denoted as year 0. Studies, which include the primary citation and any supplemental citations, are identified by country, age group in years of children at time of NP specimen collection, and by first author's last name (with reference number in brackets).^,,,,,,