Evidence that pneumococcal serotype replacement in Massachusetts following conjugate vaccination is now complete

Abstract

Invasive pneumococcal disease (IPD) has been reduced in the US following conjugate vaccination (PCV7) targeting seven pneumococcal serotypes in 2000. However, increases in IPD due to other serotypes have been observed, in particular 19A. How much this "serotype replacement" will erode the benefits of vaccination and over what timescale is unknown. We used a population genetic approach to test first whether the selective impact of vaccination could be detected in a longitudinal carriage sample, and secondly how long it persisted for following introduction of vaccine in 2000. To detect the selective impact of the vaccine we compared the serotype diversity of samples from pneumococcal carriage in Massachusetts children collected in 2001, 2004 and 2007 with others collected in the pre-vaccine era in Massachusetts, the UK and Finland. The 2004 sample was significantly (p >0.0001) more diverse than pre-vaccine samples, indicating the selective pressure of vaccination. The 2007 sample showed no significant difference in diversity from the pre-vaccine period, and exhibited similar population structure, but with different serotypes. In 2007 the carriage frequency of 19A was similar to that of the most common serotype in pre-vaccine samples. We suggest that serotype replacement involving 19A may be complete in Massachusetts due to similarities in population structure to pre-vaccine samples. These results suggest that the replacement phenomenon occurs rapidly with high vaccine coverage, and may allay concerns about future increases in disease due to 19A. For other serotypes, the future course of replacement disease remains to be determined.

Keywords: Infectious disease epidemiology; Nasopharyngeal carriage; Population genetics; Streptococcus pneumoniae.

Figure 1

A) Frequencies of individual serotypes in the three pre-vaccine datasets. Sample details are described in the main text and Table 1. For reasons of space only the 20 most common serotypes in the combined dataset are shown. Vaccine serotypes are underlined. B) The same data arranged by rank (most-least common).

Figure 2

Rank frequency distributions of serotypes in the MA samples from 1998-9 (a), 2001 (b), 2004 (c) and 2007 (d). Details of the samples are as described in the text and table. Serotypes are shown as indicated in the legend. The median values obtained from 1000 samples of the same size drawn from the combined pre-vaccine distribution (as described in the text) are shown as a solid line with dashed lines either side representing the 5^th and 95^th percentiles for each point. Larger numbers of serotypes in the later samples reflect larger sample size.