Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001–2018

<b>Background.</b> Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.<b>Methods.</b> We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (<i>n</i>=61) or IPD (<i>n</i>=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.<b>Results.</b> The serotype 3 population structure was characterized by three dominant subpopulations: <i>clade II</i> (<i>n</i>=90, 46.9 %) and <i>clade Iα</i> (<i>n</i>=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (<i>n</i>=43, 22.4 %). The proportion of <i>clade II</i>-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; <i>P</i><0.001) but not in children (27.3-33.3 %; <i>P</i>=0.84). Over the same period, the proportion of <i>clade II-</i>associated carriage increased; this was statistically significant among children (23.3-52.6 %; <i>P</i>=0.04) but not adults (0-50.0 %, <i>P</i>=0.08).<b>Conclusions.</b> In this setting with persistent serotype 3 IPD and carriage, <i>clade II</i> has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time.