Population genomics of pneumococcal carriage in South Africa following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) immunization

Abstract

Streptococcus pneumoniae is a major human pathogen responsible for over 317000 deaths in children <5 years of age with the burden of the disease being highest in low- and middle-income countries including South Africa. Following the introduction of the 7-valent and 13-valent pneumococcal conjugate vaccine (PCV) in South Africa in 2009 and 2011, respectively, a decrease in both invasive pneumococcal infections and asymptomatic carriage of vaccine-type pneumococci were reported. In this study, we described the changing epidemiology of the pneumococcal carriage population in South Africa, by sequencing the genomes of 1825 isolates collected between 2009 and 2013. Using these genomic data, we reported the changes in serotypes, Global Pneumococcal Sequence Clusters (GPSCs), and antibiotic resistance before and after the introduction of PCV13. The pneumococcal carriage population in South Africa has a high level of diversity, comprising of 126 GPSCs and 49 serotypes. Of the ten most prevalent GPSCs detected, six were predominantly found in Africa (GPSC22, GPSC21, GPSC17, GPSC33, GPSC34 and GPSC52). We found a significant decrease in PCV7 serotypes (19F, 6B, 23F and 14) and an increase in non-vaccine serotypes (NVT) (16F, 34, 35B and 11A) among children <2 years of age. The increase in NVTs was driven by pneumococcal lineages GPSC33, GPSC34, GPSC5 and GPSC22. Overall, a decrease in antibiotic resistance for 11 antimicrobials was detected in the PCV13 era. Further, we reported a higher resistance prevalence among vaccine types (VTs), as compared to NVTs; however, an increase in penicillin resistance among NVT was observed between the PCV7 and PCV13 eras. The carriage isolates from South Africa predominantly belonged to pneumococcal lineages, which are endemic to Africa. While the introduction of PCV resulted in an overall reduction of resistance in pneumococcal carriage isolates, an increase in penicillin resistance among NVTs was detected in children aged between 3 and 5 years, driven by the expansion of penicillin-resistant clones associated with NVTs in the PCV13 era.

Geographic migration and vaccine-induced fitness changes ofStreptococcus pneumoniae

“…We were able to refine this model to look at the fitness of individual serotypes and found a wide range of fitness across serotypes. Among NVTs serotypes 15A, 35B, and 8 had the greatest fitness advantage post-PCV (Figure S12-14) concordant with what has been previously described (13,14,26). We also found that shifts in lineage fitness result in changing patterns of spread.…”

“…We found that the implementation of PCV7 in 2009 and PCV13 in 2011 was associated with a substantial disruption in the patterns of circulating serotypes, consistent with what has been observed elsewhere (4,13,24,25). By 2014, serotypes included in PCV13 represented 33.2% of all isolates in our dataset, down from 85.0% in the pre-vaccine era (Figure 4A).…”

“…Despite their success at reducing disease, their use has been linked to serotype replacement by non-vaccine serotypes (NVTs) in both IPD and carriage ( 4 ). In South Africa this has been characterized by increases in NVT serotypes 8 and 15B among IPD, and increases in NVT serotypes 16F, 24, 35B, and 11A among carriage isolates( 13, 14 ). At the population level, quantitative measures of serotype-specific fitness changes following vaccine implementation are lacking.…”

“…This includes quantifying the time it takes after implementation for vaccines to impact the serotype composition in the country as well as quantifying the serotype changes pre-and post-vaccine at different time points. In addition, vaccine implementation has resulted in reductions in antimicrobial resistance among both IPD and carriage isolates (13)(14)(15). It still, however, remains unclear if these reductions will persist over time at the population level, or if AMR may rebound.…”

Genomic epidemiology of Streptococcus pneumoniae serotype 16F lineages

“…For isolates with resistance that formed clusters -which suggests emerging resistant lineages -the estimated tMRCA for the cluster with penicillin resistance in GPSC33 is 1937 (95 % HPD 1927(95 % HPD -1946 and that for the cluster with cotrimoxazole resistance in GPSC46 is 1922 (95 % HPD 1821-1988). The tMRCA of lineages is between the 1920s and the 1930s, coinciding with the discovery of penicillin and cotrimoxazole, but prior to their widespread use [17,18]. The tMRCA confidence intervals for the cluster with resistance to cotrimoxazole are wide, and antimicrobial use may have contributed to the emergence of this cluster.…”