Genomic surveillance of invasive Streptococcus pneumoniae isolates in the period pre-PCV10 and post-PCV10 introduction in Brazil

Abstract

In 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) into the national children’s immunization programme. This study describes the genetic characteristics of invasive Streptococcus pneumoniae isolates before and after PCV10 introduction. A subset of 466 [pre-PCV10 (2008–2009): n=232, post-PCV10 (2012–2013): n=234;<5 years old: n=310, ≥5 years old: n=156] pneumococcal isolates, collected through national laboratory surveillance, were whole-genome sequenced (WGS) to determine serotype, pilus locus, antimicrobial resistance and genetic lineages. Following PCV10 introduction, in the <5 years age group, non-vaccine serotypes (NVT) serotype 3 and serotype 19A were the most frequent, and serotypes 12F, 8 and 9 N in the ≥5 years old group. The study identified 65 Global Pneumococcal Sequence Clusters (GPSCs): 49 (88 %) were GPSCs previously described and 16 (12 %) were Brazilian clusters. In total, 36 GPSCs (55 %) were NVT lineages, 18 (28 %) vaccine serotypes (VT) and 11 (17 %) were both VT and NVT lineages. In both sampling periods, the most frequent lineage was GPSC6 (CC156, serotypes 14/9V). In the <5 years old group, a decrease in penicillin (P=0.0123) and cotrimoxazole (P<0.0001) resistance and an increase in tetracycline (P=0.019) were observed. Penicillin nonsusceptibility was predicted in 40 % of the isolates; 127 PBP combinations were identified (51 predicted MIC≥0.125 mg l−1); cotrimoxazole (folA and/or folP alterations), macrolide (mef and/or ermB) and tetracycline (tetM, tetO or tetS/M) resistance were predicted in 63, 13 and 21.6 % of pneumococci studied, respectively. The main lineages associated with multidrug resistance in the post-PCV10 period were composed of NVT, GPSC1 (CC320, serotype 19A), and GPSC47 (ST386, serotype 6C). The study provides a baseline for future comparisons and identified important NVT lineages in the post-PCV10 period in Brazil.

Multiplex real-time PCR using SYBR Green: Unspecific intercalating dye to detect antimicrobial resistance genes of Streptococcus pneumoniae in cerebrospinal fluid

“…In Brazil, it was observed an increase of 7% to 16.4% in the incidence of invasive pneumococcal disease caused by serotype 19A, after the 10-valent pneumococcal conjugate vaccine introduction, especially in 2016–2017 [ 29 ]. The molecular detection of both ermB and mef genes in pneumococcal invasive strains was higher in comparison with other studies in Brazil (3 in 159 strains– 1.9%) during 2010–2012 [ 30 ] and 7% during 2012–2013 [ 31 ]. Probably, because these studies evaluated the genes’ presence in isolated strains.…”

Comparison of next generation technologies and bioinformatics pipelines for capsular typing of Streptococcus pneumoniae

“…At present, there is an increasing number of reports that have utilized WGS for surveillance of capsular types of S. pneumoniae causing IPD ( 21 , 48 – 51 ), but this methodology has not been widely adopted yet ( 52 – 56 ). These may be in part due to the lack of accessibility of Illumina sequencing to medium and small-size laboratories, making it necessary to send the samples to reference laboratories, as well as to the fact that most programs utilized for in silico serotyping require some bioinformatics skills not available in all laboratories ( 18 , 19 ).…”

Increase of Macrolide-Resistance in Streptococcus pneumoniae Strains After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Lima, Peru

“…In this study, the macrolide resistance did not change (from 40.6% to 38.7%), but the rate of resistance to macrolides in the non-vaccine serotypes increased from 21.0% to 27.0% ( Farrell et al., 2007 ). In Brazil, before and after introduction of PCV10 the frequency of macrolide-resistant isolates was 12.0% and 21.0% respectively ( Almeida et al., 2021 ). In Germany, the frequency of macrolide-resistant pneumococcus after the introduction of PCV7 decreased from 24.7% to 17.2%, and it continued decreasing after the introduction of PCV13 (8.2%) ( Imöhl et al., 2015 ).…”

“…Our erm (B) frequency was similar that reported in Colombia before PCV13 (98.0%) ( Ramos et al., 2014 ). On the other hand, in Brazil before the introduction of PCV13 erm (B) was detected in an lower frequency, 10.0% of intermediate or resistant erythromycin S. pneumoniae isolates and 7.0% of those isolates had both genes ( Almeida et al., 2021 ). In the United States, after the introduction of PCV7, was found an increase in 18.0% the proportion of strains positive for both genes between the first and last year of surveillance study, with a corresponding decrease in the prevalence of positive isolates for only mef (A) (72.0% to 58.0%) and only erm (B) (15.8% to 11.2%) ( Farrell et al., 2007 ).…”