Key features of pneumococcal isolates recovered in Central and Northwestern Russia in 2011-2018 determined through whole-genome sequencing

Abstract

Invasive pneumococcal disease remains one of the leading causes of morbidity and mortality worldwide. In Russia, 13- valent pneumococcal conjugate vaccine (PCV13) was introduced into the childhood immunization programme nationwide in 2014. As part of the Global Pneumococcal Sequencing Project (GPS), we used genome data to characterize 179 pneumococcal isolates collected from Russia in 2011-2018 to investigate the circulating pneumococcal strains using a standardized genomic definition of pneumococcal lineages (global pneumococcal sequence clusters, GPSCs), prevalent serotypes and antimicrobial resistance profiles.We observed high serotype and lineage diversity among the 179 isolates recovered from cerebrospinal fluid (n=77), nasopharyngeal swabs (n=99) and other non-sterile site swabs (n=3). Overall, 60 GPSCs were identified, including 48 clonal complexes (CCs) and 14 singletons, and expressed 42 serotypes (including non-typable). Among PCV13 serotypes, 19F, 6B and 23F were the top three serotypes while 11A, 15B/C and 8 were the top three among non-PCV13 serotypes in the collection. Two lineages (GPSC6 and GPSC47) expressed both PCV13 and non-PCV13 serotypes that caused invasive disease, and were penicillin- and multidrug-resistant (MDR), highlighting their potential to adapt and continue to cause infections under vaccine and antibiotic selective pressure. PCV13 serotypes comprised 92 % (11/12) of the CSF isolates from the children aged below 5 years; however, the prevalence of PCV13 serotype isolates dropped to 53 % (31/58) among the nasopharyngeal isolates. Our analysis showed that 59 % (105/179) of the isolates were predicted to be non-susceptible to at least one class of antibiotics and 26 % (46/179) were MDR. Four MDR lineages (GPSC1, GPSC6, GPSC10 and GPSC47) accounted for 65 % (30/46) of the MDR isolates and expressed PCV13 serotypes (93 %, 28/30).This study provides evidence of high genetic and serotype diversity contributed by a mix of globally spreading and regionally circulating lineages in Russia. The observations suggest that the PCV13 vaccine could be important in reducing both invasive disease and antimicrobial resistance. We also identify potential lineages (GPSC6 and GPSC47) that may evade the vaccine.

Keywords: Russia; Streptococcus pneumoniae; WGS (whole-genome sequencing); antimicrobial resistance; global pneumococcal sequence cluster (GPSC); serotypes.

Fig. 1.

Distribution of global pneumococcal sequence clusters (GPSCs) among Streptococcus pneumoniae isolates from cerebrospinal fluid (n=77) and nasopharyngeal swabs (n=99) from acute URI samples, Russia, 2011–2018. The number of isolates is plotted by GPSC and coloured by serotypes. Vaccine serotypes are represented by solid fill while non-vaccine serotypes are coloured by hatched patterns. The horizontal bars in red indicate the percentage of antibiotic resistance in each lineage. %PEN, penicillin resistance predicted based on the pbp1a, pbp2x, pbp2b sequences; %CHL, chloramphenicol resistance is predicted by the presence of chloramphenicol acetyltransferase gene, cat; %ERY, macrolide resistance is predicted by the presence of erythromycin resistance methylase gene ermB or macrolide efflux pump gene mefA; SXT, cotrimoxazole non-susceptibility was determined by the presence of mutation I100L in folA and/or any indel within amino acid residue 56–67 in folP; TET, tetracycline resistance is predicted by the presence of tetM, tet(O) or tet(S/M) gene without disruption in the promoter region. CSF, cerebrospinal fluid; NPS, nasopharyngeal swab; URI, upper respiratory tract infection.

Fig. 2.

(a) Serotype distribution among 12 CSF and 58 nasopharyngeal pneumococcal isolates from children aged <5 years (n=70), Russia, 2011–2018. (b) Serotype distribution among 65 CSF and 41 nasopharyngeal pneumococcal isolates from individuals aged ≥5 years (n=106), Russia, 2011–2018. CSF, cerebrospinal fluid; NPS, nasopharyngeal swab; NT, nontypeable isolates. Three isolates from other non-sterile sites were not included: serotypes 22F, 15B/C and 19F. Vaccine serotypes, PCV13 serotypes; non-vaccine serotypes, non-PCV13 serotypes.

Fig. 3.

Yearly distribution of PCV13 and non-PCV13 serotypes identified among the pneumococcal isolates obtained from (a) cerebrospinal fluid (CSF) (n=77) from patients aged <5 years (n=12) and ≥5 years (n=65) and (b) nasopharyngeal swabs (NPSs) (n=99) from patients aged <5 years (n=58) and ≥5 years (n=41) between 2011–2018 in Russia. Three isolates from other non-sterile sites were not included: serotypes 22F, 15B/C and 19F.

Fig. 4.

Maximum-likelihood tree of Streptococcus pneumoniae isolates from CSF (IPD) (n=77), nasopharynx and other non-sterile sites (n=102) from Russia, 2011–2018. The tree nodes are coloured by serotypes. The colours of serotypes and GPSCs that are represented by <5 isolates in this collection are not shown in the legend. The clusters highlighted in black boxes represent predominant MDR lineages with ≥3 isolates (GPSC1, 6, 10 and 47). CSF, cerebrospinal fluid; IPD, invasive pneumococcal disease; MDR, multidrug-resistant. Other non-sterile sites, vaginal swab (n=1) and eye swabs (n=2). This figure can be visualized interactively at https://microreact.org/project/ GPS_Russia.