Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study

Abstract

Background Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits. Methods We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacement by comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model. Findings The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could be associated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0•0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0•0031) in the PCV13 period compared with the pre-PCV period. Interpretation Globally spreading line...

The Role of Streptococcus pneumoniae in Community-Acquired Pneumonia

“…65 Irrespective of the mechanisms that may be operative in the setting of pneumococcal, nonvaccine serotype antibiotic resistance in particular, the findings of a very recently reported international whole-genome sequencing study are noteworthy. 66 This study was focused on pneumococcal lineages associated with serotype replacement and antibiotic resistance based on whole genome sequencing of strains of the pathogen isolated from children aged <3 years hospitalized with IPD in the pre-and postimmunization periods. 66 The authors reported a significant increase in the prevalence of resistance to penicillin in nonvaccine serotypes in the post-PCV period relative to the pre-PCV13 period (29 vs. 21%, Fig.…”

“…66 This study was focused on pneumococcal lineages associated with serotype replacement and antibiotic resistance based on whole genome sequencing of strains of the pathogen isolated from children aged <3 years hospitalized with IPD in the pre-and postimmunization periods. 66 The authors reported a significant increase in the prevalence of resistance to penicillin in nonvaccine serotypes in the post-PCV period relative to the pre-PCV13 period (29 vs. 21%, Fig. 1 Exposure of both antibiotic-susceptible (A) and erm(B) macrolide resistance gene-expressing (B) strains of the pneumococcus (depicted as ) to cigarette smoke results in induction of genes which trigger biofilm formation and expression of an ABC transporter, seemingly involved in efflux of antibiotics.…”

Improved inference and prediction of bacterial genotype-phenotype associations using pangenome-spanning regressions

“…Furthermore, this cohort is a mix of sequences isolated from both asymptomatic carriage and disease, whereas SPARC and Maela contain only asymptomatic carriage. The GPS cohort is enriched with more virulent strains, which have more frequently faced treatment with antibiotics, and have a higher rate of resistance (1,63) .…”

Identification of Pneumococcal Serotypes by PCR–Restriction Fragment Length Polymorphism

“…Latex agglutination is an alternative, and a cheaper option than Quellung reaction, but also requires culture of the isolates. Alternative typing methods not based in antisera are described for S. pneumoniae using DNA molecular methods: multiplex PCR [14][15][16], real-time PCR, microchip, sequencing-typing, reverse-hybridization, MALDI-TOF MS, and whole genome sequencing [8,[17][18][19].…”