Genomic epidemiology of Streptococcus pneumoniae serotype 16F lineages.

Due to the emergence of non-vaccine serotypes in vaccinated populations, Streptococcus pneumoniae remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). To characterize lineages and antimicrobial resistance in 16F isolates obtained from South Africa and place the local findings in a global context, we analysed 10 923 S. pneumoniae carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and global pneumococcal sequence clusters (GPSCs) from genomic data. To ensure global representation, we also included S. pneumoniae carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (n=19 607, collected from 49 countries across 5 continents, 1995-2018, accessed 17 March 2022). Nine per cent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2 %(419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of S. pneumoniae, with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26 % (346/1353) and 53 % (716/1353), respectively. Serotype 16F isolates were identified globally, but most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95 % CI) 0.24 (0.09-0.66); P=0.003], while GPSC46 was associated with disease [OR (95 % CI) 19.9 (2.56-906.50); P=0.0004]. Ten per cent (37/346) and 15 % (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18 % (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters, which may suggest emerging resistant lineages. Serotype 16F lineages were common in southern Africa. Some of these lineages were associated with disease and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine the long-term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. This paper contains data hosted by Microreact.

Evidence of virulence and antimicrobial resistance in Streptococcus pneumoniae serotype 16F lineages.

Introduction: Due to the emergence of non-vaccine serotypes in vaccinated populations, Streptococcus pneumoniae remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). Aim: To characterise lineages and antimicrobial resistance in 16F isolates obtained from South Africa and placed the local findings in a global context. Methodology: We analysed 10923 S. pneumoniae carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and Global Pneumococcal Sequence Clusters (GPSCs) from genomic data. To ensure global representation, we also included S. pneumoniae carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (n=19,607, collected from 49 countries across five continents, years covered (1995 - 2018), accessed on 17 th March 2022). Results: Nine percent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2% (419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of S. pneumoniae, with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26% (346/1353) and 53% (716/1353), respectively. Serotype 16F isolates were identified globally, however, most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95% CI) 0.24 (0.09 - 0.66); p=0.003], while GPSC46 was associated with disease [OR (95% CI) 19.9 (2.56 - 906.50); p=0.0004]. 10% (37/346) and 15% (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18% (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters which may suggest emerging resistant lineages. Discussion: Serotype 16F lineages are common in Southern Africa. Some of these lineages are associated with disease, and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine long term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. DATA SUMMARY: The sequencing reads for the genomes analysed have been deposited in the European Nucleotide Archive and the accession numbers for each isolate are listed in Supplementary Table1 . Phylogenetic tree of serotype 16F pneumococcal genomes and associated metadata are available for download and visualisation on the Microreact website: Phylogenies of seotype 16F, GPSC33 and GPSC46 are available on the Microreact serotype-16F , GPSC33 and GPSC46 , respectively. IMPACT STATEMENT: This study shows that serotype 16F lineages are predominant in Southern Africa and are associated with disease and antimicrobial resistance. Although serotype 16F has been included in the newer formulation of the upcoming vaccine formulations of PCV21 and IVT-25, continuous surveillance to determine long term impact of serotype 16F lineages on vaccines and antimicrobial therapy remains essential.

Meningitis-associated pneumococcal serotype 8, ST 53, strain is hypervirulent in a rat model and has non-haemolytic pneumolysin which can be attenuated by liposomes.

Introduction: Streptococcus pneumoniae bacteria cause life-threatening invasive pneumococcal disease (IPD), including meningitis. Pneumococci are classified into serotypes, determined by differences in capsular polysaccharide and both serotype and pneumolysin toxin are associated with disease severity. Strains of serotype 8, ST 53, are increasing in prevalence in IPD in several countries. Methods: Here we tested the virulence of such an isolate in a rat model of meningitis in comparison with a serotype 15B and a serotype 14 isolate. All three were isolated from meningitis patients in South Africa in 2019, where serotype 8 is currently the most common serotype in IPD. Results and Discussion: Only the serotype 8 isolate was hypervirulent causing brain injury and a high mortality rate. It induced a greater inflammatory cytokine response than either the serotype 15B or 14 strain in the rat model and from primary mixed-glia cells isolated from mouse brains. It had the thickest capsule of the three strains and produced non-haemolytic pneumolysin. Pneumolysin-sequestering liposomes reduced the neuroinflammatory cytokine response in vitro indicating that liposomes have the potential to be an effective adjuvant therapy even for hypervirulent pneumococcal strains with non-haemolytic pneumolysin.