Evidence of virulence and antimicrobial resistance inStreptococcus pneumoniaeserotype 16F lineages
Authors: Mokaya Jolynne , Mellor Kate C , Murray Gemma G R , Kalizang’oma Akuzike , Lekhuleni Cebile , Zar Heather J , Nicol Mark P. , McGee Lesley , Bentley Stephen D , Lo Stephanie W , Dube Felix ,   The Global Pneumococcal Sequencing Consortium
Published: August 2023

ABSTRACTIntroductionDue to the emergence of non-vaccine serotypes in vaccinated populations,Streptococcus pneumoniaeremains 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).AimTo characterise lineages and antimicrobial resistance in 16F isolates obtained from South Africa and placed the local findings in a global context.MethodologyWe analysed 10923S. pneumoniaecarriage 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 includedS. pneumoniaecarriage 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 17thMarch 2022).ResultsNine 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 ofS. 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.DiscussionSerotype 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 SUMMARYThe sequencing reads for the genomes analysed have been deposited in the European Nucleotide Archive and the accession numbers for each isolate are listed inSupplementary 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 Microreactserotype-16F,GPSC33andGPSC46, respectively.IMPACT STATEMENTThis 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.