Global Distribution of Invasive Serotype 35D Streptococcus pneumoniae Isolates following Introduction of 13-Valent Pneumococcal Conjugate Vaccine

• Type of Material: Article
• Authors: Stephanie W. Lo, Wellcome Trust Sanger Institute; Rebecca A. Gladstone, Wellcome Trust Sanger Institute; Andries J. van Tonder, Wellcome Trust Sanger Institute; Paulina A. Hawkins, Emory University; Brenda Kwambana-Adams, Medical Research Council Unit The Gambi; Jennifer E. Cornick, University of Liverpool; Shabir Madhi, University of Witwatersrand; Susan A. Nzenze, University of Witwatersrand; Mignon du Plessis, University of the Witwatersrand; Rama Kandasamy, University of Oxford; Philip E. Carter, Kenepuru Science Centre; Özgen Köseoglu Eser, Hacettepe University; Park Leung Ho, University of Hong Kong; Naima Elmdaghri, Hassan II University of Casablanca; Sadia Shakoor, Aga Khan University; Stuart C. Clarke, University of Southampton; Martin Antonio, Warwick Medical School; Dean B. Everet, University of Edinburgh; Anne von Gottberg, University of the Witwatersrand; Keith P Klugman, Emory University; Lesley McGee, Centers for Disease Control and Prevention; Robert F Breiman, Emory University; Stephen D. Bentley, Wellcome Trust Sanger Institute
• Language: English
• Date: 2018-07-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Lo et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1128/JCM.00228-18
• Title of Journal or Parent Work: Journal of Clinical Microbiology
• ISSN: 0095-1137
• Volume: 56
• Issue: 7
• Grant/Funding Information: This work is funded by the Bill and Melinda Gates Foundation (grant OPP1034556), the Wellcome Trust Sanger Institute, and the Centers for Disease Control and Prevention (Atlanta, GA).
• Keywords: CLONE; 35D; PCV; Life Sciences & Biomedicine; VARIANTS; UNITED-STATES; Microbiology; LOCUS; 11A; CARRIAGE; whole-genome sequencing; CHILDREN; Science & Technology; novel serotype; DISCOVERY
• Research Categories: Health Sciences, Pathology; Biology, Microbiology

Abstract

A newly recognized pneumococcal serotype, 35D, which differs from the 35B polysaccharide in structure and serology by not binding to factor serum 35a, was recently reported. The genetic basis for this distinctive serology is due to the presence of an inactivating mutation in wciG, which encodes an O-acetyltransferase responsible for O-acetylation of a galactofuranose. Here, we assessed the genomic data of a worldwide pneumococcal collection to identify serotype 35D isolates and understand their geographical distribution, genetic background, and invasiveness potential. Of 21,980 pneumococcal isolates, 444 were originally typed as se-rotype 35B by PneumoCaT. Analysis of the wciG gene revealed 23 isolates from carriage (n= 4) and disease (n= 19) with partial or complete loss-of-function mutations, including mutations resulting in premature stop codons (n= 22) and an inframe mutation (n= 1). These were selected for further analysis. The putative 35D isolates were geographically widespread, and 65.2% (15/23) of them was recovered after the introduction of pneumococcal conjugate vaccine 13 (PCV13). Compared with serotype 35B isolates, putative serotype 35D isolates have higher invasive disease potentials based on odds ratios (OR) (11.58; 95% confidence interval[CI], 1.42 to 94.19 versus 0.61; 95% CI, 0.40 to 0.92) and a higher prevalence of macrolide resistance mediated by mefA (26.1% versus 7.6%; P= 0.009). Using the Quellung reaction, 50% (10/20) of viable isolates were identified as serotype 35D, 25% (5/20) as serotype 35B, and 25% (5/20) as a mixture of 35B/35D. The discrepancy between phenotype and genotype requires further investigation. These findings illustrated a global distribution of an invasive serotype, 35D, among young children post-PCV13 introduction and underlined the invasive potential conferred by the loss of Oacetylation in the pneumococcal capsule.