title: Genomic analysis of nontypeable pneumococci causing invasive pneumococcal disease in South Africa, 2003-2013.
abstract: The capsular polysaccharide is the principal virulence factor of Streptococcus pneumoniae and a target for current pneumococcal vaccines. However, some pathogenic pneumococci are serologically nontypeable [nontypeable pneumococci (NTPn)]. Due to their relative rarity, NTPn are poorly characterized, and, as such, limited data exist which describe these organisms. We aimed to describe disease and genotypically characterize NTPn causing invasive pneumococcal disease in South Africa.
  
  
  
  Isolates were detected through national, laboratory-based surveillance for invasive pneumococcal disease in South Africa and characterized by whole genome analysis. We predicted ancestral serotypes (serotypes from which NTPn may have originated) for Group I NTPn using multilocus sequence typing and capsular region sequence analyses. Antimicrobial resistance patterns and mutations potentially causing nontypeability were identified. From 2003-2013, 39 (0.1 %, 39/32,824) NTPn were reported. Twenty-two (56 %) had partial capsular genes (Group I) and 17 (44 %) had complete capsular deletion of which 15 had replacement by other genes (Group II). Seventy-nine percent (31/39) of our NTPn isolates were derived from encapsulated S. pneumoniae. Ancestral serotypes 1 (27 %, 6/22) and 8 (14 %, 3/22) were most prevalent, and 59 % (13/22) of ancestral serotypes were serotypes included in the 13-valent pneumococcal conjugate vaccine. We identified a variety of mutations within the capsular region of Group I NTPn, some of which may be responsible for the nontypeable phenotype. Nonsusceptibility to tetracycline and erythromycin was higher in NTPn than encapsulated S. pneumoniae.
  
  
  
  NTPn are currently a rare cause of invasive pneumococcal disease in South Africa and represent a genetically diverse collection of isolates.
authors.affiliation: Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD), National Health Laboratory Services (NHLS), Johannesburg, South Africa. thabom@nicd.ac.za.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. thabom@nicd.ac.za.
authors.forename: Thabo
authors.initials: T
authors.lastname: Mohale
authors.affiliation: Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD), National Health Laboratory Services (NHLS), Johannesburg, South Africa.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wolter
authors.affiliation: Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD), National Health Laboratory Services (NHLS), Johannesburg, South Africa.
authors.forename: Mushal
authors.initials: M
authors.lastname: Allam
authors.affiliation: Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD), National Health Laboratory Services (NHLS), Johannesburg, South Africa.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Kedibone
authors.initials: K
authors.lastname: Ndlangisa
authors.affiliation: Public Health Surveillance and Response, National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, South Africa.
authors.forename: Penny
authors.initials: P
authors.lastname: Crowther-Gibson
authors.affiliation: Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD), National Health Laboratory Services (NHLS), Johannesburg, South Africa.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Mignon
authors.initials: M
authors.lastname: du Plessis
authors.affiliation: Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD), National Health Laboratory Services (NHLS), Johannesburg, South Africa.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D049674:History, 21st Century; D006801:Humans; D058885:Multilocus Sequence Typing; D010802:Phylogeny; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000266:history / Q000382:microbiology*; D011159:Population Surveillance; D012703:Serotyping; D013019:South Africa / Q000453:epidemiology; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000187:drug effects / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins
keywords: Invasive pneumococcal disease; Nontypeable; South Africa; Streptococcus pneumoniae; Whole genome sequencing