Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 206, Issue 1, Pages 73-80Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jis307
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Funding
- Cynthia Bishop
- Dan Godoy at Imperial College
- Wellcome Trust
- Grand Challenges in Global Health initiative
- Bill & Melinda Gates Foundation
- Foundation for the National Institutes of Health
- Canadian Institutes of Health Research
- Native American Research Centers for Health [U26IHS300013/03]
- Centers for Disease Control and Prevention National Vaccine Program Office
- Thrasher Research Fund
- Royal Society
- National Institute of General Medical Sciences [U54GM088558]
- Pfizer
- Sanofi-Pasteur
- Merck
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Background. Pneumococci could evade pneumococcal conjugate vaccines (PCV) by modifying, mutating, or deleting vaccine-serotype capsule genes or by downregulating capsule production. We sought to assess whether pneumococci that are nontypeable (NT) by the Quellung reaction truly lack capsule genes or are failing to produce capsule in vitro. Methods. We applied multilocus sequence typing and a microarray for detection of pneumococcal polysaccharide capsule biosynthesis genes to NT carriage (children aged <5 years; years 1997-2000, 2006-2008) and NT invasive disease (IPD) (all ages; years 1994-2007) isolates from Native American communities. Results. Twenty-seven of 28 (96.4%) NT IPD isolates had sequence types (STs) typically found among type-able IPD isolates and contained whole or fragments of capsule genes that matched known serotypes; 1 NT-IPD isolate had a profile resembling NT carriage isolates. Forty-nine of 76 (64.5%) NT carriage isolates had STs that typically lack capsule genes and were similar to NT carriage isolates found globally. Conclusions. This is the first documentation of IPD from an NT strain confirmed to lack all known capsule genes. Most NT IPD isolates have or had the capacity to produce capsule, whereas a majority of NT carriage isolates lack this capacity. We found no evidence of pneumococcal adaptation to PCV7 via downregulation or deletion of vaccine-serotype capsule genes.
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