@article{1416dbcbf7ee4d36bb7c725850c51352,
title = "Nontypeable pneumococcal isolates among navajo and white mountain apache communities: Are these really a cause of invasive disease?",
abstract = "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 typeable 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.",
author = "Scott, {Jennifer R.} and Jason Hinds and Gould, {Katherine A.} and Millar, {Eugene V.} and Raymond Reid and Mathuram Santosham and O'Brien, {Katherine L.} and Hanage, {William P.}",
note = "Funding Information: Financial support. This work is part of the research of the Pneumo-Carr Consortium funded by the Grand Challenges in Global Health initiative, which is supported by the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, the Wellcome Trust, and the Canadian Institutes of Health Research. This study was supported by the Native American Research Centers for Health (U26IHS300013/03), a joint initiative between the National Institutes of Health and Indian Health Service to reduce native health disparities and build tribal autonomy in conducting health research. This study was also funded by the Centers for Disease Control and Prevention National Vaccine Program Office and the Thrasher Research Fund. W. P. H.{\textquoteright}s contribution to the project was funded by the Royal Society (University Research Fellowship) and the National Institute of General Medical Sciences (award number U54GM088558). Funding Information: Acknowledgments. The authors express their sincere appreciation to the children and adults from the Navajo and White Mountain Apache communities who participated in the studies. We gratefully acknowledge the tireless efforts of the Center for American Indian Health field staff who collected these data over many years and the dedicated support provided by Delois Jackson, Bob Gertz, and Dr Bernard Beall at the Centers for Disease Control and Prevention (CDC) for NP sample storage and serotyping. We also gratefully acknowledge the serotyping of the invasive strains by Karen Rudolph and Marcella Harker-Jones at the CDC Arctic Investigations Program, Anchorage, Alaska. We appreciate the MLST support provided by Cynthia Bishop and Dan Godoy at Imperial College and acknowledge the Wellcome Trust for funding the Bacterial Microarray Group at St. George{\textquoteright}s, University of London. We also thank Marc Lipsitch at the Harvard School of Public Health and Lawrence Moulton at the Johns Hopkins School of Public Health for their helpful comments on this work.",
year = "2012",
month = jul,
day = "1",
doi = "10.1093/infdis/jis307",
language = "English (US)",
volume = "206",
pages = "73--80",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "1",
}