Matthew S Kelly1,2, Michael G Surette3, Marek Smieja3,4,5,6, Laura Rossi3, Kathy Luinstra6, Andrew P Steenhoff1,7,8, David M Goldfarb1,9, Jeffrey M Pernica5, Tonya Arscott-Mills1,7, Sefelani Boiditswe1, Tiny Mazhani10, John F Rawls11, Coleen K Cunningham2, Samir S Shah12,13, Kristen A Feemster7,8, Patrick C Seed14,15. 1. From the Botswana-UPenn Partnership, Gaborone, Botswana. 2. Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC. 3. Department of Medicine. 4. Department of Pathology and Molecular Medicine. 5. Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada. 6. St. Joseph's Healthcare, Hamilton, Ontario, Canada. 7. Global Health Center. 8. Division of Pediatric Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA. 9. Department of Pathology and Laboratory Medicine, BC Children's Hospital, Vancouver, British Columbia, Canada. 10. University of Botswana School of Medicine, Gaborone, Botswana. 11. Duke Microbiome Center, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC. 12. Divisions of Hospital Medicine and Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. 13. University of Cincinnati College of Medicine, Cincinnati, OH. 14. Division of Pediatric Infectious Diseases, Ann and Robert Lurie Children's Hospital, Chicago, IL. 15. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Abstract
BACKGROUND: Nasopharyngeal colonization precedes infections caused by Streptococcus pneumoniae. A more detailed understanding of interactions between S. pneumoniae and the nasopharyngeal microbiota of children could inform strategies to prevent pneumococcal infections. METHODS: We collected nasopharyngeal swabs from children 1 to 23 months of age in Botswana between August 2012 and June 2016. We tested samples for S. pneumoniae and common respiratory viruses using polymerase chain reaction. We sequenced the V3 region of the bacterial 16S ribosomal RNA gene and used random forest models to identify clinical variables and bacterial genera that were associated with pneumococcal colonization. RESULTS: Mean age of the 170 children included in this study was 8.3 months. Ninety-six (56%) children were colonized with S. pneumoniae. Pneumococcal colonization was associated with older age (P = 0.0001), a lack of electricity in the home (P = 0.02) and household use of wood as a cooking fuel (P = 0.002). Upper respiratory symptoms were more frequent in children with S. pneumoniae colonization (60% vs. 32%; P = 0.001). Adjusting for age, nasopharyngeal microbiota composition differed in colonized and noncolonized children (P = 0.001). S. pneumoniae colonization was associated with a higher relative abundance of Moraxella (P = 0.001) and lower relative abundances of Corynebacterium (P = 0.001) and Staphylococcus (P = 0.03). A decision tree model containing the relative abundances of bacterial genera had 81% sensitivity and 85% specificity for the determination of S. pneumoniae colonization status. CONCLUSIONS: S. pneumoniae colonization is associated with characteristic alterations of the nasopharyngeal microbiota of children. Prospective studies should determine if nasopharyngeal microbial composition alters the risk of pneumococcal colonization and thus could be modified as a novel pneumonia prevention strategy.
BACKGROUND: Nasopharyngeal colonization precedes infections caused by Streptococcus pneumoniae. A more detailed understanding of interactions between S. pneumoniae and the nasopharyngeal microbiota of children could inform strategies to prevent pneumococcal infections. METHODS: We collected nasopharyngeal swabs from children 1 to 23 months of age in Botswana between August 2012 and June 2016. We tested samples for S. pneumoniae and common respiratory viruses using polymerase chain reaction. We sequenced the V3 region of the bacterial 16S ribosomal RNA gene and used random forest models to identify clinical variables and bacterial genera that were associated with pneumococcal colonization. RESULTS: Mean age of the 170 children included in this study was 8.3 months. Ninety-six (56%) children were colonized with S. pneumoniae. Pneumococcal colonization was associated with older age (P = 0.0001), a lack of electricity in the home (P = 0.02) and household use of wood as a cooking fuel (P = 0.002). Upper respiratory symptoms were more frequent in children with S. pneumoniae colonization (60% vs. 32%; P = 0.001). Adjusting for age, nasopharyngeal microbiota composition differed in colonized and noncolonized children (P = 0.001). S. pneumoniae colonization was associated with a higher relative abundance of Moraxella (P = 0.001) and lower relative abundances of Corynebacterium (P = 0.001) and Staphylococcus (P = 0.03). A decision tree model containing the relative abundances of bacterial genera had 81% sensitivity and 85% specificity for the determination of S. pneumoniae colonization status. CONCLUSIONS: S. pneumoniae colonization is associated with characteristic alterations of the nasopharyngeal microbiota of children. Prospective studies should determine if nasopharyngeal microbial composition alters the risk of pneumococcal colonization and thus could be modified as a novel pneumonia prevention strategy.
Authors: Jonathan M Mansbach; Kohei Hasegawa; David M Henke; Nadim J Ajami; Joseph F Petrosino; Chad A Shaw; Pedro A Piedra; Ashley F Sullivan; Janice A Espinola; Carlos A Camargo Journal: J Allergy Clin Immunol Date: 2016-04-06 Impact factor: 10.793
Authors: Osman Abdullahi; Angela Karani; Caroline C Tigoi; Daisy Mugo; Stella Kungu; Eva Wanjiru; Jane Jomo; Robert Musyimi; Marc Lipsitch; J Anthony G Scott Journal: PLoS One Date: 2012-02-20 Impact factor: 3.240
Authors: Adam K A Wright; Daniela M Ferreira; Jenna F Gritzfeld; Angela D Wright; Kathryn Armitage; Kondwani C Jambo; Emily Bate; Sherouk El Batrawy; Andrea Collins; Stephen B Gordon Journal: PLoS Pathog Date: 2012-04-05 Impact factor: 6.823
Authors: Matthew S Kelly; Marek Smieja; Kathy Luinstra; Kathleen E Wirth; David M Goldfarb; Andrew P Steenhoff; Tonya Arscott-Mills; Coleen K Cunningham; Sefelani Boiditswe; Warona Sethomo; Samir S Shah; Rodney Finalle; Kristen A Feemster Journal: PLoS One Date: 2015-05-14 Impact factor: 3.240
Authors: Shu Mei Teo; Danny Mok; Kym Pham; Merci Kusel; Michael Serralha; Niamh Troy; Barbara J Holt; Belinda J Hales; Michael L Walker; Elysia Hollams; Yury A Bochkov; Kristine Grindle; Sebastian L Johnston; James E Gern; Peter D Sly; Patrick G Holt; Kathryn E Holt; Michael Inouye Journal: Cell Host Microbe Date: 2015-04-09 Impact factor: 21.023
Authors: Ellen Heinsbroek; Terence Tafatatha; Christina Chisambo; Amos Phiri; Oddie Mwiba; Bagrey Ngwira; Amelia C Crampin; Jonathan M Read; Neil French Journal: Am J Epidemiol Date: 2015-12-01 Impact factor: 4.897
Authors: Astrid A T M Bosch; Giske Biesbroek; Krzysztof Trzcinski; Elisabeth A M Sanders; Debby Bogaert Journal: PLoS Pathog Date: 2013-01-10 Impact factor: 6.823
Authors: Matthew S Kelly; Catherine Plunkett; Yahe Yu; Jhoanna N Aquino; Sweta M Patel; Jillian H Hurst; Rebecca R Young; Marek Smieja; Andrew P Steenhoff; Tonya Arscott-Mills; Kristen A Feemster; Sefelani Boiditswe; Tirayaone Leburu; Tiny Mazhani; Mohamed Z Patel; John F Rawls; Jayanth Jawahar; Samir S Shah; Christopher R Polage; Coleen K Cunningham; Patrick C Seed Journal: ISME J Date: 2021-09-11 Impact factor: 10.302
Authors: L Patrick Schenck; Joshua J C McGrath; Daphnée Lamarche; Martin R Stämpfli; Dawn M E Bowdish; Michael G Surette Journal: mSphere Date: 2020-12-16 Impact factor: 4.389