title: High nasopharyngeal pneumococcal density, increased by viral coinfection, is associated with invasive pneumococcal pneumonia.
abstract: BACKGROUND
  We identified factors associated with pneumococcal colonization, high colonization density, and invasive pneumococcal pneumonia among patients hospitalized with acute lower respiratory tract infections (ALRTIs).
  
  
  METHODS
  In 2010, 4025 cases were enrolled in surveillance in South Africa. A total of 969 of 4025 systematically selected nasopharyngeal-oropharyngeal specimens (24%) were tested for respiratory viruses and Streptococcus pneumoniae by real-time polymerase chain reaction. Of these, 749 (77%) had blood tested for S. pneumoniae.
  
  
  RESULTS
  Pneumococcal colonization was detected in 55% of cases (534 of 969). On multivariable analysis that controlled for age and tuberculosis treatment, infection with influenza virus (adjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1-4.5), adenovirus (adjusted OR, 1.7; 95% CI, 1.1-2.7), rhinovirus (adjusted OR, 1.6; 95% CI, 1.1-2.3), and human immunodeficiency virus (HIV; adjusted OR, 1.6; 95% CI, 1.1-2.4) were associated with pneumococcal colonization. High colonization density was associated with respiratory virus coinfection (adjusted OR, 1.7; 95% CI, 1.1-2.6) and invasive pneumococcal pneumonia (adjusted OR, 2.3; 95% CI, 1.3-4.0), after adjustment for age and sex. Seven percent (52 of 749) had pneumococci detected in blood. On multivariable analysis among colonized cases, invasive pneumococcal pneumonia was associated with HIV (adjusted OR, 3.2; 95% CI, 1.4-7.5), influenza virus (adjusted OR, 8.2; 95% CI, 2.7-25.0), high colonization density (adjusted OR, 18.7; 95% CI, 2.3-155.1), and ≥5 days of hospitalization (adjusted OR, 3.7; 95% CI, 1.7-8.2).
  
  
  CONCLUSIONS
  Respiratory virus infection was associated with elevated colonization density and, in turn, invasive pneumococcal pneumonia.
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service Faculty of Health Sciences Medical Research Council: Respiratory and Meningeal Pathogens Research Unit.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wolter
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service Influenza Division, Centers for Disease Control and Prevention.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tempia
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service Faculty of Health Sciences.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service Medical Research Council: Respiratory and Meningeal Pathogens Research Unit Department of Science and Technology/National Research Foundation: Vaccine-Preventable Diseases.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service Zoonoses Research Unit, Department of Medical Virology, University of Pretoria.
authors.forename: Marietjie
authors.initials: M
authors.lastname: Venter
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Moyes
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service.
authors.forename: Sibongile
authors.initials: S
authors.lastname: Walaza
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service.
authors.forename: Babatyi
authors.initials: B
authors.lastname: Malope-Kgokong
authors.affiliation: Department of Science and Technology/National Research Foundation: Vaccine-Preventable Diseases.
authors.forename: Michelle
authors.initials: M
authors.lastname: Groome
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service Faculty of Health Sciences Medical Research Council: Respiratory and Meningeal Pathogens Research Unit.
authors.forename: Mignon
authors.initials: M
authors.lastname: du Plessis
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service Medical Research Council: Respiratory and Meningeal Pathogens Research Unit.
authors.forename: Victoria
authors.initials: V
authors.lastname: Magomani
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service.
authors.forename: Marthi
authors.initials: M
authors.lastname: Pretorius
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service.
authors.forename: Orienka
authors.initials: O
authors.lastname: Hellferscee
authors.affiliation: Pietermaritzburg Metropolitan Hospitals University of KwaZulu Natal.
authors.forename: Halima
authors.initials: H
authors.lastname: Dawood
authors.affiliation: MRC/Wits Rural Public Health and Health Transition Research Unit Research Unit (Agincourt), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg Centre for Global Health Research, Umeå University, Sweden INDEPTH Network, Accra, Ghana.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kahn
authors.affiliation: Klerksdorp/Tshepong Hospital, South Africa.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Variava
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service Hubert Department of Global Health, Rollins School of Public Health Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service Faculty of Health Sciences Medical Research Council: Respiratory and Meningeal Pathogens Research Unit.
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000453:epidemiology* / Q000382:microbiology; D058491:Bacterial Load; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000382:microbiology* / Q000821:virology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000382:microbiology / Q000821:virology; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012141:Respiratory Tract Infections / Q000382:microbiology* / Q000821:virology*; D013019:South Africa; D013296:Streptococcus pneumoniae / Q000302:isolation & purification; D014777:Virus Diseases / Q000150:complications* / Q000821:virology; D014780:Viruses / Q000145:classification / Q000302:isolation & purification; D055815:Young Adult
keywords: bacterial loads; colonization; invasive pneumococcal disease; pneumococcus; respiratory virus