title: Pneumococcal colonisation density: a new marker for disease severity in HIV-infected adults with pneumonia.
abstract: OBJECTIVE
  A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome.
  
  
  METHODS
  Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci.
  
  
  RESULTS
  There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01).
  
  
  CONCLUSIONS
  In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St Gallen, St Gallen, Switzerland Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Werner C
authors.initials: WC
authors.lastname: Albrich
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Adrian
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nadia
authors.initials: N
authors.lastname: van Niekerk
authors.affiliation: Emerging Pathogens Laboratory, Fondation Mérieux, Lyon, France.
authors.forename: Jean-Noel
authors.initials: JN
authors.lastname: Telles
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: N
authors.initials: N
authors.lastname: Ebrahim
authors.affiliation: Emerging Pathogens Laboratory, Fondation Mérieux, Lyon, France.
authors.forename: Melina
authors.initials: M
authors.lastname: Messaoudi
authors.affiliation: Emerging Pathogens Laboratory, Fondation Mérieux, Lyon, France.
authors.forename: Glaucia
authors.initials: G
authors.lastname: Paranhos-Baccalà
authors.affiliation: Thermo Scientific Biomarkers, Hennigsdorf, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Giersdorf
authors.affiliation: Emerging Pathogens Laboratory, Fondation Mérieux, Lyon, France Centre Pasteur du Cameroun, Yaoundé, Cameroun.
authors.forename: Guy
authors.initials: G
authors.lastname: Vernet
authors.affiliation: Department of Internal Medicine, Medical University Department, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Mueller
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa Hubert Department of Global Health and Division of Infectious Diseases, Emory University, Atlanta, Georgia, USA Pneumonia Program, Bill and Melinda Gates Foundation, Seattle, Washington, USA.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
mesh_terms: D000293:Adolescent; D053607:Adrenomedullin / Q000097:blood; D000328:Adult; D016470:Bacteremia / Q000382:microbiology; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D017714:Community-Acquired Infections / Q000150:complications / Q000382:microbiology; D015658:HIV Infections / Q000150:complications*; D006760:Hospitalization; D006801:Humans; D009305:Nasopharynx / Q000382:microbiology*; D011014:Pneumonia; D011018:Pneumonia, Pneumococcal / Q000150:complications / Q000382:microbiology*; D011498:Protein Precursors / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D013019:South Africa; D013296:Streptococcus pneumoniae / Q000254:growth & development*
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide
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