title: The diagnostic and prognostic accuracy of five markers of serious bacterial infection in Malawian children with signs of severe infection.
abstract: BACKGROUND
  Early recognition and prompt and appropriate antibiotic treatment can significantly reduce mortality from serious bacterial infections (SBI). The aim of this study was to evaluate the utility of five markers of infection: C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), CD163 and high mobility group box-1 (HMGB1), as markers of SBI in severely ill Malawian children.
  
  
  RESULTS
  Children presenting with a signs of meningitis (n = 282) or pneumonia (n = 95), were prospectively recruited. Plasma samples were taken on admission for CRP, PCT, sTREM-1 CD163 and HMGB1 and the performance characteristics of each test to diagnose SBI and to predict mortality were determined. Of 377 children, 279 (74%) had SBI and 83 (22%) died. Plasma CRP, PCT, CD163 and HMGB1 and were higher in HIV-infected children than in HIV-uninfected children (p<0.01). In HIV-infected children, CRP and PCT were higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and PCT and CD163 were higher in non-survivors (p = 0.001, p = 0.05 respectively). In HIV-uninfected children, CRP and PCT were also higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and CD163 was higher in non-survivors (p = 0.05). The best predictors of SBI were CRP and PCT, and areas under the curve (AUCs) were 0.81 (95% CI 0.73-0.89) and 0.86 (95% CI 0.79-0.92) respectively. The best marker for predicting death was PCT, AUC 0.61 (95% CI 0.50-0.71).
  
  
  CONCLUSIONS
  Admission PCT and CRP are useful markers of invasive bacterial infection in severely ill African children. The study of these markers using rapid tests in a less selected cohort would be important in this setting.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. edcarrol@liv.ac.uk
authors.forename: Enitan D
authors.initials: ED
authors.lastname: Carrol
authors.forename: Limangeni A
authors.initials: LA
authors.lastname: Mankhambo
authors.forename: Graham
authors.initials: G
authors.lastname: Jeffers
authors.forename: Deborah
authors.initials: D
authors.lastname: Parker
authors.forename: Malcolm
authors.initials: M
authors.lastname: Guiver
authors.forename: Paul
authors.initials: P
authors.lastname: Newland
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Banda
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Molyneux
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Hart
mesh_terms: D000293:Adolescent; D001424:Bacterial Infections / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D015415:Biomarkers / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008295:Malawi / Q000453:epidemiology; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D015203:Reproducibility of Results; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers
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