title: Performance characteristics of combinations of host biomarkers to identify women with occult placental malaria: a case-control study from Malawi.
abstract: BACKGROUND
  Because of its propensity to sequester in the placental intervillous space, Plasmodium falciparum can evade detection by peripheral smear in women with placental malaria (PM). We evaluated host biomarkers as potential indicators of occult PM infections.
  
  
  RESULTS
  Using a case-control design, we evaluated the ability of biomarkers to identify PM in the absence of circulating peripheral parasites (n = 24) compared to placental smear-negative controls (n = 326). We measured levels of biomarkers (C3a, C5a, CRP, angiopoietin-1, angiopoietin-2, sTie-2, sEndoglin, VEGF, sFlt-1, tissue factor, and leptin) in maternal peripheral plasma at delivery. Using ROC curve analysis, we assessed the ability of clinical parameters and biomarkers to accurately detect PM infections identified by placental smear. We show that decreases in sFlt-1 and leptin and increases in CRP were associated with occult PM infections (p<0.01) and correlated with placental parasitaemia (p<0.01). Individually, all markers had moderate ability to diagnose occult PM infections with areas under the ROC between 0.62 and 0.72. In order to improve diagnostic performance, we generated simple scoring systems to identify PM infections using either a clinical score (0-2), a biomarker score (0-3) or a clinical plus biomarker score (0-5). The combinatorial model that incorporated both clinical parameters and biomarkers had an area under curve (AUC) of 0.85 (95% CI, 0.81-0.89), which was significantly better at identifying occult PM infections than the clinical score alone (p = 0.001).
  
  
  CONCLUSIONS
  These data suggest that host biomarkers in the maternal peripheral blood may improve the detection of PM in the absence of peripheral parasitaemia.
authors.affiliation: Sandra A. Rotman Laboratories, McLaughlin-Rotman Centre for Global Health, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Conroy
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood; D016778:Malaria, Falciparum / Q000097:blood* / Q000175:diagnosis* / Q000469:parasitology; D008295:Malawi; D010920:Placenta / Q000469:parasitology*; D011247:Pregnancy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D020738:Leptin; D002097:C-Reactive Protein; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1