title: Diagnosis of placental malaria in poorly fixed and processed placental tissue.
abstract: BACKGROUND
  Placental histopathology has been considered the gold standard for diagnosis of malaria during pregnancy. However, in under-resourced areas placental tissue is often improperly fixed and processed; the resulting formalin pigment is difficult to distinguish from malaria pigment. This study examines two alternative diagnostic methods: polymerase chain reaction (PCR) and a novel immunohistochemistry (IHC)-based method using an antibody against histidine-rich protein 2 (HRP2).
  
  
  METHODS
  Placental histopathology from 151 pregnant women in Kinshasa was assessed by two blinded microscopists and compared with peripheral blood PCR and IHC for HRP2. The Cohen's kappa coefficients were calculated to assess the test agreement. The sensitivity and specificity of individual tests were calculated using PCR or IHC as the reference standard as well as latent class analysis (LCA).
  
  
  RESULTS
  PCR and IHC correlated fairly well. The correlation between the two blinded microscopists was poor, as there was widespread formalin pigment. Using LCA, all of the tests had high specificities. The most sensitive test was IHC (67.7 %), with PCR as second-best (56.1 %).
  
  
  CONCLUSIONS
  PCR and/or IHC are suitable diagnostics when the presence of formalin pigment substantially compromises placental histopathology.
authors.affiliation: Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA. yl6b@live.unc.edu.|Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA. yl6b@live.unc.edu.
authors.forename: Yunhao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: RTI International, Research Triangle Park, NC, USA.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Griffin
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Atis
authors.initials: A
authors.lastname: Muehlenbachs
authors.affiliation: Department of Medicine at Peter Doherty Institute, University of Melbourne, Melbourne, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Anya J
authors.initials: AJ
authors.lastname: Bailis
authors.affiliation: Immunopathology Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sullivan
authors.affiliation: Kinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo.
authors.forename: Antoinette K
authors.initials: AK
authors.lastname: Tshefu
authors.affiliation: Glaxo-Smith-Kline, Worldwide Epidemiology, Uxbridge, Middlesex, UK.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Landis
authors.affiliation: Department of Medical Biology, Service of Pathology, University of Kinshasa Medical School and University Hospital, Kinshasa, Democratic Republic of the Congo.
authors.forename: Jean-Marie M
authors.initials: JM
authors.lastname: Kabongo
authors.affiliation: Division of Infectious Diseases & International Health and Duke Global Health Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Steve M
authors.initials: SM
authors.lastname: Taylor
authors.affiliation: Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
mesh_terms: D000293:Adolescent; D000328:Adult; D015023:Democratic Republic of the Congo; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008288:Malaria / Q000175:diagnosis* / Q000469:parasitology / Q000473:pathology; D010920:Placenta / Q000469:parasitology* / Q000473:pathology*; D010922:Placenta Diseases / Q000175:diagnosis* / Q000469:parasitology / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods*; D011247:Pregnancy; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult
keywords: Histopathology; IHC; Latent class analysis; Malaria; Molecular epidemiology; PCR