title: How hidden can malaria be in pregnant women? Diagnosis by microscopy, placental histology, polymerase chain reaction and detection of histidine-rich protein 2 in plasma.
abstract: BACKGROUND
  Accurate diagnosis of malaria infection during pregnancy remains challenging because of low parasite densities and placental sequestration of Plasmodium falciparum. The performance of different methods to detect P. falciparum in pregnancy and the clinical relevance of undetected infections were evaluated.
  
  
  METHODS
  P. falciparum infections were assessed in 272 Mozambican women at delivery by microscopy, placental histology, quantitative polymerase chain reaction (qPCR) and detection of histidine-rich protein 2 (HRP2) in plasma by enzyme-linked immunosorbent assay (ELISA) and a rapid diagnostic test (RDT). Association between infection and delivery outcomes was determined.
  
  
  RESULTS
  Among the 122 women qPCR-positive for P. falciparum in peripheral and/or placental blood samples, 87 (71.3%) did not receive a positive diagnosis by peripheral microscopy, 75 (61.5%) by HRP2 ELISA, and 74 (60.7%) by HRP2 RDT in plasma. Fifty-seven of the 98 qPCR-positive placental infections (58.2%) were not detected by histology. Women who were qPCR-positive but negative in their peripheral blood by microscopy or HRP2 RDT in plasma (n = 62) were at increased risk of anemia, compared with negative women (n = 141; odds ratio, 2.03; 95% confidence interval, 1.07-3.83; P = .029).
  
  
  CONCLUSIONS
  Microscopy, placental histology and HRP2-based plasma diagnostic methods fail to identify the majority of the P. falciparum infections detected by qPCR in peripheral and placental blood. Undetected infections were associated with maternal anemia, highlighting the urgent need for more accurate malaria diagnostic tools for pregnant women to avoid the negative clinical impact that hidden infections can have during pregnancy.
  
  
  BACKGROUND
  NCT00209781.
authors.affiliation: Barcelona Center for International Health Research, Hospital Clínic-Universitat de Barcelona, Spain. agmayor@clinic.ub.es
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.forename: Laura
authors.initials: L
authors.lastname: Moro
authors.forename: Ruth
authors.initials: R
authors.lastname: Aguilar
authors.forename: Azucena
authors.initials: A
authors.lastname: Bardají
authors.forename: Pau
authors.initials: P
authors.lastname: Cisteró
authors.forename: Elisa
authors.initials: E
authors.lastname: Serra-Casas
authors.forename: Betuel
authors.initials: B
authors.lastname: Sigaúque
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
mesh_terms: D000328:Adult; D000953:Antigens, Protozoan / Q000097:blood; D019411:Clinical Laboratory Techniques / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006651:Histocytochemistry / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000175:diagnosis*; D008853:Microscopy / Q000379:methods; D009073:Mozambique; D010920:Placenta / Q000473:pathology; D010949:Plasma / Q000737:chemistry; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis*; D015800:Protozoan Proteins / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods
chemical_list: D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins