title: Submicroscopic malaria infection during pregnancy and the impact of intermittent preventive treatment.
abstract: BACKGROUND
  Malaria during pregnancy results in adverse outcomes for mothers and infants. Intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) is the primary intervention aimed at reducing malaria infection during pregnancy. Although submicroscopic infection is common during pregnancy and at delivery, its impact throughout pregnancy on the development of placental malaria and adverse pregnancy outcomes has not been clearly established.
  
  
  METHODS
  Quantitative PCR was used to detect submicroscopic infections in pregnant women enrolled in an observational study in Blantyre, Malawi to determine their effect on maternal, foetal and placental outcomes. The ability of SP to treat and prevent submicroscopic infections was also assessed.
  
  
  RESULTS
  2,681 samples from 448 women were analysed and 95 submicroscopic infections were detected in 68 women, a rate of 0.6 episodes per person-year of follow-up. Submicroscopic infections were most often detected at enrolment. The majority of women with submicroscopic infections did not have a microscopically detectable infection detected during pregnancy. Submicroscopic infection was associated with placental malaria even after controlling for microscopically detectable infection and was associated with decreased maternal haemoglobin at the time of detection. However, submicroscopic infection was not associated with adverse maternal or foetal outcomes at delivery. One-third of women with evidence of placental malaria did not have documented peripheral infection during pregnancy. SP was moderately effective in treating submicroscopic infections, but did not prevent the development of new submicroscopic infections in the month after administration.
  
  
  CONCLUSIONS
  Submicroscopic malaria infection is common and occurs early in pregnancy. SP-IPT can clear some submicroscopic infections but does not prevent new infections after administration. To effectively control pregnancy-associated malaria, new interventions are required to target women prior to their first antenatal care visit and to effectively treat and prevent all malaria infections.
authors.affiliation: Center for Vaccine Development, School of Medicine, University of Maryland, Baltimore, Maryland, USA. lcohee@medicine.umaryland.edu.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Cohee
authors.forename: Linda
authors.initials: L
authors.lastname: Kalilani-Phiri
authors.forename: Sarah
authors.initials: S
authors.lastname: Boudova
authors.forename: Sudhaunshu
authors.initials: S
authors.lastname: Joshi
authors.forename: Rabia
authors.initials: R
authors.lastname: Mukadam
authors.forename: Karl B
authors.initials: KB
authors.lastname: Seydel
authors.forename: Patricia
authors.initials: P
authors.lastname: Mawindo
authors.forename: Phillip
authors.initials: P
authors.lastname: Thesing
authors.forename: Steve
authors.initials: S
authors.lastname: Kamiza
authors.forename: Kingsley
authors.initials: K
authors.lastname: Makwakwa
authors.forename: Atis
authors.initials: A
authors.lastname: Muehlenbachs
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
authors.forename: Miriam K
authors.initials: MK
authors.lastname: Laufer
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use; D058070:Asymptomatic Diseases; D016054:DNA, Protozoan / Q000097:blood*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004351:Drug Resistance; D004912:Erythrocytes / Q000469:parasitology; D004983:Ethanolamines / Q000627:therapeutic use; D005188:False Negative Reactions; D005260:Female; D005315:Fetal Diseases / Q000517:prevention & control*; D005449:Fluorenes / Q000627:therapeutic use; D005500:Follow-Up Studies; D006420:Hemeproteins / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008288:Malaria / Q000175:diagnosis / Q000188:drug therapy / Q000196:embryology / Q000517:prevention & control* / Q000635:transmission; D008295:Malawi / Q000453:epidemiology; D018512:Parasitemia / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control*; D010920:Placenta / Q000469:parasitology; D010961:Plasmodium / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000517:prevention & control*; D011256:Pregnancy Outcome; D011264:Pregnancy Trimesters; D015995:Prevalence; D011739:Pyrimethamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011803:Quinine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D016054:DNA, Protozoan; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D006420:Hemeproteins; C001205:fanasil, pyrimethamine drug combination; C020753:hemozoin; D013413:Sulfadoxine; D011803:Quinine; D011739:Pyrimethamine