title: HRP2 and pLDH-Based Rapid Diagnostic Tests, Expert Microscopy, and PCR for Detection of Malaria Infection during Pregnancy and at Delivery in Areas of Varied Transmission: A Prospective Cohort Study in Burkina Faso and Uganda.
abstract: BACKGROUND
  Intermittent screening and treatment (IST) of malaria during pregnancy has been proposed as an alternative to intermittent preventive treatment in pregnancy (IPTp), where IPTp is failing due to drug resistance. However, the antenatal parasitaemias are frequently very low, and the most appropriate screening test for IST has not been defined.
  
  
  RESULTS
  We conducted a multi-center prospective study of 990 HIV-uninfected women attending ANC in two different malaria transmission settings at Tororo District Hospital, eastern Uganda and Colsama Health Center in western Burkina Faso. Women were enrolled in the study in the second or third trimester of pregnancy and followed to delivery, generating 2,597 blood samples for analysis. Screening tests included rapid diagnostic tests (RDTs) targeting histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH) and microscopy, compared to nPCR as a reference standard. At enrolment, the proportion of pregnant women who were positive for P. falciparum by HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT, microscopy and PCR was 38%, 29%, 36% and 44% in Uganda and 21%, 16%, 15% and 35% in Burkina Faso, respectively. All test positivity rates declined during follow-up. In comparison to PCR, the sensitivity of the HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT and microscopy was 75.7%, 60.1% and 69.7% in Uganda, 55.8%, 42.6% and 55.8% in Burkina Faso respectively for all antenatal visits. Specificity was greater than 96% for all three tests. Comparison of accuracy using generalized estimating equation revealed that the HRP2- detecting RDT was the most accurate test in both settings.
  
  
  CONCLUSIONS
  The study suggests that HRP2-based RDTs are the most appropriate point-of-care test currently available for use during pregnancy especially for symptomatic women, but will still miss some PCR-positive women. The clinical significance of these very low density infections needs to be better defined.
authors.affiliation: Foundation for Innovative New Diagnostics, Kampala, Uganda.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kyabayinze
authors.affiliation: Institut de Recherche en Sciences de la Santé (IRSS), Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
authors.forename: Issaka
authors.initials: I
authors.lastname: Zongo
authors.affiliation: UNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases (TDR), Geneva, Switzerland.
authors.forename: Jane
authors.initials: J
authors.lastname: Cunningham
authors.affiliation: School of Public Health and Social Work, Queensland University of Technology, Queensland, Australia.
authors.forename: Michelle
authors.identifier: http://orcid.org/0000-0003-1188-609X
authors.initials: M
authors.lastname: Gatton
authors.affiliation: Foundation for Innovative New Diagnostics, Kampala, Uganda.
authors.forename: Patrick
authors.initials: P
authors.lastname: Angutoko
authors.affiliation: Foundation for Innovative New Diagnostics, Kampala, Uganda.
authors.forename: John
authors.initials: J
authors.lastname: Ategeka
authors.affiliation: Institut de Recherche en Sciences de la Santé (IRSS), Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
authors.forename: Yves-Daniel
authors.initials: YD
authors.lastname: Compaoré
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Atis
authors.initials: A
authors.lastname: Muehlenbachs
authors.affiliation: Foundation for Innovative New Diagnostics, Kampala, Uganda.
authors.forename: Jerry
authors.identifier: http://orcid.org/0000-0001-8106-5057
authors.initials: J
authors.lastname: Mulondo
authors.affiliation: Department of Obstetrics & Gynecology, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Miriam
authors.identifier: http://orcid.org/0000-0001-7569-8173
authors.initials: M
authors.lastname: Nakalembe
authors.affiliation: Institut de Recherche en Sciences de la Santé (IRSS), Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
authors.forename: Fabrice A
authors.initials: FA
authors.lastname: Somé
authors.affiliation: Institut de Recherche en Sciences de la Santé (IRSS), Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
authors.forename: Aminata
authors.initials: A
authors.lastname: Ouattara
authors.affiliation: Institut de Recherche en Sciences de la Santé (IRSS), Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
authors.forename: Noél
authors.initials: N
authors.lastname: Rouamba
authors.affiliation: Institut de Recherche en Sciences de la Santé (IRSS), Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
authors.forename: Jean-Bosco
authors.initials: JB
authors.lastname: Ouédraogo
authors.affiliation: Foundation for Innovative New Diagnostics, Kampala, Uganda.|Foundation for Innovative New Diagnostics, Geneva, Switzerland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hopkins
authors.affiliation: Foundation for Innovative New Diagnostics, Geneva, Switzerland.
authors.forename: David
authors.identifier: http://orcid.org/0000-0002-7010-6340
authors.initials: D
authors.lastname: Bell
mesh_terms: D000328:Adult; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D002050:Burkina Faso; D003955:Diagnostic Tests, Routine / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D006790:Host-Parasite Interactions; D006801:Humans; D007231:Infant, Newborn; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000469:parasitology* / Q000635:transmission; D008853:Microscopy / Q000379:methods; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019095:Point-of-Care Systems; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011295:Prenatal Care / Q000706:statistics & numerical data; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D012621:Seasons; D012680:Sensitivity and Specificity; D014454:Uganda; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D007770:L-Lactate Dehydrogenase