title: Absence of Association Between Sickle Trait Hemoglobin and Placental Malaria Outcomes.
abstract: Heterozygous hemoglobin S (HbAS), or sickle trait, protects children from life-threatening falciparum malaria, potentially by attenuating binding of Plasmodium-infected red blood cells (iRBCs) to extracellular ligands. Such binding is central to the pathogenesis of placental malaria (PM). We hypothesized that HbAS would be associated with reduced risks of PM and low birth weight (LBW). We tested this hypothesis in 850 delivering women in southern Malawi. Parasites were detected by polymerase chain reaction in placental and peripheral blood, and placentae were scored histologically for PM. The prevalence of HbAS was 3.7%, and 11.2% of infants were LBW (< 2,500 g). The prevalence of Plasmodium falciparum was 12.7% in placental and 8.5% in peripheral blood; 24.4% of placentae demonstrated histological evidence of P. falciparum HbAS was not associated with reduced prevalence of P. falciparum in placental (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.50-3.23, P = 0.61) or peripheral blood (OR: 2.53, 95% CI: 1.08-2.54, P = 0.03), prevalence of histological PM (OR: 0.97, 95% CI: 0.40-2.34, P = 0.95), or prevalence of LBW (OR: 0.82, 95% CI: 0.24-2.73, P = 0.74). Mean (standard deviation) birth weights of infants born to HbAS (2,947 g [563]) and, homozygous hemoglobin A (2,991 g [465]) mothers were similar. Across a range of parasitologic, clinical, and histologic outcomes, HbAS did not confer protection from PM or its adverse effects.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Community Health, College of Medicine, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Division of Infectious Diseases and International Health and Duke Global Health Institute, Duke University Medical Center, Durham, North Carolina jaymin.patel@unc.edu.
authors.forename: Jaymin C
authors.initials: JC
authors.lastname: Patel
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Community Health, College of Medicine, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Division of Infectious Diseases and International Health and Duke Global Health Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Victor
authors.initials: V
authors.lastname: Mwapasa
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Community Health, College of Medicine, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Division of Infectious Diseases and International Health and Duke Global Health Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Linda
authors.initials: L
authors.lastname: Kalilani
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Community Health, College of Medicine, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Division of Infectious Diseases and International Health and Duke Global Health Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Feiko O
authors.initials: FO
authors.lastname: Ter Kuile
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Community Health, College of Medicine, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Division of Infectious Diseases and International Health and Duke Global Health Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Carole
authors.initials: C
authors.lastname: Khairallah
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Community Health, College of Medicine, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Division of Infectious Diseases and International Health and Duke Global Health Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Kyaw L
authors.initials: KL
authors.lastname: Thwai
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Community Health, College of Medicine, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Division of Infectious Diseases and International Health and Duke Global Health Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Community Health, College of Medicine, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Division of Infectious Diseases and International Health and Duke Global Health Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Steve M
authors.initials: SM
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000469:parasitology*; D008295:Malawi / Q000453:epidemiology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000473:pathology*; D011256:Pregnancy Outcome; D015995:Prevalence; D011739:Pyrimethamine / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D012805:Sickle Cell Trait / Q000378:metabolism*; D013413:Sulfadoxine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D006451:Hemoglobin, Sickle; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine