title: Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination.
abstract: BACKGROUND
  Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge.
  
  
  METHODS
  We recruited healthy PM+ and PM- infants at birth. At six and 12 months, we stimulated PBMCs with tuberculin purified protein derivative (PPD) and compared expression of CD154, IL-2 and IFNγ by CD4 T-cells to a negative control using flow cytometry.We measured the length, weight and head circumference at birth and 12 months.
  
  
  RESULTS
  IL-2 and CD154 expression were low in both groups at both timepoints, without discernable differences. Expression of IFNγ was similarly low at 6 months but by 12 months, the median response was higher in PM- than PM + infants (p = 0.026). The PM+ infants also had a lower weight (p = 0.032) and head circumference (p = 0.041) at 12 months, indicating lower growth rates.At birth, the size and weight of the PM+ and PM- infants were equivalent. By 12 months, the PM+ infants had a lower weight and head circumference than the PM- infants.
  
  
  CONCLUSIONS
  Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.
authors.affiliation: MRC Laboratories Gambia, PO Box 273, Banjul, Gambia.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Walther
authors.forename: David J C
authors.initials: DJ
authors.lastname: Miles
authors.forename: Pauline
authors.initials: P
authors.lastname: Waight
authors.forename: Melba S
authors.initials: MS
authors.lastname: Palmero
authors.forename: Olubukola
authors.initials: O
authors.lastname: Ojuola
authors.forename: Ebrima S
authors.initials: ES
authors.lastname: Touray
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Marianne
authors.initials: M
authors.lastname: van der Sande
authors.forename: Sarah
authors.initials: S
authors.lastname: Crozier
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000096:biosynthesis; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008288:Malaria / Q000150:complications* / Q000276:immunology*; D010922:Placenta Diseases / Q000276:immunology*; D011247:Pregnancy; D014373:Tuberculin / Q000276:immunology*; D014374:Tuberculin Test; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D014373:Tuberculin; D032581:Tuberculosis Vaccines; D023201:CD40 Ligand; D007371:Interferon-gamma