title: Impact of Placental Malaria and Hypergammaglobulinemia on Transplacental Transfer of Respiratory Syncytial Virus Antibody in Papua New Guinea.
abstract: BACKGROUND
  Passively acquired respiratory syncytial virus (RSV) neutralizing antibody protects against RSV-associated lower respiratory infections, but placental malaria (PM) and maternal hypergammaglobulinemia might interfere with transplacental immunoglobulin transport.
  
  
  METHODS
  We measured RSV plaque-reduction neutralization (PRN) antibody in 300 full-term maternal/cord serum pairs in 2 cohorts in malaria-endemic Papua New Guinea: Alexishafen (2005-2008) and the Fetal Immunity Study (FIS) (2011-2013). We defined impaired transport as a cord-to-maternal titer ratio <1.0 and a protective RSV PRN titer (PRNT) ≥1:200.
  
  
  RESULTS
  PM and hypergammaglobulinemia occurred in 60% and 54% of Alexishafen mothers versus 8% and 9% of FIS mothers, respectively. 34% of Alexishafen and 32% of FIS pairs demonstrated impaired transport. Multivariate modeling revealed significant associations between increasing maternal IgG (log2) and impaired transport (adjusted OR, Alexishafen: 2.68 [1.17-6.14], FIS: 6.94 [1.94-24.8]) but no association with PM. 34% of Alexishafen and 31% of FIS cord PRNTs were <1:200.
  
  
  CONCLUSIONS
  Impaired RSV antibody transport was observed in approximately one-third of maternal/cord pairs. Hypergammaglobulinemia, but not PM, was associated with impaired transport, particularly among women with low RSV PRNT. Detection of RSV PRNT <1:200 in one-third of cord sera confirms the need to increase levels of RSV neutralizing antibody in pregnant women through maternal immunization.
authors.affiliation: Department of International Health, Center for Immunization Research, Johns Hopkins School of Public Health, Baltimore, Maryland.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Atwell
authors.affiliation: Department of International Health, Center for Immunization Research, Johns Hopkins School of Public Health, Baltimore, Maryland.
authors.forename: Bhagvanji
authors.initials: B
authors.lastname: Thumar
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang & Goroka Walter and Eliza Hall Institute Department of Medical Biology, The University of Melbourne, Parkville, Victoria.
authors.forename: Leanne J
authors.initials: LJ
authors.lastname: Robinson
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang & Goroka.
authors.forename: Roselyn
authors.initials: R
authors.lastname: Tobby
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang & Goroka.
authors.forename: Phantica
authors.initials: P
authors.lastname: Yambo
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang & Goroka.
authors.forename: Maria
authors.initials: M
authors.lastname: Ome-Kaius
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang & Goroka Division of Tropical Health and Medicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville City, Queensland.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siba
authors.affiliation: Department of Medicine, The University of Melbourne, Australia.
authors.forename: Holger W
authors.initials: HW
authors.lastname: Unger
authors.affiliation: Department of Medicine, The University of Melbourne, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.affiliation: Center for Global Health and Disease, Case Western Reserve University and Veterans Affairs Medical Center, Cleveland, Ohio.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
authors.affiliation: Department of International Health, Center for Immunization Research, Johns Hopkins School of Public Health, Baltimore, Maryland.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Karron
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood; D006801:Humans; D006942:Hypergammaglobulinemia; D018445:Infectious Disease Transmission, Vertical; D008288:Malaria / Q000150:complications* / Q000453:epidemiology / Q000635:transmission; D008875:Middle Aged; D010219:Papua New Guinea / Q000453:epidemiology; D010922:Placenta Diseases / Q000469:parasitology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000469:parasitology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D012307:Risk Factors; D010948:Viral Plaque Assay; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral
keywords: RSV; hypergammaglobulinemia; maternal immunization; placental malaria; transplacental transfer of antibody