title: The Association of Cytokines and Micronutrients with Hepatitis E Virus Infection During Pregnancy and the Postpartum Period in Rural Bangladesh.
abstract: Hepatitis E virus (HEV) infection is severe during pregnancy, with a pregnant case fatality rate around 30%. In Bangladesh, plasma samples from 1,100 women during the first trimester (TM) and third TM of pregnancy and 3 months postpartum (PP) were tested for anti-HEV IgG. During this time, 40 women developed antibody responses to HEV. These seroconverters are classified as the cases (incidence = 46 infections per 1,000 person-years). All except one seroconversion occurred between the third TM and 3 months PP. The cases and 40 matched non-seroconverters (controls) underwent analysis of a panel of 10 cytokines, 12 vitamins and minerals, and two markers of inflammation. Throughout pregnancy, seroconverting cases displayed higher concentrations of both pro- and anti-inflammatory cytokines compared with the non-seroconverting controls, even prior to infection. In the first TM, seroconverters had lower circulating zinc concentrations (P = 0.03), an increased prevalence of vitamin D deficiency (25-hydroxy vitamin D [25(OH)2D] < 50 nmol/L, P = 0.08), and anemia (hemoglobin < 110 g/L, P = 0.05) compared with controls. There were no differences in C-reactive protein or α-1-acid glycoprotein. Antecedent micronutrient deficiencies may lead to dysregulated cytokine expression and immunologic compromise, increasing the risk of HEV infection, especially during pregnancy. This exploratory analysis reveals potential novel associations that deserve further study.
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Kmush
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland alabriqu@gmail.com.
authors.forename: Alain
authors.initials: A
authors.lastname: Labrique
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Sabra L
authors.initials: SL
authors.lastname: Klein
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Kerry
authors.initials: K
authors.lastname: Schulze
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Saijuddin
authors.initials: S
authors.lastname: Shaikh
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Hasmot
authors.initials: H
authors.lastname: Ali
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Engle
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Lee
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Sucheta
authors.initials: S
authors.lastname: Mehra
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Parul
authors.initials: P
authors.lastname: Christian
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Keith
authors.initials: K
authors.lastname: West
authors.affiliation: Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland; The JiVitA Maternal and Child Health Research Project, Gaibandha, Bangladesh; Hepatitis Viruses Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, Maryland.
authors.forename: Kenrad
authors.initials: K
authors.lastname: Nelson
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001459:Bangladesh / Q000453:epidemiology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D016751:Hepatitis E / Q000097:blood / Q000378:metabolism* / Q000821:virology; D016752:Hepatitis E virus / Q000502:physiology*; D006801:Humans; D018977:Micronutrients / Q000097:blood*; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000378:metabolism*; D012424:Rural Population; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D018977:Micronutrients