title: Does oral polio vaccine at birth affect the size of the thymus? Observations within a randomized trial.
abstract: BACKGROUND
  There is increasing evidence that vaccines have an effect on general mortality which goes beyond specific disease protection. Oral polio vaccine (OPV) is widely used in low-income countries, but in observational studies in Guinea-Bissau we observed that not receiving OPV at birth was associated with reduced overall male infant mortality and enhanced immune response to BCG vaccine. We therefore initiated a randomized trial to test the overall effect of OPV at birth (OPV0).
  
  
  OBJECTIVE
  A small thymic gland is a predictor of mortality in high-mortality settings. Within the trial we aimed to test whether no-OPV0 was associated with increased thymic size.
  
  
  METHODS
  In 511 normal birth weight infants who were randomized to receive or not receive OPV0, thymic index and thymus/weight index were measured before randomization and after 2 weeks (N=49), 4 weeks (N=308) or 6 weeks (N=27). The association between OPV0 and the log transformed thymic size indicators were analyzed in ANCOVA models with thymic size at follow-up as the outcome and adjusting for thymic size at enrollment and age at follow-up. Estimates were reported as geometric mean ratios (GMR) with 95% confidence intervals, comparing no-OPV0 to OPV0.
  
  
  RESULTS
  No-OPV0 was not associated with thymic index after 2 weeks (GMR: 1.14 (0.99-1.30)), after 4 weeks (GMR: 0.98 (0.93-1.05)) or after 6 weeks (GMR: 1.00 (0.81-1.23)). However, no-OPV0 was associated with increased thymus/weight index after 2 weeks (GMR: 1.22 (1.06-1.40)), but the effect was not seen after 4 weeks (GMR: 0.97 (0.92-1.03)) and 6 weeks (GMR: 0.99 (0.82-1.19)). There were no strong sex-differences.
  
  
  CONCLUSIONS
  Overall there was no effect on thymic size of OPV0 when administered with BCG. The results could indicate that if an effect occurs, it is only within the first weeks after vaccination.
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, 2300 København S, Denmark; Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, Kettegårds Alle 30, 2650 Hvidovre, Denmark. Electronic address: h.eriksen@bandim.org.
authors.forename: Helle Brander
authors.initials: HB
authors.lastname: Eriksen
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, 2300 København S, Denmark. Electronic address: najaaraq.lund@gmail.com.
authors.forename: Najaaraq
authors.initials: N
authors.lastname: Lund
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, 2300 København S, Denmark; Bandim Health Project, INDEPTH Network, Bissau, Apartado 861, 1004 Bissau Codex, Guinea-Bissau. Electronic address: s.biering@bandim.org.
authors.forename: Sofie
authors.initials: S
authors.lastname: Biering-Sørensen
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Apartado 861, 1004 Bissau Codex, Guinea-Bissau. Electronic address: cizetecorreia@gmail.com.
authors.forename: Cizete
authors.initials: C
authors.lastname: Correia
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Apartado 861, 1004 Bissau Codex, Guinea-Bissau. Electronic address: amarildo77@yahoo.com.br.
authors.forename: Amarildo
authors.initials: A
authors.lastname: Barbosa
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, 2300 København S, Denmark. Electronic address: aae@ssi.dk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Andersen
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, 2300 København S, Denmark; Bandim Health Project, INDEPTH Network, Bissau, Apartado 861, 1004 Bissau Codex, Guinea-Bissau. Electronic address: p.aaby@bandim.org.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: Pediatric Department, Copenhagen University Hospital, Hvidovre, Kettegårds Alle 30, 2650 Hvidovre, Denmark. Electronic address: dorthe.lisbeth.jeppesen@regionh.dk.
authors.forename: Dorthe L
authors.initials: DL
authors.lastname: Jeppesen
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, 2300 København S, Denmark; Bandim Health Project, INDEPTH Network, Bissau, Apartado 861, 1004 Bissau Codex, Guinea-Bissau; OPEN, University of Southern Denmark, Windsløwparken 19, 3., 5000 Odense C, Denmark. Electronic address: cb@ssi.dk.
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
mesh_terms: D005260:Female; D006169:Guinea-Bissau; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage* / Q000009:adverse effects*; D013950:Thymus Gland / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D014463:Ultrasonography
chemical_list: D011055:Poliovirus Vaccine, Oral
keywords: Neonate; Non-specific effects; OPV; Polio; Thymic size