Helle Brander Eriksen1, Najaaraq Lund2, Sofie Biering-Sørensen3, Cizete Correia4, Amarildo Barbosa5, Andreas Andersen6, Peter Aaby7, Dorthe L Jeppesen8, Christine Stabell Benn9. 1. 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. 2. Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, 2300 København S, Denmark. Electronic address: najaaraq.lund@gmail.com. 3. 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. 4. Bandim Health Project, INDEPTH Network, Bissau, Apartado 861, 1004 Bissau Codex, Guinea-Bissau. Electronic address: cizetecorreia@gmail.com. 5. Bandim Health Project, INDEPTH Network, Bissau, Apartado 861, 1004 Bissau Codex, Guinea-Bissau. Electronic address: amarildo77@yahoo.com.br. 6. Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, 2300 København S, Denmark. Electronic address: aae@ssi.dk. 7. 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. 8. Pediatric Department, Copenhagen University Hospital, Hvidovre, Kettegårds Alle 30, 2650 Hvidovre, Denmark. Electronic address: dorthe.lisbeth.jeppesen@regionh.dk. 9. 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.
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. DISCUSSION: 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.
RCT Entities:
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. DISCUSSION: 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.