title: Investigating the non-specific effects of BCG vaccination on the innate immune system in Ugandan neonates: study protocol for a randomised controlled trial.
abstract: BACKGROUND
  The potential for Bacillus Calmette-Guérin (BCG) vaccination to protect infants against non-mycobacterial disease has been suggested by a randomised controlled trial conducted in low birth-weight infants in West Africa. Trials to confirm these findings in healthy term infants, and in a non-West African setting, have not yet been carried out. In addition, a biological mechanism to explain such heterologous effects of BCG in the neonatal period has not been confirmed. This trial aims to address these issues by evaluating whether BCG non-specifically enhances the innate immune system in term Ugandan neonates, leading to increased protection from a variety of infectious diseases.
  
  
  METHODS
  This trial will be an investigator-blinded, randomised controlled trial of 560 Ugandan neonates, comparing those receiving BCG at birth with those receiving BCG at 6 weeks of age. This design allows comparison of outcomes between BCG-vaccinated and -naïve infants until 6 weeks of age, and between early and delayed BCG-vaccinated infants from 6 weeks of age onwards. The primary outcomes of the study will be a panel of innate immune parameters. Secondary outcomes will include clinical illness measures.
  
  
  CONCLUSIONS
  Investigation of the possible broadly protective effects of neonatal BCG immunisation, and the optimal vaccination timing to produce these effects, could have profound implications for public healthcare policy. Evidence of protection against heterologous pathogens would underscore the importance of prioritising BCG administration in a timely manner for all infants, provide advocacy against the termination of BCG's use and support novel anti-tuberculous vaccine strategies that would safeguard such beneficial effects.
  
  
  BACKGROUND
  ISRCTN59683017 : registration date: 15 January 2014.
authors: Wellcome Trust - Bloomsbury Centre for Global Health Research, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Sarah.prentice@lshtm.ac.uk.|Clinical Research Department, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Sarah.prentice@lshtm.ac.uk.|MRC/Uganda Virus Research Institute on AIDS, Plot 51-59, Nakiwogo Road, PO Box 49, Entebbe, Uganda. Sarah.prentice@lshtm.ac.uk.
authors: Sarah
authors: S
authors: Prentice
authors: Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Emily.webb@lshtm.ac.uk.
authors: Emily L
authors: EL
authors: Webb
authors: Wellcome Trust - Bloomsbury Centre for Global Health Research, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Hazel.dockrell@lshtm.ac.uk.|Department of Infection and Immunology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Hazel.dockrell@lshtm.ac.uk.|MRC/Uganda Virus Research Institute on AIDS, Plot 51-59, Nakiwogo Road, PO Box 49, Entebbe, Uganda. Hazel.dockrell@lshtm.ac.uk.
authors: Hazel M
authors: HM
authors: Dockrell
authors: MRC/Uganda Virus Research Institute on AIDS, Plot 51-59, Nakiwogo Road, PO Box 49, Entebbe, Uganda. pontiano.kaleebu@mrcuganda.org.
authors: Pontiano
authors: P
authors: Kaleebu
authors: Wellcome Trust - Bloomsbury Centre for Global Health Research, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. alison.elliott@mrcuganda.org.|Clinical Research Department, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. alison.elliott@mrcuganda.org.|MRC/Uganda Virus Research Institute on AIDS, Plot 51-59, Nakiwogo Road, PO Box 49, Entebbe, Uganda. alison.elliott@mrcuganda.org.
authors: Alison M
authors: AM
authors: Elliott
authors: Department of Infection and Immunology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Stephen.cose@lshtm.ac.uk.|MRC/Uganda Virus Research Institute on AIDS, Plot 51-59, Nakiwogo Road, PO Box 49, Entebbe, Uganda. Stephen.cose@lshtm.ac.uk.
authors: Stephen
authors: S
authors: Cose
mesh_terms: D000367:Age Factors; D001500:BCG Vaccine / Q000008:administration & dosage*; D002985:Clinical Protocols; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D014454:Uganda; D014611:Vaccination
chemical_list: D001500:BCG Vaccine