Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

"Declaration of interests YL, SD, LPJ, MBL, and KMN receive funding from the TyVAC grant (grant number OPP1151153). KMN is a voting member of the WHO Strategic Advisory Group of Experts on Immunization (SAGE). RSH is a UK National Institute for Health and Care Research Senior Investigator. All other authors declare no competing interests."

"AcknowledgmentsWe thank the trial participants, their parents and guardians, and community leaders in Ndirande and Zingwangwa; the staff of the Malawi Ministries of Health and Education; the Blantyre District Health Officer; the staff of the Paediatric Department of the Queen Elizabeth Central Hospital; the staff of the health centres in Ndirande and Zingwangwa, the Gateway Health Clinic, and the Nancholi Youth Organization Clinic; the director and the staff of the departments of the Malawi–Liverpool–Wellcome Programme, in particular the late Clemens Masesa, head of the Data Research Support Unit; the Malawi trial team (John Ndaferankhande, Mark Haward, Chrissy Banda, Josephine Chilongo, Patricia Phula, James Tamani, Amisa Chisale, David Banda, and Chancy Nyirongo); Victoria Mapemba (Blantyre Malaria Project); the University of Maryland team (Fleesie Hubbard and Tamar Pair); the members of the data and safety monitoring board (Roma Chilengi [chair], Prakash Ghimire, A K M Nurul Anwar [deceased], Nur Haque Alam, Tisungane Knox Titus Mvalo, and Mary E Putt); and Bharat Biotech International for donating Vi-TT. The Typhoid Vaccine Acceleration Consortium (TyVAC) is a partnership between the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, the Oxford Vaccine Group at the University of Oxford, and PATH, an international non-profit. This study was conducted under TyVAC. TyVAC is funded by the Bill & Melinda Gates Foundation (grant number OPP1151153). The Malawi–Liverpool–Wellcome Programme is supported by core funding from the Wellcome Trust (grant number 206545/Z/17/Z). MAG is supported by the UK National Institutes of Health and Care Research, UK Department of Health and Social Care as a Research Professor (grant number NIHR300039)."

"This trial is registered at ClinicalTrials.gov, NCT03299426. Methods: In this phase 3, double-blind, randomised controlled efficacy trial in Blantyre, Malawi, healthy children aged 9 months to 12 years were randomly assigned (1:1) by an unmasked statistician to receive a single dose of Vi polysaccharide conjugated to tetanus toxoid vaccine (Vi-TT) or meningococcal capsular group A conjugate (MenA) vaccine. Children had to have no previous history of typhoid vaccination and reside in the study areas for inclusion and were recruited from government schools and health centres. Participants, their parents or guardians, and the study team were masked to vaccine allocation. Nurses administering vaccines were unmasked. We did surveillance for febrile illness from vaccination until follow-up completion. The primary outcome was first occurrence of blood culture-confirmed typhoid fever. Eligible children who were randomly assigned and vaccinated were included in the intention-to-treat analyses. This trial is registered at ClinicalTrials.gov, NCT03299426."