Inferring_pneumococcal_transmission_routes_to_infants_during_a_cluster_randomised_vaccine_trial_in_Nha_Trang__Vietnam
Background and goals A cluster randomised trial in Nha Trang, Vietnam was initiated to assess the potential non-inferiority of a reduced dose schedule of pneumococcal conjugate vaccine (PCV) at a population level. The trial is funded by the Bill and Melinda Gates foundation and is set to conclude in 2021. Co-applicants for the grant were Lay-Myint Yoshida, Kim Mulholland and Stefan Flasche. Also, several trials measuring the efficacy of such reduced dose schedule in comparison to common 3-dose schedules via carriage or immunogenicity endpoints are now underway. A key gap in the understanding of the prospects of such a reduced dose schedule and the ability to extrapolate findings across settings is the understanding of transmission pathways for pneumococcal infections in those infants who will receive less direct protection in a reduced dose schedule.  The overarching goal of this study is to establish the transmission pathways for pneumococcal infection in young infants to quantify the risks for a cost saving reduced dose vaccine schedule.  This will require addressing a number of scientifically interesting and challenging questions on the way that include eg the inference of transmission events and the direction of transmission from cross-sectional data, as well as the statistically appropriate inclusion of individual-level contact patterns from a nested contact study into the phylogenetic inference.  Ultimately the results from the phylogenetic analyses on transmission events will be embedded into a transmission modelling framework to assess risk factors for transmission, account for unobserved carriage and transmission events and the ability to extrapolate results to other settings.  #Description of Samples As part of the ongoing vaccine trial in Nha Trang cross-sectional nasopharyngeal carriage samples of 1440 infants, 1440 toddler and their respective caretakers are obtained. The project will deep sequence 2500 samples that are positive for S. pneumoniae.