Title of PhD project / theme
Unravelling pneumococcal transmission in a densely sampled city in coastal Vietnam through genomic inference.
Brief description of project / theme
The transmission of Streptococcus pneumoniae is not well understood despite its importance for evaluating the use case of pneumococcal vaccination schedules that rely on indirect protection (e.g. [1,2]). In Nha Trang, Vietnam, we have collected more than 30,000 nasopharyngeal swabs from young children and their care giver in 5 cross-sectional city-wide studies between 2017 and 2020. After covid-related delays during which the robustness of inference pipelines has been explored, all approvals are now in place to sequence about 3,000 of the 8,000 samples tested positive for S. pneumoniae. Whole genome and ultra-deep sequencing of these samples is expected to start in early 2022. All samples are linked to demographic, clinical and epidemiological information collected at the time of sampling. This provides a uniquely dense sampling frame for a single city that will allow the exploration of spatio-temporal transmission patterns of the pneumococcus and the identification of the pathogen’s prominent routes of transmission.
The PhD candidate will use this rich dataset to develop, test and implement a robust methodology to (i) infer pneumococcal transmission from genomic and epidemiological data, (ii) distinguish direct transmission events between recruited individuals from those involving an unsampled intermediary, (iii) identify who infects infants and toddlers with pneumococci using those techniques, and (iv) investigate the role of subdominantly carried serotypes in transmission.
1. Poehling et al. Invasive pneumococcal disease among infants before and after introduction of pneumococcal conjugate vaccine. JAMA. 2006; 295: 1668-1674 LSHTM-NU Joint PhD Programme – Project Application 2022/23 2
2. Loughlin et al. Direct and indirect effects of PCV13 on nasopharyngeal carriage of PCV13 unique pneumococcal serotypes in Massachusetts' children. Pediatr Infect Dis J. 2014; 33: 504-510
The role of LSHTM and NU in this collaborative project
SF, LMY, TM and SH all have ongoing joint projects and have fostered close collaborative work for over half a decade. The successful applicant will be primarily based in London with a substantial amount of time spent with the teams of NGU, NIHE, the Institute Pasteur and Khan Hoa in Vietnam, as well as the group at NGU in Nagasaki. Regular joint teleconferences will ensure a highly collaborative nature of the PhD.
Particular prior educational requirements for a student undertaking this project
A high degree of personal motivation is essential. Expertise in computer programming, ideally in R and/or Python, as well as good command in English is required. Prior knowledge of genomic analysis, phylogenetics and statistical proficiency are also desirable.
Skills we expect a student to develop/acquire whilst pursuing this project
The student will acquire in depth knowledge about pneumococcal epidemiology, vaccinology and advanced statistics, pathogen molecular evolution, genomic sequence analyses and phylogenetic inference.