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Genomic investigation of pneumoccocal transmission in a densely sampled Vietnamese city

Title of PhD project

Genomic investigation of pneumoccocal transmission in a densely sampled Vietnamese city

Supervisory team

LSHTM 

Lead: Stéphane Hué (Stephane.Hue@lshtm.ac.uk, Faculty of Epidemiology and Popuaion Health) 

Stefan Flasche (Stefan.Flasche@lshtm.ac.uk) 

Nagasaki University 

Michiko Toizumi (toizumi@nagasaki-u.ac.jp) 

Lay Myint Yoshida (LMYoshi@nagasaki-u.ac.jp)                                                                               

Brief description of project

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, about 3,000 of the 8,000 samples tested positive for S. pneumoniae are presently being sequenced. This will result in a large dataset of whole genome and ultra-deep sequences linked to demographic, clinical and epidemiological information collected at the time of sampling, available at the beginning of 2023.  

This dataset 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 multidisciplinary 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 modelling, and (iv) investigate the role of sub-dominantly carried serotypes in transmission.  

References  

  1. Poehling et al. Invasive pneumococcal disease among infants before and after introduction of pneumococcal conjugate vaccine. JAMA. 2006; 295: 1668-1674  

  1. 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 the Nha Trang National Institute of Hygiene & Epidemiology, 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, dynamic modelling, pathogen molecular evolution, genomic sequence analyses and phylogenetic inference.