Title of PhD project / theme
Viral metagenomics of severe febrile illness with unknown aetiology in the Philippines.
Supervisory team
LSHTM
Lead: Damien Tully (Damien.Tully@lshtm.ac.uk, Faculty of Epidemiology and Population Health)
David Allen
Nagasaki University
Chris Smith (Christopher.Smith@lshtm.ac.uk)
Koya Ariyoshi
(inputs from visiting researchers Reiko Miyahara, Motoi Suzuki)
Brief description of project / theme
Viral infections pose a significant health burden and remain a leading cause of global morbidity and mortality. Yet, identifying the causative pathogen remains challenging in several clinical syndromes. Viral metagenomic next-generation sequencing enables the systematic detection of a full spectrum of known and novel viral pathogens and has numerous advantages compared to conventional diagnostic tests.
Dengue virus infection is the most common arthropod-borne viral disease of humans, with an estimated 100 million clinical infections occurring annually worldwide. Dengue infection typically manifests clinically as dengue fever or more severe dengue shock syndrome. In dengue-endemic countries such as the Philippines actual number of dengue cases are underreported due to mild symptoms and low percentage of diagnostic tests.
Hospitalised dengue cases are also often misdiagnosed as other febrile illness. As hospital-based acute febrile illness study is currently be performed in the Philippines. This additional study will focus on employing metagenomic sequencing to determine the aetiology of febrile illness in severe hospitalised cases and those cases whom current diagnostic assays have yielded negative results. The spectrum of viruses found will be compared against conventional diagnostic methods and the feasibility of integrating such tools as part of public health surveillance efforts assessed.
References
-
Metsky HC, Siddle KJ, Gladden-Young A, … Tully DC… Sabeti PC, Matranga CB. Capturing sequence diversity in metagenomes with comprehensive and scalable probe design. Nature Biotechnology. 2019 Feb;37(2):160-168.
-
Chiu CY, Miller SA. Clinical metagenomics. Nature Reviews Genetics. 2019 Jun;20(6):341-355.
-
Jerome H, Taylor C, Sreenu VB, Klymenko T, Filipe ADS, Jackson C, Davis C, Ashraf S, Wilson-Davies E, Jesudason N, Devine K, Harder L, Aitken C, Gunson R, Thomson EC. Metagenomic next-generation sequencing aids the diagnosis of viral infections in febrile returning travellers. J Infect. 2019 Oct;79(4):383-388.
The role of LSHTM and NU in this collaborative project
NU: Support for sequencing, specimen management and clinical tropical medicine
LSHTM: Support for metagenomic sequencing, phylogenetic and computational analyses
Particular prior educational requirements for a student undertaking this project
A BSc in a relevant biological sciences discipline (virology, microbiology, molecular biology) is essential. An MSc in a relevant biological science (virology, microbiology) which included a laboratory-based project is highly desirable.
Skills we expect a student to develop/acquire whilst pursuing this project
Next-generation sequencing, Molecular Biology, Phylogenetics, Virology, Data Analyses, Bioinformatics