Next Generation sequencing approaches to understand fevers of unknown origin in African populations at the University of Edinburgh

Supervisors: Dr Stella Mazeri, Prof Mark Bronsvoort, Dr Melissa Sander

Closing Date:  5th January 2022

Endemic zoonoses such as brucellosis, leptospirosis, rickettsioses, bartonellosis, Rift Valley fever and many others, pose considerable challenges for clinicians in both human and animal health. They frequently present with general symptoms that are shared with many infectious diseases common in the tropics, and are hard to differentiate clinically. Furthermore, the lack of diagnostic tools that can help differentiate these infections results in large scale mis-diagnosis of fevers, pneumonias and other acute human infections and an almost complete lack of diagnosis of infection in livestock in LMICs. As a consequence, the true burden of endemic zoonoses is largely underappreciated and awareness among clinicians and policymakers remains limited. For example, Crump et al (2013) in Tanzania found many febrile cases classed as malaria, to be zoonoses and in over 50% of febrile illness no cause was identified.  This creates a huge knowledge/data gap that results in extensive misuse of antibiotics in both humans and livestock driving the antimicrobial resistance crisis and also an information blackhole for public health and livestock disease prioritization and disease control planning.

The specific objectives of this PhD are:

1. Establish a diagnostic metagenomic (mNGS) pipeline and demonstrate its use to identify zoonotic pathogens in clinical and screening samples from humans and animals

1. Quantify the major causes of febrile illness in the human population attending the regional and Baptist Mission hospitals in North West Cameroon

1. Using this develop a testing algorithm for use in resource limited settings and estimate its efficiency and cost benefits

This pilot project builds on links with the Tuberculosis Reference Laboratory and Baptist Mission hospital network in Cameroon. We wish to implement a metagenomics approach using the MinION platform and the SURPI pipeline (Greninger et al 2015) to pilot specific pathogen diagnosis and test its validity in febrile patients against conventional diagnoses.

References

Mbu ET, Sauter F, Zoufaly A, Bronsvoort BMC, Morgan KL, Noeske J, Abena JF, Sander MS. Tuberculosis in people newly diagnosed with HIV at a large HIV care and treatment center in Northwest Cameroon: Burden, comparative screening and diagnostic yields, and patient outcomes. PLoS One. 2018 Jun 26;13(6):e0199634. doi: 10.1371/journal.pone.0199634. PMID: 29944701; PMCID: PMC6019259.

Crump JA, Morrissey AB, Nicholson WL, Massung RF, Stoddard RA, Galloway RL, Ooi EE, Maro VP, Saganda W, Kinabo GD, Muiruri C, Bartlett JA. Etiology of severe non-malaria febrile illness in Northern Tanzania: a prospective cohort study. PLoS Negl Trop Dis. 2013 Jul 18;7(7):e2324. doi: 10.1371/journal.pntd.0002324. PMID: 23875053; PMCID: PMC3715424.

Alexander L. Greninger, Samia N. Naccache, Scot Federman, Guixia Yu, Placide Mbal, Vanessa Bres, Doug Stryke, Jerome Bouquet, Sneha Somasekar, Jeffrey M. Linnen, Roger Dod, Prime Mulembakani, Bradley S. Schneider, Jean-Jacques Muyembe-Tamfum , Susan L. Stramer and Charles Y. Chiu (2015) Rapid metagenomic identification of viral pathogens in clinical samples by real-time nanopore sequencing analysis. Genome Medicine 7:99

Funding information and application procedures

We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 5th January 2022 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships 

This opportunity is open to UK and international students and provides funding to cover stipend, tuition fees and consumable/travel costs.  Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [email protected].

When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.

A webinar will be held on Tuesday 14th December at 13.00hrs (UK time) to assist you in the application process and tell you a little more about studying for a PhD with us.  It will also give you an opportunity to ask any questions you may have.  If interested in joining us please send your name and email address to [email protected]by Friday 10th December and we will send you a link to the on line meeting

ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 5th JANUARY 2022