Metagenomics approach to rapidly diagnosing sepsis in neonates from low-middle income countries
Antimicrobial resistance (AMR) is now recognized as one of the most serious global threats to human health in the 21C. There is now evidence of political traction, with endorsements of statements by the WHO, UK and US governments, and CDC describing a global crisis and an impending catastrophe of a return to the pre-antibiotic era. These serious concerns have been catalysed by the rapid increase in Multi-Drug Resistant (MDR) Gram-negative bacteria, particularly, Enterobacteriaceae. Despite the availability of most antibiotics, neonatal mortality in low-middle income countries (LMIC) is higher than high income countries as the treatment of infections in neonates is becoming increasingly difficult due to the occurrence of MDR pathogens. Pathogens. For example, in Pakistan has the third highest mortality rate and there are only two other countries, Afghanistan and Iraq that ranked higher. This PhD proposal is a silo project from an established £2M Infection and Immunity study called BARNARDS funded by the Gates Foundation. The project will use whole genome sequencing (WGS) on maternal rectal swabs to examine whether certain clones carried by the mother are responsible for the neonatal sepsis; the data from which will allow LMIC intervention studies and exploration of rapid techniques for diagnosis of sepsis in LMICs.
(i) Proposed Plan of Research
Bacterial isolates from neonates from these mothers who develop both early (7 days) will also be studied, and compared to isolates from the mother. Rectal samples taken from mothers whose infants do not present with infection will be used as a control group. These samples have already ethical and transport clearance, and represent a unique sample pool supported by detail clinical data. The analysis rectal swabs, mining the metagenome and equating these data with the aetiology of neonatal sepsis, will provide unique insights into exploring technologies for rapid diagnosis of sepsis in LMICS and potentially saving millions of lives.
The molecular platform is a dedicated genomic hub that will provide data on strain type, virulence/pathogenic potential and novel genetic data/mechanisms of resistance. The genomic hub is situated on the 6th Floor of the Heath Park and is dedicated to WGS supporting Welsh and International studies on AMR with the support of Prof. Sam Sheppard and clinical lead, Dr. Lim Jones. The student will be surrounded by expertise such as Dr. Maria Carvalho who runs the day-day operations of the WGS hub and further supported by Dr. James Colley, Welsh Gene Park. The student will learn about big data handling combining clinical indices with genomic data and will be taught molecular biology, laboratory microbiology, genomic library preps, DNA sequencing, bioinformatics analysis, and merging files and spreadsheets. These skills are highly in demand and will enable the student to establish a career in an emerging and critical area of modern science.
(ii) Potential impact of the research
This study will be the first of its kind in the world to blend clinical and molecular epidemiology from LMICs with respect to rapidly diagnosing neonatal Gram-negative infections. This area of science is highly topical and has potential for independent innovation. The data generated will be used to inform, local LMIC and international health bodies, and is publishable in high-end medical journals with respect to REF2020.
UK/EU tuition fees
Doctoral Stipend matching UK Research Council National Minimum (£14,057 p.a. for 2015/16 updated each year)
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FTE Category A staff submitted: 59.01
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