Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

Early Career

Status: Funded - Open

Integrating Genomic Epidemiology Into Public Health Microbiology for Meningococcal Disease

Charlene Rodrigues, BSc, MBChB, MRCPCH, PGDip

Summary

BACKGROUND: Neisseria meningitidis is a major cause of sepsis and meningitis (invasive meningococcal disease, IMD) in children and adolescents globally. Vaccination offers the optimal means of protection; identifying those at risk and providing effective vaccines are key public health goals and central to the WHO’s “Defeating meningitis by 2030” agenda. GAP: As genomics makes increasingly important contributions to microbiology and infectious diseases, the translation of microbial genomics into clinical and public health microbiology remains extremely limited. Since 2018, NHS Scotland routinely whole genome sequence (WGS) all IMD isolates and we aim to develop analysis platforms to support clinicians and public health teams use genomic data to inform decision-making. HYPOTHESIS: With appropriate platforms and support, real-time meningococcal genome analysis can enhance IMD outbreak/cluster investigations and inform the use of preventative strategies (vaccines) for non-genomics specialists. METHODS: Meningococcal isolates linked in a transmission chain, identified epidemiologically and genomically, will be analysed using core genome (1605 loci) multilocus sequence typing (cgMLST), phylogenetic analysis and single-linkage clustering. Comparative genomics methods will also be used to study geotemporal stability of carriage and disease meningococci. For the vaccine traffic light system, genotype-phenotype analysis will be performed and a data visualization devised. RESULTS: The MenDeVAR (Meningococcal Deduced Vaccine Antigen Reactivity) Index is a translational genomic application providing rapid identification of vaccine antigen reactivity of Bexsero and Trumenba for any meningococcal isolate linking genotypic and phenotypic data accessible at PubMLST.org. IMPACT: Both outbreak investigation methods and the vaccine traffic light system will be integrated into the NHS Scotland public health management system, by the microbiologists, bioinformaticians and epidemiologists collaborating on this project ensuring immediate clinical implementation to inform the management of childhood, adolescent and adult IMD.

Publications:

Supervising Institution:
University of Oxford

Mentors
Martin Maiden

Project Location:
United Kingdom

Award Amount:
$26,750