Rapid metagenomics based diagnosis of childhood meningitis

Meningitis is an infection of the protective membranes that surround the brain and spinal cord (meninges). It can affect anyone but is most common in people aged 0-30. While viral meningitis is usually self limiting with good prognosis, bacterial meningitis is very serious and can be deadly if not treated quickly. Death can occur in as little as a few hours. Bacterial meningitis causes about 4,100 cases and 500 deaths in the United States each year and is estimated to cause ~2% of all child deaths globally. Those who recover can suffer permanent disabilities such as brain damage,hearing loss, and learning disabilities.

Rapid diagnosis of meningitis is crucial to differentiate bacterial and viral meningitis and to identify the pathogen and the correct treatment options (if bacterial); yet culture remains the gold standard test, which is too slow (48 hours) and often fails to grow the pathogen. Rapid PCR based tests are becoming more widely available but are not sufficiently comprehensive to detect all potential pathogens and antibiotic resistances. Nanopore metagenomics sequencing combines rapidity with comprehensiveness and has the potential to revolutionise the way we diagnose or type infection. Any potential pathogen, bacterial or viral, plus any known resistance gene can be identified in a single test and we have demonstrated turnaround times as short as 4 hours from sample to result. The aim of the PhD project is to develop and evaluate a rapid metagenomics sequencing based method to characterise meningitis pathogens directly from cerebrospinal fluid (CSF) samples. The PhD student will also study the genomic basis of the pathogenesis of invasive S. pneumoniae, one of the leading causes of childhood meningitis, using bacterial genome wide association studies.