The application of clinical metagenomics to central nervous system infections in a resource-limited setting

Clinical metagenomic sequencing (CMS) is a powerful tool that can overcome both the need for pathogen viability and a priori test selection, but infrastructure, expertise and reagent costs limit its accessibility, particularly in low- and middle-income countries. The recent expansion of genomic surveillance infrastructure in these regions presents an opportunity to redirect reserve capacity from decreased SARS-CoV-2-related demand to other applications. We evaluated the performance of a cerebrospinal fluid CMS assay and total cost of conventional investigations for central nervous system (CNS) infections in a referral centre in Cape Town, South Africa. Methods: Cerebrospinal fluid from 43 participants with suspected CNS infections, without an aetiological diagnosis at the time of sampling, underwent unbiased Illumina-based sequencing to evaluate for RNA and DNA from potential pathogens. CMS results were evaluated based on criteria for target genome coverage, clinical compatibility, likelihood of the target representing contamination and a score calculated from the target reads per million and genome size. Findings: CMS showed a positive percent agreement and negative percent agreement relative to conventional investigations of 76% (CI: 53-90%) and 90% (CI: 74-97%). A pathogen was detected by CMS in 8 (38%, n=8/21) immunocompromised and 2 (9%, n=2/22) immunocompetent participants. The median cost of conventional CNS infectious disease investigations was £180,80 (IQR: £127,40-£281,40) in immunocompromised participants and £68,56 (IQR: £9,81-£127,40) in immunocompetent individuals. Interpretation: CMS implementation with currently available sequencing infrastructure in low- and middle-income countries that perform SARS-CoV-2 genomic surveillance is feasible. Immunocompromised individuals may represent a priority group for CMS implementation in resource limited settings as a greater number of pathogens were identified at a comparable cost to conventional diagnostics.

Grantor dc:publisher.institution

Department of Pathology

Year dc:date.issued

2025

Author dc:creator

• Marais, Gert

Advisor dc:contributor.advisor

• Hardie, Diana

• Clinical metagenomic sequencing

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/11427/41742

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/41742