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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 surv...
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| Format: | Thesis |
| Language: | English English |
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Department of Pathology
2025
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| _version_ | 1867613190285688832 |
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| access_status_str | Open Access |
| author | Marais, Gert |
| author2 | Hardie, Diana |
| author_browse | Hardie, Diana Marais, Gert |
| author_facet | Hardie, Diana Marais, Gert |
| author_sort | Marais, Gert |
| collection | Thesis |
| description | 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. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/41742 |
| institution | University of Cape Town (South Africa) |
| language | English eng |
| last_indexed | 2026-06-10T12:32:12.136Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Department of Pathology |
| publisherStr | Department of Pathology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/41742 The application of clinical metagenomics to central nervous system infections in a resource-limited setting Marais, Gert Hardie, Diana Clinical metagenomic sequencing 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. 2025-09-10T09:13:45Z 2025-09-10T09:13:45Z 2025 2025-09-10T08:38:25Z Thesis / Dissertation Masters MMed http://hdl.handle.net/11427/41742 en eng application/pdf Department of Pathology Faculty of Health Sciences Universty of Cape Town |
| spellingShingle | Clinical metagenomic sequencing Marais, Gert The application of clinical metagenomics to central nervous system infections in a resource-limited setting |
| thesis_degree_str | Master's |
| title | The application of clinical metagenomics to central nervous system infections in a resource-limited setting |
| title_full | The application of clinical metagenomics to central nervous system infections in a resource-limited setting |
| title_fullStr | The application of clinical metagenomics to central nervous system infections in a resource-limited setting |
| title_full_unstemmed | The application of clinical metagenomics to central nervous system infections in a resource-limited setting |
| title_short | The application of clinical metagenomics to central nervous system infections in a resource-limited setting |
| title_sort | application of clinical metagenomics to central nervous system infections in a resource limited setting |
| topic | Clinical metagenomic sequencing |
| url | http://hdl.handle.net/11427/41742 |
| work_keys_str_mv | AT maraisgert theapplicationofclinicalmetagenomicstocentralnervoussysteminfectionsinaresourcelimitedsetting AT maraisgert applicationofclinicalmetagenomicstocentralnervoussysteminfectionsinaresourcelimitedsetting |