Molecular phenotypes of critical illness confer prognostic and biological enrichment in sub-Saharan Africa: a prospective cohort study from Uganda
The generalisability of critical illness molecular phenotypes to low- and middle-income countries (LMICs) is unknown. We show that molecular phenotypes derived in high-income countries (hyperinflammatory and hypoinflammatory, reactive and uninflamed) stratify sepsis patients in Uganda by physiological severity, mortality risk and dysregulation of key pathobiological domains. A classifier model including data available at the LMIC bedside modestly discriminated phenotype assignment (area under the receiver operating characteristic curve (AUROC) 0.80, 95% CI 0.71 to 0.90 for hyperinflammatory vs hypoinflammatory; AUROC 0.74, 95% CI 0.65 to 0.83 for reactive vs uninflamed). Our findings highlight the potential for a globally relevant, clinicomolecular classification of critical illness and may support the inclusion of diverse populations in phenotype-targeted critical care trials. Improved laboratory capacity and access to rapid biomarker assays are likely necessary to optimise phenotype stratification in LMIC settings.
Authors
- Kai Nie (ORCID: https://orcid.org/0000-0002-8253-9688)
- Barnabas Bakamutumaho (ORCID: https://orcid.org/0000-0003-4259-8509)
- Misaki Wayengera (ORCID: https://orcid.org/0000-0001-7239-8079)
- John Kayiwa (ORCID: https://orcid.org/0000-0002-1840-1801)
- Matthew J. Cummings (ORCID: https://orcid.org/0000-0003-2906-0966)
- Xiaoyu Che (ORCID: https://orcid.org/0000-0002-9738-7664)
- Alin S. Tomoiaga (ORCID: https://orcid.org/0000-0003-2221-8484)
- Julius J. Lutwama (ORCID: https://orcid.org/0000-0002-3210-722X)
- Seunghee Kim‐Schulze (ORCID: https://orcid.org/0000-0003-0192-4400)
- Irene Nayiga
- Xiaohong Lu (ORCID: https://orcid.org/0000-0001-6417-0250)
- Moses Muwanga
- Nicholas Owor
- Max R. O’Donnell (ORCID: https://orcid.org/0000-0002-1232-3718)
- Walter Ian Lipkin (ORCID: https://orcid.org/0000-0002-8768-9386)
- Jesse Ross (ORCID: https://orcid.org/0009-0008-3405-0897)
- Christopher Nsereko
Institutions
- Ministry of Agriculture, Animal Industry and Fisheries (UG)
- Manhattan University (US)
- Makerere University (UG)
- Columbia University (US)
- Uganda Virus Research Institute (UG)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Thorax
- Published
- 2024-12-25
- DOI
- https://doi.org/10.1136/thorax-2024-222412
- Citations
- 3
- Primary Topic
- Sepsis Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- National Institute of Allergy and Infectious Diseases
- Fogarty International Center
- National Center for Advancing Translational Sciences