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 physiologic...

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Bibliographic Details
Published in:Thorax Vol. 80; no. 3; pp. 175 - 179
Main Authors: Cummings, Matthew J, Lutwama, Julius J, Tomoiaga, Alin S, Owor, Nicholas, Lu, Xuan, Ross, Jesse E, Muwanga, Moses, Nsereko, Christopher, Nayiga, Irene, Nie, Kai, Kayiwa, John, Che, Xiaoyu, Wayengera, Misaki, Kim-Schulze, Seunghee, Lipkin, W Ian, O’Donnell, Max R, Bakamutumaho, Barnabas
Format: Journal Article
Language:English
Published: England BMJ Publishing Group Ltd and British Thoracic Society 17.02.2025
BMJ Publishing Group LTD
Subjects:
Adult
Biomarkers
Blood pressure
Cohort analysis
Critical care
Critical Illness
Cytokine Biology
Female
Genotype & phenotype
Heart rate
HIV
Human immunodeficiency virus
Humans
Hypotension
Illnesses
Infections
Influenza
Malaria
Male
Mann-Whitney U test
Medical prognosis
Middle Aged
Mortality
Oxygen saturation
Pathogens
Patients
Phenotype
Probability
Prognosis
Prospective Studies
Protein expression
Regression analysis
Sepsis
Sepsis - mortality
Severity of Illness Index
Tuberculosis
Uganda - epidemiology
Urine
Variables
Uganda
Africa
Critical Care
Cytokine Biology
ISSN:0040-6376, 1468-3296, 1468-3296
Online Access:Get full text
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Summary: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.
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ISSN:0040-6376
1468-3296
1468-3296
DOI:10.1136/thorax-2024-222412