Sepsis & infection

Identification of transcriptomic sepsis endotypes in sub-Saharan Africa: derivation, validation, and global alignment in two Ugandan cohorts

Intensive Care MedPublished Prospective observational cohort study

Main finding · Mortality by endotype (discovery cohort)Result — go to the resultAbsolute difference 19.3% 95% CI 7.6–30.9%

Authors' conclusion

We identified two transcriptomic sepsis endotypes in Uganda that reflect inter-individual differences in targetable pathobiology and confer prognostic enrichment across high-burden infections.

Study context

Population
Critically ill adults with sepsis in Uganda (discovery cohort Tororo, rural, N = 243; validation cohort Entebbe, urban, N = 112)discovery N = 243
Exposure
USE-2 vs USE-1 transcriptomic sepsis endotypes
Outcome
Mortality by endotype (discovery cohort)
Methodological detailstwo cohorts (discovery and validation), unsupervised clustering of whole-blood RNAseq, random forest classifier
  • Two cohorts (discovery and validation)
  • Unsupervised clustering of whole-blood RNAseq
  • Random forest classifier

Main finding

As reported in the abstract

Absolute difference

19.3%

95% CI 7.6–30.9%

By group

USE-2 vs USE-1
absolute difference 19.3% (95% CI 7.6–30.9%)

Observational data: associations, not effects.

Further findings

Validation cohort replication (13-gene classifier)

Classifier misclassification rate
1.43%
Two endotypes replicated with similar biological and clinical profiles

Alignment with HIC-derived endotypes

USE-2 strong transcriptional overlap with SRS1 and inflammopathic endotypes but only modest concordance in patient-level assignments
Overlap with Mars1 variable

Original publication

Identification of transcriptomic sepsis endotypes in sub-Saharan Africa: derivation, validation, and global alignment in two Ugandan cohorts. Intensive Care Med. Published 29 July 2025. doi:10.1007/s00134-025-08047-0

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