# Sepsis Characterization in Kilimanjaro

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $675,496

## Abstract

PROJECT SUMMARY
Sepsis is a leading cause of in-hospital death in high-income countries, and it likewise causes a formidable
burden of disease in low-income countries, where in-hospital mortality for severe sepsis can exceed 60%.
Building upon Duke University’s strong collaborative clinical research platform in Kilimanjaro, Tanzania, these
studies will use data-driven clustering methods and Bayesian latent class models to define clinically meaningful
subtypes of sepsis that are specific to the infectious disease epidemiology and population sub-structures of sub-
Saharan Africa (sSA). In doing so, we seek to advance the long-term goal of improving detection, risk
stratification and, eventually, tailored interventions for sepsis among adults in resource-limited settings. The
rationale driving this project is that sepsis subtype characterization holds great promise for improving the
evaluation, management and clinical investigation of sepsis in sSA. To perform our characterizations of adult
sepsis subtypes, we will leverage existing samples and data from our research platform’s 2016-2019 severe
febrile illness cohort to inform a two-year prospective observational study of sepsis admissions at district
hospitals in Kilimanjaro. By developing a precision medicine-based approach to classify the key pathophysiologic
subtypes of sepsis in sSA, this project promotes the US National Institutes of Health’s mission to uncover new
knowledge that will lead to better health for everyone—in this case, better health for the most severely ill in the
region with the highest burden of sepsis in the world. To achieve this, the project has set out SPECIFIC AIMS
that will develop clinical phenotype clusters of adult sepsis derived from clinical bioinformatics using Bayesian
statistics (Aim 1) as well as immunologic sepsis clusters based upon the molecular characterization of the host
immune response to infection (Aim 2). We will integrate the approaches in Aim 1 and Aim 2 in order to identify
robust and clinically meaningful subtypes of sepsis in Kilimanjaro (Aim 3). In Year 1, we will use the existing
samples and data collected 2016-2019 to develop and refine the statistical and analytical models for our Aims.
This will inform the analytical framework for the prospective sepsis patient cohort in Years 2-3, which will be the
basis for both derivation and validation of the clinical and molecular sepsis subtype classifications. The clinical
clusters and molecular characterizations discovered in Aim 1 and Aim 2 will also be compared to findings from
clinical bioinformatic and gene expression signature analyses that have described sepsis subtypes in Europe
and North America. The disease epidemiology of sepsis in sSA—high prevalence of advanced HIV infection and
more diverse sepsis etiologies—as well as potential host genetic differences compared to European and North
American sepsis patients necessitate that subtype identification be specifically derived and validated for
...

## Key facts

- **NIH application ID:** 10908347
- **Project number:** 5R01AI155733-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Matthew P Rubach
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $675,496
- **Award type:** 5
- **Project period:** 2020-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908347

## Citation

> US National Institutes of Health, RePORTER application 10908347, Sepsis Characterization in Kilimanjaro (5R01AI155733-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10908347. Licensed CC0.

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