# Phenotyping sepsis in Uganda using molecular pathogen diagnostics and latent class modeling

> **NIH NIH F32** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $91,356

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal describes a research, training, and career development plan for Dr. Matthew Cummings, a
pulmonary/critical care fellow at Columbia University. Working with collaborators and mentors at Columbia and
in Uganda, Dr. Cummings is establishing himself as a clinical-translational investigator focused on sepsis and
infection-related critical illness in low-income settings. Sepsis, with ~30 million incident cases annually, is a
severe, heterogeneous clinical syndrome of acute organ dysfunction resulting from a complex host response to
infecting pathogens. In sub-Saharan Africa, a low-income region where limited diagnostic capacity and an
expansive microbiological differential diagnosis challenge prompt and accurate diagnosis of severe infections,
sepsis is a leading cause of death. Despite a high burden of disease, circulation of diverse pathogens, and
unique host factors including epidemic HIV infection, understanding of the heterogeneous sepsis phenotype in
sub-Saharan Africa and the impact of infecting pathogens on this heterogeneity remains imprecise. While
latent class analyses (LCA) have identified distinct sepsis subphenotypes (subtypes) associated with differing
sites of infection, illness severity, and mortality in high-income settings, the presence of clinically-meaningful
sepsis subtypes requiring divergent diagnostic and treatment strategies remains unknown in sub-Saharan
Africa. Elusiveness of the invading microorganism attributable to the insensitivity of traditional diagnostics has
also challenged understanding of the extent to which phenotypic heterogeneity in sepsis involves the
pathogen. To address these gaps, Dr. Cummings proposes to detect and characterize high-impact pathogens
among adults with sepsis in Uganda using a novel, highly sensitive nucleic acid probe-capture sequencing
platform (Aim 1) and; identify clinically-relevant sepsis subtypes in Uganda through integration of high-
resolution microbiological data and LCA (Aim 2). The research component of this proposal will leverage data
from a prospective cohort study of sepsis conducted through a collaboration between researchers at Columbia
University and Uganda Virus Research Institute. The training component will provide the applicant with course-
based and practical training in epidemiology, biostatistics, and cutting-edge molecular diagnostics that will
facilitate his development into an independent clinical-translational investigator and leader in global health
research. This proposal represents an innovative approach that will advance understanding of high-impact
pathogens associated with sepsis in sub-Saharan Africa while classifying sepsis patients into meaningful
subtypes for whom diagnostic and treatment strategies can be more precisely tailored. This research will also
inform development of a prospective study focused on identifying sepsis biological endotypes in sub-Saharan
Africa that will be proposed in a subsequent K-award app...

## Key facts

- **NIH application ID:** 10003811
- **Project number:** 5F32AI147528-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Matthew John Cummings
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $91,356
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003811

## Citation

> US National Institutes of Health, RePORTER application 10003811, Phenotyping sepsis in Uganda using molecular pathogen diagnostics and latent class modeling (5F32AI147528-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10003811. Licensed CC0.

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